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pmc-8571988-1 | A 22-year-old male presented to the Department of Emergency Medicine with complaints of sudden onset right flank pain accompanied by gross hematuria. Pain was moderate in intensity, nonradiating with no history of trauma or fever. Vitals including pulse, blood pressure, and respiratory rate were within normal limits. Urine microscopy demonstrated multiple red blood cells suggesting hematuria. The patient was referred to the Department of Radiology for ultrasonography of the abdomen which revealed a well-circumscribed, heteroechoic, cortical based lesion measuring 2.0 × 1.8 cm located in the upper pole of right kidney. Color Doppler demonstrated no significant internal vascularity within the lesion (). Furthermore, a well-defined heteroechoic mass was noted at the dependent portion of the urinary bladder, suggestive of a giant retained clot (). Chest radiograph, chest computed tomography (CT), and bone scans were all negative for metastasis. Based on the radiological findings, a diagnosis of renal oncocytoma with symptomatic hematuria leading to giant clot retention in the urinary bladder was made. The patient was referred to the Department of Urology for further management where she underwent laparoscopic partial nephrectomy of the right kidney and tumor resection. The resection margins were free of tumor, and there was no evidence of perinephric invasion or lymphadenopathy. Histopathological examination of the resected specimen revealed round and polygonal cells within a loose stromal background, eosinophilic granular cytoplasm, round nuclei with inconspicuous nucleoli, and absent or rare mitotic figures consistent with a diagnosis of renal oncocytoma (). The patient was further catheterized, and urinary bladder irrigation with clot retraction was performed. The patient recovered well with no complications and was discharged home in good condition on the seventh day post operation. At 3 months follow-up, the patient was free of symptoms and had no signs of recurrence.
The patient has given written informed consent to publish his case and clinical images. |
pmc-8571990-1 | A 50-year-old male presented with hematuria, increased frequency, and burning sensation during micturition along with left flank pain for 2 months. There was a history of generalized weakness, weight loss, and loss of appetite during this period. On examination, the patient was poorly nourished with the presence of a palpable left-sided abdominal mass.
Ultrasonography (USG) of the abdomen showed the presence of right ectopic kidney and left-sided hydronephrosis. A heterogeneous mass was noted in the left kidney. Another polypoidal mass was also seen in the lumen of the urinary bladder, attached to its posterolateral wall.
Contrast-enhanced computerized tomography (CECT) of the abdomen helped in the renal anatomy and characterization of the mass, which revealed L-shaped crossed fused renal ectopia. The right kidney was not present in the right renal fossa and was in the midline, anterior to the aortic bifurcation at the L4-L5 level. It was malrotated and fused with the lower pole of the left kidney. The left kidney was enlarged, with a large soft heterogeneous tissue density mass involving the interpolar and lower pole regions that exhibited heterogeneous enhancement with central non-enhancing areas. Few calcified foci were seen in the mass, along with moderate hydronephrosis. In the delayed phase (15 minutes), no contrast excretion from the left kidney was recorded. The interpolar region of the right kidney was contiguously infiltrated by the left lower pole renal mass. Small tumor thrombi were present in the segmental right renal veins draining the interpolar region. Aortocaval, para-aortic and left renal hilar lymphadenopathy were also noted.
Along with these findings, a well-defined polypoidal mass was seen in the left posterolateral wall of the urinary bladder, infiltrating the left vesicoureteral junction. The middle and distal parts of the left ureter were contiguously involved by this urinary bladder mass. A peripheral rim of calcification was present.
Because of the involvement of multifocal enhancing masses of the moieties of crossed fused renal ectopia, urinary bladder, and left ureter, the radiological differential diagnoses offered were multifocal transitional cell carcinoma, renal cell carcinoma (RCC)- mucinous adenocarcinoma variant with multifocal spread, and renal sarcoma.
No distant lesion was found on metastatic work-up.
Initially, transurethral resection of the bladder lesion was done. Microscopic examination showed features of noninvasive papillary urothelial carcinoma, predominantly low-grade with high-grade focal areas, along with extensive dystrophic calcification and necrosis, and focal osseous metaplasia ().
The patient was then taken up for surgery for resection of the renal mass, and a left nephrectomy with partial right nephrectomy was also performed. The specimen was submitted for histopathological examination. The results showed that the capsule was intact. Cut section of the left kidney showed a tumor measuring 14x11x10 cm, replacing the entire normal structure. The renal pelvis was not identified, and part of the right kidney consisted of cystic and solid areas, with tumor measuring 3x2.5x2 cm ().
Multiple sections examined from both the kidneys showed a tumor composed of large areas of cartilaginous differentiation along with tumor cells arranged in diffuse sheets and fascicles. Marked pleomorphism and mitotic activity were noted, 18-19/10hpf. There was an abrupt transition to well-differentiated nodules of hyaline cartilage. Intervening stroma showed consistent focal areas of myxoid change with chronic inflammatory cell infiltrate. The focal osteoid formation was present, with numerous giant cells and apoptotic debris. Areas of chicken-wire calcification and hemorrhage were also identified, along with large necrotic sections ().
The tumor cells were immunopositive for CD99 with strong S100 protein expression in the areas of cartilaginous differentiation, immunonegative for pan-cytokeratin, CK7, CK20, p63, desmin, and myogenin, and with retention of INI1 expression ( and ). These morphological and immunohistochemical features suggested the presence of primary chondrosarcoma in crossed fused renal ectopia involving both moieties.
The patient was lost to follow-up after discharge from the hospital after an uneventful postsurgical period of 2 weeks. |
pmc-8710040-1 | A 25-month-old boy with fever and maculopapular rashes was admitted to Mofid Children's Hospital. His parents explained that fever began three days ago and rashes developed after one day. The rashes started with mild itching in the feet, spreading to the thighs and the genital area on the second day. Despite taking antihistamines, the fever and rashes continued on the third day. The patient presented to the hospital with fever, malaise, poor feeding, mucosal involvement of the mouth, lips, conjunctiva, and maculopapular rashes, which resulted in ulcer and bulla formation (). On arrival, he had the following vital signs. Temperature: 39.5°C, blood pressure = 82/10 mmHg, respiratory rate = 28, and pulse rate = 86. The patient's clinical course, blistered skin lesions, and mucosal involvement led to the primary diagnosis of SJS/TEN. Reviewing his medical history revealed that ranitidine was the only medication he had used in the past three weeks. Moreover, his mother had a history of upper respiratory infection (URI) three weeks ago, which was accompanied by low-grade fever and resolved in three days. The patient received supportive care, steroids, and intravenous immune globin (IVIG) based on the primary diagnosis of SJS/TEN. In the meantime, laboratory work up and a COVID-19 PCR test were performed. The results showed white blood cells (WBC) count = 3200/μl (Polymorphonuclear (PMN): 58% and lymph: 41%), hemoglobin (Hgb) = 12.3 gr/dl, and platelet count = 29000/μl. Additionally, the erythrocyte sedimentation rate (ESR) was 36 mm/hr and the CRP level was 58 mg/l. Liver function test, blood urea nitrogen (BUN), creatinine (Cr), albumin, and lactate dehydrogenase (LDH) were within the normal ranges. However, ferritin and fibrinogen levels were elevated (517 μg/L and 615 mg/dL, respectively) and the COVID-19 PCR result was positive. The findings of the chest CT scan were unremarkable. Considering the patient's general conditions, fever, and laboratory findings, MIS-C was diagnosed and atazanavir was added to his treatment. On the following day, his fever subsided and he began to eat and drink. After four days, he was discharged from the hospital with minimal skin lesions and a normal condition (). The patient was followed after one week, indicating that his laboratory test results were within the normal ranges and he was doing great. |
pmc-8718394-1 | A 53-year-old woman was referred to our clinic with waist and back pain and numbness of the lower limbs for more than 1 month. The pain was not related to her posture and became more prominent when she moved. She had a medical history of lumbar disc herniation and no history of trauma. On initial evaluation, her vital signs were stable. Apart from the pain of the waist and back, physical examination revealed unremarkable findings. Routine blood tests were obtained. Further, liver function tests revealed normal results. The blood CA199, CA125, CEA, and AFP levels were also within normal limits.
Computed tomography of the chest revealed scattered pulmonary nodules with calcifications associated with a soft tissue mass measuring 3.3 cm × 2.4 cm and without pleural thickening at the superior lobe of the right lung () (SOMATOM definition, Siemens Healthcare, Erlangen, Germany; tube voltage, 100-120 kVp; tube current, 450 mA; slice thickness, 0.625 mm; pitch, 0.992:1; rotation speed: 0.5 s/rot; ASIR-V:30%.). Enlarged lymph nodes of the right hilar were also evident. Abdominal contrast-enhanced CT revealed diffuse lesions with massive calcifications in the liver, which shows faint peripheral enhancement in the arterial phase and low enhancement in the portal phase (Iopromide Injection, Bayer Pharma AG; the arterial phase and portal venous phase were obtained at 25 s and 60 s after contrast injection.). The largest lesion measuring 10.2 cm × 5.9 cm was located in the right lobe of the liver and (). CT examination also revealed osteolytic lesions with a massive thick sclerotic rim in the right second rib, 11th thoracic vertebra, and first lumbar spine. Bone scintigraphy with 99mTc-methylene diphosphonate showed multiple hypermetabolic activities in the involved bones (). Cerebral magnetic resonance imaging (MRI) revealed no anomalies. The patient underwent transthoracic needle biopsy of the largest pulmonary lesion located in the right superior lobe. Histopathological analysis revealed epithelioid cells arranged in a glandular pattern with clear cytoplasm (). Immunohistochemical staining showed that the neoplastic cells were positive for CD31, CD34, CAMTA1, and EMA, but negative for ERG, TFE3, PCK, and desmin, with a Ki-67 index rate of 10%. Histopathological examination indicated a rare low-grade malignant vascular neoplasm, confirming the diagnosis of EHE.
Considering the multiple intra-pulmonary, right hilar lymph node, liver, and bone metastases, the patient was treated with chemotherapy with paclitaxel liposome (240 mg/m2; day 1) and carboplatin (550 mg/m2; day 1). At 8 months, the patient had completed four cycles of combination therapy. There were no changes in the patient’s disease status on CT at the 8-month follow-up visit. |
pmc-8718405-1 | The following case is presented to illustrate, using a biopsychosocial-ecological perspective, three different approaches to serving persons with dementia and their caregiver(s) in clinical practice.
Presenting concerns: Janice is an 85-year-old woman who lives independently in senior housing in the Canadian province of Alberta. In response to Janice's increasing needs for support, Gwen, her daughter and primary caregiver, scheduled an appointment for them to meet with her mother's Geriatrician to discuss changes in Janice's health and function related to her progressing dementia, and planned to discuss her own needs for support as well.
Gwen reported to the geriatrician that her mother's decline had been steady since her last appointment, most notably in her short term memory such that she was increasingly losing items, struggling to recall recent events, forgetting names, and having difficulty finding words, managing complex tasks, and planning. She shared that her mother had developed paranoia and visual hallucinations over the past year during which she imagines that strangers are trying to get into her home to steal her treasured belongings. The hallucinations had increased steadily and had worsened over the past month now occurring multiple times per week usually at night. Gwen also reported that Janice calls her frequently asking for help, and she noticed her mother being more irritable, angry, and frustrated than she used to be. She shared that her mother wanders out of her room but has not gotten lost.
Gwen also noted a “quite rapid” decline in Janice's function. Because she was no longer able to use the stove and had burned pots, she ultimately stopped cooking and depends on microwave-ready meals and easy snacks. Even with Gwen bringing her meals, however, Janice has had a 20 pound weight loss over the past year. Janice can still perform basic activities of daily living such as dressing, grooming, bathing, feeding, toileting, transfers and mobilization. She can still use the phone and does housekeeping and laundry on her own, but Gwen finds clothes soaked in urine in the laundry and believes that her mother has not bathed in a month. Gwen now manages her mother's money, medical appointments, and medications, and does her shopping and other errands as well.
Janice's neighbors and building management started to raise concerns to Gwen about her mother's safety, which Gwen reported has greatly increased her own anxiety about her mother's living situation. They reported that Janice is seen wandering around the facility at all hours and often checks in with other residents when she gets confused about day and time. There are times when she will knock on her neighbors' doors asking for help while experiencing hallucinations. They know her well and reassure and redirect her but Gwen wonders how long they will be willing to do this. Janice adamantly denies needing assistance but Gwen was finally able to get her to accept homecare for help with medications. The agency recently informed Gwen, however, that Janice does not always open the door for the homecare attendants and that she sometimes calls them derogatory names and yells at them to “get out.”
Concurrent problems: While Janice has experienced urinary incontinence for years, she was managing on her own with pads and then protective underwear as the incontinence worsened. Gwen describes her mother's bladder control as “good during the day” but notes that she “occasionally soaks her night clothes and bed during the night.” Janice also has occasional bowel incontinence and Gwen noticed that her pericare had declined and shared that she had found smeared stool around the toilet. The geriatrician also expressed concern about Janice's sensory deprivation noting that she is legally blind due to macular degeneration and that she suffers from bilateral hearing loss and has been unable to manage hearing aids on her own. Janice's other medical conditions include hypertension, osteoporosis, osteoarthritis, and hypothyroidism. She never smoked, rarely consumes alcohol, and gave up driving 3 years ago because of her vision loss.
Mental exam: The geriatrician noted that Janice was alert and cooperative and that she needed a pocket talker to hear. She scored 24/30 on the Mini-Mental State Exam () and 18/30 on the Montreal Cognitive Assessment (), both of which indicate “mild dementia.” The Clock Drawing Test (), a measure of spatial dysfunction and neglect, was abnormal. She correctly placed the numbers on the clock face but could not tell time. She had problems with orientation and displayed both short and long term memory deficits. Language skills were intact other than occasional word finding problems. She appeared anxious and got easily irritated. She needed reassurance to complete the assessment. She was occasionally distracted by visual hallucinations (e.g., she saw people in the room and wanted them chased away). She denied symptoms of depression. She had poor insight into her cognitive and functional decline and displayed poor mental reasoning when it came to supports needed to help her with her health and housing. She overestimated her abilities and did not recognize the degree of supports being provided to her. She acknowledged that her daughter provides some help but said she could manage without it. She expressed annoyance with having homecare.
Physical exam: No apparent distress.
Family and social history: Janice completed education through Grade 8 and worked as a secretary until she had children. She has been widowed for 20 years after having been a caregiver to her husband who died of cancer. She has 3 daughters, 1 son, and 8 grandchildren. Gwen, the youngest, her primary caregiver, and “the baby” of the family, is married, has 2 children, and lives 10 min away. Janice's son, Jack, is an accountant who lives out of town, helps with higher level financial management such as taxes, and is a source of emotional support for Gwen. Janice often mentions that Jack “leads a busy life with work and family” as an explanation for his infrequent visits. Her two older daughters are both married, retired, and live in other provinces. They check in about their mother periodically and visit once a year. Neither of the two older daughters is close to Janice or Gwen with the emotional distance rooted in their shared belief that their mother favored their two younger siblings when they were growing up. Gwen and Jack have remained close and frequently discuss their mother's deteriorating health and function. Janice has lived in her current residence, a subsidized senior housing facility, for the past 30 years. She has limited finances, including her husband's pension and her own, and she relies on her children to assist with money as needed.
Patient's values and beliefs: Janice does not want to leave her home. She is feisty and wishes to remain independent. She is fond of her belongings and takes pride in them– e.g., furniture, paintings, pictures, collectibles, etc. She believes that she raised her children well and gave them a good education, and she now expects reciprocity. She acknowledges the support provided by her daughter but is not particularly empathic toward her stress.
Medical and legal issues: Janice designated Gwen and Jack as the agents in her Personal Directives and Enduring Power of Attorney (EPOA), respectively. The EPOA was activated at the time it was established. Janice's Goals of Care Designation, a medical order used in Alberta to describe and communicate the general focus of care including the preferred care location, indicates that goals and interventions are for cure or control of illness. Her goals exclude the option of ICU care, while transfer to an acute care facility may be considered if required for diagnosis and treatment.
Caregiver stress: Gwen is committed to caring for her mother and determined to support her at home. She reported that she had promised not to relocate her to a “nursing home.” However, she admits to feeling “very stressed” caring for her mother. She is the only one in town and has taken over the majority of the responsibilities. Janice is quite demanding and calls her day and night asking for help. She gets easily irritated and angry with Gwen who has already reduced her hours at work by going part-time. Gwen believes at this rate she will have to quit work all together. This adds to her stress because she feels guilty about harming her family's financial situation. She and her husband annually spend $6,000 subsidizing her mother's housing, food, and health care supplies. Gwen is keenly aware that their daughters are approaching college age and that this is not the time to leave the workforce. She feels that her life is “on hold.” Her husband and children are supportive and help however they are able. She resents the lack of support from her sisters but finds her brother more supportive as he provides her with emotional support and helps to support their mother financially. At the same time she feels he could visit more often. She shared that caregiving is taking a toll on her health as she is experiencing panic attacks, insomnia, poor concentration, feelings of guilt, and chronic migraines, in addition to having emotional and physical symptoms associated with perimenopause. |
pmc-8718503-1 | We present a case of a 58-year-old female patient with a large recurrent ventral hernia. Six years before, the patient had been operated on for the umbilical hernia, with the simple repair without a mesh. The patient was an active smoker who suffered from morbid obesity with a body mass index of 43 kg/m2 and COPD as comorbidities relevant for this case report.
The patient was introduced to the surgeon during hospitalization at the gastroenterology department where a diagnostic workup due to a clinical picture of chronic small bowel obstruction was conducted. While taking the anamnesis, the patient reported frequent abdominal cramps, swelling, and pain in the area of the hernia that had intensified in the last few weeks. The physical examination revealed a large irreducible ventral hernia in the lower abdomen that was quite painful on palpation, but soft and, at that time, without signs of incarceration or strangulation. Taking into account the clinical picture with threatening hernia incarceration, the surgeon did not opt for preoperative optimization of the patient in terms of smoking cessation and starting a weight loss program but made an indication for semielective surgery.
On operative procedure, greater omentum, part of the transverse colon, and a cluster of small bowel loops with signs of chronic obstruction were found as hernial content. After adhesiolysis hernial content was reduced into the abdominal cavity. Hernial defect measuring about 7 cm in diameter and about 15 cm in the vertical line with significant rectus diastase in the supraumbilical part of the abdomen was revealed. Using the Rives-Stoppa technique a wide retromuscular space was created. Lateral dissection boundaries of this space were perforating neurovascular bundles in the area of the lateral edges of the rectus muscle on both sides. The posterior fascia was easily closed using also a portion of the hernia sac to bridge the defect between the posterior rectus sheaths. A 30 × 25 cm polypropylene mesh was placed in the retromuscular space ensuring adequate mesh overlap over the edges of the hernia defect of a minimum of 5 cm in all directions.
When we observed that the anterior fascia, due to the size of the defect and decreased abdominal wall elasticity, would not close entirely and cover the mesh, we opted for rectus mobilization by the ACS method to avoid bridging. Upon extensive dissection of the anterior abdominal wall subcutaneous space without preservation of the rectus perforator vessels, relaxing incisions of the external oblique muscle aponeurosis were performed. Using the Ramirez technique, long longitudinal incisions of aponeurosis were made bilaterally, adjacently to the semilunar line, extending from the costal arch to the groin. This procedure resulted in the considerable mobilization of the vital musculofascial flap medially, and the hernial defect was closed at the midline without tension. Then, four redon drains were placed, i.e., 2 in the retrorectus space and another 2 in the subcutaneous space.
The postoperative course was complicated by skin ischemia. Ischemic lesions of the abdominal wall skin on the right with signs of necrosis along the midline were observed already on day 8 (). On postoperative day 11, multi-slice computed tomography (MSCT) of the abdomen was performed because of the ever more abundant wound discharge. MSCT findings showed a large subcutaneous seroma, a normal musculofascial component of the abdominal wall, appropriate mesh position, and normal intra-abdominal status. Percutaneous puncture of seroma was performed and about 800 ml of clear seroma was evacuated. During the next 10 days, ischemia progressed, along with the development of another two full-thickness skin necrotic foci paramedially (). Considering the relatively strict demarcation area of necrosis, we opted for the operative procedure of necrosectomy.
Following abdominal wall necrosectomy with a safety margin of healthy tissue and considering an appropriate amount of vital residual abdominal skin, as well as the absence of signs of local tissue infection or mesh infection, primary wound closure was performed in consultation with a plastic surgeon (). As early as day 4 of the second operation, increased wound discharge and signs of skin wound dehiscence occurred, which required removal of skin sutures (). Then, a wound dressing with a hypertonic solution was applied for a week.
When inflammation subsided, negative pressure wound therapy (NPWT) with the “Renasis Ez Max VAC® system” (Smith & Nephew, Mississauga, Canada) was initiated (). NPWT was delivered in continuous mode with negative pressure maintained at −100 mm Hg. Dressing in the form of a sponge of polyurethane black hydrophobic foam was changed every third day. After 2 weeks of NPWT administration, considerable improvement was recorded in wound cleaning and formation of healthy granulation tissue (). NPWT was continued for the next 2 months, which resulted in further improvement of condition of the patient, along with decreased wound discharge and cavity reduction. The wound swab obtained twice during dressing change was sterile. The patient was discharged from the hospital and regular changing of silver-impregnated antimicrobial wound dressing (Aquacel Ag, ConvaTec, Reading, United Kingdom) was continued in ambulatory care that led to complete wound closure in 7 months (). |
pmc-8718506-1 | A 16-year-old male with DOCK8 deficiency (homozygous for DOCK8 variant NM_203447.3:c.4153+1G>A) enrolled on an IRB-approved National Cancer Institute HSCT trial for patients with DOCK8 (NCT01176006). His disease, diagnosed at age 8 years, manifested with recurrent sinopulmonary infections, chronic molluscum contagiosum, and eczematous dermatitis. Recent complications included diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL) 4 months pre-HSCT. Treatment with rituximab (4 doses) and LMB regimen (, ) (2 cycles), including vincristine, doxorubicin, corticosteroids, methotrexate and with cumulative cyclophosphamide dose of 3300 mg/m2 as per ANHL1131, Group B (R-COPADM), was complicated by chemotherapy-associated grade III BKV-HC managed with cidofovir and 2 infusions of third-party donor-derived quadrivalent anti-cytomegalovirus (CMV), -Epstein-Barr virus (EBV), -adenovirus (ADV), and -BK virus specific T-cells (VSTs) at 5x107 cells/m2 (NCT02532452) (). VSTs were well tolerated without any infusion reaction. HC symptoms subsequently resolved while asymptomatic BK viremia persisted. Achieving a complete remission, he proceeded to HSCT with his father as the haploidentical bone marrow donor. Reduced intensity (RIC) conditioning was comprised of fludarabine 30 mg/m2 x 5 days (days -6 to -2), busulfan dosed with target area under the curve (AUC) of 3600-4000 uM.min/day x 3 days (days -4 to -2), cyclophosphamide 14.5 mg/kg x 2 days (days -6 and -5), and low-dose total body irradiation (TBI, 200 cGy) on day -1. Graft-versus-host disease (GVHD) prophylaxis was comprised of post-transplant cyclophosphamide (PT/Cy) on days +3 and + 4 along with mycophenolate mofetil (MMF) x 30 days and tacrolimus x 6 months, both of which started on day +5 (). Mild cystitis without hematuria developed on HSCT day 0. BK viremia simultaneously increased from 588,844 copies/mL (3 days pre-HSCT) to 6,456,542 copies/mL on day +4 ().
His immediate post-HSCT course was complicated by gross hematuria and painful bladder spasms with PT/Cy (50 mg/kg) on days +3 and +4. Grade IV gross hematuria, managed with daily blood product transfusions, persisted alongside worsening acute kidney injury (AKI, day +14) (). Continued transfusion dependence led to significant fluid retention and 11 kg weight gain over 11 days. Daily platelet infusions were used to maintain platelet count ≥ 30 K/mcL, and platelet engraftment ≥ 50 K/mcL was not attained. Neutrophil engraftment was achieved at day +21; chimerism studies demonstrated 100% donor-derived cells without evidence of GVHD.
Progressive hydronephrosis and hydroureter prompted Foley catheter and bilateral nephrostomy tube placement by day +30. Gross hematuria from the left nephrostomy tube occasioned left renal arteriography which revealed active bleeding unrelated to the nephrostomy at multiple sites and features suggestive of vasculitis. Coil embolization performed on two separate occasions (days +35 and +38) provided only transient stabilization. Ongoing bleeding and transfusion needs were accompanied by increasing total and direct hyperbilirubinemia (2.9 mg/dL and 2.7 mg/dL, respectively (day +43)). Complete left renal artery embolization on day +42, followed by initiation of intravenous cidofovir (), stabilized the patient for transport to receive an additional infusion of third-party VSTs (day +43) produced using the same donor as his second pre-HSCT infusion (NCT02532452). BK viremia measured 5,754,399 copies/mL at third infusion, nearly a full log increase from viral load with pre-transplant VSTs ().
Two days after VST infusion (day +45), onset of cytokine release syndrome (CRS) was evidenced by fever, hypotension, worsening lung opacities, and bilateral pleural effusions. Inflammatory markers indicative of CRS were also elevated. CRP peaked at 268.7 mg/L on day +43 following VST infusion. Interestingly, CRP had been rising in the days leading up to VST infusion, potentially in the context of significant bleeding and interventional procedures. A rapid rise in ferritin was seen from 4,641 mcg/mL pre-VSTs (day +40) to 5,313 mcg/mL post-infusion (day +45) and 17,456 mcg/mL on day +47 (). Plasma IL-6 rose from 360 pg/mL pre-infusion (day +41) to 2,182 pg/mL on day +45 with CRS onset and prior to initiation of the IL-6R (receptor) blocker tocilizumab (). Concurrent blood, urine, and viral testing remained negative for any signs of new infection. Aggressive fluid resuscitation, bilateral chest tube placement, vasopressor support, continuous renal replacement therapy (CRRT), and 4 doses of tocilizumab (8 mg/kg) were given over 48 hours. Following fluid resuscitation for CRS, liver studies (day +47) demonstrated worsening hyperbilirubinemia. Liver ultrasound showed hepatosplenomegaly and sluggish flow through the main portal vein, raising concern for late-onset sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD). Given prior life-threatening hemorrhage, defibrotide was contraindicated. Multiorgan failure and worsening coagulopathy led to hypoxic arrest on day +63. Autopsy was declined but limited postmortem single core liver, kidney, and lung biopsies demonstrated hepatic SOS/VOD with zone 3 hemorrhagic necrosis, acute renal tubular injury, and early pulmonary exudative phase diffuse alveolar damage (). Limited tissue SV40 immunostain for polyomavirus was negative at all 3 sites. |
pmc-8718547-1 | A 77-year-old man had CAD and underwent percutaneous coronary intervention (PCI) in November 2017 and October 2019. The patient had severe AS with trans-aortic valve mean pressure gradient of 47 mmHg and received TAVR with a 29 mm Edwards Sapien 3 valve uneventfully in November 2019. A day after TAVR, echocardiographic-derived mean trans-aortic valve pressure gradient of the patient was 15 mmHg (). Dyspnea was improved, and the patient had good exercise tolerance thereafter. One year later (October 2020), the patient suffered from worsening heart failure with pulmonary edema. ECG of the patient revealed a new-onset Af and the echocardiogram disclosed an increased mean THV pressure gradient to 48 mmHg (), worsening mitral regurgitation (MR), and pulmonary hypertension (PH). Response of the patient to standard heart failure treatment, such as intravenous inotropics and diuretics, was poor. MDCT revealed HALT and RLM (). On the top of the concurrent single antiplatelet medication for CAD of the patient, a NOAC (rivaroxaban) was added for the new-onset Af and leaflet thrombosis. A series of follow-up echocardiograms within 3 months showed a progressive drop in trans-aortic valve pressure gradient to 17 mmHg (), together with reduced MR and PH. MDCT showed resolution of HALT and RLM () 4 months after NOAC treatment. Heart failure symptoms improved gradually but Af persisted. Unfortunately, the patient had a passage of tarry stool and drop of hemoglobin to 7.2 mg/dl in the fifth month after concomitant use of clopidogrel and rivaroxaban. The patient received a therapeutic endoscope, proton pump inhibitors, and blood transfusion for stopping the upper gastrointestinal bleeding. The patient discontinued clopidogrel but kept on using rivaroxaban and was free from heart failure symptoms and bleeding events thereafter. |
pmc-8718638-1 | A 70-year-old man presented shortness of breath in July 2017. He did not report any oncological or autoimmune familial medical history, but had a personal history of type 1 diabetes, dyslipidemia, and arterial hypertension. A thoracoscopy allowed pleural fluid evacuation and the diagnosis of epithelioid malignant pleural mesothelioma. Frontline chemotherapy by cisplatin-pemetrexed was started and was switched to carboplatin-pemetrexed due to deterioration of renal function (6 cycles). In November 2017, he started vinorelbine due to pleural effusion relapse.
In March 2021, as he presented an increase of dyspnea and needed several thoracentesis, CT scan showed a nodular thickening of pleura. The tumor board decided to treat him with nivolumab in 3rd line (240 mg every 2 weeks). After the 1st infusion (March 18, 2021), he presented with grade 2 asthenia, grade 1 vomiting, and gastroesophageal reflux disease (GERD) with a 3-kg weight loss. Two days after the second infusion (March 31, 2021), the patient contacted us for asthenia, vomiting, and grade 3 diarrhea, limiting his quality of life (treated at home by diosmectite, loperamide, and racecadotril). The 3rd infusion was reported by 2 weeks. He was hospitalized just before the 3rd infusion because of watery and foul-smelling diarrhea, without blood, GERD, fluctuating nausea, and vomiting, complicated by dehydration and hypotension. Physical examination revealed a grade 1 sinus tachycardia, a known pleural effusion, and a normal abdomen. Biologically, he had normal plasmatic values of ionogram, TSH, ACTH, and cortisol. The dosage of total immunoglobulins was normal, and the serum protein electrophoresis only showed an inflammatory profile. Stool culture, Clostridium difficile research, and parasitological examination of the stool were negative.
To progress toward a diagnosis, we performed endoscopic evaluation. Ileocolonoscopy with ileal and colic biopsies were normal, eliminating Crohn’s disease, ulcerative colitis, or ICI-induced colitis. Esophago-gastroduodenoscopy (EGD) showed a major duodenitis with erythematous aspect and diffuse superficial ulcerations (). To eliminate infectious enteropathy, we performed intestinal biopsies with normal bacteriological and virological examination. Surprisingly, histological examination revealed elementary lesions of CeD: increased intraepithelial T lymphocytes (IEL) (>30 IEL/100 enterocytes), crypt hyperplasia, marked villous atrophy, and alteration of normal crypt/villous ratio (3:1) (). The CeD was graded type 3b according to the modified Marsh classification of histologic findings in CeD (Oberhuber). Serum IgA antibodies to tissue transglutaminase were positive (128 U/ml, with a lab norm of 10 U/ml) and anti-endomysial IgA were positive (80 U/ml, with a lab norm of 10 U/ml). Altogether, the endoscopic, histological, and biological results led us to the diagnosis of CeD induced by immune checkpoint inhibitors (anti PD-1 nivolumab).
He was initially treated with proton pump inhibitors (PPI) intravenously 200 mg/day for 48 h and then 120 mg/day (40 mg 3 times a day). He received PPI at 80 mg for 1 month. In the face of persistent diarrhea despite anti-diarrheal medication, methylprednisolone 1 mg/kg/day was introduced initially intravenously for 3 days, then prednisolone per os at a dose of 1 mg/kg/day for 2 months, followed by a progressive decrease until 10 mg/day. A test to eliminate adrenal insufficiency was performed, before stopping corticosteroid. A gluten-free diet was also introduced in hospitalization for a long-term perspective. The patient remained in the hospital for 2 weeks and nivolumab was stopped. Ten days after the end of hospitalization, he only had three diarrheas per day.
Two months later in the consultation, he mentioned a good clinical improvement and a weight gain with a good adherence of gluten-free diet. A control EGD was realized, finding a complete healing of the inflammatory aspect and of the ulcerations of the duodenum (). Duodenal biopsies showed grade I villus atrophy and mild chronic aspecific gastritis (without atrophy, metaplasia, dysplasia, or Helicobacter pylori). A control EGD is planned 6 months later and a lifelong gluten-free diet is recommended.
In an oncological perspective, 7 months after the last nivolumab infusion, the patient still had a stable disease, without requiring any additional line of systemic treatment (). |
pmc-8718648-1 | A 78-year-old female with past medical history including autoimmune hepatitis, hypothyroidism. She presented to the hospital via emergency medical services with left arm weakness and jerky movements. This event was witnessed by family while she was eating. No recent trauma or fall. No earache, hearing loss, or discharge. No loss of consciousness reported. Of note, she is on azathioprine for autoimmune hepatitis. She was evaluated by the stroke team upon arrival. Vital signs included: elevated blood pressure at 153/72 mmHg, normal pulse 91, and normal respiratory rate at 17. She was afebrile. Laboratory work up revealed normal white cell count (WBC) of 7.2 109/L, and normal hemoglobin of 12 gm/dL. Platelets noted to be low at 80 109/L. Serum chemistry was unremarkable except for low sodium of 129 mEq/L. Urine toxicology drug screen was negative. COVID-19 PCR (polymerase chain reaction) test was negative.
A Computed Tomography (CT) head on admission revealed left temporoparietal intraparenchymal hemorrhage, right frontal sulcal subarachnoid hemorrhage, and left parietal sulcal subarachnoid hemorrhage. Vessel images with Computed Tomography Angiogram (CTA) head and neck revealed extensive venous sinus thrombosis involving superior sagittal sinus, bilateral transverse, and sigmoid sinuses. She subsequently underwent Magnetic Resonance Imaging (MRI) of the brain with and without contrast and Magnetic Resonance Venogram (MRV) which confirmed extensive venous sinus thrombosis and multicompartment bleeding. No restricted diffusion noted ().
Patient was evaluated by interventional neurology, neurosurgery, and neuro critical care team. She was started on levetiracetam for symptomatic treatment of focal seizures with left upper extremity shaking. She was started on anticoagulation with heparin drip and was admitted to neuro ICU for close neurological monitoring.
Desired therapeutic level of activated Partial Thromboplastin Time (aPTT) at 67.2 s was achieved at 24 h and patient remained in the neuro critical intensive care unit. After a thorough multidisciplinary team discussion due to persistent left-sided weakness, diffuse CVST, multicompartment bleeding while being on anticoagulation, low platelets, and anticipation of moderate to high risk of unfavorable outcome; the decision was to perform endovascular mechanical venous thrombectomy (Approximately 48 h after admission). She underwent a successful mechanical venous thrombectomy using the INARI FlowTriever system with large clot burden extracted. She remained clinically stable after the procedure and her left upper extremity weakness improved at day 5. No new symptomatic ICH. The 22 French (7.33 mm) venous access was sutured with figure of 8 technique followed by manual pressure. No post-procedure groin complications noted. She was switched to novel oral anticoagulation prior to discharge. During the 3 months follow-up–MRI brain with and without contrast revealed near complete resolution of the clot burden in superior sagittal sinus and left transverse-sigmoid complex. Her 3 months modified Rankin score was at 0. She was resumed on apixaban for 12 months with a follow-up brain magnetic resonance venogram planned. |
pmc-8718678-1 | A 44-year-old man with acute lymphoblastic leukemia (ALL) underwent induction chemotherapy (IC) (day 0). An outline of the episodes is showed in . Bone marrow suppression with fever and septic shock occurred on day 10. Patient suffered serious infection, and empirical treatments were used with imipenem (IPI, 1 g, every 8 h, intravenous injection), vancomycin (VAN, 1 g, every 12 h, intravenous injection) and voriconazole (VRC, 200 mg, every 12 h, intravenous injection) as broad-spectrum antibacterial and antifungal prophylaxis and empirical treatments were used with broad-spectrum antibiotics including antifungal prophylaxis. The patient's blood pressure recovered but recurrent fever occurred after 3 days. At that time, a series of cultures of peripheral blood (PB) were negative from day 10 to day 28. No pathogen could be detected, and the patient experienced neutropenia from day 10 to day 25 (). However, hemiplegia and hemiconvulsions suddenly occurred on patient's right limb, and computed tomography (CT) scans of patient's brain showed a hyperdense lesion with surrounding edema, which was highly suspected as cerebral infarction in the right parietal lobe and small hypodense areas in the left and right parietal lobes. No obvious abnormality was showed by magnetic resonance angiography (MRA) of patient's brain, but CT scans of the lung showed multiple hyperdense lesions on day 18 (). Febrile neutropenia in patients after chemotherapy with cerebral symptoms may be highly indicative of infections in the brain (, ).
Treatment was continued VRC and IPI, and changed to teicoplanin (TEC, 400 mg, daily, intravenous injection) as antibacterial and antifungal drugs Treatment was changed to voriconazole (VRC) and imipenem as antifungal and antibacterial methods after a positive result for the test of (1,3)- β-D-glucan (100.70 pg/mL, Guangzhou Zhaokang Biotechnology Co., Ltd) on day 22. However, the fever was unresponsive and the lesions in the brain and lung were more serious a week later. The procalcitonin (PCT) level was elevated to 4.40 ng/mL, and c-reactive protein (CRP) reached 218.33 mg/L. Aminoleucine transferase (ALT) and aspartate transaminase (AST) reached 145 U/L and 242 U/L, respectively. Other drugs were applied to protect patient's liver function. Rhizomucor miehei infection was shown by mNGS (Genskey Medical Technology Co., Ltd, Beijing, China. NextSeq 500) of PB with high relative abundance about 99.94% on day 25 (), and liposome-associated amphotericin B (AmBL, 100 mg, daily, intravenous injection) was immediately used as antifungal therapy from day 25 to day 55. The patient's body temperature returned to normal (36–37°C) after 3 days of treatment and his complete blood count (CBC) recovered from neutropenia on day 28. Infection with Rhizomucor miehei was also proven by mNGS both in CSF with relative abundance about 0.35% on day 28 and BAL with relative abundance about 28% on day 35 (), and the routine and biochemical examinations of CSF were negative (). After 2 and 3 weeks of antifungal treatment, CT scans showed that lesions were obviously absorbed both in the brain () and the lung (), and PCT and CRP were also recovered following antifungal therapy (). Finally, the patient's general condition improved, and his right limb function partly recovered on day 55. He requested to go back to the local hospital to continue antifungal therapy due to his family reasons.
After 2 months of follow-up by telephone, we learned that patient changed to receive antifungal treatment with amphotericin B (AmB, 150 mg, daily, intravenous injection) and posaconazole (Pos, 300 mg, daily, orally) for other 2 months, because patient's liver had recovered to normal function. Besides, significant reduction in the size of the lesions on imaging tests of this patient were reported. The next chemotherapy for ALL was also prepared to carried out. The antifungal drug regimen was well-tolerated and achieved a remarkable effect. |
pmc-8718702-1 | In January 2021, a 2-year-old boy of white Caucasian origin presented to his local ophthalmologist for acute unilateral sixth nerve palsy and was subsequently transferred to our pediatric emergency department for further evaluation. The patient, generally being fit and well, had developed a sudden dysfunction in lateral movement of his left eye, resulting in a continuous abduction deficit with consecutive fixated turn of the head to the left side. His medical history was unremarkable for trauma, headache, vomiting or fever. He had not received any vaccinations within the last few weeks. Apart from a mild gait instability, there were no concomitant symptoms or other focal neurological deficits on clinical examination. The patient did not suffer from any chronic diseases and did not take any regular medication; his vaccination status was complete according to national recommendations.
Three weeks prior to onset of symptoms the patient had experienced a respiratory tract infection resulting in an increased respiratory rate, dry cough, intermittent fever and loss of appetite, lasting for 2 weeks. Symptomatic treatment was initiated by his local pediatrician, who attributed the patient's symptoms to a common cold rather than COVID-19. Thus, no oropharyngeal swab for SARS-CoV-2 or other viruses was obtained. At the same time, the patient's father and his uncle developed cough, dyspnea, sore throat and muscle aches; the uncle tested positive for SARS-CoV-2 on PCR from oropharyngeal swab (). The child's uncle does not live in the same household but had been in close contact to the patient 4 days prior to his positive test for several hours due to an indoor-birthday party. The patient's relatives were unvaccinated as at that time the COVID-19 vaccines were still unavailable for the general public.
On admission, laboratory inflammatory markers including C-reactive protein were negative. Full blood count showed mild thrombocytopenia (186 109/) but was unremarkable otherwise. Cranial contrast-enhanced magnetic resonance imaging (MRI) showed an hypoplastic left abducens nerve and atrophy of the corresponding left lateral rectus muscle compared to the contralateral side (). There were no signs suggesting any inflammatory intracranial process or elevated intracranial pressure, no papilledema. A lumbar puncture was performed. The cerebrospinal fluid (CSF) opening pressure was 24 cmH2O corresponding to the upper limit of normal range () thus diagnostic lumbar puncture was followed by therapeutic drainage of 8 ml CSF. Routine CSF laboratory parameters yielded a normal result; no oligoclonal bands were detected on CSF/serum. Multiplex-PCR (Filmarray, BioFire, Biomerieux Lyon, France) from CSF was negative for cytomegalovirus (CMV), enterovirus, herpes simplex viruses 1 and 2, human herpesvirus 6, human parechovirus, varicella zoster virus, Cryptococcus neoformans and gattii, E. coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitides as well as Streptococcus agalactiae and pneumoniae. An additional multiplex-PCR performed on an oropharyngeal swab sample yielded a negative result for adenovirus, coronaviruses 229E, HKU1, NL63 and OC43, human metapneumovirus, human rhino-/ enterovirus, influenza virus A and B, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), SARS-CoV-2, parainfluenza virus 1–4, respiratory syncytial virus, Bordetella pertussis, Bordetella parapertusssis, Chlamydophila pneumonia and Mycoplasma pneumoniae. Testing for Borrelia burgdorferi showed no antibodies in neither serum nor CSF. An EEG was unremarkable. Repeated ophthalmologic examinations revealed incomitant squint angles due to left-sided sixth nerve palsy and a significant abduction deficit of the left eye, consistent with the diagnosis of left abducens nerve palsy. An underlying retraction syndrome was considered unlikely due to the sudden onset of symptoms and absent globe retraction. Optic nerve examination was unremarkable.
Real-time reverse transcriptase PCR (rRT-PCR) test for SARS-CoV-2 (oropharyngeal swab sample) was negative on admission, while serology turned out to be positive for SARS-CoV-2 anti-spike IgG (Euroimmune, Germany). Of particular note in this context, SARS-CoV-2 specific IgG was also detected in CSF. Pathogen-specific antibody index as an indicator for potential intrathecal antibody production was negative, suggesting involvement of central nervous system being secondary to systemic infection rather than direct viral infection (). An rRT-PCR for SARS-CoV-2 from CSF was negative.
Given the boy's history of recent respiratory tract infection, COVID-19 very likely in his father and proven in his uncle, and detection of SARS-CoV-2-IgG antibodies in the patient's serum and CSF, post-infectious abducens nerve palsy appeared to be the most likely diagnosis. During inpatient stay, symptoms already showed spontaneous mild improvement without therapeutic measures. Following discharge, the boy was regularly seen for ophthalmologic follow-ups. Three months following onset of abducens nerve palsy, the family noticed a distinct improvement in eye movement and the child eventually made a full recovery 2 weeks later. |
pmc-8718755-1 | A 42-year-old Chinese man presented to the outpatient clinic of otorhinolaryngology at Xijing Hospital, Fourth Military Medical University, in September 2018, complaining of right ear discharge accompanied by discomfort for 3 years. The patient had a history of seawater contact in August 2015, including underwater diving near the coast of the Yellow Sea near Qingdao City, Shandong Province. After a couple of days, the patient noticed a small volume of clear drainage from both ears, accompanied by mild discomfort and ear pruritus. As the condition progressed, drainage from the left ear gradually vanished within half a month, whereas the drainage from the right side increased and became a thick, purulent exudate containing debris, eventually turning a dark brown or chocolate color. As the ear canal became almost entirely obstructed by the thick excretion, the patient experienced mild hearing loss, coupled with intermittent tinnitus, and experienced a sensation of ear fullness. Without the use of any medications, he removed debris from the right ear using cotton swabs, resulting in a return to normal hearing and the relief of symptoms. Within a few days, new thick drainage would obstruct the ear canal, and the symptoms would reappear. The patient sought health care twice at local hospitals in Xi’an City from Shaanxi Province; however, the underlying illness remained unidentified and did not improve. The discharge from the right ear gradually reduced and turned from brown to white until March 2018, when a low-concentration hydrogen peroxide solution was used to rinse the right ear canal at a local hospital. During the course of the illness, the patient denied any accompanying symptoms, such as fever, chills, headache, vertigo, diarrhea, or flatulence, and he did not have a history of infectious diseases, diabetes, or any immunocompromising condition. Before the diagnosis, the patient underwent audiometric and otoscopic examinations, in addition to radiological examinations using computed tomography imaging to examine the temporal bone. The exudate was collected from his right ear using a sterile swab and was transferred to the clinical microbiology laboratory for examination. All specimen processing and bacteriological analysis procedures were performed with approval from the ethics committee of the Xijing Hospital, Fourth Military Medical University, with assigned number KY20183304-1. The patient provided written informed consent prior to participation in this project. |
pmc-8718908-1 | The patient is a 52-year-old white post-menopausal woman and a non-smoker. Eight years prior to the study start in 1997, the diagnosis SLE was made by a senior internist (P.K.) and a senior dermatologist (N.S.) according to the following ACR criteria: kidney involvement (histological evaluation of chronic mesangial proliferative glomerulonephritis, WHO classification IIIa) with microscopic hematuria; arthralgia; urticarial vasculitis; oral ulcers; facial rash. Moreover, she showed decreased complement C4 (hypocomplementemia), leukopenia and enhanced antinuclear antibodies (ANA, 1:2560); analyses of antinuclear anti-double-stranded DNA antibodies (ds DNA) were negative.
Pharmacologic treatment lasted three years and consisted primarily of steroids (4–20mg) in combination with other non-steroidal anti-inflammatory medication (paracetamol). The patient did not tolerate antimalarials; moreover, she refused further immune suppressive therapy (e.g. azathioprine, mycophenolate, cyclophosphamide) although her disease fulfilled WHO classification IIIa for SLE. Nevertheless, her laboratory values improved (no proteinuria, no pathological urine sediment) during pharmacologic treatment. The patient attended psychotherapy for three years following diagnosis.
During regular check-ups between first diagnosis in 1989 and study start in 1997, the following minor clinical disease manifestations related to SLE had been identified: oral ulcers, urticarial vasculitis lesions at various body sites (e.g. facial rash), small joint pain, fatigue, tiredness and fever. These symptoms did not require steroidal or immunosuppressive drug therapy and were treated by the patient symptomatically (e.g. mouth rinsing with hexetidin solution). At study start, the patient presented with elevated ANA (1:160, ds DNA negative, SS-Ro-antibody positive) with the above-mentioned mild clinical symptoms, which did not require steroid treatment. |
pmc-8719313-1 | A 60-year-old woman was admitted with a continuously enlarged neck mass for 1 year and hoarseness for 1 week. In addition, she presented with dyspnea for 5 months. The patient had no family history of parathyroid diseases or hyperparathyroidism-jaw tumor syndrome. Physical examination showed a firm left neck mass of approximately 6.0 cm * 5.0 cm. Laboratory findings revealed elevated serum PTH (188.1 pg/ml, reference range: 15–65 pg/ml) and hypercalcemia (total serum calcium: 3.29 mmol/L, reference range: 2.1–2.6 mmol/L). Indicators related to thyroid function were within normal limits. Laryngoscopy showed left vocal cord paralysis. Ultrasonography showed that the left thyroid lobe was enlarged significantly, a hypoechoic lesion nearly occupied the whole lobe, and comparable signs were presented on the neck CT (). Tc-99m sestamibi scintigraphy demonstrated two-phase nuclide accumulation on the left thyroid (). Chest CT showed multiple micro pulmonary nodules ().
During the surgical exploration, we found that the tumor invaded the anterior cervical muscle group and left recurrent laryngeal nerve. Only the superior parathyroid was found in the left neck. En bloc resection (including part of the invaded recurrent laryngeal nerve and muscle tissue and entire thyroid) and left central lymph node dissection were performed to completely remove the affected tissue. The tumor profile showed that the thyroid was markedly infiltrated, and the normal gland was almost invisible (). Postoperative histopathological findings revealed that SaPC widely invaded the ipsilateral thyroid, and 1/6 of the lymph nodes showed metastasis. Immunohistochemical staining was further performed to confirm the diagnosis (); results were presented below: (1) Carcinomatous components: Some PC cells show negative nuclear staining of parafibromin (); Cytokeratin (AE1/AE3) (+); Chromogranin A (+); E-Cadherin (+); PTH (+); Calcitonin (–); Thyroglobulin (-); Desmin (-); KI-67 index 10%; (2) Spindle cell components: Desmin (+; ); Cytokeratin (AE1/AE3) (-); Chromogranin A (-); E-Cadherin (-); Calcitonin (-); KI-67 index 30%. In addition, the existence of transition zones () and positive N-cad staining in both carcinomatous and sarcomatoid components () was found during pathological examination.
The patient recovered soon postoperatively and remained hoarse. She did not experience choking when drinking water, and dyspnea significantly improved. Three months later, the patient complained of progressively aggravating dyspnea and a gradually growing neck mass. Serum calcium and PTH levels were without abnormal elevation during this time (). Clinical examinations suggested regional relapse and multiple pulmonary metastases (). In contrast to the chest CT before, it seemed that pulmonary metastasis had occurred before the first surgery. Enhanced MRI showed extensive local organ and tissue invasion by the recurred tumor (). At last, the patient gave up the medical treatments. |
pmc-8719982-1 | The patient was a 75-year-old man with a body mass index of 23.4 kg/m2 and an American Society of Anesthesiologists (ASA) class of three. He had a history of end-stage renal disease on hemodialysis and was initially transferred to our hospital from an outside facility for subacute functional decline and encephalopathy. His admission work-up was notable for a leukocytosis of 12,800 cells/μL, Enterococcus faecalis bacteremia, and bilateral pleural effusions. His 12-lead electrocardiogram showed sinus rhythm with first-degree atrioventricular block and a right bundle branch block. The patient was started on broad spectrum antibiotics for bacteremia and later narrowed to ampicillin. Repeat blood cultures were negative. On hospital day one, the patient underwent a transthoracic echocardiogram which demonstrated a left ventricular ejection fraction of 45-50% with global systolic dysfunction, moderate RV dysfunction, mild pulmonary hypertension with a pulmonary artery systolic pressure (PASP) of 41 mmHg, and no visible valvular vegetations.
The patient underwent thoracentesis of the right sided pleural effusion, and bacterial cultures of the pleural fluid grew Enterococcus Faecalis. Given this multifocal enterococcus infection, TEE was pursued.
On hospital day nine, the patient underwent TEE under monitored anesthesia care. The anesthesia service was consulted due to pulmonary hypertension as per the institutional guideline. The patient was connected to standard monitoring as recommended by the ASA. Supplemental oxygen was provided by a face mask, with end-tidal carbon dioxide monitoring. The patient received a total of 70 mg of propofol administered over the first ten minutes of the procedure in boluses of 10 mg-20 mg. Hemodynamically, the patient's blood pressure at the beginning of the procedure was 140/50 mmHg with a pulse in the low 60 s. His blood pressure dropped precipitously after receiving propofol down to 60/40 mmHg fifteen minutes into the procedure. At that point, the patient became bradycardic and went into a PEA cardiac arrest. The TEE probe was withdrawn, and chest compressions were initiated under the advanced cardiac life support algorithm. The patient was intubated, and return of spontaneous circulation (ROSC) was achieved after four rounds of chest compressions and epinephrine administration. The patient's cardiac rhythm then deteriorated into ventricular fibrillation requiring defibrillation and further chest compressions. ROSC was achieved once again, and the patient was transferred to the intensive care unit. Upon review of the images captured by TEE at the onset of PEA arrest, it was noted that the RV was severely dilated with minimal contractile function, and a small pericardial effusion was found (Video ). Due to the patient's critical condition, his family decided to transition him to comfort measures only. |
pmc-8719983-1 | One of the authors (TS Tsai, a 48-year-old man) was bitten on the right palm near the base of the index finger by D. siamensis () in the Reptile and Amphibian Facility at the National Pingtung University of Science and Technology in Pingtung, Taiwan. The accident might have occurred when the patient's fingers stuck to the skin of the snake when he grasped the neck of the snake to inspect its mouth and nostrils for symptoms and signs of infection. After inspection, the patient attempted to release the snake back into the snake box, and it then turned its head around and bit the patient's hand while he was releasing it. Two fang bite marks, scratches, and bruises were visible on the spot.
The patient started to feel numbness and tingling of the ankles and experienced slight difficulty in walking approximately 30 min after the snakebite. The patient visited a local hospital 30 min later and was administered 4 vials of monovalent antivenom for D. siamensis at the emergency department within 1 h of being bitten. However, the swelling and redness had progressed to the wrist () approximately 9 h after the snakebite. Therefore, 4 more vials of antivenom were administered, for a total of 8 vials within 10 h. Blood tests showed acute kidney injury, disseminated intravascular coagulation, and coagulopathy (). No leukocytosis or anemia was observed, and antibiotics, such as ceftazidime, were prescribed.
The patient was admitted after which the right hand showed the most obvious swelling and pain for the first 2-3 days. The swelling and pain even extended to the right elbow. The patients' fingers were almost unable to bend. Ice pillow packing was used to relieve the pain, local heat, and swelling. Fortunately, there were no blisters, hemorrhagic bullae, or finger ischemia. The patient also received two courses of hyperbaric oxygen treatment on days 3 and 4, and the swelling of the hand quickly subsided after that. Then, the patient's fingers were able to bend slightly on the third night and were able to bend more than 90° on day 4. During hospitalization, the patient's daily stool was soft or fluid and dark blue-green but not black, whereas the urine color was normal. The patient was discharged from the hospital on day 5, and on day 8, a large area of elevated red skin rash and itching of the body occurred at home. After administration of antihistamines, the symptoms disappeared. The patient still sometimes experienced mild numbness and painful sensations at the bite site for up to one month after the snake envenomation. |
pmc-8719986-1 | A 41-year-old gravida 6 para 3 female (uncompleted pregnancies due to miscarriages) presented to the emergency department with a chief complaint of chest pain. Pain started two hours prior to presentation, was dull, left sided, substernal, radiated to her left arm, and with a severity of 7/10. One month prior to presentation the patient was complaining of an abnormal uterine bleeding and was started on oral norgestimate/ethinyl estradiol pills.
The patient has no significant past medical history. Her social history is significant for smoking 1/2 a pack per day for the past 10 years. Her family history is not significant for premature coronary artery disease or thrombosis. Her past surgical history is significant for dilatation and curettage two weeks prior to presentation. Home medications include daily oral norgestimate/ethinyl estradiol pills. Her only cardiac risk factors were smoking and the use of oral contraceptives.
Upon arrival to the emergency department, the patient was vitally stable. Her physical exam was noncontributory. Cardiac and lung exams were unremarkable. A twelve-lead ECG showed 1 mm ST elevations in inferior leads with no reciprocal changes and a sinus rhythm at a rate of 60 beats/minute (). A STEMI code was called, and the patient was taken emergently to the Cath Lab. She was started on acute coronary syndrome (ACS) treatment including oral aspirin 324 milligrams, oral clopidogrel 600 milligrams, and intravenous heparin 5000 U. Significant laboratory data showed a troponin of 0.615 ng/mL (0-0.04 ng/mL), hemoglobin of 8.7 g/dL (12.0-15.5 g/dL), and white blood cell count of 13.7 × 109/L (4.5 − 11.0 × 109/L).
Coronary angiogram revealed a saddle clot (thrombus) involving the distal left main artery, left circumflex, and proximal LAD (). TIMI flow grade was 3 throughout, and no intervention took place during the coronary angiogram. There was also an occlusion in the apical portion of the LAD. The right coronary artery did not have any abnormalities. An echocardiogram revealed an estimated ejection fraction of 55-60% with apical septal hypokinesis and a normal diastolic function. There was no evidence of an intra-atrial shunt or left atrial appendage. Patient was admitted to the cardiac care unit (CCU) and was started on intravenous tirofiban for 10 hours, oral aspirin 81 milligrams daily, oral clopidogrel 75 milligrams daily, and intravenous heparin drip as per ACS protocol. Troponin peaked at 11 ng/mL. The patient was given 2 units of PRBC due to persistent vaginal bleeding. Doppler of the lower extremities did not reveal any evidence of a DVT. Telemetry over 48 hours of the hospital stay did not show any evidence of cardiac arrhythmia.
Thrombophilia testing lab results showed antithrombin activity of 88% (80-120%), antithrombin III AG 79%, cardiolipin AB IGA < 9.4 APL (<20.0 APL), beta − 2 glycoprotein IGG < 9.4 U/mL (<20.0 U/mL), beta − 2 glycoprotein IGM < 9.4 U/mL (<20.0 U/mL), cardiolipin AB IGM MCLIP < 9.4 MPL (<15 MPL), cardiolipin AB IGG GCLIP < 9.4 GPL (<15 GPL), prothrombin G20210A gene negative, beta − 2 glycoprotein AB IGA < 9.4 U/mL (<15.0 U/mL), PS/PT IGG < 9.4 U (<30.0 U), PS/PT IGM 20.0 U (<30.0 U), and platelet count of 376 K/μL (149-400 K/μL).
OBGYN were consulted, and placement of IUD was recommended to help prevent bleeding. After 48 hours, heparin was discontinued. EKG prior to discharge showed resolution of ST elevations (). A repeat angiography was not done as symptoms had resolved and EKG showed resolution of STEMI. OCPs were held, and patient was discharged on oral anticoagulation. |
pmc-8720013-1 | A 29-year-old man presented from a psychiatric hospital with 2 days of sudden onset, progressive chest pain, and troponin elevation after recently initiating clozapine therapy.
The patient had a history of alcohol abuse and treatment-resistant schizoaffective disorder with multiple suicide attempts. After intentional ingestion of acetaminophen and lithium, he was involuntarily hospitalized for intensive treatment, including initiation of clozapine therapy.
The differential diagnosis included acute coronary syndrome, myopericarditis from viral or drug-induced etiology, pulmonary embolism, and pneumonia. The patient first noted substernal chest pain worse with deep inspiration 8 days after clozapine initiation. Symptoms worsened over the following two days. Electrocardiogram (EKG) demonstrated ST elevations most prominent in V2-V3 (). Serum labs were notable for leukocytosis and elevated troponin, brain natriuretic peptide, and inflammatory markers ().
Chest pain persisted, and he was transferred to the cardiology service. Cardiovascular exam was notable for tachycardia without murmurs or rubs. He had no peripheral edema or elevated jugular venous pressure. Lungs were clear. Cardiac magnetic resonance (CMR) imaging showed global hypokinesis with a left ventricular (LV) ejection fraction (EF) of 45% (Figure ) and subtle late gadolinium enhancement of the epicardial lateral wall and lateral pericardium with abnormal parametric mapping () consistent with myopericarditis. Respiratory viral panel was negative. Clozapine was discontinued. Metoprolol was initiated for impaired LV function with colchicine and ibuprofen for pericarditis with prompt symptomatic relief. Repeat EKG showed resolution of ST-elevation and no arrhythmic events on telemetry. He was discharged back to the psychiatric hospital with planned cardiology follow-up for echocardiogram and repeat laboratory testing. |
pmc-8720017-1 | A 60-year-old man presented with sudden left leg pain in L4 nerve root area. The patient demonstrated neurogenic paralysis on left quadriceps femoris muscle with manual muscle testing 3, hyporeflexia on left patella tendon, and positive left straight leg raising test. MR images revealed left L4-5 foraminal herniated disc without fragment in the spinal canal (). Left L4 selective nerve root block remarkably affect. According to the above results, the patients was diagnosed as left L4 nerve root entrapment by left L4-5 foraminal disc herniation.
The patient underwent discography for the presurgical imaging diagnosis. The double-needle was inserted to the L4-5 disc, and tip of the needle was located at middle of the nucleus pulposus. Finally, 3.0 cc of Iohexol was injected cautiously without reproduction of left L4 radicular pain. After discography, the patient complained deterioration of left leg numbness without neurological deficit. On disco-CT and postdiscogram MR images, herniated fragment was migrated from neural foramen to cranial central canal which was not detected in previous images (Figures and ).
Herniotomy was performed by osteoplastic approach [, ]. Observing the neural foramen, the herniated disc fragment was migrated from neural foramen to cranial central canal. 2.5 g-weighted disc fragment with annulus fibrosus was extirpated with one piece (). After surgery, neurological status was fully recovered immediately. |
pmc-8720017-2 | A 74-year-old man presented with right leg pain in L4 nerve root area. He was treated in previous clinic with diagnose of right L4-5 foraminal disc herniation (). After disc block with 1.9 mg of Dexamethasone sodium phosphate and 1.5 ml of mepivacaine hydrochloride, the patients complained of deterioration of right leg pain.
The patient was introduced to our facility, and reexamined MR images showed herniated fragment migrated from neural foramen to cranial central canal which was not detected in previous images (). No neurological deficit was observed. Transforaminal lumbar interbody fusion with right L4-5 facetectomy was performed to extirpate the herniated fragment. |
pmc-6000309-1 | A 65-year-old man with continuous irritable cough over 15 days was admitted to our department for a mass lesion in the right hilum. He presented with no face swelling and superficial varicose veins. He was a former smoker, and medical history included hypertension and diabetes mellitus. At bronchoscopy, the tumor was found occluding the right upper lobar bronchus and infiltrating the bronchus intermedius. It was diagnosed as squamous cell carcinoma by transbronchial tumor biopsy. Chest contrast computed tomography (CT) revealed that the mass of 80 mm in the maximum diameter located in the right upper lobe. The tumor directly invaded the arch of the right PA and a wide range of SVC. It was discovered that the left brachiocephalic vein (BCV) along the left margin of mediastinum walking down the line directly into the coronary sinus (). A venous flow was detected in the anterolateral descending aorta with dilatation of the coronary sinus (diameter of 21 mm) without other heart abnormalities by transthoracic echocardiography. Based on these findings, the diagnosis of PLSVC was made. There were no detectable metastases in other organs through brain magnetic resonance imaging (MRI), upper abdomen CT scan and bone nuclear scan.
The right posterolateral thoracotomy was performed on October 31, 2006. As expected, the tumor invaded the wall of SVC and no left brachial cephalic vein bifurcation was observed. The SVC was separated, clamped and resected following intravenous injection of 5, 000 IU of sodium heparin. The ringed PTFE graft of 12 mm in diameter was interpositioned between the right brachial cephalic vein and the origin of SVC by running sutures with 4-0 polypropylene. The tumor resection was completed by double sleeve lobectomy of right upper and middle lobes. The anastomosis between the right main bronchus and the cut end of the lower lobe bronchus was performed by interrupted suture using 3-0 Vicryl (Ethicon, USA). Right PA trunk and right lower PA reconstruction was completed by the running suture with 4-0 polypropylene (). And systematic mediastinal lymph node dissection was performed. All excised margins were tested microscopically negative for malignancy. As anticoagulation treatment, we began with low molecular Heparin on the operative day, then switched and continued to warfarin when thoracic drains removed. The postoperative course was uneventful, and the patient was discharged from the hospital on the 12th postoperative day. Final pathological diagnosis was poorly differentiated squamous cell carcinoma invaded the right SVC, right PA and mediastinal nodes were positive for malignancy.
After 4 cycles of chemotherapy (Gemzar and cisplatin) and 1 cycle of radiotherapy, Chest MRI showed patency of the graft and PLSVC (). He died 21 months after operation because of remote metastasis. |
pmc-6000673-1 | A 15-year-old boy was admitted with a 2-month history of fever, decreased appetite and nonproductive cough. Cough and fever progressed despite of antibiotics prescription for presumed community-acquired pneumonia a few weeks prior to admission.
At the time of admission, he had fever, tachycardia, respiratory distress and splenomegaly. In laboratory findings, he had pancytopenia; urine analysis and ESR was normal, blood and urine culture was negative. Gram stain of his sputum showed gram positive cocci. Acid fast bacillus was not found in sputum smear. HBsAg and Anti-HCV and Anti-HIV were negative. ANA, Anti ds-DNA, p-ANCA and c-ANCA were requested but all of them were negative. Peripheral blood smear and bone marrow aspiration were normal. Echocardiography also was normal. His chest X-ray and CT-scan of thorax showed bilateral and peripheral nodular and alveolar pattern, predominantly in lower lobes of the lung. Mediastinal lymphadenopathy and pleural effusion were not seen (). Abdominal sonography and CT showed hepatosplenomegaly. Splenomegaly was more prominent than hepatomegaly. Para-aortic lymphadenopathy was not seen. Bronchoscopy and open lung biopsy were not performed because the patient's guardian did not permit. Two days later, we saw a few small brown nodular lesions on the left leg (). Skin excisional biopsy was taken. One day later, he developed right hemiplegia, seizure and aphasia. Brain CT scan showed a broad hypo dense area on the left temporal and basal ganglia that had little enhancement after injection of Ⅳ contrast (). At this time, the result of skin biopsy was prepared. There was severe infiltration of lymphocytes and histiocytes and atypical lymphocytes on the subcutaneous and deep parts of the derma. The main aggregation of the cells was around the vessels and nerves and appendices of the skin. The endothelial layer of the vessels had inflammation, but there was no morphologic pattern of vasculitis. Lymphoid cells had positive reaction with CD45RO: so lymphomatoid granulomatosis (LG) was diagnosed (). He was treated with steroid pulse therapy and oral cyclophosphamide but after 12 days he expired without any clinical improvement and any response to the treatment. |
pmc-6000835-1 | A 51-year-old Thai woman was hospitalized in July 2012 with edema at the left lower extremities and painful left inguinal mass for 6 months.
Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size with hard consistency, erythema, and tenderness without fluctuation or ulcer. Marked swelling at both lower extremities was observed. There was no other superficial lymphadenopathy. Otherwise, physical examinations were normal.
Incisional biopsy of the left inguinal lymph node revealed metastatic round cell tumor which is immunohistochemistry positive for vimentin, S100, and HMB-45. The immunophenotype is consistent with malignant melanoma ().
Therefore, primary tumors in the lower extremities, abdominal cavity, and anogenital organ were suspected. By complete skin examination, no cutaneous lesion was identified. Ophthalmoscopy, gastroscopy, colonoscopy, and cystoscopy were completely normal. Genital and pelvic examinations did not show any evidence of lesion. She denied previous abnormal or removal of cutaneous lesion. Computer tomography of the whole abdomen showed multiple enlarged lymph nodes throughout the abdominal and pelvic cavity up to 9.5 cm, along with compression of both iliac veins without an organ-specific lesion (). CT chest was unremarkable. The patient was diagnosed with metastatic melanoma of unknown primary. The molecular testing had not been done due to the patient's reimbursement issue, and the specimen was poor in quality for further testing. During the investigation, she developed severe pain requiring high-dose opioid, so she has undergone 20 Gy of palliative radiotherapy for bilateral inguinal lymph nodes. Despite radiotherapy, the remaining tumors were up to 7.4 cm based on the CT scan. For the subsequent systemic therapy, according to a national reimbursement policy, she could not access an immune checkpoint inhibitor or targeted drug. Chemotherapy was prescribed with carboplatin (AUC5) and paclitaxel 175 mg/m2 for 6 cycles. After completion of the planned chemotherapy, the symptom was slightly improved. The CT scan at the first 3 months showed that the response was stable disease, but the following CT scan demonstrated a gradual decrease in size over time from August 2012 to November 2017 (). During the follow-up period, the patient developed multiple depigmented patches around the lips, trunk, and periorbital and inguinal area, which are typical of vitiligo. |
pmc-6000836-1 | A 50-year-old male patient presented with a one-day history of right leg weakness, numbness, and urinary retention. There was mild back pain and right leg weakness for two weeks which worsened significantly during the last 24 hours. On neurological examination the patient‘s right leg was weaker than the left (2/5 and 4/5 on Lovett test, respectively), the patellar reflex was exaggerated, and Babinski sign was positive bilaterally. Also, on the right side, there was sensory loss in the leg and below the Th8 dermatome. On the left, there was sensory loss below Th10 dermatome and distal loss of temperature sensation.
Past medical history revealed a cervical trauma which occurred 30 years ago when a glass chip lodged into the left side of the patient's neck. The patient removed the visible glass shard from his neck and did not seek medical attention; therefore no clinical and radiological investigations were carried out. No neurological symptoms followed this incident.
Computed tomography (CT) of the lumbosacral and thoracic regions showed a mild convexity of the L5-S1 intervertebral disc with no other clinically significant findings (“Siemens SOMATOM Emotion 6”) (images not shown). To further explore the possible causes of the patient's symptoms, magnetic resonance imaging (MRI) of the C1–L2 segments was performed (“Siemens MAGNETOM Avanto 1.5 T”). At the level of C4–Th3 the spinal cord was thickened and hyperintense on T2W images, features consistent with myelitis; however there was no appreciable contrast uptake (Figures and ). At the level of C6–C7 an oblong (1.6 x 0.4 cm), T1 and T2 hypointense lesion was found (). Because a foreign body was suspected, CT scan of the C1–Th3 levels was performed and demonstrated a hyperdense lesion occupying the spinal canal and the left intervertebral foramen ().
Combining the CT and MRI results with the past medical history of an old injury with a glass fragment, it was determined that the lesion represented a glass foreign body in the spinal canal. The patient also had an X-ray of the cervical spine but the foreign body could not be visualized, most likely due to being located at the level of C6-C7, where it was obscured by the surrounding structures ().
Taking into account the clinical picture, an extensive period of time between the trauma and current presentation, and MR imaging findings, an acute demyelinating episode rather than traumatic spinal cord injury was suspected. Further diagnostic work-up would typically have included a lumbar puncture to identify oligoclonal bands, cells, and protein, but it was contraindicated due to the risk of disturbing the foreign body and causing it to migrate upon a sudden decrease in pressure during puncture. Serum Aquaporin-4-specific antibodies could not be performed at the time and were planned for a later time.
The patient fulfilled the inclusion criteria for acute transverse myelitis: bilateral and not necessarily symmetrical sensory, motor, and autonomic spinal cord dysfunction, a clear sensory level, peak of symptoms within 4 hours and 21 days after onset of symptoms, and exclusion of other causes (neoplastic, vascular, and compressive) []. Compressive cause was excluded because the spinal cord pathology seen on MRI extends far from the location of the glass shard, which would be unlikely given the size of the foreign object and its possible effect upon the spinal cord if it migrated within the spinal canal. Thus, because the glass fragment lay dormant for the last 30 years, it was deemed not to be the direct cause of the patients' symptoms.
Treatment with methylprednisolone 500 mg intravenously daily for 6 days was initiated.
After consultation with the neurosurgeons it was decided not to remove the foreign body from the spinal canal, because the risks of surgery would outweigh the benefits. At the time of consultation, the patient was already showing improvement on medical management. Given that the situation was not hyperacute, the symptoms were better explained by the inflammatory and demyelinating reaction within the spinal cord rather than direct contact with the foreign body. Also, it could not be guaranteed that removing the glass shard would result in symptomatic improvement. Upon removal of the foreign body some diffuse bleeding would be expected, which combined with the already inflamed spinal cord parenchyma would likely further compromise the spinal cord, potentially causing vascular complications and myelomalacia, all of which would further decrease the chance of clinical improvement. Risk of general surgical complications (postoperative infection, bleeding, and thromboembolism) further argued against surgical treatment. An absolute indication for surgical treatment would be an infectious complication of the foreign body, which was not present. The patient agreed with the treating physicians that surgery would not be the best option and did not want the operation. If current medical treatment would have proven unsuccessful, and the patient's clinical condition worsened, surgery would have been indicated.
During the course of treatment the patient's condition improved. Sensory loss diminished, and the right leg strength improved to 4/5 on Lovett test, but urinary retention remained. Intermittent catheterization was prescribed.
The patient returned for a follow-up visit 10 months later with a stable and improved neurological state. Lower limb strength was 3/5 proximally and 4/5 distally, with positive bilateral Babinski sign. Minimal intermittent urinary retention remained but did not significantly impair the patients' quality of life. The patient resumed his activities of daily living and continues to work as a security guard. Follow-up MRI of the cervical spine shows the same oblong hypointense object and normal spinal cord after the resolution of myelitis (Figures and ).
Further follow-up is scheduled every 6 to 12 months, with an outpatient brain MRI to identify any other demyelinating lesions that may be present in case this episode was part of neuromyelitis optica (NMO), acute demyelinating encephalomyelitis (ADEM), or multiple sclerosis (MS). |
pmc-6000840-1 | A 51-year-old woman presented with fatigue, nausea, and vomiting for three days. She was diagnosed with metastatic melanoma to pelvic nodes in July 2014 and was treated with ipilimumab (anti-CTLA-4) in combination with nivolumab (PD-1 inhibitor) between September 2014 and April 2015, receiving a total of 4 cycles of combination therapy and 9 cycles of nivolumab monotherapy with an initial mixed response followed by slow progression of disease. In April 2015 she was enrolled on a study of radiation (to pelvic mass) in combination with pembrolizumab (PD-1 inhibitor), receiving a total of 9 cycles of pembrolizumab with no toxicities. In December 2016 she was found to have new brain metastases and in January 2017 pembrolizumab was added. The day following her second dose of pembrolizumab, she developed fatigue and nausea and began having intermittent vomiting and diarrhea. Abdominal CT scan demonstrated diffuse colitis. Infectious studies including C. difficile antigen, stool culture, viral PCR, and ova and parasites exam were all negative. She was started on methylprednisolone 2m/kg/day. Over four days of hospitalization, her abdominal pain worsened and she developed melena, which progressed to bright red blood per rectum. She was given infliximab at 10mg/kg. Repeat imaging performed 48 hours later due to severe abdominal distension showed large amounts of free air with gaseous distention of large and small bowel loops, consistent with perforation in the context of colitis with ileus. She was taken to the operating room for emergent bowel resection and a perforation site was identified at the transverse colon. The resected transverse colon serosa was congested and dusky with site of perforation identified (). The colonic mucosa revealed diffusely edematous folds as well as confluent areas of yellowish exudate and multifocal ulcers (). Histologic sections confirmed the presence of transmural necroinflammation and multifocal ulceration (Figures and ). The findings were of a fulminant colitis with multifocal ulceration and perforation. No evidence of metastatic melanoma to the bowel was identified. |
pmc-6000842-1 | A 65-year-old right hand dominant, African American male presented to the ED via emergency medical service. He had just finished smoking crack cocaine when he developed left arm pain that he described as “cramping”. He reported that the pain was so intense that he became weak causing him to fall onto the ground. The pain made him feel like “jumping out of the window.” He denied any head injury and he had no loss of consciousness (LOC). The patient had no chest, shortness of breath, or dyspnea on exertion. He denied any neck, back, or abdominal pain.
The patient's past medical history included diabetes, hypertension, hepatitis C, sick sinus syndrome, paroxysmal atrial fibrillation, hyperlipidemia, deep vein thrombosis, chronic kidney disease, hilar mediastinal adenopathy, diastolic heart failure, valvular heart disease, and cardiac arrhythmia of nonsustained ventricular tachycardia with a permanent pacemaker. The patient admitted to intermittent cocaine abuse. His medications include atorvastatin, furosemide, isosorbide mononitrate, acetaminophen with codeine, apixaban, hydralazine, metformin, albuterol sulfate, amlodipine, and tamsulosin.
Vital signs were essentially within normal limits with the exception of a blood pressure of 142/83 mmHg.
The patient had a strong left radial pulse and brisk capillary refill of the left hand with no tenderness or deformity. The patient was noted to have left arm weakness and what looked like choreiform or clumsy left arm movements. His left leg was also noted to be weak. There was no numbness. Interestingly, light touch to any part of the left arm produced significant discomfort to the point where he did not want anything touching the left arm. He was noted to have decreased rapid alternating movements on the left upper extremity as well as mild difficulty with fine motor control. His left arm and left leg motor strength was 4/5. His cranial nerves II to XII were grossly intact. There were no visual fields cuts noted. Extraocular motility was intact. The grimace was symmetric. There was no evidence of double simultaneous extinction.
There were no pulsatile abdominal masses on exam and the bilateral radial pulses were equal. The patient was unable to tell the exact time of onset of his symptoms. The patient's left arm pain improved with morphine 4 mg intravenously.
The electrocardiogram (ECG) showed sinus tachycardia with first degree atria-ventricular block, as well as ST and T wave abnormality suggestive of lateral ischemia []. This is however unchanged compared to his ECG from two years previously []. His cardiac enzyme was negative.
A computed tomography (CT) scan of the head without contrast showed an acute 2.2 cm intraparenchymal hemorrhage with vasogenic edema in the posterior right parietal lobe [see ]. X-rays of the upper extremity were unremarkable. The chest X-ray showed normal cardiac silhouette and pulmonary vasculature.
Laboratory data showed a creatinine of 1.34 mg/dL. The urine drug screen showed cocaine.
The patient was placed on a continuous nicardipine infusion to maintain a systolic blood pressure of 140 mm Hg as per neurosurgical consultation. He was transferred to a neurointensive care unit. His left arm pain resolved after 24 hours. The carotid ultrasound showed no hemodynamically significant carotid stenosis and antegrade flow was present in the bilateral vertebral arteries. A CT angiography of the head and neck did not show any aneurysms. His serial cardiac enzymes remained negative throughout his hospitalization. A cardiac catheterization was not performed as the patient had it done one year previously showing angiographically normal coronaries. A cardiology consult was obtained and the patient was found to have no evidence of acute coronary syndrome (ACS) or ischemia. He was subsequently discharged to a rehabilitation facility. |
pmc-6000843-1 | A 42-year-old man presented with a nine-year history of intermittent productive cough. He also endorsed recurrent episodes of fevers, chills, and night sweats but denied shortness of breath, chest pain, hemoptysis, or weight loss. He presented to the Emergency Department for similar symptoms two months prior and was given a seven-day course of levofloxacin, with temporary improvement in symptoms. Past medical history was significant only for diabetes mellitus. He had no prior surgery and did not take any medications. He worked as a gardener and denied any history of smoking, alcohol, or drug use. On examination, vital signs were stable with normal oxygen saturation on room air. Chest auscultation revealed mildly decreased breath sounds and rhonchi in the left lower lung field. The remainder of the examination was normal.
A chemistry panel and CBC were unremarkable, including a WBC of 7.0. Sputum AFB smears and bacterial cultures were all negative. Chest radiograph showed left basilar lung consolidation with tree-in-bud opacities and stenosis of the LMSB (). Chest CT scan showed extensive tree-in-bud opacities with confluent consolidation in the left lung base, enlarged hilar and mediastinal lymph nodes, and stenosis of the LMSB ().
Flexible bronchoscopy revealed near-occlusion and distortion of the mid-LMSB (). Mechanical debulking with endoscopic biopsy forceps allowed for passage of the bronchoscope to the distal LMSB where a metallic foreign body was appreciated (). Histologic analysis of the biopsied endobronchial tissue revealed inflammation and squamous metaplasia, but no evidence of malignancy.
Subsequently, the patient underwent rigid bronchoscopy and a 2.7 centimeter metal foreign body was retrieved using rigid bronchoscopy forceps (). Granulation tissue occluding the LMSB was treated with argon plasma coagulation. The patient reported immediate improvement in his symptoms. Upon further questioning, he recalled a previous aspiration of a small piece of an aluminum beverage container that he used in lieu of dental floss 12 years before. This object was retained over that time period until we removed it.
Follow-up surveillance bronchoscopy demonstrated persistent endobronchial stricture in the distal LMSB. Rigid bronchoscopy with radial incisions by electrocautery knife and balloon dilation was used to restore luminal patency. Repeat CT scan one month after endobronchial therapy showed resolution of the left lung tree-in-bud opacities and consolidation and restored patency of the LMSB. The patient's chronic cough resolved and he remains asymptomatic. |
pmc-6000848-1 | A 66-year-old Caucasian gentleman presented to his GP with a singular, raised, crusted, scaly lesion of 21 × 20mm size with marginal erythema on the dorsum of his left hand (). He reported that the lesion was present for several years but had noted recent growth.
Medical history included AK, basal cell carcinoma (BCC), and seborrheic keratoses in various distributions over recent years, putting him at a higher risk of keratinocyte carcinoma []. The lesion was diagnosed in the primary care setting as an AK, though possibility of BCC and SCC was considered.
The previous BCC had been managed successfully with six weeks of topical imiquimod treatment. Procedural removal of the AK was offered to the patient, but he expressed interest in trying a different approach. The patient was contemporaneously enrolled in a clinical trial examining the use of Kanuka honey on rosacea [] and decided to try using the Kanuka honey topically on his AK.
Honevo® medical grade Kanuka honey (90% Kanuka honey, 10% glycerin) was topically applied once daily using a small amount on the fingertip rubbed into the lesion and surrounding 5 mm of normal skin for 10–30 seconds. It was left on for 30–60 minutes and then washed off with water. This was done consecutively for five days, after which the patient took a treatment break of two days due to lesion tenderness. During the break, the lesion was gently picked at, thereby debriding it. This process was repeated for a total of three months; there were no other treatments used prior to or during this regimen and there were no adverse reactions. The lesion gradually reduced in size with an initial rapid reduction in its dry, crusted nature.
After three months, residual appearance of the lesion was a 20 mm by 17 mm area of pink skin with no elements of hypertrophy, crusting, or loss of skin integrity (). At six months, there were no signs of recurrence. At nine months, the appearance of the skin had fully returned to normal. A telephone follow-up was conducted at two years after treatment, and the patient reported that his skin in the area was still completely normal and that there were no signs of recurrence. A photograph was taken at this time (). |
pmc-6000850-1 | A 66-year-old woman presented for an outpatient colonoscopy for evaluation of six months of iron deficiency anemia, diarrhea, and rectal bleeding. Her history was significant for gastroesophageal reflux disease and chronic low back pain, on twice-daily naproxen. Serologic studies were notable for hemoglobin of 7.4 g/dL and a mean corpuscular volume of 70.6 fL. Colonoscopy demonstrated four diaphragm-like strictures, with scarring and ulceration, interspaced between normal mucosa in the cecum and ascending colon (). Biopsies obtained from the cecal and ascending strictures revealed ulceration, acute inflammation, and reactive changes (). The patient was instructed to discontinue naproxen and avoid all other NSAIDs. Patient was subsequently scheduled for a repeat colonoscopy in three months to monitor for resolution. Subsequent colonoscopy revealed both endoscopic () and pathologic resolution () of the diaphragm-like proximal colonic strictures. |
pmc-6000855-1 | A 19-year-old Caucasian male presenting with severe primary sclerosing cholangitis underwent orthotopic liver transplantation and required a retransplant 5 weeks later due to a liver insufficiency caused by ligation of ruptured arterial pseudoaneurysm. He received more than 40 blood transfusions. The second donor was a 76-year-old male without a history of liver disease. The patient's postoperative course after retransplant included prolonged hemodialysis (8 weeks) due to acute kidney injury, cytomegalovirus (CMV) infection, hepatitis E infection, and hepatic artery stenosis in the anastomosis area, treated by angioplasty and stent insertion. Of note, hepatic artery stenosis resulted in ischemic-like cholangiopathy and prolonged cholestasis.
The patient's condition stabilized eight months after transplantation. Cyclosporin and Myfortic were administered for immunosuppression, in addition to aspirin and ursodeoxycholic acid. A liver biopsy performed at that period revealed numerous hypertrophic, iron-loaded macrophages and severe bile duct damage and loss, consistent with early mild chronic rejection (). Hemosiderosis was attributed to secondary iron overload, considering the numerous risk factors for this complication presenting before and after the retransplant (multiple blood transfusions, kidney injury, and CMV infection).
Eight months later, elevation of liver enzymes was observed: alanine transaminase (ALT), 127 IU/L, aspartate transaminase (AST), 61 IU/L, alkaline phosphatase, 209 IU/L, and gamma-glutamyl-transpeptidase (GGT), 222 IU/ L. Extensive laboratory and radiologic evaluations showed no abnormalities, aside from iron-related parameters: serum iron, 110 ng/ml, ferritin, 3170 mg/dl (versus 29 mg/dL before transplant), transferrin, 119 mg/dL, and transferrin saturation, 66%. Repeated liver biopsy revealed sinusoidal fibrosis with mild cholangiolar proliferation. Iron staining showed significant accumulation of iron in macrophages and hepatocytes, consistent with marked hemosiderosis ().
The combination of abnormal laboratory iron parameters and biopsy findings showing clear worsening of iron accumulation, without apparent new risk factors for secondary iron overload, led us to suspect primary rather than secondary hemosiderosis. Genetic testing of the patient's DNA ruled out preexisting HH and did not show any common HFE mutations (C282Y or H63D). Genetic high-resolution melt curve analysis of a biopsy sample revealed compound C282Y/H63D heterozygosity, confirming a genetic defect in the donor tissue, which elicited hereditary hemochromatosis in a recipient without any known HFE mutation.
Magnetic Resonance Imaging (MRI) performed or iron assessment revealed mild hepatic iron overload, consistent with 5 mg/gr, and did not show accumulation of iron in other organs: pancreas, adrenals, spleen, and heart.
Following the confirmation of the diagnosis, the patient was enrolled in a phlebotomy program. |
pmc-6000865-1 | A five-year-old male began experiencing a popping sensation followed immediately by the sensation of heat and pressure starting medially at the base of the skull which radiated two centimeters bilaterally. He was a product of a nonconsanguineous union, whose birth history did not involve instrumentation and whose past medical, surgical, and developmental histories were all noncontributory. This sensation was experienced simultaneously with bilateral numbness of the posterior tongue and difficulty in speaking, both of which lasted fifteen seconds with gradual attenuation. The above would occur upon abrupt lateral rotation (either direction) of the head approximately five to ten times a year unrelated to trauma, diminishing in frequency as the patient aged.
Between the ages of eleven and fifteen, as a competitive fencer, the patient would experience the same symptomology when performing actions involving extreme, abrupt lateral rotation of the head, translating to a frequency of approximately once to twice weekly.
At the age of nineteen, during military training and combat, the same symptomology was experienced approximately fifteen times when abrupt lateral rotation of the head prompted by various forms of minor external head trauma was experienced. After discharge from the military, frequency of these episodes was sustained with simple lateral rotation of the head outside the context of trauma for six months with spontaneous abatement.
At the age of twenty-one, the first time the patient came to medical attention for the above complaint, the patient's physical and neurologic examinations were completely normal, including cranial nerve exam. Of note, the patient was not hyperelastic, nor was there a family history of the same. Magnetic resonance imaging (MRI) of the cervical spine (Figures –) was performed revealing slight dysplastic enlargement of the anterior arch of C1 vertebrate, mild degenerative changes of the atlantoaxial junction, and spinal canal caliber on the lower end of normal limits. No evidence for abnormal bone spurring or abnormality of the hypoglossal canal was found.
Of note, upon further query, it was found that the patient's grandmother also had the same condition. |
pmc-6000869-1 | A 72-year-old woman was referred to our hospital with pancreatic head and neck carcinoma for more evaluations and surgical operation. She had been suffering from abdominal pain for about 1 year, and the pain has become more intense in the last 6 months. The pain was postprandial and localized to the right upper abdomen. She has become icteric with generalized spread plus itching since past 2 months. The patient had no history of alcohol consumption or smoking. The patient was referred to us with a highly probable diagnosis of pancreatic head and neck carcinoma to be consulted for surgery. Also, a plastic stent was implanted for her in the previous health center due to intra- and extrahepatic duct dilation for the relief of patient symptoms and signs. After admission to our hospital, she was evaluated by abdominal computed tomography (CT), endosonographic imaging, and diagnostic ampullary biopsy. The abdominal CT scan with contrast exhibited an 18 mm × 20 mm hypodense mass at the head and neck of the pancreas (). Also, endosonographic imaging was performed to rule out periampullary lesions (). A 20 mm × 19 mm lesion was seen in the pancreatic head and neck region, and the main pancreatic duct was slightly dilated in the body of the pancreas. Moreover, the common bile duct (CBD) was distally thickened and contained sludge. Subsequently, diagnostic biopsy for pathological assessment was done. The biopsy revealed an irregular gray-creamy soft tissue which had undifferentiated malignant tumor features at microscopic evaluations. During the Whipple procedure, after cutting the neck of the pancreas in the left side of the portal vein, the frozen section revealed more involvement of pancreatic tissue. Although additional 2 cm was resected, the pancreas residue still had tumor involvement, macroscopically. Therefore, the patient was undergone total pancreatectomy.
Postoperative pathological studies were established and indicated a tumor with the greatest dimension of 4 cm which was extended to the duodenum. Invasion of the venous, lymphatic vessels and perineural sites was seen; however, no exact evidence of distant metastasis was found. The periampullary occlusion had hindered the bile flow over time, leading to chronic cholecystitis and pancreatitis which was confirmed by histopathological assessments. The hematoxylin and eosin staining revealed the presence of two cellular populations including spindle fibroblast-like and pleomorphic cells within the tumor. In addition, the proliferation pattern of the mesenchymal cells was storiform (). There was not any well-differentiated component in the tumor tissue or adjacent tissue. Overall, the pathologic stage II A was assigned to the tumor. The immunohistochemical staining was performed, and the tumor was positive for CD68, lysozyme, alpha 1-antichymotrypsin, and vimentin (). Also, it was negative for S-100P, cytokeratin, epithelial membrane antigen, desmin, CD34, smooth muscle antigen, MDM2, and CDK4. Therefore, the tumor diagnosis was compatible with UPS. The tumor Ki-67 expression was more than 30%. To evaluate metastasis occurrence, contrast-enhanced thoracic high-resolution CT scan and multidetector CT scan of abdominopelvic were done at 6, 12, 18, 24, and 36 months after operation, and no evidence of metastasis was detected. Insulin and Creon were started after surgery for long life. The further follow-up investigations were done by periodic CT scan and ultrasonic imaging. Fortunately, she was disease-free during 5-year follow-up and tolerated total pancreatectomy, well. |
pmc-6000873-1 | A 64-year-old man with a medical history of micropapillary thyroid cancer and stage IIIb lung adenocarcinoma with no evidence of active disease for 3 years after chemotherapy and radiation presented with subjective complaints of new onset fatigue, nausea, scalp tenderness, and xeroderma. His medications included gabapentin 300 mg four times a day for chemotherapy-induced neuropathy, erlotinib 150 mg once daily for epidermal growth factor receptor- (EGFR-) positive lung adenocarcinoma, and omeprazole 40 mg once daily for subjective gastroesophageal reflux disease. A screening magnetic resonance image of the head revealed a new hypovascular pituitary mass measuring approximately 1 cm by 0.8 cm ().
On examination, the patient's vital signs were within normal limits. On physical exam, xeroderma was appreciated in all extremities. Finger size was proportional and no prognathism, acromegaly, or Cushingoid features were appreciated. The cardiopulmonary exam was normal.
Initial lab values demonstrated normal free triiodothyronine (T3) of 2.4 pg/mL (normal range (NR) 1.8–4.2 pg/mL), normal T3 of 86 ng/dL (NR 70–172 ng/dL), and normal free thyroxine of 1.00 ng/dL (NR 0.84–1.68 ng/dL). Prolactin was elevated at 28.9 ng/mL (NR 2.5–17.0 ng/mL). The patient's morning cortisol was immeasurably low at <1.0 mcg/dL (NR > 10 mcg/dL) as was the patient's testosterone level at <20 ng/dL (280–1100 ng/dL). Luteinizing hormone was low at 0.05 mIU/mL (NR 1.8–12.0 mIU/L).
The patient was started on prednisone 20 mg by mouth daily, at which point he noticed immediate improvement in his energy and appetite as well as decrease in his nausea. For chronic steroid replacement therapy, the patient's treatment was changed from prednisone to hydrocortisone 20 mg of hydrocortisone in the morning and 10 mg in the evening. The patient was additionally instructed about the dangers of adrenal crisis and told to increase his hydrocortisone to 90 mg daily if acutely ill.
Within a month of initial diagnoses, the patient suffered acute visual bilateral field cut and loss of peripheral vision. A repeat MRI demonstrated rapid enlargement of his pituitary mass, nearly doubled in size and described as a 2.2 cm by 1.2 cm mass impinging on the overlying optic chiasm ().
The patient subsequently underwent transsphenoidal resection of his pituitary mass. Gross histology characterized the mass as firm and fibrous. Macroscopic analysis revealed metastatic lung adenocarcinoma described as adenohypophysis fibrosis. Further histologic analysis revealed positive identification of cytokeratin 7, TTF-1, Ki-67, and epidermal growth factor receptor (EGFR) positive with EGFR gene nucleotide change demonstrating T790M and L858R positivity. This histopathology demonstrated further EGFR mutation of the patient's known history of lung adenocarcinoma which initially was only positive for EGFR mutation L585R.
After transsphenoidal resection and subsequent whole-brain radiation, further results demonstrated a continued low morning cortisol at <1.0 mcg/dL (NR > 10 mcg/dL) and testosterone level at <20 ng/dL (280–1100 ng/dL). Luteinizing hormone was low at <0.1 mIU/mL (NR 1.8–12.0 mIU/L) as was follicle-stimulating hormone 0.8 mIU/mL (NR 1.5–12.4 mIU/mL). Free T4 was low at 0.65 ng/dL (NR 0.84–1.68 ng/dL) and thyroid-stimulating hormone was low at 0.019 MCI/mL (NR 0.4–4.0 MCI/mL). Prolactin was lower than previous but still elevated at 14.9 ng/mL (NR 2.5–17.0 ng/mL). |
pmc-6000876-1 | A 32-year-old male presented with progressive shortness of breath and leg swelling. He had a past medical history significant for HIV disease and metastatic transitional cell cancer of the renal pelvis and left nephrectomy. He had metastatic involvement of the spinal bones, mediastinal lymph nodes, and lungs. He received gemcitabine and cisplatin followed by salvage treatment with atezolizumab. He was also on combination antiretroviral therapy (elvitegravir/cobicistat/emtricitabine/tenofovir/alafenamide) with undetectable viral load and CD4 count of 444 cells/mm3.
The physical exam was remarkable for tachycardia, respiratory distress, decreased breath sounds in the right hemithorax, and lower extremity swelling. A chest X-ray showed a right-sided pleural effusion and an enlarged nodular density in the left upper lobe. Laboratory data revealed anemia and an elevated troponin I. Patient symptoms resolved partially after he received a blood transfusion and underwent therapeutic thoracentesis. Transthoracic echocardiography revealed normal left ventricular function and a large, mobile, cystic mass in the right and left atrium. Transesophageal echocardiography revealed a large mass composed of solid and cystic components. The solid component, a 5 × 2.3 cm2 mass, had invaded the basal half of the interatrial septum and the cystic component was found to protrude into the left atrium (). Multiple enhancing neoplastic masses in the muscular compartment in both calves were detected on MRI of the lower extremities, which were in favor of neoplastic lesions (Figures –). The patient was not a candidate for surgery considering the extent of disease and he expired few days after presentation. |
pmc-6000878-1 | The subject was a 75-year-old woman who had suffered from postherpetic neuralgia for 8 years. In December 2016, she underwent a Gasserian ganglion nerve block at the Department of Anesthesiology of our hospital. Gasserian ganglion nerve block was performed to treat the first branch neuralgia of the trigeminal nerve in the right at the point which is 2.5 cm lateral to the right angle of the mouth, following a straight line directed toward the pupil. A needle was inserted under guidance of X-ray imaging on the monitor display. When the tip of the guiding needle reached the foramen ovale, the location of the needle tip was confirmed to be slightly inside from the median in the frontal view. Next, after confirming dysesthesia, 2% xylocaine was injected. And then loss of sensation was confirmed in the V1 and V2 regions. After injecting 99.5% ethanol (0.2 mL), radiofrequency thermocoagulation was added continuously for 180 seconds at 90°C.
On the following day, the patient noticed a sudden visual acuity (VA) decline and hyperemia in the right eye. She visited a neighborhood ophthalmologist and was diagnosed with conjunctival hyperemia, corneal epithelial defect, and Descemet's folds in the right eye. Because no improvement was achieved, she visited our hospital two days later. The initial VA was 0.03 (n.c.) in the right eye. A slit-lamp examination revealed severe conjunctival hyperemia all around the periphery, remarkable corneal superficial neovascularization, especially, at 11 to 5 o'clock, corneal epithelial defects of the size approximately 3 × 4 mm, Descemet's membrane folds, and mild stromal edema were observed; however, no signs of inflammation were seen in the anterior chamber. The patient did not experience any eye pain and corneal sensitivity measured with Cochet-Bonnet esthesiometer was <10 mm in the right eye and 60 mm in the left, showing remarkable decline of corneal sensitivity in the right. She was diagnosed with NK stage 2 ().
Treatment was started with 0.3% ofloxacin ophthalmic ointment (Tarivid® ophthalmic ointment 0.3%; Santen Pharmaceutical Co., Ltd., Osaka, Japan) twice daily and rebamipide ophthalmic suspension (Mucosta® ophthalmic suspension unit dose 2%; Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) 4 times daily. The corneal epithelial defects were gradually alleviated at 1 week after ganglion nerve block (Figures and ).
Because severe conjunctival hyperemia persisted, we added fluorometholone ophthalmic suspension (fluorometholone® ophthalmic suspension unit dose 0.1%; Santen Pharmaceutical Co., Ltd.) 3 times daily. At 1 month after ganglion nerve block () severe conjunctival hyperemia, very severe corneal superficial neovascularization at 11 to 5 o'clock, persistent corneal defects with smooth and rolled edges, and stromal swelling in the central cornea occurred. At 2 months (), superficial punctate keratopathy (SPK), conjunctival hyperemia, corneal superficial neovascularization at 11 to 5 o'clock, irregularity of corneal epithelium, stromal scarring in the central cornea, and the right corneal sensation of 10 mm remained. Evaluation with the HRT II RCM was made in April 2017 and no corneal subbasal nerve fibers were observed in the right eye (Figures and ). Five months after the trigeminal nerve block, slight irregularity of corneal epithelium and stromal scarring in the central cornea were observed; however, conjunctival hyperemia and corneal superficial neovascularization were overall improving and the corneal sensation in the right eye also recovered to about 50 mm although SPK remained (). At this point, corneal epithelial defect was overall improving; therefore, ofloxacin eye ointment was stopped. Rebamipide and fluorometholone eye drops were continued and the patient was followed up. According to the patient, she had regained the sense of touch on the cheek. Corneal erosion sometimes recurred but it recovered in about a week. Six months after the trigeminal nerve block, the corneal sensation in the right eye was 60 mm. SPK and conjunctival hyperemia, corneal superficial neovascularization, and corneal stromal edema were all ameliorated (). Therefore, fluorometholone eye drops were tapered off and only rebamipide eye drops were continued. In addition, at this point, regenerated corneal subbasal nerve fibers in the right eye were detected by the HRT II RCM although they appeared to be smaller and thinner than those in the fellow eye (Figures and ). |
pmc-6000879-1 | A 65-year-old man with no relevant family or personal history was admitted due to a 2-day history of mild dysarthria and naming impairment with difficulty finding words and holding a conversation. Furthermore, his family reported at least one-month history of motor awkwardness and gait instability. During the neurological examination, the patient was well oriented, displayed fluent, coherent spontaneous language, and had mild dysnomia. He had remarkable clinical symptoms of parkinsonism: glabellar reflex was persistent; the patient presented a decreased blinking rate, hypomimia, moderate bradykinesia and hypokinesia in the right limbs, and slow gait with reduced right arm swing (Hoehn & Yahr stage I). The examination revealed no further abnormalities. With the clinical suspicion of parkinsonism, we performed a complete blood test performed at baseline, with either normal or negative. A brain MRI scan revealed increased signal intensity in the left putamen with diffusion restriction, suggesting lacunar infarction (). By the initial findings obtained in the MRI, vascular study was completed with echocardiogram, Holter monitoring, and Doppler ultrasound of the supra-aortic trunks which showed no significant alterations. Parkinsonism was studied using 123I-ioflupane SPECT (DaTSCAN), which revealed asymmetrical tracer uptake in the caudate nuclei (decreased uptake in the left caudate nucleus) and a near-complete lack of activity in the putamina, particularly on the left side (). On discharge, the initial working diagnosis was ischemic stroke and idiopathic Parkinson's disease. The patient remained at home. Progression was poor: dysphasia persisted and mobility decreased dramatically until the patient was unable to walk or even hold a standing position. He was readmitted 2 weeks later in a state of stupor. An emergency EEG revealed short-interval (<2 s) lateralized interictal epileptiform discharges in the left hemisphere (triphasic sharp waves and spikes); discharges were of greater amplitude in anterior regions and occasionally spread to the contralateral hemisphere. Within 24 hours, the patient went into coma (Glasgow Coma Scale 3) and was admitted to the intensive care unit. In the following days, and despite administration of several antiepileptic drugs (levetiracetam, valproate, propofol, and midazolam), he remained comatose and displayed clonic movements in the right arm. An additional brain MRI scan performed a month after the initial scan revealed progression of the lesions, with a patchy, gyriform hyperintensity predominantly affecting the cortex of the left hemisphere and the right temporoparietal cortex, visible in diffusion sequences only ().
Our patient's rapid neurological deterioration, the presence of myoclonus, and MRI findings pointed to a diagnosis of Creutzfeldt-Jakob disease. To rule out other possible causes of rapidly progressive dementia, we conducted a tumour extension study including tumour markers, onconeural antibodies, and a thoracic-abdominal CT scan; the study yielded negative results. The results from a CSF cell count and a biochemical and microbiological analysis were negative; Harrington test for the determination of 14-3-3 protein on CSF was positive (test was performed at Spain's National Microbiology Centre). An additional EEG performed 2 months after the first EEG revealed disorganised slow background activity, with generalized periodic sharp-wave complexes (PSWCs) at a frequency of 1 Hz (). A genetic study found no mutations in the PRNP gene; the study of codon 129 polymorphisms revealed methionine/valine heterozygosity (M129V). The probable diagnosis of sporadic CJD was reached based on the World Health Organization (WHO) diagnostic criteria []. He died 5 months after disease onset; autopsy was not granted. |
pmc-6000880-1 | The patient was a 40-year-old primiparous woman. She was diagnosed with submucosal fibroids by her previous gynecologist 5 years prior, based on chief complaints of atypical genital bleeding and hypermenorrhea. She underwent hysteroscopic myomectomy for one 1 cm sized and one 3 cm sized submucosal fibroid located between 2 and 3 o'clock in the uterine fundus. Asherman's syndrome was suspected after the patient exhibited secondary hypomenorrhea 10 months after surgery. Therefore, hysterosalpingography and magnetic resonance imaging (MRI) were performed. Intrauterine adhesions were suspected based on hysterosalpingography findings, while uterine cavity narrowing was identified using MRI. Hysteroscopy revealed filmy adhesions consistent with myomatous tissue at the excision site, and the patient was diagnosed with Asherman's syndrome.
Eight months after diagnosis, the patient underwent hysteroscopic adhesiolysis. The filmy adhesions observed on the left side of the fundus were easily separated with Hegar cervical dilators, and an intrauterine device was inserted after dilation. The patient was diagnosed with stage I Asherman's syndrome defined by European Society for Hysteroscopy classification of intrauterine adhesions, and menstrual flow returned to normal after the operation.
While the patient had a strong desire to bear children, her inability to conceive for 7 years led her to pursue in vitro fertilization (IVF). After having a miscarriage at 7 weeks of gestation, she underwent cervical dilatation and uterine curettage.
Six months after the miscarriage, the patient became pregnant again through IVF and was referred to our hospital at 7 weeks of gestation. At 19 weeks of gestation, tissues with a free edge were visualized within the amniotic cavity using obstetric ultrasound and were determined to be amniotic sheets on MRI at 31 weeks of gestation (). The course of pregnancy was uneventful thereafter, and an elective cesarean section was performed at 38 weeks and 2 days of gestation because of a breech presentation.
The placenta adhered to the uterine wall after childbirth and could not be easily separated manually. The blood vessels on the uterine surface at the placental implantation site were engorged (), leading us to diagnose the patient with placenta increta. The placenta remained firmly adherent to the uterine wall, and although there was almost no bleeding from the uterine cavity, cesarean hysterectomy was performed after informed consent was obtained from the patient. In the abdominal cavity, 4 cm subserosal uterine fibroids were observed on the left side of the fundus, and adhesions thought to be caused by endometriosis were found in the right adnexa, posterior uterus, and anterior rectum. The operative time was 101 minutes, while the total blood loss was 1,584 ml (including amniotic fluid). Blood transfusion was not required. Macroscopic examination of the uterus after extraction showed the presence of placenta from the fundus to the posterior wall, diffusely adherent to the myometrium (), along with partial thinning of the fundus.
Placenta increta was confirmed based on postpartum histological findings of placental villi invading the myometrium, without an interposed decidual plate.
The postoperative course was uneventful, and the patient was discharged in good health on the 7th postpartum day. |
pmc-6000912-1 | The patient was a 45-year-old Hispanic male who had end-stage renal disease of unknown etiology, hypertension, and hyperlipidemia. His HLA typing was A 2,- B 7, 35, Cw 4, 7, DR 4,- DQ 8,-. His donor was a 46-year-old Hispanic female with history of hyperlipidemia with a measured 24-hour urine creatinine clearance of 151 ml/min. Her HLA typing was A 2,31, B 35,44, Cw 4,5, DR 4,-, DQ 7,8. The patient had been on intermittent hemodialysis for two years prior to undergoing living related kidney transplant. Induction therapy consisted of basiliximab and solumedrol. Maintenance therapy was with tacrolimus, mycophenolate mofetil, and prednisone. His two-year course after transplant had been unremarkable, with a baseline serum creatinine of 1.5–1.7 mg/dL (134–150 μmol/L), without proteinuria or hematuria.
Two years after transplant he presented to the renal transplant clinic with complaints of lower extremity edema that had appeared over the previous three days. He stated he had experienced a flu-like illness a week prior. In addition, he admitted to inadvertently taking tacrolimus 1 mg q12h, rather than his prescribed dose of 3 mg twice a day for almost one month. He had corrected the dose approximately 3 weeks prior to presentation. On examination, he was normotensive and afebrile. Cardiovascular and respiratory examinations were normal. He had periorbital edema and 6 mm pitting edema in lower extremities. He did not have graft tenderness or bruit.
Laboratory data was remarkable for creatinine of 2.2 mg/dL (194 μmol/L). Urinalysis showed moderate blood and 3+ protein (previously no proteinuria), urinary sediment of more than 50 red blood cells (RBCs), 11–20 white blood cells (WBCs) per high power field (HPF), and urine protein/creatinine ratio of 8.2 g (previously 100 mg). Tacrolimus trough was 4.9 ng/mL.
Due to acute kidney injury, proteinuria, and hematuria in the setting of suboptimal immunosuppression, there was a high concern for acute rejection versus rapidly progressive glomerulonephritis perhaps due to recurrence of the unknown primary disease. Renal ultrasound and a renal biopsy were ordered. Given the risk of acute rejection due to inadvertent medication noncompliance, prednisone was increased from 10 mg daily to 50 mg daily, tacrolimus was increased from 3 mg twice a day to 5 mg twice a day, and mycophenolate mofetil was increased to 1500 mg twice a day. Of note, BK virus and donor specific antibodies were negative a month prior.
The renal US was negative for hydronephrosis or calculi. Three days later, a biopsy was performed.
Preliminary biopsy report was consistent with postinfectious glomerulonephritis (). Due to the recent infection, anti-streptolysin O (ASO) antibodies, C3, and C4 were ordered. Since initial biopsy did not have any glomeruli for immunofluorescence (IF), he was scheduled for repeat biopsy.
In the interim, C3 and C4 were reported. C3 was low at 59 mg/dL with a normal C4 at 35 mg/dL (). Tacrolimus trough was 8.6 ng/mL.
Second kidney biopsy one week later revealed minimal residual subendothelial electron dense deposits, but no evidence of large subepithelial electron dense deposits (). IF showed nonspecific patchy staining with C3 in glomeruli and some tubules. All other reagents were negative, including C4d in peritubular capillaries, BK, and SV40 in tubular cells. There is no evidence of cell-mediated or antibody mediated glomerulonephritis. Overall, biopsy was consistent with resolving postinfectious glomerulonephritis. Anti-streptolysin O (ASO) was elevated at 603 IU/mL (), highly indicative of Streptococcus being the causative agent.
Given that his AKI did not appear to be due to rejection, tacrolimus was decreased back to his basal dose of 3 mg twice a day and prednisone was tapered to 10 mg daily. Fluid management was achieved with furosemide. He was not prescribed any antibiotics. A month later, creatinine had decreased to 1.9 mg/dL (168 μmol/L), and in a 3-month period, it had returned to baseline and proteinuria and hematuria had completely resolved ( and ). |
pmc-6000913-1 | A 2-year-old healthy boy underwent an office-based surgical circumcision by his physician. During the procedure, profound bleeding was observed that was not controlled by applying direct pressure. The physician attempted to control the bleeding by multiple deep suturing; the bleeding was stopped successfully and the patient was discharged home. During the postoperative period, the child had progressive painful and difficult voiding with only few drops of urine after straining. During this period the child was prescribed painkillers for his discomfort and no additional evaluation was done. After about a week he was referred to a district hospital with fever (temperature=38.1C), agitation, vomiting, urinary retention, and significant abdominal distension. Abdominal examination showed decreased bowel sounds, dull percussion, and severe guarding. Urgent abdominopelvic ultrasound revealed large volume of free fluid in the abdomen and pelvis, with small amount of urine in the bladder. The initial lab tests also showed leukocytosis with left shift and increased blood creatinine and blood urea nitrogen. Catheterization with a 6-Fr feeding tube failed because it did not pass beyond the subcoronal urethra. The patient underwent emergency midline laparotomy with the diagnosis of acute abdomen and the fluid was drained. A small intraperitoneal bladder rupture was noticed at the dome of bladder. The gastrointestinal tract was inspected precisely and was intact. The diagnosis of intraperitoneal bladder rupture with urinary ascites was made probably due to near-total urethral obstruction. The rupture site was repaired in two layers and a suprapubic cystostomy catheter was fixed.
Two months later, the patient was referred to our center for further evaluation and treatment. Antegrade voiding cystourethrography (VCUG) was performed via the suprapubic catheter that showed terminal urethral obstruction (). Urethroscopy was attempted under general anesthesia that failed due to complete obstruction at 1 cm from the meatus.
Decision was made to explore the area and to repair the urethra. Through a circumferential incision, distal urethra was elevated from the corpus spongiosum. A 3-Fr ureteric catheter also did not pass the obstructed part (). A 5-mm fibrotic tissue was encountered at the site of obstruction (). The corpus spongiosum was dissected free from the corpora cavernosa to prevent iatrogenic chordee after end-to-end urethral anastomosis. The obstructed fibrotic part of urethra was completely resected and an end-to-end urethral anastomosis was performed along with spongioplasty over an 8-Fr silicon catheter in two layers; dartos pedicled flap was used to cover the site of anastomosis. The postoperative period was uneventful and the patient was discharged home with suprapubic and urethral catheter. The urethral catheter was removed seven days following the surgery. The suprapubic catheter was removed four weeks after the surgery following normal urethral voiding and normal ultrasound. A VCUG was performed six weeks after the surgery that showed normal bladder and urethra with acceptable voiding per urethra (). During a 2.5-year follow-up period, the patient was asymptomatic with normal renal function, ultrasound, and voiding pattern. He had a maximum flow rate of 15.3 ml/sec in uroflowmetry study. |
pmc-6000923-1 | Donor 1 was a 6-year-old boy from Guangxi province in China. The initial symptoms on 13 May 2015 were fever of unknown cause with insomnia and refusal to eat or drink. He was sent to a local hospital due to subsequent agitation, screaming and incoherent speech. Three days later, he suffered from dysphagia and hypersalivation. His condition subsequently worsened despite treatment with ribavirin. Finally, he died on 26 May after receiving an initial diagnosis of viral encephalitis of unknown cause (Fig. ). Cerebrospinal fluid (CSF) analysis revealed an opening pressure of 60 drops/min, transparent and limpid fluid, a glucose level of 4.7 mmol/L, and a protein level of 265 mg/L. Computed tomography (CT) revealed a slightly decreased density in the bilateral temporal lobes. Tests for HIV, hepatitis B, hepatitis C, and syphilis yielded negative results. Earlier, the donor had frequent contact with domestic dogs but no longer had this type of exposure since moving to live with his grandmother in another city. His family members denied either exposure to potentially rabid animals or history of rabies vaccinations. His kidneys and corneas were donated for transplantation.
Donor 2 was an 11-year-old girl who lived in Hebei province in China. Her initial symptoms were nausea, chills and vomiting on 22 Sep 2016. One day later, her condition worsened, and she suffered from fever, disorder of consciousness, coma, respiratory failure and decreased blood pressure, followed by insipidus and myasthenia gravis on 5 Oct. She died on 11 Oct after an initial diagnosis of acute disseminated encephalomyelitis (Fig. ). The results of CSF analysis were normal. Magnetic resonance imaging (MRI) revealed diffuse signal abnormalities throughout the brain and cervical spinal cord. Tests for HIV, hepatitis B, hepatitis C, syphilis, cytomegalovirus, Epstein Barr virus, coxsackie virus, herpes simplex virus, adenovirus and rubella virus yielded negative results. Her family members denied exposure to potentially rabid animals or history of rabies vaccinations. Her kidneys and liver were donated for transplantation.
Recipient 1 was a 55-year-old male who received a kidney transplant from donor 1 on 27 May 2015. The allograft recovered successfully, and the immunosuppressive regimen included tacrolimus, mycophenolate sodium and prednisone. The patient initially became symptomatic on 10 Jul 2015 (Fig. ). MRI revealed mottled signal abnormalities around the bilateral ventricles and deep white matter (low or equal signal on T1WI and high signal on T2WI and Flair), which indicated white matter demyelination. He was clinically diagnosed with rabies on 24 Jul according to the typical symptoms; this diagnosis was confirmed 4 days later by detectable rabies virus-specific nucleic acids in saliva, urine, and sputum samples. The patient died on 23 Aug. His family members denied exposure to potentially rabid animals or history of rabies vaccinations.
Recipient 2 was a 43-year-old male who received a kidney transplant from donor 1 on 27 May 2015. The allograft recovered successfully, and the immunosuppressive regimen included tacrolimus, mycophenolate sodium and prednisone. The patient initially became symptomatic on 14 Jul 2015 (Fig. ). CT revealed a suspicious mottled low-density region in the right basal ganglia region. He was clinically diagnosed with rabies on 24 Jul according to the typical symptoms, which was confirmed 4 days later by detectable rabies virus-specific nucleic acids in saliva and urine samples. The patient died on 17 Aug. His family members denied exposure to potentially rabid animals or history of rabies vaccinations.
Recipient 3 was a 57-year-old female who received a liver transplant from donor 2 on 11 Oct 2016. The allograft recovered successfully, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil and methylprednisolone. The patient initially became symptomatic on 18 Mar 2017 (Fig. ). CT revealed a suspicious mottled low-density region in the left basal ganglia region. She was clinically diagnosed with rabies on 24 Mar according to the typical symptoms, which was confirmed 2 days later by detectable rabies virus-specific nucleic acids in a saliva sample. The patient died on 26 Mar without invasive mechanical ventilation. Her family members disclosed that she had contact with a domestic pet half a year before transplantation but denied exposure to potentially rabid animals or history of rabies vaccinations.
Recipient 4 was a 50-year-old male who received a kidney transplant from donor 2 on 11 Oct 2016. The allograft recovered successfully, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil and prednisone. The patient received post-exposure prophylaxis (PEP) immediately after confirmation of rabies in deceased recipient 3 on 26 Mar 2017, which consisted of a 5-dose vaccination regimen (5 doses of purified chick embryo cell rabies vaccine, the first given directly after suspected exposure and subsequently on days 3, 7, 14, and 28) with 1 dose of rabies immunoglobulin (20 IU/kg). However, he still became initially symptomatic on 10 Aug 2017 (Fig. ). He was clinically diagnosed with rabies on 14 Aug according to the typical symptoms, which was confirmed 1 day later by detectable rabies virus-specific nucleic acids in saliva, urine, and sputum samples. The patient died on 16 Aug without invasive mechanical ventilation. His family members denied exposure to potentially rabid animals or history of rabies vaccinations.
Recipient 5 was a 46-year-old male who received a kidney transplant from donor 2 on 11 Oct 2016. The allograft recovered successfully, and the immunosuppressive regimen included tacrolimus, mycophenolate sodium and prednisone. The patient received PEP immediately after confirmation of rabies in deceased recipient 3 on 26 Mar 2017, which consisted of a 5-dose vaccination regimen with 1 dose of rabies immunoglobulin. The recipient currently remains asymptomatic (Fig. ). Unfortunately, the level of rabies-specific neutralizing antibody was not quantified.
Rabies virus-specific nucleic acids were detectable in saliva, urine, and sputum samples from recipient 1 and were also detectable in saliva and urine samples from recipient 2. The same results were found in a saliva sample from recipient 3 and in saliva, urine, and sputum samples from recipient 4. According to diagnostic criteria in China [], these recipients were laboratory-confirmed as positive for rabies. |
pmc-6000971-1 | A 51-year-old man was admitted to the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University (Nanjing, China) in June 2016 because of hypercalcemia and renal failure. The patient was well until he developed persistent leg and low back pain 20 days before admission. Prior testing at a local hospital showed progressive abnormal renal function (serum creatinine, 304.2 μmol/L), a high serum calcium level (4.86 mmol/L), and an extremely high level of parathyroid hormone (PTH) (1551 ng/L; reference level, 12–88 ng/L). After hydration with saline and diuresis with loop diuretics and hemodialysis, the patient was transferred to our hospital. He had no unusual issues with the exception of a 1-year history of stage 3 chronic kidney disease.
On admission, the patient reported fatigue, bone pain, and polyuria. A physical examination on admission revealed blood pressure of 119/80 mmHg and heart rate of 71 beats per min, but no specific findings of the lymph nodes, head, neck, heart, lung, abdomen, or joints. Laboratory testing revealed corrected serum calcium of 3.39 mmol/L, phosphorus of 0.84 mmol/L, PTH of 540 ng/mL, serum creatinine of 151 μmol/L (after hemodialysis), and hemoglobin of 120 g/L. Urine calcium was 9.2 mmol/24 h. An electrocardiogram (ECG) showed complete right bundle branch block and a precordial abnormal ST segment and normal corrected QT (QTc) interval (Fig. ). Myocardial marker analysis showed serum myoglobin of 31 μg/L and high-sensitivity troponin T of 826 ng/L. Ultrasonography revealed a nodule at the left lower pole of the parathyroid gland. Single-photon emission computed tomography results indicated an adenoma of the left lower pole of the parathyroid gland. Due to no family history of such disease and no medication history of thiazide or lithium, a diagnosis of primary hyperparathyroidism caused by a parathyroid adenoma was made. Because of the high level of troponin T and changes to the ST segment on an ECG, acute myocardium injury was considered, thus parathyroidectomy was deferred for multidisciplinary consultation. The final diagnoses were hypercalcemia, primary hyperparathyroidism, parathyroid adenoma, acute renal injury, chronic kidney disease, and acute myocardium injury.
Hydration with 3000 mL of fluid [60% saline (0.9%) and 40% dextrose (5%)] per day, furosemide at 40 mg three times per day, cinacalcet at 25 mg per day, and RRT were utilized to reduce serum calcium levels. Double lumen catheterization of the right femoral vein was used for vascular access. Slow extended dialysis with low-calcium dialysate (1.25 mmol) at bedside was started using a commercially available continuous RRT device (multiFiltrate, Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany). The dialysate flow was 4800 mL/h for 8 h each session. Changes in serum corrected calcium levels are shown in Fig. . Due to an unsatisfactory lowering of serum calcium and preparation for parathyroidectomy, slow extended dialysis was switched to 8-h RCA-predilutional hemofiltration at a replacement rate of 4300 mL/h. The replacement solution was prepared by a local pharmacy (Na, 105 mmol/L; bicarbonate, 21.5 mmol/L; zero calcium; magnesium, 0.5 mmol/L; and glucose, 6.7 mmol/L). The infusion rate of 4% trisodium citrate (citrate dose 4.2 mmol/L) was 220 mL/h and the blood flow was 120 mL/min when hematocrit was 32%.
Given the time limit of treatment, we gradually reduced the rate of calcium supplementation from 5.6 to 2.2 mmol/h in the first session of RCA-hemofiltration (Fig. ). The post-filter ionized calcium was 0.34–0.53 mmol/L during RCA-hemofiltration. The corrected serum calcium level decreased from 3.5 to 3.2 mmol/L and ionized calcium decreased from 1.97 to 1.67 mmol/L. This result was not inspiring, despite estimated 30 mmol calcium loss during RCA-hemofiltration.
A lower infusion rate of calcium (1.1 mmol/h) was started at the second session of RCA-hemofiltration (Fig. ). However, chest discomfort and palpitations were reported by the patient after treatment for 15 min. At that time, his blood pressure was 110/64 mmHg and heart rate was 125 beats per min. Blood gas analysis showed potassium of 3.8 mmol/L and a rapid serum ionized calcium decrease (from 1.91 mmol/L to 1.71 mmol/L). Hence, calcium supplementation immediately increased to 5.6 mmol/h and 2 min later, the chest discomfort and palpitation disappeared. However, the 12-lead ECG demonstrated sinus tachycardia with a prolonged QTc interval as compared to baseline at 3 days before (Fig. and Table ). One hour later, the calcium infusion was gradually reduced to 2.2 mmol/h to reduce the level of serum calcium without inducing sinus tachycardia. The ionized calcium decreased from 1.91 to 1.61 mmol/L with unaltered corrected serum calcium.
The third RCA-hemofiltration session began at a calcium infusion rate of 2.2 mmol/h, which resulted in a decrease in corrected serum calcium from 3.5 to 2.7 mmol/L and in ionized calcium from 1.91 to 1.18 mmol/L without arrhythmia (Fig. ).
After the third RCA-hemofiltration session, high-sensitivity troponin T decreased to 89.8 ng/L and the patient was deemed sufficiently stable to undergo parathyroidectomy. An untypical parathyroid adenoma was pathologically confirmed. Postoperatively, PTH dropped to 16.9 ng/L and serum calcium dropped to 2.25 mmol/L. Serum calcium was 2.11 mmol/L and serum creatinine was 173 μmol/L at discharge. The patient received a telephone follow-up at 2 months after discharge and reported serum calcium of 2.13 mmol/L and serum creatinine of 112 μmol/L without calcium supplementation. |
pmc-6001027-1 | A 42 year old male presented to his primary care physician with a 20 pound unintentional weight loss over a 3 month period and new left axillary lymphadenopathy. A core biopsy of his axillary mass revealed metastatic malignant melanoma. He had no prior history of a primary melanoma. A staging PET/CT revealed abnormal FDG uptake in his left axilla and small bowel. A left axillary lymph node dissection was performed and revealed 2 of 19 lymph nodes involved with metastatic melanoma, BRAF wild type, the largest of which measured 10.1 cm. His medical history was significant for oligodendroglioma, which was surgically resected eight years prior to presentation, followed by radiation therapy for recurrence five years prior to presentation. He received four doses of systemic ipilimumab for his metastatic melanoma without incident. Post-treatment imaging revealed disease progression with new diffuse subcutaneous, lung, liver and bilateral axillary lymph node metastases.
He subsequently enrolled on a genetically engineered T-cell trial, targeting tyrosinase. He received fludarabine and cyclophosphamide as a conditioning regimen, then his engineered T-cells were infused, followed by one week of low dose IL-2, (72,000 U/kg IV q8 hours). Per the treatment protocol, unfractionated creatinine kinase (CK) levels were obtained just prior to and for two weeks after infusion of the genetically engineered T-cells. The CK levels were within normal limits during the course of this treatment. He initially experienced disease response, however, four months after his T-cell therapy, he again developed diffuse progression with new hilar lymphadenopathy and progression of his lung and axillary lymph node metastases.
He was next treated with three doses of pembrolizumab but post-treatment imaging again revealed disease progression in his lungs. CK levels were not checked during treatment with either ipilumumab or pembrolizumab. Despite multiple lines of therapy, the patient continued to have an excellent performance status, so he thus proceeded to treatment with HD IL-2 (600,000 IU/kg IV over 15 min every 8 h day 1–5 and day 15–19), which began nine months after receiving his engineered T-cell infusion.
During cycle one of course 1 (day 1–5) of HD IL2, he received 10 out of 14 possible doses and experienced the expected adverse effects of hypotension, sinus tachycardia, oliguria, metabolic acidosis, and acute kidney injury. Serum CK was monitored per protocol and was initially normal but peaked at 641 (50–320 IU/L) during the fourth day of treatment without associated symptoms or cardiac findings on EKG.
He had an uncomplicated recovery and was re-admitted to the hospital for cycle 2 of course 1 (day 15–19) of HD IL-2, without complaints and a normal serum CK level of 133 (50–320 IU/L). After 6 doses of HD-IL2, he began to experience diffuse myalgias and rigors. He was noted to have a rapid rise in CK to 2700 and increase in his serum creatinine from 2.5 to 4.4 (0.6–1.4 mg/dL). An EKG revealed sinus tachycardia and his serum troponin level was normal at 0.02 (0.00–0.04 ng/mL). The rise in CK was attributed to rigors and he was continued on therapy. He went on to receive 2 additional doses of HD IL-2. When his CK rose further to 3900 and the myalgias became more severe despite resolution of his rigors, subsequent doses were held.
Further investigation revealed an elevated serum aldolase of 32.7 (1.2–7.6 U/L), and elevated urine myoglobin of 132 (< 28 mcg/L). MB fractionation of CK was not performed. Urinalysis demonstrated large blood without red blood cells. Serial EKGs demonstrated sinus tachycardia but not sequelae of hyperkalemia, such as peaked T waves. Other labs for serologic autoimmunity, e.g. anti-nuclear antibody, anti-double stranded DNA anti-striated muscle antibody and anti-smooth muscle antibody, were not checked. Muscle function was not assessed with electromyography (EMG). He received supportive care and aggressive intravenous hydration with normal saline. He recovered fully from this episode of rhabdomyolysis.
Subsequent staging with a PET/CT revealed a mixed response in his pulmonary nodules with mild improvement in his hilar and axillary lymphadenopathy. Given his full recovery from previous toxicity and the mixed response on imaging, the decision was made to proceed with a second course of HD-IL2 therapy with close monitoring of CK levels and a low threshold for discontinuation of therapy.
He received only two doses of HD IL-2 and again developed diffuse myalgias with a rapid rise in his serum CK level from 184 to 1680. Serum aldolase and urine myoglobin were again significantly elevated, at 16.2 and 3430, respectively. All further doses of HD IL-2 were held and he was again supported with aggressive intravenous hydration. His clinical symptoms resolved and his CK level trended down to the normal range.
Due to this unusual toxicity, a muscle biopsy was performed to further evaluate for rhabdomyolysis and to ascertain if his engineered T-cells were present in his muscle tissue. The biopsy revealed rare myofiber necrosis and myophagocytosis and scant endomysial infiltrate. The infiltrate consisted of a mixture of CD3 and CD4 positive T-lymphocytes, CD68 positive macrophages and lesser numbers of CD8 positive T-lymphocytes, suggestive of an immune-mediated toxicity causing necrotizing myopathy (Fig. ). It was difficult to ascertain if the T-lymphocyte present represented his engineered T-cells. Of note, the engineered T-cells remained detectable in the circulation at this time. He was discharged home and follow up PET/CT imaging revealed a near complete response. At the time of this follow up, he was found to have new onset vitiligo involving his neck, upper back, chest, and upper arms (Fig. ). A skin biopsy at the edge of his neck vitiligo again revealed CD3+ T-cell infiltration (Fig. ).
No further HD-IL2 therapy has been administered and he continues to experience a durable response on imaging nearly two and a half years since completion of his HD IL-2 therapy. Of note, CK levels had not been checked when the patient had received prior therapy with ipilumumab or pembrolizumab. CK levels were, however, monitored at the time of treatment with engineered T-cells and were noted to be within the reference range. |
pmc-6001049-1 | A 32-year-old healthy pregnant woman was referred to the Medical Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. The pregnant woman was 160 cm tall and weighed 53 kg with normal hallmark developmental milestones. She delivered a boy 10 years ago. During the second trimester maternal serum screening in another hospital, she was notified that the foetus had an increased risk of developing T18 syndrome. The study participant was at 16 weeks’ gestation. As is routine practice, an ultrasound was conducted to monitor the developmental status of the foetus. The ultrasound examination at a gestational age of 16 weeks showed that the foetus was normal. To avoid invasive prenatal diagnosis procedures, an NIPT was offered to further screen for common foetal chromosomal abnormalities. This project was approved by the Research Ethics Committee of Ganzhou Maternal and Child Health Care Hospital. Written informed consent was obtained from all of the participants or guardians that participated in this research. |
pmc-6001145-1 | A 56-year-old Japanese male was referred to our hospital with dyspnea and hypotension. He had a history of Parkinson’s disease with psychosis. He complained of left-sided chest pain and productive cough in the 2 months before admission. He reported no risk factors for HIV infection, occasional alcohol consumption, and was a current smoker with a 30-pack/year smoking history. Initial vital signs were as follows: blood pressure, 77/56 mmHg; heart rate, 106/min; body temperature, 36.1 °C (97.0 °F). There was no lymphadenopathy or hepatosplenomegaly. Examination of the oral cavity revealed poor dentition and inadequate hygiene. Jugular venous pressure was elevated to the angle of the jaw at 45° and did not change with respirations. The breath sounds attenuated at both sides, and dullness was present at the base of the bilateral lung. Cardiovascular examination revealed regular rhythm, tachycardia, and distant heart sounds. Laboratory test values were as follows: white blood cells, 29,950/mm3 with a left shift; hemoglobin, 10.6 g/dl; platelets, 453,000/mm3; random serum glucose, 125 mg/dl (normal, 75–115 mg/dl); serum lactate dehydrogenase (LDH), 260 U/l (normal,119–229 U/l); serum aspartate and alanine aminotransferase (AST and ALT), 80 U/l and 24 U/l (normal, 0–35 U/l); serum albumin, 3.1 g/dl (normal, 4–5 g/dl); serum C-reactive protein (CRP), 17.25 mg/dl (normal, < 0.2 mg/dl). The chest radiograph (Fig. ) revealed a mass in the left upper lung, bilateral pleural effusions and cardiac enlargement. The chest computed tomography (CT) scan showed a wedge-shaped and pleural-based mass in the left upper lobe (LUL), a thick-walled cavitary lesion containing only water density in the left lower lobe (LLL), bilateral pleural effusions and pericardial effusion (Fig. ). An electrocardiogram was normal. The patient received acute pericardiocentesis and pericardial drainage tube placement, which yielded approximately 800 ml of dark yellow fluid and restored blood pressure. Thoracentesis on both sides was performed and revealed yellow and turbid pleural fluid. Gram stain and cytologic examination of both pericardial and pleural fluid showed no organisms and also malignant cells. Examination of sputum showed no pathogen on staining. Two sets of blood culture specimens drawn at the time of admission did not yield any organisms. The patient was initially diagnosed with a bacterial pericarditis and lung abscess in the LLL. Intravenous ceftriaxone was started as an empirical antimicrobial treatment.
After the admission, the patient continued to be afebrile and his respiratory and cardiovascular status was stable. On day 6, there was minimal pericardial fluid in the drainage tube so the drain was removed. In the morning of day 9, a fever of 39.0 °C (102.2 °F) and sinus tachycardia (150/min) occurred. The tachycardia continued for 4 h, and he experienced atrial fibrillation (Af). Immediately after the onset of Af, a cardiac arrest with asystole occurred. He underwent an immediate cardiopulmonary resuscitation, which restored sinus rhythm and blood pressure. Chest CT scan obtained on the same day revealed the remaining thick-walled cavitary lesion in the LLL and the reduced pericardial effusion. After the cardiopulmonary state was stabilized, he underwent ultrasound-guided pneumocentesis of the cavitary lesion in the LLL and 35 ml of purulent fluid was obtained (Fig. ). Gram stain of the fluid revealed Gram-positive filamentous rods, and cultures of the fluid grew Actinomyces species (Fig. ). We analyzed the fluid using a method for clone library sequencing of the 16S ribosomal DNA (rDNA) gene and Actinomyces meyeri along with other anaerobes (Fusobacterium species) were detected []. Transbronchial biopsy and bronchial washings of the mass lesion in both the LUL and LLL were performed. The biopsy revealed non-specific inflammation and organization of the lung tissue with no bacteria. On day 11, antibiotics were changed to intravenous penicillin, and his condition continued to be stable. After 4 weeks of intravenous penicillin therapy, antibiotics were switched to oral doxycycline therapy and he was discharged. Echocardiogram before the discharge showed no evidence of pericardial effusion or constrictive physiology. The patient completed the total six-month antibiotic therapy. At follow up, 6 months after discharge, the patient was gaining weight, felt well, and his CT images had continued to show improvement (Fig. ). |
pmc-6001149-1 | Nivolumab was initiated to treat a 56-year-old woman, with unresectable NSCLC who initially received an adjuvant chemotherapy consisting of 4 cycles of cisplatin-pemetrexed. New lesions appeared and were classified pT3N0M0. Nivolumab therapy was then initiated. Figure summarizes the key clinical and immunological data of the index case as well as the timeline of immune checkpoint analysis.
No sign of SLR was detectable before the treatment with nivolumab (Fig. and ). A partial response was observed after 5 infusions of nivolumab as suggested by CT scan (Fig. and ). Skin lesions appeared after 5 nivolumab infusions (Fig. ), then mediastinal nodes size started to increase and a micronodular interstitial syndrome was observed (Fig. and ) after 20 nivolumab infusions. Biopsies showed epithelioid cells and Langhans multinucleated giant cells without necrosis, microorganisms or refringent bodies, compatible with sarcoid-like inflammation (Fig. ). Tumor cells, alcohol-acid resistant bacilli and fungus or parasite were not detected (data not shown). Nivolumab was then discontinued. According to RECIST criteria, the patient had a partial response at this time.
Mediastinoscopy revealed sarcoid lesions. Mediastinal nodes sizes (Fig. ) and skin lesions were decreased 155 days later (data not shown), while the interstitial syndrome had deteriorated (Fig. ). Bronchoalveolar lavage showed hypercellularity comprising 41% of lymphocytes without pathogens or cancer cells (data not shown). 348 days later, CT scan showed normal mediastinal nodes and regression of the interstitial syndrome (Fig. ).
The expression of PD-1, PD-L1 and PD-L2 was analyzed on PBMC at various time-points after stopping nivolumab (defined as day 0). An important increase of PD-L1 expression was observed on B and T cells at d56 with a peak at d147, compared to other patients treated with nivolumab without relevant immune related reactions (Fig. ). An elevated expression of PD-L1 was observed on monocytes at d147 (Fig. ). PD-L1 expression by PBMC of the index case returned to basal levels at d251 (Fig. ). If we hypothesize that the increase of PD-L1 expression was consecutive to a rebound effect after stopping the treatment, we would have observed a similar increase in patients treated with nivolumab that did not exhibit immune related events. Moreover, expression of PD-1 on T cells was punctually undetectable at d147 at a time when PD-L1 expression was maximal (Fig. ). No marked change of PD-L2 expression was observed. Intriguingly, the increased PD-L1 expression was evidenced only from day 56 to day 147 after nivolumab arrest (Fig. ). This observation suggests that an elevated expression of PD-L1 consecutive to blocking PD-1/PD-L1 interaction can be associated with sarcoid-like reaction (SLR). |
pmc-6001174-1 | A 56-year-old lady presented with a 6 month history of rectal bleeding, passage of mucus and a change in bowel habit to more frequent stools. She had no abdominal pains and her weight was maintained. The patient had been born with bladder exstrophy and had multiple surgeries culminating in a cystectomy with ileal conduit formation at 5 years of age. She had suffered with recurrent urinary tract infections for most of her childhood and adult life but was otherwise well with no other major co-morbidities or risk factors for colorectal malignancy and had no family history of colorectal disease.
Colonoscopy revealed two large sessile polyps in the sigmoid colon in close proximity to each other and adjacent to a diverticulum-like structure (Fig. ). Each polyp was approximately 3 cm in size and both exhibited a type IV pit pattern with areas of irregularity suggestive of focally advanced disease. Histological examination confirmed both polyps were adenomas comprising both low and high grade dysplasia, without submucosal invasion (Fig. ). On closer inspection the mucosa around the diverticulum was also atypical but not adenomatous. The remainder of the colonoscopy was unremarkable with no other evidence of diverticular disease or polyps elsewhere.
Endoscopic resection was considered as a therapeutic option however in view of the above characteristics as well as difficult endoscopic access surgery was preferred. Furthermore, radiological imaging had initially raised the possibility of invasive disease in view of sigmoid thickening. The patient underwent high anterior resection and an open approach was chosen because of suspected intra-abdominal adhesions following extensive pelvic surgery. An end colostomy was formed at the patient’s pre-operative request. At laparotomy the right fallopian tube was adherent to the sigmoid colon and adjacent to this a blind ending tube was noted to emerge from the anti-mesenteric border of the colon. This was marked for pathological identification.
Our patient went on to have an uneventful recovery and her quality of life following surgery was good. Her wish to have a permanent colostomy stemmed from the fact that she had always suffered from an erratic bowel habit and that she was already knowledgeable with regards to stoma care in view of her pre-existing ileal conduit. |
pmc-6001686-1 | We report a case of a 23-year-old female who presented with a 4-month history of fluctuating weakness of the right upper and lower extremities associated with a band-like sensation of the trunk along with bowel and bladder disturbances. There was no consult done. One month prior to her admission, she noted electric-like sensation on her nape, which was worsened by neck movement. The weakness eventually progressed to the left lower extremity causing difficulty in ambulation. The patient eventually became quadriparetic and needed to be assisted in all activities of daily living. She also developed dysphonia, dysphagia, difficulty of breathing and projectile vomiting that prompted consult to our institution.
The patient was hemodynamically stable upon admission. There were no spinal deformities noted. The sphincter tone was lax. Higher cortical function was normal. On cranial nerve examination, there was weak gag and shoulder shrug bilaterally. Manual motor testing revealed 2–3/5 on both upper extremities and left lower extremity and strength of 4/5 on the right lower extremity. Hypesthesia was also described at the C4 dermatomal level and dissociated sensory loss was also noted. The patient was hyper-reflexic on both the upper and lower extremities along with bilateral extensor toe sign. The patient's neck was paratonic.
Initial work-up included a cranio-spinal magnetic resonance imaging (MRI) revealing a long expansile contrast-enhancing mass involving the entire spinal cord, from the level of the cervical region to the conus medullaris with extension to the lower medulla oblongata (A–D). The patient was started on dexamethasone, which provided minimal relief of symptoms. She was also referred to the neurosurgery service. The patient was advised surgery, however, on the 20th hospital day, the patient's symptoms progressed to quadriplegia and respiratory failure. She subsequently developed healthcare-associated pneumonia succumbing to septicemia.
On autopsy, all lobes of the lungs were consolidated secondary to pneumonia (A & B). There was swelling of the entire spinal cord with white to yellow mucoid material coming out from the central canal (C). Cut sections showed that the entire spinal cord and caudal medullary region were replaced by mucoid material (D). The rest of the examination was unremarkable. Histopathologic examination of the spinal cord revealed a cellular tumor arranged around the central canal of the cord. The cells are generally small, with round to slightly ovoid nuclei. The chromatin materials are generally vesicular with occasional clumping seen. Fibrillary processes were noted in the cytoplasm (E & F). Immunohistochemical studies were done. S100 showed staining of the cytoplasmic globules with weak staining of intact cytoplasms. GFAP, synaptophysin, κ, λ and leucocyte common antigen had negative results. Further genetic characterization of the tumor such as IDH, 1p/19q codeletion, MGMT, EGFR and TP53 mutations was not done because of its unavailability in the institution but its histologic and immunochemical features are consistent with holocord oligodendroglioma. |
pmc-6001695-1 | A 28-year-old female was referred to our dermatology clinic because of persistent swelling of the earlobes several months after ear piercing. Clinical examination showed symmetrical nodes on both earlobes (Figure ). Histology showed epithelioid granulomas with a lymphocytic infiltrate, as seen in sarcoidosis and foreign body reactions. There were no further signs of sarcoidosis (normal chest X-ray and normal angiotensin-converting enzyme findings) or foreign material. Patch testing with the European baseline series and a dental series (including various metals) was performed. Positive reactions to nickel sulfate 5% pet. [+ on day (D) 2 and D3] and palladium chloride 1% pet. (+ on D3) were observed. Four weeks after the patch test, a persistent reaction on the patient's back remained at the palladium test site. A biopsy showed epitheloid granulomas similar to those previously seen in the excised nodes.
Inductively coupled plasma mass spectrometry (ICP-MS) (ICP-quadrupole-MS, Varian 810-MS) detected palladium (105Pd) in all of our skin samples (thickness, 4 μm) and showed a 3-fold higher signal than that from skin samples of control patients. The content of 105Pd in each sample was semiquantitatively determined to be 0.6 ng of 105Pd per sample. |
pmc-6002327-1 | A 65-year-old healthy Japanese woman presented with a chief complaint of malaise and hematochezia. The physical examination revealed a 10-cm-diameter hard mass at the right lower quadrant of the abdomen without tenderness or cutaneous involvement. Laboratory findings demonstrated severe anemia and elevated tumor markers (hemoglobin, 2.9 mg/dl; carcinoembryonic antigen, 10.8 ng/ml; carbohydrate antigen 19-9, 21.6 U/ml). A colonoscopy showed a circumferential neoplastic lesion at the ascending colon which did not allow the scope to pass through (Fig. a). The biopsy reported a moderately differentiated tubular adenocarcinoma (Fig. b). RAS mutation was not detected. A CT showed an 8.6-cm-diameter tumor at the ascending colon which seemed to infiltrate the abdominal wall, small intestine, and retroperitoneum (Fig. a). Regional lymphadenopathies and ascites were also observed, but apparent distant metastases were not. Based on these findings, we made a clinical diagnosis of locally advanced ascending colon cancer stages T4b, N2a, M0, and IIIC according to the TNM classification []. Considering the possible extensive invasion to the surrounding structures, we recommended initial neoadjuvant chemotherapy followed by radical resection of the tumor.
The patient underwent 4 cycles of modified FOLFOX6 with panitumumab, and the tumor shrank only slightly to 6.9 cm in diameter (Fig. b). An additional 4 cycles of the same regimen were administered but the tumor actually enlarged to 10 cm in diameter (Fig. c), and thus, the disease was determined to be a progressive disease according to the Response Evaluation Criteria in Solid Tumors []. At this point, we felt more chemotherapies and/or surgeries were not recommended because of the evidence of disease progression and because the patient’s condition was quite frail. Instead, we recommended radiotherapy of 60 Gy in 30 fractions (Fig. ). The patient tolerated the treatments well, and no serious adverse effects were reported. After the radiotherapy, the tumor shrank to 6.6 cm in diameter with intratumor liquefactive degeneration (Fig. d). One month after the radiotherapy, she underwent right hemicolectomy with D3 lymphadenectomy. Metastatic lesions of the liver or peritoneum were not observed. The right ovarian vessels and ileum at 10 cm proximal from the ileocecal valve were infiltrated by the tumor and resected concomitantly. The adjacent abdominal wall was intact. The transverse colon and ileum at 30 cm proximal from the ileocecal valve were cut and anastomosed. The macroscopic exam of the resected specimen showed a 9.0 × 7.0-cm circumferential tumor with a 4.5 × 3.5-cm ulcer at the ascending colon, which extensively penetrated the colon serosa and infiltrated the ileum and the ovarian vessels (Fig. a). Histopathologically, the primary tumor of the ascending colon and enlarged regional lymph nodes consisted in its totality of granuloma-like or fibrous tissues and no residual cancer cells were found (Fig. b). Pathological findings revealed complete response, and the final findings were ypT0, ypN0 (0/15), and ypStage0. Neoadjuvant treatment effect was grade 0 according to American Joint Committee on Cancer System []. The postoperative course was uneventful. The patient remains alive without any additional therapies after 24 months for follow-up, with no signs of recurrence. |
pmc-6002328-1 | A 62-year-old man with chronic hepatitis C was referred by his physician to our hospital for surgical treatment of hepatocellular carcinoma. Imaging findings on enhanced computed tomography (CT) and dynamic magnetic resonance imaging (MRI) revealed two tumors located in segments 5 and 8, respectively (Figs. and ). Although the alpha-fetoprotein level was within the reference range, the serum level of prothrombin induced by the absence of vitamin K or antagonist-II was high (530 mAU/ml). After a preoperative evaluation based on a three-dimensional (3D) imaging study, anterior segmentectomy was performed. Each branch of the hepatic artery, portal vein, and biliary duct for the anterior segment were ligated together as the Glissonean bundle (so-called, fully simultaneous transection of the Glissonean pedicle [FSTG]) (Fig. ). Perihilar FSTG involved a transfixation suture by using an absorbable thread. The tumor in segment 8 was in contact with the middle hepatic vein. However, this tumor was well-encapsulated, and the tumor and vein were easily dissectable. The patient’s postoperative course was uneventful, and he was discharged on postoperative day 14.
Three months later, dynamic MRI was performed to check for intrahepatic recurrence, and no imaging findings of recurrence were observed. However, an arterioportal fistula and portal vein aneurysm were incidentally detected (Fig. ). Layers of old and subacute hematomas were clearly observed, and these layers surrounded the aneurysm. Surprisingly, the patient did not have subtle symptoms and showed no episodes of pain, ascites, liver dysfunction, or other abnormalities. We suspected a pseudoaneurysm at that time. Although a perfect angiographic evaluation could not be ensured, IVR was needed to avoid sudden rupture and possible death. Therefore, we decided to attempt IVR after evaluation of the vessels on dynamic CT, and transcatheter arterial embolization was proposed thereafter.
First, angiography via the celiac artery was performed. Arteriography was subsequently used to create a portogram via this APF, and portography clearly revealed hepatofugal flow of the portal vein. Portography also showed that the stump of the anterior portal vein had developed a portal vein aneurysm (PVA) with a diameter of 40 mm (Fig. a). Selective catheterization of the common hepatic artery was then performed. This arteriography clearly demonstrated a fistula between the hepatic artery and portal vein (i.e., APF) at the stump of the anterior branches (Fig. b). Based on these angiography findings, we definitively diagnosed PVA due to an APF, not a pseudoaneurysm.
Next, an adequate length of APF to perform embolic therapy was confirmed to avoid any occlusion and disturbance at the bifurcation of the right hepatic artery (Fig. b). Selective embolization of the anterior hepatic artery was then accomplished by placing several titanium coils in the whole length of the stump of the anterior hepatic artery. Finally, the flow of blood through the APF was drastically reduced (Fig. c). Arteriography via the superior mesenteric artery showed a remarkable restoration of portal venous flow, and hepatopetal portal flow was clearly observed (Fig. d).
Complete closure of the APF could be estimated by additional expansion of the metallic coils over time after IVR. Dynamic CT and 3D images 3 days after embolization clearly demonstrated perfect interruption of the APF and disappearance of the PVA (Fig. ).
Imaging studies and serum biomarkers showed no evidence of recurrence. At the time of this study, the patient was good in health and had been reintegrated into society. |
pmc-6002423-1 | Case 13 concerns a 25-year-old man who was found dead in his flat. The autopsy revealed that the immediate cause of death was acute cardiac failure in the mechanism of arrhythmias due to chronic focal lesions in the myocardium. Moreover, according to the forensic pathologist, considering the pathomechanism of his death, the acute cardiac failure does not contradict the possibility of an unknown substance being co-responsible for the intoxication. This is suggested by the presence of gastric contents in his respiratory tract as a result of vomiting. Therefore, this case may be considered death resulting from a mixed causes of myocardium lesions with 4-CMC and amphetamine intoxication, as the concentrations determined in his blood (394 and 2200 ng/mL, respectively) are relatively high, and the detected concentration of amphetamine can be fatal to a nonaddict []. |
pmc-6002423-2 | Case 14 concerns a 38-year-old man who was found dead in his flat. During autopsy, blood and a fragment of abdominal wall containing a pill were collected for toxicological tests. Analyses showed that the pill contained disulfiram, although it was not detected in the blood. Ethyl alcohol was not detected either. The autopsy did not reveal any bodily injuries. However, signs of sudden death were found, including recent passive congestion of internal organs, presence of liquid blood in the heart and great vessels, and intensive livor mortis. Moreover, the forensic pathologist indicated the action of a psychoactive substance on the body probably as the primary cause of his death. Therefore, it is highly probable that the death resulted from an overdose of 4-CMC only, because only nordazepam at therapeutic concentration was additionally determined. |
pmc-6002785-1 | A 65-year-old man was admitted to our department for a routine CABG due to left main coronary artery disease. The patient’s medical history included smoking, family history of early coronary artery disease, hypertension, diabetes, hyperlipidaemia, percutaneous transluminal coronary angioplasty to the left descending artery (LAD) and to the right coronary artery (RCA) 12 years earlier, and myocardial infarction 11 years earlier due to in-stent stenosis. In his past medical history, there was an unclear history of sensory or motor impairment after coccyx cyst surgery.
All laboratory data were within normal limits except for the erythrocyte sedimentation rate (521st, 1 132nd) and a C-reactive protein (CRP) > 2 mg/l. Echocardiographic findings were left ventricular ejection fraction (LVEF) of 45% and mild left ventricular hypertrophy. Coronary artery CT-angiography was performed and stenosis of three coronary arteries was established.
The induction of anaesthesia was performed with Dormicum 5 mg, Propofol 150 mg, Esmeron 60 mg and Sevoflurane. The patient underwent triple coronary artery bypass grafting as follows: left internal mammary to left anterior descending artery (LIMA–LAD), a saphenous vein graft to the first obtuse marginalis (SVG–OM1) and another saphenous vein graft to the right coronary artery (SVG–RCA). During surgery his vital signs were stable and the arterial blood gasses (ABGs) were within normal limits.
After surgery the patient was moved to the cardiac ICU while intubated and unconscious, with a blood pressure of 110/60 mmHg, heart rate of 77 beats/min and normal sinus rhythm, central venous pressure of 8 cm H2O and peripheral capillary oxygen saturation of 100%. After admission to the ICU, his primary vital signs were normal. The patient was successfully weaned and extubated on the same day. The post-surgery drugs were: enoxaparin 40 mg daily, furosemide 20 mg daily, metoprolol 100 mg twice daily, clopidogrel 75 mg daily, atorvastatin 20 mg daily and acetylsalicylic acid 100 mg daily.
On the first postoperative day, laboratory findings in the ICU were: haemoglobin 10 g/dl, haematocrit 30.5%, platelets = 242 000 cells/l, white blood cell count = 9 100 cells/l, prothrombin time = 15.3 sec, activated partial thromboplastin time = 32 sec, INR = 1.47, sodium = 139 mEq/l, potassium = 4.9 mmol/l, blood urea nitrogen (BUN) = 17 mg/dl, creatinine = 0.94 mg/dl, creatine phosphokinase (CK) = 847 U/l, CK-MB = 58 U/l. He was moved to the cardiac surgery department. During this first postoperative day, the patient was stable, awake and oriented. No signs of haemodynamic instability or cardiac dysrhythmias were seen.
The second day after CABG, the overall condition of the patient was good but he had difficulty moving his lower limbs. Neurological consultation was done and the cranial nerves were found to be intact, cerebellar tests and sensory examinations were normal, muscle strength of the lower limbs was 3/5 and symmetric and plantar reflexes were double flexor.
On the third postoperative day, the overall condition of the patient was good but he still had difficulty moving the lower limbs. Progressive paraparesis developed and the muscle strength and deep tendon reflexes (DTRs) began to decrease gradually. Paraparesis progressed and muscle strength decreased from 4/5 to 3/5 and then to 2/5. In the evening, severe weakness of the lower and upper limbs developed, absence of DTRs, no plantar reflexes, and muscle strength was 1/5 on the left and 0/5 on the right side. That night the patient presented with respiratory failure; he was intubated and moved to the ICU.
On the fourth day, the patient was haemodynamically stable and he was transferred to the radiology laboratory in order to undergo magnetic resonance imaging (MRI). During the MRI examination, the patient experienced an episode of ventricular fibrillation and cardiac arrest. He was resuscitated after 20 minutes of cardiopulmonary resuscitation and two defibrillations. He was in haemodynamic instability and received high doses of dobutamine, norepinephrine and adrenaline.
The laboratory findings were: creatinine = 3.0 mg/dl, urea 111 mg/dl, aspartate transaminase (AST) 1 000 U/l, alanine transaminase (ALT) 6182, LDH 9 119 U/l, CK 3 915 U/l, CK-MB 315 U/l, troponin 10 000 ng/ml. The echocardiogram findings were left atrium 39 mm, telo diastolic volume of the left ventricle 50 mm, the left ventricle showed diffuse hypokinesis and akinesis, with a LVEF of 25%, and pulmonary artery systolic pressure was 40–45 mmHg.
The MRI report showed at the level of the fifth and sixth cervical vertebrae that there were posterior osteophytes and circular degeneration of the annulus fibrosis with high-grade stenosis and compressive phenomena in the spinal cord. From the second to the sixth cervical vertebrae, there was a pathological zone and oedema due to myelopathy and ischaemia ().
On the sixth day after surgery, the patient was better and was haemodynamically supported with low-dose norepinephrine. However he presented manifestations of post-cardiac arrest brain injury such as coma, seizures and myoclonus. He died 10 days after surgery due to septic shock. |
pmc-6002801-1 | A 53-year-old sub-Saharan African man with poorly controlled hypertension was referred to the cardiac intensive care unit (CICU) by his cardiologist for the management of a sudden-onset, severe and intractable retrosternal chest pain of approximately 50 hours’ duration. The pain was tearing in character, radiating to the back and lumbar regions, non-positional and associated with shortness of breath and headache. 50 hours’ duration. The pain was tearing in character, radiating to the back and lumbar regions, non-positional and associated with shortness of breath and headache.
The electrocardiogram (ECG), done three hours after the onset of pain, showed sinus rhythm and non-specific repolarisation changes (flattened or inverted T waves in leads I, aVL and V3–V6). Although ECG changes were suggestive of left ventricular strain, the presence of chest pain and a mildly raised troponin level (0.11 μg/ml) favoured myocardial infarction, and the patient was started on low-molecular weight heparin (LMWH) at a therapeutic dose, aspirin and nitrates.
Persistence of the pain after initial therapy prompted referral to our centre. On examination, he was anxious, dyspnoeic (NYHA functional class III with a respiratory rate of 28 breaths/ min) and diaphoretic. His temperature was 36.9°C, heart rate was 79 beats/min, and blood pressure was 187/73 mmHg in the right arm and 145/56 mmHg in the left arm. Physical examination showed a systolic murmur (grade 3/6) in the aortic area, which radiated to the left carotid, but there were no signs of heart failure. The neurological examination was unremarkable.
Chest X-ray () showed enlargement of the mediastinum with cuffing of the aortic knob. The ECG () at our unit showed a normal sinus rhythm, normal QRS axis with sub-epicardial ischaemia in the inferior and apico-lateral leads. Echocardiography () showed a dilated left atrium, good left ventricular systolic function (ejection fraction 72%), and severe aortic insufficiency with dilatation of the aortic root and ascending aorta (44 mm).
Contrast-enhanced CT (CECT) angiogram of the thorax () showed dissection of the aorta from the ascending aorta to the iliac arteries, including the coeliac trunk and left renal artery, and causing splenic infarction. Doppler ultrasound of the carotid arteries did not show extension to the carotid arteries. These observations led to a working diagnosis of Standford type A acute aortic dissection. shows biological investigations done at presentation and throughout hospitalisation.
The patient was placed on high-flow oxygen at 5 l/min, nicardipine in an electric syringe titrated to a maximum of 10 mg/h, bisoprolol 5 mg/12 h, analgesics and compressive stockings. The LMWH was stopped. On day five of hospitalisation, he developed superficial thrombophlebitis on the left forearm (along the peripheral intravenous line). By day six of hospitalisation, blood pressure and heart rate targets (< 120/80 mmHg and < 60 beats/min, respectively) were achieved.
On day 10 of hospitalisation, the patient developed a temperature of 39.1°C and sudden dyspnoea at rest. Physical examination showed a heart rate of 119 beats/min, blood pressure of 124/76 mmHg and oxygen saturation of 98%. Chest examination revealed crepitation in both lung bases, more marked on the right. We decided on a presumptive diagnosis of severe pneumonia. A repeat chest X-ray () showed bilateral interstitial heterogeneous opacities.
The C-reactive protein (CRP) level was 310.43 mg/l with leucocytosis of 17.7 × 106 cells/l (). Blood samples were collected for culture, and antibiotics (amoxicillin–clavulanic acid 1 g eight hourly and clarithromycin 1 000 mg 12 hourly) were introduced. Blood culture results (which returned after the patient’s demise) were positive for Klebsiella pneumonia. About three hours later he had persistent dyspnoea and hypoxaemia (SpO2 ≤ 65% and PaO2 ≤ 60 mmHg). He was intubated and during the process sustained a cardiac arrest. The patient later died on day 12 of hospitalisation following cardiopulmonary arrest despite life support. |
pmc-6002982-1 | An 18-year-old female was admitted to Peking Union Medical College Hospital in November 2016 with the chief complaints of abnormal limb movements and slurred speech for two years, which worsened 20 days ago. Initially, her movements were slower, her hands were clumsy, and she could not speak clearly. In the past 20 days, she gradually developed dysdipsia, unsteady gait, dyskinesia, significantly increased involuntary movements of limbs and fell > 4 times. Cranial magnetic resonance imaging (MRI) showed abnormal signals in bilateral basal ganglia and thalamus. Electroencephalography (EEG) demonstrated diffused 4–6 Hz theta waves. Slit-lamp examination showed Kayser–Fleischer (KF) ring in both eyes. Her serum ceruloplasmin concentration was 0.033 g/L (Normal range: 0.2–0.6). The symptoms progressively worsened, and she had a fever, with temperature between 37.5 and 38.0 °C, without chills, cough or diarrhea. The patient had difficulty in opening her mouth, could only speak one word at a time, and had occasional torsion spasm at the time of admission.
The patient had xerostomia, keratoconjunctivitis sicca, frequent oral ulcers, with no significant weight loss. There was no history of other diseases, but her mother recalled that she talked less, had behavioral changes, abnormal gait, involuntary smile and involuntary movements of all limbs since five years. The parents and older sister did not have similar symptoms. Physical examination revealed that the patient had normal comprehension, with low-grade fever, hepatomegaly, splenomegaly, dystonia, lack of coordination, slight tremor, dysarthria, dysphagia and right side Babinski sign positive.
After admission, routine tests revealed decreased white blood cell count of 2.87*109/L (Normal range: 4–10). Liver function test showed slightly elevated transaminase level and normal bilirubin level. Albumin level was decreased to 32 g/L (Normal range: > 35). Renal parameters were marginally elevated with proteinuria (1.12 g/24 h) and hematuria (++). Lumbar puncture showed elevated intracranial pressure, normal white blood cell count of 2/ul, elevated protein of 0.69 g/L and elevated immunoglobulin G (IgG) of 58.8 mg/L (Normal range: 0–40). Anti-AQP-4 (Anti-aquaporin 4) IgG and myelin basic protein were negative. MRI revealed symmetric abnormal signals with low signal in T1-weighted image, and high signals in T2-weighted and FLAIR images of bilateral basal ganglia thalamus, midbrain, and pons (Fig. ). Computed tomography (CT) scans revealed diffused lesions in the liver, uneven density, and hepatosplenomegaly. The patient, her parents and her sister underwent genotype test for WD, which showed that the patient had a compound heterozygous mutation, while her family members did not.
Other laboratory findings included elevated ESR, C-reactive protein, IgG, IgM and hypocomplementemia. The titers of antinuclear antibody (ANA) (S1:640), anti-SSA antibody (+++) and anti-rRNP antibody (+++) were remarkably increased, while anticardiolipin antibodies (ACL), Lupus anticoagulants (LA), and anti-β2-glycoprotein-1 (anti-β2GP1) antibodies were all positive. Stomatological and ophthalmological evaluations provided objective evidence of salivary gland (salivary flow rate and parotid sialography) and ocular (Schirmer’s test and ocular dye score) involvement. Salivary gland biopsy showed typical histopathology of Sjögren syndrome. Magnetic resonance angiography (MRA) showed normal arteries, and ultrasound examinations of arteries and veins of bilateral legs, bilateral subclavian, supra-mesenteric, inferior-mesenteric, bilateral renal found no thrombotic evidence.
Based on all the findings, the final diagnosis for this patient was WD, SLE, secondary Sjögren syndrome with anti-phospholipid (aPL) antibodies. Therefore, we started therapy with iv sodium dimercaptopropane sulfonate (DMPS), full dose zinc sulfate for WD, and methylprednisolone (80 mg iv for 7 days, then 40 mg po for 3 weeks), and hydroxychloroquine po for SLE, respectively. Since has three kinds of aPL antibodies were positive, the patient was also treated with anticoagulant therapy (low molecular weight heparin, and then aspirin po). One month later, her neurological symptoms and laboratory tests showed improvement. WBC count, liver function test including transaminase level, bilirubin level and serum albumin level, urine test, ESR, CRP, IgG and complement levels were all normal. Repeat lumbar puncture showed normal parameters. The titer of ANA had declined (S1:160), and aPL (ACL, LA, anti-β2GP1) antibodies were negative. The steroid dosage was gradually tapered and the patient was given oral dimercaptosuccinate (DMSA), zinc sulfate, hydroxychloroquine and aspirin for maintenance.
The patient was followed-up every three months at the outpatient clinic. Six months after discharge, her symptoms recurred, and she developed hyponatremia, hematuria and proteinuria, when the steroid was reduced to 2 mg/day. Hence, methylprednisolone dosage was increased to 16 mg/day, while the other treatment remained unchanged. Symptoms and abnormal laboratory findings were relieved in the next follow-up. |
pmc-6002987-1 | A 30-year-old gravida 2 para 0 presented at 31 + 3 weeks gestation with sudden onset, unprovoked, epigastric and left sided pleuritic chest pain. This was associated with nausea, vomiting and shortness of breath. Her bowels had opened that day and she was passing flatus. She denied any uterine tightenings, urinary symptoms or vaginal loss and reported normal foetal movements.
The patient was an otherwise well South Asian woman with good social supports and no significant medical, surgical or family history. She did however, have a similar presentation at 13 weeks gestation and was diagnosed with left lower lobe pneumonia and a possible empyema on chest x-ray. (Fig. ) Bronchoscopy and washings at this time were negative and she was managed conservatively with intravenous antibiotics. Her pregnancy then progressed uneventfully.
On presentation, her observations were unremarkable with oxygen saturations at 100% on room air, a respiratory rate of 20 and a normal cardiotocograph (CTG). She was, however, in significant distress secondary to pain, despite opiate analgesia. Respiratory examination revealed decreased breath sounds on the left hand side and abdominal palpation showed left upper quadrant and epigastric tenderness with normal bowel sounds and no signs of peritonism. Routine biochemical investigations including a full blood count, biochemistry and lactate were unremarkable. A chest x-ray, however, revealed evidence of a raised or ruptured left hemi-diaphragm with bowel visible in the chest. (Fig. ) A subsequent CT chest confirmed the diagnosis of a large left diaphragmatic defect with stomach, small and large bowel, and spleen in the chest cavity. (Fig. ) There was no evidence of a gastric volvulus or bowel ischemia. On retrospective review of her previous chest x-ray at 13 weeks gestation, what was originally presumed to be an empyema likely represented a small diaphragmatic hernia. (Fig. ) On further questioning, the patient reported that she was asymptomatic prior to pregnancy and had no prior chest or abdominal imaging for comparison.
The patient received a course of steroids for foetal lung maturation and was transferred to our tertiary centre for consideration of urgent delivery and repair of the diaphragmatic defect. On arrival, the patient was found to be haemodynamically stable and her pain was now better controlled with regular doses of opiate analgesia. Given no immediate evidence of bowel obstruction, visceral ischaemia, respiratory compromise or concerns for foetal wellbeing were present, a decision was made, jointly by the surgical and obstetric teams, to conservatively manage the patient. Delivery and repair were planned ideally for after 34 weeks gestation, or in the event of maternal or foetal deterioration. Due to her inability to tolerate sufficient oral intake, a nasogastric tube was inserted and the patient commenced on nasogastric feeds on day five of admission with dietician input. In order to meet nutritional requirements of pregnancy, feeds were titrated from 10 ml/hr. with the aim to achieve 60 ml/hr. However, the patient was unable to tolerate the required feed volume, experiencing nausea, pain and increased nasogastric aspirates. Due to the inability to meet nutritional requirements and the possibility of a partial intestinal obstruction, a decision was subsequently made for an earlier delivery at 32 + 3 weeks gestation.
We performed a lower uterine segment caesarean section followed by a left thoracotomy on day 7 of admission. The caesarean section was uncomplicated and a liveborn female infant weighing 1731 g was delivered. The thoracotomy identified a likely Bochdalek hernia involving stomach, small bowel, colon, appendix, spleen and omentum. The contents were reduced and the defect was repaired with four figure of eight Prolene sutures. The patient made an uneventful recovery and was discharged on day nine post-operatively. The neonate was admitted to the special care nursery due to issues of prematurity, specifically, mild respiratory distress, difficulty establishing feeds and jaundice. |
pmc-6003039-1 | The patient was a 69-year-old man with no history of urinary abnormalities or renal dysfunction. When he was 68, he underwent his first health checkup in several years and was found to have occult blood in his urine, proteinuria, and renal dysfunction. Urinalysis at the first examination showed urine protein of 0.49 g/gCr, urine red blood cells of 30–49/high-power field, and pathological granular casts, for which we decided to perform further studies including a renal biopsy. The patient had a history of untreated dyslipidemia. His family history was unremarkable. The patient was not taking any regular medication at the time of the first examination. Physical findings at the first examination were unremarkable. His blood pressure was normal (112/66 mmHg). There was no edema, lymph node involvement, splenomegaly, purpura, or bone pain. Table shows the results of urinary and blood analyses on admission for the purposes of the renal biopsy (dipstick test for occult blood 2+, urine protein 2+, and urine protein-to-creatinine ratio 0.30 g/g on a spot measurement). The number of dysmorphic red blood cells was 20–29 per high-power field. There were no abnormalities in complete blood count or the blood coagulation system. Serum urea nitrogen was 14.9 mg/dL, serum creatinine was 1.19 mg/dL, and estimated glomerular filtration rate by creatinine was 47.6 mL/min/1.73 m2. Serum cystatin C level was 1.73 mg/L and estimated glomerular filtration rate by cystatin was 37.1 mL/min/1.73 m2. Immunoglobulin levels were normal. Autoantibodies were negative. Serum and urine monoclonal immunoglobulin (immunofixation electrophoresis) were positive. The serum levels of the IgG κ and λ chains were 31.40 mg/dL and 33.60 mg/dL, respectively. The κ/λ ratio was 0.935. Serum cryoglobulin was negative.
With light microscopy, 54 glomeruli were observed, and two glomeruli showed global sclerosis. The remaining glomeruli were enlarged and showed lobular accentuation. In addition to mesangial cell proliferation, all glomeruli showed prominent endocapillary hypercellularity (Fig. –). Neutrophils and eosinophils showed marked infiltration. There was no hyaline thrombus, crescent formation, and double contour of the capillary walls. Interstitial fibrosis and tubular atrophy was mild. Direct fast scarlet staining was negative. Immunofluorescence was positive for C3 (1+) and C1q (2+) along the glomerular capillaries. However immunoglobulin G (IgG) was negative. The clone we used to originally test for IgG was produced by Medical & Biological Laboratories Co., Ltd. (Lot No. 104AG; Aich, Japan). All immunoglobulins were negative (Fig. ). Electron microscopy revealed marked endocapillary hypercellularity. There was infiltration of polymorphonuclear leukocytes and monocytes, occluding glomerular capillary lumens. In the subendothelial space, there were many tubular structures in parallel arrays. With higher magnification, the microtubules had a hollow core and the diameter was approximately 40 nm (Fig. ). Most of the deposits contained microtubular structures.
Based on the characteristic electron microscopy findings, ITG was suspected; however, negative staining for immunoglobulins was an unusual finding for ITG. IgG detection by paraffin-immunofluorescence following pronase pretreatment was strongly positive within the capillary spaces of a glomerulus (Fig. ). Immunofluorescence examination of frozen sections using a different clone of anti-IgG antibody (55,144; MP Biomedicals, Tokyo, Japan) showed positive staining in capillary walls. Immunofluorescence for C4d was positive along glomerular capillaries (Fig. ). Collectively, the patient was diagnosed with ITG with false-negative IgG staining.
Additional laboratory data revealed that serum and urine were positive for monoclonal immunoglobulins. In a bone marrow biopsy specimen, the proportion of plasma cells was 1.6%, excluding plasma cell myeloma. Chromosomal aberrations were not found. 18F-fluoro-deoxy-glucose positron emission tomography demonstrated no significant uptake. |
pmc-6003133-1 | A 32-year-old man was admitted to our hospital with appetite loss. He had a history of traumatic transverse cervical spinal cord injury at the C5 level due to suicide attempt at the age of 18. As a result of cervical spinal cord injury, he was paralyzed in the lower body. Contrast-enhanced computed tomography (CT) revealed a late-onset traumatic diaphragmatic hernia with strangulated ileum (Fig. ). The small intestine, transverse colon, and omentum were displaced into the left thoracic cavity, and some portions of these organs showed a decrease in blood flow. Left lung collapse and a compressed right lung with mediastinal shift were evident. The patient underwent emergency surgery. After replacing the incarcerated organs to their original positions, scattered areas of necrosis were identified in the small intestine, transverse colon, and omentum (Fig. ). By using interrupted sutures with non-absorbable 1–0 monofilament, the diaphragmatic orifice was closed. Wedge resection with primary closure was performed for the colonic necrosis in two places. Partial resection, 45 cm long, with end-to-end anastomosis was performed for the small intestine. The necrotic omentum was removed (Fig. ). In addition, a gastrostomy tube was placed since delayed initiation of oral intake was expected. The patient developed severe septic shock postoperatively. Treatment-resistant critical hypotension with non-compensatory tachycardia developed, likely due to parasympathetic nervous system damage related to the cervical spinal cord injury. On postoperative days (POD) 3 and 6, cardiac arrest occurred. Fortunately, he was rescued by cardiopulmonary resuscitation with administration of large doses of vasopressin and catecholamine. However, peripheral vasoconstriction, increased intra-abdominal pressure, and ischemia of the gastrointestinal tract developed, which resulted in colonic anastomotic leakage with diffuse peritonitis, abdominal wound dehiscence, and collapse of gastrostomy on POD 6 (Fig. ). The patient was unable to undergo surgical repair because of his poor general condition with continuing severe septic and neurogenic shock. Therefore, he underwent AVS through the open abdominal wound and it was the first procedure at the intensive care unit. The procedure of AVS was as follows: 1. the open wound and peritoneal cavity were rinsed with normal saline and necrotic and/or contaminated tissues were debrided (Fig. ); 2. wound dressing materials (DUOACTIVE® ConvaTec, New Jersey, USA) for protecting healthy skin around the open wound were patched along the abdominal wound in piecemeal fashion so as to adjust dressing materials to the complicated shape of the wound (Fig. ); 3. two drainage tubes with multiple side holes, up to 30 cm from the tip, were placed in the abdominal cavity through the open abdomen and the enteric contents were suctioned through the drainage tubes using a Continuous Suction Unit MERA Sacuum (Senko Medical Instrument Manufacturing CO, Tokyo, Japan) set to 50–75 mmHg continuous negative pressure; and 4) the entire wound was filled with saline-moistened gauzes and covered with polyurethane drape (Fig. ). The colonic anastomotic leakage showed gradual healing over the course of 2 months, followed by contraction and closure of wound dehiscence (Fig. ). Because the gastric fistula remained, a gastrostomy balloon catheter was placed through the gastric fistula. The patient resumed oral intake on POD 112 and left the hospital on POD 190 with the gastrostomy balloon catheter and without incisional hernia. |
pmc-6003150-1 | A three-year-old girl was referred to the Reference Centre of Rare Diseases in Paris. Her medical history was noncontributory. According to her mother, she complained with pain while eating, moderate sensitivity during tooth brushing and above all poor aesthetic aspect of her teeth. Intraoral examination revealed a hypoplastic AIH with yellow teeth and rough surfaces (Fig. ). Brown extrinsic discoloration was seen in the hypoplastic area. Enamel was reduced in thickness and severely hypoplastic, giving the idea of a false microdontia with multiple diastemas. Molars were the most affected teeth showing reduced crown height. In addition, anterior open bite was noted without thumb sucking. Treatment was planned following 3 objectives at this age:Pain prevention and treatment Protection of dental tissue integrity in order to maintain occlusal function and limit dental biofilm retention Restoration of smile aesthetics.
On primary molars, the choice of treatment was stainless steel crowns (3 M™ ESPE™) because the occlusal morphology was lost (Fig. ). This way, vertical dimension was slightly increased and maintained. The incisors and canines were isolated with a rubber dam and direct dental composite restorations were placed (Herculite, Kerr [, ] with ER2 adhesives Optibond SL). Teeth were not prepared; we etched with 35% Phosphatidic acid for 30 s, rinsed for 30 s with air and water. Then teeth were air dried, adhesive was applied with an applicator tip, excesses were removed with air before polymerization for 45 s. Affected enamel was not removed but bonding was directly applied to it. As enamel surface appeared rough, a flow composite (Tetric Evoflow, Ivoclar) was applied and served as intermediate material. Its higher fluidity and wettability would allow penetrating enamel roughness (Fig. ). Because tooth morphology of anterior teeth was not severely altered, “Odus” molds were not useful to offer a correct restoration. Composite resins were applied in one layer. Finishing and polishing were achieved with abrasive discs (Sof-lex/3 M ESPE). Patient follow-ups were done 6 months and 1 year after treatment. Composite sealing and oral hygiene were controlled. |
pmc-6003150-2 | A 16-year-old girl was referred by an orthodontist to the Reference Centre of Rare Diseases in Paris. Orthodontic treatment was performed with classical bracket technique in order to close anterior open bite (Fig. -). At the end of the treatment, the patient requested full mouth rehabilitation. She complained first of all about aesthetics but she also reported difficulties and painful chewing. Intraoral examination revealed hypomineralized AI associated with some hypoplasia. A little open bite remained after orthodontic treatment. Teeth were small with diastemas that were not closed as requested by the practitioner. In this occlusal context dental rehabilitation may be done without teeth reduction. Treatment was discussed according to several objectives taking into account the patient’s age:Functional restoration Aesthetic restoration Lasting treatment Minimally invasive treatment
Master impression of the two arches was recorded with a silicone material and working cast was mounted onto a semi-adjustable articulator using a centric relation record. Composite veneers were applied on incisors and composite full crowns on all other teeth (Fig. ). Nanohybrid indirect composite (Premise Indirect System, Kerr) was used with dentin and enamel shades mimicking the clinical shade (A3 shade was used cervically, A2 in the core and A1 in the incisal edge). Each layer was polymerised. Rigorous polishing was done in order to obtain shiny surfaces (Tool kit, Kulzer). The restoration was bonded using dual cured composite resin (Variolink Esthetic, Ivoclar™ Vivadent™) taking care to separate each proximal contact with metal matrix. Carefully polishing was made especially at the gingival border with a Touati bur. The patient was very satisfied with the aesthetic appearance. She did not report any trouble with mastication. She was followed every 6 months. Oral hygiene and integrity of the restoration were scrupulously monitored. Direct composite was applied 3 years later, on the cervical part of the crown because gingival maturation occurred. She had only difficulty to control calculus deposition on the lingual part of mandibular incisors. Five years later, the restorations were still satisfactory (Fig. ). |
pmc-6003275-1 | In November 2012, a 72-year old man was diagnosed with wet AMD in his left eye, based on fundus examination and optical coherence tomography (OCT), which was requested for the onset of metamorphopsia. At that time, he was treated with combination of angiotensin converting enzyme inhibitor plus thiazide diuretic for a 20-year history of well controlled hypertension.
His best-corrected visual acuity in the right and left eyes was 10/10 and 8/10, respectively. On slit-lamp examination, both anterior chambers showed clear aqueous humor and no inflammatory reaction. Dilated fundus examination revealed a subretinal whitish mass and adjacent subretinal hemorrhage. OCT confirmed the presence of a subretinal lesion and intraretinal edema. After obtaining informed consent, the patient was monthly treated with intravitreal administration of 0.5 mg ranibizumab for three months, without any complication and with complete retinal hemorrhage and edema resolution and increased visual acuity of left eye (10/10). Thereafter, the patient underwent routine follow-up visits, on a 2-month basis, including fundus examination and OCT which did not document any abnormal finding. In May 2014, a reduction of visual acuity (from 10/10 to 7/10) was registered. The patient was periodically followed-up but not treated with anti-VEGF drugs as there was no sign of neovascularization. In May 2015, visual acuity further reduced to 3/10 and both fundus examination and OCT revealed a reactivation of the neovascular membrane, edema and pigment epithelial detachment. For this reason, the patient was again treated with intravitreal injections of ranibizumab (0.5 mg), firstly on a monthly basis and thereafter using treat and extend approach, with overall six injections till the end of February 2016, when visual acuity increased to 6/10. At the follow-up visit in May 2016, the neovascular membrane appeared inactive and the visual acuity was stable at 6/10, so the ophthalmologist decided for a pro re nata approach (i.e., as needed).
In the same period, the patient referred to the Movement Disorders Clinic due to intermittent tremor on the left hand, started around February 2016. He did not complain non-motor symptoms.
Neurological examination disclosed resting tremor on the left hand, mild bradykinesia of left lower limb, and mild rigidity of head and trunk. His motor Unified Parkinson’s Disease Rating Scale (UPDRS) was 11/108.
The patient had no family history of PD or other neurodegenerative diseases nor had he been ever exposed to pesticides. Magnetic Resonance Imaging of the brain showed rare small subcortical white matters hyperintensities on T2 (mainly periventricular and frontal) and some bilateral hypointensities in T1 in the striatum, more prominent on the right, compatible with small ischemic lesions.
Single Photon Emission Computerized Tomography (SPECT) of the Dopamine Transporter (DAT) with 123I-ioflupane documented a significant and clear low uptake of DAT, mostly in the right striatum (Figure ). A diagnosis of clinically established PD was made based on new criteria of the Movement Disorders Society ().
A treatment with levodopa/carbidopa (300 mg/daily) was started at the beginning of 2017, due to worsening of tremor and bradykinesia leading to gait impairment and fatigue (motor UPDRS = 15/108). At follow-up examination in May 2017, response to levodopa was demonstrated by improvement of motor symptoms (motor UPDRS = 6/108), particularly of gait. Up to November 2017 other two injections of ranibizumab were intravitreally administered with visual acuity equal to 3/10 and the patient was in stable treatment with levodopa/carbidopa (300 mg/daily). |
pmc-6003786-1 | A 35-year-old male presented to the Emergency Department of Civil Hospital Karachi with a 10-day history of high-grade fever, shortness of breath, palpitations, and joint pain. The patient had poor appetite and fatigue. He denied any history of trauma, allergies, any other medical conditions, or weight loss. A review of the cardiopulmonary, gastrointestinal, and genitourinary systems was unremarkable. He did not smoke or use alcohol, and there had been no changes in his daily routine. However, he was an intravenous drug abuser. The patient had no history of any major surgery. His history demonstrated an ostium secundum of 22.18 mm with left to right shunt, which was diagnosed previously by transoesophageal echocardiography (Figure ).
On physical examination, he was found to be dehydrated but oriented to time, place, and person. His blood pressure was 100/70 mm Hg and his heart rate was 100 beats/minute. The respiratory rate was 20 breaths/minute and his temperature was 102°F. His fever was associated with chills, rigors, and sweating with multiple joint pains. On cardiovascular examination, no murmur was auscultated. The lungs were clear on auscultation. The abdomen was non-tender; hepatomegaly or lymphadenopathy was not detected. However, his spleen was enlarged 2 cm below the costal margin. Motor and sensory examination of all four limbs were normal. Past and family history of the patient was insignificant.
The patient's workup was initiated. Laboratory findings included complete blood cell count (CBC) showing Hb level = 12.6g/dl (normal range: 13.0 - 16.5 gm/dL) and total leukocyte count (TLC) = 15,000/μL (normal range: 4 - 11 x 103/μL). Malarial parasite and dengue tests were insignificant. Other tests including serology for human immunodeficiency virus (HIV) and hepatitis showed normal findings. Due to his persistent high-grade fever, IE was suspected in the patient. Therefore, echocardiography and blood culture were performed.
Echocardiography did not show any vegetation. However, two blood samples drawn from two different sites (12 hours apart for culture) were found to be positive for methicillin-resistant Staphylococcus aureus (MRSA). The patient was treated with intravenous (IV) vancomycin, 1 gm once daily, and IV gentamicin, 80 mg twice a day, for a period of six weeks for S. aureus. The fever eventually subsided, and subsequently, a surgery for the closure of ASD was planned and executed successfully. The patient was discharged from the hospital after he recovered well from surgery. He was further referred to the rehabilitation centre for drug abuse treatment. The patient visits on a monthly basis for follow–up and continues to do well. |
pmc-6003787-1 | Our patient is a 39-year-old male who presented with metastatic stage IVa cT2cN2M1a rectal adenocarcinoma located 12 cm from the anal verge with metastases to the liver. He underwent neoadjuvant chemotherapy with seven cycles of capecitabine-oxaliplatin, followed by long-course chemoradiation. This course consisted of intensity modulated radiation therapy (IMRT) at an outside center, 45 Gy in 25 fractions to the pelvis with a subsequent pelvic cone down of 5.4 Gy in three fractions and an additional 3.6 Gy in two fractions to the gross rectal tumor, given concurrently with capecitabine and trastuzumab. He subsequently underwent laparoscopic-assisted low anterior resection with colorectal pelvic anastomosis and diverting loop ileostomy. Pathology from this revealed ypT4N1b rectal adenocarcinoma with lymphovascular invasion. Throughout this period, his liver lesions were successfully treated with several courses of microwave ablation and chemoembolization. Restaging positron emission tomography-computed tomography (PET-CT) scan five months later demonstrated a new single site of FDG-avidity within a 1.1 cm left pelvic sidewall lymph node with no other sites of disease. He was referred for curative intent radiation therapy to this lymph node to treat his only active site of disease.
This patient had already exceeded the ideal dose constraints for bowel tolerance utilized by our institution and as outlined in RTOG 0822 and RTOG 0529 [,]. Specifically, his prior radiation treatment included a maximum point dose to the small bowel of 54 Gy, with V (50 Gy) of 16 cc, V (45 Gy) of 105 cc, V (40 Gy) of 198 cc, and V (35 Gy) of 329 cc; the latter two volumes are nearly double the ideal volume receiving 35 and 40 Gy. Large bowel had also exceeded ideal constraints, with V (45 Gy) of 41 cc. However, in the context of this young patient with oligorecurrent disease, we aimed to offer this patient curative-intent treatment.
The patient was thus treated with MR-guided SBRT, 35 Gy in five fractions delivered every other day to the left pelvic sidewall lymph node plus a 3 mm planning target volume expansion (Figure , panel A). Cumulative EQD2 (using α/β = 3) maximum point dose to the small and large bowel was 71.5 and 84.5 Gy, respectively.
The location of the recurrence in relation to the prior irradiated field is demonstrated in Figure .
The simulation and daily setup pre-treatment MRI scans were obtained on the ViewRay system (ViewRay, Inc., Oakwood Village, OH) incorporating a 0.35 T MRI. The same imaging protocol using a True Fast Imaging with Steady State Free Precession (TRUFI) sequence was performed to acquire the 3D MRI images with 1.5 mm thickness and a field of view of 50 x 45 x 43 cm without contrast injection. The total acquisition time was 172 seconds.
After image acquisition each day, a physician assessed the target and relation to surrounding anatomy. In the case of movement of critical structures close to the target, the physician had the option to create an adaptive plan that minimized the dose to critical structures. In this case, no adaptive planning was required as the position of the bowel relative to the target did not move significantly. Treatment was delivered using IMRT on the ViewRay system with three Cobalt-60 sources spaced at 120 degrees apart. During treatment delivery, cine MRI imaging at a rate of four frames per second was performed through a sagittal plane to track the intra-fractional motion of the target.
The patient experienced no acute toxicity. One month after completion of SBRT, the patient underwent a successful ileostomy reversal, with excellent progression toward return of normal bowel function. Repeat MRI at two months post-SBRT demonstrated no evidence of disease. |
pmc-6003789-1 | A 67-year-old woman was admitted to hospital for an evaluation of worsening right upper abdominal tenderness associated with episodes of nausea and vomiting for the last month. She described the pain as mild to moderate, continuous, radiating to the back, unrelated to eating, and without alleviating or exacerbating factors. She denied fevers, jaundice, or issues with bowel movements and urination. She admitted to a 10 kg weight loss over the last two months. Her medical history was significant for sinus tachycardia with good medical control on metoprolol. She admitted smoking and drinking on social occasions. Her family history was unrevealing.
At initial evaluation, her vital signs were within normal limits with a body temperature of 98°F, a pulse rate of 61 beats per minute, a respiratory frequency of 12 breaths per minute, and a blood pressure of 130/85. The abdominal exam revealed a palpable, poorly defined, mildly to moderately tender tumor-like firmness in the right upper quadrant (RUQ) without rebound tenderness. The remainder of her physical examination was unremarkable. The laboratory evaluation revealed a white blood cell (WBC) count of 10.2×109/L, hemoglobin 135 g/L, glucose 6.1 mmol/L, creatinine 0.8 mg/dL, alanine aminotransferase (ALAT) 9 U/L, aspartate aminotransferase (ASAT) 18 U/L, total bilirubin 6.8 mmol/L (direct bilirubin 3.6 mmol/L), and an international normalized ratio of 0.94. Tumor marker cancer antigen 19-9 (CA 19-9) was 14.4 U/mL (normal limit: < 34 U/mL) and carcinoembryonic antigen (CEA) was 0.6 ng/mL (normal limit: < 5 ng/mL).
Abdominal ultrasonography (US) and computed tomography (CT) of the chest, abdomen, and pelvis revealed a large, ill-defined, heterogeneous mass completely replacing the gallbladder body and fundus with an extensive involvement of the adjacent liver segments, the duodenum, the head of the pancreas, and the hepatic flexure of the colon (Figures -). There were several, enlarged, loco-regional lymph nodes with no other lesions suspicious of distant metastatic disease. There was no intra- or extrahepatic biliary tree dilatation confirmed by magnetic resonance cholangiography.
Advanced stage IIIb-IVa CG was the main differential diagnosis and the possibility of acute or chronic cholecystitis with diffuse mass-forming XG was lower on the list. A detailed discussion of the possible intraoperative scenarios and the extent of the surgical resection with the risks, benefits, and prognosis was carried out, and informed consent was obtained. Surgical exploration confirmed the preoperative imaging findings and revealed a mass occupying the entire subhepatic space adherent to the adjacent liver segments, omentum, hepatoduodenal ligament, the second portion of the duodenum, and proximal one-third of the transverse colon. No intra-abdominal collections, abscesses or lesions suspicious of metastatic malignant disease were seen. Intra-operative frozen-section biopsies were not performed. Despite the extensive fibrosis and adhesions, we were able to define and dissect through soft tissue planes and safely separate the involved structures to perform a resection of the entire mass with adjacent liver segments and loco-regional lymph nodes for proper staging and prognosis.
Surgical pathology revealed an 8x11 cm XG tumor with diffuse, marked thickening of the gallbladder wall (up to 1.5 cm) and lumen filled with spongiform purulent matter. Histology showed deep, ruptured Rokitansky-Aschoff sinuses penetrating the muscle layer with areas of tumor-resembling adenomyosis (Figure ). There were multiple foci of crowding of foamy macrophages and xanthoma cells (Figure ) alongside foreign body granulomas consisting of cholesterol (Figure ) and tiny bile lakes (Figure ). There were mild to moderate reactive inflammatory changes of the adjacent hepatic tissue with lymphocytic infiltration of portal tracts and fatty degeneration. No atypical cells or malignant cells were observed and the enlarged periportal lymph nodes showed a nonspecific inflammatory reaction.
The postoperative course was uneventful, and the patient was discharged home on day seven after surgery. Six months after the operation, the patient remains asymptomatic and in good health. |
pmc-6003790-1 | Patient 1 was a 13-month-old female who sustained a flame injury from a house fire. She had 73% TBSA third-degree injuries. Her right knee had an open joint injury that was treated with four skin grafting procedures prior to SEF placement. SEF was placed 46 days after the injury and was kept on for three weeks. K-wires and a 140-mm bar were used as a micro-SEF system. The patient required one additional skin grafting procedure to her right knee after SEF was in place. She had an eight-month follow-up after the injury and her PT/OT notes reported ROM within normal limits (WNL) and a 5/5 motor strength. She did have continued joint instability after SEF that required eight weeks of knee immobilizer use. However, no long-term complications requiring additional surgeries were recorded. |
pmc-6003790-2 | Patient 2 was a 10-year-8-month-old male who sustained a flame injury after a motor vehicle accident (MVA). He had 62.5% TBSA third-degree injuries. His right elbow had an open joint injury that was treated with seven skin grafting procedures prior to SEF placement. SEF was placed 55 days after the injury and was kept on for six weeks. Shantz pins and bars were placed as the external fixator system; this was locked in full extension. The patient required no additional skin grafting procedures to his right elbow after SEF placement. He had a 10-month follow-up after the injury and his PT/OT notes documented a final ROM of 30–110° in the extension and flexion arc, supination of 30° and pronation WNL, and a 5/5 motor strength. No other complications were recorded for this patient. |
pmc-6003790-3 | Patient 3 was a 4-year-4-month-old male who sustained a flame injury from a house fire. He had 41.5% TBSA third-degree injuries. His right elbow had an open joint injury that was treated with two skin grafting procedures prior to SEF placement. SEF was placed 43 days after the injury and was kept on for four weeks. Shantz pins and bars were placed using the Synthes medium external fixator system; this was locked in full extension. The patient required no additional skin grafting procedures to his right elbow after SEF placement. He developed an elbow contracture that was treated with an antecubital soft tissue plastic surgery contracture release. Prior to his surgical release, he had an ROM of 0–25° in the extension and flexion arc, supination of 0°, and pronation 0°. He had a 13-month follow-up after the injury and his PT/OT notes reported a final ROM of 0°–119° in the extension and flexion arc, supination of 69° and pronation 80°, and a 5/5 motor strength. His only complication was the elbow contracture. |
pmc-6003790-4 | Patient 4 was a 17-year-9-month-old male who sustained a flame and electrical injury after an MVA involving a power line. He had 30% TBSA third-degree injuries. His right elbow had an open joint injury that was treated with two skin grafting procedures prior to SEF placement. Other unknown procedures were performed in Mexico before transfer to our institution. SEF was placed 23 days after the injury and was kept on for 7.5 weeks. Four-millimeter Shantz pins and bars from the Synthes small external fixator set were placed; the fixator was secured in full extension. The patient had an SEF failure likely due to under sizing. The fixator was revised with a Synthes large external fixator system eight days after the initial one. The patient required three additional skin grafting procedures to his right elbow after SEF placement. He had a 12-month follow-up after the injury and his PT/OT notes reported a final ROM of 0°–110° in the extension and flexion arc, supination of 30°, and pronation 70°. He did have some continued weakness with elbow flexion at 4/5, extension 2/5, and pronation/supination 1/5 motor strength. His complications were SEF failure and weakness. |
pmc-6003790-5 | Patient 5 was a 7-year-4-month-old-male who sustained an electrical burn involving a power line. He had 32% TBSA third-degree injuries. His left knee had an open joint injury that was treated with three skin grafting procedures prior to SEF placement. SEF was placed 24 days after the injury and was kept on for 8.5 weeks. Shantz pins and bars were placed as the external fixator; this was locked in full extension. The patient required two additional skin grafting procedures to his left knee after SEF placement. He also required a bony prominence resection while in SEF. He had no PT/OT notes or follow-up recorded. He had no significant complications. |
pmc-6003790-6 | Patient 6 was an 11-year-6-month-old male who sustained a flame burn from an MVA. He had 25% TBSA third-degree injuries. His left knee had an open joint injury that was treated with three skin grafting procedures prior to SEF placement. SEF was placed 74 days after injury and was kept on for nine weeks. Shantz pins and bars were placed as the external fixator system; this was locked in full extension. He required no additional skin grafting procedures to his left knee after SEF placement. The patient had no ROM measurements recorded because the left knee was immobilized in full extension for a prolonged period of time. Complications were extensive. The patient ended up with significant damage to the medial collateral ligament and the medial femoral epiphysis from the injury developed a spontaneous knee fusion. Because of the growth plate disturbances, he developed a varus deformity and leg length discrepancy of 4.0 cm which caused persistent pain. He ended up requiring an osteotomy and Ilizarov placement for alignment correction and lengthening. |
pmc-6003790-7 | Patient 7 was an 8-year-5-month-old male who sustained a flame burn from an MVA. He had 79% TBSA third-degree injuries. His right knee had an open joint injury that was treated with six skin grafting procedures prior to SEF placement. SEF was placed 61 days after the injury and was kept on for five weeks. An SEF was placed using the Smith Nephew Richards system with 5.0-mm Shantz pins and bars. The patient required no additional skin grafting procedures to his left knee after SEF placement. He had a 10-month follow-up after the injury and his PT/OT notes recorded a final ROM of 0°–45° in the extension and flexion arc. His last recorded motor strength was 3+/5. His complication was residual knee stiffness and weakness. |
pmc-6003790-8 | Patient 8 was a 16-year-6-month-old male who sustained an electrical burn from contact with a power line. He had 48% TBSA third-degree injuries. His right elbow had an open joint injury that was treated with six skin grafting procedures prior to SEF placement. SEF was placed 53 days after the injury and was kept on for six weeks. An SEF was placed using the Smith Nephew Richards system with 5.0-mm Shantz pins and rods. The patient required no additional skin grafting procedures to his left knee after SEF placement. However, he did require two additional surgeries after the SEF was removed because of complications, including one surgery that incorporated an ulnar nerve transposition, heterotopic ossification removal, and contracture release with arthrofibrosis excision. The second surgery was a flap to cover soft tissue deficit that occurred after the elbow release. The patient had a 13-month follow-up after the injury and his PT/OT notes reported a final ROM of 20°–90° in the extension and flexion arc, supination and pronation were not tested, and a 4-/5 motor strength. Prior to his elbow contracture release, he had an ROM of 0°–30° in the extension and flexion arc, supination of 25° and pronation 85°, and motor strength was not tested. Complications included heterotopic ossification, cubital tunnel syndrome, and elbow stiffness. |
pmc-6003790-9 | Patient 9 was a 2-month-old female who sustained a flame burn from a house fire. She had 49.5% TBSA third-degree injuries and 3% TBSA second-degree injuries, 53% total. Her left elbow had an open joint injury that was treated with one skin grafting procedure prior to SEF placement. SEF was placed 74 days after the injury and was kept on for 8.5 weeks. Three-millimeter Shantz pins and rods were placed as an external fixator. The patient required no additional skin grafting procedures to her left elbow after SEF placement. However, she did require an SEF revision because the initial fixator was pulled out. She was lost to follow-up owing to a major natural disaster and transfer to a different hospital. The patient did develop some elbow stiffness and contracture at the time of SEF removal; however, her final ROM and strength are unknown. |
pmc-6003791-1 | A 64-year-old female was admitted with progressively worsening dyspnea and cough of one-month duration. These symptoms were associated with an unintentional eight-pound weight loss. She was seen two weeks earlier by her primary physician and started on levofloxacin for what was thought to be pneumonia. Initial antibiotic therapy failed to improve symptoms and patient eventually required supplemental oxygen. A CT scan of the chest showed innumerable cystic lesions with diffuse ground glass opacities in both lungs and a lesion in the liver (Figure , Figure ).
The patient underwent extensive workup for lung and liver disease including viral, bacterial, and fungal infection workups, human immunodeficiency virus testing, hepatitis panel, expanded connective tissue disease workup, and comprehensive interstitial lung disease markers. Cancer markers revealed an elevated cancer antigen 19-9. An abdominal ultrasound revealed innumerable cystic lesions throughout the liver; the majority were simple in appearance. It also showed intrahepatic and extrahepatic biliary and pancreatic duct dilatation. Liver biopsy was suggestive of a benign simple cyst wall and acute inflammation of hepatocytes. These findings raised a differential diagnosis including bile duct obstruction, mass effect, adjacent abscess, or adverse drug/toxin effect. Eventually, due to the unusual findings on CT scan and the failure of liver biopsy to provide a diagnosis, a lung biopsy was performed. Lung tissue was obtained by videoscopic-assisted fluoroscopic surgery to the right chest with wedge resection. Pathological examination showed metastatic with moderately differentiated adenocarcinoma in the right upper lobe, middle lobe, and lower lobe. |
pmc-6003792-1 | An 87-year-old man was conveyed to the emergency department after being found to be drowsy by his helper. He was watching television before he was found slumped in a chair, staring into space with saliva drooling. There was no history of recent fever, headache, fall, or trauma, and no recent hospitalization. Past medical history was significant for hypertension, stage 5 chronic kidney disease, a cerebrovascular accident, pacemaker insertion for sick sinus syndrome, a transurethral resection of the prostate for benign prostatic hyperplasia and pulmonary tuberculosis. His long-term medications were aspirin, omeprazole, amlodipine, and furosemide.
On examination, his Glasgow coma scale was 7 (M4E2V1), and his pupils were equal and reactive. His vital signs were stable, with a temperature of 36.7 degree Celsius, pulse rate of 66 beats per minute, respiratory rate of 18 breaths per minute, oxygen saturation of 99% on room air, and blood pressure of 144/84 mmHg. He had a new onset right hemiparesis and normal reflexes. There was no evidence of any head injury or cerebrospinal fluid otorrhea or rhinorrhea. Stat capillary blood glucose was 8.7 mmol/L. Infective markers were normal, white blood count was 5.6 x103/µL, C-reactive protein was 0.3 mg/L, urea was 17.7 mmol/L (stable), sodium was 137 mmol/L, potassium was 5.1 mmol/L, creatinine was 331 µmol/L (stable), and corrected calcium was 2.29 mmol/L. The liver function test was normal. Electrocardiogram (ECG) did not show any evidence of acute myocardial ischemia. An urgent CT brain revealed air bubbles within the dural venous sinuses (bilateral cavernous, superior sagittal, straight, and left sigmoid sinuses) (Figure ). There was no definite evidence of ischemic changes on CT brain. Pneumocephalus was initially thought to be the cause of his drowsiness and right hemiparesis. The neurosurgery team suggested conservative management of the pneumocephalus.
A facial bone CT was ordered to rule out trauma, as it is the commonest cause of pneumocephalus. The CT scan, done two days later, demonstrated a minimally displaced fracture of the lateral wall of the right maxillary sinus. Of note, there was an acute left middle cerebral artery territory infarct with hemorrhagic conversion, a mass effect on the left ventricle, and a resultant midline shift (Figure ). The pneumocephalus had resolved.
In view of a poor premorbid state, the severity of the stroke, and a lapse in the diagnosis of stroke, the patient was conservatively managed. He was started on statins; antiplatelets were held off in view of significant hemorrhagic conversion causing the midline shift. He underwent physiotherapy but remained bed-ridden.
A repeat CT brain one month later showed improvement in hemorrhagic transformation and a resolution of midline shift. He was then started on dual antiplatelet therapy. Despite the medical management, he demised one month after the initial presentation. |
pmc-6003794-1 | A 23-year-old woman presented with left lower quadrant abdominal pain and mildly elevated creatinine of 1.21 mg/dl (baseline 0.8-1 mg/dl) that was identified on routine blood draw at a one-month follow-up urology appointment. She had no urinary symptoms at that time and the review of systems was otherwise unremarkable. The physical examination was unremarkable without any focal abnormalities. Urinalysis and pregnancy testing were negative. Computed tomography abdomen revealed hydronephrosis of the left kidney as well as bilateral ureteral thickening (Figures -). One month prior, she had a right ureter stent placed after she presented with acute kidney injury, and the CT abdomen at that time showed evidence of right hydronephrosis and bilateral proximal ureteral thickening. In addition, biopsies of ureter specimens found normal urothelium with signs of chronic inflammation during that initial hospitalization. Further workup was negative, including chest x-ray, sexually transmitted infection testing, complement activity levels, and other autoimmune markers. During this admission, a stent was placed in the left ureter and the right ureter stent was replaced. Repeat biopsies of both the right and left ureters showed findings of benign epithelial growth and chronic inflammation that were previously noted the month prior. Per the operative report, the region of the ureter thickening had the gross appearance of ureteritis cystica. However, upon further questioning, the patient had a history of only one urinary tract infection, no nephrolithiasis, and no other risk factors for this presentation. The patient was discharged home symptom-free and proceeded with close urological follow-up. |
pmc-6003795-1 | A two-week-old female was brought in with an initial complaint of multiple masses that failed to regress since birth. She was born from a nonconsanguineous union and the mother’s pregnancy was uneventful. The baby was delivered vaginally at 37 weeks of gestation and multiples masses were found over the body. The treating physician advised follow-ups on discharge. However, the parents decided to seek more medical help for the child and she was admitted for more investigations.
On physical exam, the child was alert and active. She was not jaundiced and no pallor was noted on the extremities. Her vitals were all within the normal range and the birth weight and changes in weight corresponded properly. Two masses measuring 26 mm by 19 mm and 19 mm by 17 mm were observed on the forehead and the scalp (Figures -). One smaller mass was seen on the abdomen, measuring 11 mm by 10 mm (Figure ). All three masses were red and non-hemorrhagic. The parents reported that the size of the masses did not change since birth. No similar family history was found and both parents were healthy. Any hepatosplenomegaly was not observed on palpation nor were any other cutaneous lesions detected. She did not present with any other systemic abnormalities. An ultrasound was performed, and it revealed a normal liver, spleen, and kidneys with no masses or lesions. A Doppler examination also showed a fast-flow vascular lesion, as reported by many other articles []. The full blood count showed normal levels of white blood cells, platelets, hematocrit, and red blood cells.
The diagnosis of congenital hemangioma was confirmed and the family was properly educated about the condition as well as possible complications. A wait and watch approach was adopted and the child was scheduled for regular visits at three months. The family was asked to properly monitor the size of the masses and informed that appropriate surgical treatment would be provided if the masses fail to regress or if they continue to grow. |
pmc-6003796-1 | A 19-year-old female suffered a motor vehicle accident causing her to be ejected from the car. Complete spinal precautions were followed at the scene and her neck was immobilized with a rigid collar. The patient then was transported to our emergency room. She was complaining of neck pain. Her vital signs and neurological examination were normal. She was found to have an associated left comminuted femur fracture. CT of the cervical spine showed concomitant atlanto-occipital and atlanto-axial dissociation (Figure ). MRI of the cervical spine confirmed the diagnosis with total ligamentous disruption at the craniovertebral junction (CVJ) and distraction of the atlanto-axial joints bilaterally (Figures -). While the CCI was normal (1.2 mm), the BDI was 19 mm, which is diagnostic of AOD.
The patient was immobilized with a crown-halo vest and a posterior occipitocervical fusion was performed urgently (Figure ). The patient then was discharged on a rigid collar and followed up in the clinic. During her one year appointment, the patient was neurologically normal, reported no neck pain, and denied any dysphagia. |
pmc-6003799-1 | A 71-year-old woman with a history of a right hip intra-capsular fracture in 2006 presented to the emergency department after a fall at her home. In 2006 she had a DHS (dynamic hip screw) as a result of right hip intra-capsular fracture. She developed osteonecrosis which led to a total hip replacement in 2010. Her medical history was relevant for hypertension and had a left mastectomy 25 years ago due to breast cancer. Prior to this episode she denied any trouble with this hip since her surgery in 2010.
Her radiographs demonstrate a Vancouver B3 peri-prosthetic fracture (Figures -), with lateral extrusion of the highly polished double taper stem through the cement mantle and through lateral wall of the proximal femur. Two treatment options were considered;
i) A femoral component revision with an allograft and
ii) A proximal femoral replacement.
The former option is often preferred for low-demand patients with extensive medical co-morbidities, while the latter- while representing a larger surgical insult for the patient- facilitates immediate weight bearing and early rehabilitation.
The patient underwent a both component revision arthroplasty procedure (Figure ); using an the multiple fracture lines already present through the proximal femur in lieu of an extended trochanteric osteotomy, the prosthesis and cement were removed from the proximal femur, and a modular endoprosthesis (LPS ® DePuy Limb Preservation System (Warsaw, IN, USA) proximal femoral replacement) inserted. The acetabular component was also revised. While representing an addition extra step and a slightly increased magnitude of the surgical insult, it allows use of a larger head, and the optimsation of any version issues to reduce the risk of post-operative dislocation. An additional trochanteric claw plate was used to re-attach the bone of the proximal femur to the prosthesis, thus ensuring good abductor function. The patient tolerated the surgery without incident. She was able to commence immediate full weight-bearing, protected with a Zimmer frame, on postoperative day one. At her six-week postoperative evaluation, she was ambulating independently, though had continued with the use of her walking frame for ‘balance and confidence’. |
pmc-6003800-1 | A 59-year-old left-handed female with a history of hypertension, steatohepatitis, hypothyroidism, and obstructive sleep apnea (OSA) was brought to the emergency department (ED) with progressive altered mental status, abulia, and inability to care for herself. The family reported inadequate dietary intake and increasing forgetfulness in the last week. Her history was significant for laparoscopic Roux-en-Y gastric bypass bariatric surgery one month prior. The post-operative course was uneventful, and she was discharged home with normal mental status on nightly continuous positive airway pressure (CPAP). Three days later she was brought to the ED in a lethargic state after falling out of bed in the setting of CPAP noncompliance. She was admitted to the surgical intensive care unit for acute hypoxic respiratory failure and was intubated. Computed tomography (CT) chest only showed small bilateral pleural effusions. She was eventually extubated and placed on a regimen of CPAP when asleep and transferred to the regular nursing floor. Despite adequate oxygenation, the patient remained arousable but disoriented with decreased attention span. Cranial nerve, motor and sensory examinations were normal. Magnetic resonance imaging (MRI) brain showed nonspecific white matter disease of the centrum semiovale (Figure ).
Lumbar puncture revealed an elevated myelin basic protein. Her vitamin D-25 and methylmalonic acid levels were low. Her thyroid function workup was consistent with hypothyroidism. The rest of her metabolic workup was unremarkable. She was eventually discharged to a skilled nursing facility (SNF) with neurology follow-up. |
pmc-6003800-2 | A 71-year-old female with a history of in situ ovarian adenocarcinoma status post appendectomy and right-sided hemicolectomy developed generalized tonic-clonic seizure activity. An initial seizure was noted while undergoing an endobronchial biopsy procedure for evaluation of a perihilar mass. Pathology was consistent with a benign reactive lymph node. During the procedure, she developed mottled discoloration of her skin, spreading from her abdomen to both shoulders. Bag ventilation was started, and she was transferred to the surgical intensive care unit (ICU) and intubated. CT head revealed multiple air emboli (Figure ).
Continuous electroencephalography (CEEG) monitoring revealed frequent periodic lateralized epileptiform discharges. Her anti-epileptic medication was rapidly escalated to pentobarbital in addition to levetiracetam, lacosamide, and phenytoin. Her Glasgow Coma Scale was 3 (E:1;V:1;M:1). Neurological examination was significant for sluggish but reactive bilateral pupils and areflexic quadriplegia. She was transferred to the neurological ICU at that time. Her neurological examination remained same thereafter. On day 14 of her admission, EEG showed changes consistent with bilateral cortical dysfunction in bifrontal regions indicating severe diffuse encephalopathy. No seizure activity was noted on EEG. Cerebrospinal fluid (CSF) analysis revealed an elevated myelin basic protein but with undetected white blood cells (WBCs), red blood cells (RBCs), and negative cytology. MRI brain scan the following day showed progressive diffuse white matter changes in a watershed distribution and centrum semiovale (Figure ).
She was weaned from her antiepileptic regimen to levetiracetam monotherapy. She slowly improved, but required tracheostomy and percutaneous gastrostomy tube. She was eventually transferred to an acute rehabilitation facility. |
pmc-6003802-1 | An 87-year-old Caucasian male with a past medical history of benign prostatic hyperplasia and irritable bowel syndrome presented to the hospital with urinary incontinence, diarrhea, abdominal pain, hypotension and altered mental status. A diagnosis of septic shock secondary to urinary tract infection was made on arrival based on symptomology and initial investigation. The patient had a history of lower abdominal pain for last two weeks. He visited his primary care physician and underwent a computed tomography (CT) scan of the abdomen and pelvis which showed hypertrophy of the prostate and bilateral hydronephrosis. The patient had progression of symptoms leading to hospitalization. On arrival to the hospital, the patient was hemodynamically stable but quickly decompensated. Vitals showed a blood pressure of 88/55 mmHg, heart rate of 143 beats per minute, respiratory rate of 20 breaths per minute, and temperature of 96.3°F. Initial pertinent laboratory findings included acute kidney injury with serum creatinine of 12 mg/dL (from a baseline of 1.2 mg/dL) and blood urea nitrogen (BUN) of 161 mg/dL. Labs demonstrated an anion gap metabolic acidosis secondary to lactic acidosis. Urinalysis showed evidence of infection, and blood and urine samples sent for cultures. Physical exam at arrival was significant for a minor distress, diaphoresis, enlarged and tender prostate, abdominal distension without tenderness to palpation, guarding, rebound tenderness, or abnormal dermatological findings. The white blood cell values from the day of surgery until discharge are detailed in Table .
The patient received empiric intravenous antibiotics and fluid resuscitation in the emergency department along with placement of a urinary catheter to relieve urinary obstruction. Urinary catheter placement revealed gross hematuria, but hematuria resolved by the next day. Blood and urine cultures were positive for E. coli and initial antibiotics were deescalated to ceftriaxone, to which the organism was sensitive.
No acute cardiopulmonary changes were visualized on chest X-ray taken three days prior (Figure ).
On day five of his admission, the patient experienced increased abdominal pain, constipation, and subjective fevers. Vitals showed a temperature of 97.2°F, a blood pressure of 111/70 mmHg, a pulse of 87 beats per minute, respiratory rate of 20 respirations per minute, and oxygen saturation of 97%. Abdominal exam was significant for hypoactive bowel sounds, mild distension, guarding, tympany on percussion, and diffuse tenderness to palpation. An upright chest X-ray was ordered. Upright chest X-ray revealed free intraperitoneal air (Figure ).
An abdominal X-ray showed a nonobstructive bowel gas pattern without signs of dilated loops of bowel or air-fluid levels. The surgical team was emergently consulted for evaluation of pneumoperitoneum, and an urgent exploratory laparoscopy was recommended without further evaluation or imaging. The patient underwent emergent exploratory laparoscopy that was converted to laparotomy, as there was no evidence of a perforation visualized on laparoscopy. Meticulous examination of the abdominal cavity revealed no evidence of an intestinal or genitourinary tract perforation or any other surgical causes, peritonitis, free fluid, or abscess formation. Post-operative X-ray, completed on post-operation day one, demonstrated resolution of the pneumoperitoneum (Figure ). |
pmc-6003803-1 | History and physical examination
A 75-year-old female with a past medical history of fibromyalgia and Sjogren’s syndrome presented to the emergency department with severe hypertension. The patient was not taking any medication at home.
On physical examination, the patient was in slight distress. The vitals were as follows: blood pressure of 182/91 mmHg, heart rate of 72 beats per minute, respiratory rate of 15 breaths per minute, and oxygen saturation of 93% on room air. The patient had 2+ pitting edema of lower extremities. The rest of the physical examination was unremarkable.
Hospital course
The blood pressure of the patient improved after giving hydralazine and clonidine. Nephrology was consulted for evaluation of increased creatinine (3.8 mg/dl) with blood urea nitrogen of 29 mg/dl. Review of the past medical record in the hospital showed her creatinine level of 2.5 mg/dl, a year ago. Further workup revealed 24-hour proteinuria of 3.89 grams. Urine dipstick showed 3+ protein, 5-10 red blood cells and 10-15 white blood cells per high power field.
Considering the past medical history of Sjogren’s syndrome, the patient was suspected to have acute interstitial nephritis or possible immune-complex-mediated disease. Her C3 and C4 complement levels were low. Serum immunofixation did not reveal any monoclonal immunoglobulin. Serologies for antinuclear antibody was positive (titer, 1:640), negative for anti-double-stranded DNA, hepatitis B and C, and antineutrophilic cytoplasmic antibodies.
On light microscopy (LM), three glomeruli were present for evaluation, two of which were globally sclerotic and one showed segmental scarring. The segmental lesion had an accompanying fibrous reaction, suggestive of a possible healed/fibrous crescent. The glomeruli also featured noticeable mesangial expansion, which was negative for Silver methenamine and positive for Periodic acid-Schiff (PAS) staining. Congo-red stain was also negative. No capillary wall deposits were seen on special stains and no active necrotizing or crescent lesions were present. Moderate interstitial fibrosis was present in the interstitium. Furthermore, moderate intimal fibrosis was seen in vessels, with no thrombosis or vasculitis.
Immunofluorescent (IF) showed diffuse global 3+ smudgy mesangial; the capillary wall was positivity noted with immunoglobulin G (IgG) (Figure ). Glomerular staining showed 1+ IgM, C1q, 2+ C3, 1+ staining with both kappa and lambda light chains (Figure ). IgG and albumin stained protein reabsorption granules in the tubular cytoplasm were noted. No significant staining was seen with fibrinogen.
EM confirmed the presence of extensive electron dense deposits in the expanded mesangial regions and throughout the thickened glomerular basement membranes (Figures -). These deposits had a distinct fibrillary substructure and they did not show any transmembranous spicule formation. No extra-glomerular deposits were seen. |
pmc-6003805-1 | A 49-year-old woman with a past medical history of hypertension, preeclampsia, anxiety, and bipolar disorder on buspirone, presented to the emergency department with triage complaint of “multiple complaints”. Her history of present illness revealed a persistent headache that initially started one week prior to arrival. The patient recalled onset in the evening associated with nausea and vomiting. She went to an urgent care the next day and received medications, after which she felt better for about two days. When her symptoms recurred, she went to an outside hospital where she had a computed tomography scan of the head and lumbar puncture, both of which were negative. The patient was admitted for an elevated troponin level and received a cardiac catheterization without intervention, findings significant for 60% blockage of a single vessel. The patient presented to us one day post discharge due to persistent headache. She described the headache as similar to her prior preeclampsia headache, feeling "like a grip around" her entire head.
Her initial vital signs were as follows: blood pressure 172/92 mmHg, pulse 81, respiratory rate 18, and oxygen saturation 99% on room air. A physical exam revealed a woman in pain but nontoxic appearing. Her heart and lung sounds were normal. Her neurological exam was unremarkable with no focal numbness, weakness, or abnormalities with coordination, gait, or cranial nerves. The chest plain film, initial lab, and electrocardiogram results were normal.
The patient received one liter intravenous fluids, metoclopramide intravenous, and ketorolac intravenous with minimal improvement and still appeared uncomfortable on multiple reassessments. The patient was placed in the observation unit and a magnetic resonance imaging (MRI) of the brain was ordered.
The magnetic resonance imaging (MRI) of the brain showed three punctate regions of focal restricted diffusion in the left middle frontal gyrus, right parietal lobe, and left temporal lobe that appeared consistent with acute infarcts. The image is provided below (Figure ).
Neurology was consulted and the patient was admitted to the stroke service. Her stroke workup, which included computed tomography angiography of the head and neck, transthoracic echocardiogram, and a transesophageal echocardiogram, was unremarkable. The differential at that point was narrowed down to vasculitis versus RCVS as the cause of the severe headache associated with acute infarction. Neurosurgery was consulted and an angiogram was performed, showing evidence of RCVS in the middle cerebral artery, M1 segment, and distal middle cerebral artery territories as well as the right posterior cerebral artery and distal anterior cerebral artery. Dual antiplatelet therapy with aspirin and clopidogrel was initiated and the patient was discharged to follow up with the stroke clinic and her primary care provider. |
pmc-6003897-1 | A 71-year-old man was referred to our hospital from his primary physician because of suspected LC. Computed tomography (CT) revealed a primary tumor in the right middle lobe and metastases in the lymph nodes (hilum of the right lung, bifurcation of the trachea, and left side of the neck), brain, both adrenal glands, and bones (Fig. ). Pathological examination of a needle biopsy of the left cervical lymph node clearly revealed adenocarcinoma. Immunohistological findings showed positive staining of cytokeratin 7 and thyroid transcription factor 1 (TTF-1) and negative staining of cytokeratin 20. Therefore, we definitively diagnosed pulmonary adenocarcinoma and multiple metastases. His LC was categorized as stage IVB (T2a N3 M1c) according to the TNM classification [].
This patient received chemotherapy with carboplatin, paclitaxel, and bevacizumab. One month later, he presented with right lower quadrant pain when he visited our hospital to receive his scheduled chemotherapy. His serum level of C-reactive protein was clearly increased at 11.67 mg/dL, although his white blood cell count was within the normal range. Enhanced CT findings showed an enlarged appendix and fluid collection near the distal appendix (Fig. ). A diagnosis of AA was made, and laparoscopic appendectomy was promptly performed. A swollen appendix and pus collection were clearly observed during surgery (Fig. ). Laparoscopic survey of the abdominal cavity revealed no additional metastases (e.g., appendiceal tumor or peritoneal dissemination).
Histological analysis by hematoxylin eosin staining revealed invasive adenocarcinoma in the appendix that infiltrated the mucosal, submucosal, and muscular layers. Positive immunostaining of TTF-1 indicated that the appendiceal metastasis was from pulmonary adenocarcinoma, not a primary appendiceal malignancy (Fig. ).
The postoperative course was uneventful, and the patient was discharged on postoperative day 7. The patient’s pulmonary internist resumed continuous chemotherapy after surgery. |
pmc-6004088-1 | Our patient was a 19-year-old primigravida Greek Pomak woman who was recently diagnosed as having hereditary AT deficiency. She had been previously referred for thrombophilia testing, due to a history of two first trimester pregnancy losses. She had no history of deep vein thrombosis (VTE), but her mother had suffered from postpartum VTE at a young age. Her basic screening for thrombophilia was normal: protein C, free protein S, AT, activated protein C (APC) resistance, lupus anticoagulant, FV Leiden, factor II (FII) G20210A mutation, fasting serum homocysteine, anticardiolipin antibodies, anti-beta-2 glycoprotein 1 (anti-b2 GP1) antibodies; however, she showed an AT activity of 51% (normal range 70–120%; chromogenic Liquid Antithrombin; Instrumentation Laboratory, Milano, Italy). Her mother and two out of three of her siblings were also found to have AT deficiency, so a diagnosis of hereditary heterozygous AT deficiency was established. AT antigen testing was not available so we cannot classify the disorder as type I or II deficiency.
Three months after diagnosis she was pregnant again. We decided to manage her with adjusted dose of low molecular weight heparin (LMWH) throughout pregnancy due to the high incidence of fetomaternal complications in this disorder and our patient’s history of miscarriages. She was monitored monthly with d-dimers, AT activity, and anti-Xa measurements (liquid anti-Xa, one-stage chromogenic assay with no exogenous AT; Instrumentation Laboratory, Milano, Italy). After titrating tinzaparin dose, using chromogenic anti-Xa activity, she continued with a daily dose of 14,000 IU applied subcutaneously. With this dose the peak anti-Xa activity ranged between 0.46 and 0.79 IU/ml during the first 6 months of pregnancy, which was in great discordance with her body weight of 50 kg. This was attributed to the well-known heparin resistance phenomenon in patients with AT deficiency. During the last trimester anti-Xa activity dropped and ranged between 0.23 and 0.45 IU/ml. An attempt to raise the heparin dose did not result in significant increase in anti-Xa, but further decreased the AT levels; so we resumed the 14,000 IU dose. Throughout pregnancy d-dimers were low (93–317 μg/L) and AT was 33–35% until the 28th week, rising to 46–57% thereafter. Her pregnancy was uneventful. A cesarean section was scheduled at the 39th week due to breech presentation of the fetus. The last tinzaparin dose was given 24 hours before surgery. Prior to delivery, AT activity was 54%. In order to overcome the risk of thrombosis, 3 hours before delivery she received Kybernin P (human AT III concentrate; CSL Behring) prophylactically at a dose of 3000 IU intravenously administered, calculated according to current recommendations as follows: concentrate dose = (120% − current AT(%)) × body weight (kg) divided by 1.4. She proceeded to have general anesthesia and received tinzaparin subcutaneously 8 hours later at the conventional dose of 4500 IU. She delivered a healthy, 2610 g weight, small for gestational age male baby, who was also tested a year later and was found to have normal AT levels. There was no increased bleeding during and after caesarean section. Her AT level 2 hours after infusion was 112% and trough level the next day was 65%. Functional AT levels were measured daily prior to each dose of AT and levels were maintained between 60 and 100% by using approximately 66% of the initial AT dose or 2000 IU. We planned to administer AT for 6 days, according to various literature data, but in total she received AT for 4 days because she developed an allergic reaction after the fifth dose, so AT was discontinued and tinzaparin increased at the prior dose of 14,000 IU/day. She was discharged 6 days after delivery without complications and tinzaparin 4500 IU daily was continued for 6 weeks postpartum. |
pmc-6004287-1 | A 56-year-old Chinese Han female presented to Shanghai Dermatology Hospital in 2016 with symptoms of erythematous plaques and pain over her left upper limb for 2 days and foreign object sensation in the throat when swallowing for 3 days. The patient had a 6-year history of leprosy. She was diagnosed with BB in 2011 and received multidrug therapy (MDT) (600 mg of rifampin and 300 mg of clofazimine monthly; 100 mg of dapsone and 50 mg of clofazimine daily) for 1 year, resulting in a clinical cure in 2012.
T1LR were initially considered, followed by treatment with 20 mg/day of methylprednisolone given orally. Two days later, the patient’s symptoms were aggravated, with neck muscle tension and difficulty in opening her mouth, and the erythematous plaques had spread over most of her left upper limb.
On physical examination, the patient had a normal blood pressure and pulse with a temperature of 37.8 °C, but she displayed shortness of breath. Her facial expressions included a wry smile and trismus, with the corners of her mouth pulling outward and upward, and she had difficulty speaking. The patient’s abdominal muscles were too stiff for palpation of the patient’s liver and spleen. Persistent stiffness was found in the neck and four limbs, together with opisthotonus and occasional paroxysmal spasms. Anesthetic erythematous plaques were observed over her left upper limb (Fig. ). The bilateral ulnar nerves and right common peroneal nerve were thickened and exhibited tenderness. The patient exhibited right foot drop, atrophy of the extensor of the right lower leg, and an ulcer on the right foot. Laboratory examinations showed a white cell count of 12 000/mm3 (reference value: 3690–9160/mm3) and neutrophils 81% (reference value: 50–70%). Her liver and renal function tests were normal. Slit skin smears showed the presence of acid-fast bacilli ranging from negative to a score of 1+ at 6 different sites. According to her medical history and clinical symptoms, she was diagnosed with tetanus and BT accompanying T1LR.
This patient was given the following: 100 000 IU tetanus antitoxin in a 500-ml 5% glucose-saline intravenous infusion daily; 200 000 U penicillin in an intramuscular injection four times a day; and 200 mg of hydrocortisone in a 250-ml 5% glucose intravenous infusion daily. Additionally, 10 mg/day of diazepam and 50 mg/day of phenergan were given by intramuscular injection. The patient was hospitalized in a dark, quiet room to reduce light stimulation and prevent spasms. In addition, a dental pad was placed in the oral cavity to prevent the patient from biting her tongue. The ulcer on her right foot was debrided every day, followed by rinsing with 3% hydrogen peroxide and injection of 20 000 IU tetanus antitoxin around the wound. The paroxysmal spasticity and intensity of the spasms started to decrease after 5 days. Twelve days later, she was discharged from the hospital in stable condition. She was followed up in our outpatient department and treated with MDT and 40 mg/day of prednisone orally with taper to prevent T1LR for 4 months; the erythematous plaques and neuropathic pain eventually subsided. |
pmc-6004288-1 | A 39-year-old Italian man presented to our department suffering from headache and nausea over the past months. CT and MRI revealed an ill-defined, 39 × 37 × 29 mm (anterior-posterior×transverse×cranial-caudal) tumor. On CT, the lesion presented as slightly hypointense with poor contrast enhancement. On MRI, a hyperintensity on fluid-attenuated inversion recovery (FLAIR) sequence and on T2-weighted imaging was detected. On T1-weighted imaging, the lesion showed a hypointensity. The lesion showed poor contrast enhancement of the right cerebellar hemisphere without an obstructive hydrocephalus on T1-weighted images with contrast enhancement (Fig. ).
Our patient did not suffer from any other comorbidities; he had not undergone any surgeries. He did not use medication. He had never consumed alcohol, smoked tobacco, or used other drugs. He is married, has two children, and works as a cook in a family owned restaurant. Similar cases were not reported in his family; no relatives had suffered from a tumor in the past. Neurological examinations at admission showed no sensorimotor deficits, no cranial nerve deficits, normal response of his reflexes, and normal standing and walking abilities without any unstableness. Blood pressure, pulse, temperature, and laboratory findings (that is, complete blood count, liver function, renal function, and C-reactive protein) were within normal range.
Surgery was indicated and written consent was obtained. Surgery was performed under general anesthesia with our patient in a semi-sitting position. Monitoring was done with somatosensory and muscle-evoked potentials. A right-sided suboccipital craniotomy was performed. On intraoperative examination, we observed a glassy gray-black tumor that was not well demarcated from the surrounding tissue. Piecemeal tumor removal was performed by microsurgical technique using the Sonoca 300 (Söring GmBH, Quickborn, Germany).
A postoperative CT scan revealed a regular finding without hydrocephalus and hemorrhage. Our patient was observed in our neurosurgical intensive care unit for one night and was transferred to a general ward the following day without neurological deficiency. Postoperative MRI, which was performed 48 hours after surgery, showed no residual tumor. His postoperative course was uneventful. He received no adjuvant treatment and there has been no evidence of tumor recurrence over a period of 15 months (Fig. ). A neurological examination at last follow-up, 15 months after surgery, revealed no neurological deficits. The preoperative nausea and headache he experienced had stopped.
On histopathological examination, hematoxylin and eosin-stained paraffin sections showed predominantly small to moderately cellular tumor growing compactly, sometimes diffuse, infiltrating the surrounding cerebellar tissue. Tumor cells contained mainly light eosinophilic, sometimes clear, cytoplasm and round to oval nuclei and smaller nucleoli. Some tumor cells showed an astrocytic differentiation. Furthermore, around 10% of the tumor area comprised focal lipidized cells (Fig. ). No significant mitotic activity, < 1 mitosis/20 high-power field (HPF), and no necrosis were observed. In immunohistochemical analysis NeuN (Fig. ) was detected in 80% and synaptophysin (Fig. ) was detected in 30% of the non-lipomatous cells. Tumor cells were negative for neurofilament (Fig. ; surrounding CNS tissue stained positive) and chromogranin A. Glial fibrillary acid protein (GFAP) was observed in 20% of the tumor cells (Fig. ). Ki-67/MIB-1 proliferation index (Fig. ), as determined by nuclear MIB1 monoclonal antibody staining, was around 2% (Fig. ). |
pmc-6004679-1 | A 60-year-old white unmarried man with chronic schizophrenia fell to the floor and was unable to get up or walk. When examined he had an asymmetrical smile and apparent paresis of his left leg. He was hospitalized with a tentative diagnosis of stroke.
From his relatives we learned that he had grown up in a village on the Norwegian coastline as the fourth of five siblings. He did not excel at school, and started at an early age to work in the local fishing industry. He held the job until at the age of 30 he moved to another part of the country. There he worked as a custodian at a hotel. At age 37 he went back to his home village to live close to his compassionate family of origin. He was then employed as an assistant custodian (supported employment) in the local fishing industry until he was 56-years old. He was treated for psychotic symptoms on-and-off from his mid-twenties. He was not diagnosed as having schizophrenia until he was 40-years old. Since then he received out-patient psychiatric treatment until the present illness occurred. At the age of 55, diabetes mellitus type 2 was diagnosed. Osteoporosis was diagnosed 2–3 months prior to the present illness.
This was the first time he had been hospitalized. His family members said that he had had swallowing problems, difficulties with speech, and unsteady gait for the last 4–5 years. This information was corroborated by our patient’s general practitioner. He had deteriorated physically over the last 3–4 months with increased fatigue. He had developed general inertia and was easily exhausted after a short period of physical labor. He had developed hypersomnia, with 10–12 hours of sleep per night, a weight loss of 4–5 kg, and an unsteady gait. To descend the stairs he preferred to sit on his buttocks and slide down the staircase one step at a time until reaching the lower floor. He had been a heavy tobacco smoker for several decades. His alcohol use was modest.
His main psychiatric symptoms before being hospitalized were social withdrawal and delusions about several small persons, the size of dolls, attached to his body. Furthermore, he had auditory and visual hallucinations. He was very reluctant to talk about the contents of the, probably imperative, auditory hallucinations. Antipsychotic medication, risperidone tablets, was first started in 1997. A year later the medication was switched to olanzapine tablets. The dosage varied between 7.5 and 15 mg per day without any objective or subjective side effects. There had been no unambiguous extrapyramidal side effects.
On physical examination, he was alert and orientated, but in some pain in his left hip and knee. He was afebrile with a body temperature (ear) of 37.4 °C, blood pressure was 136/83 mmHg, he had a regular pulse rate at 82 per minute, and oxygen saturation (SaO2) was 97%. Auscultation of his carotid arteries revealed no bruits. His heart rhythm was regular without any pulse deficit. There were no heart murmurs. A lung examination was suboptimal as inspiration was weak. It was possible that some crackles could be heard bilaterally at the base of his lungs. A neurological examination revealed impaired tongue wiggling when tested for quick side-to-side movements, dysarthria, symmetrically reduced muscle force (5−/4+) in his upper extremities, reduced force in his left leg (not quantified), and asymmetrical plantar reflexes (downward movement on the right side, indifferent on the left). His regular medication before admission was olanzapine tablets 12.5 mg/day (7.5 mg + 5 mg), metformin tablets 500 mg three times a day, calcium/cholecalciferol 500 mg/400 IU tablets two times a day, and paracetamol 500 mg two times a day. His complete blood count was normal: hemoglobin (Hgb) was 14.0 g/dL, hematocrit was 0.44, his white blood cell count was 8.2 × 109/L, his platelet count was 275 × 109/L, his neutrophil count was 5.6 × 109/L, his lymphocyte count was 1.5 × 109/L, his monocyte count was 0.7 × 109/L, his eosinophil count was 0.4 × 109/L, and his basophil count was < 0.1 × 109/L. The only pathological tests from the chemistry panel were a low creatinine level of 59 μmol/L (reference range, 60–105), a high glucose level of 10.0 mmol/L (reference range, 4.0–6.0), a high glycated hemoglobin (HbA1c) level of 7.5% (reference range 4.3–6.1), a high alanine transaminase level of 94 U/L (reference range 10–70), and a high alkaline phosphatase level of 130 U/L (reference range 35–105). Urine, collected from a urine catheter on the day of admission, was delivered immediately to the microbiology laboratory in the same hospital building, and cultivated. There were > 100,000 bacteria per ml, identified as Staphylococcus epidermidis, probably representing contamination. There was no bacterial growth in a repeat urine test taken 3 days later.
The day after admission a left dislocated hip fracture was identified. This information, in combination with a normal cerebral magnetic resonance imaging (MRI) and disappearance of his facial asymmetry, caused the clinicians to reject the stroke hypothesis. His hip fracture was operated on the following day. Antibiotic medication (cefalotin 2 grams administered intravenously) was given twice: at the beginning and at the end of the surgery. Blood cultures with two sets, each consisting of one aerobic and one anaerobic bottle (Virtuo® blood culture, bioMérieux), were taken from his antecubital veins the day after admission. The cultures were brought to the microbiology laboratory immediately for further cultivation. No bacterial growth was seen.
Although the hip surgery was technically successful, it was not possible to physically mobilize our patient. The 12th day after hospital admission, a psychiatrist was consulted as our patient suffered from clouding of consciousness, episodic agitation, and increased anxiety. Olanzapine tablets were increased from 12.5 mg to 15 mg per day. On day 15 he was transferred to an acute psychiatric ward as it was considered the appropriate place for further treatment. This was unsuccessful as he deteriorated physically. As a consequence, he was returned to the intensive care unit. He was diagnosed as having bilateral lung emboli and suspected sepsis. New blood cultures were taken. Cefotaxime administered intravenously, 1 g three times a day, was started on day 18. Two days later, the cefotaxime dosage was increased to 2 g three times a day. The blood cultures revealed no growth.
Unfortunately, from now on a clinical downhill course followed. Our patient got aspiration pneumonia and was unable to swallow food or fluids. It was decided to stop further oral nutrition (fluids, food, pills) in an attempt to prevent further aspirations to his lungs. Instead, total parenteral nutrition was started. The tentative neurological diagnoses being discussed at this point were motor neuron disease, diabetic neuropathy, and extrapyramidal side effects of antipsychotics.
On the 20th day, a neurological examination found only slightly reduced muscle strength (grade 4–4+) for adduction and abduction of his shoulders bilaterally and a tendency to lead pipe rigidity in his wrist joints. No conclusive diagnosis was made. Three days later (day 23), a repeat neurological examination by another neurologist showed essentially the same clinical picture. The lead pipe rigidity in his upper extremities lessened significantly, almost to normal muscle tone, when our patient managed to relax. However, his wrist joints were strongly flexed and his hands tightly clenched to the bed rails bilaterally. Still, no conclusive neurological diagnosis was made. A videofluoroscopic swallow study and an assessment by a speech therapist were suggested but never performed because he did not regain the ability to cooperate.
The 23rd day was also the time for the second psychiatric consultation at the intensive care unit. Our patient was awake with a clear consciousness. He was oriented for time, place, and situation. Rapport was satisfactory. He was relaxed when engaged in a conversation or otherwise taken care of in his room; when left alone, he was stressed and obviously not at ease. He denied hallucinations. However, his dysarthric speech was a hindrance to an adequate psychiatric evaluation. All in all, there had been some improvement in his psychiatric state since the first psychiatric consultation on the 12th day. Haloperidol tablets, sporadically used as on demand medication to calm him, were discontinued. On the 24th day, metronidazole 500 mg administered intravenously was added to the treatment. Both antibiotics were continued through the 28th day, and then terminated.
On the 38th day the neurologist found that the electromyography (EMG) and nerve conduction studies showed changes consistent with a sensorimotor polyneuropathy affecting his lower extremities. There was no EMG pathology in his upper extremities. The EMG/neurography findings were not compatible with motor neuron disease or acute polyneuropathy. No causal explanation for his dysarthria and dysphagia was found.
The one symptom that he confirmed on all psychiatric consultations (that is, on day 12, 23, 31, 32, 35, and 42 after admission) was anxiety. This was a generalized anxiety with fluctuating intensity that responded satisfactorily to diazepam 2–2.5 mg intravenously administered 4–5 times a day. The anxiety stressed him much more when he was left alone in his room. Having a nurse or a family member nearby calmed him significantly. Apart from adding antibiotics for pneumonia, the regular medication was re-evaluated throughout the course. Antidiabetic treatment was switched from metformin tablets to insulin in order to improve his blood glucose level. The antipsychotic medication (olanzapine) was reduced to 10 mg per day as we suspected the drug to be a cause of his hypersomnia and fatigue. Despite a range of efforts from specialists in orthopedic surgery, hand surgery, anesthesiology, pulmonology, neurology, and psychiatry, our patient did not recover. He died 44 days after being admitted to hospital.
The focus of this case presentation, however, is on the unusual observation of his clenched hands. Thus, we have to step back. During the second psychiatric consultation on day 23 after admission, he was observed clutching his hands onto the side rails of the bed. With some assistance he managed to let go of the rails, but his hands were still tightly clenched. When asked if he could extend his four ulnar fingers he only managed a slight active extension of them, just enough to let the doctor inspect and palpate his palms. On the four later psychiatric consultations, he no longer held onto the side rails. Both hands from now on lay on the duvet with his wrists in palmar flexion, the left one more strongly than the right one. His four ulnar fingers were fully flexed giving the impression of clenched fists (Fig. ).
During these later examinations, he was still unable to open his hands voluntarily. Neither could he extend his wrists. On testing for passive extension of the wrist joints, proximal and distal interphalangeal joints, and metacarpophalangeal joints of his four ulnar fingers only slight extension was allowed for. His thumbs, however, could be fully extended, although with some resistance.
During the extension of his four ulnar fingers there was a resistance that increased proportionally to the force applied by the examiner, giving it an “elastic feel.” Furthermore, there was a non-pitting swelling on the dorsum of his left hand and lower arm. Passive extension of his fingers allowed for examinations of his palms. There was no visible or palpable sign of Dupuytren’s contracture on either side. Neither were there signs of traumas to the hands. However, he had small wounds in the left fossa cubiti caused by syringes and peripheral venous catheters associated with blood test and intravenous infusions. This could have been the culprit for the abovementioned swelling.
The neurological work-up revealed no plausible organic pathology.
Attempts to treat the clenched hands were obsolete as our patient was unable to cooperate in any way. However, he accepted a palliative application of hand orthoses that counteracted the wrist flexion to some degree during the last week of his life. According to information from family members he had had normal function of his hands prior to this hospital stay. They had a theory that his holding his hands clutched on the side rails was his attempt to prevent falling or being pulled out of his bed. Our patient himself could not explain why his hands were clenched. He had no pain in his hands, but he confirmed having more or less continuous anxiety during all six psychiatric consultations. Every attempt at mobilization in order to get him out of bed failed as he resisted both verbally, by crying out, and physically.
On day 42, a junior doctor at the Department of Hand Surgery responded to a request to examine our patient. After discussing the case with her senior colleagues, the doctor could not conclude on any plausible organic disorder. She recommended putting some insulating material between fingertips and palms to prevent maceration and wounding. She also suggested a repeat neurological examination in case he improved.
An autopsy concluded that the cause of death was aspiration pneumonia. In addition, an old infarction was found in the pons and medulla oblongata. Furthermore, there were discrete thickenings of blood vessels and old, small perivascular infarcts consistent with lacunar state in the brain. His relatives had never observed or heard our patient report symptoms compatible with stroke or cerebral insults prior to the current illness course. |
pmc-6005095-1 | A 42 year-old woman was referred to the Master of Endodontics of the University of Santiago de Compostela with a chief complaint of a subgingivally fractured permanent maxillary left central incisor as a result of a domestic accident. Her medical history was unremarkable. Clinical and radiographic examinations were conducted. Clinical examination revealed a heavily restored maxillary left central incisor that was tender to palpation (Fig. A,B) and periapical radiograph and a CBCT revealed an oblique crown-root fracture that extended approximately one-third of the root length (Fig. C,D). Radiographic findings showed periapical radiolucencies in the adjacent upper left lateral incisor and canine (Fig. C), both teeth remaining negative to cold testing. The diagnosis was a globulomaxillary cyst, both teeth were root canal treated (Fig. E) and the cyst enucleated (Fig. F).
In order to regain the lost biologic width, orthodontic extrusion of the fractured permanent maxillary central incisor was required to move the vestibular fracture line approximately 6 mm above the alveolar crest. For the orthodontic extrusion, brackets were attached from upper right first premolar to upper left first premolar. An extrusion of approximately 6 mm was obtained within 6 months (Fig. A) and the extruded tooth was retained for 6 months. Periodontal surgery was performed to recontour the altered gingival and osseous margins at the end of the retention period. The root canal retreatment was performed and a fiber post was placed using a dual-cure cement. The post core was built up with a composite and the tooth was prepared for a crown (Fig. A). During the time it took to obtain the permanent restoration, the tooth was restored with a temporary crown and an external full mouth tooth whitening was performed before determining the shade of the permanent crown. The ceramic crown was seated to the prepared tooth (Fig. B,C) and the upper right central incisor was restored using composite. Good aesthetics were achieved and the patient reported no problems after 4 years of treatment (Fig. D). Patient’s informed consent was obtained. |
pmc-6005096-1 | A 47-year-old caucasian female was referred to the Endodontic Clinic of Dental Faculty at the University of Strasbourg). Her medical history found no outstanding findings that would contribute to treatment problems. Clinical examination revealed that the tooth had a MOD composite restoration. This was tender on percussion, and hence the patient reported periodic episodes of spontaneous pain. The periapical radiographic examination, with an orthoradial projection, showed the presence of a single root with an unusual anatomic variation, suggesting a probable endodontic dilacerated anatomy.
The endodontic treatment was performed in a single session. After local anesthesia, a rubber dam was placed, and endodontic access was performed with a # C 801L 012 round diamond bur (NTI, Kahla, Germany). The lingual and buccal canal orifices were localized with a START X 1 (DentsplySirona Ballaigues, Switzerland) using the operating microscope (Leika M320).
During all instrumentation steps an aqueous 6% NaOCl solution was used for irrigation.
In order to avoid the risk of procedural errors the strategy was was not to use initial manual scouting, but to remove immediately the coronal and middle interferences with initial rotary preflaring to then perform a manual apical scouting of last 2 mm of the root canal.
At first, an initial mechanical preflaring was performed with the OneG (Micromega Besançon, France) until just above the first root canal curvature, using an inward and outward movement, without any pressure, and then with TS1 (Micromega Besançon, France) short of 1mm in regarding to the portion of canal preflared with OneG, using an endodontic engine (300 rpm/2 Ncm).
Thanks to the initial preflaring a #10 stainless steel MMC-file (Micromega Besançon, France) scouted the canal up to working length + 0, 5 mm. Length determination was obtained using an electronic apex locator (Root ZX; J Morita Co, Kyoto, Japan).
At this point of therapy we took a radiograph to allow subsequent execution of the following steps:
Glide path until to a full working length in both the buccal and palatal canals with a One G (300 rpm/5 Ncm) instrument.
Shaping canals in minimal invasive way was performed with TS1 (300 rpm/2 Ncm), 25/04, extending until to full length of the buccal canal, until to the merged point for the palatal canal in order to avoid an apical zip and hazardous stress with the endodontic instrument, especially dangerous when navigating second canal curvatures.
Apical gauging: the foramen was gauged introducing a 25/02 NiTi hand file, which was snug at its working length.
After the shaping procedure, in order to assure a three-dimensionally cleaning of the root canal system, an aqueous 17% solution of EDTA flooded into the pulp chamber was activated using a manual-dynamic activation by of some gutta-percha points for 120 seconds in each canal. After rinsing with physiological saline, a solution 6% of NaOCl flooded into the pulp chamber was activated again using a manual-dynamic activation for 120 seconds in each canal.
The canal system was then dried using sterile paper points. After having applied a drop of Kerr EWT pulp canal sealer (Kerr, Romulus, MI) with a coated paper point at the entrance of each canal, both canals were filled with Thermafil 2. The final radiographs showed two well-obturated canals of this single rooted maxillary premolar (Fig. ). |
pmc-6005096-2 | A 58-year-old caucasian female was referred to the Endodontics Clinic of the University of Strasbourg Dental Faculty for retreatment of a left maxillary second premolar. Endodontic treatment was performed in two sessions. Findings of a clinical examination revealed that the tooth had a prosthetic metal crown, that was tender on percussion with episodes of spontaneous pain.
The periapical radiographic examination, with different angle-shots, showed the presence of only one root with an unusual anatomic variation, and a probable endodontic dilacerated anatomy.
After local anesthesia and crown removal, the walls of the access cavity were reconstructed with SDR composite (DentsplySirona Ballaigues, Switzerland), thanks to the installation of an orthodontic band.
A rubber dam was placed, the buccal and lingual canals were located with Start X1 using an operating microscope (Leika M320) and the previous perforation was visualized.
During the first session the perforation was treated with biodentine.
For this tooth we decided to plane using 2 different shaping techniques in order to compare the two different techniques.
During all instrumentation steps an aqueous 6% NaOCl solution was used for irrigation.
The lingual canal was treated with an usual technique:
manual scouting
glide path
shaping
In order to improve the access to the canal, a SX instrument (DentsplySirona Ballaigues, Switzerland),)(300 rpm/5 Ncm) from ProTaper Universal system was used.
After the use of Sx opener a # 08 stainless steel K-file (DentsplySirona Ballaigues, Switzerland),) wasn’t able to go up to the WL, ), falling 8mm short of the WL.
In order to facilitate the apical scouting a # 10 K file was used short of 9 mm and # 15 K-file short of 10 mm.
So at the second wave # 08 K-file was 7mm short from the WL so again # 10 K file and # 15 K-file were used short of 8 and 9mm, respectively from the WL
After having repeated the scouting sequence numerous times and extensive use of a pre-curved manual K file we ended the scouting step.
A mechanical glide-path with Proglider DentsplySirona Ballaigues, Switzerland), at working length was performed using an endodontic engine (300 rpm/5 Ncm).
Root canal preparation was performed using ProTaper Next X1(DentsplySirona Ballaigues, Switzerland) until to WL and ProTaper Next X2 (operating at 300 rpm and torque of 5 N/cm) until to 2.5 mm shorter from the WL. Then manual 20/02 and 25/02 NiTi hand file (Dentsply/Maillefer) sliding down the glide path up to working length, the shaping procedure finished after 58’ 45’’.
The buccal canal was treated with a modern step down-technique without initial manual scouting:
Initial preflaring above of second curve with in and out movement
Apical scouting
Glide path
Shaping
The initial mechanical preflaring was performed at first with proglider (Dentsplysirona) until to above the first root canal curvature applying an in and out movement, using an endodontic engine (300 rpm/5 Ncm).
Thanks to the initial preflaring using a #10 stainless steel K-file (Dentsply Maillefer) we scouted the canal up to working length + 0. 5 mm. Length determination was taken using an electronic apex locator (Root ZX; J Morita Co, Kyoto, Japan).
A mechanical glide-path with proglider at working length was performed using an endodontic engine (300 rpm/5 Ncm).
Root canal preparation was performed by preparing the root canals to working length with a ProTaper Next X1, a Pro Taper Next X2 (operating at 300 rpm and torque of 5 N/cm) 2.5 mm shorter from the WL. After manual 20/02 nd 25/02 NiTi hand file (Dentsply/Maillefer) sliding down the glide path up to working length. The shaping procedure was finished after 6’ 17’’.
After the shaping procedure, in order to assure a three-dimensionally cleaning of the root canal system, an aqueous 17% solution of EDTA was flooded into the pulp chamber was then activated using a manual-dynamic activation by a gutta-percha point for 120 seconds in each canal. After rinsing with physiological saline, a solution 6% of NaOCl flooded into the pulp chamber was activated using a manual-dynamic activation for 120 seconds in each canal.
Then the canal system was dried using sterile paper points. After having applied a drop of EWT pulp canal sealer (Kerr) with a coated paper point in the entrance of each canal, both sites were filled with Thermafil 25. The final radiographs showed two well-obturated canals, with some lateral canal, of this single rooted maxillary premolar (Fig. ). |
pmc-6005273-1 | An 8-year-old female spayed Dachshund weighing 7.45 kg was presented to the University of Tennessee Veterinary Medical Center with a large, firm, bilaterally symmetrical, painful protrusion in the perineal region that had appeared acutely 2 days before presentation. The dog had a one-month history of dysuria and pollakiuria that was suspected to be a urinary tract infection; when the dog did not respond to amoxicillin-clavulanic acid, a free catch urine sample was submitted for culture. A few colonies of a Staphylococcus organism were grown from the culture, and treatment was changed to marbofloxacin. The dog also had a 2-day history of tenesmus associated with the appearance of the perineal protrusion. The dog had been spayed 2 years prior to presentation after multiple types of unsuccessful breeding.
Physical exam abnormalities revealed an otherwise normal dog with an approximately 5 × 4 × 2 cm firm, painful protrusion on midline of her perineal region, ventral to the anus. A fluid-filled structure was noted ventral to the rectum and distal colon on digital rectal exam; no pelvic diaphragm weakness was palpable, making perineal hernia unlikely. Serum chemistry and complete blood count were unremarkable.
The dog was anesthetized for computed tomography (CT) and vaginoscopy. On abdominal and perineal CT (Figures –), a large, tubular, fluid-filled structure was noted, measuring 4 cm in diameter at its widest point and 16.3 cm long. The structure extended from the perineum cranially, blindly terminating at the level of L5. It occupied the majority of the pelvic canal and much of the caudal abdomen, compressing the colon and rectum dorsally and the urethra ventrally and displacing the bladder within the abdomen to the left of midline. There was also mild dilation of both renal pelves and proximal ureters, which could have been secondary to pyelonephritis or backpressure from the dilated urinary bladder. The structure was interpreted to be the vagina and uterine stump and, based on results of physical exam, blood work, and CT, a hydrocolpos secondary to imperforate hymen was suspected. The ratio of vestibulovaginal junction width to maximal vaginal width was 0.825, ruling out vestibulovaginal stenosis.
On digital vaginal exam, a large, thin-walled, fluctuant structure was palpably filling the vaginal lumen just cranial to the urethral meatus. Digital pressure was used against the wall of the structure to perforate it; approximately 200 mL of brown, mucoid fluid was immediately released from the vulva. A sample was collected for cytology and culture. Within a minute, the drainage had ceased, and vaginoscopy was performed, revealing remnants of an imperforate hymen just cranial to the external urethral orifice. No fluid remained in the distended vagina, and no other abnormalities were seen. The remainder of the hymen was removed endoscopically with grasping forceps and submitted for histopathology.
On cytology, the fluid was moderately cellular, primarily consisting of neutrophils with rare clusters of epithelial cells. No bacteria were seen on cytology, and no organisms were cultured from the fluid. Histologically, the tissue was composed of a dense band of fibrous connective tissue covered by a nonkeratinized stratified squamous epithelium. It contained a medium-sized blood vessel and several smaller blood vessels that were surrounded by rare neutrophils. Findings were consistent with the hymen of a nonpregnant mammal. After recovery, the dog's dysuria, pollakiuria, and perineal swelling resolved. The dog was discharged with instructions to complete the previously prescribed course of marbofloxacin. At follow-up 2 months later, the dog was clinically normal. |
pmc-6005277-1 | Case 1 was a 28 kg, 11-year-old, neutered male Border Collie that presented with malaise, inappetence, and external signs of internal bleeding. Ultrasonography demonstrated a large renal mass and evidence of metastatic spread to the lungs. A biopsy of the renal mass was performed, and histological examination revealed sarcoma of endothelial origin.
Under the care of a licensed veterinarian, this dog was entered into our research protocol employing high dose oral DHEA (60 mg/kg/day) and ubiquinone (0.1 mg/kg/day), in divided daily doses. A dramatic improvement in quality of life (appetite, playfulness) occurred within a few days of initiation of the protocol. The patient was reexamined at biweekly intervals by his veterinarian, and complete blood chemistry panels were routinely performed, without identification of significant abnormalities. By one month of treatment, repeat ultrasonography demonstrated no further growth of the renal mass, that is, stable disease. However, the dog developed a generalized inflammatory condition that involved the skin, eyes, and nasal passages. Skin lesions ranged from nonpruritic maculopapular rash to urticaria, erythema nodosum, and purpura. The oral mucosa was inflamed, and uveitis was prominent. There was also episodic fever and an apparent increase in the patient's arthritis. Because the dog's owner had previously fed him large amounts of vegetable matter rich in phytates, the inflammatory reaction was originally postulated to be due to zinc deficiency caused by phytate sequestering of this critical metal. Zinc deficiency is known to produce symptoms very similar to those observed in this case. However, zinc supplementation did not improve his condition, and alternative causes for the inflammatory reaction were sought.
Based upon our earlier in vitro work [, ], we considered the possibility that inhibition of the mevalonate pathway might be the cause of the autoinflammatory reaction observed. This proved to be the case. Administration of oral, encapsulated geraniol (60/mg/kg/day) was followed by a rapid clearing (3.5 days) of all lesions. This dog survived 315 days from original diagnosis, with pulmonary metastasis being the cause of death. |
pmc-6005277-2 | Case 2 is a four-and-one-half-year-old, 28.4 kg, intact female Doberman pinscher who presented with lameness in her rear right leg in November of 2013. At that time, she was diagnosed with decreased conscious proprioception in the right hind limb. The patient was subsequently referred to the Oregon State University College of Veterinary Medicine in October of 2015 after presenting with non-weight bearing lameness and muscle atrophy on the right hind limb. Radiology of the hips revealed periosteal reaction on the right ischiatic table with a mass-like effect in the adjacent musculature. Ultrasound of the musculature adjacent to the right ischium showed an intramuscular mass. A fine needle aspirate of the mass was performed and confirmed a soft tissue sarcoma. Amputation followed by traditional chemotherapy was recommended, which was declined by the owners of this dog. The patient's hepatorenal values were also noted to be consistently elevated, which would potentially have complicated traditional chemotherapy.
This dog was entered into our G6PD inhibition protocol in October of 2015 and was treated daily with 60 mg/kg/day DHEA and 0.1 mg/kg/day ubiquinone. During treatment, an acute inflammatory reaction involving the eyes was noted (). This was followed by multiple inflammatory cutaneous lesions on the legs, foot pads, and trunk (). These lesions closely resembled those observed in Case 1. Additionally, this dog had intermittent episodes of fever and an apparent increase in arthralgia. Upon administration of oral geraniol (60 mg/kg/day in divided doses for seven days), all symptoms completely subsided. Of note, posttreatment radiographs showed complete tumor regression (). As of May 2017, this patient is alive and well with no evidence of tumor recurrence or recurring inflammation. Incidentally, she became pregnant during high dose DHEA treatment, subsequently delivering five healthy puppies, demonstrating that G6PD inhibition is surprisingly nontoxic to the developing fetus.
Besides the similarity in gross appearance of the skin lesions, histologically both cases showed a neutrophilic exudate, and numerous bacteria (cocci or coccobacilli) were visible in surface keratin and hair follicles. There was a diffuse infiltrate of plasma cells, lymphocytes, neutrophils, macrophages, and eosinophils and, in Case 1, clear hypertrophy of dermal sebaceous and apocrine glands. Additionally, both cases responded to geraniol with clearing of the autoinflammatory lesions. In subsequent studies, it was demonstrated that simultaneous administration of geraniol or other terpenes with DHEA could prevent the formation of such autoinflammatory lesions. |
pmc-6005278-1 | A six-year-old female boxer dog presented with a 13-month history of progressive and mildly pruritic skin lesions. The dog was current on vaccinations and deworming and was being fed on dry commercial food of high quality. Previous treatments included amoxicillin plus clavulanic acid (20 mg/Kg/12 h), cefalexin (25 mg/Kg/12 h) alone or in combination with prednisolone (0.5 mg/Kg/24 h for 1 week and then every other day) for a period of approximately 3 to 4 weeks each, but of no avail. The owner also reported that the dog had intermittently been experiencing nonambulatory lameness on the right front leg.
Physical examination of the dog upon admission revealed no abnormality. On dermatological examination, 9 ulcerated and nonulcerated skin nodules were observed, ranged from 1 to 7 cm in diameter, and distributed mainly over bony prominences of distal extremities and digits of the front legs (), left elbow, and right hock. Other skin lesions included footpad hyperkeratosis, crusting, depigmentation, and erosions ().
At that time the main differentials included infectious or sterile nodules and neoplasia.
Fine needle aspiration (FNA) cytology made from material obtained from nonulcerated skin nodules revealed pyogranulomatous inflammation and numerous mainly extracellular round-shaped organisms, ranging from 20 to 30 μm in diameter, most containing 2 spores of approximately 10 μm in diameter. A tentative diagnosis of systemic mycosis was made. Culture of FNA material in dermatophyte test medium (DTM) was performed at room temperature. Furthermore, skin biopsies were obtained from intact nodules (the owner refused footpad lesions biopsy) along with blood and urine samples for further laboratory workup and serology. Survey thoracic and abdominal radiographs were also taken but were unremarkable.
Hematology, serum biochemistry, and urinalysis did not display any abnormalities and serology (snap ELISA, IDEXX®) for all of Leishmania infantum, Ehrlichia canis, and Anaplasma phagocytophilum antibodies and Dirofilaria immitis antigen was negative. After 4 days of incubation, smooth, creamy, yeastlike colonies were grown on DTM. Light microscopy of lactophenol cotton blue slide preparations made of these colonies revealed round sporangia containing spherical sporangiospores similar to those of P. wickerhamii (). P. zopfii cells are oval or cylindrical in shape, producing sporangia of larger diameter (15–25 μm) containing up to 20 sporangiospores. In contrast, P. wickerhamii cells tend to be round, forming sporangia (7–13 μm) containing up to 50 spherical sporangiospores [].
Histopathology revealed nodular-to-diffuse, pyogranulomatous dermatitis and panniculitis (with lymphocytes, plasma cells, macrophages, and neutrophils) with numerous elements exhibiting Prototheca spp. morphology; their cell wall stained vividly purple with periodic acid Schiff (PAS) stain () and most of microorganisms were extracellular, either single or more often in groups, with only a few seen to be phagocytosed.
Approximately 1 mm3 of culture material was used for DNA isolation, by employing the QIAamp Mini Kit (QIAGEN, Hilden, Germany), and following the manufacturer's instructions. A portion of the 28S rRNA gene was amplified by using already published primers []. The band was excised from the gel and DNA was isolated using the DNA Isolation Spin-Kit Agarose (AppliChem, Darmstadt, Germany). The isolated DNA was subsequently sequenced with the PCR primers; PCR produced a ~350 bp band. As sequencing of the complete length of PCR product was not possible, a 77 bp sequence was obtained by employing the U2 primer. Beyond that fragment the double peaks were indicative of the presence of more than 1 strain. Similar sequences were searched in the GenBank with the aid of the Web interface of Blast software which returned 9 of these sequences that belonged to Prototheca wickerhamii strains; the higher similarity applied to GenBank number AB183198 sequence (). This result confirmed the diagnosis of cutaneous protothecosis due to Prototheca wickerhamii.
As no treatment guidelines are available, the patient was treated with oral fluconazole (10 mg/Kg twice a day), based on reported agents likely to be most useful against Prototheca species such as amphotericin B (AMB), fluconazole, itraconazole, and possibly terbinafine []. Although significant clinical improvement was witnessed in footpad lesions after one month on fluconazole, this treatment regimen did little to slow the progression of skin nodules, because Prototheca organisms were found on cytology. At that time fluconazole administration was withdrawn and AMB was administered twice weekly as a subcutaneous infusion using a protocol developed to treat canine cryptococcosis []. Specifically, 0.5 mg AMB/Kg/sc per dose was administered twice weekly in 500 mL of 0.45% NaCl/2.5% dextrose fluids. The dog was given concurrently itraconazole (5 mg/Kg/per os, once daily). Due to nephrotoxicity, AMB was withdrawn after 7 infusions and the patient is still being treated with itraconazole alone for about six months. However, although skin nodules have not been improved with this treatment regimen, footpads remain close to normal. |
pmc-6005281-1 | A satin 2-year-old female guinea pig weighing 560 g was admitted to a private practice with anorexia, low weight, previous history of cheek teeth overgrowth and coronal reduction of 3 cheek teeth in recent months. Ten months before this visit the guinea pig was attended to for left forelimb lameness and lumbar deformity; a radiologic study was declined by the owner, and the lameness responded to meloxicam (Metacam; Boehringer Ingelheim, Sant Cugat, Spain) (0.3 mg/kg body weight, per os q 12 hrs, 15 days). Diet was appropriate, including nutrients rich in vitamin C.
A physical examination revealed total loss of mobility of the left carpal joint, malocclusion of the incisors, and cheek teeth overgrowth. The radiological study of the head showed mandibular deformation, a marked bone trabecular pattern, areas of sclerosis, and incisor malocclusion. Before sedation achieved with midazolam (Midazolam Normon; Laboratorios Normon, Tres Cantos, Spain) (0.5 mg/kg body weight, intramuscular) and butorphanol (Torbugesic; Zoetis, Alcobendas, Spain) (0.5 mg/kg body weight, intramuscular) urine was obtained by cystocentesis and blood was collected from the cranial vena cava. A hematological (Chemray 120, Rayto, Shenzhen, China) and biochemical (MS4 Vet, Melet Schloesing, Osny, France) panel, hormonal determinations, ionized calcium, and urinalysis were performed (). A whole body radiograph showed deformity, double cortical line, marked trabecular pattern, and loss of definition of the medullary cavity in virtually all of the long bones (). Left carpal synarthrosis and misalignment of the spine at the L5-L6 level were also observed on the radiographs.
A remarkable improvement was observed in the guinea pig's health after incisor and cheek teeth coronal reduction. As long-term management coronal reduction was performed when considered necessary (2-3 times per year), the diet was closely monitored and annual analytical controls were performed (). Three years later, the guinea pig had a good quality of life according to the owner, analytical values were stable (), and radiographs showed hyperostosis, sclerosis, and partial remodeling of the previously affected bone (). |
pmc-6005282-1 | A privately owned two-year-old female guinea pig was referred for a repeated loss of material from the uterus and progressive weight loss. Anamnestically, the animal never conceived despite several attempts at mating. The day of the appointment, the pet expelled a large amount of hemorrhagic material. During the visit, the patient was quiet, depressed, and moderately responsive to stimulation. At physical exam, the patient showed tachypnea, vocalization upon manipulation of the abdomen that was tense, and dilated abdomen with a palpable mass. Ultrasonographic investigation evidenced a large well-defined 2 × 2 cm mass in the anatomic area of the uterus. The guinea pig underwent emergency surgery upon sedation with an association of butorphanol 0.7 mg/kg (Dolorex 10 mg/ml, MSD), medetomidine 0.07 mg/kg (Sedator 1,0 mg/ml, ATI), and ketamine 7 mg/kg (Imalgene 1000 100 mg/ml, MERIAL) administrated intramuscularly. Anesthesia was maintained with isoflurane 3% with a not cuffed endotracheal tube. The procedure was monitored with a multiparameter monitor, including ECG (II derivation) CO2, O2, and no invasive pressure and temperature. During the anesthesia, intravenous fluid (NaCl 0.9%) was administered at the rate of 5 ml/kg/h with infusion pump via intravenous catheter 24 G (Terumo). Surgical examination of the abdomen evidenced an enlarged and congested ovary and uterus and signs of peritonitis, including intra-abdominal fluid. The two organs were excised and submitted for histopathology. The patient was discharged on antibiotic (enrofloxacin 5 mg/kg bid/po Baytril flavour sosp os 25 mg/ml Bayer) and nonsteroidal anti-inflammatory drugs (meloxicam 0.3 mg/kg/sid/po Metacam sosp os 1,5 mg/ml flac 10 ml Boheringer) and ranitidine (3 mg/kg/bid/po Zantadine sol os 30 mg/ml Ceva) []. Histopathologic analysis revealed characteristic features of endometriosis both in the uterus and in the ovary. In detail, adenomyosis was described in the uterus because of the presence of ectopic glandular tissue in the muscular wall of the uterus (). On the other hand, at the level of the ovary, cystic enlargements filled with fluid were seen macroscopically; histologically, these cystic structures presented the classic glandular epithelium of the endometrium with one layer of cuboidal or tall cells, thus representing classic cystic endometriosis of the ovary (). Immunohistochemical staining was performed, by using the ABC method and diaminobenzidine, by means of specific antibodies for estrogen and CD10 in order to confirm the ability of the glandular epithelium to secrete estrogen and the presence of a stromal reaction surrounding the ectopic endometrial tissue (Figures and ) [, ]. The histopathological and immunohistochemical features described are strongly suggestive of endometriosis.
The guinea pig recovered from the surgery and was rechecked on a monthly basis. The patient died of unrelated causes three months later. A necropsy was performed at that time and did not show any sign of endometriosis. |
pmc-6005283-1 | A 3-day-old, 9.5 kg female alpaca cria was presented for progressive weakness and dyspnea of a few hours' duration. The cria had an uneventful birth, stood, nursed, and passed urine and feces normally, but was less active than normal. The cria nursed regularly but only for very short periods. On presentation, the patient was tachycardic (heart rate 148) and appeared to be dyspneic (respiratory rate 28) with cyanosis of the oral mucous membranes and had a capillary refill time of 3 seconds. Cardiac auscultation revealed no significant abnormalities (excluding the tachycardia) and pulse pressure was considered normal. During examination, the cria intermittently lowered its head, became ataxic, and collapsed. These episodes were precipitated by handling or when nursing. After a few moments the cria sat sternal and then stood, appearing normal. Behavior and neurologic exam between episodes were normal. Differential diagnosis included septicemia, pneumonia, choanal atresia, meningitis, persistent fetal circulation, and cardiac abnormalities. No significant abnormalities were noted on complete blood cell count and blood chemistry. Standard lateral thoracic radiographs (evaluated by a board certified veterinary radiologist) revealed slight loss of cranial cardiac waist, distention of the caudal vena cava, and a mild diffuse interstitial lung pattern () without significant evidence of pulmonary venous congestion or overcirculation. A dorsoventral or ventrodorsal view may have provided additional information regarding the heart, but it is not routinely obtained in an unsedated or unanesthetized cria []. An attempt was made to perform upper airway endoscopy to assess for suspected choanal atresia; however, the procedure was aborted as the cria became progressively more distressed. The cria was subsequently anesthetized and placed on 100% oxygen. An endoscopic examination of the nasal passages and distal trachea revealed no significant abnormalities. An arterial blood gas was performed while on oxygen supplementation which revealed a marked hypoxemia (PaO2 19 mmHg, PaCO2 29.6 mmHg, and SaO2% 31.7) making cardiac disease with right to left shunting of blood more likely. As such, with no evidence of respiratory diseases or septicemia as the cause of the clinical signs, a congenital cardiac malformation was highly suspected and a cardiac evaluation was performed.
Two-dimensional (2D) echocardiography, color flow, and spectral Doppler examinations were performed under general anesthesia with an ultrasound unit (Vivid 7, General Electric Medical System, Waukesha, WI, USA) equipped with 1.5–3.6, 2.2–5, and 4.4–10 MHz phased-array transducers. Two-dimensional images revealed severe dilation of the right atrium and ventricle. Thickening of the right ventricle free wall was also identified. No significant dilation of the left atrium or thickening of the left ventricle was noted. The interventricular septum (IVS) was flattened and there was paradoxical motion of the IVS. At the base of the IVS a large ventricular septal defect (VSD) was detected (). Additionally, a patent foramen ovale (PFO) was noted in the atrial septum () and a single large artery overriding the VSD was also identified. The right ventricular outflow tract, origins of the pulmonary arteries, and a patent ductus arteriosus could not be visualized during the echocardiographic examination. Systolic function appeared normal as estimated by 27% fractional shortening (normal 32.8 ± 7.6) []. Color flow Doppler evaluation revealed bidirectional but primarily right to left shunting across both the defect in the atrial septum and VSD. Mild regurgitation across mitral, tricuspid, and the valve of the single large artery was noted. A contrast study was performed by injecting agitated heparinized saline into the external jugular vein while viewing the heart from the right parasternal view. Presence of bubbles from the right heart crossing the VSD into the left heart and main artery during systole confirmed the presence of a right to left shunting VSD (; Supplementary Information: Video 1 and Video 2 in Supplementary Material available online at ). Differential diagnosis based on the echocardiographic findings included Tetralogy of Fallot, severe pulmonic stenosis or pulmonary atresia with a VSD, and common arterial trunk (CAT). Surgical implantation of a vascular shunt and open-heart surgical correction of the malformation was discussed with the owners but due to the poor prognosis and limited treatment options, the owner elected humane euthanasia and postmortem examination.
On macroscopic examination, there was evidence of both right sided (liver congestion and pleural, pericardial, and peritoneal effusion) and left sided (marked pulmonary edema) congestive heart failure. Examination of the heart revealed marked dilation of the right atrium, a small PFO, a large VSD, and a single large vessel overriding the IVS. The vessel had a mildly thickened quadricuspid valve and appeared to be the only outflow tract for both the right and left ventricles consistent with a CAT. A separate pulmonary artery originating from the right ventricular outflow tract could not be identified despite careful dissection. However, a single pulmonary trunk arose from the common trunk prior to the arch and branched to the right and left pulmonary arteries. A patent ductus arteriosus was not identified. Coronary artery structure appeared to be normal. Histological examination identified the presence of pulmonary edema and hepatic congestion consistent with left and right sided congestive heart failure. There was an incidental finding of a cerebellar pseudocyst. Based on the postmortem examination, a diagnosis of a type I CAT (according to Collett and Edwards' classification) and PFO was made. |