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pmc-6011128-1

A 50-year-old Asian male with a past medical history of supraventricular tachycardia and obstructive sleep apnea on CPAP at night presented with one month of intermittent flu-like symptoms, orthopnea, and dyspnea on exertion. At the onset of these symptoms, he presented to a walk-in clinic and was diagnosed with influenza. He was treated symptomatically and noted improvement, but one week later he had a recurrence of symptoms while playing volleyball. From that time on, he noticed dyspnea on exertion, continued malaise, fevers, and diffuse joint pains so he presented multiple times to outpatient providers. He received doxycycline without improvement, and follow-up testing showed a mild leukocytosis, negative EBV, and an unremarkable chest X-ray. He was diagnosed with lingering postviral symptoms from influenza. He ultimately presented as a walk-in patient to the cardiology clinic when he started having chest tightness, palpitations, and his dyspnea progressed to occurring at rest, relieved only with a tripod position. EKG on presentation () showed right axis deviation and abnormal ST-T wave segments in V1 through V3 which was new compared with a prior EKG. Due to the concern for pulmonary embolism, a CT angiogram of the chest was obtained which displayed moderate bilateral pleural effusions, a mass in the right ventricle, and a mass in the left atrium extending through the mitral valve invading into the left ventricle (). Echocardiogram exhibited normal LVEF but some mitral valve occlusion due to the mass. Cardiac MRI was obtained () and confirmed the masses. The patient required debulking of the left atrial tumor, and pathology revealed an undifferentiated, high-grade pleomorphic sarcoma. Due to tumor infiltration into the left pulmonary veins, as well as focal areas of uptake in the small bowel at a site of intussusception, he was started on pembrolizumab chemotherapy with concurrent radiation therapy to the heart and small bowel.

pmc-6011133-1

A 64-year-old white male with no prior medical history presented to his primary care physician for routine follow-up. There was no history of hypertension. During work-up for elevated liver transaminases, he was found to have hepatitis C. Before initiation of Harvoni, he underwent CT imaging of the abdomen with contrast which found a 5 × 6.7 × 7 cm right adrenal mass (). On physical examination, he was afebrile with a pulse of 47 and normotensive at 118/68. His abdominal exam was nontender, nondistended, without masses, or hernias. Review of systems was negative for abdominal pain, hypertension, weakness, palpitations, headache, diaphoresis, or weight gain. He was a current smoker with a 33 pack-year history. He had no history of endocrine disease. His family history was significant only for a father with pancreatic cancer. His remaining laboratory values were within normal values including a normal potassium value. The patient was seen by the endocrine service for evaluation, and biochemical work-up revealed that the ACTH level was 9.1 pg/ml (nl 7.2–63.3); AM cortisol was normal at 10.01 mcg/dl, and 24-hour urine metanephrines was less than 50 mcg (nl). On CT imaging, the right adrenal mass contained scattered calcifications with small regions of fat. It enhanced in a peripheral globular fashion with central progression. The absolute contrast washout of 22.9% was indeterminate for adrenal adenoma (). The mass was noted to abut but did not appear to invade the adjacent liver, right kidney, and inferior vena cava. There was no adenopathy or free fluid. There was no evidence of metastatic disease. Due to the size and atypical features of the mass, right adrenalectomy was performed. An open thoracoabdominal approach was chosen due to the patient's low lying costal margin, the size of the mass, and retrocaval extension of the mass medially towards the vertebral body. The patient recovered well postoperatively and was discharged four days after surgery. The resected specimen weighed 126 grams and measured 7.5 × 6.5 × 4.7 cm on gross pathology (). Within the specimen was a 6.4 × 5.5 × 4.7 cm intraparenchymal nodule, which on histologic examination proved to be a cavernous hemagioma (). The patient has had no evidence of recurrence for nearly 18 months.

pmc-6011134-1

A 34-year-old Gravida 11 Para 3073 at 16 weeks and 1 day gestation presented to the emergency room of an outside hospital with a 2-day history of progressively worsening nausea, vomiting, and diarrhea, exacerbated by eating. The pregnancy had been unremarkable. Her past medical history included endometriosis and infertility. Her past surgical history was significant for two cesarean sections and left salpingo-oophorectomy secondary to an ectopic pregnancy. Physical exam elicited severe, diffuse abdominal tenderness. Fetal heart tones were taken to be in the 140s and positive fetal movement was reported. Laboratory investigations, including complete blood count, comprehensive metabolic panel, amylase, and lipase, were within normal limits. The ER physician's leading differential diagnosis was of gastrointestinal etiology. An MRI and MRCP were performed to rule out appendicitis and gallbladder disease. The MRI was notable for a large amount of intraperitoneal fluid of unknown etiology; an intrauterine fetus was visualized. The patient continued to experience intractable pain, worse with movement and breathing, despite IV pain medication. At that point she has been at the outside facility for approximately 12 hours. The patient was transferred to our facility under the joint care of the Obstetrics/Gynecology and General Surgery teams. Upon arrival, the patient's hemodynamic status had deteriorated. She presented with tachycardia, dyspnea, chest pain, and worsening abdominal pain. Her hemoglobin had fallen from 11.7 g/dL to 7.9 g/dL. Transabdominal ultrasound imaging revealed a single intrauterine pregnancy that was positioned low in the uterus, with marked thinning of the anterior myometrium at the site of the pregnancy, and significant hemoperitoneum. Fetal heart tones were steady in the 140s. The MRI images were reevaluated prior to surgery (see ). At this point, the patient was taken for emergency laparotomy and the staff Gynecologic Oncologist was consulted. The patient underwent a modified radical hysterectomy with right ureteral lysis and cystotomy with bladder repair. The intraoperative findings were consistent for a placenta percreta and uterine rupture with a 2 x 1 cm defect in the right lower uterine segment. There were significant intra-abdominal blood and evidence of invasion of the placenta into the posterior aspect of the bladder. Total estimated blood loss for the surgery was 3,150 mL. The patient received 900 mL of cell saver and 1 unit packed red blood cells (PRBC) intraoperatively. The patient was admitted to the ICU following surgery. She was transferred out of the unit on postoperative day 1. Two more units of PRBC were transfused over the course of the postoperative period. She was discharged on postoperative day 4 after having met her postoperative milestones. Due to the cystotomy, she was discharged with Foley urinary catheter in place for a minimum of 7 days with cystogram scheduled prior to removal. Patient was referred for grief counseling. Pathologic examination of the uterus included placenta percreta with uterine rupture (see for gross specimen). There was absence of decidua identified in the lower uterine segment in the area of the uterine rupture.

pmc-6011142-1

The first case concerns a 26-year-old prelingually Deaf male, with a prior history of Tourette's syndrome, bipolar disorder, and HIV, who was placed under a Baker Act at a local hospital for “acting erratic and psychotic.” A Baker Act is a 72-hour involuntary psychiatric hold within the state of Florida that can be initiated by healthcare professionals and police officers in the event of a patient being a danger to self or others. The preliminary diagnosis on the involuntary form, as per the emergency room physician, was “psychosis.” The patient was subsequently given an emergency treatment order of intramuscular lorazepam and was transferred to a psychiatric hospital where he was observed by nursing as “calm and nonthreatening.” Prior to initial psychiatric interview, an ASL-interpreter was called to assist. The patient asked where he was at and became angry after discovering the truth of his hospitalization. He reported he initially came to the hospital as he had been having anxiety and physical pain attributed to his Tourette's Disorder. He reported his neurologist had him on carisoprodol and diazepam to help relieve these symptoms, but that they were stopped one month prior. The family was called and stated there was questionable abuse of medications but they were adamant that he was safe for himself and others. When the patient was seen by the ED physician initially there was no interpreter present. The patient reported becoming frustrated and was trying to sign aggressively which he believes was misinterpreted. He also expressed in spoken word to the staff there that he had been “hearing voices” secondary to his pain level. He purportedly was never told what was occurring prior to seeing the interpreter at the transfer facility nearly 12 hours later. The patient adamantly denied SI, HI, AVH, or mania and maintained a linear and coherent thought process. He expressed a history of bipolar disorder which had been diagnosed after a similar incident in the past. He had been on several antipsychotics previously but had not taken any for several years without incident. He had only been taking anxiolytics and pain meds for multiple years which he felt stable on, as well as antiretrovirals for his HIV diagnosis. The patient later admitted that he had been buying oxycodone off the street since his neurologist had stopped prescribing medications due to questionable abuse. A clinical opiate withdrawal scale was performed and was only positive for minor anxiety elevation. A full medical workup was performed and excluded any medical causes to his admission. Through further interview, OCD was excluded as a diagnosis but substance use disorder remained high on the differential for his current and past behavior. The patient was kept overnight for observation and discharged the next morning following positive report from staff. He was given extensive education on substance use as well as coping strategies to prevent readmissions. Upon discharge “unspecified psychosis” was given as his diagnosis.

pmc-6011142-2

The second case involves a 30-year-old Deaf, Hispanic male who presented to the Emergency Department after his mother reported that the he was behaving oddly and not taking his risperidone. Per reports, the patient was talking to his mother about going places in a UFO and exhibiting disorganized and illogical behaviors. He was subsequently placed under a Baker Act by the emergency room physician who documented that the patient was exhibiting auditory hallucinations. Initially an interpreter was brought to the hospital prior to his admission. Per the ASL-interpreter, the patient stated that he felt “fine and not crazy” and that all of these events are happening because his mother does not “understanding Deaf culture.” He also conveyed that he did not like to take his meds because they interfered with him being able to drink alcohol and caused drowsiness. Upon initial psychiatric interview an interpreter was not present as the hospital only agreed to set periods of time for the interpreter. As an effort to communicate, questions were prepared for the patient to answer via written responses. highlights a portion of the questions and answers that were constructed. From the responses he maintained bizarre delusions but denied current SI, HI, or AVH. When the ASL-interpreter arrived, the patient appeared jovial and yearned to express himself. The interpreter stated she had difficulties reading his rapid signing at first and had to have him slow down several times. However she did note that this was a common occurrence when addressing Deaf individuals. With the interpreter's assistance, the patient was answering questions logically with a linear thought process. He reported that he had been diagnosed with schizophrenia as a teenager after having several interpersonal issues with his mother. She is Spanish speaking only and he stated that she has never fully understood how to communicate effectively with him. He had been taking risperidone for several years but was tired of continuing with the medication due to the side effects of drowsiness and weight gain, which he was never able to fully discuss with his psychiatrist. Patient reported he was in an ASL school and learning a career in massage therapy. After meeting a girlfriend there he began to develop a sense of independence that he reported his mother disapproved of. This caused an altercation that he reports his mother misinterpreted which precipitated his admission. The patient continued to express that he was abducted by aliens as a child and could understand their language, but besides this he expressed no other psychotic processes. He was observed for two days without medications and remained calm/cooperative but was unable to participate in most activities due to limitations of the interpreter availability. After a family session was completed the patient was discharged home with plans to follow up with his community psychiatrist. The patients' diagnosis was changed to delusional disorder upon his discharge.

pmc-6011145-1

A 36-year-old male, a seasoned cyclist with no past medical history, presents to the emergency department with complaints of lightheadedness and diaphoresis after a bicycle fall. Patient was participating in a bicycle race when another rider ahead of him fell causing the patient to swerve to avoid him. Patient states that he fell on his left side and hit a tree with his right leg. Patient was wearing a helmet and did not suffer any chest or head trauma. After the fall, he felt lightheaded and diaphoretic and complained of mid back pain. Patient denied any chest pains or shortness of breath. Patient was subsequently brought to the hospital directly following the accident by ambulance. In the emergency department, patient was noted to be in no acute distress; initial blood pressure was 128/69 mmHg with pulse of 65 beats per minute. He was afebrile, not tachypneic, and well appearing with marked right thigh swelling and tenderness to his medial thigh. Given the dizziness and diaphoresis initially, patient had an ECG performed which showed lateral ST segment elevation () and had a subsequent troponin I that was positive, 0.49ng/mL, with a Creatine Phosphokinase (CPK) of 617 U/L. There was initial concern for a possible cardiac contusion, although the patient had no chest wall trauma and thus was admitted for further evaluation. As an inpatient, an echocardiogram was performed demonstrating normal right and left ventricular function and trace pericardial effusion while the patients troponin continued to trend upwards towards a maximum of 21ng/mL. He was loaded with Aspirin and Clopidogrel as well as initiation of a heparin infusion, Lisinopril, and a Beta Blocker. Coronary angiography was subsequently performed demonstrating a spontaneous coronary artery dissection of left anterior descending coronary artery. No further diagnostic study was performed at that time. Further history revealed that he took multiple caffeine Jello shots and drank a large cup of coffee prior to participation in the race. He denied cocaine, amphetamine, or other performance enhancing drug use (). The patient's CPK and troponin trended downwards on conservative medical management and his back pain resolved; therefore a stent was not placed. The patient was visiting from outside the area; discharge planning included repeat coronary angiography in 6 weeks and instructions that he will not be able to perform competitive cycling again. Should his dissection extend at that period of time or patient become symptomatic, stent placement would be considered. Patient was to continue the Aspirin and Clopidogrel until the repeat angiography was performed. Patient was discharged with plans to follow up with a cardiologist in his home state. Multiple follow-up phone calls made us unable to reach the patient and he was subsequently lost to follow-up.

pmc-6011150-1

A 30-year-old male with history of active smoking (1 pack per day for 10 years) and external hemorrhoids came to the preop anesthesia clinic for anesthesia evaluation fitness and was found to have high blood pressure (BP) (234/144). He was referred immediately to the emergency room (ER) for BP control. In the ER, BP was 221/125 and heart rate (HR) was 50 beats/minute. Routine electrocardiogram (EKG) showed 3rd-degree heart block (TDHB) and left ventricular hypertrophy (LVH) with strain pattern (). He denied chest pain, palpitation, dyspnea, dizziness, or syncope. The patient was started on antihypertensive medication for BP control and was admitted to the cardiology ward for evaluation and management of complete heart block. Further physical exam revealed absent arterial pulses except the left radial pulse which was weak. BP was significantly different between both upper limbs and between upper and lower limbs (right upper limb 126/86 and lower limb 85/54, left upper limb 145/85 and lower limb 75/50). His initial blood work showed mild renal impairment. Computerized tomography (CT) thoracic aortogram was done to rule out coarctation of the aorta, which was normal; CT coronary angiogram showed no evidence of coronary artery disease (CAD). Magnetic resonance imaging (MRI) of the heart was normal as well. Transthoracic echocardiogram (TTE) showed moderate hypokinesia of the left ventricle (LV), ejection fraction (EF) 35–40%, grade 2/4 diastolic dysfunction, and moderate concentric LVH. Holter monitoring did not reveal any pauses. Ultrasound/Doppler of the kidneys showed increased parenchymal echogenicity with poorly defined corticomedullary junction impressive of renal parenchymal disease. CT abdominal aortogram showed large thrombus seen in the abdominal aorta starting at the level of renal arteries completely occluding the aorta and common iliac arteries with no blood flow seen beyond the renal artery level up to the aortic bifurcation; moderate to severe stenosis is noted at the origin of both renal arteries because of thrombus (Figures and ). Multiple abdominal collaterals are seen with multiple collaterals in the anterior and lateral abdominal wall and paraspinal collaterals (). Extensive blood work-up including thyroid function test and autoimmune and thrombophilia work-up was all unremarkable. No cause of aortic thrombosis and TDHB was identified. Initial recommendation of the vascular surgeon was to follow up in the clinic with no intervention as it is a chronic process, and the patient was asymptomatic. Since the patient had uncontrolled hypertension despite being on maximum doses of four antihypertensive medications, eventually he underwent percutaneous stenting of bilateral renal arteries which was followed by an improvement in the BP and renal function and reduction in doses of antihypertensive medications. The patient also underwent permanent pacemaker insertion for TDHB. The patient was also placed on warfarin and was advised to see the vascular surgeon after 3 months. Unfortunately, the patient did not follow up.

pmc-6011152-1

Case 1 concerned a 71-year-old male presenting with gait difficulties and vertigo. Cranial MRI revealed a low and focal contrast-enhancing nodular tumor in the left cerebellar hemisphere and upper vermis (). The lesion appeared hypointense relative to gray matter on T1 weighted (T1w) images and moderately hyperintense on T2w images. Tumor margins were best displayed on diffusion weighted images (DWI). The suspected clinical diagnosis was metastasis from an unknown primary tumor. Microsurgical resection of the tumor was performed. Histopathological work-up revealed a highly cellular tumor consisting of small cells with scant cytoplasm and round-oval or pleomorphic, hyperchromatic cells in the cerebellum. A part of the tumor showed a nodular architecture and a desmoplastic component (Gomori staining). Some tumor cells expressed the neuronal differentiation marker synaptophysin. The diagnosis was paucinodular desmoplastic MB (WHO grade IV). Tumor cells showed nuclear YAP1 and cytoplasmic GAB1 staining, while nuclear staining for ß-catenin and staining for p53 was negative. There was no MYC- or MYCN-amplification detectable (). The patient's condition was stable in the continuing course; however a week later he was affected by a severe pneumonia and died due to respiratory insufficiency.

pmc-6011152-2

Case 2 was a 72-year-old male who was referred to the hospital because of change of personality and loss of weight. Cranial MRI showed a large low contrast-enhancing mass in the right cerebellar hemisphere consisting of a lateral solid component and a small medial cystic. The tumor caused occlusive hydrocephalus but no surrounding edema (). MR revealed diffusion restriction of the solid tumor part and peripheral susceptibility effects, e.g., hemosiderin deposits. Once again, the first suspected diagnosis was metastasis without presence of any neoplasm in the patient history; the second radiological diagnosis was MB. The possibility of a high-grade glioma was discussed but neglected due to its rare occurrence in the cerebellum in this age group. Prior to surgery an external ventricular drainage was inserted. Complete tumor resection was performed. Histopathological examination showed a highly cellular cerebellar tumor consisting of sheets of uniform cells with a high nuclear/cytoplasmic ratio and round to oval hyperchromatic nuclei. Many tumor cells reacted for synaptophysin. There was no evidence of a nodular or desmoplastic component in the Gomori staining. The diagnosis was that of a classical MB (WHO grade IV) (). The tumor cells did not show staining for YAP1, GAB1, and p53 or nuclear staining for ß-catenin. Evidence of MYC- or MYCN-amplification was not found. The postoperative course was uneventful and the ventricular drainage was removed without evidence of an enlarged ventricular system. However, the patient was found dead seven days later in his room. The cause of unexpected death could not be clarified, since an autopsy was not allowed.

pmc-6011155-1

An 86-year-old female with a history of metastatic ovarian cancer presented to the ED with painful bilateral lower extremity edema and a left lateral leg ulceration. Her metastatic ovarian cancer had been diagnosed by malignant pleural effusion five months earlier, and she had completed neoadjuvant chemotherapy with carboplatin and Taxol approximately one week prior to this presentation. She was admitted to the hospital and started on cefazolin for left lower extremity cellulitis on hospital day one. On admission, plain films and ultrasound did not reveal any evidence of osteomyelitis, fracture, DVT, or abscess to the left lower extremity. On exam, she had 3+ pitting edema below the knee bilaterally as well as chronic venous stasis changes. The patient also had a venous ulcer (approximately 2 cm in diameter) on the anterolateral aspect of the distal third of her left lower leg. At the time of admission, this venous ulcer had some serous weeping but no purulent drainage or fluctuance on examination. Her initial Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was 4, suggesting a low risk for necrotizing fasciitis; however, on hospital day 3, her CRP began to uptrend and she became febrile. At this point, her antibiotics were switched from cefazolin to vancomycin to cover MRSA. On hospital day five, the patient was noted to have a new erythematous area over the anterior left knee, inferior to the patella (). Ultrasound revealed a small fluid collection superficial to the patellar tendon in the infrapatellar region measuring 3.3 × 2.5 × 0.4 cm (). The infrapatellar bursa was aspirated and sent for culture. The patient was started on piperacillin-tazobactam, given the patient's immunocompromised status and subsequent risk for atypical and gram-negative organisms. An MRI was performed on hospital day seven (this was delayed due to the patient's pacemaker) but did not reveal any evidence of osteomyelitis. The patient was clinically improved after starting piperacillin-tazobactam, and vancomycin was discontinued on hospital day seven. On hospital day eight, aspirate cultures returned with Pseudomonas aeruginosa; she was stable for discharge at that time and was sent out with a ten-day course of levofloxacin (culture was pan-sensitive) and close follow-up with infectious disease.

pmc-6011161-1

A 48-year-old female with known breast carcinoma was screened for possible dissemination with whole-body computed tomography (CT) and a bone scintigraphy scan. The bone scan revealed a tumor in the entire right tibia. The patient reported no symptoms from the tibia tumor. A plain X-ray and magnetic resonance image (MRI) confirmed an intraosseal tumor that extended from 4 cm below the knee joint proximally to about 4 cm from the ankle joint distally (). An open biopsy confirmed an adamantinoma histology. Different treatment options were thoroughly discussed with the patient, including a lower leg amputation with disarticulation of the knee, a total tibia resection and reconstruction with a tibia allograft, or a custom-made tibia EPR, which was eventually selected. The tumor was resected with an extensive anteromedial approach, and the defect was reconstructed with a custom-made, silver-coated, modular endoprosthesis of the Modular Universal Tumor and Revision System (Implantcast®, Buxtehüde, Germany) (). The knee joint was reconstructed with a metal-on-poly articulation with a (unique) metal-on-metal hinge mechanism (). The ankle joint was reconstructed with a metal-on-poly hinge joint with a talar replacement, stabilized with a trans-talar and trans-calcanear hydroxyapatite-coated stem. A supplementary screw was used to add stability in the subtalar joint. The endoprosthesis was enveloped in a Trevira (Implantcast®) tube to facilitate the attachment of soft tissues and the patella tendon (). A microvascular latissimus dorsi musculocutaneous flap was anastomosed to the tibia artery (end-to-side) and concomitant vein and wrapped around the prosthesis to avoid dead space and allow tension-free closure. In addition, a medial gastrocnemius muscle flap was transposed to cover the patellar tendon region; this was covered with a meshed split-thickness skin graft. A histological analysis of the resected specimen showed an adamantinoma that had spread throughout the entire tibia and the margins were wide: an unaffected periosteum as an anatomic barrier and a minimum of clear soft tissue margin of 3 mm. Due to intracortical location of the tumor, no massive muscle excision was needed. The knee joint was immobilized in extension for 6 weeks to facilitate patella ligament attachment to the tube. Then, the joint was gradually mobilized. After 6 months, the patient's gait was almost normal, with mild limping. Local MRI and chest radiographs performed during the 8 years of follow-up showed no signs of local recurrence or distant metastasis. No loosening of the stem or other mechanical problem was reported. In a routine follow-up, in addition to radiographs, we used a local MRI with a metal artifact reduction sequence (MARS) technique [], which enables to observe local recurrences of the tumor around the massive titanium endoprosthesis. Eight years postoperatively, the patient had most of the time no pain and could mobilize freely. The patient resumed working full-time as a kindergarten teacher, and she has maintained her previous active lifestyle (except downhill skiing). On her latest follow-up visit (at 8 years), the knee range of motion was 0–105 degrees, ankle dorsiflexion was 5 degrees, and ankle flexion was 35 degrees. In the latest follow-up visit, we used 4 patient-related outcome (PRO) measures. The Musculoskeletal Society Tumor Score (MSTS) was 77%; the Oxford Knee score (OKS) was 35/48; the Toronto Extremity Salvage Score (TESS) was 80/100; and the 15D was 0.87/1. The metal-on-metal prosthesis caused an increase in metal ion concentrations: cobalt was 6 ppb and chromium was 8 ppb. The silver coating created a mild, local skin argyria pigmentation, with cosmetic discomfort [] ().

pmc-6011162-1

A 26-year-old male healthy Asian student presented to an emergency department in Australia with sudden onset generalised weakness affecting predominantly his lower limbs after eating dinner. The patient reported difficulty standing and difficulty lifting his arms without any muscle pain or paraesthesia, headache, or back pain. Although he had experienced multiple similar episodes over the past month, these had been less severe and always self-resolved. It was unclear to the patient if these episodes of weakness were associated with food intake or exercise. On further questioning, the patient reported 15-kilogram weight loss over the past three months and a four-day history of nonbloody diarrhoea, which resolved one week prior to presentation. He had otherwise been well and was playing soccer regularly. He had no relevant family history, was on no regular medications, and denied using illicit drugs. On examination, the patient appeared mildly diaphoretic but was afebrile. Heart rate was irregular, at 92 beats per minute and blood pressure was 118/60 mmHg. He had a normal respiratory rate at 18 breaths per minute with oxygen saturations of 98% on room air. Neurological examination revealed symmetrical proximal weakness of upper and lower limbs with normal tone, reflexes, and sensation. The decrease in power was more noticeable in the lower limbs compared to the upper limbs. In addition, there was a mildly enlarged painless thyroid gland, with a slight hand tremor, but no signs of thyroid acropachy or thyroid eye disease. Heart sounds were normal with no murmurs, gallops, or rubs, and lung fields were clear to auscultation and percussion. There was no abdominal tenderness to palpation. Bedside electrocardiogram revealed atrial flutter with a variable ventricular rate. Initial biochemistry showed hypokalaemia with potassium of 2.3 mmol/L (reference range: 3.5–5.2 mmol/L) and hypomagnesaemia with magnesium of 0.59 mmol/L (reference range: 0.70–1.10 mmol/L). Plasma glucose level was 7.1 mmol/L. Complete blood count, urea and creatinine, liver function, phosphate, and creatinine kinase were unremarkable. Hypokalaemic periodic paralysis was suspected and thyroid function testing was performed. This revealed hyperthyroidism with a TSH of <0.01 mU/L (reference range: 0.40–4.00 mU/L), T4 of 44 pmol/L (reference range: 9–19 pmol/L), and T3 of 25 pmol/L (reference range: 3.0–5.5 pmol/L), suggesting a diagnosis of TPP. TSH receptor antibodies were elevated at >40 U/L (reference range: <1.8 U/L), confirming a diagnosis of Graves' disease. This was further supported by a radionuclide thyroid scan showing diffuse uptake in the thyroid gland. Antithyroperoxidase antibodies, antithyroglobulin antibodies, and urinary electrolytes were not measured in this case. Initial treatment in the emergency department included 40 mmol of intravenous KCl and 10 mmol of intravenous MgSO4. The patient's weakness resolved during inpatient admission. Potassium was 4.7 mmol/L and magnesium was 0.88 mmol/L on repeat testing 6 hours after the initial biochemical tests. Thereafter, potassium remained normal throughout the admission, without rebound hyperkalaemia or the need for further replacement. The patient was discharged home the next day on Carbimazole 20 mg twice a day and Propranolol 20 mg three times a day. No potassium supplementation was prescribed on discharge and he was not started on anticoagulation for the atrial flutter due to his low risk of thromboembolism. One month after discharge, the patient reported no further episodes of weakness. His T4 and T3 had normalised, although TSH remained at <0.01 mU/L. His potassium was normal at 4.1 mmol/L. Ongoing monitoring of thyroid function was recommended, with a plan for radioiodine ablation or thyroid surgery if antithyroid medical therapy was unsuccessful. However, further follow-up information was not attainable as the patient returned to his home overseas.

pmc-6011163-1

Thirty-three-year-old male with diabetes and seizure disorder presented to the emergency department (ED) with worsening dyspnea and hemoptysis. Two weeks prior to his ED presentation, he was treated with antibiotics for community acquired pneumonia with minimal improvement. Upon further inquiry, patient admitted to vaping for the past 2 months with overtly increased exposure time and has experimented on new flavors. He denied previous or current recreational drug use. CT scan of the chest showed diffuse ground glass opacities and bilateral patchy consolidation (). He had worsening hypoxia that required noninvasive ventilation. His echocardiogram was otherwise normal. Bronchoscopic examination failed to demonstrate airway lesions. Bronchoalveolar lavage (BAL) revealed increasing blood in four sequential aliquots confirming diagnosis of DAH (). BAL cell count showed greater than 30,000 RBCs and 800 WBCs, 42% neutrophils, 36% lymphocytes, 1% eosinophils, and 21% macrophages. All inflammatory serologies were unremarkable: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibody (ANA), and anti-antineutrophil cytoplasmic antibodies (ANCA). In addition, serum eosinophil count, anti-glomerular basement membrane (GBM) antibodies, and anti-phospholipid antibodies were all normal. Urine toxicology screen which includes amphetamines, cannabinoids, and cocaine was negative. There was no microbiologic growth on all BAL specimens. Patient was treated with pulse dose steroids after DAH was confirmed with BAL aliquots (). He underwent right wedge resection lung biopsy which revealed evidence of bland pulmonary hemorrhage () with no evidence of capillaritis or diffuse alveolar damage (DAD). Prussian blue iron staining was also noted which reflects old hemorrhage (). His symptoms improved with complete resolution of alveolar hemorrhage on chest CT scan after 2 weeks (). His steroids were tapered quickly and he has not used a personal vaporizer since then.

pmc-6011165-1

A 41-year-old man without any underlying diseases such as cardiovascular disease was hospitalized for spontaneous gum bleeding, epistaxis, and lower limb ecchymosis. Laboratory data on the admission date showed leukocytosis (WBC, 15,820/mm3; promyelocyte, 66%, with Auer rod), anemia (Hb, 9.5 g/dL), thrombocytopenia (PLT, 22,000/mm3), and abnormal coagulation profile (fibrinogen, 29 mg/dL; fibrin degradation product (FDP), 68.5 mcg/mL; d-dimer, 19.81 mcg/mL; prothrombin time (PT), 20.5 sec; international normalized ratio (INR), 1.92; partial thromboplastin time (PTT), 29 sec). Other laboratory data were as follows: C-reactive protein (CRP), 8.97 mg/dL; total bilirubin (T-bil), 0.73 mg/dL; aspartate aminotransferase (AST), 60 U/L; alanine transferase (ALT), 100 U/L; and serum creatinine (Scr), 0.9 mg/dL. His baseline electrocardiogram (ECG) was normal (). Bone marrow aspiration and biopsy disclosed APL with PML-RARα. ATRA at a dose of 45 mg/m2/day (40 mg twice daily) was administered. On the third day of therapy, oxygen saturation abruptly dropped to 90% without oxygen supplementation. Chest X-ray (CXR), ECG, and echocardiography did not show any abnormalities. In order to prevent DS, intravenous methylprednisolone was administered at a daily dose of 80 mg–120 mg according to the clinical signs and symptoms. Idarubicin (12 mg/m2/dose) was administered starting on the fourth day for four doses. WBC progressively elevated to 46,830/mm3; therefore, 1000 mg hydroxyurea twice daily was also added starting on the seventh day. On the 11th day of therapy, WBC and promyelocyte decreased to 6,310/mm3 and 14%, respectively. ATO infusion at a dose of 0.15 mg/kg was initiated; however, dizziness and chest pain occurred during infusion. ECG showed complete AV block with a heart rate (HR) of 40–50 beats/min (bpm) (). The electrolytes and liver function tests were all within normal limits (Na, 138 mmol/L; K, 4.6 mmol/L; Ca, 2.29 mmol/L; Mg, 0.95 mmol/L; T-bil, 0.77 mg/dL; AST, 15 U/L; ALT, 14 U/L). Thus, ATO and ATRA were immediately discontinued, and aminophylline was administered. After interruption of ATRA for three doses, complete AV block persisted, but his HR partially recovered to 60 bpm. ATRA was rechallenged with 40 mg once daily on the 13th day of therapy under relatively stable vital signs. On the following morning, his HR decreased to 30 bpm and he required a nonrebreathing mask to maintain oxygen saturation. CXR showed bilateral pulmonary edema, and echocardiogram revealed a large amount of pericardial effusion with signs of cardiac tamponade. In addition, ECG showed complete AV block with QRS widening, and acute renal failure also occurred (Scr, 1.4 mg/dL; blood urea nitrogen (BUN), 45.2 mg/dL; Na, 133 mmol/L; K, 5.2 mmol/L; Ca, 2.22 mmol/L; Mg, 0.93 mmol/L; P, 4.9 mg/dL; T-bil, 1.22 mg/dL; ALT, 17 U/L). Therefore, ARTA was immediately postponed, and a temporary pacemaker was inserted. Steroid treatment was switched to dexamethasone (8 mg twice daily) because of suspected DS. Pericardiocentesis and thoracentesis were performed. Two days after stopping ATRA, ECG showed sinus bradycardia with a first-degree AV block and diffuse ST elevation. The Naranjo adverse drug reaction probability scale [] indicated a score of 7 for ATRA, suggesting it was the probable cause of arrhythmia in this episode. The PML-RARα mutant was still detected using polymerase chain reaction (PCR) of blood sampled on the 19th day of therapy. Consequently, ATRA was resumed the following day with 10 mg twice daily. His HR decreased from 70–90 bpm to 60–70 bpm with stable vital signs. ECG demonstrated sinus rhythm with first-degree AV block. The dose of ATRA was gradually titrated up to 30 mg twice daily on the 24th day. Sinus tachycardia with occasional premature ventricular complexes was noted. The pacemaker was removed on the 27th day. During follow-up, ECG showed normal sinus rhythm (), and echocardiogram revealed minimal pericardial effusion. Complete molecular remission was documented by bone marrow aspiration done on the 38th day of therapy using flow cytometry and PCR for PML-RARα. Thereafter, the patient received three cycles of consolidation with ATRA-based chemotherapy. No further bradycardia episode was reported. The patient has been free of leukemia for 1.5 years after the diagnosis.

pmc-6011167-1

A 20-year-old fit and healthy man presented with sudden collapse after running for 3 hours under the hot sun (ambient temperature 39°C) during a marathon competition. After finishing his run for 35 km, he felt unwell and collapsed. He was brought to the hospital immediately. No measures were taken to lower his temperature during the 30-minute transferral to the hospital. Upon arrival to the hospital, he was confused (Glasgow coma scale: 13/15, E4M5V4). His blood pressure was 100/60 mmHg, heart rate 120/min, rectal temperature 42.2°C (axillary temperature 41.5°C). He was given 2 L of intravenous normal saline and rapidly cooled with ice pillow and ice water-soaked towel. He was then transferred to ICU for close monitoring. His rectal temperature was brought down to 39°C (axillary temperature 38.5°C) in an hour time. He was then transferred to ICU. His cerebral CT scan, electrocardiogram, chest X-ray, and bedside echocardiogram were unremarkable. Laboratory results was shown in . He remained oliguric (urine output < 10 ml/hour) despite initial fluid resuscitation. Hemodialysis was commenced on Day 1 of admission. On Day 3 of admission, his arterial blood pH, renal panel, and electrolytes were all normalized and he had regained urine output (urine output 10–20 ml/hour). He was fully conscious and alert (GCS 15/15). Unfortunately, on Day 4 of admission, he started to complain of severe headache followed by 6 episodes of generalized tonic-clonic seizures, each episode lasting for 1-2 minutes, in a one-hour time. There was no regaining of consciousness in between seizures. The episodes were associated with drooling of saliva, tongue biting, and postictal drowsiness. He was intubated and started on intravenous midazolam infusion, intravenous phenytoin, and intravenous levetiracetam. Electroencephalogram done on the same day showed generalized continuous slowing. However, no epileptic activity was observed during the bedside EEG monitoring. MRI brain done on the same day () showed bilateral, symmetrical vasogenic oedema involving both frontal and posterior parieto-occipital, cerebellar hemispheres, and predominantly the cortex and subcortical white matter regions. DWI and ADC sequence showed no area of restricted diffusion. The finding was consistent with posterior reversible encephalopathy syndrome (PRES). He had another 2 episodes of generalized tonic-clonic seizures on Day 5 of admission that lasted less than 1 minute. Loading dose of intravenous sodium valproate 1 g was added. His repeat blood tests, including renal panel, complete blood count, pH, and electrolytes, were all normal. On Day 6 of admission, he was able to produce 3 L of urine per day and hemodialysis was stopped. His midazolam infusion was weaning off slowly. He was fit-free since then. On Day 7 of admission, he was extubated and transferred to general ward. His antiepileptics agents were changed to oral form. His seizure was well controlled with oral phenytoin, valproate, and levetiracetam. A repeat MRI brain done on Day 14 of admission () showed near complete resolution of the previous vasogenic oedema. He was discharged well with oral valproic acid and levetiracetam.

pmc-6011169-1

A 63-year-old woman was transferred to our department from the internal medicine clinic of the hospital with a diagnosis of acute abdomen due to possible rupture of the bladder. The patient was admitted in the internal medicine clinic three days earlier due to acute abdominal pain. She had a known medical history of uncontrolled type 2 diabetes and cirrhosis of the liver with extensive ascites. The bladder had been drained and urinary retention was observed (over 2 liters of urine). The white blood cell count was 21300, C-reactive protein (CRP) was 14,83 mg/dl, and procalcitonin was 1,1 ng/ml. Intravenous empiric antibiotic treatment with ciprofloxacin (800 mg/day) and amikacin (1000 mg/day) was immediately initiated, with good recovery until the third day. On day 3, the patient presented rebound tenderness, involuntary guarding, and a completely rigid “washboard” abdomen with percussion tenderness. Bowel sounds were absent. She was haemodynamically unstable. Blood pressure was 85/42 mmHg and heart rate was 114 beats per minute. Urine analysis was normal and urine culture was negative. The blood findings were as follows: WBC was 11,900 and CRP was 8,35 mg/dl. Although there was amelioration in the blood tests (as compared with baseline values), the clinical symptoms and the condition of the patient deteriorated. The computed tomography (CT) scan of the abdomen indicated presence of gas within the anterior bladder wall. The latter was not enhanced with contrast material, indicating necrosis (Figures and ). Instillation of contrast solution in the bladder through the indwelling catheter during CT revealed extravasation in the peritoneal cavity (). Based on these results, emergency surgery was decided. During laparotomy, we initially encountered extensive necrosis of the perivesical fat with presence of pus in the retropubic space. After the incision of the bladder, full thickness necrosis of the wall was revealed, with the exception of the anatomical area of the trigone. A partial cystectomy with debridement of the necrotic tissue and preservation of both ureters was decided (Figures –). The abdominal cavity was further explored and peritoneal lavage was performed due to the presence of diffuse peritonitis. A suprapubic catheter and two surgical drains (one in the hepatorenal fossa and the other in the rectouterine pouch) were used. The patient was transferred to the intensive care unit in a critical condition and succumbed 12 hours later due to multiple organ dysfunction and septic shock. Histology revealed extensive necrosis of the entire bladder wall.

pmc-6011170-1

Our case is of a 9-year-old Caucasian male who lives with his mother, stepfather, older brother (15 years), and sister (12 years). He has preexisting diagnoses of Autistic Spectrum Disorder (ASD) and Attention Deficit Disorder (ADD), inattentive subtype, but was not taking any regular medication at the time of presentation. He presented to our inpatient service as an emergency from a local acute hospital due to concerns regarding minimal dietary intake. He was detained under Section 2 of the Mental Health Act for assessment and treatment, due to his resistance of treatment in the community and lacking Gillick competence. He was admitted to a specialist psychiatric ward for children under 12 years. At the time of presentation his most prominent and concerning symptoms were refusing food and fluids, mutism, school refusal, and self-neglect, including refusal to engage in his personal care regime. It was the severity of these symptoms that was particularly concerning to his family and to professionals. His restriction of dietary intake resulted in severe weight loss and admission to hospital for nasogastric (NG) tube feeding, his body mass index (BMI) being less than 12kg/m2 at the time of admission (less than 0.5th percentile). His sole method of communication was typing on an iPad to his mother and his personal care was restricted to wearing his pyjamas and a coat for several days without washing or changing. His mother reports that prior to admission there were also incidents of urinary and faecal incontinence. He would not sleep in his bed but was instead sleeping on the floor outside his parents' bedroom in the “foetal position”. When family members attempted to touch him, he became physically aggressive and hit out at them. He was diagnosed with Pervasive Refusal Syndrome at this time. In May 2015, his stepfather gave him a haircut, which he particularly disliked. This appears to have been a trigger for the subsequent observed behaviours. Following this, he became more controlling of his dietary intake and became selectively mute. In particular, he stopped talking to his stepfather and eating any food that he had prepared. This progressed in severity to the extent that, in January 2016, he completely stopped eating and drinking and became completely mute. He was admitted to the local acute hospital for NG tube insertion and intravenous (IV) fluids at this point. Blood biochemistry indicated acute reduced renal function which resolved with administration of IV fluids. Subsequently, he began to eat and drink small amounts and was discharged after a few days. However, a pattern of refusal to eat and drink developed, resulting in further six admissions to hospital with similar symptoms of dehydration and acute kidney injury over the following 6 months. During this time, his presentation deteriorated to the severity of behaviours described above. He also communicated via letters to his mother and typing on his iPad that he would like to die and return as a Labrador dog or as a superhero. On two occasions, during his admissions to the acute hospital, attempts were made to administer medication to him. However, on each occasion he refused and only one dose of fluoxetine was administered via his NG tube. He also refused administration of aripiprazole and no doses were given. Intramuscular administration of psychotropic medication did not seem proportional given the lack of evidence for medication being successful in PRS cases []. Given that he began to accept oral intake and made attempts to remove his NG tube, it was also not appropriate or practical to continue with administration of psychotropic medication via this route. Our patient was born at full term by Caesarean section with no complications. The pregnancy was described as uneventful and there was no exposure to alcohol, tobacco, or illicit substances. He achieved his developmental milestones within a normal timeframe. No concerns were raised prior to starting nursery school (age 4 years). He was noted to be “different” to other children in his class and was diagnosed with ASD at the age of 6 years using Autism Diagnostic Observation Schedule (ADOS) and extensive interviews with his mother. A cognitive assessment, the Wechsler Intelligence Scale for Children (WISC-IV), was completed at age 6, which showed an IQ of 78, indicating a low normal intelligence (and therefore no intellectual disability). In this case it is pertinent to consider the nature and extent of his preexisting ASD symptoms prior to his symptoms at presentation in 2016. In his records, he is described as struggling with understanding abstract questions, complex reasoning, and problem solving skills. He displayed formal speech at times and had difficulties with reciprocal conversation. He spoke quietly with deficits in prosody and struggled to contribute in class at school, but there was no history of muteness at the time of ASD diagnosis. He could misinterpret instructions and had a literal understanding of language. He showed avoidance of eye contact and limited facial expressions. He preferred to be alone, struggled with imaginative play, and did not initiate interaction with other children. He had specific interests in superheroes and dressing in these costumes. In younger childhood, he showed specific interest in vacuum cleaners and washing machines. He also was observed to make repetitive movements in the form of a “jerking” of his neck. Since admission to the ward in July 2016, he made comparatively quick progress and was discharged into the community in November 2016. Initially he began to eat only a small amount of prepackaged food. He was reviewed by the dietician, who advised prescribing supplement drinks, which he initially accepted two of. The rationale of the admission to hospital was clearly explained to him and that, as long as he was not eating or drinking, he would need to be in hospital. We believe that this triggered his decision to begin to accept diet and fluids. He accepted a change in clothes and in his personal hygiene routine with the assistance of nursing staff. He made it clear to his mother (via written letters) that he wanted to be at home and that he believed that there was no need for him to be in hospital as he was accepting diet and fluids and had changed his clothes. He also attended his tribunal himself to appeal his detention under Section 2 of the Mental Health Act but did not communicate to the tribunal panel, verbally or otherwise. He made steady progress with regard to dietary intake and gradually accepted full meals served on the ward. His engagement with nursing and allied therapy staff began to improve; he began to communicate with hand gestures (“thumbs up or down”) and use written notes. We therefore agreed to allow him to leave the ward to his family home at weekends. He also started to very quietly verbally communicate with his mother. He began to smile and laugh appropriately with staff and peers. However, he would hide his mouth with his fingers to avoid others seeing this. When asked if he would like to participate in activities, he declined, but when asked if he would, he engaged in a full timetable and appeared to enjoy some of the activities. We believe this is an indication of his preference to avoid activities and a symptom of his ASD. After a period of assessment, speech and language therapy (SALT) advised staff on the phrasing of questions to avoid confusion. Occupational therapy (OT) guided nursing staff, with whom he had established a better therapeutic relationship, with regard to reestablishing his daily skills including dressing and self-care. He progressed to having day leave from the ward and started to attend a specialist school with support in the classroom to assist his communication and learning needs. Although he is not verbally communicating other than with his mother, we believe that his prognosis is good based on his current progress. We expect him to make a full recovery to his premorbid functioning with support in the community. It is difficult to comment upon what his ultimate level of communication will be like as his ASD is likely to have an impact upon this. However, given his young age, with specialist support for his ASD he has the potential to develop coping strategies. At discharge from hospital, he indicated no signs of distress with his level of communication and interaction (i.e., verbally with his mother). However, he will require further input from the community team to accurately assess his long term goals regarding verbal communication for the future.

pmc-6011174-1

A 46-year-old Japanese woman with known SLE was admitted to our hospital due to sudden weight loss and respiratory distress. Her vitals on arrival were a temperature of 37.1°C, heart rate of 96 bpm, blood pressure of 148/82 mmHg, respiratory rate of 18 per minute, and oxygen saturation of 95% in room air. The patient was given 50 mg of oral prednisolone immediately after admission. Approximately 3 weeks after the start of treatment, the dosage of prednisolone was reduced to 45 mg/day. However, the patient suddenly developed hemoptysis and respiratory distress. A chest X-ray () revealed infiltrative shadows in both lung fields, with greater density in the right lung. A computed tomography (CT) scan showed pulmonary infiltrates along the peripheral bronchovascular bundles and ground-glass opacities (). We diagnosed the patient with DAH-induced hypoxemia accompanying SLE and initiated high-dose corticosteroid therapy (methylprednisolone 500 mg/day). However, respiratory distress worsened, and we began immunosuppressive therapy (cyclophosphamide 750 mg/day) 3 days after the start of high-dose corticosteroid therapy. The patient was also transferred to the intensive care unit (ICU) and placed on mechanical ventilation. Although the patient produced copious quantities of bloody secretions after intubation, the secretions were reduced when APRV was set to the highest airway pressure (35 cmH2O). We administered oxygen through an oxygen mask (flow rate: 6 L/min) while in the ICU. Under these conditions, the arterial oxygen partial pressure (PaO2) was 55.1 mmHg, and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F ratio) was 125.2. APRV resulted in substantial improvements to respiratory function, with a fraction of inspired oxygen (FiO2) of 0.60 and a PaO2 of 117.6 mmHg. High-dose corticosteroid therapy was administered using 500 mg/day of methylprednisolone for 3 days, 250 mg/day of methylprednisolone for 3 days, and 125 mg/day of methylprednisolone for 3 days, after which the patient was given 50 mg/day of intravenous prednisolone every day while in the ICU. During approximately 3 consecutive weeks of APRV and steroid therapy, the patient demonstrated gradual improvements in respiratory function, and a CT scan after extubation showed that the pulmonary infiltrates and ground-glass opacities had disappeared (). Mechanical ventilation was discontinued 25 days after admission to the ICU. The patient was moved to the general ward and continued on oral steroid therapy (methylprednisolone 16 mg/day) until discharge. The patient's respiratory and hemodynamic parameters from admission to ICU discharge are summarized in . The patient was successfully discharged from hospital 102 days after admission.

pmc-6011191-1

A 38-year-old North African man, with no past medical history, consulted our out-patient clinic for a painless left scrotal mass. There was no history of previous orchitis or scrotal contusion. He noted the mass a month ago. A physical examination found a 2 cm palpable mass in the upper pole of his left testis. There were no signs of scrotal inflammation. The mass had a firm consistency and regular margins. Palpation of his right testis and the lower pole of his left testis were normal. Routine blood tests were normal. As a testicular tumor was strongly suspected, a bioassay of testicular tumor markers was ordered. Alpha-fetoprotein, human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) were in the normal ranges. There was no bacterial growth in urine analysis, including Mycobacterium tuberculosis screening. A scrotal ultrasound showed a homogeneous testicular parenchyma, with a conserved vascularization on Doppler. An extratesticular mass was observed, attached to the upper pole of his testis. The mass was isoechoic to the testis parenchyma, and poorly vascularized Doppler (Fig. ). He underwent a radical inguinal orchiectomy. We first performed a high ligation of the spermatic cord. The operative specimen included the testis and the tunica vaginalis in one piece (Fig. ). The macroscopic aspect of the supratesticular mass looks similar to splenic tissue (Fig. ). There were no macroscopic lesions of the testis and the spermatic cord. His postoperative course was uneventful. He was discharged on the second postoperative day. Histological examination of the operative specimen confirmed the presence of regular splenic tissue in the suspect mass, without any signs of malignancy. The splenic proliferation had its proper and regular capsule, demarcating it from the testis. Testicular pulp, the albuginea and the tunica vaginalis had a preserved microscopic architecture (Fig. ). He was examined 3 weeks after orchiectomy and he was examined again 2 months after the orchiectomy in our out-patient unit. An abdominal ultrasound showed an habitual location with standard measurements and a regular aspect of his spleen.

pmc-6011201-1

The present case involves a 62-year-old woman admitted to surgical oncology unit for a planned transanal excision of a large polyp of the mid rectum. Following a positive faecal occult blood test, colonoscopy detected the presence of a large flat neoplastic lesion, 50 mm in maximum diameter, tending to grow laterally and involving one-third of the rectal lumen (Fig. ). The lesion was located in the mid rectum, 8 cm from the anal verge and, based on its detailed endoscopic appearance during chromoendoscopy, was labelled as a lateral spreading tumour granular type (LTS-G). The endoscopic biopsy demonstrated a tubular adenoma with high-grade dysplasia. In view of the size of the lesion, endoscopic mucosal resection was considered unfeasible and it was decided to proceed with surgical excision transanally by TAMIS. The day before surgery, patient had standard mechanical bowel preparation and at the time of anaesthetic induction received preoperative antibiotics (Cefazolin 2 g and Metronidazole 500 mg). The procedure was performed under general anaesthesia and the single incision laparoscopic surgery port (SILS™ Port, Covidien) was adopted and traditional laparoscopic instruments were used. The surgery lasted 2 h with no intraoperative complications. The rectal wall defect was washed with a povidone-iodine solution (Fig. ) and then closed by a running suture performed with a barbed suture (Covidien V-Loc™). Patient had unremarkable past medical history and on admission routine laboratory profile was in normal range: WBC, 6.34 × 103/μL (reference value, 4–10 × 103/μL); platelets, 231 × 103/μL (reference value, 150–400 × 103/μL); prothrombin time (PT), 11.4 s (reference value, 10.0–13.4 s); activated partial thromboplastin time (APTT), 34 s (reference value, 22.0–43.0 s); fibrinogen, 301 mg/dL (reference value, 160–450 mg/dL). Following surgery, the patient was allowed to be mobilised and to have a regular diet with no restriction, and standard prophylaxis for venous thrombosis was started with low molecular weight heparin (LMWH). On day 3, the patient developed a spike in temperature without any suspicious clinical evidences. She was passing flatus associated with the mucous discharge, the abdomen was soft and not tender, and digital rectal examination did not show any lump or collection. Laboratory data disclosed both a deranged coagulation profile with marked APTT prolongation (126 s), PT 12.5 s, fibrinogen 897 mg/dL, raised white blood cells count (WBC 21.00 × 103/μL) and procalcitonin 0.52 ng/mL (reference value, < 0.5 ng/mL). Cross-mixing studies of patient plasma and normal pooled plasma (25, 50, and 75%) insufficiently corrected the APTT (99, 71, and 56 s, respectively) after 2 h of incubation at 37 °C. Lupus anticoagulant assay was negative by dilute Russel viper venom test (DRVVT). FVIII, FXI, and FIX were in normal range whereas coagulant activity of FXII was < 1%, tested using one-stage APTT-based clotting assay. Considering the spike in temperature and laboratory data, a computed tomography (CT) of abdomen and pelvis was performed to rule out any collection and source of infection. The CT scan did not show any pelvic abscess, but there was evidence of perirectal fat suffusion related to the recent procedure. A rigid proctoscopy was performed showing the evidence of the partial dehiscence of rectal wall defect suture; no other abnormalities were noticed. Antibiotic therapy was started with intravenous ciprofloxacin and metronidazole (500 mg) three times a day. From a therapeutic point of view, there is a general consensus that patients with an FXII inhibitor do not need any correction of the APTT and so our patient did not receive any therapy in addition to antibiotics. LMWH standard prophylaxis for venous thrombosis, initially suspended, was resumed. In the next 7 days, the patient had no more fever and laboratory data improved while APTT was still prolonged (70 s). She was discharged home with no further intervention. The histopathological report demonstrated a tubular adenoma with low- and high-grade dysplasia with free excision margins. 45 days later endoscopy showed a complete mucosal healing, APTT and FXII activity were back to the normal value (38 s and 50%, respectively). Time course of APTT and FXII activity during follow-up after surgery is pictured in Fig. . Blood and tissue samples used were prepared and stored by CRO-Biobank (CRO National Cancer Institute, Aviano, Italy).

pmc-6011251-1

A 20-year-old male patient was referred to our clinic in December 2017 for acute liver failure (ALF) of unknown origin. History revealed no pre-existing medical conditions, anamnesis was empty for exposition with predisposing agents such as previous drug-use, promiscuity, pork consumption or autoimmune disorders. The initial presentation at the peripheral hospital occurred due to indolent jaundice and fatigue-syndrome. Physical examination of the patient showed distinct jaundice and hepatic encephalopathy grade I. Laboratory studies revealed massively elevated transaminases with an alanine aminotransferase (ALT) level of 4645 U/l and an aspartate aminotransferase (AST) level of 4956 U/l (normal < 50 U/l) while cholestatic liver enzymes were merely elevated (alkaline phosphatase (AP) 216 (normal 25–124) U/l and gamma-glutamyl-transferase (γ-GT) 91 (normal < 55 U/l)). Furthermore, liver synthesis parameters were significantly impaired with a total bilirubin of 14.8 (normal 0.3–1.2) mg/dl, an international normalized ratio (INR) of 2.39, and a factor V activity of < 35 (normal 70–120) % with a consecutive MELD score of 28 points. Additionally, there was no serological evidence for autoimmune hepatitis, viral hepatitis (A-E), Wilson’s disease or hemochromatosis. Laboratory parameters on admission are presented in Table . According to the above-mentioned parameters and circumstances, the patient was diagnosed with a cryptgenic ALF and treated supportively by substitution of vitamin K, ursodeoxycholic acid, and lactulose. Accordingly, liver maximum capacity (LiMAx) test on admission revealed significant impairment of enzymatic liver function of 147 (normal > 315) μg/h/kg. Two days later, laboratory parameters further deteriorated: the patient now fulfilled the KCC for non-acetaminophen-induced ALF ((1) unknown etiology; (2) INR > 3.5; (3) bilirubin > 17.4 mg/dl), and he was considered for urgent liver transplantation at Eurotransplant. Three days later, the patient became anuric and hemodialysis was necessary with a MELD score of 40 points. However, a suitable donor organ was not available. Two days later, the patient developed hepatic encephalopathy grade III-IV accompanied by increasing inflammatory parameters in blood (increase of leukocytes, C-reactive protein, and procalcitonin) and respiratory insufficiency, which made mechanical ventilation necessary. Computed tomography scan revealed bilateral pneumonia and antibiotic (imipenem) and antifungal (caspofungin) therapy was initiated (Fig. ). Bloodstream infection with evidence of Staphylococcus aureus was ascertained concurrently. Due to pulmonary Staphylococcus aureus sepsis the patient was no longer suitable for urgent LT at that critical juncture. Interestingly, LiMAx test, which was performed under mechanical ventilation, showed an improvement of enzymatic liver function to 169 μg/h/kg indicating liver regeneration, though laboratory tests (deterioration of conventional liver synthesis parameters, rapid increase of inflammatory parameters in blood) and clinical course (multi-organ system failure: liver and renal insufficiency, encephalopathy, sepsis due to Staphylococcus aureus pneumonia) indicated lethal outcome. However, from then on, clinical condition of the patient improved, inflammatory parameters were declining, urine excretion resumed, and extubation was possible after 6 days of mechanical ventilation. Accordingly, CT scan showed regressive pulmonary infiltrations (Fig. ). Slowly, with significant time delay of 11 days, liver synthesis parameters recovered, and the patient could be moved out from the intensive care unit after 21 days of treatment. At that time point, the LiMAx test demonstrated distinct improvement to 299 μg/h/kg. The following mini-laparoscopy revealed cholestatic changes of liver parenchyma with regenerative nodules and capsular fibrosis (Fig. ). Histopathology of the obtained liver biopsy illustrated advanced connective tissue of the parenchyma in sense of septal fibrosis (F3) accompanied by severe cholestatic liver damage without evidence for precise etiological correlation (Fig. ). Finally, the patient could be dismissed from our clinic in markedly ameliorated condition after 38 days. Outpatient three-month follow-up examination showed complete clinical recovery while biochemical parameters were entirely within normal ranges (AST: 21 U/l, ALT: 34 U/l, total bilirubin 0.4 mg/dl, INR: 1.07, MELD score: 7). Accordingly, LiMAx illustrated complete restitution of enzymatic liver function with a value of 614 μg/h/kg (normal > 315 μg/h/kg). Figure shows the timespan between events and summarizes the diagnostic/ therapeutic measures that were taken.

pmc-6011332-1

The second patient is a 5-year old boy, born as a first child to healthy non-consanguineous parents. The mother reported two previous early spontaneous abortions. Otherwise, the family history is unremarkable. He was born after an uneventful pregnancy in the 37th week of gestation after a spontaneous start of the delivery. The boy’s birth weight was 2430 g (10-25P), birth length 46 cm (10-25P), and head circumference 34.5 cm (75-90P). He had gastroesophageal reflux in the first few months, the abdominal ultrasound was normal. Due to apnoic attacks the boy was administered to hospital at the age of 5 months. The pH-metry confirmed gastroesophageal reflux, ECG and CMCRF were normal. The neurologist described a mild hypertonus and related mild motor delay. He sat independently at 9 months of age and he started walking at 20 months of age. The parents noted shortness of breath and tiredness after simple physical tasks, therefore, he was evaluated by a paediatric cardiologist. Two haemodynamically significant ASDs were noted and a slightly dilated right ventricle; corrective surgery is planned. The tests of acylcarnitine profiles and aminoacids in blood and organic acid in urine were normal. At the age of four his height and weight were in the normal range (height 99.2 cm (17P), weight 16.1 kg (46P)), however, the head circumference showed macrocephaly - 53.8 cm (>97P). Microarray analysis (180 K CGH array, Agilent Technologies- Fig. ) revealed a de novo microduplication of 2.06 Mb in chromosome 2p16.1p15 region (arr[GRCh37] 2p16.1p15(60308869_62368583)× 3 dn). No other pathogenic genomic imbalance was detected in the proband’s sample.

pmc-6011335-1

The patient is a 43-year-old woman who was admitted for the first time for a progressive non-painful, mobile mass of the right inguinal fold evolving for 7 months. The medical history of the patient included childhood asthma, chronic tonsillitis, seven pregnancies and four children, caesarean section and abortions. Pelvic ultrasound showed a heterogeneous suspicious non-circumscribed mass measuring 5 cm in its longer axis. It was localised in the right inguinal region and showed cutaneous adhesions. CT scan confirmed the presence of this inguinal mass, measuring 5.8 × 4.9 × 3.2 cm and extending within the right femoral triangle in contact with the long adductor muscle, without enhanced contrast, and without locoregional lymph node (Fig. ). The patient underwent a chirurgical biopsy. The pathological analysis diagnosed a granular cell tumor (Abrikossoff’s tumor) without any malignant signs (absence of mitosis, necrosis and cytonuclear atypias). Tumorectomy of this inguinal mass were performed three weeks later. At the gross pathology examination, the tumoral tissue was homogeneous with a greyish stain. Its margin was not well defined and the hypodermic, dermic were involved. One lymph node was discovered and was invaded. The epidermis was not ulcerated (Fig. ). Histologically, collagen bundles were infiltrated by cords of large, polygonal cells with inconspicuous cell membrane and homogenous finely granular cytoplasm. Nuclei were round or oval and presented large nucleoli, vesicular of dark chromatin and sometime an intranuclear vacuole. Mitosis were rare and the mitotic index was low (1 mitosis/ 10 High Power Field). There was a slight increase of the nucleo-cytoplasmic ratio. We observed no necrosis (Fig. ). Fanburg-Smith score of malignancy was of 3: nuclear pleomorphism, tumor cell spindling, vesicular nuclei with large nucleoli. Immunohistological finding showed a cell expression of S-100 protein, vimentin, calretinin (slight), α-Inhibin, CD56, CD57, CD68 and neuron specific enolase (NSE). (Fig. ) Cytokeratin AE1-AE3, EMA, calponin, caldesmon, desmin, smooth muscle actine, myosin, myogenin, chromogranin, synaptphysin, Neurofilament proteins, Glial fibrillary acidic protein, CD1a, renal cell carcinoma antibodies were all negative. Therapeutic marker, estrogen receptors, progesterone receptors, androgen receptor, HER2, CD117 ALK, C-MET, ROS1 and PDL-1 were negative too. Due to microscopic resection and the nodal status, a large surgical revision with an inguinal curage was then decided at the oncology committee. Pathological evaluation did not reveal tumor tissue in the tumorectomy region but showed metastatic invasion by granular cells in four of twelve lymph nodes, without capsular rupture. Adjuvant chemotherapy was excluded because of very low mitotic activity. To reduce the risk of local recurrence, adjuvant radiotherapy on the tumor bed and right inguinal area of ​​50 Gy in conventional fractionation was delivered. After 10 months after the end of radiotherapy, the patient is in complete remission. Due to the unpredictable tumor, the follow up strategy is a physical examination with a CT scan every 4 months for the first 2 post-operative years, then every 6 months for up 5 years and yearly thereafter, as a sarcoma.

pmc-6011350-1

Patient: a 9-year, 7-month-old Japanese girl (height 127 cm, body weight 33 kg, body mass index 20.5 kg/m2). Primary complaint: severe deformity of the femur. Past medical history: no notable history. The patient was referred to our facility with complaints of progressive deformity of her right femur associated with an SBC and pathological fractures. The girl experienced a pathological fracture of her right femur due to bone tumor when she was 4-years, 6-months old (Fig. ), which her previous physician treated with lesion curettage and fixation (Fig. ). Pathological findings confirmed the presence of an SBC. Bone healing was confirmed 6 months later, at the age of 5 years. The fixator was removed and steroids were injected simultaneously with an artificial bone graft into the lesion (Fig. ). She wore a functional brace after the surgery. However, 1 week after removing the fixator, a new fracture developed in the same location of the bone, following a minor external injury (Fig. ). After a 5-week trial of conservative treatment using steel wire skeletal traction, she underwent fixation with application of a hip spica cast. Five months after the second fracture, at the age of 5 years and 5 months, weight-bearing on the affected limb was progressively initiated, and she was discharged with full weight-bearing status at the age of 5 years and 7 months. She was monitored as an out-patient (Fig. ). Subsequently, she developed a fracture again at the age of 6 years and 4 months, following a fall (Fig. ). She was once again treated with a steel wire skeletal traction. Once bone healing was achieved, the inside of the cyst was curetted and a cannulated screw was inserted to reduce localized pressure (Fig. ). Approximately 6 weeks after surgery, a hip spica cast was applied, which was followed by the use of a functional brace. During the follow-up period, severe bowing of her right femur developed, which was progressive (Fig. ). At the age of 9 years and 6 months, the femur fractured, with the fracture originating at the cannulated screw. The screw was subsequently removed (Fig. ) and the patient was referred to our facility at the age of 9 years and 7 months. On first examination at our facility, the femur was deformed, with a bowing of approximately 90° in the central area of the femur and an internal rotation of 60°, with incomplete fractures observable in the same area (Fig. ). We proceeded with resection of a 7-cm portion of the bone, which included the SBC, corrected the alignment and applied an Ilizarov fixator to gradually lengthen the thigh. We also cut a portion of healthy bone from the proximal femur (approximately 10 cm from resected lesion), for use as bone extension at the site of resection (Fig. ). One week after surgery, extension of the bone was initiated at a speed of 1 mm/day, completing the process in 4 months. Fixation was then maintained until the callus matured (Fig. ). Once callus maturation was achieved, the external fixator was gradually removed to prevent re-deformation. On histopathologic examination of the surgically resected bone, fibrillation of the medullary cavity was increased, and a small formation, identified as inorganic-like material, was scattered throughout; these findings were consistent with a fracture due to a bone cyst (Fig. ). At present, 3 years after surgery, correction of the deformity has been maintained, and our patient does not experience any limitations in daily activities or regular exercise (Fig. ).

pmc-6011475-1

We describe the case of a 27-year-old white woman who had experienced an emergency caesarean delivery at 39 weeks for fetal distress with no postpartum complications. As part of our ongoing study “Vaginal delivery after caesarean section”, she underwent saline contrast sonohysterography 6 months after the caesarean section. The caesarean scar had a small indentation and the remaining myometrium over the defect was 7.5 mm (Fig. ). In the current pregnancy, she had a dating scan at around 11 weeks with no remarks. She came for a transvaginal ultrasound examination at around 13 weeks as part of our study. This scan revealed a duplex pregnancy with one viable intrauterine fetus with normal anatomy and placenta located high on the anterior wall and a small gestational sac (8 mm) with a yolk sac without embryo was located in the caesarean scar (Fig. ). There was no extensive vascularity surrounding the sac. One corpus luteum was found in each of the two ovaries. She was asymptomatic. She was informed that not enough evidence existed to advise a specific management of this condition. After discussion with her and her husband, expectant management was chosen with a new ultrasound examination after 5 weeks. She came to our ultrasound department at 18 weeks, 22 weeks, and 30 weeks of gestation. She remained asymptomatic. The ectopic gestational sac was not visualized with transvaginal or transabdominal scans at the 18 weeks examination (Fig. ). The niche in the scar and the thickness of the thinnest part of the remaining myometrium appeared unchanged at all visits. The intrauterine pregnancy developed normally with no signs of abnormal placentation. At 30 weeks of gestation the ultrasound appearance of the scar area did not indicate any contraindications for vaginal delivery. The thickness of the lower uterine segment (LUS) was 4.9 mm (Fig. ). In agreement with our patient, vaginal delivery was planned. The staff of the labor ward was fully informed. She was admitted to the labor ward with irregular contractions in week 37 + 0. Her cervix dilated to 3 cm with no further progress. Due to that oxytocin augmentation was administered for 3 hours. The duration of active labor was 6.5 hours. A healthy male neonate weighing 2985 g was delivered, with Apgar scores 9–10 at 1 and 5 minutes and umbilical cord pH 7.27. The placenta delivered spontaneously and total blood loss was 250 ml. The postpartum period was without any complications, and she was discharged home the next day. At a follow-up visit 6 months postpartum, saline contrast sonohysterography showed no signs of the previous CSP, and the remaining myometrium over the hysterotomy scar defect was 5.7 mm (Fig. ). Ethical approval for the ongoing study was obtained by the Ethics Committee of the Medical Faculty of Lund University, Sweden, reference number 2013/176. Our patient has given permission for publication of this case report in a scientific journal.

pmc-6011843-1

A 60-year-old female patient met with a traffic accident while walking. The patient had a coma and was taken to a nearby hospital for emergence treatment, then shifted to our hospital for further treatment after 2 weeks. On presentation, the patient was conscious, oriented and hemodynamically stable. The left lower limb was tracting, there was contusion over the hip. The right elbow was casting. The radiographs revealed a fracture of the right Ulna olecranon, a combination of ipsilateral left femoral neck and sub-trochanteric fracture. His neurovascular examination is normal. Evaluations are femoral neck fracture Garden II (nondisplaced) and sub-trochanteric fracture Seinsheimer IIIB (AO 32A1.1), AIS 14, ISS 27 (). Eventually the fracture was treated with a long Gamma3 nail () with ORIF to the sub-trochanteric fracture, and the femoral neck fracture was treated with closed reduction. During fluoroscopy, care was taken to ensure that all the screw threads crossed the fracture lines and compression was obtained at the femoral neck region. After 12-month follow-up, the fracture was union and has no evidence of avascular necrosis (). But at 4-year follow-up, the patient began to complain of the pain. The X-ray showed an evidence of the necrosis of the femoral head (). One year later, she had a total hip arthroplasty for the severe pain.

pmc-6011856-1

The patient was a healthy 25-year-old man with a one-year history of right ankle pain following trauma. He had met a car accident while walking. One year earlier, he had undergone open reduction and internal fixation on his right ankle for fracture at another hospital. A tibia diaphysis spiral fracture was fixed by the anterograde intramedullary nail with infra-patellar approach. An ankle malleolar fracture was fixed by the locking plate and cannulated cancellous screws with direct lateral and medial approach. He had finally consulted us because of worsening ankle pain while walking. On physical examination, there was tenderness in the anteromedial joint space of the right ankle. Slight ankle swelling was noted. Dorsiflexion of the right ankle was 10°, similar to that of the left ankle, but plantarflexion was restricted to 38°, compared with 60° on the left, but the ankle instability test was negative. The first three months, even though we performed intra-articular injections, arthroscopic synovectomy for osteoarthritis, and the fixation implant removal in order to release implant irritation, his ankle pain persisted. The AOFAS ankle score at that point in time was 50 . Radiographs showed moderate narrowing of the ankle joint and forward displacement of the talus (-A, B). Computed tomography of the right ankle showed an osteochondral defect on the anterolateral surface of the distal tibial plafond (). This was diagnosed as progressive osteoarthritis caused by an osteochondral defect on the anterolateral surface of the distal tibial plafond, and surgical repair of the osteochondral defect was recommended. Three months later, the osteochondral graft was performed on the patient's right ankle. The patient was placed in the supine position under general anesthesia. The lower extremity was prepared and draped in the standard sterile fashion. We inserted the 2.0 mm K-wire in his right calcaneus, then skeletal traction was done in order to open his right ankle joint space if necessary. Next, 10 mL of fluid was injected intra-articularly to distend the ankle. The anterolateral ankle arthroscopy portal was established in the routine fashion, and global arthroscopy was performed. The osteochondral defect was identified about the anterolateral plafond which site was enthesis of the anterior tibiofibular ligament (), and osteochondral lesions of the tibia and talus were identified. An anteromedial portal was established. The osteochondral lesions were probed, and the osteochondral lesions were diagnosed as grade 2 according to the classification of the International Cartilage Repair Society . We performed multiple OAT in the anterolateral plafond at the anterolateral wall with extension of the anterolateral portal. The anterolateral osteochondral defect was measured 9 mm × 20 mm (). The plug donor site was the lateral corner of the patellar groove in the right knee joint. Under direct vision, we harvested 2 bone plugs from the normal bone deeper than the osteochondral defect for the preparation of the recipient site in order to accept the osteochondral plugs from the donor site in maximum plantarflexion. Then, the dilator was interpositioned into the recipient site, and a radiograph was taken to calculate the inclination angle between the dilator and tibial plafond. Therefore, we thought that the smooth surface was obtained by the inclination of the grafted plugs. According to the angle required, two 8-mm osteochondral autograft plugs ramped 35° and 45° were harvested from the donor site (), and transferred into the anterolateral plafond at an angle to re-contour the articular surface and make it smooth. Both harvest and transplantation of osteochondral autograft plugs were performed by open approaches for transplantation in the exact slope. After this procedure, the surface of the anterolateral wall of plafond was almost completely smooth (). The depth of these plugs was 20 mm, deeper than the osteochondral defect. It was confirmed that the deepest area of the plugs consisted of a macroscopically normal bone. We used press-fit technique in order to stabilize the osteochondral plugs. Stabilization of the osteochondral fragments relied on tight interference with the host bone. In case of difficulty with press-fit technique, a screw made of polylactic acid and hydroxyapatite was prepared, but it was never used. Postoperatively, the foot was placed in a short leg cast, and the patient was advised to ambulate non-weightbearing for a 4-week period. The patient had an uneventful postoperative course, and a range of motion exercises were initiated immediately after cast removal at 4 weeks, with partial progressive weightbearing allowed during the next 4 weeks. The patient was able to return to standing work 10 months after surgery. The most recent magnetic resonance imaging scans at 2 years after surgery showed that the cartilage in the anterolateral joint surface was almost intact, and there was no osteonecrosis (). At 3 years the post-operative X-rays of the ankle joint depicted a larger osteophyte, compared with the pre-operative situation, in the anterolateral corner of the right tibial plafond. No forward displacement of the talus was evident on the lateral view of the right ankle joint, while the respective joint space was preserved (). On the latest physical examination, the patient complained of mild pain in his right ankle while walking, but could walk for 30 min. Dorsiflexion of the right ankle was 0°, compared with 10° on the left, and plantarflexion was 30°, compared with 60° on the left. The postoperative AOFAS ankle score was 80. The patient remained asymptomatic with respect to the donor sites of the right knee. He was able to return to carpenter's work on a five-day week, but remained with minor ankle pain on standing up and walking for more than half an hour over the 3-year observation period.

pmc-6011861-1

A 35 year-old male was referred to our unit with a right distal tibial non-union, which had progressively deviated into varus deformity. He had initially sustained a high-energy, multifragmentary compound (Gustilo–Anderson Type 3A) fracture in a road traffic accident 4 months earlier. After successful treatment of the soft tissue injuries he had been managed in a below-knee, weight-bearing Sarmiento cast. His non-union (, ) was stabilised with a retrograde 10 mm × 340 mm expandable nail. Regular clinical and radiological follow-up revealed that the non-union had solidly united within 6 months of the operation (). The patient was able to walk comfortably and return to work as a carpet fitter. Nine months after insertion of the nail there were radiological appearances suggestive of calcaneal resorption around the neck of the nail, therefore we recommended removal of the nail. This was attempted under general anaesthesia using the kit and technique described by the manufacturer. After deflation of the nail, attempts were made to “back-slap” the nail out of the tibia. This failed as the nail fractured at the junction between the valve and the metal fins (). Further attempts to remove the nail using grabbers and a mole wrench were unsuccessful and the procedure was abandoned. The patient returned to theatre for a second attempt. Initial attempts at removal through the entry point using grabbers and large diameter crown drills were unsuccessful as the broken end of the nail had split, with the fins separating, like an inverted cone. A further attempt at pushing the nail down using an antegrade nail was also unsuccessful. Eventually, the nail was removed piecemeal through a 6 cm × 2 cm antero-medial tibial window using a Midas Rex® burr (Medtronic Ltd., Watford) (). The tibia was protected in a below-knee walking cast for 6 weeks and the patient made an uneventful recovery with no further complications.

pmc-6011861-2

A 67 year-old female was referred with a right distal tibial non-union with progressive valgus deformity following a fragility fracture five months previously. It was initially treated with locked antegrade intra-medullary nailing. The initial nail was removed and an expandable retrograde nail was inserted. Two months later an Ilizarov frame was applied over the nail to provide further compression. The non-union united and the frame were removed three months later. The nail was left for six more months in order to allow further consolidation of the non-union. The first attempt to remove the expandable nail was made ten months after insertion. The standard technique to remove the nail was attempted, but again the procedure failed because the nail fractured at the junction between the valve and the fins. Further attempts to remove the nail with grabbers at that time were unsuccessful and the procedure was abandoned. Two months later, a second attempt was undertaken as the patient was complaining of ankle pain. The track from her primary nail was re-opened from the proximal end and the expandable nail was successfully pushed out using an antegrade nail. This procedure passed without incident and she made a good post-operative recovery.

pmc-6011861-3

A 73 year-old male presented to our unit with a multifragmentary Pilon fracture and was treated with primary retrograde expandable Fixion® nail. Regular follow-up revealed good union at 22 weeks and the patient was able to walk without significant pain. Although we recommended the removal of the nail, the patient didn't consent on it. Two and a half years later the patient requested removal of the nail because of chronic heel pain presumably due to slight prominence at the bottom end of the nail. Using the standard extraction technique an attempt to remove the nail was performed but resulted in fracture of the nail at the junction of the valve and fins (). The end cup and valve were removed but attempts to remove the remaining part of the nail with grabbers failed and the procedure was abandoned. The patient was advised to keep the nail remnant unless it becomes symptomatic. He is still under follow-up and currently asymptomatic.

pmc-6012632-1

A 79-year-old male with a past medical history significant for pancreatic pseudocyst secondary to idiopathic acute pancreatitis diagnosed two years ago presents with severe acute gastrointestinal bleed with a hemoglobin of 5.8 g/dL. Throughout the week prior to admission, the patient had been experiencing melena. He was admitted to the intensive care unit for supportive care including pantoprazole infusion, blood transfusion and close monitoring. CT scan of the abdomen revealed a complex pancreatic mass representing a bleeding pancreatic pseudocyst with an interval increase in size when compared with the previous CT scans (Figure ). The patient underwent esophagogastroduodenoscopy (EGD)/endoscopic ultrasound (EUS) which showed submucosal bulging likely from extrinsic compression on the proximal gastric body and fundus with small clean-based ulcer on the top of this bulge (Figure ). No fresh or old blood was noted in the stomach, and the esophagus and duodenum both appeared normal. EUS confirmed the presence of anechoic lesion with hyperechoic shadowing suggestive of cyst/pseudocyst with bleeding located in the tail of the pancreas. The lesion measured approximately 50 x 50 mm in the maximal cross-sectional diameter. The patient continued to have melena and a decrease in hemoglobin to 6.3 g/dL for which an additional two units of packed red blood cells (PRBCs) were provided. Interventional radiology was asked to perform mesenteric angiogram with hope that may help identify and control the source of bleeding, however, angiogram did not demonstrate any active bleeding vessel (Figure ). Ultimately, the bleeding stopped spontaneously. The patient had another EGD/EUS which again noted two openings over the greater curvature of the stomach suggestive of fistulous communication of the lesion with the stomach lumen. A bullet-tipped catheter was inserted into the lumen and aspiration showed blood consistent with hemorrhagic pancreatic pseudocyst fistulizing into the stomach and causing severe upper gastrointestinal bleed. Follow-up CT abdomen one year later revealed calcification in the head and uncinate process of pancreas along with scarring in the uncinate process, consistent with chronic pancreatitis (Figure ). Additionally, the pseudocyst that was abutting the stomach wall had resolved.

pmc-6013867-1

A 73-year-old white man presented to our emergency department with a 3-day history of left lower extremity swelling and acute-onset shortness of breath. On evaluation, he was tachycardic with a pulse of 113, hypertensive with a systolic blood pressure of 130-170 mmHg, and demonstrated poor oxygen saturation of 81% on room air. He was supported with continuous positive airway pressure (CPAP) and supplemental oxygen while a computed tomography angiogram (CTA) was obtained, which revealed a saddle PE (Fig. ). Tissue plasminogen activator (tPA) was administered and he was started on a heparin infusion and admitted to our intensive care unit (ICU) for management. He remained on the heparin infusion for 3 days, during which he continuously improved and was eventually weaned to 3 L oxygen via nasal cannula. On hospital day 2, he was transferred to intermediate level of care. Per hematology recommendations, he would have to be on indefinite anticoagulation due to the massive PE he had sustained, the source of which was a left lower extremity popliteal deep vein thrombosis (DVT). The plan was to transition him from the heparin infusion to enoxaparin twice per day with hematology follow-up in 1 month. On the day of discharge, however, he had sudden onset of right leg numbness and weakness below the level of his hip. He had previously been working with physical therapy and had been able to walk 200 feet with the assistance of a walker during each session. A physical examination revealed decreased sensation to light touch, 2/5 strength in right hip flexion and right knee extension and flexion, and loss of right patellar reflex. Left leg physical examination was normal at that time. An emergent head computed tomography (CT) scan was ordered due to concern for a possible stroke, and neurology was consulted. The head CT was negative for infarction or hemorrhage. Neurology was concerned for spinal cord infarction versus hematoma and recommended emergent magnetic resonance imaging (MRI) of his thoracic and lumbar spine. The MRI revealed a left psoas hematoma (Fig. ). A CT of his pelvis performed the same day also showed a right psoas and iliacus hematoma. Due to these findings, hematology recommended discontinuing enoxaparin and reverting to a low intensity heparin infusion, as well as placement of an inferior vena cava (IVC) filter. The following day his left leg began exhibiting the same symptoms as his right leg. There was concern regarding the risk of progressive and irreversible nerve damage due to compression if the hematomas were not promptly drained. IR was consulted and advised that if the drainage were to occur while our patient was on anticoagulation, the risk of rebleeding into the retroperitoneum would be high and potentially nullify any benefit from drainage. Our patient would also be at risk of hemodynamic instability if the current hematomas were acting as tamponades against further bleeding. An additional complicating factor was the risk of further thrombosis due to the presenting saddle PE. Hematology was consulted for recommendations on pausing anticoagulation, but they were hesitant to offer a timeframe as there was no established safe period to enable this type of procedure to take place. Eventually, a window period of pausing the heparin infusion for 3 hours pre-procedure and up to 6 hours post-procedure was decided upon in the event that our patient agreed to have the drainage performed. Throughout this sequence of events, our patient and his wife were aware of the plans and considerations on how to proceed. They were informed of the recommendations and concerns made by neurology, hematology, and IR, as well as the risks and benefits of intervention versus non-intervention. After speaking with his wife, our patient decided to undergo the procedure. The low intensity heparin infusion was stopped 3 hours beforehand and the IR team then performed drainage of the right retroperitoneal hematoma, placing two pigtail catheters in our patient’s right flank (Fig. ). In total, the hematoma was drained of 215 milliliters of blood, 10 milliliters of which were drained during the procedure itself. The left psoas hematoma was not found to be amenable to drainage. Our patient tolerated the procedure well, and the heparin infusion was restarted 6 hours after it was completed. A repeat neurological examination demonstrated improved lower extremity strength bilaterally as well as the return of sensation to light touch. Hip flexion improved to 3/5 bilaterally, and knee flexion and extension improved to 4/5 bilaterally. Deep tendon reflexes remained absent. Four days later, the pigtail catheters were removed. His recovery was complicated by anemia requiring blood transfusions totaling 4 units of packed red blood cells (PRBC). Other sources of potential bleeding were evaluated and not found. A repeat CT on hospital day 10 (Fig. ) showed a stable right-sided hematoma, and our patient did not experience any further neurologic deficits. He was transitioned again from the heparin infusion to enoxaparin after 3 more days. His hemoglobin and hematocrit remained stable. During this time, he worked with physical therapy, who recommended discharge to a skilled nursing facility where his strength began to improve somewhat. Follow-up was scheduled with neurology and hematology. On hospital day 18, he was safely discharged.

pmc-6013898-1

A nine-year-old entire male greyhound presented with head trauma resulting from a collision with a park bench. The dog had no previous significant clinical history. On examination, cardiovascular parameters were stable overt distress in the animal not apparent. The dog was ambulatory with normal gait and posture devoid of proprioceptive deficits. Thorough head inspection revealed subcutaneous emphysema between the eyes and a superficial cut to the right dorso-orbital region. Mild right unilateral epistaxis was noted. The dog resented palpation of the right frontal bone and a communication with the sinonasal cavity was inferred by the presence of a flail segment movement of the bone synchronous with respiration. Cranial nerve examination demonstrated bilateral delayed pupillary light reflex (PLR) and normal pupil size, the remainder of the neurological examination was within normal limits. A right-sided frontal bone depression fracture was suspected founded on clinical findings. Radiographs and Computer Tomography (CT) imaging with a three-dimensional reconstruction of the skull were performed under general anaesthesia (see Fig. -). Radiographs of the cervical spine were unremarkable. CT imaging revealed a comminuted, depressed fracture of the frontal bone that extended from the level of the maxillary recesses up to the caudal aspect of the frontal sinuses at the level of the dorsal aspect of the right maxillary, nasal and frontal bones. Surgical repair of the defect was warranted to reestablish sinus architecture and mechanical stability []. Further, fracture comminution is associated with soft tissue contracture leading to cavitation with connective tissue scarring and sequestrum formation [], fracture repair addresses soft tissue injury and may minimize long-term risks of complication []. Surgery was carried out three days after admission. A standard dorsal approach to the frontal bone was taken (Fig. -). A malleable highly porous Ti mesh (0.2 mm thickness with 1.4 mm by 0.6 mm elongated pores) was contoured to the patient’s skull (Fig. -). The Ti mesh was firmly seated against the skull and a 1.6 mm drill bit, with a 6 mm stop, was used to drill pilot holes through the mesh into the skull. A 2.1 mm diameter resorbable poly-L, D-lactic acid (PLDLA) thermoplastic pin was placed into the pilot hole and the ultrasonic trode applied to the proximal end of the pin (Fig. -). The ultrasonic device was activated melting the outer surface of the pin and allowing it to be advanced into the pilot hole. Further pilot holes were drilled around the periphery of the Ti mesh at 20-25 mm intervals and thermoplastic pins inserted until the Ti mesh was adequately secured. The surgical site was flushed with copious volumes of sterile saline and a sheet of gentamycin-impregnated collagen (Collatamp®, EusaPharma) was overlaid on the implant to prevent infection and assist in achieving a pneumatic seal. Prophylactic intravenous antibiotic cover was provided by clavulanated amoxicillin (20 mg/kg; Augmentin, GSK) given 30 min pre-operatively and every 90 min thereafter for surgery duration. Recovery from anaesthesia was uneventful. Post-operative analgesia was provided with intravenous methadone (0.2 mg/kg q4hours; Comfortan, Dechra). Postoperative radiographs and CT images showed satisfactory positioning of the Ti mesh and adequate coverage of the calvarial defect (Fig. -). The dog was discharged two days after surgery with a 10 day course of oral carprofen (2 mg/kg q24hours; Rimadyl, Zoetis) and oral clavulanic acid-amoxicillin (20 mg/kg q12h; Synulox, Zoetis). The dog re-presented two weeks after discharge, with hyperthermia and swelling around the surgical site. Subcutaneous oedema was present in the absence of emphysema. Sampling for culture and sensitivity was prevented by the absence of nasal and surgical site discharge, exposure of the wound to obtain a swab sample was deemed inappropriate. Antibiotic therapy effective against common nasal pathogens [] was introduced with oral cefalexin (20 mg/kg q 12 hours; Therios, Ceva) for ten days. Clinical signs had resolved at 1 week post treatment. At the six weeks recheck, the physical examination was within normal limits. No pain was elicited upon palpation of the surgical site and no indications of infection recurrence was found. Radiographs and CT of the skull revealed a slight uplift of the mesh at its most rostral aspect from the frontal bone. Mesh uplift was not a clinical concern at this stage. Radiographs and CT scan at 6 months revealed soft tissue swelling between the rostral mesh portion and the skull (see Fig. -). Decision was made to trim and re-contour the uplifted mesh. The procedure and recovery were uneventful and no further complications were experienced. At 2 years assessment, radiographs and CT scan confirmed adequate contouring and positioning of the Ti mesh. Radiographs revealed a bone-dense opacity between the rostral part of the mesh and the skull potentially associated with mesh micromotion stimulating periosteal reaction (Fig. -). The degree of new bone formation around the mesh periphery was difficult to ascertain radiographically, however, clinical examination was unremarkable and cosmetic result was satisfactory. The owners did not raise any further concerns regarding the patients ability to participate in normal lifestyle and activity.

pmc-6013898-2

A ten-year-old neutered female Cavalier King Charles Spaniel presented for a gradually enlarging mass on the right frontal bone with no associated clinical signs. The mass was bone-like and non-painful upon palpation. The remainder of clinical examination was within normal limits. Fine needle aspirates of the mass revealed evidence of bone remodeling compatible with a neoplastic process yet were not diagnostic, further investigation was declined and mass excision by surgery was planned. Radiography and CT imaging of the skull were performed under general anaesthesia to advise surgical planning and custom 3D Ti mesh design for use in reconstruction following tumour resection. Thoracic and abdominal CT scan were also taken for staging and were negative for metastatic disease. CT imaging of the skull revealed a 25 mm (h) × 20 mm (diam.) ovoid mass arising from the right frontal bone above the right orbital globe (see Fig. -). Surgery was implemented a week later. The same surgical approach was performed (Fig. -). A craniotomy with resection margins guided by the use of customised template was performed (Fig. -). The resection guide was computer modelled from CT imaging and printed using a sterolithographic system. A pre-contoured Ti mesh aided by computer modeling and computed manufacture was firmly seated to the patient’s skull covering the defect (see Fig. -). The protocol for thermoplastic pin placement and application of gentamycin-impregnated collagen sheet was as described for patient 1. Non-resorbable methacrylate-butadiene-styrol (MBS) pins were used in case 2 for fixation in contrast to resorbable PLDLA described in case 1. Prophylactic intravenous antibiotic cover was provided by cefuroxime (20 mg/kg; Zinacef, GSK) given 30 min pre-operatively and every 90 min thereafter for surgery duration. Recovery from anaesthesia was uneventful. Post-operative analgesia was provided with intravenous methadone (0.2 mg/kg q 4 h) and in travenous paracetamol (10 mg/kg q12hours; Perfalgan, BristolMyers squibb). Postoperative radiographs and CT images showed satisfactory positioning of the Ti mesh and adequate coverage of the calvarial defect (Fig. -). The dog was discharged six days after surgery after uneventful hospitalisation. The dog re-presented two weeks after discharge for suture removal. Surgical wound has healed and physical examination was within normal limits. At the ten weeks recheck, physical examination was within normal limits and the owner reporting no restrictions on the patient’s activity. There was no pain elicited upon surgical site palpation. Radiographs and CT of the skull revealed satisfactory positioning of the mesh. A histological diagnosis of multilobular osteochondrosarcoma was made with potential of local recurrence advised. At 7 months assessment, owners reported a small bone-like mass near the resection site. This clinical finding was consistent with either local recurrence or reactive osseus proliferation. CT scan identified the region of proliferation as dorsal and to the right side of the Ti mesh. The mesh remained well localised and confluent with the skull. The remaining clinical examination was unremarkable and cosmetic result was satisfactory. Owners did not raise concerns regarding overall quality of life and further investigation of the mass was declined. A request to examine the patient at 1 year follow up was again declined by the owner due to long travel distance.

pmc-6013943-1

A 44-year old male was referred following investigation for chest pain and dyspnoea. He had no pre-existing co-morbidities. Physical examination revealed feeble femoral pulses and he was found to be hypertensive with marked differences between the upper and lower limbs (systolic blood pressure upper limb 190mmmHg, lower limb 75 mmHg, with an ankle brachial index (ABI) of 0.39). Electrocardiogram revealed evidence of severe left ventricular hypertrophy. This was confirmed with echocardiography which also demonstrated a tricuspid aortic valve with significant aortic regurgitation in the presence of an aortic root aneurysm of approximately 9 cm. Left ventricular function was preserved. Computerised tomography angiography (CTA) was performed to evaluate the aortic pathology in further detail (Fig. ). The scan noted an aortic root aneurysm (8.8 cm), in addition to the presence of severe aortic coarctation, with subtotal occlusion and a lumen less than 6 mm in size. The coarctation was just distal to the left subclavian artery, at the aortic isthmus. There was clear evidence of collateral circulation to the descending thoracic aorta via the subclavian and intercostal arteries. Coronary angiography confirmed a right dominant coronary system with no significant coronary disease. A multidisciplinary team meeting took place and a consensus was agreed to proceed with a two staged hybrid approach, with the first phase involving an endovascular approach to stent the coarctation, followed by a second stage to perform the surgical repair of the aortic root aneurysm. The first stage to stent the coarctation was unsuccessful via the femoral approach, as the guidewire could not cross the coarctation. Assessment through angiography via the left brachial artery showed complete obstruction at the aortic isthmus. The decision was then made to proceed to a single stage surgical approach to treat both lesions. After induction of anaesthesia, arterial lines were placed in the left radial and left femoral artery. A right infraclavicular incision and a right groin incision was made this was to establish peripheral arterial cannulation access to the right axillary and right femoral artery. An 8 mm dacron graft was anastomosed to each vessel for indirect cannulation. Median sternotomy was performed to access the mediastinum and expose the heart and aorta. Following heparinisation cardiopulmonary bypass (CPB) was established with venous return from bi-caval cannulation. The body temperature was cooled to 25 degrees Celsius. The right superior pulmonary vein was used for venting. Once the cross clamp was applied, complete cardiac arrest was achieved using Custodiol 25 ml/kg crystalloid cardioplegia via a retrograde cannula through the coronary sinus. A further top up of cardioplegia was given once the aorta was opened through direct cannulation of the coronary ostia. The aortic root, valve and ascending aorta were excised. The coronary ostia were fashioned as buttons from the native aortic root. The coronary ostia were noted to be significantly displaced, with distorted anatomy due to the patient’s disease process. Therefore, 8 mm dacron grafts were attached end-to-end to each ostia, with view to performing the modified Cabrol technique later following replacement of the root. The heart was then retracted in a cephalad position to access the posterior pericardium. A vertical incision was made to expose the descending thoracic aorta (DTA). An end to side anastomosis was formed with a 20 mm dacron graft to the DTA (Fig. ). This graft was then routed posterior to the inferior vena cava (IVC) and anterior to the right inferior pulmonary vein (RIPV), adjacent to the right atrium (RA). Root replacement was then performed with a 25 mm biological valved-conduit, as this was favoured by the patient over a mechanical prosthesis, despite the risk of a difficult redo procedure in the future. The 8 mm dacron grafts attached to the coronary ostia were anastmosed to the root conduit as neo coronary ostia. The distal part of the valved-conduit was anastomosed to the proximal arch under selective antegrade cerebral perfusion (SACP). Finally, an end to side anastomosis was fashioned between the 20 mm extra-cardiac graft (attached to the descending thoracic aorta) and the ascending portion of the valved-conduit. Valve-sparing root replacement was not considered in this patient due to the grossly abnormal aortic anatomy. Following rewarming and deairing the patient was successfully weaned off CPB. The bypass time was 160 min, the cross-clamp time was 120 min, and the SACP time was 40 min. Haemostasis was achieved and thereafter a routine closure of all incision sites. The patient remained in ICU for less than 48 h, and made excellent progress on the ward. Minimal anti-hypertensives were required and the patient was discharged on 8th day post operatively neurologically intact and independent. At 3 months follow up the patient underwent a repeat CTA scan which showed complete patency in the extra-anatomical graft and resolution of the collateral arterial network (Fig. ).

pmc-6013953-1

A 79-year-old Japanese woman with a weight of 72 kg who has been maintained on anti-hypertensive drugs, including hydralazine, for more than 10 years, was advised on acute onset of proteinuria and microscopic hematuria by her family doctor. At this time, her serum creatinine (Cr) level was within normal range (0.8 mg/dl). One month later, however, the Cr level was elevated to 1.6 mg/dl. Therefore, she was referred to our hospital for admission. On admission, vital signs revealed body temperature of 36.9 °C, blood pressure of 150/70 mmHg, and pulse rate of 80 per minute. The white blood cell count was 8700/μl with 2.0% eosinophils, red blood cell count was 307 × 104/μl, and platelet count was 26.6 × 104/μl. The following values indicated renal dysfunction; blood urea nitrogen: 25.0 mg/dl, Cr: 1.9 mg/dl, urinary protein: 2.5 g/day, and the presence of microscopic hematuria. Dysmorphic red blood cells were noted in the urine sample microscopically. In the serum, MPO-ANCA was 107 IU/ml (normal limit, 3.5 IU/ml), whereas C-reactive protein (CRP) was 0.2 mg/dl. PR3-ANCA and other ANCAs, including anti-elastase and anti-lactoferrin antibodies, were negative. The titer of anti-nuclear antibody (ANA) was less than 1:40. Anti-DNA antibody was negative. Complement values were as follows: C3 162.2 mg/dl (normal range, 71–135 mg/dl) and C4 37.7 mg/dl (normal range, 11–34 mg/dl). Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (Fig. ). Hydralazine-induced MPO-AAV was considered regardless of absence of skin involvement, elastase- and lactoferrin-ANCAs, anti-nuclear and anti-DNA antibodies, and hypocomplementemia, which are usually observed in the disease []. By discontinuation of the causative drug, the serum Cr level decreased gradually. At 10 months later, the serum Cr and MPO-ANCA levels recovered to 1.1 mg/dl and 13 IU/ml, respectively. Proteinuria and microscopic hematuria also disappeared. Since the clinical course was consistent with hydralazine-induced MPO-AAV and the serum CRP level was not high throughout the clinical course, no additional medication was administered. After another 6 months of observation, the serum Cr and MPO-ANCA levels were re-elevated (Cr, 2.0 mg/dl; MPO-ANCA, 195 IU/ml) and proteinuria and microscopic hematuria were re-appeared. The titer of ANA was 1:40. Other ANCAs, including PR3-ANCA, and anti-DNA antibody were negative even at this time. Complement values were as follows: C3 149.4 mg/dl and C4 38.5 mg/dl. Renal biopsy was performed again and revealed cellular crescents in some glomeruli (Fig. ). These findings suggested the relapse of MPO-AAV. Since she had fever (38.3 °C), and the serum CRP level was elevated to 10.0 mg/dl at this time, administration of 30 mg prednisone (0.5 mg/kg body weight) was initiated. The illness improved rapidly, and remission was achieved 5 months after the beginning of treatment. The patient has remained in remission thereafter (Table ). This study was approved by the Ethical Committee of Osaka General Medical Center (Permission No. 29-C0313) and the Ethical Committee of Faculty of Health Sciences, Hokkaido University (Permission No. 15–90). After acquisition of written informed consent from the patient, serum samples were obtained at the disease onset (Serum A; MPO-ANCA, 107 IU/ml), at relapse (Serum B; MPO-ANCA, 195 IU/ml), at 3 months after treatment (Serum C; MPO-ANCA, 4.5 IU/ml), and at remission (Serum D; MPO-ANCA, 2.4 IU/ml). To assess the involvement of NETs in the pathophysiology of this patient, we determined the NET degradation activity in the serum samples at first. In brief, peripheral blood neutrophils from a healthy volunteer were seeded in slide chambers (1 × 106/ml), incubated for 15 min at 37 °C, and then made to react with 100 nM phorbol myristate acetate (PMA; Sigma-Aldrich, St. Louis, MO) for 3 h at 37 °C. We have confirmed that this stimulation induces NETs conspicuously []. After washing with PBS, the cells were incubated in 10% Serum A, B, C, or D for 6 h at 37 °C. For positive control, 10% serum of a healthy volunteer (49 years old, male) was employed. This sample exhibited the average value for NET degradation in our previous study []. To stop the serum nuclease activity, 2 mM EDTA was added, and then the remaining cells on the slides were fixed with 4% paraformaldehyde (PFA) followed by mounting with the solution containing DAPI. Photomicrographs (magnification, × 200) were taken randomly under a fluorescent microscope (6 fields/well of chamber slides), and then the residual NET area was determined using Image J software. NET degradation rate (%) was calculated as follows; {(residual NET area, incubated with PBS) – (residual NET area, incubated with serum) / (residual NET area, incubated with PBS)} × 100. As a result, the NET degradation activity was entirely low in Sera A, B, C, and D compared with the healthy control (Fig. ). Correspondingly, the DNase I activity as determined using ELISA kit (Orgentec GmbH, Mainz, Germany) was low in Sera A (21.7%), B (28.3%), C (22.8%), and D (33.5%) compared with the healthy controls {mean ± standard deviation (SD), 52.6 ± 12.1%}. Next, we determined the NET induction activity of IgG, which was isolated from the serum samples, using immunoadsorbent columns (Protein G HP SpinTrap, GE Healthcare, Tokyo, Japan). Contamination of endotoxin in the IgG samples was ruled out using the Limulus test kit (Wako Pure Chemical, Osaka, Japan). Peripheral blood neutrophils from a healthy volunteer were seeded in slide chambers (1 × 106/ml), pre-treated with 5 ng/ml TNF-α for 15 min at 37 °C to express MPOs on the cell surface, and then made to react with 250 μg/ml of the IgG samples. Serum IgG samples from a 65-year-old woman patient with MPO-AAV (MPO-ANCA, 93.2 IU/ml) and the healthy volunteer were employed as positive and negative controls, respectively. These samples exhibited the average values for NET induction in our previous study []. After incubation for 3 h at 37 °C, the supernatants were removed and the remaining cells on the slides were fixed with 4% PFA. Finally, the remaining cells were mounted with the DAPI-containing solution. Photomicrographs (magnification, × 200) were taken randomly under a fluorescent microscope (6 fields/well of chamber slides), and then the rates of NET-forming neutrophils were determined using ImageJ software. As a result, the NET induction activity was high in Sera A, B, and C, whereas that in Serum D was equivalent to the healthy control (Fig. ). Lastly, we conducted immunofluorescent (IF) tests to determine the presence of ANETA in the serum samples. Briefly, peripheral blood neutrophils from a healthy volunteer were seeded in slide chambers (1 × 106/ml), incubated for 15 min at 37 °C, and then made to react with 20 nM PMA for 2 h at 37 °C. After washing with PBS, the cells were fixed with 4% PFA, and then made to react with 250 μg/ml of the IgG samples for 1 h at 37 °C. After washing with PBS, the cells were next allowed to react with 1:5000 dilution of FITC-conjugated anti-human IgG antibodies for 1 h at 37 °C followed by mounting with the solution containing DAPI. As shown in Fig. , ANCA was detected in Sera A and B but not in Sera C or D; thus, these findings were consistent with the ELISA titers of MPO-ANCA. On the other hand, ANETA was detected in Sera B and C but not in Serum A or D.

pmc-6013965-1

A 54 year-old Caucasian male without significant comorbidities was diagnosed with IgG kappa multiple myeloma in 2005. Initial treatment consisted of doxorubicin, vincristine, and dexamethasone followed by an autologous stem cell transplant (SCT) with melphalan 200 mg/m2 conditioning. He remained in remission for 2.5 years, at which time he relapsed and was treated with a series of doublet regimens followed by a second autologous SCT in 2011, with melphalan 200 mg/m2 conditioning. He relapsed 4 months after the second transplant and was treated with carfilzomib but quickly progressed. The patient eventually achieved a very good partial response with bendamustine and dexamethasone and underwent reduced intensity conditioning with fludarabine 30 mg/m2 on days − 6 to − 2 and melphalan 50 mg/m2 on days − 3 to − 2, followed by a 9/10 matched unrelated allogeneic SCT in November 2012. GVHD prophylaxis consisted of sirolimus and tacrolimus starting day − 3 as well as methotrexate on days + 1, 3, 6, and 11. On day + 27 post-transplant the patient developed acute kidney injury (creatinine of 2.6 mg/dL from a baseline of 0.7) that was attributed to calcineurin inhibitor toxicity. The patient was switched to mycophenolate mofetil and corticosteroids for GVHD prophylaxis, with normalization of kidney function. By day + 130 the patient was felt to be in at least very good partial remission based on negative serum protein immunofixation and 99.8% peripheral blood donor chimerism. On day + 132, the patient returned to the hospital with diarrhea with scant blood. He underwent colonoscopy with biopsy. Histologic analysis demonstrated findings consistent with CMV colitis and GVHD: crypt apoptotic bodies, ulcerations, and CMV inclusions were noted. He was started on ganciclovir, and prednisone was increased from 60 mg daily to 60 mg twice daily. He was discharged 2 weeks later, at which time the platelet count had decreased from 93,000/μL on admission (normal 150,000–450,000/μL) to 29,000/μL. The thrombocytopenia was attributed to a combination of antiviral medication and CMV infection. He returned to the hospital 1 week later (day + 146) with recurrence of profuse diarrhea with small amounts of blood and associated abdominal cramping. Diarrhea was attributed to worsening GVHD. He was restarted on tacrolimus but continued to have maroon-colored stool output. A colonoscopy was repeated and was notable grossly for pancolitis with scattered ulcerations, ileocecal valve ulceration, mild ileitis, anorectal junction ulcers, and internal hemorrhoids that were not bleeding. The pathology report again suggested CMV infection and GVHD (increased crypt apoptotic bodies, focal erosions, and a positive CMV immunostain). During that admission, a diagnosis of TMA was considered due to a persistently low hemoglobin of approximately 9 g/dL (normal 13–17 g/dL) and thrombocytopenia that persisted in 30,000–50,000/μL range. A peripheral smear at that time showed 2–4 schistocytes/HPF in the setting of a haptoglobin of 22 mg/dL (normal 36–195 mg/dL) and a lactate dehydrogenase (LDH) of 731 U/L (normal < 260 U/L). Overall, the patient met 6 out of 7 of the TA-TMA criteria proposed by Cho et al. His tacrolimus was again discontinued, and he was maintained on a combination of sirolimus (goal level 5–7), mycophenolate mofetil, and steroids for GVHD treatment. At the time of discharge, his hemoglobin was 8.7 g/dL and platelets were 20,000/μL. On day + 156 the patient returned to the hospital with multiple episodes of bright red blood per rectum. He had diffuse patchy ecchymoses on physical exam. The platelet count was 17,000/μL. A colonoscopy was repeated, and per visual inspection the GVHD was felt to be improved. Hemorrhoidal bleeding was suspected as the cause of the bleeding, and colorectal surgery was consulted. He underwent sclerotherapy for hemorrhoids prior to discharge. On day + 188 TMA was again considered in the setting of an LDH of 1147 U/L. Sirolimus was discontinued. A peripheral blood smear, however, showed no schistocytes, and haptoglobin returned within low-normal range at 43 mg/dL. TMA was therefore felt to be unlikely. A CT scan of the abdomen and pelvis, performed for another indication, revealed an unexpected finding of pneumatosis intestinalis involving the ascending and transverse colon. This finding was attributed to GVHD and CMV and, as the patient was felt to be relatively asymptomatic, no specific intervention was performed. Sirolimus was restarted given the concerning imaging findings and lack of strong evidence for TMA. The patient was re-admitted on day + 211, this time with melenic stool. A tagged red blood cell scan identified the ascending colon as a source of bleeding. An angiogram with attempted embolization was unsuccessful due to inability to identify a bleeding vessel. Hemolysis labs were repeated given persistent cytopenias, including a hemoglobin of 7.1 g/dL and a platelet count of 37,000/μL. Haptoglobin was undetectable, and LDH was elevated at 1254 U/L. A repeat peripheral smear demonstrated a normocytic, normochromic anemia without increase in schistocytes. Sirolimus was again discontinued. The patient remained anemic and intermittently refractory to red blood cell transfusions, prompting two additional attempts at angiogram/embolization, neither of which successfully identified a bleeding vessel. A bone marrow biopsy was repeated and revealed a hypocellular marrow without evidence of myeloma relapse. On day + 217 the patient was transferred to the medical ICU for high volume bloody stool output, a hemoglobin of 6.3, and lightheadedness. The INR was 1.0 with a PTT of 22. A wireless capsule endoscopy and a repeat tagged red blood cell scan were both unsuccessful at identifying a source of bleed. A colonoscopy with biopsy was repeated; 2 visible vessels were identified and clipped. Histologic analysis did not show evidence of persistent GVHD or CMV colitis. An EGD with biopsy revealed no abnormalities on histologic analysis. He was managed supportively with transfusions as needed but then began to develop confusion, agitation, and increasing anger. Psychiatry was consulted for delirium. LDH was 767 U/L, and the haptoglobin was low at < 35 mg/dL. Platelets were 47,000/μL, and the INR was 1.1. A peripheral smear was repeated and did not show schistocytes. An ADAMTS13 level was ordered given recurrent suspicion for TMA, and therapeutic plasma exchange (TPE) was initiated empirically pending that result. The patient’s confusion was noted to improve following TPE, and he completed a total of 5 exchanges. LDH improved to 372 U/L. ADAMTS13 level ultimately returned at 60% (normal > 66%). Shortly thereafter, the patient developed copious hematochezia associated with a drop in hemoglobin from 8.9 to 6.9 g/dL. He was taken urgently to the operating room for visceral angiogram, which did not identify a bleeding vessel. An ileocolectomy was performed, but the patient suffered a cardiac arrest intra-operatively and expired shortly thereafter. A post-mortem analysis of the resection specimen revealed TMA involving numerous arteries and arterioles in the ileal and colonic submucosa as well as few thrombosed arterioles in the muscularis propria and deep lamina propria of the mucosa (Figs. and ). Rare thrombosed arterioles were identified in the appendix. The TMA in many of the vessels was active, characterized by endothelial cell swelling, endothelial cell detachment with intimal expansion by pale plasma protein material (“mucoid intimal edema”), and accumulation of fibrin and red cell fragments within expanded intimal zones and vascular lumina. A smaller number of arteries and arterioles showed features of persistent or chronic microangiopathic changes, such as concentric layers of new basement membrane material alternating with intimal edema well as focal presence of foam cells within artery intimal zones. All venous structures were patent without thrombosis. In areas of more severe TMA, there were foci of perivascular hemorrhage and deep ulceration extending into the superficial muscularis propria. Non-ulcerated mucosa showed architectural distortion and crypt regenerative features, consistent with previous injury. Additionally, there were areas of crypt dropout with replacement of mucosa by healing granulation tissue and an overlying layer of regenerative epithelium. Scattered CMV inclusions were visible within endothelial cells of the granulation tissue. However, there was no evidence of CMV infection by light microscopy or immunohistochemistry within endothelium of vessels affected by TMA. There was no significant increase in crypt apoptosis, arguing against GVHD. A retrospective review of the patient’s previous colonic biopsies was performed. In addition to the initially reported findings, biopsies from days 146 and 217 showed subtle features of TMA (Fig. ); these included rare thrombosed arterioles in the deep lamina propria and superficial submucosa surrounded by perivascular hemorrhage as well as few arterioles with subendothelial expansion by pale material accompanied by underlying layers of new basement membrane material.

pmc-6013977-1

A 25-year-old woman was hospitalized due to frequent premature ventricular beats of high grade (17,000 per day) and repeated episodes of bidirectional non-sustained ventricular tachycardia without syncope. Echocardiography revealed enlarged left ventricular dimension and local ventricular wall thinning. Upon routine clinical examination bilateral symmetrical hand abnormality was noted, namely the fifth finger camptodactyly (Figure ). Additionally, hypoplasia of the breast with inverted nipples was observed (Figure ). Facial features included wide-set eyes, a broad nasal tip and thin upper lip vermilion and strabismus (Figure ). Dental abnormalities were represented by tooth malalignment and hypoplasia involving canines and back teeth (Figures ). No defects were documented in her lower limbs. Apart from physical defects, intellectual deficit was noted and included mild mental retardation and learning disabilities. Family history reported that proband’s mother died due to congenital heart defect and congestive heart failure at the age of 30. Grandmother from mother side was not affected. No other relatives were available for examination. Due to the lack of family data, it is hard to conclude the mode of inheritance unambiguously. However, keeping in mind the mother’s phenotype, the dominant inheritance could be suggested (Supplementary Figure ).

pmc-6014015-1

The patient, a 52-year-old female, was admitted to the department of gastrointestinal surgery of Peking University Cancer Hospital & Institute in September, 2016, due to space-occupying lesions in the colon found by colonoscopy during medical examination 2 weeks before. Histopathological examination of endoscopic biopsy specimens indicated moderately differentiated colonic adenocarcinoma. Contrast-enhanced computer tomography (CT) of her abdomen demonstrated that the intestinal wall was thickened about 14 mm in the transverse colon, and several small lymph nodes (7 mm) scattered around the intestine were detected (Fig. and ). Laboratory examination revealed that the levels of CEA and CA72.4 increased to 15.17 ng/ml and 20.88 U/ml respectively. Laparoscopic examination confirmed the tumor (6 cm × 5 cm) was located in the hepatic flexure of the colon (Fig. and ). The patient (III7) had no other major medical history, except a family history of colon cancer in 3 out of 5 first-degree relatives (mother II2; sister, III5; brother, III6). In particular, the patient’s mother (II2) was diagnosed two separate primary colon cancer at the age 54 and 61 at different sites. Her sister (III5) was diagnosed with endometrial cancer and colon cancer at the age of 54 and 61 respectively (Fig. ). The patient was referred to our cancer genetic counseling clinic for LS genetic testing. Based on Amsterdam II criteria, the proband was diagnosed with LS. To confirm the diagnosis, all affected individuals (III5, 6 and 7) underwent genetic testing of a 101-gene panel by next generation sequencing. Peripheral blood was collected to extract genomic DNA (gDNA). The gDNA was then used to generate libraries according to the protocols suggested by Illumina. A custom targeted capture kit, covering all exons of the 101 genes, was designed (Agilent Technologies, Additional file : Table S1) []. Qualified libraries were subsequently sequenced on the Illumina HiSeq 2500 platform with 2 × 150 bp configuration. Reads were aligned to the reference human genome GRCh37 with BWA and PCR duplications were marked using Picard tools (version 1.57). To further increase the specificity for mutation calling, realignment and base recalibration were conducted using Genome Analysis tool kit (GATK). All samples were tested at least in an average depth of 200-fold coverage. Bases with a minimum of 30-fold coverage was required at every targeted position (Additional file : Table S2). The missense, nonsense, indel and splice site mutations that located at the upstream or downstream 1-2 bp of exon, whose frequency are below 5% in at least one pubic population database were retained (Additional file : Table S3). According to the American College of Medical Genetics (ACMG) standards and guidelines for the interpretation of sequence variants, all the gene variants were classified into 5 grades. Therefore, 14 mutations at least carried by two first-degree relatives were listed. A pathogenic variant (class 5) in MLH1 (c.1852_1854delAAG, p.K618del) was identified in all patient’s blood samples (Table ). Laparoscopy-assisted colectomy was performed on the proband to resect right colonic mass and its surrounding tissue followed by ileocolonic anastomosis. In addition, the clinicopathologic stage was pT3N0M0 and no complications occurred in the perioperative period. Conventional hematoxylin and eosin staining and immunohistochemistry were performed on resected specimens to confirm the malignancy (Fig. and ). Additionally, abdominal CT of III5 showed a obstructing mass in the same location of colon as the proband (III7) (Fig. and ). Moreover, according to the medical record for the proband’s brother (III6) in another hospital, a tumor was found in his hepatic flexure of colon. Immunohistochemistry results showed MMR deficiency in all tumor tissues of the 3 cancer patients (Table ). Subsequently, MSI testing was performed using MSI Analysis System Version 1.2 (Promega). Tumor DNA was extract from formalin fixed paraffin embedded sections. Genomic DNA extracted from white blood cell was used as normal control. Seven markers were amplified using fluorescent PCR. The PCR products were separated by capillary electrophoresis using Applied Biosystem 3130 Genetic Analyzer. GeneMapper Analysis Software was used to analyze the output data. The MSI results indicated that the 3 siblings with cancer (III5, 6 and 7) were all microsatellite instability-high (MSI-H) (Table ). Based on the results of MSI and the proband’s clinical stage, no adjuvant chemotherapy was given after surgery. To screen and evaluate the cancer developing risk in the offspring, children of affected individuals were also enrolled for genetic testing. And 1 (IV8) out of 3 carries the same MLH1 mutation to the proband. However, this carrier has no symptoms or confirmed diagnosis of cancer. Endoscopy was performed on IV8 for further examination and the ileocecal mucosa showed signs of dysplasia, including chronic inflammation with erosion, lymphoid hyperplasia and mild atypical hyperplasia of glandular epithelium (Fig. ). The asymptomatic individual was given oral administration of aspirin as a preventative treatment, and 6-months follow-up showed improved appearance with colonoscopy examination (Fig. ). A healthcare plan was proposed to this offspring including colonoscopy and urine test once a year, and gastroscopy every 3~ 5 years after 35 years old. All individuals carrying the MLH1 mutation in this family will be monitored on a long term basis. The CARE guidelines were followed in reporting this case.

pmc-6014478-1

Patient 2, a 1-year-old boy, presented with microcephaly (OFC 43.5 cm; −2.8 SD) and attacks of abnormal arm extension. His motor and speech development were delayed. He showed truncal hypotonia on physical examination. His length was 84 cm, he weighed 10 kg. EEG results were normal. MRI showed a short and hypoplastic corpus callosum of which the splenium was affected more than the rostrum (Figure ). He had an upward slant, a small and somewhat sloping forehead, depressed nasal bridge, small and upturned nose tip and nostrils, elongated philtrum and a thin upper lip. A de novo nonsense variant was found: Chr1(GRCh37):g.244217655G>A, NM_205768.2(ZBTB18): c.579G>A (p.(Trp193*)) that leads to a premature stop codon.

pmc-6014478-2

Patient 3, a 13-year-old boy, presented with mild to moderate speech and developmental delay and attention deficit disorder (ADD). He did not have hypotonia. His OFC was 52.5 cm (−1.25 SD). He was 156 cm tall (−0.75 SD). No structural brain anomalies were seen on MRI. He had retrognathia, mild hypertelorism, and a slightly elongated philtrum and thin upper lip. His hands were broad and short. Mild syndactyly of the second and third toe with a sandal gap were seen in both feet. WES analyses showed a de novo frameshift variant Chr1(GRCh37):g.244217335del, NM_205768.2(ZBTB18):c.259del(p.(Leu87Cysfs*21)), that leads to a premature termination codon located more than 400 codons upstream of the canonical termination codon.

pmc-6014478-3

Patient 4, a 4-year-old boy, presented with severe speech delay, motor delay, and hypotonia. MRI showed agenesis of the splenium of the corpus callosum. At 3 years of age, an OFC of 49 cm was measured (−1 SD). His height was 98 cm (0 SD). He had hypertelorism, a prominent nasal tip, and a bulbous nose, a small mouth and retro- and micrognathia. His fingers showed broad tips. He carried a missense variant in ZBTB18 (Chr1(GRCh37):g.244218467G>A, NM_205768.2(ZBTB18):c.1391G>A(p.Arg464His)). This heterozygous de novo missense variant is predicted to be deleterious (SIFT score 0; Polyphen score 0.991) and affects a highly conserved amino acid residue located in the ZNF domain of the ZBTB18 protein (conserved up to Tetraodon). This variant has not been found in individuals from the ExAC database. We reviewed four patient cohorts containing one or more patients with pathogenic variants in ZBTB18 (Cohen et al., ; Depienne et al., ; Lopes et al., ; Rauch et al., ) and included one case report (de Munnik et al., ). So far, a total of 25 patients with a pathogenic ZBTB18 variant have been reported in literature and in this study. All patients presented with developmental delay in varying degrees with prominent speech delay. Fifteen patients underwent an MRI scan. Nine of them showed corpus callosum abnormalities. Results of clinical evaluation of congenital anomalies in 13 patients were present: dysmorphic facial features were seen in 10 patients, epilepsy was described in five patients, hypotonia in seven, and dystonia in two. Data about growth, development, neurological, or congenital anomalies was incomplete in 13 cases. Clinical data of cases included in this study and patients from literature are presented in Table . Variants in the ZBTB18 gene are schematically depicted in Figure .

pmc-6014500-1

A 60-year-old man was transferred to our department with complaints of chest distress and wheezing for 3 d. The patient reported no significant comorbidities apart from a 3-year history of hypertension. An examination revealed the following: temperature, 36.8 °C; blood pressure, 162/98 mm Hg; pulse rate, 78 beats/min; and respiratory rate, >20 breaths/min. He was thin and had no eyelid edema. The breath sounds over both lungs were rough, and a few moist rales were heard. The abdomen was soft, without tenderness or rebound pain. The laboratory findings were as follows: serum creatinine, 1283 μmol/L (25–123 μmol/L); blood urea, 40 mmol/L (2.29–7.2 mmol/L); white blood cells, 12.6 × 109/L (3.5–9.5 × 109/L); red blood cells, 4.12 × 1012/L (3.8–5.1 × 1012/L); hemoglobin, 107 g/L (115–150 g/L); platelets, 269 × 109/L (125–350 × 109/L); B-type natriuretic peptide, 146 pg/mL (0–100 pg/mL); prothrombin time, 12.00 s (10–14 s); activated partial thromboplastin time, 35.50 s (23–35 s); fibrinogen, 4.01 g/L (2–4 g/L); K+, 6.2 mmol/L (3.5–5.3 mmol/L); Na+, 133 mmol/L (135–145 mmol/L); calcium, 2.05 mmol/L (2.2–2.7 mmol/L); phosphorus, 2.13 mmol/L (0.5–1.5 mmol/l); and parathyroid hormone, 472 pg/mL (16–65 pg/mL). Tumor marker, thyroid-function, chest X-ray, and electrocardiographic assessments yielded normal results. Chest computed tomography (CT) revealed inflammatory areas in both lungs and bilateral pleural effusion. Urinary tract color ultrasonography showed that the left kidney measured 9.0 cm × 5.1 cm and had 1.2-cm-thick parenchyma; the right kidney measured 8.8 cm × 5.0 cm, and had 1.3-cm-thick parenchyma. No abnormalities were observed in the ureters or bladder. Owing to the risk of cardiac arrest because of hyperkalemia, hemodialysis was performed. The right femoral vein was catheterized under local anesthesia, and 5000 IU low-molecular weight heparin was administered for anticoagulation. Four hours after LMWH was administered, the patient felt increasing pain in the lower abdominal region after straining at stool and an urgent desire to micturate. A physical examination revealed a tender mass in the lower abdomen. Urgent bedside urinary tract ultrasonography showed large amount of fluid in the bladder. A 20-Fr in-dwelling catheter was inserted, but there was no obvious outflow of urine through the catheter, and the abdominal pain was not improved. Therefore, abdominal and pelvic CT was performed, which revealed marked hematoma that extended to the prevesical space and bilateral rectus sheath hematomas (RSHs; type III). The following emergency measures were undertaken immediately: bed rest, ice bag application, and compression bandaging. In addition, a blood coagulation profile was obtained, which showed the following: prothrombin time, 12.80 s (10–14 s); activated partial thromboplastin time, 47.40 s (23–35 s); and fibrinogen, 3.04 g/L (2–4 g/L). Given the abnormal coagulation function and risk of continuing hemorrhage, we transfused the patient with 180 mL fresh frozen plasma, supplemented with the injection of 2 U hemocoagulase agkistrodon for hemostasis and 2 U red blood cell suspension. We then performed heparin-free continuous renal replacement therapy (CRRT) 3 times per week, and closely monitored the patient. After 1 week, a repeat CT showed that the hematoma had not expanded. After six sessions of heparin-free CRRT, the hematoma was slightly reduced, and did not recur when 2500 IU LMWH was administered for hemodialysis. We then increased the heparin dose to 5000 IU without further complications. A follow-up clinical examination 6 months later showed that the abdominal mass had completely resolved.

pmc-6014571-1

Patient 1 is a 74-year-old male who underwent HoLEP for refractory bladder outlet obstruction and bladder stones. His medical history included BPH complicated by recurrent urinary tract infections and bladder stones, elevated prostate specific antigen (biopsy negative), hyperlipidemia, and hypertension. Preoperative transrectal ultrasound (TRUS) estimated prostate volume to be 150 cc. HoLEP was performed utilizing a two-incision technique. Owing to the large amount of adenoma, extended time was spent during morcellation (120 minutes) because of poor observation secondary to bladder neck bleeding. There was noted to be an area of capsular perforation at the 5 o'clock position in the mid gland. When the operative drapes were removed, significant abdominal distention was noted. In discussion with anesthetist, the patient's airway pressures upon induction ranged from 10 to 20, however, at this point in the procedure, the airway pressures had increased >30. The patient was also experiencing systolic pressures ranging from 80 to 90, whereas preoperatively he was >110 systolic. The drapes were removed at this time and the abdomen appeared distended and was firm on examination. Given the significant abdominal distention and concern for a bladder injury secondary to poor observation during morcellation, general surgery was consulted intraoperatively. Per the recommendation of general surgery, they elected to proceed with a subumbilical minilaparotomy, after initial laparoscopy was unsuccessful because of increased opening pressures with the Veress needle. Less than 400 cc of bloody-colored fluid was suctioned out of the abdomen, and an intraoperative cystogram was performed that revealed retroperitoneal extravasation without intraperitoneal bladder injury or perforation. As there was not a significant amount of intraperitoneal fluid, it was theorized that the capsular perforation resulted in extraperitonealization of intraoperative saline. Thus, a 10F Jackson Pratt drain was placed in the pelvis, and the fascia and skin were closed. He was given 20 mg of IV Lasix intraoperatively. The patient was extubated effectively and transferred postoperatively to the ICU for hemodynamic monitoring and observation. In the ICU, cardiology was consulted because of a prolonged PR interval and bradycardia that ultimately warranted no further work-up. On postoperative day (POD) 1, the patient was progressing well, and he was transferred to the floor in stable condition. The Jackson-Pratt drain output was 710 cc on POD 0, 81 cc on POD 1, and then removed on POD 2 after draining 20 cc. The patient was discharged on POD 3. His catheter was removed on POD 10. Pathologic analysis of the specimen revealed no evidence of malignancy and 167 g specimen.

pmc-6014571-2

Patient 2 is a 78-year-old male who was experiencing persistent lower urinary tract symptoms despite combined medical therapy with alpha blockade and 5-alpha reductase inhibitors. His medical history included coronary artery disease status post-coronary artery bypass grafting and percutaneous coronary intervention, and a history of pneumonia. Preoperative cystoscopy revealed enlarged median and lateral lobes, as well as severe trabeculations of the bladder with a TRUS measuring a 41 cc prostate. HoLEP was carried out utilizing a two-incision technique. Upon completion of morcellation, it was noted that the patient's abdomen was distended, but his peak airway pressures were normal, the abdomen was soft, and the catheter drainage was noted to be clear. In addition, there was no suspicion for a significant mismatch between irrigation used and fluid output collected in the drainage system. Given the previous similar presentation in Case 1 with no suspicion of bladder injury, we suspected that the patient had extraperitoneal extravasation of the saline irrigation through a capsular perforation as occurred in Case 1. The decision was made for the patient to be awakened, extubated, and transferred to the recovery room where he was further monitored. A stat noncontrast abdominal CT scan was performed that revealed a moderate amount of free fluid in the pelvis and upper abdomen; the fluid in the pelvis and lower abdomen was distributed in the extraperitoneal region with no evidence of hematoma (). The patient remained hemodynamically stable and was transferred to the floor with continuous bladder irrigation. The patient was given a 40 mg dose of Lasix ∼8 hours after the operation was completed. Overnight, there were no acute events. On POD 1, the patient's abdomen was soft and significantly less distended. The Foley catheter drained 3950 cc of urine overnight without evidence of hematuria. The patient was discharged with a catheter on POD 1. The patient had his catheter removed on POD 9. A postoperative CT cystogram revealed no evidence of leak with resolution of the pelvic and perivesical fluid (). Thirty grams of benign prostate tissue was removed on final pathology analysis. The patient was noted to have a bladder neck contracture seen on cystoscopy 4 months after his procedure for which he underwent cystourethroscopy and laser incision of bladder neck contracture.

pmc-6014576-1

A 19-day-old male infant was urethral catheterized with a 6F infant feeding tube followed by a VCUG for evaluation of vesicoureteral reflux. After the procedure, the catheter could not be removed. Therefore, the pediatric unit consulted us regarding the problem. Under fluoroscopic guidance, a guidewire was inserted through the feeding tube to uncoil it, but this failed (). Therefore, we planned to cut the knot endoscopically under general anesthesia. The patient was taken to the operating room and put under general anesthesia. Considering the relaxation effect of the anesthesia before cystoscopy and the danger of urethral trauma, it was then planned to remove the catheter by gently pulling it out. Since there was no resistance encountered and no serious tension on the catheter was observed, the operation proceeded as planned. The catheter seemed to be removed with ease. There are cases in the literature that report of removing knotted catheters using the said method. After the catheter was removed fully with the knot at the tip (), cystoscopy was performed to check for any potential urethral injury. Mucosal integrity of the urethra was observed to be intact and the patient was discharged after a short follow-up and observing spontaneous micturition.

pmc-6014577-1

The patient was a 65-year-old woman who presented with a 1-month history of bloody stool. A digital colonoscopy with biopsies revealed adenocarcinoma in the sigmoid colon. The patient elected to undergo primary laparoscopic colon resection, and the procedure was reported to be uneventful. However, on the 6th postoperative day, the patient noticed a large amount of yellow fluid coming out of a left side abdominal drain. The fluid appeared to be urine. An abdominal ultrasonography showed a collection of fluid in the patient's pelvis. A contrasted computed tomography (CT) scan showed contrast extravasation in the pelvis and around the descending colon (). The patient had decreased serum protein and albumin; however, complete blood count, creatinine, liver functions, and urine analysis were normal. On the 8th postoperative day, the patient was taken to the operating room for a ureteroscopy. The ureteroscopy revealed that the left ureter was completely severed about 4 to 5 cm from the ureteral orifice (, transected distal end of the ureter). The bowels could be seen through the ureteroscope (, intraabdominal cavity with bowels seen through the distal end of the transected ureter). No other obvious injury was identified. With patience, persistence, and some difficulty, the severed upper end of the ureter was identified and entered (, the proximal end of the transected ureter). We estimated that there was a 3- to 4-cm gap between the two ends of the ureter. Two 0.035″ guidewires were first passed, followed by the placement of two 4.5F Double-J ureteral stents. After placing the Double-J stents, the abdominal drainage quickly subsided. An abdominal ultrasonography 6 days after tube placement showed complete resolution of the abdominal fluid collection. The abdominal drain was removed and the patient was discharged. At the 3-month follow-up, a repeat CT scan showed no hydronephrosis, no abdominal fluid collection, and no contrast extravasation. The patient, however, had an asymptomatic urinary tract infection from Klebsiella pneumoniae, which was treated and resolved. A follow-up ureteroscopy over a guidewire showed excellent healing and realignment of the disrupted ureter. The only obvious sign of the transacted ureter was that the mucosa was paler than normal. Because of this unconventional treatment, we decided to continue stenting the ureter with two fresh 4.5F Double-J stents for an additional 4 weeks. Stents were removed 4 months after the injury. Follow-up contrast-enhanced CT scans taken 8 and 14 months after the initial endoscopic treatment showed mild but unchanged residual dilation of the renal pelvis and ureter with good drainage. There were no other abnormalities.

pmc-6015456-1

A 12-year-old Cameroonian girl from the "Baka" ethnic group and residing in a remote area of the East region of Cameroon presented with a progressively extensive, pruritic, and painless pigmented skin lesion on her back, persistent since she was 2-days old. She was born through normal vaginal delivery at term from an uneventful pregnancy. Her past medical and family histories were unremarkable. On our initial physical examination, she had normal anthropometric characteristics for age, as well as normal vital parameters. Examination of her skin revealed a large, irregular, well-demarcated and unequally pigmented (bluish-brown to black) multinodular hypertrophic nevus occupying almost all her back (Fig. ). The largest diameter of this lesion was 45 cm. Its surface was rough and had several excoriation marks. No other malformation was apparent. An examination of her lungs, heart, abdomen, and extremities was otherwise normal. Despite the unavailability of histopathology in our setting, the aforementioned clinical findings were highly suggestive of a GCMN. She was scheduled for a free of charge surgical campaign due within the same year in her community. This surgical excision would provide several benefits namely the reduction of the risk of melanoma, improvement in aesthetics, and obtaining histopathology samples. Taking into consideration the psychosocial aspect of this pathology, our patient and her parents were also oriented to the consult of a psychologist. Meanwhile, her parents were counseled on signs of complications which should warrant urgent admission. At 3-month follow-up, she was still pending surgical intervention. Currently, she is being followed-up clinically and psychologically on a weekly basis while waiting for surgery.

pmc-6015461-1

A 52-year-old menopausal woman complained of intermittent vaginal spotting for 1 month. She denied any systemic disease, dysmenorrhea, menorrhagia, body weight loss, abdominal pain, or abdominal fullness. Gynecologic history was gravida 2 and para 2. Transvaginal ultrasound revealed a 10-cm multi-lobular cystic pelvic mass containing the mixed heterogeneous solid component, fluid and papillary growth in the inner surface of cystic wall Significant venous flow was detected in the solid part and papillary growth lesion. Serum AFP (< 20 ng/ml), cancer antigen (CA)-125 (< 35 U/ml), and carcinoembryonic antigen (< 5 ng/ml), and CA19–9 (< 37 U/ml) were 60,721, 38.1, 84, and 97 ng/ml, respectively. All of these tumor markers from serum have their own specific cut off values and sensitivities, and they come from the same assay methods and from the same laboratory. All are elevated. Computed tomography (CT) showed a 9-cm heterogenous mass probably developed from the left adnexa (Fig. ) and a 4-cm well-defined mass located at the right subphrenic region (Fig. ), suggesting the diagnosis of left ovarian carcinoma with peritoneal seeding. The patient underwent optimal debulking surgery, including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy (Fig. ). All gross tumors were almost completely resected. Histologically, sections of the left ovarian tumor showed a clear cell carcinoma (Fig. ). The tumor is composed of polygonal, cuboidal to columnar cells with clear cytoplasm arranged in solid nests and tubule-cystic growth patterns. Numerous hyaline globules are present. Some tumor cells also showed high-grade anaplastic nuclear features. Right ovarian tumor showed metastatic clear cell carcinoma (Fig. ). Typical yolk sac tumor differentiation and Shiller-Duval body were absent. Sal-like protein 4 (SALL4) was strongly positive (Fig. ). Immunohistochemically, the tumor cells were positive for glypican-3 (GPC3) and AFP and negative for CD30. Meanwhile, the tumor cells showed weak positive staining for hepatocyte nuclear factor1-beta (HNF-1beta) (Fig. ). The tumor cells were focally positive for cytokeratin (CK) 20 and Cdx2 (caudal type homeobox 2) and negative for CK7 (Fig. ). To rule out potential artifacts due to antibody issues, we titrated the antibody used for AFP staining (Fig. ). For every immunohistochemical stain, positive controls were included. As a negative control, we also stained the classical clear cell carcinoma (Fig. ). Combination of all made a diagnosis of AFP-producing clear cell type EOC with fetal gut differentiation, FIGO (International Federation of Gynecology and Obstetrics) IIIc. After surgery, the patient received adjuvant multi-agent chemotherapy (carboplatin and paclitaxel). After treatment, CT showed a 2-cm hypodense nodule at the right subphrenic region and wedge-shaped hypoperfusion over segment 7 of the liver, suspicious tumor seeding, and liver metastasis (Fig. ) and serum level of AFP was 1831 ng/ml. Tumor excision for liver metastasis was done. Dose-intensity chemotherapy with weekly paclitaxel was given. CT scan, 1 year later, showed a lobulated mixed solid and cystic lesion at the right paracolic gutter measuring 5 cm in size in favor of peritoneal seeding (Fig. ). Exploratory laparotomy was done, including the use of Cavitron Ultrasonic Surgical Aspirator. After operation, chemotherapy was given through intraperitoneal route. After additional 18 months, tumor recurrence was found, including persistent liver metastases (Fig. ), with increasing serum level of AFP of 330,014 ng/ml. The patient finally died of disease. Based on our search of PubMed (from January 1960 to July 2018; search terms: “Alpha-fetoprotein”, “clear cell”, “ovarian cancer”; ), there are a few cases of AFP-producing clear cell type EOC available in the literature [–]. A total of three articles are included and the detailed information, including microscopic finding and immunohistochemical staining results are summarized in Table . All patients were middle aged (range, 54–63 years). Tumor size ranged from 14 cm to 22 cm, but all were advanced FIGO stage (IIb–IIIc). Among these [–], including the current case, half of patients died of disease.

pmc-6015595-1

In December 2006, a 31-year-old woman was referred to a neurologist because of consciousness disorder and fainting. Her main problems were obesity, snoring and waking up with a feeling of suffocation in the middle of sleep. The intraoral examination showed a large soft palate (). The soft palate was scored as class III according to the Mallampati classification (visualization of the soft palate and the base of the uvula) []. The electroencephalogram (EEG) showed focal dysrhythmia during hyperventilation with scattered sharp waves (). The patient was depressed and had sleep disorders such as sleep apnea and myoclonus, especially at the onset of sleep. She had experienced several occurrences of complete loss of consciousness during swimming and at work. The patient was on anticonvulsants and antidepressants (at first, she had been prescribed with Lamotrigine for 5 months, but later she was given 500mg Sodium valproate per day). One of the best treatments for snoring during sleep is UUUP. The success rate of this type of surgery is reported to be between 16% and 83% []. We chose a minimally invasive surgical procedure for the present case since the patient had a proper facial profile and a large soft palate (class III according to the Mallampati classification) []. In May 2007, after analyzing the lateral cephalogram, we evaluated the craniofacial and pharyngeal airway morphology before the surgery. Under general anesthesia, 1cm of the soft palatal mucosa, from the right tonsil to the left tonsil, was removed. The patient’s tonsils were also removed during the surgery, and the anterior and posterior tonsillar pillars were sutured together (). The symptoms were significantly decreased after the recovery. The patient no longer had sleep apnea, and antidepressants and antiepileptic drugs were discontinued. After the surgery, sharp waves were detected on the EEG at the level of the trachea (), but the patient was clinically asymptomatic. The 10-year follow-up showed no symptoms of sleep apnea or seizure. The patient did not lose any weight during the follow-up period.

pmc-6015668-1

A fit and active 38-year-old female presented to the Accident and Emergency Department with a four-day history of worsening right shoulder pain radiating down the right arm, with swelling around the shoulder. This was accompanied by intermittent fevers for the preceding two days. The patient graded the pain to be 8/10 on a visual analogue scale for pain. The patient reported an episode of right shoulder pain three weeks prior to current presentation which developed while she was boxing with a punch bag and resolved spontaneously in 2-3 days without seeking any medical advice. The patient denied any history of infections in the previous 6 weeks. She had a significant past medical history of cellulitis around the leg 6 months prior and a Bartholin cyst that was treated conservatively 8 months before this presentation. She was not on any routine medications and did not have any predisposing medical conditions such as immunosuppression or diabetes. At presentation, all her observations were essentially unremarkable except temperature which was recorded to be 38.6°C. On examination, the right shoulder was tender and swollen with severely restricted active and passive range of movements. No cellulitis, erythema, or differential warmth was noted. Haematological investigations showed mild leukocytosis with a white cell count of 11.1 × 109/L with predominant neutrophilia and a C-reactive protein (CRP) level of 233 mg/L. Liver functions tests, urea and electrolytes, bone profile, and coagulation studies were all within normal limits. Plain radiographs of the chest and shoulder were essentially unremarkable. Shoulder aspirate analysis was negative for any organisms, however showed some scanty pus cells. The patient was started on IV flucloxacillin 1 g intravenous four times a day as she was continuing to have temperature spikes, although shoulder aspirate cultures and blood cultures were negative. Due to the patient's severe symptoms and markedly elevated CRP level, urgent magnetic resonance imaging (MRI) of the right shoulder was performed. This revealed marked oedema throughout the subscapularis muscle with a relatively well-defined ovoid area of hyperintensity on short-tau-inversion-recovery (STIR) () and isointensity to muscle on T1 (). The area measured 9 cm on the oblique axial diameter, almost 3 cm in depth, and over 3.5 cm craniocaudally, with fluid extending inferiorly from the subscapular region overlying the chest wall axially measuring over 5 cm transversely and 1.5 cm in depth on T2-weighted images (). This MRI confirmed abscess formation within the subscapularis muscle as the cause of the presentation. The patient underwent surgical open drainage of the right subscapularis abscess under general anaesthesia via a standard deltopectoral approach. During mobilisation of the conjoined tendon, approximately 150 mL of blood-stained pus exuded from the subscapularis muscle. The subscapularis muscle was left with a defect but subscapularis tendon integrity was maintained. Following irrigation, the wound was closed. Cultures of the evacuated pus grew PVL-positive S. aureus, sensitive to flucloxacillin. No per operative signs of intraarticular infection were found, and an on table aspirate yielded no organisms on gram stain and cultures. The case was discussed with musculoskeletal microbiologist, and the patient was given a further two-week course of flucloxacillin. At the 6-week follow-up to assess improvement, the patient's wound had healed well and shoulder pain had resolved with no signs of recurrence of the infection. She still had some restriction in the movement of her shoulder for which she was referred to physiotherapy.

pmc-6015673-1

A 50-year-old female (BMI = 35) presented to our clinic in Salt Lake City, Utah, USA, with a chief complaint of right shoulder pain. She has a history of non-insulin-dependent diabetes, hypertension, anxiety, depression, and fatigue. Her medications included hydroxyzine for anxiety, ibuprofen for joint pains, lisinopril for hypertension, and pioglitazone tablets and liraglutide (Victoza®; Novo Nordisk A/S, Bagsvaerd, Denmark) subcutaneous injections for diabetes. She had a several-year history of intermittent low-grade right shoulder pain that was attributed to subacromial bursitis. This had been treated with subacromial corticosteroid injections and physical therapy, which only gave moderate pain relief. Her right shoulder pain worsened acutely in April 2016 after her dog jerked on the leash, almost causing her to fall. Radiographs obtained one month later demonstrated a hooked acromion and subtle decrease in trabecular bone density adjacent to the greater tuberosity, but no distinct bone lesions were noted (). The subtle decrease in trabecular bone was considered to possibly reflect disuse osteopenia associated with a long-standing rotator cuff tear [–]. Subsequent MRI with intra-articular contrast was obtained which demonstrated what was interpreted as a small full-thickness tear of the supraspinatus tendon. The MR images also revealed multiple quasi-circular lesions within the proximal humerus that were suggestive of metastases or multiple myeloma (). Bone lesions were also in close proximity to the insertion of the supraspinatus tendon. Ten days prior to the radiographs, she had an unrelated skin biopsy of a facial lesion that was diagnosed as sarcoidosis. A biopsy of the humeral lesions seen on MRI revealed noncaseating granulomatous inflammation, confirming osseous sarcoid of the humerus (). Additionally, mediastinal and hilar adenopathy seen on a subsequent chest computed tomography (CT) were consistent with the diagnosis of sarcoidosis. With osseous sarcoid lesions, there is concern that pathologic disturbances in bone architecture could make surgical repair involving cortical bone difficult []. For example, Ungprasert et al. [] reported an increased incidence of fragility fracture in the proximal humerus in patients with sarcoidosis of the humerus. However, given that our patient's humeral lesions involved cancellous bone, while cortical bone was spared, we concluded that the lesions were not a contraindication to a standard surgical repair of the rotator cuff tear. This is because only a small amount of cortical bone needs to be removed during the repair of a small rotator cuff tear [, ]. However, larger tears and/or cases with more invasive sarcoid lesions might require advanced repair techniques [, ]. This was not a concern in our patient's case because during surgery only a low-grade partial tear was found. Surgical treatment was done by JGS and included arthroscopic debridement, bursectomy, and acromioplasty [, ]. The shavings from the surgical procedure were not obtained for histological analysis. However, the tissues did not appear to be grossly abnormal. Despite being enrolled in a physical therapy program at two weeks after surgery, she had an unusually prolonged recovery because of flares of pain in addition to shoulder stiffness. Treatment for this included a one-time seven-day course of an oral corticosteroid on a tapered dose schedule (methylprednisolone tablets; Medrol® dose pack; Pfizer Inc., New York, USA). Because the improvement with this was less than satisfactory, two sets of subacromial and glenohumeral corticosteroid injections (Depo-Medrol injectable suspension; Pfizer Inc., New York, USA) were administered two months apart []. Supervised physical therapy was also continued. Because of continuing shoulder and generalized pain flares coupled with a great sense of fatigue, the patient consulted with a rheumatologist who prescribed adalimumab (Humira®, AbbVie Inc., North Chicago, Illinois, USA) subcutaneous injections once every other week. Adalimumab is a tumor necrosis factor-alpha (TNF-α) inhibitor that was selected over other first-line therapies for sarcoidosis because of its greater effect on sarcoidosis-associated fatigue []. Our patient reported that the adalimumab injections greatly improved her fatigue and thereby enhanced her ability to participate in physical therapy. At final postoperative follow-up at 48 months after her shoulder surgery the patient reported that she had an excellent result that included complete pain relief and restoration of full range of motion and strength.

pmc-6015681-1

We present a case of 40-year-old building and construction male worker who slipped and fell from a height of three (3) meters and sustained a deep penetrating wound on the right side of the anterior neck a week prior to presenting at our facility. He was apparently working from the above height when he slipped and fell on a sharp piece of iron rod which penetrated deep into the right anterior neck. He quickly pulled the sharp iron rod out when he got up from the floor. According to him, the bleeding was not profuse and stopped when he arrived at the local hospital to search for remedy (). He did not have hemiplegia, paraplegia, or quadriplegia when we saw him. He is not known to be hypertensive. He did not take alcohol prior to the fall although he takes alcohol occasionally. He had a left femoral fracture at the age of 24 and a right femoral fracture at the age of 32; both incidences were operated on successfully. On examination at our facility we saw a middle aged man who was conscious and alert but however acutely ill with his neck fixed in cervical collar. General as well as systemic examination did not yield much. All the systems where grossly normal. Neurological examination revealed normal pupils which reacted normally to light. Cranial nerves examination was unremarkable. Power on four limbs as well as reflexes was normal. Digital rectal examination revealed a normal spinster tone. Routine laboratory as well as other ancillary (ECG, CXR, etc.) investigations were normal. Neck CT-scan done at the local hospital revealed C2-C4 transverse process fractures on the right side, fracture at the right lamina of C3, and right common carotid artery dissection. CT-scan of the head showed no abnormalities (Figures and ). Explorative three-dimensional reconstruction plain and enhanced scan imaging of the cervical spine, chest, and abdomen done at our facility revealed two segmental stenoses of the right common carotid artery with very pale V1 and V3 segment of the right vertebral artery as well as blockage at V2 segment (Figures –) as well as fracture at the right lamina of C3 and C2-C4 transverse processes with free bone fragments and peripheral soft tissue swelling (Figures –). The skin at the right anterior cervical region is discontinuous, with adjacent soft tissue swellings and gas accumulation. The bilateral carotid artery sheath lymph nodes slightly enlarged. At the upper lobe of the right lung there were multiple calcifications, some of which were adjacent to the pleura. There was also slight thickening of the left pleura. The heart was not enlarged but we observed slight accumulation of gas in the anterior mediastinum. Multiple low-density lesions were seen in the liver which we think are constant cysts. A working diagnosis of right common carotid artery dissection with C1-C4 fractures was made. After preoperative education and counselling of the patient as well as the relatives, surgery was scheduled the next day. Intraoperative cerebral angiography showed right carotid artery dissection and right vertebral artery occlusion. There was some reparation at the distal end of the right vertebral artery. The left vertebral artery was however normal. We introduced the guiding catheter guide wire to the proximal end of the right common carotid artery with continued infusion of heparinized saline, after which we introduced a guide wire with a Cordis stent (10 ∗ 60mm) to completely cover the right common carotid artery dissection site with stenosis and released the stent gradually until it completely filled the stenosis area (Figures –)). We delivered contrast agent into right common carotid artery to make sure it was patent before removing the guiding catheter followed by withdrawal of the femoral arterial sheath. Control contrasted angiograph done revealed stenting was successful (Figures and ). The patient recovered markedly and was discharged home a week after. Scheduled outpatient visit every 6 months for 2 years revealed no neurological complications.

pmc-6015682-1

A 45-year-old male from the Netherlands presented with a painless right parotid swelling that was progressively increasing in size for the past 8 months. Though occasionally he suffered from jaw lock, other symptoms associated with neurologic deficit such as drooling, facial weakness, paresthesia, or auditory defects were absent. Apart from being a social alcohol consumer, there was no history of smoking, prior radiation, or significant family medical history, especially in regard to his present illness. Physical examination revealed a tender right parotid swelling below the ear lobule, which extended inferiorly to the angle of the mandible (). The skin overlying the swelling was slightly erythematous, thickened, and nodular. The swelling was firm, diffused, and fixed to the underlying muscles, and there was no associated lymphadenopathy. Otoscopic examination of both ears was within normal limits. The patient initially had a neck ultrasound and then a magnetic resonance imaging (MRI) to characterize the nature of the lesion. The neck CT scan revealed a well-defined altered signal enhancing mass measuring 3.5 × 2.2 × 2.0 cm at the posterior aspect of the superficial part of the right parotid gland (). The radiologist's impression was an altered signal enhancing mass lesion, likely to be a benign pleomorphic adenoma. The patient then underwent MRI of the parotid glands, which showed a well-defined focal lesion of altered signal intensity at the posterior aspect of the superficial part of the right parotid gland, measuring 3.5 × 2.2 × 2.0 cm along its maximum transverse, craniocaudal, and anteroposterior diameters, respectively. The impression was again benign pleomorphic adenoma of the right parotid gland. However, the radiologist could not exclude other diagnostic possibilities and recommend fine-needle aspiration cytology. Fine-needle aspiration cytology of the mass was nonconclusive as the smears only showed polymorphous population of lymphoid cells in keeping with intraparotid lymph node. In view of these clinical findings, a superficial parotidectomy with facial nerve monitoring and preservation was planned. A modified Blair incision was done, with elevation of a skin flap and control of hemostasis during the surgery. The dissection was rather difficult! The superficial parotidectomy was done in piecemeal as the mass was unexpectedly adherent to the skin and underlying fascia (). The facial nerve was intact and was examined branch by branch. No frozen section was done during the operation. Histopathologic examination showed a widely infiltrative tumor involving the parotid parenchyma and extending into the surrounding adipose tissue and skeletal muscles (). The tumor was predominantly composed of bland spindle cells with wavy nuclear contours, embedded within a fibrillary, pale pink matrix, which resembled a neurofibroma (). Of concern, there were evidently distinct scattered more cellular foci of epithelioid tumor cells with nuclear atypia and increased mitotic activity (). The tumor was diffusely and intensely positive for the S100 protein and neuron-specific enolase (NSE) immunohistochemical stains, with a low Ki-67 proliferation index. In addition, the CD34 immunohistochemical stain was focally positive in tumor cells. On the other hand, the tumor lacked immunoreactivity for AE1/AE3, p63, EMA, Melan-A, and HMB-45 immunohistochemical stains, thus excluding carcinomas, clear-cell sarcoma, melanoma, and other salivary gland tumors. Based on morphologic and immunophenotypic features of the tumor, the diagnosis rendered was low-grade malignant peripheral nerve sheath tumor (MPNST) arising in a diffuse neurofibroma. Given the rare presentation and the association of such tumors with NF1, the patient was evaluated clinically for features of the syndrome. Multiple café au lait macules were subsequently discovered on his trunk (). The patient was referred to a cancer center for further management and follow-up. Further clinical examination of the patient and MRI revealed no distant metastasis. The patient underwent several courses of radiotherapy and is currently eighteen months' disease free.

pmc-6015693-1

This 34-year-old male, who was medically free, was presented to the emergency department by the Red Crescent after an assault injury. He was conscious, alert, oriented, and complaining of right shoulder pain and bleeding due to assault by a cleaver. On examination, there was a wound around 20 cm on the posterior aspect of the right shoulder extending to the glenohumeral joint, acromion was exposed, and no active bleeding was present. There was no vascular or neurological injury, and passive motion and active motion of the shoulder were painful and limited. Computed tomography (CT) scan with 3D reconstruction was done prior to surgery, which confirmed a minimally displaced coronal-oblique fracture at the base of the acromion (Figures and ). Informed consent was taken from the patient to publish this case report.

pmc-6015694-1

A 53-year-old male presented with hoarseness of 12-year duration. He gave no history of breathing or swallowing difficulty. On enquiring further, he had complaints related to gastric acid reflux. He was a smoker but had quit smoking 6 months back. He is a politician with a history of voice abuse. On flexible fibreoptic evaluation, there was a 0.5 cm polypoidal, cystic mass pedicled on the medial free edge of the middle 1/3 of the right true vocal fold. There was no abnormality of vocal fold mobility. Rest of the ENT examination was normal. Based on a history of long-standing hoarseness, voice abuse, and presence of a solitary polypoidal lesion over the true vocal fold, a preoperative diagnosis of a laryngeal polyp was made. No preoperative radiology was taken due to the unambiguous nature of the clinical findings. The patient was taken up for microlaryngeal surgery (MLS), and the lesion was excised with cold instruments. Postoperative period was uneventful with patient reporting near-normal voice during first follow-up after one week. Surprisingly, the postoperative histology showed features consistent with laryngeal myxoma. On histological examination, our case showed a polypoidal tumour lined by hyperplastic stratified squamous epithelium (). A subepithelial unencapsulated lesion was noted. The latter was paucicellular formed by small, bland, spindle to stellate cells having indistinct cytoplasmic margins and hyperchromatic nuclei (). No significant atypia or mitotic activity or any necrosis was noted (). These cells were embedded within an abundant myxoid matrix. Immunohistochemically (IHC), the cells were negative for CD34, smooth muscle actin (SMA), and S100 (Figures –). Thus, a final diagnosis of laryngeal myxoma was rendered. The absence of stromal vasculature, hemorrhage, hemosiderin-laden macrophages, and hyalinization of basement membrane helped to differentiate it from a vocal fold polyp [].

pmc-6015696-1

A 68-year-old man who was diagnosed with myasthenia gravis three months prior to admission presented with acute nonpruritic painless 1 cm erythematous papules over the upper torso, accompanied with subjective fevers, chills, nausea, vomiting, and frontal headache for 2 days. His past medical history was significant for heart failure with preserved ejection fraction of 65% and mechanical mitral valve replacement for which he was on warfarin. He was started on prednisone 40 mg daily and pyridostigmine 120 mg four times daily, two and a half months prior to admission, and azathioprine 150 mg daily, 10 days prior to admission. Upon presentation, he was found to have a temperature of 102.7 degrees Fahrenheit, with a heart rate of 107 beats per minute, blood pressure of 159/87 mmHg, and oxygen saturation of 95% on room air. A complete blood count with differential was remarkable for a white blood cell count of 15,000 cells/mm3, with 89% neutrophils and venous lactate of 2.6 mmol/L. All other laboratory parameters including electrolytes, blood urea nitrogen, creatinine, blood glucose, and liver function tests were within normal limits. Given the fever, leukocytosis, and elevated lactate, the initial concern was for sepsis. Infectious workup included blood cultures, chest X-ray, urinalysis with urine culture, respiratory viral panel, Lyme titers, and procalcitonin. The chest X-ray showed a possible new left lower lobe basilar opacity, procalcitonin was 0.59 ng/mL, and the patient was started on antibiotics with ceftriaxone and azithromycin for suspected lower respiratory tract infection. Of note, his azathioprine was discontinued on presentation, due to concern for continued immunosuppression and possible infection. Two days after presentation, given the improvement in clinical symptoms the azathioprine 150 mg was reinitiated. Within a few hours, he became acutely ill, febrile to 103.7 degrees Fahrenheit and tachycardic to 115 beats per minute, with return of the initial presenting symptoms and new onset photophobia. Initially, there was concern for worsening sepsis; repeat procalcitonin was ordered along with C-reactive protein and erythrocyte sedimentation rate (ESR), with antimicrobial therapy broadened to vancomycin, piperacillin/tazobactam, and intravenous acyclovir. Notably, a diffuse 1 cm papulopustular rash erupted over the scalp, head, neck, thorax, abdomen, and upper and lower extremities including the palmar and dorsal aspects of the hand (). As the cutaneous findings were nonspecific, the differential remained broad and infectious workup included bacterial, fungal, viral, or drug hypersensitivity. Drug hypersensitivity was suspected given the return of symptoms along with rash after rechallenge of azathioprine and the temporal response to the symptoms. The repeat procalcitonin was now elevated further to 5.36 ng/mL along with an elevated C-reactive protein of >270 mg/L and an ESR of 44 mm/hr. The azathioprine was discontinued and the symptoms subsided with the pustules reduced in size and number. Biopsy of the pustule showed suppurative folliculitis, which is expected from a neutrophil driven process, consistent with azathioprine hypersensitivity (). All pustule stains, bacterial, viral, including herpes zoster and varicella zoster, and periodic acid-Schiff-diastase (PAS-D) stains, were negative. Repeat liver function tests including AST/ALT remained within normal limits, and a complete blood count revealed a white blood cell count of 9,300 cells/mm3 with 0% eosinophils. Antimicrobial therapy was deescalated. Over the next few days, the rash and symptoms resolved and the CRP decreased to 108 g/L. We utilized the Naranjo algorithm to estimate the probability of azathioprine causing hypersensitivity and found that our patient had a probable hypersensitivity reaction to azathioprine [].

pmc-6015701-1

An 80-year-old female presented to clinic with a mass over the superior aspect of the right scapula. The mass was achy but did not interfere with performing activities of daily living. However, it was bothersome for the patient and she stated that it had been enlarging over the previous few months. She denies any local injuries or recent surgeries on the affected side. She denied having weakness in the left arm when compared to the contralateral side. She denied having trouble with overhead activities. She had not noticed any constitutional symptoms or nighttime pain. She did give a history of having a similar mass on the contralateral side, which was excised 10 years previously with a favorable result. She was very interested in having the new mass excised as well. Inspection of the area is unremarkable, but palpation of the area demonstrates a firm, nonmobile, and nonpulsatile mass in the area of the upper trapezius overlying the scapula. The mass is longer in its medial to lateral dimension than craniocaudad. With deeper palpation, slight tenderness can be elicited. Examination of the shoulder does not yield signs of rotator cuff weakness or shoulder pain with provocative maneuvers. Plain X-ray demonstrates narrowing of the posterior glenohumeral joint space with sclerosis secondary to osteoarthritic changes. The acromiohumeral interval is measured to be 8 mm without signs of superior migration of the humeral head. Magnetic resonance imaging (MRI) shows an elongated lesion arising from the AC joint and tracking medially to superficial and within the trapezius muscle (Figures and ). It measures 2 cm (AP) × 13 cm (transverse) × 1.8 cm (craniocaudad). The lesion appears cystic with peripheral enhancement. There is also suspected full-thickness tear of the anterior fibers of the supraspinatus. Although the mass did not prevent the patient from performing her activities of daily living, it was bothersome enough for her that she wanted it removed. Under a general anesthetic, an incision was made directly over the palpable mass. With careful dissection, a stalk emanating from the AC joint was identified. The mass extended laterally from the AC joint within the trapezius muscle for approximately 13 cm (). Once it was dissected free, the mass was removed en bloc. A distal clavicle excision was then performed using an oscillating saw. After the cyst was excised, it was incised revealing thick mucoid content (Figures and ). The patient was followed up at three weeks and three months postoperatively. She said she felt pain relief immediately after the surgery and she continued to have full, pain-free range of motion with no signs of recurrence.

pmc-6015702-1

A 74-year-old male patient was admitted to our hospital in March 2017 to undergo liver resection to treat a malignant hepatic lesion diagnosed with CT and PET and a fine-needle biopsy positive for squamous carcinoma. The hepatic tumour discovered during follow-up for a previous bladder cancer submitted to endoscopic surgery three years before measured 22 mm in diameter and was located in the VIII Couinaud's segment [] of the liver in association with three smaller hypodense liver lesions with a focal dilatation of peripheral biliary tree (). The case is discussed with radiologists, oncologists, and pathologists of our hospital. Even if the lesion had been the single site of disease; due to the proximity/doubtful infiltration of the lesion to the biliary tree, we decided to submit the patient to an explorative staging laparotomy and possible palliative surgery. Our internal protocol states that during the preadmission every patient who is a candidate for a liver resection is subjected to a routine liver function test with ICG to determinate the most appropriate surgical procedures []: 0,5 mg/Kg ICG are routinely injected intravenously up to seven days before surgery to evaluate the ICG retention rate at 15 min (R15). In our case 45 mg of ICG was intravenously administrated to test hepatic function, ten days before the surgery (patient R15 = 8.9). Thanks to the ICG property of being fluorescent with the light emitted from the photodynamic eye of the laparoscopic system in our possession, it is possible to visualize the lesion during the surgical procedure. To this target, timing of administration and dose of ICG are key points. Several studies have demonstrated that the effective dose of ICG depends on the timing of injection; in particular, if the function liver test had been performed more than 7 days before surgery it would have been necessary to administer an adjunctive dose (0,1 mg/Kg) the day before []. In this case, it was necessary to administrate an adjunctive dose of ICG the day before the surgery (9 mg of ICG injected intravenously). After laparotomy, exploration of the abdominal cavity, and exposure of the liver, we easily confirmed the superficial lesion in the VIII Couinaud's segment. The liver surface has been analysed with the fluorescent imaging system. The fluorescing tumour has been clearly identified and defined on the liver surface, as shown in . We have also identified that a large area of fluorescent parenchyma that gets from the peripheral of the lesion up to the portal pedicle such as the neoplasia would interest the right biliary tree in the form of neoplastic lymphangitis (). This datum was not preoperatively known. A right hepatectomy would have been the oncologically correct surgical procedure due to the infiltration of right biliary duct. Considering the probable metastatic nature of the lesion, the absence of a clearly primary lesion, the age, the comorbidities, and the small size of residual liver, we have decided to perform an atypical segmental resection of S8 associated with cholecystectomy and lymphadenectomy of the hepatic pedicle nodes, including the area of impaired biliary excretion. At the histological examination, the lesion, the lymph nodes of the hepatic pedicle region, and the right biliary branch, respectively, resulted in hepatic metastases from squamous cell carcinoma and sites of metastatic location. As expected the resection margin was interested by neoplasia. In particular, the histological examination showed the following:Macroscopical exam: the neoplasia, in a site, appears to be in contact with the resection margin Microscopical exam: parenchymal hepatic section that showed metastatic localization of squamous carcinoma moderately differentiated. The neoplasia interest the surgery resection margin. In this case, fluorescent imaging has revealed a fluorescing ring around the hepatic metastasis (). The fluorescence of the cholestatic area was shown on the cut surface ().

pmc-6015706-1

A 45-year-old woman was admitted to an emergency department with dyspnea and swelling on her hands and face for at least three days. She was nonsmoker and did not have any chronic disease. Her dyspnea and hypoxemia were getting worse and she was accepted to ICU. Noninvasive mechanical ventilation (MV) was used for initial treatment but hypoxemia was worsened; hence, she was intubated and invasive MV was used. On her physical examination, we auscultated mild crackles bilateral on lower lung zones. Her chest X-ray showed bilateral nonhomogenous infiltration at middle and lower zones (). While initial fraction of inhaled oxygenation (FiO2) was 80% on MV, her PaO2 was 65 mmHg and lung protective MV strategies were applied. An appropriate fluid replacement, antibiotics, and other medical treatments were applied. Undergoing MV, FiO2 level was decreased gradually and she was weaned from MV on her fifth day of ICU stay and MV. After weaning, we observed that her oral secretions increased and her left nasolabial sulcus wiped out. On her neurological examination, abnormal findings were not found except left facial paralysis. We did not study out any pathological imagination neither on her cranial computed tomography (CT) nor on cranial magnetic resonance imaging (MRI). Peripheral facial paralysis (PFP) was diagnosed and intravenous steroid treatment 1 milligram per kilogram (methylprednisolone) was added to her therapy by neurologist. At the same time, dermatological lesion occurred and, on her dermatologic examination, oedema on her face, pustular lesions on her skin, and fissure on her tongue were detected; therefore labium mucosal biopsy was taken and mucositis was reported (). When we talked to the patient about her symptoms, she informed us that she had recurrent and spontaneous facial paralysis in previous years. According to her medical history, signs of orofacial oedema, fissure on the tongue, and PFP, MRS was diagnosed. She was transferred from ICU to department of neurology and then she was discharged from the hospital.

pmc-6015711-1

A healthy 7-year-old girl of Indian descent presented with one-year duration of hypochromic linear bands in two regions. The lesions were present on the right forearm and left leg and buttocks. Neither the patient nor her parents were able to recall any inciting illness, allergy, or environmental or social exposure that may have preceded the onset, which was gradual. There was no associated pruritus, pain, hair loss, or nail involvement. No recent growth had been noted. The patient had not received any previous topical or systemic treatment for the lesions. The patient's past medical history was negative for atopy and otherwise unremarkable, as was her family history. On examination 2 mm hypopigmented lichenoid macules were noted coalescing into a linear patch on the dorsal aspect of the patient's right forearm (Figures and ). The eruption ended at the distal forearm, sparing the right hand, fingers, and nails. The distribution was consistent with BL. Similar lesions were also noted on the left buttock, though somewhat more diffuse, but also progressing distally along a BL to the left posterior thigh (Figures and ). The lesions in both locations were nonscaling, nonpainful, nonpruritic, and stable in appearance according to the patient's parents. No biopsies were taken at the request of the patient's parents. A diagnosis of LS was made clinically, and observation was recommended with explanation of the disease course. A follow-up visit was scheduled but the patient did not return to the clinic.

pmc-6015712-1

A 58-year-old man underwent pancreatoduodenectomy and right hepatic lobectomy with choledochojejunostomy for a duodenal gastrointestinal stromal tumor with multiple liver metastases. Ten years after the operation, he developed recurrent fever and upper abdominal pain with hepatobiliary enzyme elevation. He underwent double-balloon endoscopy (DBE) and anastomotic stenosis was revealed. There was no evidence of malignancy, and we diagnosed cholangitis due to benign anastomotic stenosis. Balloon dilation for stenosis and biliary stenting with a plastic stent (PS) was performed. As relapsing cholangitis occurred 6 times a year, he underwent EUS-HGS with MS. We used a GF Type UCT 260 (Olympus Medical Systems, Tokyo, Japan) endoscope. The B3 duct was visualized from the stomach. After the absence of blood vessels crossing the puncture route was confirmed, the bile duct was punctured with a 19-G needle (EZ shot 3; Olympus) (). Then, a 0.025-inch guidewire (VisiGlide 2; Olympus) was introduced into the jejunum in an antegrade manner. Subsequently, the puncture site was dilated with a 3.6-Fr double-lumen catheter (Uneven Double Lumen Catheter; PIOLAX, Tokyo, Japan), and another 0.035-inch wire (Revowave; PIOLAX, Tokyo, Japan) was introduced into the jejunum (). An 8 mm covered MS (Niti-S; TaeWoong Medical Inc., Seoul, Korea) was placed (). No adverse events occurred. Before EUS-HGS, fever and hepatobiliary enzyme elevation frequently recurred. After EUS-HGS, the enzymes normalized, and cholangitis has not recurred in 5 months.

pmc-6015712-2

A 68-year-old man underwent extended right hepatectomy and bile duct resection with choledochojejunostomy for hilar cholangiocarcinoma. Relapsing cholangitis occurred because of anastomotic benign stenosis after the operation. Biliary stenting with PS had repeatedly been performed, but the stenosis did not improve. Thus, he underwent EUS-HGS with MS. The B3 duct was punctured with a 19-G needle (Expect; Boston Scientific, Natick, MA, USA). Then, a 0.025-inch guidewire (Radifocus; Terumo, Tokyo, Japan) was introduced into the jejunum. Subsequently, the puncture site was dilated with a 6-Fr diathermic dilation catheter (Cysto-Gastro-Set; ENDO-FLEX, Voerde, Germany). The wire was changed to another 0.035-inch wire (THSF; Cook Medical, Winston-Salem, NC, USA), and an 8 mm covered MS (Niti-S) was placed. No adverse events occurred. Nine months after EUS-HGS, cholangitis occurred only once due to debris and granulation. We performed balloon sweeping for debris and placed a PS into the MS. Twelve months after EUS-HGS, we replaced the PS with an MS. As in case 1, hepatobiliary enzymes normalized, and cholangitis has not recurred in 11 months.

pmc-6015715-1

A 33-year-old man was involved in an automobile accident and was brought to our hospital by ambulance. He had been in the front passenger seat and had been wearing a three-point seatbelt. He reported severe back pain, but showed no neurological deficit. Anteroposterior and lateral radiographs of the spine showed an increased gap between the 1st and 2nd lumbar spinous processes and 2nd lumbar vertebral fracture (figures not shown). Magnetic resonance imaging (MRI) of the spine also demonstrated an L2 vertebral fracture and disruptions of the posterior ligamentous complex between L1 and L2, in combination with extensive subcutaneous hematoma (). Computed tomography (CT) of the spine in the sagittal orientation and 3-dimensional (3D) CT further revealed the involvement of the superior end plate of the L2 vertebra, comprising horizontal splitting from the left pedicle, through the left transverse process, and reaching the center of the neural arch (). The right-sided L2 pedicle was intact. After checking the general condition of the patient and excluding intra-abdominal injury by enhanced CT and ultrasonography, the patient underwent L1-L2 single-level instrumented fusion using a posterior approach. Initially, monoaxial pedicle screws with conventional trajectory were placed at L1 and L2 pedicles on the right side (intact pedicle side). A rod slightly bent in lordosis was then introduced and connected with these pedicle screws with a compression force applied between screws. This procedure achieved reduction and the fracture gap at the left L2 pedicle and lamina was completely closed. Polyaxial pedicle screws were used on the left side. A pedicle screw with a conventional trajectory was placed at the left L1 pedicle. A CBT pedicle screw was then inserted through the fractured L2 pedicle under fluoroscopy. This CBT screw was used as an alternative to an osteosynthesis screw. A rod was introduced on the left side, bilateral facet fusion with local bones obtained from the lower one-third of the L1 spinous process was performed, and the wound was closed. Although the merits of cross connectors for CBT screws remain unclear, we applied the connector in this case because connecting bilateral pedicle screws along conventional trajectories has been reported to increase the pullout strength of these screws []. Postoperative X-rays showed good reduction by this single-level fixation (). The postoperative period was uneventful. Although rigid fixation was obtained with this procedure, a thoracolumbosacral orthosis (TLSO) was applied for 6 weeks, since this case was our first experience. Physical activities were not restricted with the TLSO. Sagittal CT and 3D-CT obtained at 6 months and 1 year postoperatively showed proper trajectory of the CBT pedicle screw and complete bone union ().

pmc-6015717-1

A 20-year-old male presented with worsening bloody diarrhea of 4 months' duration associated with cramping abdominal pain and weight loss of 4 Kg. On admission, he was hemodynamically stable. Physical examination showed mild tenderness to deep palpation in the left lower quadrant. Laboratory tests were consistent with anemia (hemoglobin = 10.5 mg/dl, hematocrit = 33.5%), thrombocytosis (platelets = 568000/mm3), low iron level (iron = 25mg/dl), and normal C-reactive protein (CRP). Stool analysis, ova and parasite test, Clostridium difficile toxin assay, and stool culture were negative. Colonoscopy revealed left-sided colitis with marked erythema, absent vascular pattern, and friability erosions (Mayo score 2). Biopsies showed chronic active colitis consistent with UC. Based on the clinical presentation and laboratory, endoscopic, and pathologic findings, the patient was diagnosed with moderate left-sided UC and was started on oral and topical 5-aminosalicylic acid (5-ASA) without any response to treatment: bloody diarrhea (more than 5 bowel movement per day), severe abdominal pain, low grade fever, and additional weight loss in addition to severe anemia (hemoglobin = 7.3g/dl) and high CRP with negative stool tests. High dose steroids therapy was started with marked improvement. Steroid tapering caused recurrence of symptoms and anemia at 20mg prednisone per day. Relying on the findings above, the patient had left-sided UC and is steroid-dependent, so Infliximab 5mg/kg was initiated at 0, 2, and 6 weeks, then every 8 weeks without any improvement after 4 months of treatment with persistent bloody diarrhea and severe iron deficiency anemia. Repeated colonoscopy showed severe inflammatory mucosa with deep ulcerations and pseudopolyps formation at the splenic flexure and the distal part of the left colon, separated by healed mucosa. Biopsies from the pathologic area revealed severe chronic active colitis consistent with inflammatory bowel disease/UC without any evidence of cytomegalovirus inclusions. Given the lack of response to Infliximab and the worsening endoscopic findings, resistance to therapy was suspected. Additional laboratory tests showed low Infliximab through level with high antibodies level to Infliximab. The patient was switched to combination therapy with Adalimumab 160mg at week 0, 80mg at week 2, and 40mg every other week plus Azathioprine 2.5mg/Kg with only partial response: improvement of diarrhea but persistence of severe nocturnal colicky abdominal pain. Adalimumab trough level was very low with the absence of anti-drug antibodies. So, Adalimumab was increased to 40mg per week. Two months later, he continued to have severe colicky abdominal pain and distension with weight loss. New colonoscopy revealed complete mucosal healing and a giant pseudopolyp in the left colon and another obstructive one at the level of the splenic flexure (Figures and ). Biopsies were consistent with chronic inflammation with architectural distortion and cryptic abscess. Abdominal CT scan confirmed the presence of two giant pseudopolyps with evidence of obstruction at the splenic flexure (Figures and ). The patient had total colectomy () with ileoanal anastomosis and J pouch.

pmc-6015717-2

A 71-year-old male, previously healthy, was seen for the first time in May 2011 for diarrhea and rectal bleed. His physical examination was unremarkable. Laboratory tests were within normal range. Ileocolonoscopy showed mucosal inflammation and ulcerations over a segment of 7cm at the level of transverse colon. Biopsies were in favor of chronic active colitis. The patient was treated as colonic IBD and was started on Mesalamine 4g per day but he was lost to follow-up. Four years later, he was seen again in January 2015 for the same previously described symptoms. He stated that he took Mesalamine for 6 months and stopped by his own after marked improvement and he was asymptomatic since then until the reappearance of symptoms associated with abdominal pain few days prior to the presentation. Physical examination and lab tests were normal. Colonoscopy revealed an obstructive giant pseudopolyp () at the level of the transverse colon; biopsies showed chronic inflammation with architectural distortion and granulation tissue formation. Abdominal CT scan confirmed the presence of giant pseudopolyp (). The patient was treated with segmental colonic resection and the surgical pathologic report was CD. The final diagnosis was colonic CD complicated by an obstructive giant pseudopolyp.

pmc-6015989-1

A 32-year-old male presented to the emergency department with 20 mins of cramping retrosternal chest pain radiating to his left shoulder accompanied by sweating and shortness of breath. He did not have a history of any cardiovascular risk factors, such as a history of smoking, diabetes, or hypertension. He did not have any family history of cardiac events in family members at an early age. He had a self-reported diagnosis of hypothyroidism for which he was self-administering 120 mg of Armour Thyroid daily. At the time of presentation, his blood pressure was 171/106 mm of Hg, heart rate was 88 beats per minute, and respiratory rate was 16 breaths per minute. Physical exam was notable for well-developed musculature and cystic acne. Other physical examination findings were unremarkable. A 12-lead electrocardiogram (ECG) (Figure ) demonstrated ST-segment elevations in leads aVL, I, and v1-v6, as well as ST segment depressions in leads II, III, and aVF, suggestive of an acute ST elevation myocardial infarction (STEMI). Initial lab work reported markedly increased levels of cardiac troponin. Urine drug screen was negative, eliminating cocaine as a potential etiology. Transthoracic echocardiography (TTE) displayed a moderate increase in left ventricular (LV) wall thickness, reduced ejection fraction (EF) of 40%, grade 1 diastolic dysfunction, and hypokinetic anterior and anteroseptal walls in the distribution of the left anterior descending (LAD) coronary artery. Emergent left heart catheterization was performed via the right radial artery using the Seldinger technique. An LV pressure of 117/5 mm of Hg with an LV end-diastolic pressure of 14 mm of Hg was noted. A coronary angiogram revealed a complete occlusion of the LAD at the ostium (Figure ). The remainder of the coronary arteries were patent without evidence of atherosclerotic changes. Manual thrombectomy of the LAD was performed, and a XIENCE Alpine 3.25 mm x 15 mm drug-eluting stent (Abbott Laboratories; Abbott Park, IL, USA) was positioned leading to return of TIMI-III flow (Figure ). The patient was started on dual antiplatelet therapy with aspirin and clopidogrel, in addition to heparin and eptifibatide infusions. His subsequent fasting lipid profile was normal with low-density lipoprotein of 127 mg/dL, a high-density lipoprotein of 31 mg/dL, and triglycerides of 44 mg/dL. Focused questioning to elicit the potential cause of the myocardial infarction led to the revelation that the patient participated in recreational bodybuilding for which he self-administered exogenous testosterone therapy and was using Armour Thyroid as a weight loss supplement. His testosterone levels were elevated at 1,311 ng/dL with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels below trace levels of 0.20 mIU/mL, confirming exogenous testosterone supplementation. Free triiodothyronine (T3) was high at 4.08 pg/mL with a suppressed total thyroxine (T4) at 1.2 mcg/dL and a thyroid stimulating hormone (TSH) at 0.20 mIU/mL, confirming Armour Thyroid administration.

pmc-6015993-1

A 64-year-old African-American male presented with an elevated PSA of 9.3 ng/mL and no previous history of prostate biopsy. He had a systematic TRUS-guided extended sextant biopsy with two of 12 cores demonstrating prostate cancer, one with GS 4+3 and a second with GS 3+4, both in the left apical region. He had no baseline urinary or bowel problems, but did have erectile dysfunction adequately managed with sildenafil taken as needed for sexual performance. His AUA urinary symptom score was 3 and SHIM score was 14 without use of PDE5 inhibitors. Using the web-based Memorial Sloan Kettering Cancer Center nomogram, his risk of nodal involvement was estimated to be 7% []. He was in good overall health and his age-adjusted life expectancy was estimated to be 19.4 additional years using the Social Security Administration life tables. After discussion of all treatment options with the multidisciplinary team, he elected to pursue definitive treatment with prostate SBRT. Diagnostic multi-parametric prostate MRI and review by the multidisciplinary prostate imaging conference previously demonstrated a 1.7 cm T2-weighted hypointense lesion with corresponding restricted diffusion in the anterior apical transition zone left of midline that was considered high suspicion based on imaging parameters but associated well to the systematic biopsy cores positive for prostate cancer (Figure ). The whole prostate volume and the area of MRI cancer suspicion were segmented using post image processing software. Following the MRI, three gold fiducial markers were placed in the urology office via a TRUS-guided approach. The radiation therapy planning CT scan was scheduled two weeks after fiducial placement. No urinary catheter, rectal balloon, or rectal spacer was used. After the simulation CT scan was completed, axial T2-weighted and post contrast T1-weighted MRI were fused with the CT images using radiation therapy planning software. Target volumes of the prostate and the high-risk lesion were then generated on the CT based on MRI segmented regions of suspicion. The radiation oncologist and urologist met to review the image fusion and target volumes prior to proceeding with final treatment planning. In this case, the highest suspicion lesion was located in the left anterior apical prostate as visible on T2-weighted MRI. Hence the prostate surrounding the high-risk lesion was included in the high-risk target volume for planned SIB (Figure ). For transition zone and central gland lesions, limiting dose to the urethra presents the greatest challenge to radiation therapy planning. However, most prostate SBRT protocols recommend achieving normal tissue dose limits over complete coverage of the high-risk target volume. In this case, adequate coverage was possible while limiting urethral dose to an acceptable range. The high-risk volume received 40 Gy SIB in five fractions while the entire prostate received 36.25 Gy. He was placed on tamsulosin during radiation therapy after developing dysuria, diminished urinary stream, and frequency corresponding to an increased AUA symptom score of 14. These irritative urinary symptoms were his only radiation-associated side effects. He did not develop any significant lower gastrointestinal symptoms. Six months after his treatment, he continued to have irritative urinary symptoms and remained on tamsulosin.

pmc-6015993-2

A 65-year-old Caucasian male presented with an elevated PSA of 8.98 ng/mL and a history of TRUS-guided extended sextant biopsy negative for prostate cancer three years prior to presentation. At the time of his prior prostate biopsy, his PSA was 7.25 ng/mL. He had mild baseline lower urinary tract symptoms with an associated AUA urinary symptom score of 14. He denied any erectile dysfunction and had a SHIM score of 25. MP-MRI was performed, and review by the multidisciplinary prostate imaging conference revealed patchy diffuse abnormal signal that is often seen in patients with prior biopsy history and/or inflammation. Despite this diffuse irregularity in signal in the right posterolateral peripheral zone, there was a focal area of well-defined hypointensity with corresponding diffusion restriction suspicious for harboring prostate cancer. There was notable central gland hyperplastic nodules with regional areas of low T2 signal intensity in the left anterior transition zone that was low suspicion for representing malignancy more likely representing benign prostatic hyperplasia nodularity. With these findings, he underwent MRI/TRUS fusion-targeted biopsy that demonstrated GS 4+3 adenocarcinoma in 80% of the specimen cores sampled from the MRI-targeted lesion in the posterior peripheral zone. After discussion of all treatment options with the multidisciplinary team, he elected to proceed with prostate SBRT. The patient then had TRUS-guided fiducial markers placed followed by the radiation therapy planning CT scan two weeks after fiducial marker insertion. CT and MRI fusion was performed to allow for CT generation of the target volumes of the prostate gland and the high-risk intraprostatic lesion which was used for MRI-targeted biopsy proven to represent the intermediate-risk prostate cancer. The radiation oncologist and urologist met to review this image fusion between treatment simulation CT and MP-MRI as well as target volumes for SBRT and SIB. In this case, the highest suspicion lesion was located in the posterior peripheral zone, well visualized on T2-weighted MRI around which the SIB region was drawn. Dose limitations in the region of the rectum were considered posteriorly, and the ipsilateral neurovascular bundle exposures were considered but not considered dose limiting (Figure ). The SIB volume in the posterior peripheral zone received 40 Gy in five fractions while the entire prostate gland was administered 36.25 Gy over the same time course. The patient was being managed with tamsulosin prior to starting radiation therapy due to his history of lower urinary tract symptoms. He developed moderate dysuria during the final two fractions of radiation therapy that was managed by increasing his tamsulosin to twice daily dosing. One week after radiation was completed, he developed a self-limited diarrhea lasting three days. By his one-month follow-up visit, his urinary and gastrointestinal symptoms had returned to baseline.

pmc-6015995-1

A 58-year-old Caucasian woman, with past medical history significant for a 2.4 cm GIST diagnosed with esophagogastroduodenoscopy (EGD) (Figures , ) (performed for persistent epigastric pain despite therapy) six months earlier and s/p laparoscopic partial gastrectomy, presented to the emergency department (ED) with new-onset jaundice initially observed by her son four days prior to arrival. Also, she reported generalized weakness, fatigue, and itching for the past several days. The patient reported no previous history of alcohol consumption, intravenous drug use, acquiring tattoos or non-sterile piercings, receiving transfusions of blood or blood products, sexual promiscuity, residence in a developing country, occupational exposure to toxins (she worked as a school teacher), or prior liver diseases. She reported no family history of liver diseases. The earlier biopsy had shown GIST, histologic grade G2 (high grade; mitotic rate > 5/50 per high-power field (HPF)), with spindle cells and no necrosis (Figures , ). The margins were negative. The tumor cells were positive / immunoreactive for CD34, CD117, and DOG-1 (Figures , ). A recent follow-up computed tomography (CT) scan showed no recurrence. At presentation, the patient appeared icteric with yellowish discoloration of the skin and sclera. She was afebrile (temperature 97.4) and hemodynamically stable (heart rate 72 beats per minute (BPM), blood pressure 110/85 mm Hg). On physical exam, the abdomen was soft and not distended, with no tenderness and normoactive bowel sounds. Murphy’s sign was negative and there was no guarding nor rigidity. Initial laboratory testing showed significantly elevated transaminases with aspartate aminotransferase (AST) of 1450 U/L (10-35 U/L) and alanine aminotransferase (ALT) of 1632 U/L (10-55 U/L). Also, there were increased total bilirubin of 4.9 mg/dL (<1.2 mg/dL) and increased direct bilirubin of 2.7 mg/dL (<0.6 mg/dL). The alkaline phosphatase (ALP) was 162 U/L (40-150 U/L), the gamma-glutamyltransferase (GGT) was 95 U/L (5-50 U/L), and the international normalized ratio (INR) was elevated at 1.9 (0.8-1.2). The serum total protein, serum albumin, serum electrolytes, and complete blood count (CBC) were within normal limits. The patient’s Model for End-Stage Liver Disease (MELD) score was calculated to be 28 upon arrival. Further laboratory testing showed that the serum iron level, total iron-binding capacity (TIBC), serum ferritin, ceruloplasmin level, and thyroid function tests (TFTs) were within normal limits. An acetaminophen level and an autoimmune workup, including antinuclear antibody (ANA), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA), were negative. And, viral serologies for hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were negative. An abdominal ultrasound revealed mild hepatomegaly. Upon medication reconciliation, it was discovered that the patient was taking imatinib, prescribed by her hematologist-oncologist, for the past four months. The medication was discontinued on hospital admission due to the concern for hepatotoxicity. No other potentially hepatotoxic medications were noted. Prior liver function tests (LFTs), before initiation of imatinib, were all within normal limits. As the LFTs were not improving with conservative management, an interventional radiology (IR)-guided liver biopsy was performed for the purpose of diagnosis as well as to assess the extent of liver injury (Figures -). After seven days, the patient’s transaminases began to decrease, ultimately falling to AST of 483 U/L and ALT of 544 U/L during the hospital admission. The transaminases, as well as the rest of the LFTs, continued to trend down and were within normal range two months later.

pmc-6015996-1

A six-year-old-African American female presented to our care in April 2010 for the evaluation of sleep attacks and apnea during sleep. According to her mother, the patient experienced cataplexy episodes with laughter. At that time, the patient underwent a nocturnal polysomnogram (NPSG) for further investigation. According to the results of the sleep study, patient slept 474.00 minutes out of 539.3 minutes in bed for a sleep efficiency of 87.9% (n=89%). Her sleep latency was decreased at 7.3 minutes and 68.1% of the total sleep time was spent in the supine position. In addition, rapid eye movement (REM) sleep and latency were logged at 17% and 68.5 minutes (n=136-156), respectively. Furthermore, the NPSG illustrated that the patient experienced five central apneas, one mixed apnea, five hypopneas, and an apnea-hypopnea index of 1.4 events/hour consistent with mild obstructive sleep apnea (OSA) by pediatric criteria []. The patient underwent another NPSG with a multiple sleep latency test (MSLT) in November 2010 for persistent symptoms. Results indicated that the patient slept for 395.50 minutes out of the 411.8 minutes in bed, which translated to a sleep efficiency of 96.0%. Similar to the previous study, the patient experienced decreased sleep latency at 3.3 minutes. In addition, REM sleep and latency were logged at 20.4% and 106.5 minutes, respectively. In contrast to the earlier NPSG study, this evaluation illustrated three central apneas, six mixed apneas, nine obstructive hypopneas, and an apnea-hypopnea index of 2.9 events/hour with <1 being normal. An MSLT is the primary diagnostic tool for narcolepsy and is typically performed following an NPSG to measure sleep latency, which is the time it takes an individual to go from wakefulness to sleep. Additionally, it measures how quickly the patient enters REM sleep, known as sleep onset REM periods (SOREMPs). This test includes four or five nap periods of 20 minutes each []. The patient is instructed to lie in the darkroom and attempt to fall asleep. Sensors transmit data such as the amount of time needed to fall asleep and enter REM sleep. Once asleep, the patient will be woken up fifteen minutes later; if 20 minutes pass and the patient has not fallen asleep, the nap trial is terminated. Next, the patient is given a two-hour break before the second nap trial can begin. During this break, the patient must stay awake and this process is repeated four more times []. The results of the study include the mean sleep latency (MSL) and the number of SOREMPs recorded. The diagnostic criterion requires an MSL of ≤8 minutes and ≥2 SOREMPs on an MSLT []. Our patient underwent a series of five nap trials with a sleep latency of 3, 2, 3, 6, and 2 minutes, respectively, and a mean sleep latency of 3.2 minutes. However, the patient did not enter REM sleep during any nap trials, thus having 0 SOREMPS. Additionally, laboratory workup for HLA-DR15 and DQ0602 was positive, and the patient had documented cataplexy.

pmc-6015999-1

We present the case of a white, Hispanic, 58-year-old, non-smoker female. She has a past medical history of obstructive sleep apnea and chronic obstructive pulmonary disease (chronic bronchitis). Her travel history includes the Dominican Republic and Caribbean Islands. She worked for several years in an automobile repair shop and was exposed to lead and paint. Her current occupation is as a telephone operator in a call center, which requires her to speak continually. Fifteen years ago, she developed a progressive cough. During the following four years, she was evaluated by more than eight pulmonologists who were unable to make a diagnosis. She developed a productive cough with white sputum and blood titer. Her alpha-1-antitrypsin serum, perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA), cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA), and rheumatoid factor were all within normal limits. Her purified protein derivative (PPD) and fungal infection tests were negative. Lung function tests revealed an obstructive pattern. Her forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 70% and total lung capacity (TLC) was 72%. A computed tomography (CT) scan showed mild ground glass infiltrates in the lung bases (Figure ). Finally, in December 2011, a lung biopsy via assisted thoracoscopic surgery (VATS) was performed, and she was diagnosed with constrictive bronchiolitis and diffuse idiopathic neuroendocrine cell hyperplasia with carcinoid tumorlets. She was treated with octreotide; however, the treatment was interrupted several times due to issues with insurance and difficulties visiting the medical center. Her treatment was restarted in our hospital after three years in May 2014. Since then, CT scans taken every six months show a stable disease. She currently has a stable radiographic disease with no new complaints during the over two years of follow-up.

pmc-6016000-1

A nine-year-old girl presented to the emergency department with abdominal pain and distention for the past one week, with sudden increase in intensity of pain for the last four hours. The patient had not yet reached the age of menarche. There was no associated nausea or vomiting and her bowel habits were not affected. Past medical, surgical, and family history was also insignificant. An abdominal examination revealed tenderness in the lower abdomen with a firm palpable mass occupying the right side of the abdomen. Her blood counts showed an elevated total leukocyte count of 13,000 cells/dL with neutrophilic predominance. Initial clinical assessment raised the possibility of an appendicular mass. The patient therefore immediately underwent a contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis, which revealed a large soft tissue mass measuring approximately 80 x 150 x 170 mm in anteroposterior, transverse, and craniocaudal dimensions, respectively, and was predominantly occupying the right mid and lower quadrant. The mass showed some areas of low attenuation, suggestive of necrosis/intratumoral edema (Figure ). There was free fluid noted adjacent to the lesion and in the pelvis (Figure ). The right ovary was separately identified and appeared normal (Figure ). Anteromedially, the mass had a tortuous, twisted vascular pedicle that was likely originating from the left adnexa (Figure ). Additionally, few speckled calcifications were noted in the mass (Figure ). No enhancing fibrovascular septa were noted in the lesion. No evidence of regional lymphadenopathy or distant metastases was found on the CT examination. On the basis of the radiological picture, an impression of left ovarian tumor with torsion was suggested. The patient then underwent an exploratory laparotomy and left salpingo-oophorectomy along with partial omentectomy. Intraoperative findings included a large bilobed edematous mass weighing approximately 1.5 kg with a twisted, thickened vascular pedicle and varicosed vessels. The left fallopian tube was slightly thickened as well. No lymphadenopathy or invasion into the surrounding structures was seen. The surgically resected specimen was then sent for histopathological analysis, which revealed a neoplastic lesion in the left ovary arranged in nests and trabeculae separated by fibrous septa. The cells were polygonal with moderate amount of clear to eosinophilic cytoplasm. The nuclei were round to oval, showed moderate plemorphism with prominent eosinophilic nucleoli and frequently visible mitotic activity. Scattered plasma cells and lymphocytes were present within the fibrous septa. In areas, tumor cells were seen scattered against edematous stroma. Thin-walled dilated and congested blood vessels were seen, suggestive of vascular compromise secondary to torsion. The neoplastic cells showed diffuse nuclear positive expression for octamer-binding transcription (OCT) 3/4 immunohistochemical stain. Intracytoplasmic glycogen was highlighted on Periodic acid-Schiff special stain (Figure ). The overall findings confirmed mature ovarian dysgerminoma that was limited to the left ovary without capsular invasion (TNM stage: T1A, N0, M0 according to FIGO staging). The excised left fallopian tube, omentum, and peritoneal washout were all negative for malignancy. Postoperatively, the patient showed satisfactory progress and was therefore discharged in a stable condition. She is planned for on oncology follow-up visit as an outpatient.

pmc-6016001-1

Informed consent was obtained from the patient prior to the submission of this paper. A 74-year-old Caucasian woman presented with fever, fatigue, and painful erythematous nodules. Her oncologic history was significant for MDS (refractory cytopenia with multilineage dysplasia subtype) diagnosed three years previously. She received 23 cycles of azacitidine (AZA). On initial presentation, her temperature was 101.4° F with tachycardia. Physical examination was significant for conjunctival pallor, tender erythematous vesicles on her right temple and bilateral ear lobes extending to the right periocular area, and tender erythematous nodules on her buttocks. A complete blood count showed pancytopenia (white blood cell count of 2.0 x 10­9/L with an absolute neutrophil count of 1,500/mm3, hemoglobin of 8.1 g/dL, and platelet count of 16 x 109/L). Given the concern for sepsis, she was started on antibiotics (1 gm of vancomycin and aztreonam every 12 hours) and antiviral medications (650 mg of acyclovir every eight hours). Despite that, she was persistently febrile with worsening of her condition and development of new erythematous plaques and nodules over her shoulders, forearms, and lower extremities (Figure 1). A 5-mm x 5-mm x 6-mm punch biopsy of an erythematous nodule over her right shoulder showed subcutaneous lobular and septal infiltrates of neutrophils and scattered histiocytes with sparing of the dermis, consistent with NP (Figure 2). Special stainings (Gram's method, Ziehl-Neelsen, and Periodic acid–Schiff stains) and tissue cultures for bacteria, mycobacteria, and fungal infections were negative. Blood cultures were negative for infection. Bone marrow biopsy did not show evidence of transformation of her MDS to acute myeloid leukemia (AML). A diagnosis of MDS-related SSS was made. She was started on oral prednisone, 60 mg/day, and had marked clinical improvement with resolution of her fever within 24 hours. Although she had relapsed painful erythematous nodules and plaques with a rapid steroid taper, she reported resolution of her cutaneous lesions weeks later at follow-up with a slow steroid taper. In the meantime, AZA was withheld.

pmc-6016002-1

A 68-year-old Caucasian man presented with generalized weakness, dizziness without syncope, polyuria, and dyspnea on exertion. He had a past medical history of hypertension, hyperlipidemia, and coronary artery disease. Physical examination was as follows: temperature 99.3°F, pulse 84 per minute, blood pressure 168/80 mmHg, respiratory rate 18 per minute. A grade IV/VI systolic murmur was heard over the apex radiating to left axilla and back, and a grade III/VI systolic murmur was best heard at the aortic area, bibasilar crackles, hepatomegaly and pitting edema of the bilateral lower extremities were noted. Laboratory data included hemoglobin of 6.5 g/dL and blood urea nitrogen (BUN)/creatinine 71 md/dL/6.3 mg/dL, white blood cell, platelet count and lactate dehydrogenase (LDH) levels were normal. Two months previously, hemoglobin and renal function studies were normal. Urinary protein excretion was increased, but not in the nephrotic range (Microalbumin/Cr ratio = 2.00). Hepatitis B and C serology, antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibody (ANA), SSA, SSB, antistreptolysin O, and anti-glomerular basement membrane (GBM) antibodies were negative and C4 complement level was normal, rheumatoid factor (RF) was 2048 IU/M and serum C3 level was 65 mg/dL (ref 80-180 mg/dL). Renal ultrasound was normal. Complete evaluation for multiple myeloma was negative. Transthoracic echocardiogram demonstrated severe mitral regurgitation and multiple hyperechoic masses on the tips of both mitral leaflets with a small mobile mass on the posterior mitral leaflet (Figure ). It also demonstrated aortic regurgitation and a mobile echogenic structure (4 mm x 4 mm), attached to ventricular side of aortic valve (Figure ). Subsequently, Streptococcus parasanguinis was isolated from blood cultures. The organism was sensitive to penicillin and ceftriaxone. Antibiotics treatment for endocarditis was initiated. Hemodialysis was required due to worsening kidney function BUN/Cr 114 mg/dL/10.3 mg/dL. Electron microscopy of renal biopsy showed crescent formation (Figure ). Immunofluorescence showed immune complex deposition (Figure ). Despite antimicrobial therapy, there was no improvement in kidney function, and the patient remained dialysis dependent. Corticosteroids and cyclophosphamide were administered. Double valve replacement surgery was performed because of severe aortic and mitral valve regurgitation. Echocardiogram after surgery did not demonstrate mitral or aortic valve regurgitation, and the bioprosthetic mitral and aortic valves were normally functioning. The patient remained on dialysis despite antibiotics, steroids and cyclophosphamide. An arteriovenous (AV) fistula was placed in the left arm and maintenance hemodialysis was recommended three times per week. On follow-up at one year, the patient remained on hemodialysis in otherwise stable condition.

pmc-6016128-1

A 53-year-old white man presented to our Department with a 2-month history of a painful and moderately swollen left wrist. His past medical history was unremarkable. Standard anteroposterior and lateral X-rays of his left wrist revealed two osteolytic lesions involving the distal ulna and the lunate fossa of the distal radius without any joint involvement (Fig. , ). Subsequent biopsy of his left ulna under regional anesthesia produced brown spongy material, histologically characterized by the presence of large numbers of multinucleated giant cells and spindle cells in a dense collagenous background. These findings were histologically consistent with a diagnosis of GCT and correlation with the clinical and radiological findings was recommended by the pathologist. As he had no other skeletal manifestations, a complete resection of the distal ulna (9.5 cm length) followed, along with curettage and cementoplasty of the distal radial metaphysis, to support the articular surface (Fig. , ). The resected distal ulna specimen and the curettings from the distal radius were submitted for histopathological evaluation; our patient was discharged 2 days later, with a forearm cast and instructions to attend the clinic in 2 weeks’ time for re-evaluation and removal of sutures. Two weeks postoperatively, he was re-admitted to our orthopedic department with diffuse musculoskeletal soreness, anorexia, constipation, nausea, and localized abdominal pain. He also reported weight loss of approximately 5 kg. On palpation he had tenderness in the thoracic wall, the second and fifth metacarpals of his right hand, the left tibia, the pelvic ring, and the left shoulder girdle and humerus. Plain radiographs revealed multiple osteolytic lesions in his ribs, right hand, left tibia, and scapula (Fig. –). A histopathological examination of both the resected ulna (Fig. –) and the curettings of the radius (Fig. ) revealed similar findings: numerous, multinucleated, osteoclast-type giant cells were noted amid a mononuclear, spindle cell, histiocytoid component (Fig. ). Many of the giant cells were clustered in large nodular aggregates separated by fibrous septa containing fibroblast-like spindle cells. The spindle cell component showed no evidence of atypia or sarcomatoid features (Fig. ). There were prominent foci of hemorrhage with relatively restricted hemosiderin deposition (Fig. ). Mitoses were observed (up to five mitotic figures/ten high power fields) but no atypical mitoses or necrosis were seen. On the resection specimen of the ulna, the lesion focally disrupted the cortex producing periosteal reaction with woven bone trabeculae, extending in the surrounding adipose tissue and skeletal muscle (Fig. ). Based on the similar findings of both lesions and the rarity of multifocal GCT of bone the histopathology report included in the differential diagnosis a BT of hyperparathyroidism, either primary or in the setting of a paraneoplastic PTH-like protein production and suggested further patient evaluation. Our patient’s laboratory examination showed high total serum calcium (14.5 mg/dl, normal range 8.8–10.4), low serum phosphorus (2.3 mg/dl, normal range 2.5–4.5), and low 25-hydroxyvitamin D (9.74 ng/ml, normal range > 30). PHPT was suspected and confirmed by the elevated PTH levels of 1453 pg/mL (normal range 15–65). Serum potassium and sodium concentrations and thyroid hormone levels were in reference range as well as the main cancer indicators: cancer antigen (CA) 15-3, carcinoembryonic antigen (CEA), CA 125, and prostate-specific antigen (PSA). Serum protein electrophoresis was also normal. His human chorionic gonadotropin (hCG) was elevated (25.3 mUl/ml, reference level < 5). An isotope bone scan showed multiple sites of uptake over his ribs bilaterally, the lower pole of both scapulae, multiple foci in his pelvis, the metacarpal bones of his right hand, and his right tibia. At subsequent radiological work-up, both computed tomography (CT) and ultrasonography of his neck revealed a 4.5 × 2.5 × 3.2 cm mass emanating from the right lobe of his thyroid gland. Parathyroid subtraction technetium-99m (99mTc) sestamibi (MIBI) scintigraphy showed extensive uptake in his right lower parathyroid gland (Fig. ). Multiple endocrine neoplasia was excluded because of the normal MRI imaging of his pituitary gland. Appropriate medical care was given to our patient including hyperhydration and high doses of diuretics and diphosphonates. After his health status improved and his serum calcium nearly normalized, a specialist surgeon was consulted for further surgical treatment. Surgery consisted of extensive resection: total thyroidectomy with removal of the parathyroid glands. A mass measuring 4.8 cm in greatest diameter, abutting the thyroid gland was documented at surgery. The mass was surrounded by a thick capsule, had a tan-brown, solid, and microcystic cut surface, and rubbery consistency. On histologic examination, the tumor comprised small cells with minimal to scanty cytoplasm and round nuclei, arranged in an organoid pattern, with frequent perivascular pseudorosettes. Thick fibrous septa emanating from the capsule were noted within the tumor. There was capsular invasion, with extension of neoplastic groups in the surrounding loose connective tissue adjacent to striated muscle, and foci of vascular invasion in the tumor capsule. The histologic findings were consistent with a parathyroid carcinoma. The neoplasm did not appear to invade the adjacent thyroid lobe and did not involve the margins of resection. Our patient experienced postoperatively persistent hypocalcemia requiring calcium and vitamin D replacement. His condition was characterized as “hungry bone syndrome.” He is now recovering 12 months after surgery, with a serum PTH level of 7.1 pg/mL and serum calcium level of 10.7 mg/dl and he is under calcium and vitamin D replacement therapy. The lytic bone lesions have almost disappeared (Fig. –) and no other additional orthopedic intervention is necessary. He is closely followed by general surgeons, oncologists, and endocrinologists.

pmc-6016132-1

On March 2017, a male, caucasian, 56-year-old, non-smoker patient came to our observation. He was employed as a truck driver. Remote clinical history included hepatitis, nasal polyposis treated with functional endoscopic sinus surgery (FESS), chronic sinusitis, gastroesophageal reflux disease (GERD) undergone laparoscopic GERD surgery (fundoplication). In 2016, a diagnosis of non-allergic asthma was made. Skin prick tests were negative. Respiratory function tests showed a moderate obstruction (FEV1 2.20 L, 68% of predicted; FEV1/FVC 67%) without bronchial reversibility after 400 μg of inhaled salbutamol. A few months later, after normalization of lung function parameters following maximal therapy, a positive bronchial provocation test with methacholine showed a degree of bronchial hyperresponsiveness congruent with the diagnosis of bronchial asthma (PDV20 FEV1 136 mcg). Antineutrophil cytoplasmic antibodies (ANCA) were negative. The therapy included formoterol/fluticasone metered-dose inhaler 250/10 μg, two inhalations twice daily and as needed (twice a day on an average), tiotropium bromide 2.5 μg soft mist inhaler, montelukast 10 mg/day. Due to frequent exacerbations and poor control of asthma, systemic corticosteroids (either oral or parenteral) had to be prescribed for over 6 months and 7 unscheduled visits were required in the previous year. On February 2017 a chest high-resolution computed tomography (CT) scan showed only mild fibrotic scarring in the anterior basal segment of the lower right lung lobe. On September 2017 the patient received a first session of BT, in the lower right lobe, without any tolerability problem. Three days before the procedure systemic oral corticosteroids (prednisone 50 mg/day) were administered according to usual protocol, to control potential exacerbation of airway inflammation. Immediately before bronchoscopy, inhaled bronchodilators (nebulized salbutamol and ipratropium bromide) were given, along with nebulized lidocaine to provide topical anesthesia. Atropine 0.4–0.6 mg was administered intravenously 15–30 min before the procedure to minimize secretions. According to our procedure, the patient is placed under moderate sedation, a peripheral intravenous (IV) line is taken and supplemental oxygen is administered. The bronchoscope is positioned at the first treatment site, usually the most distal airway in the targeted lobe and the Alair Catheter is introduced through the working channel. The electrode array at the tip of the Catheter is expanded to contact the airway wall. The bronchoscopist activates the RF Controller to deliver low-power, temperature-controlled RF energy to the airway; the energy transfer ends automatically upon completion of the cycle (about 10 s). A single activation of the Catheter delivers RF energy over a distance of approximately 5 mm. After each procedure there is a 1–2 days hospitalization with monitoring of vital parameters and control of chest radiography. On October 5, 2017 a second BT session was performed in the left lower lobe, according to the same procedure. On October 23, persistent haemoptysis appeared requiring patient admission to our ward. On physical examination there was a reduction of breath sounds at the left pulmonary base. The patient underwent a new chest CT scan: around the basal anterior segmental branch line of the left lower lobe, mild varicoid bronchiectasis and distal parenchymal infiltrate were present, in addition to mild signs of airway inflammation in the right lower lobe (Fig. a). A fibreoptic bronchoscopy showed two small nodular neoformations in the sub-segmental branches of the same lobe (Fig. b). Endobronchial ultrasound (EBUS) with radial probe exploration of the left lower lobar bronchus was also performed with evidence of peripheral infiltrate, sampled with four trans-bronchial biopsies. These changes were not present on endoscopy at the time of the BT procedure, and were detected only after the appearance of haemoptysis. On histological examination bronchial mucosa showed mild non-specific inflammation. Some large fragments of peribronchial pulmonary parenchyma (Fig. d) presented an area of haemorrhagic necrosis, with blood and fibrin, hemosiderin deposits and organizing pneumonia (Fig. d, e). No neoplastic cells were observed. Infectious agents were excluded after histochemical staining with Grocott and Ziehl–Nielsen methods. Microbiological cultures for aerobe and anaerobe bacteria were negative as well as cultures for mycobacteria. The patient was treated empirically with co-amoxiclav 1 g three times and azithromycin 500 mg daily for 6 days and prednisone 25 mg per day for 10 days. On December 18, a new chest CT showed a complete resolution of the parenchymal opacities (Fig. f). On January 9, 2018, the patient underwent the third session of BT, without recurrence of haemoptysis or subsequent radiological changes. Before performing the last BT session a fibreoptic bronchoscopy showed a complete resolution of the previously reported endoscopic findings.

pmc-6016151-1

A 54-year-old Caucasian male presented with an enlarging right neck mass in November, 2015. Fine-needle aspiration (FNA) was performed on the mass at that time which showed malignant cells consistent with squamous cell carcinoma. The patient did not have follow-up or further treatment at that time due to socioeconomic issues. His past medical history is significant for alcoholism, tobacco abuse, noninsulin-dependent type 2 diabetes mellitus, and osteoarthritis. For the next sixteen months, he reported three flares of painful neck adenopathy. He sought treatment, and short courses of antibiotics and steroids were administered each time. In March of 2017, his latest flare of right-sided neck adenopathy did not respond to antibiotics and steroid treatment course. He presented to the Emergency Department and found to have a grossly palpable mass in the right neck. He reported no symptoms of fevers, chills, night sweats, fatigue, or weight loss. Computed tomography (CT) revealed multiple low-density cystic structures in the right neck consistent with necrotic lymph nodes. The lymph nodes ranged in size from 1.4 cm to 2.9 cm in greatest dimension. No additional masses were detected in nasopharynx, oropharynx, or larynx. At this point, the patient was admitted for further workup and management. PET-CT showed right neck hypermetabolic uptake ranging from SUV of 4.3 to 4.5, and a CT of the chest showed no obvious disease and no evidence of lymphadenopathy. Following an FNA suggestive of either an anaplastic carcinoma or a hematolymphoid neoplasm, an excisional biopsy of the neck mass was performed. Hematoxylin and eosin- (H&E-) stained right neck mass excisional biopsy material demonstrated lymph node and soft tissue with sinusoidal infiltration of large atypical monomorphic cells with round nuclei, occasional prominent central nucleoli, and abundant amphophilic cytoplasm. The lymph node was mostly effaced by tumor cells, but the uninvolved areas appeared unremarkable and showed residual small mature lymphocytes (). An extensive immunohistochemical panel was performed to aid the diagnosis with appropriate reactive controls (Figures and ). The tumor cells expressed CD45, weak CD38, CD138, and EMA. ALK-1 showed a restricted granular cytoplasmic staining pattern highly suggestive of CLTC-ALK fusion protein expression. MIB-1/Ki-67 was approximately 80%. Interestingly, the tumor cells also showed strong and diffuse CD33 expression. The tumor cells were negative for PAX-5, myeloperoxidase (MPO), TIA-1, EBV, HHV8, CD2, CD4, CD5, CD7, CD8, CD20, CD30, CD34, CD79a, and kappa/lambda light chains. Other nonhematopoietic immunostains including CK OSCAR, CK7, melan-A, CK5/6, p40, and p63 were negative. Flow cytometry, cytogenetics, and FISH studies were not performed on the sample. Based on the morphology and immunohistochemistry, a diagnosis of ALK+ LBCL was rendered. The case was also reviewed at NIH, and the diagnosis was confirmed. Due to the aberrant CD33 expression, additional molecular studies were performed in an attempt to identify any myeloid malignancy-associated mutations. A myeloid malignancies mutation panel by next generation sequencing (NGS) was performed and did not reveal any significant mutations. Currently, the patient is under treatment protocol, which includes three cycles of CHOP chemotherapy to be followed by radiation therapy.

pmc-6016156-1

A 41-year-old man, a native from Rio de Janeiro and an HIV and HCV carrier, without criteria for the treatment for HCV (detectable viral load, without cirrhosis and with normal transaminase levels), who had abandoned ART, had attended the Gaffreé and Guinle University Hospital's immunology clinic complaining about continuous epigastric burning pain without irradiation and with diffuse abdominal pain that was mild and continuous, which had started approximately two months prior to admission. He also complained about intense hematochezia that had started three weeks before, with intense flow and with “pure blood” appearance without clots. He presented with daily hyperthermia since the abdominal symptoms had started with intermittent high fever and an over 10% body weight loss in the same period. The physical examination revealed oral candidiasis, bleached mucous membranes, and cachexia. At the admission time, the HIV viral load was recorded at 905,569 copies per ml, and the TCD4 lymphocyte count was 144 cells/dL. Prophylactic sulfamethoxazole-trimethoprim 400/80 mg 2 IV ampoules once daily and fluconazole 200 mg IV once daily for treatment of the oral candidiasis were prescribed. The patient's condition evolved without major occurrences or complaints, presented with high fever, above 38°C almost every day. Blood counts revealed thrombocytopenia, neutrophilia, lymphopenia, anemia, microcytosis, and anisocytosis (). The medical team requested upper digestive endoscopy () and colonoscopy (), which verified the presence of ulcer with irregular and raised edges, fibrinonecrotic base, measuring approximately 3 cm in the middle third of the esophagus and 30 cm from the incisors and the mild antrum gastritis, and swollen, irregular, and fibrinous ulcers in the ileocecal valve, descending colon, and all other segments. The lesions were similar to those found in the esophagus, which could suggest the same etiology. It was suggested by the internal medicine team that the diagnosis could be a coinfection (tuberculosis, cytomegalovirus, and herpes simplex virus disease). The diagnosis of tuberculosis and cytomegalovirus coinfection of the gastrointestinal tract was confirmed by the histopathological report (Ziehl–Neelsen staining of acid-fast bacilli, CMV intracytoplasmic inclusions in Giemsa staining, and immunohistochemical study with positive labeling for CMV in cells with clear halos), and some time later, culture with the growth of M. tuberculosis (). Treatment was started with an RIPE scheme (rifampicin + isoniazid + pyrazinamide + ethambutol) 4 tablets daily and ganciclovir 350 mg IV for 21 days with a weight gain of 4 kg and clinical and laboratory improvement. He was discharged from the hospital with ART lamivudine, tenofovir, and efavirenz (TDF + 3TC + EFV) one tablet per day and was referred to a clinical follow-up for tuberculosis and HIV/HCV coinfection monitoring. At the end of the treatment for tuberculosis and 6 months after ART was restarted, the patient's viral load was <40 copies/dL and the CD4+ T-cell count was 356 cells/dL, asymptomatic.

pmc-6016157-1

A 45-year-old male patient gazed at the sun several times during a baseball game that took place on a sunny day at 7 weeks prior to his first visit to our clinic. Immediately after gazing at the sun, the subject reported having bilateral central scotoma and decreased vision. At the time of the incident, the patient was taking etizolam for a psychiatric condition (panic disorder). At the first visit, his decimal best corrected visual acuity was 0.8 (logMAR conversion: 0.10) (with -3.00 diopters, cylinder -1.00 diopters axis 5°) in the right eye and 0.7 (logMAR conversion: 0.15) (with -3.00 diopters, cylinder -1.00 diopters axis 180°) in the left eye. Slit lamp examinations showed no abnormalities in the anterior segments and media of both eyes. Fundus examinations showed a tiny, yellowish spot in the fovea bilaterally (). FAF (Spectralis HRA; Heidelberg Engineering, Heidelberg, Germany) (), fluorescein angiography, and indocyanine green angiography all indicated that there were no remarkable abnormalities in either of the eyes. OCT (Cirrus HD-OCT; Carl Zeiss Meditec AG, Dublin, CA, USA) images showed an elevated and blurred ellipsoid zone along with loss of the interdigitation zone at the foveal area bilaterally (). There was also no vitreomacular adhesion or traction seen in either of the eyes (). When the findings were taken together, the patient was diagnosed with solar retinopathy due to the characteristic symptoms and bilateral findings present after an episode of sun gazing. Treatment was started at the first visit, with the patient given a posterior sub-Tenon triamcinolone injection in his right eye followed by being placed on oral prednisolone therapy (30 mg per day) on the same day. The prednisolone therapy was decreased over a 12-week tapering period. There were no changes noted in the decimal best corrected visual acuity at 2, 4, and 6 weeks after starting the medication. However, at 9 weeks, there was improvement to 1.2 in the right eye and 1.0 in the left eye, with this good visual acuity sustained and observed at the examinations at 12 and 21 weeks. Fundus examinations performed at 12 weeks after the initial treatment showed the tiny, yellowish spots were diminished in both eyes. Sequential OCT images obtained during the follow-up examinations showed that the blurred ellipsoid zone that was visible in both eyes at 2 weeks after initiation of the therapy along with the elevated ellipsoid zone both improved to nearly normal at 4 weeks in the right eye and at 21 weeks in the left eye. However, loss of the interdigitation zone was observed after 12 weeks in the right eye and after 21 weeks in the left eye ().

pmc-6016161-1

A 55-year-old woman with a history of type 2 diabetes mellitus, hyperlipidemia, obesity, and depression was referred to an endocrinologist with complaints of weight loss, palpitations, and diarrhea. The patient also had hypertension and was taking α-adrenergic receptor antagonists and a calcium channel blocker. She was found to have a thyroid-stimulating hormone (TSH) level of <0.10 (normal: 0.34 to 4.82) µlU/ml and a free T4 concentration of 4.28 (normal: 0.6 to 1.6) ng/dL. I123 thyroid scan revealed elevated, diffuse uptake bilaterally, without nodules, consistent with the diagnosis of Graves' disease. The patient was treated with 11.9 mCi of radioactive iodine. Ten days after the ablation treatment, the patient presented to a local hospital by ambulance after experiencing lightheadedness, diffuse abdominal pain, and one episode of bilious emesis. Upon arrival, she was hypotensive (77/44 mm Hg), pale, bradycardic, and febrile (39.4°C). An electrocardiogram (ECG) revealed accelerated junctional rhythm at a rate of 53 beats/min. The patient was given atropine 0.5 mg intravenously without effect, followed by initiation of external cardiac pacing. Continuous intravenous infusions of dopamine and norepinephrine were started along with fluid resuscitation of 4 L of normal saline over a 2-hour period. She received one ampule of calcium gluconate with no change in her blood pressure, heart rate, or rhythm. Computed tomography of the abdomen was unrevealing. The patient was endotracheally intubated and transferred via helicopter to our facility. Upon arrival to our facility, she was receiving intravenous infusions of dopamine at 20 µg/kg/min and norepinephrine at 10 µg/kg/min and remained hypotensive (92/55 mm Hg) and bradycardic (59 beats/min). ECG showed an accelerated junctional rhythm. Laboratory findings included serum sodium of 139 mEq/L, potassium of 5.3 mEq/L, chloride of 108 mEq/L, and total CO2 content of 15 mmol/L, serum glucose of 208 mg/dL, urea nitrogen of 38 mg/dL, creatinine of 1.5 mg/dL, ionized calcium of 1.15 mmol/L, total bilirubin of 0.4 mg/dL, serum alkaline phosphatase of 141 U/L, aspartate aminotransferase of 2196 U/L, and alanine aminotransferase of 2010 U/L. Plasma troponin I was repeatedly undetectable. The peripheral leukocyte count was 15.9 x 109 cells/L with no immature forms. There was evidence of an anion gap metabolic acidosis with a serum lactate concentration of 6.2 mmol/L. Blood cultures revealed no microbial growth. Thyroid function testing showed an undetectable TSH (<0.10 µlU/ml), a free T4 of 12.8 (normal: 0.6 to 1.6) ng/dL, total T4 of 21.9 (normal: 5.6 to 13.7) µg/dL, and a total T3 of 0.94 (normal: 0.8 to 1.8) ng/mL. The patient was treated for thyroid storm with 1000 mg of propylthiouracil by orogastric tube as a loading dose followed by 300 mg every 6 hours, 5 drops saturated solution of potassium iodide (SSKI) every 8 hours by orogastric tube, and 100 mg intravenously of hydrocortisone every 8 hours. The hypotension resolved, vasopressors were stopped, and the patient was extubated 25 hours after her initial presentation. During her stay in the intensive care unit, the patient exhibited fever (39.6°C maximum), tachycardia, and tremulousness. These manifestations resolved over a period of 22 hours. The patient was discharged in satisfactory condition on the fourth day of hospitalization on 100 mg of propylthiouracil orally every 8 hours. Outpatient testing days later demonstrated normalization of her thyroid function tests.

pmc-6016165-1

A 69-year-old Caucasian man with schizophrenia represented to our emergency department (ED) from a psychiatric hospital with catatonia, notable for agitation and altered mental status requiring physical restraints. Limited physical exam was revealing for increased tone and rigidity in bilateral lower extremities while the patient self-dialogued and yelled at times. Per outside records, he was observed to be persistently agitated, engaging in self-injurious behaviors such as hitting himself, banging his head, and refusing to eat or drink for a week. Three weeks prior, he was admitted to the medicine service with early signs of NMS that resolved over the course of a few days with discontinuation of neuroleptics and treatment with parenteral lorazepam. He was subsequently transferred back to the outside hospital psychiatric unit for further stabilization and optimization of his psychotropic regimen, with a recommendation to avoid high-potency neuroleptics. There, he was started on fluphenazine, a high-potency first generation antipsychotic, after a washout period of one week. His religious delusions with disorganized thought process showed minimal improvement. He was subsequently switched to haloperidol, which was rapidly increased to 35 mg per day. Clonazepam 1.5 mg per day and lorazepam 1 mg per day were also utilized over this time frame. The patient, however, became increasingly agitated, with self-injurious behavior and some posturing that was attributed to “refractory psychosis.” This prompted further antipsychotic dose escalation. He had stopped eating or drinking by this time with associated worsening of behavioral dysregulation. 75 mg of chlorpromazine was given the same day after 35 mg of haloperidol showed minimal benefit. While chlorpromazine temporarily decreased his behavioral dysregulation, his agitation continued unabated the following morning. He was given additional chlorpromazine 25 mg with fluid resuscitation in urgent care before his transfer to our facility for a delirium work-up. On arrival, standard treatment was implemented, including antipsychotic discontinuation, supportive care, and initiation of parenteral benzodiazepines consisting of lorazepam 2 mg intravenously (IV) every 8 hours. His complete blood count, electrolytes, vitamin B12, thyroid function, and liver function tests were within normal limits, except for a CK of 1090 IU/L, mildly elevated 10,680 white blood cells per mcL, low iron level of 26 ug/dL, and creatinine value of 1.26 mg/dL thought to be prerenal in nature secondary to dehydration. He tested negative for syphilis on the rapid plasma reagin test. Urinalysis did not reveal an infection. Urine drug toxicology was positive for benzodiazepines only, which the patient had been receiving on the inpatient unit. A head CT revealed no acute intracranial pathology. An electroencephalogram performed on day 4 of admission was notable only for increased beta waves, reflecting the high-dose benzodiazepines he was receiving at the time. The patient's hospital course was notable for continued fluctuating motor symptoms with episodes of severe rigidity in both upper and lower extremities, intermittent droning vocalizations, waxy flexibility, posturing, negativism, automatic obedience, and presence of mitgehen. Such periods were accompanied by diaphoresis and autonomic hyperactivity. On the fifth day, lorazepam was increased to 4 mg IV every 4 hours and amantadine 100 mg (by mouth) PO twice a day was started the following day. The doses were held past midnight due to planned ECT on the seventh day of admission. Lorazepam was resumed post-ECT but amantadine was held until after the third session. Prior to each subsequent ECT treatment, benzodiazepines were held to prevent increasing the patient's seizure threshold. He received a total of three ECT sessions, each three days apart. In between the second and the third ECT sessions, the patient became overtly delirious secondary to a urinary tract infection, which was treated with antibiotics. After the second ECT session, lorazepam was decreased to 2 mg IV every 6 hours and then switched to a longer acting diazepam 20 mg IV every 6 hours after the third ECT session. Amantadine was restarted at the same dose and was increased to 100 mg PO three times a day, four days after the last ECT session. After a three-week washout period, Clozapine 12.5 mg PO twice a day was introduced for underlying psychotic symptoms and titrated to 25 mg twice a day without recurrence of NMS or catatonia. With gradual lysing of catatonia and normalization of lab values, the patient was discharged back to the inpatient psychiatric unit after a month-long hospitalization.

pmc-6016168-1

A 67-year-old woman, gravida 1, para 1, with a medical history of psoriasis and bipolar affective disorder, presented with postmenopausal vaginal bleeding. Physical examination found an 18-week sized uterus without palpable groin lymph nodes. Both adnexa were unremarkable. Magnetic resonance imaging (MRI) of the pelvis and computed tomography (CT) with contrast of the abdomen and thorax demonstrated a localized anterior intrauterine mass with deep myometrial invasion. There was no pelvic or inguinal lymphadenopathy []. The liver was normal in size and outline, with no mass lesion demonstrated on contrast CT. All other intra-abdominal organs were unremarkable. Histologically, the uterine curettage showed carcinosarcoma composed of mixed endometrioid adenocarcinoma, chondrosarcoma, and a hepatoid component. The hepatoid component consisted of trabeculae of polygonal cells with moderate amount of eosinophilic cytoplasm, round to oval nuclei and distinct nucleoli, histologically reminiscent of hepatocellular carcinoma. Immunohistochemically (IHC), the hepatoid tumor cells are positive for AFP, HepPar-1, and arginase-1. Preoperative hepatitis B virus surface antigen was negative and liver function was normal. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Serum alpha-fetoprotein (AFP) dropped from 31896 ug/l preoperatively to 2063 ug/l postoperatively []. Carbohydrate antigen 125 (CA125) level was normal. The resected specimen weighted 575 g and measured 11.0 x 9.5 x 8.0 cm with an anterior exophytic tumor measuring 7.5 x 6.0 x 4.0 cm with a tan cut surface [] and detached hemorrhagic fragments. Microscopically, the tumor involved the outer half of the myometrium without extension to the cervix or the vagina. Bilateral ovaries were involved. Extensive lymphovascular permeation was seen. Histologic findings were those of a carcinosarcoma with endometrioid adenocarcinoma (20%), hepatoid adenocarcinoma (20%), and sarcomatous components consisting of chondroid (10%) and spindle cell components (50%) []. IHC staining was repeated and the profile was the same as the curettage specimen []. The postoperative clinical course was uneventful, and she was planned to receive taxotere and cyclophosphamide (TC) as adjuvant chemotherapy. Before adjuvant therapy was initiated, a tumor was found in the residual vaginal canal on 8-week postoperative follow-up clinical examination, and biopsy confirming histological recurrence. The patient proceeded to chemotherapy (TC), and the serum AFP level showed a decrease from 6152 ug/l to 4288 ug/l after the first cycle. Serological response was sustained throughout the six cycles of chemotherapy, with a postchemotherapy serum AFP level of 4770 ug/l []. Follow-up CT of the thorax, abdomen, and pelvis did not show any radiological evidence of disease. A subsequent rise of serum AFP to 13409 ug/l was detected 1 month after completion of chemotherapy and the patient was started on Adriamycin. Serum AFP did not show response and was further elevated to 41826 ug/l after cycle two [], accompanied by the development of ureteric obstruction, ascites, and radiological evidence of liver and peritoneal metastases []. The patient succumbed 11 months postoperation.

pmc-6016169-1

A 62-year-old Japanese female patient presented with a left abdominal mass. She was referred to our surgical outpatient clinic to undergo a detailed examination and treatment for the left abdominal mass. A clinical examination revealed an elastic soft, smooth-surfaced, painless, child-head-sized tumor with poor mobility, which was located in the left upper abdomen. Abdominal computed tomography (CT) demonstrated a child-head-sized mass with heterogeneous contrast at the left upper abdomen around the stomach, spleen, pancreas, and left kidney on a horizontal image () and coronal image (). Magnetic resonance imaging (MRI) revealed a heterogeneously hyperintense mass on T1-weighted imaging (), a relatively uniform and hyperintense mass on T2-weighted imaging (), and a hypointense mass with an enhanced border on gadolinium- (Gd-) enhanced imaging (). A retroperitoneal tumor was diagnosed. Her laboratory data were white blood cell count, 4600/mm3; hemoglobin, 12.8 g/dl; hematocrit, 36.5%; and platelet count, 182,000/mm3, with normal electrolytes, as well as normal blood urea nitrogen levels, but slight liver dysfunction. Her serum levels of corticosteroid and/or androgen were 13.3 ng/ml (10.4–35.0 in female) and 173 pg/dl (35.7–240.0), respectively, which are within the normal ranges; however, her serum level of ACTH was elevated at 138.70 pg/ml (7.2–63.3). The retroperitoneal tumor was resected (). The tumor was located at the left side of the stomach, posteriorly to the transverse mesocolon and pancreas, on the cranial side of the left kidney (Figures and ), but has not invaded the surrounding organs (Figures and ). The right adrenal gland was normal in size. The resected tumor was 20 × 18 × 10 cm in diameter and weighted 1500 g. An examination of the cut surface of the tumor revealed a multilobular yellow mass with bleeding in places (). A histopathological examination with hematoxylin and eosin staining revealed that the tumor was composed of a proliferation of mature and variable-sized adipocytes admixed with aggregates of hematopoietic elements, associated with adrenal gland tissue in the peripheral region within the tumor (). These findings were compatible with AML. The patient had an uneventful recovery and was discharged from the hospital on the 6th day after the operation. She has been followed up in our outpatient clinic without recurrence for approximately 12 years since undergoing the operation.

pmc-6016171-1

A 41-year-old man presented to the emergency department following an automotive accident where he was thrown from his motorcycle traveling approximately 35 mph. The patient denied loss-of-consciousness and chiefly complained of left wrist pain at presentation with exam demonstrating tenderness and swelling. Radiographs () revealed a volar dislocation and rotatory deformity of the proximal pole of the scaphoid. The distal pole remained properly located, articulating with the trapezium and trapezoid. No other injuries were identified. Closed reduction failed in the emergency department; therefore, the patient elected to proceed with operative management. A dorsal approach was used to access the radiocarpal joint. The scapholunate joint was completely disrupted and the lunotriquetral joint was found to be unstable as well. The distal pole of the scaphoid appeared to be appropriately located without ligamentous disruption. No fractures or chondral injuries were seen. Three 0.045-inch K-wires were placed into the proximal pole and used as a joystick in concert with dorsally directed manual pressure over the distal pole to reduce the scaphoid dislocation. These were then advanced across the scapholunate articulation to hold the reduction. Three more K-wires were passed across the lunotriquetral joint to address the instability. The distal pole was once again examined but did not demonstrate any instability. The capsule was closed with 0 VICRYL suture, and the K-wires were cut just below the skin. The subcutaneous layer was closed with buried 2–0 VICRYL suture, the skin was closed with 4–0 NOVAFIL suture, and the wrist was splinted (). The patient did well postoperatively and was brought back to the operating room eight weeks later for hardware removal. He went on to heal well and regained his wrist range of motion with occupational therapy. At most recent follow-up (), five months since injury, the patient had no complaints and had returned to work and all desired activities.

pmc-6016173-1

A 56-year-old female presented with repeated fevers in a span of four months. Her medical history was significant for systemic lupus erythematosus (SLE) with nephritis and hypothyroidism. Her medications were methylprednisolone and levothyroxine. She was allergic to cephalexin, penicillin, and levofloxacin. She was a nonsmoker, denied alcohol, and illicit drug use. In her first hospital admission, she presented with fever and chills after traveling to Jamaica. She had no other symptoms. Her physical examination was only remarkable for fever of 38°C. Diagnostics revealed blood cultures positive for Salmonella enteritidis. Urine culture was negative. Due to her complicated history of antibiotic allergies, she was treated with aztreonam and discharged on trimethoprim/sulfamethoxazole (TMP/SMX) for two weeks. She was well in the interim until one month later when she returned with fever (39°C), nausea, and dysuria. Physical examination identified costovertebral angle tenderness. Blood culture again grew the same organism, and urine culture was also positive. She was treated with aztreonam and discharged home with TMP/SMX for two weeks. Repeat urine culture as outpatient was negative for Salmonella. Within the next month, she was readmitted with generalized body and joint pains. She was then treated with steroids for a lupus flare. During this admission, there were incidental findings of elevated lipase 668 U/L (reference range 4–66), and CT scan showed pancreatitis. She did not have any abdominal pain or symptoms to suggest acute pancreatitis. Her blood and urine cultures were negative. Gastroenterology service recommended that she be managed supportively. After clinical improvement, she was discharged to a rehabilitation facility. In a week, she again developed fever accompanied by chills, nausea, and vomiting. There were no other symptoms. Physical examination was only remarkable for temperature of 38.5°C and blood pressure of 144/63 mm Hg. The examination was otherwise normal. The serum white blood cell count was 13.1 × 103 µL (ref 4.8–10.8), and hemoglobin was of 7.9 (ref 12–16). Lipase was 22 U/L (ref 4–66). Bilirubins, transaminases, and the remainder of the metabolic profile were unremarkable. Blood and stool culture grew Salmonella enteritidis sensitive to ampicillin, aztreonam, ceftriaxone, ciprofloxacin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. Computed tomography (CT) scan of the abdomen showed enlargement of the pancreatic head with adjacent stranding consistent with pancreatitis along with adjacent low-density regions anteriorly and inferiorly consistent with inflammatory liquefaction (). Other abdominal structures were normal. Magnetic resonance imaging (MRI) showed an 8 cm mass below the level of the pancreas. She was initially given aztreonam for two weeks pending sampling of the pancreatic mass. The patient then changed her mind and refused the procedure. Since she was clinically doing well and repeat cultures were negative, she was monitored off antibiotics with a plan to do the procedure if she worsened. While awaiting discharge, she had a fever of 38°C. Blood and stool cultures were again positive. This time, she was given intravenous ceftriaxone. Repeat CT and MRI demonstrated multiple complex fluid collections around the pancreas: a 9 × 6 cm mass inferior to the pancreas, a 7 × 4 cm mass superiorly, and two smaller masses abutting the head and body. CT-guided drainage was performed with purulent fluid identified. A Jackson-Pratt drain was then placed (). Fluid culture grew Salmonella enteritidis. The patient was transitioned to 4 weeks of oral ciprofloxacin, which the patient tolerated despite the reported levofloxacin allergy. She was followed up as outpatient and was doing well.

pmc-6016175-1

A 30-year-old woman was transferred to our emergency department five hours after delivering her baby at a clinic. She was a primipara at 41 weeks of gestation. She delivered a baby with vertex presentation vaginally, without dystocia. Massive vaginal bleeding started 2 hours after delivery. After excluding birth canal laceration and retaining placental tissue, the obstetrician began IV fluid and uterotonic treatment, but the bleeding continued. She was then transferred to our hospital due to PPH. However, when she arrived, she had severe tachycardia (heart rate, 160 bpm) and hypotension (BP, 44/34 mmHg). Her consciousness was clear, but she was agitated. We immediately began transfusion of packed red blood cells (6 units), fresh frozen plasma (4 units), apheresis platelets (2 units), and whole blood (2 units) as we simultaneously examined the patient. Signs of DIC developed with continuous blood loss (), and her consciousness deteriorated within 30 minutes after arriving at the emergency department. Uterine atony and an ischemic uterus were found during emergency laparotomy. A subtotal hysterectomy was completed. Intraoperative blood loss was 800 mL. The patient was transferred to the ICU after surgery. Her postoperative fibrinogen level was 54.6 mg/dL (normal: 200–400 mg/dL). We transfused fresh frozen plasma and cryoprecipitate to achieve a fibrinogen level greater than 100 mg/dL. However, unstable blood pressure and progressive abdominal distension were found 4 hours after the primary surgery. We rushed the patient back into surgery due to suspicion of internal bleeding. Hemoperitoneum of 2000 mL and active bleeding from ruptured pararectal vessels were identified. After the secondary surgery for ligation of the bleeding vessels, the patient had acute kidney injury with anuria, intractable hyperkalemia, and metabolic acidosis. Thus she underwent continuous venovenous hemofiltration (CVVH). The patient's hemodynamic status and ventilation function gradually improved after hemostasis. CVVH was shifted to intermittent hemodialysis on postoperative day 10. She was extubated on the same day. Unfortunately, hyperbilirubinemia progressed and became the main problem (). Liver enzyme levels peaked on postoperative day 3 and then settled to about 100–200 IU/L (). Thrombocytopenia continued, along with prolonged prothrombin time (INR, 1.2–1.5) and activated partial thromboplastin time (1.5–2.5 times of normal control) (). Abdominal ultrasonography revealed no biliary tract obstruction but an ill-defined hypoechoic lesion in the right lobe of the liver, about 6.5 × 6.5 cm, probably due to an inflammatory process or tumor growth. Abdominal CT was indicated to confirm the characteristic of the lesion but was postponed due to the patient's poor renal function. After consultation with a gastrointestinal expert, the lesion was thought to be a liver abscess or focal necrosis due to ischemic change. Her consciousness had been deteriorating since post-PPH day 20 in combination with intractable fever. Brain CT showed no intracranial lesion. Worsening cognition was likely due to metabolic encephalopathy of hepatic or infectious origin. A liver transplantation was indicated, and a pretransplantation CT scan showed poor enhancement of the right hepatic lobe on the periphery covering about 50% of the total area, which was suggestive of liver infarction (). Living donor liver transplantation was performed 28 days after PPH. The donor was her younger brother, and the graft liver weight was 840 gm. The graft-to-recipient weight ratio was 1.24%. Intraoperatively, there were multiple micronodular lesions on the liver surface with marked swelling of the liver parenchyma and diffuse devitalized liver tissue in the right lobe of liver with necrosis and in the left lobe peripheral zone accounting for about 70%–80 % of the total liver volume (Figures and ). The patient's bilirubin level improved on the first three days but increased again on the 4th day after transplantation. The coagulation parameters did not change significantly after liver transplantation. Serial liver ultrasonography showed acceptable vascular status of the transplanted liver, without thrombosis or biliary obstruction. Fever, tachycardia, and hypotension occurred on the 6th day after transplantation as well as vaginal and anal stool leakage. An emergency colostomy and perianal debridement were done under the suspicion of a perianal abscess and rectovaginal fistula. Unfortunately, the patient died of an intractable infection the next day.

pmc-6016216-1

A 55-year-old gentleman, ex-smoker, presented to our hospital complaining of mild epigastric pain, regurgitation, and heartburn. On top of that, he has a long-standing history of gastroesophageal reflux disease (GERD), which was managed by proton pump inhibitors. His past medical history was significant for hypertension. He was previously diagnosed with a liver hemangioma based on abdominal ultrasound two years before the presentation. He had no relevant family history. Physical examination revealed mild epigastric tenderness with no palpable abdominal mass. Laboratory data showed no anemia but positive stool occult blood test. Tumor markers including AFP, CEA, and CA 19-9 were all within normal range. Upper GI endoscopy revealed mild esophagitis, Los Angles grade A along with Barrett's esophagus without dysplasia and a 1 cm polyp at the GEJ. A sample was sent for histopathology; the rest of the stomach and duodenum were normal. The patient did not have a previous endoscopy prior to this one. Infused computed tomography (CT) of the abdomen and chest showed mild GEJ thickness with no evidence of mediastinal or celiac lymphadenopathy and no signs of metastasis. It also demonstrated a large heterogeneously enhancing mass about 6 × 9.5 cm with central necrosis in the upper abdomen that appears to be originating from the gastric antrum (greater curve). The mass was highly suggestive of GIST based on CT; it was the same mass that was previously misdiagnosed as a liver hemangioma (). Endoscopic ultrasound confirmed the previous findings. However, no biopsy was attempted due to the risk of bleeding. Histopathological examination of the GEJ polyp revealed tubulovillous adenoma with elements of adenocarcinoma in situ. The patient was admitted with a provisional diagnosis of early-stage adenocarcinoma of GEJ along with the incidental finding of enlarging gastric GIST. A trial of endoscopic mucosal resection of GEJ polyp was attempted but failed because of the polyp location that created a technical difficulty. Therefore, the patient was taken to the operating room with a plan to perform a wedge resection of the gastric mass and a submucosal resection of GEJ polyp through the same gastric opening. We planned to use frozen section (FS) to document negative margin resection and determine the need for a formal esophagectomy. Intraoperatively; a large (10 × 7 × 6 cm), extraluminal pedunculated mass was found at the posterior wall of the greater curvature of the stomach (). Wedge resection of the gastric mass with negative margins was achieved along with a transgastric submucosal resection of the GEJ polyp. Fortunately, the FS examination of the polyp showed negative margins as well with no evidence of deep invasion. Postoperatively, the patient had a smooth course and was discharged home in a stable condition. The final pathological examination revealed a GEJ polyp around 1.7 × 1.4 × 0.6 cm. Microscopically, there was a focus of invasive adenocarcinoma involving the superficial submucosa of the polypoid lesion, negative margins, and no lymphovascular invasion (T1a NxM0). Furthermore, the gastric wall mass measured around 10 × 7 × 6 cm with a 2 × 1.5 cm stalk. Histopathology revealed encapsulated high-grade epithelioid GIST tumor with negative margins (pT3). The mitotic rate of 6/50 HPF and immunohistochemical stains were positive for DOG1 and CD34 but negative for CD117 (c-Kit) (). The final diagnosis was synchronous early-stage GEJ adenocarcinoma and a high-grade gastric GIST. Therefore, the patient was started on adjuvant imatinib treatment, along with endoscopic surveillance every six months and proton pump inhibitors.

pmc-6016220-1

A 25-year-old G3 P0020 at 36 3/7 weeks of gestational age with a singleton pregnancy presents with acute-onset, severe back pain and fever. Pain was described as constant, aching, and sharp. Her prenatal course was significant for multiple left antecubital abscesses requiring drainage (culture positive for methicillin-resistant staphylococcus aureus, MRSA) at 34 weeks and she was treated with clindamycin. On initial questioning, she admitted daily tobacco use but denied intravenous drug use. She was afebrile on presentation, but nodularity was appreciated at the left antecubital fossa and she had lower back tenderness to palpation. Physical exam was otherwise unremarkable. Biophysical profile and nonstress test confirmed a reassuring fetal status. Initial white blood cell count (WBC) was 21 [K/uL], C-reactive protein (CRP) was 27 [mg/L], and erythrocyte sedimentation rate (ESR) was 63 [mm/hour]. Urine toxicology screening was negative. Empiric treatment with vancomycin and piperacillin/tazobactam was initiated after she developed hypotension and a fever. Preliminary blood cultures were positive for gram positive cocci, later found to be positive for MRSA. Magnetic resonance imaging (MRI) of lumbar spine was obtained because of severe lower back pain that did not resolve with analgesia. This study revealed a small dorsal spinal collection with edema in the left psoas muscle. Neurologic reflexes were intact and serial neurologic exams were normal. Back pain continued to increase, and the patient developed weakness of bilateral lower extremities. Given the concern for acute structural damage to the spinal cord, the patient was counseled regarding risks, benefits, and alternatives to contrast imaging during pregnancy and opted for MRI with gadolinium intravenous contrast []. This was repeated after two days of antibiotic therapy to assess for further progression of abscess. MRI revealed an epidural abscess from T5-6 to T8-9 causing mild thecal cord compression and a collection from L4 to S1 (see Figures and ). Because of concern for worsening neurologic symptoms of lower extremity weakness and difficulty ambulating, cesarean delivery was performed followed by laminectomy (T5-10) and decompression of the epidural abscess. Intraoperative cultures were obtained and were positive for MRSA. Cesarean delivery was uncomplicated. Neonate weighed 2690 grams with Apgar score of 8 and 9 and was treated with vancomycin and gentamycin for suspected sepsis. Placental pathology and cultures were negative. Postoperative course was complicated by persistent MRSA bacteremia. Repeat MRI revealed residual abscess from T6-T9, with cord compression at T6-T7, and a left psoas muscle collection (see ). Three days later, reexploration and laminectomy from T4-T7 were performed and antibiotic treatment was continued with vancomycin and ceftaroline fosamil. During her extended hospital course, she admitted to previous illicit drug use but denied current use. However, there was a high suspicion for intravenous drug use due to her poor pain tolerance and history of antecubital abscesses. Later in her clinical course she endorsed a history of intravenous drug use. Once blood cultures were negative, she was discharged home in stable condition to continue long-term antibiotic therapy. Lower extremity weakness had resolved at time of discharge; however, she continues to have residual weakness, pain, and incontinence.

pmc-6016221-1

A 32-year-old female with a past medical history significant for schizophrenia, bipolar disorder, and hepatitis C antibody positive presented from the behavioral health center for a 2-day history of a diffuse rash. The rash had started on her upper extremities and then spread to her face, chest, and thighs 2 days prior to admission. At times, the rash had been itchy and the patient had reported chills. She had been started on clozapine 10 days prior to admission. On admission she was febrile to 38.1°C, tachycardic to 113 bpm, and hypotensive to 96/63. On exam, she had a maculopapular rash that was nonblanching over her entire body except her lower legs. There was no mucosal involvement, but she had mild facial edema. Pertinent admission labs included WBC 6.9 (3.7–11.4 103/µL), Hgb 10.6 (10.8–15.3 g/dL), platelet 196 (140–393 K/µL), eosinophils 10 (0–6%), eosinophils absolute 0.7 (0.0–0.5 103/µL), aspartate aminotransferase 81 (14–36 U/L), alanine aminotransferase 125 (9–52 U/L), alkaline phosphatase 155 (38–126 U/L), and hepatitis C antibody positive. Her urinalysis showed moderate leukocyte esterase with white blood cells, squamous cells, and few bacteria. Imaging on admission included chest X-ray, which showed a small left sided pleural effusion. A CT chest was done which showed minimal bilateral atelectasis with trace pleural effusions and cholelithiasis with contracted gallbladder and pericholecystic fluid. At this point, there was concern for infectious etiology, and blood cultures were drawn. The patient was then started on broad-spectrum antibiotics with cefepime and vancomycin. Clozapine was stopped and her benztropine and lithium were initially continued as she had been on these for many years. After being seen by psychiatry, they were also discontinued. She was given Benadryl for her rash. Hepatitis C viral PCR pathogens were found to be negative. Blood cultures grew staphylococcus coagulase negative and urine culture showed mixed flora with no infection. The blood cultures were thought to be a contaminant, so they were redrawn and the second set did not grow anything. Antibiotics were discontinued, as there was no further concern for infectious etiology. Eosinophils continued to be elevated and she developed a leukocytosis. The next three days, her white blood cell count continued to rise and peaked at 26.5 103/µL. She had worsening fever and became more tachycardic. Liver enzymes continued to rise, so an ultrasound abdomen was performed due to concern for cholecystitis, which was negative. Antibiotics were restarted due to concern for infection. Her eosinophil count rose and peaked at 14%. She had an echocardiogram to rule out endocarditis, which was within normal limits. CT abdomen and pelvis with contrast was done to rule out an abdominal infection. It showed colon thickening, cholelithiasis, trace pleural effusions, and porta hepatis lymphadenopathy. Antibiotics were all discontinued again as infectious etiologies had been ruled out. At this point, there was concern for drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) as she had the classic signs of DRESS including eosinophilia, skin rash, lymphadenopathy, and elevated liver enzymes. Other viral exanthema reactivations that are associated with DRESS were also considered. EBV, HHV-6, and HHV-7 were drawn, and all came back negative. Mononucleosis testing was not done on presentation although this can present as DRESS syndrome. Dermatology was also consulted and agreed that this was DRESS syndrome. Methylprednisone IV 125 mg three times daily was started along with clobetasol twice a day. After starting prednisone, fever and white blood cell count improved. Eosinophils trended back down to normal limits and liver enzymes started trending down. She was discharged on an oral prednisone taper for 12 days. Outpatient follow-up did not show any further eosinophilia, white blood cell elevation, or elevated liver enzymes. Rash improved and disintegrated.

pmc-6016224-1

A 23-year-old woman presented with progressive headache, nausea, and vomiting for 1 week. Right-side weakness, ptosis, and diplopia were also found. Due to acute onset conscious disturbance (Glasgow Coma Scale of E3VaM5) in the hospital, brain computed tomography was arranged and revealed an enhanced brain tumor with necrotic cystic change. This tumor was located at the left temporal lobe with upward extension to the left basal ganglion and periventricular region, causing perifocal edema and midline shift (). We performed emergent craniectomy for tumor removal in December 2006. Pathology revealed pleomorphic, hyperchromatic cells with glassy, astrocytic cytoplasm, as well as hypercellularity, microvascular proliferation, and necrosis, consistent with the diagnosis of classic GBM (). The patient underwent radiotherapy 1 month later and followed by chemotherapy with temozolomide for 6 months. Her performance status improved to a Karnofsky Grade of 70, and her clinical condition was stable thereafter. However, follow-up brain magnetic resonance imaging (MRI) in June 2014 revealed a new enhanced nodular lesion, approximately 1.1 cm in diameter, at the left temporal base. The brain MRI in October 2014 revealed a progressive change of lesions, maximum 3.0 cm in diameter (). Thus, she again received surgery for gross tumor removal. Histologically, except for the necrosis feature of GBM, the tumors showed the oligodendroglial component. Neoplastic cells also showed isocitrate dehydrogenase 1(IDH1)(+), p53(diffuse +), and O6-methylguanine-DNA methyltransferase (MGMT)(−) as revealed by immunostaining (). During follow-up, signs of increased intracranial pressure were noted in May 2015. Therefore, she received a third debulking surgery. The third pathology revealed both GBM- and PNET-like components. In immunohistochemistry, the PNET-like component exhibited positivity for synaptophysin and CD56 and focal weak positivity for glial fibrillary acidic protein (GFAP) (). One month after the surgery, her condition rapidly deteriorated. The patient and her family chose to pursue hospice care. She passed away with a total 9-year survival since diagnosis ().

pmc-6016228-1

A 4-year-old boy was admitted to pediatric department because of newly occurred hypertension as status posterior right heminephrectomy of neuroblastoma. Computed tomography angiography (CTA) scan revealed renal artery severe stenosis and right kidney atrophy. He had undergone Transcatheter Arterial Embolization of right renal artery 4 days ago because of the refractory hypertension. He was stable after the surgery and transfused 1 unit of packed red blood cells due to anemia. Five hours later, he became anxious and breathless, spitted frothy sputum, and then suffered an episode of cardiac arrest. After being intubated and 20 minutes' CPR, he underwent restoration of spontaneous circulation (ROSC). The attending physician treated him with cortisone as transfusion related acute lung injury (TRALI) was suspected. Then the patient was transferred to the ICU to receive respiratory support and further treatment. At presentation, he had a heart rate of 160 times/min and blood pressure of 150/111mmHg without any vasoactive drugs. A lot of flesh-colored aqueous sputum was spurred out of endotracheal tube. Tidal volume is only about 30ml on invasive ventilation with PI 15cmH2O and PEEP 10 cmH2O (PCV mode). Before he arrived to the ICU, the patient received manual ventilation with balloon and sputum suction constantly for 1 hour. The lung was very stiff and hard to inflate by balloon. Arterial blood analysis showed pH 6.7, PO2 56mmHg, PCO2 28mmHg, lactate 16 mmol/l, and BE -30. The FiO2 was 100%. There was no urine output in the first hour. We performed critical care ultrasound using the 7-step approach workflow at that time to make the puzzle clear ().

pmc-6016228-2

A 61-year-old male patient was admitted to the liver surgery department because of discovering liver mass for 6 days. The alpha-fetoprotein (AFP) was 1009 ng/ml, and liver contrast CT scan indicated hepatic cell cancer in the right lobe. As a generally healthy status before surgery, the patient received ALTPS surgery. 20 days later, he got fever and abdominal pain and developed shock as well as hypoxia in hours. He was intubated and treated with fluid resuscitation and norepinephrine (1.8 mcg/Kg.min) and then transferred to the ICU. Auxiliary examination showed WBC 0.63×109/L, PLT 7×109/L, and PCT 45.88 ng/ml; bedside ultrasound was ordered and ascites were found. The doctors cultured and drained the ascites and treated him with Imipenem and Vancomycin. Then they ordered abdominal CT and it reveals signs of necrosis of right lobe of the liver. Later, the patient suffered the second surgery to remove the right half of the liver. Culture of ascites reports Escherichia coli. After three days, the patient got better. No fever existed and the norepinephrine had been decreased to 0.4 mcg/Kg.min, and urine output had been maintained at 2000–2500ml per day. Two days later the patient had fever again, with the highest temperature of 38.8°C, as well as an increase of norepinephrine from 0.4 mcg/Kg.min to 2.0 mcg/Kg.min, deterioration of liver function, coagulation, and oxygenation. Arterial blood gas test showed pH 6.988, PaO2/FIO2 154, PaCO2 147.7mmHg, BE -19 mmol/L, and lactate 9.7 mmol/L. We performed critical care ultrasound using the 7-step approach workflow at that time to make the puzzle clear ().

pmc-6016423-1

A 25-year-old previously healthy male patient from Yunnan province in Southern China was airlifted to the First Affiliated Hospital of Zhejiang University for “fever of unknown origin” and respiratory failure on October 29, 2017. Ten days before, he started having a fever of 38°C and mild diarrhea without an obvious etiology. A few days later, he started feeling chest tightness and shortness of breath and having cough with yellow purulent sputum. He was admitted to a local hospital, where a thoracic computed tomography (CT) scan revealed pneumonia with a small amount of pleural effusion in the right lung. He was diagnosed with “lobar pneumonia” and treated with moxifloxacin plus cefoperazone sulbactam for 5 days. However, the symptoms worsened, and the patient continued having a high fever (40°C). Another CT scan showed significant progress of consolidation in the right lung and multiple nodules and pleural effusion in the left lung. The treatment regimen was changed to imipenem, linezolid, caspofungin, and ganciclovir. Methylprednisolone was given as well. However, the patient’s condition rapidly deteriorated to respiratory failure, which required mechanical ventilation, thoracic drainage, and drug sedation, before he was transferred to our hospital. No laboratory results were available from the outside hospital. Personal history revealed the patient to be a heavy smoker. Upon admission, he was febrile (38.4°C), tachycardic (109 bpm), and hypotensive (62/51 mmHg) with leukocytosis (white blood cell count [WBC] 18.6 X10E9/L). His C-reactive protein (CRP) was 146.42 ng/L, but procalcitonin (PCT) was only 0.49 ng/L. His troponin (0.3 ng/mL) level and his liver enzyme (aspartate aminotransferase [AST] 140 U/L) were both elevated. Bronchoscopy showed profound congestion and edema in the airway mucosa accompanied by multiple bleeding ulcers. Microbiology work-ups were initiated, and the patient received daptomycin (for suspected endocarditis after bedside echocardiogram showed hyperechoic response in the right ventricle) and piperacillin/tazobactam. On hospital day (HD) 2, the respiratory viral polymerase chain reaction (PCR) panel detected adenovirus in the sputum. Ganciclovir (0.3 g qd) was started again, and immunoglobulin was added. However, the exact origin of the fever was unclear, and the severity of the condition didn’t seem to match adenovirus respiratory infection alone. A transesophageal echocardiography (negative results) was performed to rule out infective endocarditis. Bone marrow puncture and lymph node ultrasonography (negative results) were performed to rule out lymphoma. These revealed T-cell subpopulations in the bone marrow suggestive of suppressed immune status, and therefore thymosins was given. On HD 3, BAL and blood were sent for shotgun metagenomics testing to identify the source of the fever. On HD 4, BAL and sputum culture came back positive with Aspergillus fumigatus; thus voriconazole was started. At this point, the diagnosis of the unknown fever was starting to shift to a fungal pneumonia. On HD 5, the shotgun metagenomics results came back positive with large amount of adenovirus in both BAL (1301 reads) and blood (795 reads). No other pathogens, including bacteria, fungus, and parasites, were found. Aspergillus fumigatus, which was isolated in the initial sputum culture, was not detected by the shotgun metagenomics. Because the subsequent respiratory cultures also did not yield any fungus, combined with the shotgun metagenomics results, the 1-time finding of A. fumigatus in the sputum was deemed to be a result of environment contamination. The high number of adenovirus reads were sufficient for de novo assembly into several large contigs (max size, 4800 bp), which were closely matched to human adenovirus B55 (HAdV-B55). Of note, this is the same strain that has been reported to cause numerous outbreaks in military units, hospitals, and schools in China, and that often causes deaths in immunocompetent young patients []. With this information, it was very clear that this patient was suffering an invasive HAdV-B55 infection that started from pneumonia and progressed into viremia. All clinical efforts were refocused to antiviral therapy. Because cidofovir, the firstline drug for adenovirus infection, is not available in China, ganciclovir was replaced by ribavirin (0.5 g q12h) administered intravenously on the basis of more successful treatment cases reported on the literature []. On HD 8, the patient’s inflammatory markers, including WBC, CRP, and PCT, all increased significantly. Bronchoscopy showed an increased amount of purulent sputum, and the culture grew pan-drug-resistant (only susceptible to tigecycline) Acinetobacter baumannii, a common nosocomial pathogen circulating in many ICUs in China, including ours []. Piperacillin/tazobactam was then replaced by cefoperazone/sulbactam (1 g q6h) plus tigecycline (50 mg q12h). To rule out other infections and monitor the antiviral therapy, a second set of BAL and blood samples was sent for shotgun metagenomics on HD 9. The results were negative in the blood but positive in the BAL, with a reduced load of adenovirus (10 reads) and a high load of A. baumannii (1666 reads). No other pathogens were detected in the BAL. The absence of adenovirus in the blood (confirmed by PCR) and the significant decrease of adenovirus load (1 log reduction by a quantitative PCR) in the BAL suggested that the patient was responding to the ribavirin treatment. The detection of A. baumannii was consistent with the culture results. The absence of any fungus in the BAL by metagenomics testing again, supported by repetitive negative fungal culture in the respiratory samples, prompted the discontinuation of voriconazole. Ribavirin treatment was continued, and a qualitative adenovirus PCR test on the sputum was done daily to monitor viral infections in the lung. On HD 10, the patient’s liver enzymes, troponin level, and ejection fraction had all returned to their normal ranges. On HD 18, due to repeated positive cultures of A. baumannii in the sputum, the dose of cefoperazone/sulbactam was increased from 1 g q6h to 3 g q6h. On HD 21, the adenovirus PCR in the sputum finally turned negative, the amount of A. baumannii grown in sputum culture also turned from heavy to rare, and the inflammatory markers (WBC/CRP/PCT) had all dropped significantly. On HD 24, bronchoscopy showed significant improvement in the trachea and the airways; thus, the chest drainage tube was removed, and the antibiotics were discontinued. On HD 26, the patient woke up after sedation was discontinued. On HD 28, due to the concern for drug-induced liver damage (AST increased to 161 U/L), ribavirin was discontinued. His condition began to stabilize, and ventilator support was gradually reduced. However, on HD 28, the patient developed altered mental status, seizures, and muscle weakness. Head CT showed widening in the sulci and cisterns, concerning for encephalitis. Meanwhile, the patient started having fever again (38.6°C). On HD 30, the sputum adenovirus PCR test was positive again, raising concern for neurological adenovirus infection. A lumbar puncture was performed and the CSF, which surprisingly had unremarkable biochemistry (glucose 4.3 mmol/L, protein 0.331 g/L) and cellular (RBC 170/uL, WBC 33/uL, 12% neutrophils, 88% lymphocytes) results, was sent for shotgun metagenomics testing. Two days later, the metagenomics results came back positive for herpes simplex virus–1 (HSV-1; 844 reads), which was subsequently confirmed by HSV-1 PCR. Neither adenovirus nor any other pathogens was detected. A diagnosis of HSV-1 encephalitis was made, and high-dose acyclovir (500 mg Q8h) was given to the patient. After 3 days of acyclovir treatment, the fever and seizures were gone, and the limb muscle strength was improved. On HD 40, the patient showed substantial improvement and could eat unassisted; therefore, the nasogastric intubation was removed. On HD 44, ventilation support was finally withdrawn. Another lumbar puncture was done, and the CSF was sent for shotgun metagenomics testing, which came back negative (confirmed by HSV-1 PCR). The patient was discharged on HD 52. Blood cultures were never positive, and the patient’s adenovirus PCR in the sputum was intermittently positive until HD 48. The hospitalization history, including major events, treatment courses, inflammatory markers, and test results, is summarized and illustrated in .

pmc-6016639-1

A 38-year-old male was referred to the outpatient clinic at the Department of Nephrology with treatment-resistant hypertension, rapidly developing edema and overt proteinuria (week 11, Fig. A). The patient was initially followed at the outpatient clinic at the Department of Endocrinology with poorly controlled type 1 diabetes for 15 years with microvascular complications including retinopathy and albuminuria, thus presenting with urinary albumin/creatinine ratios over 1000 mg/g for at least 3 years. There were no clinical signs of neuropathy. Plasma creatinine had previously been normal, in the range 60–90 μmol/L. Through several years, the patient had hypertension that was well-controlled with ACE inhibitors. One year prior to the presentation, blood pressure increased progressively concomitant with development of edema. The patient presented with severe hypertension (200/140 mmHg, week 0, Fig. B), edema and urinary protein excretion at 18.5 g/24 h (week 1, Fig. D). Despite increasing doses and numbers of antihypertensive agents and diuretics (Fig. A), blood pressure continued to be severely elevated combined with progressive fluid overload and proteinuria (Fig. B and D). The patient was referred to the Department of Nephrology (week 11, Fig. A–D) with NS. At this time, a renography performed on treatment with an ARB revealed no perfusion of the right kidney, and ultrasound confirmed the presence of a 4 cm long, hypoechoic structure in the right retroperitoneal space believed to be a rudimentary right kidney. The left kidney was morphologically and scintigraphically normal. The antihypertensive medication at referral was thiazide, beta-blocker, calcium channel antagonist, ACE-inhibitor and mineralocorticoid receptor antagonist spironolactone with no suspicion of noncompliance (Fig. A). At presentation, the patient was alert but complained of headache, fatigue, and recent weight gain of 10 kg. On physical examination, blood pressure was 161/102 mmHg, and the patient revealed periorbital and universal pitting edema, no signs of ascites and otherwise normal examination. Based on edema, proteinuria, and hypoalbuminemia (25 g/L), he was diagnosed with NS assumed to be related to diabetes. There was negative test for M-component and no detectable autoantibodies (ANA, ANCA, anti-GBA) nor phospholipase A2 antibody. Hepatitis B and C as well as HIV serology were negative. To reduce blood pressure, treatment with a loop diuretic was initiated (furosemide 80 mg/day, Fig. A). After 2 weeks without effect on edema and blood pressure (Fig. B and D), with a decrease in eGFR and no change in plasma potassium (Fig. C), furosemide was stepped up to 160 mg/day (Fig. A). Despite treatment with five combined antihypertensive/diuretic agents, there was only a minor weight loss (~1 kg) and reduction in blood pressure. Therefore, a low dose of the ENaC blocker amiloride 5 mg/day was initiated (Fig. A) and a 7-day follow-up was scheduled, which the patient missed. At next contact after 2 weeks, this treatment resulted in effective resolution of edema, concomitant weight loss of 7 kg and reduction in blood pressure from 150/100 mmHg to 125/81 mmHg (Fig. B). The patient continued his normal diet and 24 h urinary sodium excretion increased from 127 mmol/day to 165 mmol/day. Proteinuria decreased from 8 g/day to 4.1 g/day (Fig. D), eGFR decreased from 41 mL/min to 29 mL/min and plasma potassium concentration increased from 4.6 to 7.8 mmol/L (Fig. C). The patient was immediately hospitalized for cardiac monitoring and treatment of hyperkalemia. Amiloride and spironolactone were both discontinued. At follow-up 5 weeks later, a combination-drug containing 2.5 mg amiloride and 25 mg hydrochlorthiazide was successfully reinitiated due to increased blood pressure 141/96 and edema. At the last visit to the outpatient clinic, the patient received the following antihypertensive /diuretic drugs; amiloride/hydrochlorthiazide 2.5 + 25 mg/day, metoprolol 50 mg/day, furosemide 125 mg/day, lercanidipine 10 mg/day, and lisinopril 20 mg/day and his blood pressure was 112/80, body weight was stable at 90 kg (15 kg weight loss), plasma potassium was 4.6 mmol/L, and plasma creatinine was 203 μmol/L with eGFR at 35 mL/min.

pmc-6016681-1

A 67-year-old Caucasian man came to our attention after a fixed oral prosthesis surgery. His past medical history was significant for a paroxysmal atrial fibrillation for which he was taking Amiodarone and Acenocumarol with stable International Normalized Ratio (INR) values. Following orthopantomography and CT scan, the procedure of implant insertion was performed with local anesthesia (Mepivacaine and vasoconstrictor) in area 36 [left lower jaw, designated according to the ISO system] [] without any complication. Acenocumarol had been discontinued 2 days before, switching to LMW heparin. The patient was discharged under antibiotic therapy (Amoxicillin and Clavulanic acid) and instructed to restart oral anticoagulant therapy after 2 days. About 48 h after the procedure, hiccup abruptly presented and failed to cease. The patient did not report any further symptom, and no complications were found at the revision of the surgical area. Three days after the onset, the patient came to the emergency department due to this persisting symptom: Baclofen, Metoclopramide and Bromazepam were administered without significant clinical improvement. Both ENT, neurological examinations, blood tests and a brain CT scan failed to show any abnormality. Three days later, Chlorpromazine 25 mg b.i.d. was administered for 2 weeks. Furthermore, the patient was advised to program in the next few days a brain MR scan and chest imaging that were negative. Seven days following the surgical procedure, the stitches were removed and the wound did not show any problem. The hiccup continued resulting in significant distress and sleep deprivation. Providentially, it spontaneously ceased after 18 days. Neither relapses or neurological symptoms were reported in the later months.

pmc-6016850-1

The patient, a 32-year-old Caucasian woman, presented to the West Virginia University Hospital Emergency Department via Emergency Medical Services. The patient had been at her usual baseline state of health with no significant past medical history prior to visiting the chiropractor for neck adjustment earlier that day for tension like soreness. The patient underwent neck manipulation after which she immediately complained of neck pain, diaphoresis, and proceeded to experience cardiac and respiratory arrest. Emergency Medical Services was called, and cardiopulmonary resuscitation was performed with one round of epinephrine administered. It was reported that the patient was pulseless and apneic for 3 minutes prior to EMS arrival. The patient was intubated on transport and her Glasgow Coma Scale score was 3T prior to arrival. Mean arterial blood pressure was 80 with palpable femoral pulses at arrival to the emergency department. Upon arrival in the emergency department, a CT stroke protocol was performed which demonstrated bilateral severe distal cervical vertebral artery dissections with acute thrombotic emboli seen in the left cervical vertebral artery ( and ). This was accompanied by complete occlusion of the basilar tip including the proximal posterior cervical arteries. The patient received an initial bolus of intravenous tissue plasminogen activator (IV rtPA) at this time and the decision was made to proceed with endovascular intervention given the recent onset of occlusion. The patient was brought to the neurovascular angiography suite and femoral access obtained. Angiography of the left vertebral artery demonstrated severe dissection involving the distal cervical vertebral artery segments at the C1-C2 level with presence of sub occlusive thrombi. There was an occlusive clot in the left Posterior Inferior Cerebellar Artery (PICA). Intracranial imaging demonstrated occlusion at the basilar apex with absent filling into the right Posterior Cerebral Artery (PCA). There was occlusion of the distal left PCA. Angiography of the right vertebral artery demonstrated severe dissection of the distal cervical vertebral artery at C1-C2 with the presence of trickle-like flow into the vertebrobasilar junction. No filling was observed in the right PICA territory (). At this point, it was decided that the left vertebral artery offered the best access to the basilar trunk. Subsequently, distal aspiration was begun with a Penumbra 5 Max ACE distal aspiration catheter which initially demonstrated slow flow through the suction tubing. The 5 Max ACE was withdrawn into the proximal basilar artery until flow was seen within the suction tubing. Repeat angiography at this time demonstrated recanalization of the basilar apex and proximal PCAs. TICI3 perfusion was seen in the right PCA. Occlusive clot remained in the left distal P2 segment. Given the large size of the PCA, timing of events, and patient’s age, the decision was made to attempt clot retrieval of this. At this time, the Trevo ProVue microcatheter was navigated into the left distal PCA distal to the clot. The Trevo 4 mm × 30 mm stent retriever was deployed for approximately 3 minutes. The suction canister was attached, and the stent retriever was pulled with distal aspiration. No significant recanalization was achieved with what amounted to TICI0 perfusion to the left PCA territory. No further attempts were made as it was believed that the left PCA territory had completed its infarction. Following completion of endovascular therapy, the patient was taken for immediate MRI Brain with and without contrast for assessment of brainstem integrity and cerebrovascular status prior to transport to the intensive care unit. MRI demonstrated extensive areas of restricted diffusion accompanied by perfusion abnormalities consistent with acute infarction of the posterior circulation, specifically within the bilateral cerebellar hemispheres, right medulla, pons bilaterally, midbrain, thalami, and left occipital lobe (). The following day, additional CT Brain imaging was acquired and demonstrated signs of elevation of intracranial pressure with hydrocephalus, worsening of cerebral edema diffusely, hemorrhagic transformation of the left occipital lobe, continued infarct evolution within the posterior circulation, and cerebellar tonsillar herniation.

pmc-6017126-1

A 51-year-old woman with a history of morbid obesity, obstructive sleep apnea on nocturnal continuous positive airway pressure ventilation, and non-insulin dependent diabetes mellitus presented to the urgent care clinic with an unresponsive intractable chronic headache for almost a year. The headache was 7/10, intermittent, non-radiating, throbbing, the frontal headache lasting for almost a year and was thought to be secondary to post-concussion syndrome given a history of head trauma one year ago with no loss of consciousness. At the time, computed tomography (CT) scan of the head was unrevealing (Figure ). Over the past year, the patient had visited the emergency department multiple times with a severe headache. Secondary causes of headache such as severe hypertension, pharyngitis, sinusitis, meningitis as well as tumor, subdural hematoma, and hydrocephalus were ruled out. Laboratory work up was unrevealing with a normal ESR and CRP. Magnetic resonance imaging (MRI) scan and lumbar puncture were both negative. In addition, the patient’s headache persisted despite a trial of NSAIDs, acetaminophen, tramadol, and Fiorecet. Upon reconciliation of the patient's medications, it was found that she was switched from metformin 500 mg twice daily to metformin-sitagliptin 50-1000 almost a year ago, about a week before the onset of headache. Considering the temporal association of the medication and symptom presentation, sitagliptin was discontinued as a trial treatment and the patient was switched back to metformin. The patient reported resolution of her headache two days after discontinuation of sitagliptin.

pmc-6017127-1

A 57-year-old Caucasian female presented to the hospital with a worsening, diffuse, bullous eruption. The eruption started four weeks prior and was distributed mainly on her lower extremities. The patient went to her primary care physician, who prescribed doxycycline and sulfamethoxazole/trimethoprim and told the patient that she had cellulitis. The patient took the antibiotics but the rash continued to worsen. After completing the antibiotic course without improvement, the patient presented with diffuse and erythematous tense bullae ranging from 1.5 to 2 centimeters in diameter. The lesions can be appreciated on the patient’s face, neck, back, chest, abdomen, and extremities (Figure ). Some of the lesions had ruptured and were both pruritic and painful. The patient was afebrile and without leukocytosis, yet C-reactive protein was elevated at 97.8 mg/L. An initial punch biopsy was performed and returned negative for a definitive diagnosis. A repeat punch biopsy four days later showed a subepidermal blister with eosinophils and neutrophils. The underlying dermis demonstrated severe edema and infiltrate composed of eosinophils and lymphocytes (Figure ). Direct immunofluorescence (DIF) of the skin revealed the linear deposition of immunoglobulin G (IgG) and complement C3 along the dermo-epidermal junction (Figure ). The patient was diagnosed with bullous pemphigoid and was treated with prednisone 60 mg daily. The patient responded well with a decreased number of bullae, as well as an improvement of the erythema and pruritus. The patient was discharged on a tapering regimen of prednisone 60-40-20 mg for one month per dose, along with oral sulfamethoxazole/trimethoprim 160 mg daily for prophylaxis of Pneumocystis carinii pneumonia. The patient was referred to a dermatologist to discuss adding a steroid-sparing agent such as methotrexate or azathioprine.

pmc-6017155-1

The patient is a 49-year-old male with longstanding back and left leg pain resistant to pain management. He developed acute worsening of his left sciatic pain and suffered a fall with a left wrist fracture. He subsequently developed shortness of breath and was seen in the emergency room. A computerized tomography (CT) study revealed two right retroperitoneal masses, a right prevertebral lesion measuring 4.1 x 3.6 x 5.7 cm with anterior displacement of the inferior vena cava (IVC) and a right paraspinal lesion centered in the psoas measuring 4.0 X 3.5 x 6.6 cm (Figure ). The percutaneous biopsy of these lesions was consistent with a benign nerve sheath tumor. He was sent for neurosurgical management and, during his evaluation, was noted to have an 8 x 5 x 5 cm left sciatic tumor (Figure , Figure ). This was excised uneventfully and found to be a Grade I neurofibroma. His chronic left sciatica resolved although his back discomfort persisted. Despite the multiple neurofibromas, the patient did not meet the criteria for NF1. He had a family history of multiple melanomas and other malignancies and was sent for genetic evaluation. He was found to have a large, contiguous genetic deletion of chromosome 9p21.3 extending beyond the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and spanning approximately 25 genes []. His medical comorbidities included uncontrolled insulin-dependent diabetes mellitus with a HgA1C of 11.0, complicated by neuropathy and renal insufficiency, a cerebrovascular disease with two prior cerebral vascular accidents (CVA), and mild residual left hemiparesis, a peripheral vascular disease involving iliac stenting, tobacco abuse, and obesity. The retroperitoneal masses were followed with imaging and were stable for three years. He then developed progressive back and radicular abdominal pain. Imaging revealed the growth of the right prevertebral lesion to 4.4 x 4.0 x 6.2 cm and the growth of the right paraspinal lesion to 4.7 x 4.0 x 7.5 cm (Figure ). Neither tumor had changes concerning for malignant degeneration. Given the tumor locations, the progression of the patient’s comorbidities, and his predisposition to develop malignancy, he was not felt to be a good candidate for surgical excision or radiosurgery. For these reasons, he was referred to interventional radiology for image-guided RFA. The procedure was performed with the aid of anesthesia. Under CT guidance, a 17G 3-cm burn radius ablation needle (Cool-tip, Covidien, Boulder, CO, USA) was advanced to each of the lesions, with a 12-minute burn cycle performed at each site (Figure , Figure ). He had no complications. At six weeks post-ablation, the right prevertebral lesion had decreased in size to 3.4 x 3.5 x 5.4 cm and the right paraspinal lesion now measured 3.3 x 4.2 x 6.3 cm (figure not shown). Six months after the procedure, he reported his pain had improved. He no longer required methadone for pain control. On the most recent imaging performed four years after the ablation, the anterior prevertebral lesion shows stable regression at 2.9 x 3.3 x 3.5 cm with the posterior paraspinal lesion further decreasing in size to 2.6 x 3.6 x 5.1 cm (Figure ). Table shows tumor measurements over time.