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pmc-6043705-1 | A 61-year-old woman presented with a persistent headache for 6 days which started after she received an epidural steroid injection for chronic back pain. The patient had no history of any similar headaches in the past. The headache was described as severe and throbbing. The headache was worse with activity and upright position and improved in the supine position. She rated the severity as 8/10 at peak intensity. The patient underwent magnetic resonance imaging of the brain with gadolinium enhancement that showed the mild descent of cerebellar tonsils through foramen magnum but no dural enhancement. Magnetic resonance venogram was unremarkable showing no evidence of venous sinus thrombosis. The patient underwent epidural blood injection and reported improvement in severity of headaches during upright posture to 5/10 in severity. Headache frequency and intensity were decreased over next 2 days after which she was discharged on pain medication. |
pmc-6043705-2 | A 25-year-old woman underwent fluoroscopic-guided lumbar puncture for new-onset occipital headaches primarily on the right side occasionally radiating to the temporal region. The initial pressure was 10 mmHg by fluid-coupled measurements and 11 cm of H2O by fluid column method. A total of 18 cc of clear CSF was obtained. The final pressure was 6 mmHg by fluid-coupled measurements and 7 cm of H2O by fluid column method. The patient developed headaches (rated as 10/10 in severity) that were exacerbated by upright posture postprocedure. The headache continued for 5 days postprocedure and had not improved with hydromorphone, acetaminophen, decadron, indomethacin, lorazepam, caffeine sodium benzoate, and hydrocodone-acetaminophen treatment. The patient underwent an occipital nerve block which did not reduce the severity of the positional headaches. Magnetic resonance imaging with gadolinium enhancement demonstrated protrusion of cerebellar tonsils through the foramen magnum, slit ventricles, and enhancement of dura. The patient underwent epidural injection of whole blood and reported complete resolution of headaches (0/10) and was able to ambulate without any difficulty. |
pmc-6043705-3 | A 20-year-old woman had a progressively worsening headache since delivery and epidural anesthesia at lumbar 4 and 5 vertebral level 5 days ago. The headache was initially frontal but became diffuse and was associated with nausea and vomiting. The headache was described as 9/10 in severity and worse on standing position and interfered with activities of daily living and sleep. The patient received ibuprofen, intravenous caffeine, caffeine tablets, ketorolac without any significant relief. Magnetic resonance imaging with gadolinium enhancement demonstrates cerebellar tonsils descending through the foramen magnum, slit ventricles, and enhancement of dura. The patient underwent epidural injection of whole blood and reported complete resolution of headaches (0/10) immediately postprocedure. |
pmc-6043705-4 | A 34-year-old woman with past medical history of complex regional pain syndrome developed a frontal headache which progressively worsened over a period of 7 days. She developed fever and nausea and underwent a lumbar puncture as part of the diagnostic evaluation. Multiple attempts were made to sitting position for performing a lumbar puncture and CSF pressure was not measured. She reported worsening headache with localization in the high cervical segment with extension into the occipital and frontal regions after lumbar puncture accompanied by photophobia, nausea, and chest pain. Headache was worse in an upright position with the rated severity of 10/10 and reduced to 5/10 in severity in lying position. Magnetic resonance imaging with gadolinium enhancement demonstrates cerebellar tonsils descending through the foramen magnum, slit ventricles, and enhancement of dura. The patient received oxycodone-acetaminophen, intravenous caffeine, tramadol, and butalbital-acetaminophen-caffeine without any relief. The patient underwent epidural injection of whole blood and reported an immediate complete reduction in of headache severity (4/10) in an upright position with a resolution of photophobia. |
pmc-6043705-5 | A 28-year-old man underwent fluoroscopic-guided lumbar puncture as part of the evaluation of new-onset diffuse headaches for several weeks ago which developed after coitus. The initial pressure was 5 mmHg by fluid-coupled measurements and 11.5 cm of H2O by fluid column method. A total of 10 cc of clear CSF was removed. The final pressure was 2 mmHg by fluid-coupled measurements and 3.5 cm of H2O by fluid column method. After lumbar puncture, he developed a headache which was different from an original headache with clear worsening when the patient was upright. The severity was rated as 8/10 and accompanied by nausea and vomiting. The headache was persistent for 4 days and had not improved with steroids, caffeine infusion, and hydrocodone-acetaminophen treatment. Magnetic resonance imaging with gadolinium enhancement demonstrates cerebellar tonsils descending through the foramen magnum, slit ventricles, and enhancement of dura. The patient underwent epidural injection of whole blood and reported complete resolution of headaches (0/10) and was able to ambulate without any difficulty. |
pmc-6043705-6 | A 34-year-old woman presented with severe episodic headaches that started after giving birth to a child 5 months ago which was rated 5/10 in severity. The headaches were associated with nausea, vomiting, and photophobia with no clear relationship to posture. The patient also reported visual scotomas in both the eyes. Magnetic resonance imaging demonstrated findings of empty sella syndrome but there was no distortion of optic nerves or posterior aspect of the optic globe. The patient had a fluoroscopic-guided lumbar puncture performed to measure CSF pressure to exclude intracranial hypertension. The opening CSF pressure was 7 mmHg by fluid-coupled measurements and 15 cm of H20 by fluid column method. A total of 16 cc of clear CSF was removed. The final pressure was 3 mmHg by fluid-coupled measurements and 5 cm of H2O by fluid column method. The patient reported worsening of headaches postprocedure. The patient described it as a continuous and excruciating headache that progressively worsened was rated as 10/10 in severity. A noncontrast magnetic resonance imaging demonstrated cerebellar tonsils descending into the foramen magnum. A contrast-enhanced computed tomographic scan did not demonstrate any dural enhancement. The patient received caffeine tablets, topiramate, morphine injection, intravenous hydromorphone, and caffeine infusion during admission for pain but had no significant relief. The patient underwent epidural injection of whole blood and reported complete resolution of headaches (0/10) and photophobia after the procedure and was able to ambulate without any difficulty. |
pmc-6043957-1 | A 15-year-old Japanese girl with a diagnosis of adolescent idiopathic scoliosis was admitted to our hospital to undergo posterior spinal fusion at T4–L3. She was a high school student and did not present any symptoms at admission. She did not take any medications prior to the surgery. Her past medical, social, environmental, and family history was not appreciable. She was 147 cm tall, and her weight was 40 kg. She had a Cobb angle of 60 degrees. She had no neurological symptoms. Her temperature was 36.8 °C, her blood pressure was 118/64 mmHg, and her pulse was 92 beats per minute. Laboratory findings at admission were as follows. Her white blood cell count was 6860/μl, red blood cell count 472 × 104/μl, hemoglobin 14.3 g/dl, hematocrit 42.1%, platelets 30.8 × 104/μl, aspartate transaminase 19 IU/L, alanine transaminase 15 IU/L, total bilirubin 0.5 mg/dl, γ-glutamyl transferase 16 IU/L, alkaline phosphatase 371 IU/L, total protein 8.2 g/dl, albumin 5.2 g/dl, blood urea nitrogen 11 mg/dl, creatinine 0.39 mg/dl, sodium 141 mEq/L, potassium 4.5 mEq/L, chloride 102 mEq/L, C-reactive protein 0.01 mg/dl, urinalysis pH 6.0, no uric protein, no urinary sugar, no ketone body, and no uric blood. No microbial examination was performed.
We planned general anesthesia using a target-controlled infusion of propofol and a continuous infusion of remifentanil to record MEPs and somatosensory evoked potentials (SSEPs). In addition, we planned to use both bolus and continuous infusions of ketamine, followed by intravenous patient-controlled fentanyl as postoperative analgesia because we believed that ketamine did not affect MEP monitoring.
After securing an intravenous line in the patient’s forearm, general anesthesia was induced using a target-controlled infusion of propofol 4 μg/ml and remifentanil 0.3 μg/kg/minute. After administration of rocuronium 20 mg, the trachea was intubated using a reinforced endotracheal tube. Thereafter, 1 g of cefazolin sodium was administered intravenously every 3 hours during the surgery and every 12 hours until postoperative day 1.
We started preparation for recording the MEPs and SSEPs. MEPs were evoked by transcranial electrical stimulation (a train of five pulses with an interstimulus interval of 2 milliseconds; supramaximal stimulus, 400 V) with screw electrodes fixed at 2 cm anterior to C3 and C4 (cathode and anode, respectively, following the international 10–20 system). MEPs and SSEPs were recorded using an intraoperative neurophysiologic monitoring system (Neuromaster MEE-1216; Nihon Kohden, Tokyo, Japan). MEPs were recorded bilaterally from the abductor pollicis, quadriceps femoris, tibialis anterior, and flexor hallucis brevis muscles. SSEPs were evoked by stimulation (30 mA) of the sciatic nerve and recorded from 2 cm posterior to Cz (averaging the signals generated by 200 stimulations).
After the patient was turned to a prone position, we confirmed that we could record MEPs from all targeted muscles without difficulty. We maintained general anesthesia using a target-controlled infusion of propofol 3.3 μg/ml and remifentanil 0.2 μg/kg/minute. The patient’s bispectral index values were below 60, and her vital signs were stable. Several minutes before the skin incision was made, the attending anesthesiologist evaluating the MEPs discovered that they were markedly attenuated (Fig. ). The attending anesthesiologist had not changed the propofol infusion rate and had not administered any other drugs except for intravenous bolus administration of ketamine 50 mg (1.25 mg/kg). Ketamine was administered about 3 minutes before the change in MEP waveforms. The patient’s blood pressure, heart rate, peripheral oxygen saturation, end-tidal CO2, and body temperature remained stable. The surgery had not started at that time. About 6 minutes after administration of ketamine, the MEP amplitudes were recovered.
The surgery was performed uneventfully, and the patient had no neurologic deficit when she emerged from general anesthesia. Intravenous patient-controlled analgesia (a combination of fentanyl 25 μg/ml and ketamine 2.5 mg/ml, background infusion 1 ml/hour, bolus 1 ml, and lockout time 10 minutes) was used for postoperative pain management. The patient was discharged on postoperative day 11 without any complications. She was well without complications at 2 years after the surgery. |
pmc-6043999-1 | A 12-year-old boy (height: 51 in.; weight; 44 lbs. 1.5 oz. [20.0 kg]; BMI: 11.93 kg/m2) with a history of Lesch-Nyhan syndrome presented to our office with a 1 ½ month history of dysuria, hematuria, and pain secondary to nephrolithiasis. He suffered from a non-verbal learning disorder associated with a developmental delay, was wheelchair-dependent, and had undergone extraction of 10 teeth due to biting and grinding his teeth. Due to his self-mutilating behavior, he wore braces on his arms and had surgery of his left thumb as a result of biting himself. Two years prior to presentation, the patient underwent a cystoscopy with bilateral ureteroscopy due to xanthine stones. He was stone free following the procedure. The patient’s mother denied a family history of kidney stones, thromboembolism and gout. At the age of 18 months, the boy underwent a test for organic acids in his urine which revealed highly elevated hypoxanthine without an elevation of xanthine and with a slight elevation of uracil. He was diagnosed clinically with Lesch-Nyhan syndrome at that time based on a triad of uric acid overproduction, neurologic dysfunction, and cognitive and behavioral disturbances.
Uric acid crystals were noted intermittently in the patient’s diaper which had increased significantly in the preceding days. He had been treated with the medication allopurinol since he was 2 years old. At the time of presentation, the dose of allopurinol was 200 mg administered once per day. He had never experienced gout. The patient was prescribed potassium citrate.
A renal ultrasound demonstrated multiple calculi in both kidneys with the largest measuring 1.8 cm in the right kidney as well as echogenic material in the medullary pyramids bilaterally suggesting nephrocalcinosis (Fig. ). There were no masses, hydronephrosis, or hydroureter. A urinalysis revealed the following: specific gravity = 1.010; pH = 7.0; leukocyte esterase = 500; trace microscopic hematuria; and negative nitrite. The urine culture was negative. The uric acid level in blood was 2.9 mg/dL (Normal range: 2.5–8.5 mg/dL). Uric acid levels in blood collected in the previous 2 years were all in the normal range, specifically, 5.0 mg/dL, 2.6 mg/dL, and 3.2 mg/dL. There was no evidence of renal failure. The patient underwent six separate urinalyses between the ages of 9 and 12, all of which demonstrated a pH of either 6 or 7.
A CT scan of the abdomen and pelvis demonstrated staghorn calculi in both kidneys, involving all calyces.
The patient underwent a right percutaneous nephrolithotomy (PCNL) 2 months after presentation. During the hospital stay, the patient was noted to be anemic and received 5 days of epogen and iron supplementation. He developed a thrombus in the right cephalic vein and was diagnosed with heterozygous Factor V Leiden with elevated homocysteine (16.2 umol/L [Normal range: 6.6–14.8 umol/L]). The methylene tetrahydrofolate reductase (MTHFR) and prothrombin genes were negative. Folic acid was initiated. The Factor V Leiden mutation was detected through a polymerase chain reaction (PCR) test that utilized microarray-based oligonucleotide hybridization and signal amplification to detect the Factor V Leiden mutation.
Seven weeks later, the patient began experiencing aspiration of liquids, gastroesophageal reflux, and markedly delayed gastric emptying, necessitating a laparoscopic Nissen fundoplication with gastrostomy tube and open pyloroplasty. The patient continued to suffer from nephrolithiasis, with visualization of a left renal calculus greater than 2 cm. A CT scan demonstrated staghorn calculi in the left kidney (Fig. ). He underwent a left PCNL and left nephrostomy tube exchange 6 months after the right-sided procedure. A nephrogram revealed evidence of a filling defect in the lower pole calyx which may represent organizing blood clot or residual stone. Renal ultrasounds performed 6 and 9 months later demonstrated extensive bilateral nephrocalcinosis without hydronephrosis or hydroureter. There was no evidence of calculi in the collecting systems.
The calculi that were removed during the ureteroscopies, the ones that the patient had passed while seen as an outpatient, and those that were sent for analysis following the PCNL were all consistent with xanthine calculi. |
pmc-6044070-1 | A 45-year-old female presented with bilateral upper-quadrant abdominal pain. She is a non-smoker and had no known exposure to asbestos. Family history was significant for peritoneal mesothelioma in two family members—a sister who developed peritoneal mesothelioma at age 29, and a first degree male cousin who developed peritoneal mesothelioma at age 45. Physical examination revealed tenderness in the upper quadrants. Computerized tomography of the abdomen revealed omental stranding in the upper-quadrants (Fig. ). Laparoscopy showed studding and multiple white plaques on the diaphragm and peritoneum with adhesions (Fig. a, b). Biopsies revealed epithelioid malignant mesothelioma (Fig. ). Germline DNA was extracted from a blood sample, DNA extracted and BAP1 testing was performed by polymerase chain reaction followed by Sanger sequencing, as described [, ]. Genetic testing revealed that our patient carried the following inactivating truncating germline BAP1 mutation: chr3.52406884A > G, c.604T > C, p.Trp202Arg. This mutation inactivates the catalytic domain of BAP1, preventing autodeubiquitylation of the BAP1 protein and nuclear translocation [].
She was treated with cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy with cisplatin and doxorubicin, followed by adjuvant systemic chemotherapy, specifically six cycles of cisplatin and pemetrexed. She has been followed by clinical surveillance and utilizing diffusion weighted (DW)-MRI imaging every 6 months. She is doing well without any evidence of recurrence 24 months since treatment.
The identification of a germline BAP1 mutation in this young lady with peritoneal mesothelioma, led to meetings with family members in which we explained the potential advantages and possible disadvantages of genetic testing for BAP1 mutations, consistent with the guidelines of the Consensus report on mesothelioma []. Eight family members elected to get tested: 6 were found to carry the same germline BAP1 mutation. The patient pedigree is illustrated in Fig. . Among them, 2 are tumor free and 1 has well differentiated papillary mesothelioma. Three of the carriers have other BAP1 related malignancies. Those who had not inherited the mutation were reassured that they did not carry a higher risk of developing mesothelioma or other cancers compared to the general population at large. Those who were found to carry germline BAP1 mutations, were informed of the increased risk for mesothelioma and other BAP1-associated cancers, and advised to reduce sun-exposure, minimize radiation exposure, including diagnostic/therapeutic radiation for the increased risk of cancer because of impaired DNA repair and apoptosis, and to avoid trades that could lead to asbestos exposure. In addition two of them had elected to enroll in a screening program, consisting of weighted (DW)-MRI imaging every 12 months utilizing diffusion weighted (DW)-MRI imaging rather than CT scans to avoid radiation exposure. All carriers are also undergoing annual detailed retinal exam by a retina specialist. |
pmc-6044379-1 | A 58-year-old Caucasian woman with no personal history of thyroid disease presented herself to perform a thyroid ultrasound examination.
Routine laboratory tests results were normal. BMI result was 33 kg/m2.
A sister was previously diagnosed of papillary thyroid carcinoma.
Bidimensional ultrasonography (DUS 2) using high frequency probes (13 - 15 MHz) (Toshiba Aplio 500) highlighted a highly suspicious micro-focus of the left lobe, of radial shape with markedly hypoechoic echostructure, irregular margins, size 0.3 cm (classified TI-RADS 5, very high risk lesion ATA guidelines).
(Figure -).
ADF test showed a clear flow through newly formed tortuous vessels at the periphery of the specific micro-focus (Figure , ).
FNAC procedure was proposed to the patient and, after informed consent had been obtained, it was performed under ultrasound guidance (Figure ).
Cytologic examination of the slides (Papanicolaou stain) allowed recognition of malignancy with cytologic pattern very suspicious for papillary tumor (TIR5 cathegory according to Italian Consensus, cathegory VI according to The Bethesda System for Reporting Thyroid Cytopathology (Figure , ).
The patient became candidate for thyroidectomy and subsequently underwent a Total Extracapsular Thiroidectomy procedure (TT). Some enlarged lymph nodes (ENL) were evaluated ultrasonography previous to surgical exploration, and found and removed close to the left inferior thyroid pole at the time of thyroidectomy.
Histological examination of the lesion showed a proliferation of well differentiated epithelial cells forming an purely papillary structure surrounded by blood vessels, with irregular borders, overtly infiltranting thyroid parenchyma.
The neoplasm showed no relationship to thyroid capsule and no vascular or lymphatic invasion. All the lymph nodes retrieved were devoid of metastatic cells (final TNM 8th eds. staging pT1, pN0) (Figure ).
Patient underwent hormonal and tumor markers evaluation plus ultrasonographic evaluation of the neck after 3 months. Post operative remnants therapy with Radioiodine I-131 (RAI), was not administered inasmuch the tumor was very little, contained in the thyroid and lacked vascular invasion. |
pmc-6044477-1 | An 80-year-old male patient was admitted to the emergency ward with the complaints of abdominal distention, vomiting, and constipation for three days. On examination, the patient was dehydrated with stable vital signs. The abdomen was distended with generalised guarding and rigidity. The bowel sounds were not heard. On rectal examination, rectum was empty with minimal fecal staining and no palpable mass lesion. After initial resuscitation, imaging studies, including an ultrasound of the abdomen, were done. Chest X-ray showed air under the diaphragm (Figure ).
Abdominal x-ray showed few air-fluid levels. Ultrasound showed distended bowel loops with significant free fluid in the peritoneal cavity. The patient was diagnosed to have a hollow viscus perforation with peritonitis. Routine blood investigations and blood cultures were done. Renal parameters were deranged suggesting pre-renal failure. Broad spectrum antibiotics were started in view of the high leukocyte counts. The patient was taken up for emergency laparotomy. Intraoperatively, approximately 500 mL fecal-contaminated peritoneal fluid was cleared. There was a 1 x 1 cm2 rent in the rectosigmoid junction (Figure ).
Proximal to the perforation, large bowel loops were distended. Bowel wall thickening was present in the rectosigmoid junction. Distal to the perforation, the rectum was found to be collapsed. The liver and the rest of the intestine were normal. Pelvic deposits/growths were not found. Primary closure of the rent in two layers was done after a thorough peritoneal wash. A diverting transverse colostomy was done after manual bowel decompression. The patient recovered after one week of intensive postoperative care. He was started on oral fluids on the tenth postoperative day and discharged after three weeks of hospital stay. The patient was followed up regularly, and the colostomy closure was done six weeks after the primary surgery. |
pmc-6044478-1 | A male, 52-year-old patient visited the Instituto Nacional de Cancerología (INC) in Bogotá, Colombia, because of the development of a mass in the back region. There had been progressive growth and multiple drainage attempts due to a suspected abscess at various referral sites without relief. He was given non-oncological surgical resection in another institution, and his pathology report was compatible with high-grade sarcoma with positive margins. Additionally, he referred to bilateral vision loss that had been evolving for one month. The initial clinical exam revealed a patient with normal vital signs who was disoriented with regard to space and time though awake and had poor communication with the examiner. He presented a hyperpigmented tumor measuring 10 x 8 cm in the back region, along with a scarred postsurgical lesion without inflammatory signs. The biopsy was reviewed by the INC Pathology Department, which indicated a high-grade sarcoma compatible with myxofibrosarcoma.
He was examined by the Ophthalmology Department, which considered bilateral retinal detachment probable. An abdominal computed tomography (CT) scan was performed, which showed a diffuse density alteration of the subcutaneous cellular tissue, without evidence of lesions, probably due to edema. A chest computed tomography (CT) scan with contrast showed an undefined heterogeneous mass dependent on the soft tissues in the posterior thorax wall, with infiltration signs in the muscular plane and the density alteration of the subcutaneous cellular tissue and skin (See Figure ). He was examined by clinical oncology, surgical oncology, and radiation oncology services, which indicated he was not a candidate for chemotherapy, surgical treatment, or radiotherapy because of the significant extension of the tumor into the upper and lower back, the inadequate response of these tumors to chemotherapy, and the patient’s poor Zubrod performance score.
During inpatient care, the patient showed substantial clinical worsening characterized by the progressive deterioration of his consciousness state and persistent oral cavity bleeding. Laboratory tests were requested, which showed the prolongation of blood clotting time due to extended partial thromboplastin time (PTT), with the test value for prothrombin time (PT) being 11.9 seconds and that for PTT being 50.1 seconds (normal value until 28 seconds). The mixing study showed PTT fixing with a 50:50 normal plasma sample that lasted for the first and second hour, suggesting intrinsic pathway coagulation factor deficiency. Even though the mixing study was not suggestive of the presence of inhibitors, the medical history of the patient, the presence of an active neoplasm, and the recent beginning of bleeding created a clinical suspicion of acquired hemophilia. For these reasons, a new mixing study, VIII factor assay, and Bethesda assay to measure factor VIII inhibitors were requested. In addition, treatment with prednisone at 1 mg/kg/day and factor VIII at 1700 international unit (IU) every 12 hours was initiated. The results of these assays showed a basal PTT of 67 seconds, which with the 50:50 sample with normal plasma, was reduced to 38,2 seconds and maintained at around normal values two hours afterwards, with a value of 36,3 seconds. Factor VIII was measured at 4% and remained at this same value (4%) 10 minutes after the injection of intravenous factor VIII. The specific factor VIII inhibitor assay reported 1.6 Bethesda units. A diagnosis of acquired hemophilia was made based on the presence of hidden low-titer inhibitors in the mixing study.
Based on the findings above, the persistence of oral cavity bleeding, and daily transfusion support in the form of two red blood cell units, IV treatment with an activated prothrombin complex like the factor eight (VIII) inhibitor bypassing activity (FEIBA) at a dose of 3500 units/12 h (50 U/kg every 12 hours) was initiated. During the patient’s evolution, hypofibrinogenemia development, the continuous elevation of D-dimer levels, and progressive thrombocytopenia suggested a diagnosis of disseminated intravascular coagulation (DIC). Because of the unresolved bleeding, it was decided to initiate a transfusion of cryoprecipitate and tranexamic acid oral rinse while augmenting the FEIBA dose. The patient developed a low response to the established treatment, along with more profound neurological impairment (central nervous system bleeding was ruled out) and the persistence of red blood cell, platelet, and cryoprecipitate transfusion requirements. Additionally, the patient had severe hyponatremia in the form of an electrolyte imbalance. Electrolyte correction was initiated, and because of the persistence of bleeding, oral cyclophosphamide was added to the immunosuppressive treatment, with the objective of eradicating the inhibitors. Seven days afterward, because of the lack of clinical response to management and the impossibility of providing specific antineoplastic treatment, with the agreement of the patient´s family, transfusion support was suspended, and palliative care was initiated. The patient died one week after. |
pmc-6044483-1 | The patient was a 41-year-old gentleman with a past medical history of hepatitis C, hemiplegic migraine, and diverticulitis. He was well until 2011 when he first developed a severe headache followed by right-hand weakness and numbness. He was taken to the hospital where a diagnosis of hemipalegic migraine was made. Magnetic resonance imaging (MRI) revealed some white matter changes thought to be secondary to hemiplegic migraine at that time. He recovered complete neurological function with no residual deficits.
On this admission, the patient initially presented to the hospital with right-sided facial droop and weakness in the right lower extremity. The initial computed tomography (CT) scan of the brain was negative for acute bleed. An MRI of the brain was ordered because the patient continued to experience focal neurological deficits including right arm weakness, dysarthria, and decreased cognitive function on neurological examination and neuropsychiatric testing. At this point, it was thought that he had suffered an ischemic stroke, and the MRI showed multiple areas of restricted diffusion suggestive of embolic disease (Figure ). These findings called into question the diagnosis of hemiplegic migraine.
The patient received aspirin after ruling out active bleeding on non-contrast CT of the head. The search for an embolic source included a CT-angiograph of the neck which did not reveal carotid stenosis. He then had a transthoracic echocardiograph and a trans esophageal echocardiograph both of which were unremarkable. The differential diagnosis at that time included transient ischemic attack, ischemic stroke, brain tumors, central nervous system (CNS) infection, CNS vasculitis, inherited disorders including mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), CADASIL, and hereditary telangiectasia. A lumbar puncture was performed for possible meningitis. The cytology was negative and cerebrospinal fluid (CSF) analysis was not suggestive of meningitis, neurosyphilis, or Lyme disease. Lyme serology, the Venereal Disease Research Laboratory test (VDRL), and human immunodeficiency virus (HIV) blood tests were all negative. The CSF was also screened for possible multiple sclerosis, but no oligoclonal bands were detected. At this point, there was a concern for possible vasculitis as the cause of the patient's symptoms. Genetic testing for CADASIL was ordered, but the sample had to be sent out to a lab equipped to perform the genetic test and would take several weeks to return. He was placed on a five-day course of intravenous (IV) methylprednisolone which improved his neurological symptoms. Following completion of his steroid course, it was decided that an alternative to angiogram would be brain biopsy to look for CNS vasculitis. The patient and his family were eager to have an established diagnosis by the end of the hospital course, and the differential diagnosis included CNS vasculitis for which brain biopsy would provide valuable diagnostic information. Given the recent advances in imaging and neurosurgical techniques, the complication rate for routine biopsy has been reduced significantly. The patient elected to have the procedure performed. Rheumatology was consulted and an angiogram was recommended as well to rule out CNS vasculitis or vasospasm as a possible cause for the strokes. The patient had physical therapy and his motor and cognitive function gradually improved over the course of his hospital stay. The patient was accepted into a neurological rehabilitation facility and discharged on oral steroids. The results of the brain biopsy confirmed CADASIL after the patient was discharged to the rehabilitation facility. The results of the genetic tests for mutations in the NOTCH3 gene provided further confirmation with a sensitivity approaching 100%. |
pmc-6044484-1 | A 44-year-old male with past medical history of hypertension, was in his usual state of health until the morning of admission, when he was awakened by a substernal pressure-like chest pain associated with shortness of breath. He had no prior history of tobacco use, alcohol use, illicit drug use or family history of premature coronary artery disease. On admission, the patient was hemodynamically stable. Physical examination revealed an overweight male with bilateral earlobe creases (Figure ) and no other relevant findings.
A 12-lead electrocardiogram (ECG) revealed 2 mm downsloping ST depressions in the inferolateral leads along with 1 mm ST elevation in aVR. Initial cardiac enzymes included a troponin of 0.44 ng/ml, with normal creatine kinase (CK) and creatine kinase-muscle/brain (CK-MB) levels. The patient was given aspirin and intravenous heparin in the emergency room in addition to morphine and sublingual nitroglycerin. He continued to have ongoing pain despite analgesics and nitrates, thus he was transferred to the cardiac catheterization lab where angiography revealed severe triple vessel disease (Figure ). The decision was made to proceed with coronary artery bypass surgery (CABG). A transthoracic echocardiogram (TEE) revealed hypokinesis of the inferior wall of the left ventricle and ejection fraction of 45%. |
pmc-6044485-1 | A 44-year-old previously healthy Asian female reported to the neurology clinic with complaints of episodic, persistent, uncomfortable needle-like sensations in her genitalia extending to the anal area and the tip of the coccyx. She had been suffering from these symptoms for approximately 11 years. She had difficulty describing the actual nature of this phenomenon, which, according to her, was more of an irritation and discomfort than actual pain. The discomfort was aggravated during rest and periods of inactivity, particularly at night. It responded briefly to mefenamic acid tablets for four to five hours. She also reported the pain was worse before her monthly menstrual cycle but that sexual activity did not affect her discomfort. Sometimes, the discomfort was intense and would wake her from sleep causing severe discomfort and resulting in difficulty sitting; walking would relieve her symptoms partially. She was better in the morning, but the symptoms appeared again at end of the day. She had multiple gynecology and dermatology consults with no relief or clear diagnosis. She was prescribed antifungal creams, including fluconazole and ketoconazole, topical steroids (betamethasone and hydrocortisone), and mefenamic acid for pain relief. All failed to bring relief. She also consulted a homeopathy practitioner, who labeled her as suffering from a chronic skin disease and prescribed oral and topical medication. She took it for a few months but stopped it due to lack of relief. Ultimately, due to the distress and anguish associated with the condition, lack of response to various treatments, and social embarrassment, she stopped visiting doctors for some time. However, during a recent visit, the consulting gynecologist suspected it was not a dermatological or gynecological problem and referred her for a neurology consult.
There was no history of back pain, sensory symptoms in the legs, urinary incontinence, or neurological disorder, such as Parkinsonism or restless leg disorder. She had a stable and happy marital life of 22 years and had three children. She has used no substance of abuse or recreational drugs. Her neurological and gynecological examinations, as well as magnetic resonance imaging (MRI) of the spine, were normal (Figure ). Similarly, her biochemical profile (including complete blood count, urine analysis, serum urea, and creatinine) and an ultrasound examination of abdomen and pelvis were normal.
Considering her history of circadian rhythm variations in symptoms and aggravation on rest, RGS was considered the most likely cause of her symptoms. After a detailed discussion with the patient, she was prescribed 0.5 mg of ropinirole once at night. It was increased to twice daily after seven days, to which she responded well and reported a dramatic relief of symptoms after 14 days. The dose was increased to 1 mg in the morning and 0.5 mg at night, which led to further improvement. On her third follow-up after two months, she reported taking her medication regularly, which led to almost no episodes of discomfort, with exception of one or two times. The dose of ropinirole was maintained for one month. At the three-month follow-up, she reported only one episode of pain and itching, when she missed one dose of her medicine for a few days; otherwise, she had no complaints and reported no side effects of the medication. |
pmc-6044487-1 | A 48-year-old male presented with left foot pain which started “a couple of years ago” with no injury. The patient first noticed a “knot” on his foot between the second and third toes approximately one year ago. The patient was referred to the orthopaedics foot and ankle clinic for further evaluation. The patient reported his pain as neuropathic and paresthetic, and radiating to the second interdigital space. His symptoms were worsened by walking, standing, and climbing ladders and stairs. The patient had a known history of gout and was currently being treated with allopurinol and nonsteroidal anti-inflammatory drugs (NSAIDs). Despite treatment with urate-lowering medication, the patient exhibited tophaceous lesions of various sizes on his left elbow, right knee, right foot and bilateral hands, all asymptomatic.
Upon evaluation, the patient was afebrile; the other vital signs were within normal limits. On physical examination, the patient had pain with palpation of the interspace between the second and third metatarsal heads, with no metatarsal-phalangeal instability or hyperkeratosis. The rest of the physical examination was unremarkable.
X-rays and magnetic resonance imaging (MRI) were ordered to supplement the physical examination. The anterior-posterior and lateral foot X-rays showed small periarticular erosions in the second metatarsophalangeal (MTP) joint, consistent with crystal-induced arthropathy, with no significant degenerative change, fracture, or dislocation (Figure ). The MRI study showed a well-circumscribed, heterogeneous, soft tissue mass overlying the dorsal aspect of the second MTP joint, containing multiple internal cystic areas. The lesion was measured approximately 4.1 x 2.7 x 2.6 cm, based upon coronal, sagittal and axial T1 images (Figure ). There was an extensive erosion of the second metatarsal head with associated cortical destruction. The patient’s serum uric acid level was 6.2 mg/dL (normal range 4.0-8.5 mg/dL).
The patient was consented for an excisional biopsy of the lesion and decompression of the second intermetatarsal space. The procedure started with a dorsal incision over the second intermetatarsal space. The skin was sharply dissected and the subcutaneous tissue bluntly dissected. Keeping the neurovascular structures protected, the deep tissue was completely exposed. The pseudotumoral lesion was visualized as granular, opaque and whitish, located within the second intermetatarsal space, with no involvement of the adjacent soft tissue. The lesion was excised and removed completely, measured as 2.5 x 1.6 x 1.0 cm, and sent to pathology.
Next, attention was made toward decompression of the intermetatarsal space. The intermetatarsal ligament was identified and resected while protecting the nerve underneath. The patient tolerated the procedure well without complications, and was discharged the same day with postoperative pain management medication. Postoperative instructions were to partially bear weight with a wedged shoe for two weeks, then progressively increase weight bearing as tolerated, and return to normal activities and normal shoe wear after six weeks. The patient's postoperative follow-ups were in two weeks for wound check and suture removal in six weeks and three months.
The surgical pathology report confirmed the lesion was a gouty tophus. The histologic findings are described in Figure . The patient was referred to a rheumatologist for continued treatment of gout at his first postoperative follow up visit. |
pmc-6044488-1 | We present a 43-year-old man with a past medical history only significant for a prior splenectomy who was admitted to the hospital due to right upper quadrant pain for two days. This was described as a dull “liver pain” in the right upper quadrant area. On physical exam, there was evidence of a midline scar, the abdomen was soft with mild tenderness to palpation of the right upper quadrant and the liver span was approximately 10 cm in the mid-clavicular line by percussion. A complete blood count and a basic metabolic panel were normal; however, alanine transaminase (ALT) and aspartate transaminase (AST) showed a mild elevation of 66 U/L and 51 U/L, respectively. Serum bilirubin levels and alkaline phosphatase levels were within normal limits. Due to the reported complaint of right upper quadrant pain and the associated abnormal liver function tests, an abdominal ultrasound (US) was ordered. This showed fatty liver disease and a left liver lobe isoechoic liver mass. A computed tomography (CT) triple phase abdomen scan was done demonstrating a 2.5 cm exophytic mass in the liver in segment 2 (Figure ). The next day of admission, the patient’s pain improved with analgesia. As no clear diagnosis was made, he was later discharged with an intention to perform an elective abdominal magnetic resonance imaging (MRI). This MRI revealed a single mass in segment 2 of the liver, with features of a hepatic adenoma (Figure ). The surgical team was consulted and evaluated the patient and an elective percutaneous liver biopsy was performed. Examination of hematoxylin and eosin (H&E) stained sections revealed histological evidence of splenic tissue with distinct red and white pulp areas, with evidence of passive congestion (Figure ). The red pulp included thin-walled venous sinusoids that were congested with red blood cells that were positive for CD8 stains (Figure ), with surrounding macrophages and few lymphocytes. The white pulp included thickened meshwork of cords showing arterioles sheathed by predominantly small T lymphocytes (CD3+) and scattered B-cell aggregates (CD20+), consistent with splenic Malpighian corpuscles (Figure ). On further questioning, the patient reported he had an exploratory laparotomy with subsequent emergent splenectomy at the age of 16 years due to a motor vehicle accident which caused a splenic rupture. As the patient was diagnosed with hepatic splenosis and was at this point asymptomatic, his benign diagnosis was explained, and no further workup was needed. |
pmc-6044489-1 | A 41-year-old female with no past medical history presented with acute onset of abdominal pain that was associated with weight loss and painless jaundice. She was stabilized in the emergency room and was admitted for further workup. The physical examination was unremarkable except scleral icterus. The lab workup showed liver enzymes dysfunction (alanine transaminase 144 U/L, aspartate aminotransferase 122 U/L, and alkaline phosphatase 331 IU/L) with conjugated hyperbilirubinemia (5.4 mg/dl). The screen for antinuclear antibody, antimitochondrial antibody, and anti-smooth muscle antibody was negative. There was a marginal increase in total protein to 9 g/dl and an immunoglobulins assay was performed. It showed an increase in IgG total, i.e., 15.1 g/dl, and the IgG subclass analysis showed an increase in IgG-4 level, i.e., 155 mg/dl. The tumor marker screen was negative revealing normal level of cancer antigen 19-9. Imaging showed lymph node enlargement close to celiac plexus origin along with minimal calcification of the pancreatic head. It also revealed the dilatation of the biliary tree. A gastroenterology team was consulted and endoscopic retrograde cholangiopancreatography (ERCP) was performed. The ERCP showed distal stricture in the common bile duct (CBD), which was relieved with stenting (Figure ).
The histopathology from ERCP brushing was suggestive of primary sclerosing cholangitis (PSC). The endoscopic ultrasound (EUS) was unremarkable. After exclusion of other differentials with negative imaging and tumor marker screen, the diagnosis of autoimmune pancreatitis was made. The patient was treated with steroid therapy and improvement was noticed regarding the subjective and objective aspect. Interestingly, further screening to rule out autoimmune concern revealed the patient to be hypothyroid with Hashimoto profile (increased anti-thyroid peroxidase antibodies), for which she was also started on thyroxine treatment. The patient was followed further for four to six months and she has been doing fine with no concern regarding her medical problems. |
pmc-6044491-1 | A 55-year-old male patient reported with mild swelling and pain in the left zygomatic region. The history of present illness revealed that the patient had noticed the swelling in the last few weeks and it also had an associated intraoral ulcer. The patient was a known diabetic who was under medication. He had a habit of smoking cigarettes for the past 15 years. He smoked almost 15 cigarettes per day. The clinical examination revealed a firm swelling in the left zygomatic region measuring approximately 3 cm to 5 cm. It was mildly painful on palpation. The left maxillary region had significant paresthesia, nasal obstruction, and episodes of pain. A palpable left submandibular lymph node was present, which was also tender and fixed. The cervical lymph node on the left side was also palpable (Figure ). The intraoral examination revealed an ulceroproliferative growth measuring 4 cm to 6 cm in dimension.
The lesion was extending in relation to teeth 23, 24, and 25. The ulcer was covered with necrotic slough. Purulent discharge and bleeding were present in the lesion. The other teeth in the quadrant were missing (Figure ). A panoramic radiograph revealed extruded teeth 23, 24, 25.
There was increased radiopacity in the left maxillary sinus (Figure ). Water’s view showed the opacification of the entire left maxillary sinus.
An intraoral extension of this mass was also evident. The inferior, posterior, lateral, and medial walls of the left maxillary sinus appeared to be destroyed (Figure ). A computed tomography (CT) scan showed a lesion extending into the maxillary space and the nasal cavity. A heterodense soft tissue lesion showing heterogeneous contrast enhancement in the left maxillary sinus and hard palate with the destruction of the posterolateral wall, medial wall, and floor of the left maxillary antrum, extending into the adjacent retro maxillary space and medially extending into the left nasal cavity, obliterating all meati with the destruction of nasal turbinates. It was also inferiorly extending into the oral cavity. The CT was suggestive of carcinoma antrum. The CT was sufficient to understand the extensions of the lesions and the destruction of nasal turbinates. Further radiological investigations were, hence, not considered.
Considering the patient history and clinical features and the fact that patient was experiencing paresthesia, a biopsy was deemed mandatory (Figure ). On microscopic examination, the given hematoxylin and eosin (H&E)-stained soft tissue section showed dysplastic epithelial islands arranged in sheets and nests, invading fibrovascular stroma.
As shown in Figure , the dysplastic epithelial cells exhibited an increased nuclear-cytoplasmic ratio, individual cell keratinization, and increased mitotic figures.
Keratin pearl formation was also evident, suggestive of well-differentiated squamous cell carcinoma. The patient was referred to the maxillofacial surgery department and briefed on surgical and chemotherapeutic treatment modalities. As the patient was from a poor socio-economic background and had also reported at an advanced stage, he declined treatment and was advised palliative management. The palliative treatment mainly concentrated on the pain relief and nutritional needs of the patient. The patient was treated with acetaminophen and, later, with stronger medications like opioids to manage pain. A feeding tube was inserted into the stomach through the throat since the patient was having extreme difficulty in swallowing. Sadly, the patient succumbed within a few weeks. |
pmc-6044492-1 | A 28-year-old Caucasian male with no known past medical history presented to the emergency department with a headache for six weeks. The pain was throbbing, changed locations, and was associated with mild nausea and intermittent generalized weakness, photophobia, and blurred vision. Vital signs and the physical examination were unremarkable at the time of presentation; a fundoscopic exam was not performed on initial evaluation. The patient attributed his headache to possible mold exposure in his apartment or recent smoking cessation. He did not initially have signs or endorse symptoms concerning for the life-threatening etiology of his headache, to include mass, intracerebral hemorrhage (ICH), or infection []. The initial differential diagnosis was broad, but the etiology appeared to be benign. The patient subsequently had improvement with metoclopramide and diphenhydramine. Laboratory studies and head computed tomography (CT) without contrast were ordered at triage. The reason they were ordered is unclear, as there were no clear red flags on presentation. The patient had a WBC count of 773,000 (801,000 on repeat laboratory draw) with a basophilic predominance (51%). Concern shifted to leukemia as the likely etiology of headache, with potentially a blast crisis causing leukostasis. Ophthalmology and hematology/oncology were consulted. On repeat history after laboratory studies, the patient endorsed multiple episodes of intermittent complete loss of vision lasting several seconds over the preceding few weeks, as well as recent night sweats and unintentional weight loss. Peripheral smear showed 9% blasts and had findings consistent with chronic CML, including basophilic predominance. Ophthalmologic examination demonstrated gross papilledema and retinal hemorrhage bilaterally, with a serous elevation of the right retina and turbid white cells below (Figures -). The ophthalmologic findings were consistent with a head CT without contrast that was concerning for elevated ICP.
Leukocytapheresis, or white blood cell removal, was considered due to the degree of hyperleukocytosis. As the patient was not in an acute blast crisis, he was instead started on hydroxyurea and allopurinol in the emergency department, as per recommendations by hematology/oncology [-]. In addition, he was given aggressive intravenous fluids with the aim of hemodilution and decreasing blood viscosity. Allopurinol was started to prevent TLS on initiation of hydroxyurea []. The final diagnosis by the hematology team was accelerated phase CML, given the gross elevation of leukocytosis and concurrent symptoms, despite only having 9% blasts (13). Subsequently, BCR-ABL1positive CML was identified with a bone marrow biopsy. The patient received hydroxyurea until the WBC count fell below 50,000 and was later transitioned to outpatient dasatinib, a tyrosine-kinase inhibitor []. On discharge 17 days later, the WBC count was within normal limits. |
pmc-6044494-1 | A 62-year-old female presented to the emergency department with chest pain and shortness of breath. Her past medical history was significant for hyperlipidemia, hypertension, and type 2 diabetes mellitus. A family history of coronary artery disease was present. She had recent stressors at home. Her vitals were as follows: temperature 97.6 °F, blood pressure 122/95 mmHg, heart rate 76 beats/min, respiratory rate 18/min, and SpO2 93% on room air. Her physical examination was unremarkable. Her urine drug screen was positive for opiates, benzodiazepines, and tetrahydrocannabinol. Her troponin level was 0.655 ng/mL. An initial electrocardiogram showed sinus tachycardia. She was started on intravenous nitroglycerin and beta blocker. However, she became hypotensive, 84/42 mmHg, and was given intravenous fluids and started on a norepinephrine infusion. Her repeat electrocardiogram showed T wave inversions in leads V2-V5, less prominent in II, III, aVF, suggestive of myocardial ischemia (Figure ). She was taken for cardiac catheterization immediately. Cardiac catheterization revealed mild coronary artery disease and severe apical hypokinesia with a left ventricle ejection fraction of 25-30% (Figures -). These findings were suggestive of Takotsubo cardiomyopathy.
For cardiogenic shock, an intra-aortic balloon pump was placed. She was started on carvedilol, captopril, and heparin infusion. She became hypotensive again and was started on dopamine infusion, and carvedilol and captopril were stopped. She developed pulmonary edema, with small right-sided pleural effusion and bilateral interstitial opacities on the chest X-ray, and she was started on furosemide. Echocardiogram showed a left ventricular ejection fraction of 30% with akinesia of the mid and distal anterior wall and septum, entire apex, mid and distal inferior wall, and mid anterolateral and mid inferoseptal segments. She continued to improve and the intra-aortic balloon pump was removed and dopamine was stopped. Her heparin infusion was transitioned to warfarin to prevent a left ventricular thrombus from forming. Statin was not started due to previous intolerance. She was gradually started on low dose carvedilol and lisinopril. She continued to improve and was discharged home. On a follow-up visit after two weeks, her symptoms had improved. Repeat echocardiogram showed left ventricular ejection fraction of 45% and hypokinesia of mid and distal anterior septum, apical lateral and anterior segments, and apex. |
pmc-6044604-1 | A 64-year-old male, with a past medical history of gastroesophageal reflux disease, alcohol abuse, and hypothyroidism non-compliant with medications, presented after a syncopal episode and several days of hematemesis, melena, and abdominal distension. The patient began to develop multiple daily episodes of vomiting of black liquid and melena four days prior to presentation, with associated lightheadedness and shortness of breath. He reported that he had previously been taking omeprazole, but stopped taking all medications several months prior. He reported taking ibuprofen for the past few weeks, consuming 400-1200 mg per day for one to two weeks for chronic back pain. The physical examination was notable for a significantly distended abdomen with findings consistent with ascites, which was reportedly new for him. Laboratory testing showed low hemoglobin (Hgb: 6.4 g/dL, which worsened to 5.1 g/dL over the same day), elevated aspartate aminotransferase (AST: 104 IU/L), significantly elevated thyroid stimulating hormone level (TSH: 60 units/mL), and an undetectable free thyroxine level (FT4). He was given two units of blood and was started on intravenous (IV) levothyroxine and hydrocortisone. He was admitted to the intensive care unit (ICU) and underwent an upper endoscopy, which showed an adherent clot in the distal esophagus, just proximal to a hiatal hernia in the distal esophagus, and received three clips and an epinephrine injection. A right upper quadrant ultrasound was performed, which demonstrated clear yellow fluid and fluid analysis notable for nucleated cells: 150/uL, neutrophils: 0%, mesothelial cells: 4%, lymph: 57%, monocytes: 38%, protein: 2.0 g/dL, albumin: 1.2 g/dL, lactate dehydrogenase (LDH): 106 IU/L, serum albumin: 3.1 g/dL, and serum-ascites albumin gradient (SAAG): 1.9. Infectious workup was also performed on the ascites, which was overall negative. However, amylase and lipase were not checked on the fluid. He then underwent a transjugular liver biopsy and hepatic venous pressure gradient measurement, which showed a normal liver, without any signs of cirrhosis (liver fibrosis 1/6) (Figure ), and a normal hepatic venous pressure gradient (HVPG) of 3 mm Hg. The diagnosis of myxedema ascites secondary to longstanding hypothyroidism was presumed based on the history of untreated hypothyroidism and lack of portal hypertension or cirrhosis. During his hospitalization, the ascites clinically improved over eight days after the initiation of 300 mcg of IV levothyroxine and titrated to 150 mcg PO levothyroxine daily, which he continued upon discharge. |
pmc-6044856-1 | In this article, we report the case of a 9-year-old female patient with no previous medical history and no significant family history of osteosarcoma or any other bone tumor, who presented in our clinic on January 2016 with a 1 year history of pain in her low back and left lower limb. She was diagnosed with osteosarcoma of the left tibia with a solitary metastasis in her L3 vertebrae on February 2016. She was subsequently treated with a left below knee amputation and L3 corpectomy with posterior spinal fusion and instrumentation from L1 to L5 with decompression laminectomy at L2-3, and L3-4 through a posterior and left thoracoabdominal approach in March 2016 ().
She was found to have an abnormal bone scan with a lesion at the L3 level 3 months after completing chemotherapy in November 2016. MRI scan and ultrasound guided fine-needle aspiration cytology (FNAC) of right paraspinal psoas tissue confirmed recurrent osteoblastic osteosarcoma on December 2016 (). On physical examination, she was able to ambulate with use of a below knee prosthesis and demonstrated no neurological deficits. The patient was started on second line drugs, including two cycles of ifosfamide/etoposide. Previous implants were well in place. Imaging was performed with radiographs, CT scan, bone scan, PET scan, and MRI scan with contrast enhancement to confirm only a single metastatic site (). For therapeutic strategy determination, the patient was introduced to our local tumor board. Preoperative workup was completed, and surgery was planned for a complex en bloc resection of L2, L3, and L4 with removal of deep spinal implants with anterior and posterior spinal fusion and instrumentation (). The option of nonoperative palliative care was offered to the patient and her family, but they elected to proceed with en bloc resection to maximize her chances of survival, in spite of high surgical risk and an overall poor prognosis. They were informed preoperatively that a complete resection would require sacrificing her nerve roots at L2, L3 and L4. A palliative decompression was not offered for the revision procedure as a treatment option as the patient was not complaining of pain or neurological symptoms, and it would not have improved her life expectancy. |
pmc-6044857-1 | An 80-year-old lady suffered a comminuted intratrochanteric fracture following a mechanical fall, with an AO classification of 3.1A2.3. After we excluded all contraindications, drew up a series of preoperation plans, consist of measure medullary cavity diameter, anterior femoral arch angle and the optimal entry point and so on. We treated with satisfied close reduction with traction on a traction operating table, and then captured the best point to insert the guide needle (). In sequence, reamed medullary cavity was performed step-by-step. Unfortunately, the reamer was stuck into femoral medullary cavity tightly at last, we could not move out by traction or rotation. What's the worst, the reamer head was ruptured completely finally, and remained in femoral shaft isolated (). The broken reamer located much more distal to the femoral intertrochanteric fracture site and jammed with cortex of bone firmly. So an extreme tough challenge for removal was in front of us.
The guide needle was removed easily, on account of less experience to refer, and no instrument to use. Therefore we performed an open technique and created a 2.0 cm ×0.4 cm long strip bony window by using an osteotome, which is just right for inserting a bone detacher, then put the detacher head adjoin the reamer, we moved out the broken reamer head by knocking back the inserted detacher and pulling out through the medullary cavity using a Kocher's clamp (). A set of PFNA was inserted to fixation and the bony window was full with bony bar taken down before, and the fracture got a good bone union after 2 months (). |
pmc-6045564-1 | A 47-year-old woman was referred with a 6-month history of a right anterior chest mass. A physical examination showed a palpable firm mass with tenderness in the right anterior chest. Her routine laboratory investigations were within the biological reference range. Enhanced chest computed tomography (CT) showed a dumbbell-shaped mass with calcification, and its anterior portion was located under the pectoralis minor muscle and the posterior portion projected to the thoracic cavity (Fig. a). Chest magnetic resonance imaging (MRI) showed an invasive tumor, which was isointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images (Fig. ). Aspiration biopsy cytology performed by a previous physician had shown malignancy, and no evidence of distant metastasis was found. Therefore, we planned surgical resection of the tumor with chest reconstruction. The patient was placed in the supine position. We first examined inside the thoracic cavity with thoracoscopy through the seventh intercostal space and found no lung invasion of the tumor. Wide resection, including the middle part of the pectoralis major muscle, the pectoralis minor muscle, and the third and fourth ribs, was performed. A negative margin of the tumor was identified by frozen sections. We used a 2-mm expanded polytetrafluoroethylene (ePTFE) patch (Gore Dualmesh; W.L. Gore & Associates, Flagstaff, AZ, USA) for chest wall reconstruction and covered it with spared skin and breast (Fig. ). The operation time was 3 h and 33 min, and intraoperative blood loss was 64 ml.
The resected specimen was a firm tumor that surrounded the third rib (7.5 cm) (Fig. ). Microscopically, the tumor cells showed an epithelioid appearance with cytoplasmic eosinophilia. The epithelioid cells had large vesicular nuclei and were arranged in sheet-like pattern. In some locations, scattered microcalcification was observed (Fig. a, b). Immunohistochemical staining showed expression of CD34 and cytokeratin (AE1/AE3) (Fig. c, d), but no expression of CD31, Sox10, Stat6, and integrase interactor 1 (INI1) in tumor cells. The diagnosis was proximal-type ES in the right chest wall. The French Fédération Nationale des Centres de Lutte Contre Le Cancer grading system was grade 2.
We started physical therapy on postoperative day 6 for local pain and limitation of shoulder motion. These symptoms improved by physical therapy, and she was discharged on postoperative day 18. Although weakness of the arm and chronic pain had been persistent, she could be reinstated in former factory work. We did not perform postoperative adjuvant chemotherapy or radiation therapy. She has remained alive for 1 year and 10 months without recurrence. |
pmc-6045687-1 | A 21 year old female presented to gynecology out patient department with complaints of inability to concieve for the last 5 years. Her menstrual history was within normal limits except for the last 5 months whe she developed irregular menstrual bleeding and dysmennorhea. There was no history of any chronic illness like tuberculosis in the past. She had undergone appendicectomy 11 years back for acute appendicitis. On general physical examination she had pallor and mild pedal edema. On per abdomen examination there was a lump in abdomen measuring approximately 8 X 8 centimeters in the left iliac fossa. Her per vaginum examination revealed bilateral tender fornices and a bulky uterus while per speculum examination showed healthy vagina and cervix.
Patient was further investigated and on Ultrasonography was found to have left sided ovarian cyst measuring 5 X 4 cm, diagnosed as a complex cyst with septations. Uterus was found to be anteverted, bulky and with multiple fibroids both on anterior and posterior walls. Kidney also showed hydronephrotic changes. On Hysterosalpingography, bilateral tubes were blocked. Laparotomy was perfomed which revealed a large tubo-ovarian mass on left side measuring 6 X 7 cm. Omentum and bowel were found to be adherent to this mass. Along with a large 5 X 2 cm fibroid found in anterior wall of uterus. Right sided falllopian tube was tortuous and edematous while right ovary was apparently normal. So a Left salpingo ophrectomy was performed and sent for histopathological examination. Pus drained from omentum was sent for culture and sensitivity. However it did not reveal any growth (including Mycobacterium tuberculosis) even after 4 weeks .Other investigation of the patient revealed CA 125 levels to be 246 U/ml and serum LH levels to be 7.58mIU/ml. Thyroid profile was normal.
We received a mutilated specimen in three pieces. The largest piece measured 5×3×2 cm. Outer surface was exudate covered and congested. Cut surface revealed red brown areas with a luminal structure likely to be tube. Second and third pieces were measuring 4×3×1 cm and 1×1×0.5 cm. Sections from the ovary showed sheets of foamy histiocytes along with the presence of inflammatory infiltrates in the form of lymphocytes, plasma cells and some neutrophils and eosinophils. There were fair number of foamy histiocytes with abundant lipid laden vacoules in the cytoplasm and hypochromatic nuclei. There was fibrosis along with some vascular proliferation in the ovarian parenchyma. Sections from fallopian tubes also showed the presence of xanthogranulomatous inflammation in the lamina propria and the serosa of the tube walls (as shown in ). Periodic Acid Schiff (PAS) and Acid fast stains were negative. Subsequent immunohistochemical stains demostrated positive CD68, CD 3 snd CD 20 were suggestive of a mixed inlflammatory infilterates in both tube and ovary. Based on the above features a diagnosis of xanthogranulomatous salpingo ophritis was rendered. |
pmc-6045817-1 | A 10-year-old girl was referred to the Children’s Hospital of Fudan University because of polydipsia and polyuria. She was born to non-consanguineous healthy parents of Chinese Han ethnicity and good socioeconomic status. She was the only child of the family, and there was no family history of FS. Newborn hearing screening failed. There was no history of birth defects. She was not receiving any medication and did not take alcohol or smoke tobacco. She was in Grade 4 of primary school and was not good at studying.
At 3 months of age, she presented with jaundice, hepatomegaly (3.5 cm below the costal margin), and splenomegaly (4 cm below the costal margin). She was admitted to our hospital. Laboratory findings revealed: elevation of direct bilirubin (DB), that is, total bilirubin (TB) 66.1 μmol/L (normal range, 0–6 μmol/L) and DB 61.4 μmol/L (normal range, 5.1–17.6 μmol/L); and almost normal transaminases, that is, alanine aminotransferase (ALT) 24 IU/L (normal range, 0–40 IU/L) and aspartate aminotransferase (AST) 46 IU/L (normal range, 0–40 IU/L)). Laboratory tests for hepatotropic viruses were negative. Magnetic resonance cholangiopancreatography excluded bile duct obstruction. After treatment with ursodiol, the jaundice resolved gradually. During the follow-up years, her liver functions were normal. Hypoglycemia was initially noticed during hospitalization, and fasting blood glucose ranged from 1.4 to 2.8 mmol/l. Prior to this, there was no record of a hypoglycemic episode. At the time of hypoglycemia (blood glucose 1.4 mmol/l), an inappropriate glycemic response to glucagon (increase of 4.3 mmol/l) was consistent with excess insulin action, confirming hyperinsulinism. Frequent feeding combined with intravenously administered glucose (6–7 mg/kg per minute) was required to maintain normoglycemia. She was discharged from the nursery with stable glucose levels (4.3–6.5 mmol/l) on the condition of frequent feeds. At 1 year of age, she experienced an episode of hypoglycemia, and the symptoms resolved after feeding. Subsequently, no symptoms of hypoglycemia appeared again.
Short stature was noticed (height and weight were below the third percentile) by routine physical examination at the age of 5. Laboratory investigations revealed proteinuria and glycosuria, mild acidosis, and hypophosphatemic rickets. Prior to this, she had recurrent urinary tract infections, suggesting an earlier onset of abnormal urine. Based on the clinical impression of FS, she was treated with calcitriol, phosphorus, and potassium citrate. Over the ensuing years, sodium citrate and other medications were used to maintain acid-base balance, but there was no improvement in her short stature, and her serum creatinine remained elevated by age 10.
At 10 years of age, she was admitted to our clinic because of symptoms of FS and elevated serum creatinine: 75 μmol/L (normal range, 21–65 μmol/L). On this admission, her height was 126.5 cm (below the third percentile) and her weight was 28 kg (25th percentile). Laboratory investigations revealed: renal glycosuria in the absence of hyperglycemia; proteinuria with a urinary protein to creatinine ratio (pro/Cr) of 2.17 (normal range, 0–0.2); hypercalciuria with a urinary calcium to creatinine ratio (U-Ca/Cr) of 0.31 (normal range, < 0.21); and hypouricemia with 66 μmol/L (normal range, 90–420 μmol/l). Fasting glucose and post-prandial glucose were normal. No known cause for FS was identified. Glomerular filtration rate (GFR) was 55.7 ml/minute/1.73 m2 measured by 99mTc-diethylenetriaminepentacetate (DTPA) renal dynamic imaging. Renal ultrasonography showed nephrocalcinosis (Fig. ). A radiological examination showed complete recovery of rickets. Pure tone audiometry revealed a bilateral hearing loss of more than 50 dB. Because of multisystem involvement, she underwent whole exome sequencing and mutational analysis, revealing a heterozygous p.R63W mutation in the HNF4A gene. Both parents tested negative for the mutation. No genes associated with deafness phenotypes were found. |
pmc-6045832-1 | An 11-year-old female with no previous medical history presented with floater symptoms in her right eye. She had no medical or ophthalmological history that may contribute to the condition, such as hypertension and thrombocytopenia, which can cause bleeding. The patient had no trauma or medication history. Her BCVA (best-corrected visual acuity) by the Snellen chart was 20/20 in both eyes, with intraocular pressure of 15 mmHg in her right eye and 16 mmHg in her left eye. Slit lamp examination revealed no specific findings in the anterior segment of both eyes and no relative afferent pupillary defect, but − 3.5 diopters of myopia was noted in both eyes. Fundus examination and optical coherence tomography showed tilted disc, intrapapillary hemorrhage, peripapillary subretinal hemorrhage, and mild vitreous hemorrhage in her right eye (Fig. ), Fluorescein angiography showed blocked fluorescence due to peripapillary subretinal hemorrhage at the early phase, but no definite leakage or new vessels were noted at the late phase (Fig. ). We recommended further evaluations, including brain magnetic resonance imaging (MRI), but the patient (with their guardian) chose to undergo only ophthalmological evaluation. After 4 weeks, the hemorrhage had partially resolved without any treatment (Fig. -, ), and complete resolution was noted after 3 months, with a BCVA of 20/20 in her right eye (Fig. -, ). |
pmc-6045832-2 | A 16-year-old male presented with symptoms of blurry vision and black filamentous floaters for 1 day. He had no previous medical history, and no trauma or medication history. His BCVA was 20/20 in both eyes, with intraocular pressure of 15 mmHg in his right eye and 19 mmHg in his left eye. The patient had − 7.0 diopter myopia in his right eye and − 7.5 diopter myopia in his left eye, with no definite relative afferent pupillary defect. Slit lamp examination showed no specific findings except mild vitreous hemorrhage in his right eye. Fundus examination showed intrapapillary hemorrhage and peripapillary subretinal hemorrhage in his right eye, and mild optic disc hyperemia in his left eye (Fig. ). Optical coherence tomography revealed peripapillary edema in his right eye (Fig. ). Fluorescein angiography showed blocked fluorescence because of peripapillary subretinal hemorrhage, but no fluorescence leakage or hyperfluorescence. (Fig. ) A Humphrey visual field examination of his right eye showed no specific sign except for enlarged physiological scotoma (Fig. ). No specific signs were noted in the brain and orbit MRI. After 4 weeks of observation, the intrapapillary hemorrhage and peripapillary subretinal hemorrhage subsided without any particular treatment, with a visual acuity of 20/20 (Fig. ). |
pmc-6045852-1 | In Mar 2013, a 33-year-old female came to the nephrology department because of 4 years of recurrent acute pyelonephritis. She had no other notable past medical history including polyuria, polydipsia, muscular cramps, carpopedal spasms or generalized seizures, and did not take any regular medication. Her parents, who aged 56 and 53 respectively, were second cousins and denied any remarkable medical history. Her only sibling died from renal failure without definite cause at age 25. The pedigree of the family is shown in Fig. . Physical examination revealed that her height was 160 cm (The average height of Chinese adult females at corresponding age is 159 cm.) and her weight was 55 kg with a BMI of 21.48 kg/m2. Laboratory workup revealed impaired renal function (SCr 250 μmol/L, EPI-eGFR = 21.1 ml/min/1.73m2), hypocalcemia (1.42 mmol/l, normal range 2.11–2.52), and normal serum parathyroid hormone levels (65.59 pg/ml) in the context of normal 25OH-Vitamin D levels (26 ng/ml, reference range 20.0–32.0) (Table ). Her serum magnesium level was slightly low (0.60 mmol/l, reference range 0.65–1.20), and 24-h urinary calcium was 3.9 mmol/1.73m2 (normal range 2.5–5.5) in the setting of decreased renal function. Distal renal tubular acidosis was excluded since she had normal urine acidification function (pH < 5.3) in the setting of nearly normal serum bicarbonate level (HCO3− 22 mmol/l). Renal ultrasound imaging demonstrated bilateral nephrocalcinosis and parenchymal renal calculi, with the right kidney length 9.5 cm and the left 9.4 cm. Ophthalmologic examination was normal. During the subsequent 3 years of follow-up, she had undergone six attacks of acute UPI. In the interictal phase of infections, she had accepted four times of biochemical assessment (Table ). Repeated examinations in the follow-up revealed marked renal loss of magnesium (fractional excretion 42.7 ± 7.4%, normal range less than 5%) and hypercalciuria (urinary calcium/creatine 0.52 ± 0.08 mol/mol, normal range 0.15–0.33). Treatment with calcitriol and calcium but not with magnesium was difficult to achieve a considerable effect on her serum calcium, whereas her serum magnesium concentration fluctuated within the normal range (0.70–0.91 mmol/l) under the circumstances of renal failure. Plain abdominal radiograph and abdominal CT scanning, which were performed in Mar 2014 and Feb 2016 respectively, demonstrated gradually aggravated nephrocalcinosis and atrophy of renal parenchyma (Fig. ). In the end, the patient unavoidably reached ESRD at the age of 36. The gradient of GFR decline was calculated to be 4.3 ml/min per 1.73 m2/yr. during the follow up, whereas the gradient of GFR decline was about 2.1 ml/min per 1.73 m2/yr. 3 years before the period of follow up, and the approved global slope of decline was 2.5 ml/min per 1.73 m2/yr.
Nephrocalcinosis associated with end-stage renal failure is usually seen in three genetic diseases: primary hyperoxaluria, Dent’s disease, and FHHNC. Meanwhile, hypercalciuric hypomagnesemia is mainly seen in FHHNC, autosomal dominant hypocalcemia with hypercalciuria (CASR gain-of-function), or Bartter syndrome type III. Although the patient’s family history, hypocalcemia, and hypomagnesemia suggested FHHNC, we performed whole-exome sequencing (WES) to exclude the possibilities of comorbid diseases or potential mutations of other genes that could affect the renal reabsorption of calcium and magnesium. All the family members and healthy controls gave informed consent. The study protocol was approved by the Ethics Committee on Human Studies at the Affiliated Hospital of Qingdao University. As a result, a homozygous cytosine-to-guanine substitution at position 346 of the open reading frame (c.346C > G) in exon 2 of CLDN16 gene was identified by WES. This single nucleotide alteration led to a single amino acid substitution from leucine to valine at amino acid position 116 of claudin 16 (p.Leu116Val; Of note, there is still controversy about the physiological use of the initiation codon. The numbering of the mutation regarded to the second ATG would be p.Leu46Val.) (Fig. ). Sanger sequencing validation of all family members revealed that four of her unaffected members including her parents, grandmother and one of her cousins carried heterozygous p.Leu116Val mutation in CLDN16, whereas other family members and 200 unrelated controls from the same ethnic background (Chinese Han population) did not carry this mutation. This novel variant was highly conserved among 8 different species (Human, Rat, Frog, Chimpanzee, Eagle, Horse, Turtle & Cattle) (Additional file : Figure S2) and among all 27 Human Claudins family members, and never been reported in 1000G, ExAC, or EVS. All four in silico prediction tools (SIFT, PolyPhen2, Mutation taster, and PROVEAN) showed a possibility of disease-causing for FHHNC. In addition, analysis by HSF 3.0 () software showed that no significant alteration of splicing regulatory elements occur after mutation.
A three-dimensional (3D) model of Claudin 16 was built using the homology modeling approach implemented in the modeler-9 package. The result showed that the conserved W-L-W motif of the Claudin family (Trp99, Leu116, and Trp117 in Claudin 16) was embedded in a crevice formed by the top of the four-helix bundle. Leu116 and Trp117 protrude from the tip of the β2-β3 loop and were likely associated with Trp99 to serve as a “hydrophobic anchor” for the β-sheet domain. The L116 V mutation was predicted to abolish such interaction, resulting in a displacement of the β-sheet domain from the four-helix bundle domain of Claudin 16 (Fig. ). |
pmc-6045933-1 | A two months old Iranian girl born to consanguineous parents (cousin), presented in our center (Imam Reza Hospital, Mashhad, Iran) in October 2016 for evaluation of seizure and hypotonia in Pediatric Department. She had one sibling who died in 7 months old with similar symptoms and no more specific metabolic assessment.
Her mother had pregnancy-induced hypertension. She was a full term baby with birth weight of 2500 gr, birth length of 45 cm, birth head circumference of 32 cm and normal APGAR score.
She admitted at hospital in the fifth day of life with chief complaint of neonatal jaundice. In her first presentation at 2 months old, she had a history of fever, poor feeding and vomiting for 2d after routine vaccination. Her condition deteriorated with tonic-clonic seizures, difficulties in breathing, severe restlessness, lethargy, hypotonia and come for 1 day in her admission in intensive care unit.
After first admission, she had four more episodes with similar signs and symptoms and between these crises; she was asymptomatic. Developmentally, at 8 months, she could not babble, have head drop. She could not sit with support. Physical examination revealed no organomegaly. Not hearing or visual abnormalities.
Neurological examination results showed hypotonia and decreased deep tendon reflexes.
Arterial Blood Gas test revealed metabolic acidosis with PH: 7.2, HCO3: 5mmol/L, base excess: -20, and pCO2: 12.5 mmHg in her first acute attack. High level of blood sugar and ketonuria was detected. The patient’s plasma showed normal Ammoniae (72 µmol/L) and lactate (11 mg/dl). Beside negative Urine and blood culture, serum electrolytes, liver and renal and thyroid function tests had normal results. CSF analysis revealed negative results for infection.
Brain Magnetic Resonance Imaging (MRI) showed unspecific low signal intensity basal ganglia (). Tandem mass spectrometry (MS/MS) showed hydroxy methylglutaryl CoA-lyase deficiency and 3- methyl coronyl– coalyase deficiency. Suggested diagnosis was beta keto-thiolase deficiency (oxothiolase deficiency).
The organic acids in her urine showed an elevated 2methyl -3hydroxybutiric acid, an elevated tiglyglycine and 4 – hydroxy phenyl lactic acid.
Patient referred to gene assay diagnosis by whole exome sequencing examination. Approximately 37 MB (214,405 exons) of the Consensus Coding Sequences (CCS) were enriched from fragmented genomic DNA and were evaluated by Centogene AG Department. In genetic assay, we found a novel homozygous mutation c.664A>C (p. ser 222Arg) in ACAT1 gene that was the first time we detect this variant ().
These results were consistent with a genetic diagnosis of beta-ketothiolase deficiency (alpha-methyl acetoacetic aciduria) in our patient. |
pmc-6045940-1 | A 1-month-old female with unilateral left facial palsy was referred to the Pediatric Clinic, Ali-bin-Abitaleb Hospital, Zahedan, eastern Iran in 2013. Left facial nerve palsy developed on the 13th day after birth that she could not close her eye associated with loss of tearing from the affected eye. She had low-grade fever and purulent otorrhea developed 7 and 3 d prior to admission, respectively. There was no history of pregnancy complications and abnormal delivery. The patient was a full-term baby with normal vaginal delivery. At first assessment, she was alert but irritable, ill-appearing, and hypotonic. She was febrile with respiratory distress. Lymphadenopathy and organomegaly were not detected on physical examination. She had facial asymmetry and unilateral peripheral facial nerve palsy. Other parts of neurologic examination were normal. Bilateral tympanic membranes were hyperemic and showed signs of bulging.
Informed consent was taken from the parents before reporting the case.
Initial laboratory evaluation was conducted which generated the following results: WBC: 157000/mm3, Hb: 6.2 gr/dL, Hct: 18.6%, and platelet: 130000/mm3. Analysis of CSF showed the followings: 670 RBC/dL, 630 WBC/dL (70% neutrophils, 30% lymphocytes), protein 14 mg/dL, and glucose 18 mg/dL. CRP was 1+; ESR was 70 mm/h. Cell morphology of her peripheral blood smear (PBS) showed polymorphonuclears (PMNs) and myelocytes were prominent rather than other cell types (). Basophil count was approximately 20% of the total cells. Large platelets and mild granulocytic dysplasia were visible on peripheral blood smear.
Bone marrow aspiration and biopsy was performed. The flow cytometry results were as follows: HLA DR: 2%, CD2: 3.3%, CD5: 2.8%, CD7: 2.1%, CD10: 1.3%, CD13: 86.7%, CD14: 64.8%, CD19: 1.7%, CD20: 4.7%, CD33: 37%%, CD34: 3.4%, CD64: 97.4%, and CD117: 0.8%. Cytogenetic analysis revealed the presence of the Ph chromosome, which was suggestive of the BCR-ABL fusion gene. A diagnosis of CML was ascertained for the patient.
Brain CT scan did not reveal any intracranial abnormalities or evidence of mastoiditis. Vancomycin and ceftriaxone were initiated with oxygen therapy; however, no response to this treatment was observed. On the second day after admission, the patient developed a seizure. After 4 d of hospitalization, her left facial paralysis improved. On the 6th day of hospitalization, a bone survey was conducted, which did not show any lesions or abnormalities throughout the bones. On ophthalmologic examination, opacity in the left iris was detected. On the 7th day of hospitalization, the patient developed a right submandibular mass.
Treatment with GLEEVEC® (imatinib mesylate) was started for the patient. After 12 d of hospitalization, the patient experienced cardiopulmonary arrest for which resuscitation was unsuccessful and the patient succumbed to death. |
pmc-6045941-1 | A 12 yr old boy complained of general malaise, drowsiness, appetite loss, nausea, abdominal discomfort and darkening of the urine of two days duration. He was admitted to the Clinic of Infectious Diseases, St. George University Hospital, Bulgaria with mildly jaundiced skin and conjunctivas.
Upon admission, the child was ambulatory and neurological signs and symptoms were undetected. On the following day jaundice intensified, malaise progressed, accompanied by abdominal pain, headache, and pain in the muscles of lower extremities. The child was afebrile and conscious. During the period from 2nd to 14th d after admission, the neurological examination revealed: absent Achilles and knee-jerk reflexes, diminished brachioradialis reflex, absent abdominal and cremasteric reflexes, moderately decreased muscle power in the upper extremities and more pronounced power loss in the lower extremities. The patient showed decreased mobility when lying in bed, and was unable to sit, stand and mobilize independently. Deep sensation was preserved, but superficial sensation was affected with paresthesia in the palms and soles. Facial palsy (House-Brackmann grade V) developed initially more expressed to the right, and Bell’s sign was positive bilaterally. Mouth movement was insufficient, but difficulty swallowing was absent as well as urine and fecal incontinence. Heart and respiratory rates, and peripheral arterial pressure were normal.
There was albuminocytologic dissociation of the cerebrospinal fluid (CSF): normal pressure, normal cell count (2х106/l), the sugar levels - 3.4 mmol/l (reference range 2.2-4.2 mmol/l), and about three times increased protein levels - 1.52 g/l (reference range 0.4-0.5 g/l). Treatment was initiated with intravenous immunoglobulin (IVIG) 0.400 gm/kg/ for 5 days. Over the following days, a favorable trend in the patient’s condition was observed with improved general medical condition and reduced pain syndrome. Regarding the peripheral neurological abnormalities, they reached a peak on day 14th post admission and after the brief plateau phase for about a week rapidly improved, so that on day 23rd the child was able to move independently, rise upright from a squatting position, and only absent deep tendon reflexes persisted.
On day 30th post admission the child was discharged clinically healthy in terms of the HAV infection, with significant reversal of the peripheral neuropathy. On the follow-up visits, he had no neurological deficit or electrodiagnostic changes on the fourth month after discharge.
Informed consent was obtained from the parents of the patient.
The dynamics in the ALT, AST activity, and bilirubin level, as well as the timeline of the neurological changes, are displayed in . The remaining laboratory parameters were as follows: peripheral blood count, cholestatic enzymes, serum amylase, creatine kinase, choline esterase and electrolyte levels showed no abnormalities. Uro- and coproporphyrin tests were negative. Tests for Campylobacter jejuni, Epstein-Barr virus and Cytomegalovirus were negative. Nose and throat swabs were negative, as well as fecal cultures. The study of viral hepatitis markers /ELISA/ showed: HBsAg (-) negative, Anti HAV IgM (+) positive, HCV AB (-) negative. The child had received neither HAV vaccine nor prophylactic injection of immunoglobulin. He was contacted with other children with HAV during the large epidemics ongoing at that time in the Roma (Gypsy) headquarters in Plovdiv-city (Bulgaria).
The electrodiagnostic testing - nerve conduction studies and needle electromyography (EMG) was performed on day 10 post admission and 5 day following CSF-examination, in the absence of fever at the beginning and throughout the child's disease process. The testing was conducted and the neurological disorders were further clarified in the University Pediatric Neurological Center. Here is a brief description of the electrodiagnostic findings derived from the patient's medical record: "Stimulation of the peroneus nerve bilaterally displayed a low amplitude of compound motor action potential (СМАP), prolonged distal motor latency, temporal dispersion and reduced nerve conduction velocity. Findings at facial nerve stimulation bilaterally showed: CMAP-mildly prolonged distal latency time, temporal dispersion and reduced rate of conduction. Sensory nerve conduction velocities and sensory action potentials were normal. The follow-up at 4 months post-admission documented normal deep tendon reflexes and normal motor activity of the child. The follow-up electrodiagnostic testing of the facial and peroneal nerves registered normal CMAP. Conclusion: The electrodiagnostic findings suggest acute inflammatory demyelinating polyneuropathy (AIDP)”. |
pmc-6045942-1 | In October 2016, a 9-yr-old girl with chief complaint of nausea, vomiting, lethargy, and decreased level of consciousness referred to the Neurology Department of Namazi Hospital, Shiraz, southern Iran.
The proband was the third offspring of healthy consanguineous parents (cousins). She had a healthy brother and sister. She was delivered through cesarean section due to oligohydramnios (birth weight = 2700 gr, body length = 48 cm). She had a short neck and trunk, pectus carinatum, and kyphosis. The first problem of the patient occurred at five months of age when growth retardation was detected in routine workup. Dental age was also delayed compared to chronological age. Indeed, bone survey showed delayed bone age, J-shaped sella, periarticular and diffused osteopenia, and flattening of thoracic vertebrae. She developed urinary tract infection when she was 11 months old. In voiding cystourethrogram, bilateral vesicoureteral reflux was diagnosed. Kidneys, ureters, and urinary bladder ultrasonography and renal scintigraphy were normal.
At the age of 4 yr, urine analysis showed proteinuria for the first time and after more workups, nephrotic syndrome was confirmed.
She had no new problems up to the age of 6 yr when she developed sudden onset right upper extremity paresthesia and weakness. Brain MRI was performed and showed ischemic and hemorrhagic infarct in the left parieto-occipital and left caudate lobe. Brain Magnetic Resonance Angiography (MRA) also revealed significant wall irregularity of both internal carotid arteries, left Middle Cerebral Artery (MCA), basilar artery, and left Posterior Cerebral Artery (PCA). MRI of the cervical spine was normal.
Two years later, she developed slurred speech and paresthesia, and weakness was progressed to her lower extremities. Brain MRI was performed again revealing new acute ischemic infarction in the right temporoparietal lobe. Encephalomalacia with surrounding gliosis was also noted involving the left parieto-occipital lobe because of the old infarction. Complete obstruction of the right MCA from the proximal part was seen in brain MRA. There was also evidence of significant wall irregularity and stenosis in basilar artery, PCA, Anterior Cerebral Artery (ACA), internal carotid arteries, and vertebral arteries. These findings were in favour of moyamoya syndrome (). Brain Magnetic Resonance Venography (MRV) was normal. ().
Analysis of SMARCAL1 gene was performed for detection of mutations (), which revealed a homozygous nonsynonymous homozygous mutation c. (2459G>A). This mutation was found by direct sequencing of both sense and antisense strands of the 16 coding and 2 noncoding exons of SMARCAL1 ().
Her last admission was at the age of 9 yr due to nausea, vomiting, lethargy, and decreased level of consciousness (Glasgow Coma Scale 7/15) at the Namazi Hospital, Shiraz, southern Iran, in October 2016. In the emergency room, she had four episodes of Generalized Tonic-Clonic (GTC) seizure, controlled by phenytoin and diazepam. The Electroencephalogram (EEG) was in favor of diffused brain suppression. Indeed, brain MRI noted encephalomalacia in the territory of right and left MCA with involvement of the whole right parietal lobe due to previous infractions. Besides, laminar necrosis was detected in the right parietal lobe. There was also evidence of a hematoma in the right parietal lobe. Ventricular dilatation was observed due to brain parenchymal atrophy and volume loss (). She also had hyperkalemia, metabolic acidosis and anuria, and high creatinine level due to End-Stage Renal Disease (ESRD). Hemodialysis was not done owing to her parents’ dissatisfaction with insertion of central veins catheter, and she just received conservative therapy. Finally, she expired because of cardiopulmonary arrest following pulmonary hemorrhage. The laboratory findings of the patient have been presented in .
Informed consent form was obtained from parents before participation in the study in accordance. Ethics Committee of Shiraz University of Medical Sciences approved the study. |
pmc-6046094-1 | Our patient is a 23-year-old Chinese woman with UCD who presented with seizures 2 years after the latest episode of metabolic decompensation. She was the second child of a non-consanguineous union. Her elder sister and parents were well and there was no history of early deaths in the family, especially male family members. She was delivered at full term via an emergency caesarean section for failure to progress and breech position. Her Apgar was 7 at 1 minute and 8 at 5 minutes, probably due to prolonged maternal anesthesia.
She presented at 14 months of age with gross motor delay and intermittent vomiting after meals. She was alert and interactive. However, she was ataxic and her lower limbs were hypotonic with decreased power and brisk reflexes. The tone, power, and reflexes were normal in her upper limbs. She had intention tremors of the upper limbs. Computed tomography (CT) of her brain did not show any intracranial abnormalities. Her plasma ammonia level was markedly elevated at 327 umol/L (normal range 16 to 53 umol/L). She was treated with intravenously administered sodium benzoate with improvement in the hyperammonemia. She was diagnosed as having OTC deficiency in view of hyperammonemia, elevated glutamine at 1237 umol/L (normal range 400 to 700 umol/L), and elevated urinary orotic acid at 110 mmol/mol creatinine (normal range 0.5 to 3.3 mmol/mol creatinine). Her citrulline level was normal at 17 umol/L (normal range 5 to 60 umol/L). Sequencing of the OTC gene did not detect any pathological variant. The inability to identify a pathological variant by sequencing is not unusual. Pathological point mutation variants are found in approximately 80% of patients with enzymatically confirmed OTC deficiency. The remaining patients either have variants in the regulatory regions, variants within the introns, or have large deletions, all of which would not be detected by the sequencing that was done in this patient.
Our patient had multiple hospital admissions from diagnosis to 19 years of age, due to episodes of metabolic decompensation with plasma ammonia levels ranging between 157 and 278 umol/L (Fig. ). These episodes occasionally occurred due to suboptimal compliance to protein-restricted diet, but most of the episodes occurred without any obvious trigger. She responded each time to intravenously administered sodium benzoate or sodium phenylbutyrate, L-arginine and 10% dextrose infusion with normalization of the ammonia levels. She would then resume her protein-restricted diet, with orally administered sodium benzoate and citrulline. Functionally, she was independent in the activities of daily living. However, she was intellectually impaired with an IQ score of 40 and received special education.
She presented with the first episode of seizure at 21 years of age. She did not have previous febrile seizures in childhood. There was no family history of epilepsy. She had altered mental state and incoherent speech on presentation. The plasma ammonia levels remained normal, ranging from 16 to 45 umol/L.
An electroencephalogram (EEG) recorded non-convulsive seizures with the onset of rhythmic fast activity (Fig. ), occasionally starting at the left frontotemporal region before becoming generalized (Fig. ). These were associated with clinical manifestations of oral automatisms, impaired consciousness, and right-sided head turn.
Magnetic resonance imaging (MRI), which was performed 2 days after the first seizure presentation, showed T2/fluid-attenuated inversion recovery (FLAIR) signal hyperintensity in bilateral parahippocampal gyri with loss of gray-white matter differentiation and dilatation of bilateral temporal horns suggestive of hippocampal atrophy, due to mesial temporal sclerosis (Fig. ). There was also restricted diffusion noted in the parahippocampal regions on both sides (Fig. ). There was no prior MRI imaging performed. She was started on levetiracetam and pregabalin as these anti-epileptic drugs had minimal drug–drug interaction. Pregabalin was added on as she continued to have breakthrough seizures with levetiracetam. The use of sodium valproate is contraindicated in UCDs as it predisposes to hyperammonemia. Her seizures remained well controlled with the use of the two anti-epileptic medications. |
pmc-6046101-1 | Patient 1 is a 34-year-old Caucasian male with a past medical history of gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) who presented to the emergency department of an outside hospital with sudden onset and worsening epigastric pain. A computed tomography (CT) scan of the abdomen showed mild ascites within the pelvic cavity and thickening of the gastric antrum. Transabdominal ultrasound confirmed a small amount of ascites that did not require paracentesis. Esophagogastroduodenoscopy (EGD) revealed a chronic-looking, deep ulcer with radiating folds at the antral region of the lesser curvature of the stomach measuring 1.5 cm in diameter. Biopsy of the specimen revealed poorly differentiated, signet ring cell carcinoma (SRCC) without Helicobacter pylori co-infection. Positron emission tomography (PET) scan indicated active disease in the stomach and no evidence of locoregional or distant metastasis.
At this point, the patient presented at our institution for a specialized, second opinion on the management of his malignancy. Endoscopic ultrasound (EUS) and diagnostic laparoscopy with peritoneal washings did not identify nodal involvement or intraperitoneal metastatic disease, respectively, clinically staging the tumor as cT2N0M0. Per NCCN guidelines, the patient underwent three cycles of neoadjuvant chemotherapy with ECX regimen (epirubicin 50 mg/m2, cisplatin 60 mg/m2, and capecitabine/xeloda 625 mg/m2), which were tolerated well by the patient. Re-staging CT scan of the abdomen showed moderate regression of the cancer. Four weeks after completion of the last dose of ETC, the patient underwent total gastrectomy and omentectomy with Roux-en-Y esophagojejunostomy and feeding jejunostomy tube (j-tube) placement.
Pathology of the tissue revealed invasive, poorly differentiated gastric adenocarcinoma with singlet ring cell features that invaded into the muscularis propria and subserosal tissue, but with no evidence of invasion of the visceral peritoneum (T3) (Fig. a, b). Presence of malignant tissue was also confirmed with cytokeratin 7 immunostaining (Fig. c). The size of the tumor was 2.2 × 2 × 0.6 cm with negative margins, but with 3 of 41 lymph nodes positive for metastatic adenocarcinoma as evidenced by cytokeratin AE1/AE3 immunostaining (N2) (Fig. ). With no identified distant metastases, the pathologic staging of the tumor was ypT3N2M0, stage IIIA.
The patient recovered post-operatively without complications. Upon resumption of oral and j-tube feedings, the patient was discharged from the hospital and returned to work approximately 1 month later. Six weeks post-surgery, the patient began adjuvant chemotherapy with TCX (epirubicin was substituted for taxotere) for three cycles. Patient is currently under surveillance, and the most recent CT scan of the chest, abdomen, and pelvis identified no active signs of disease. Up to the time of the preparation of this manuscript, the patient continues to follow without clinic and currently displays no evidence of disease.
During the early course of medical workup at our institution, the patient received genetic counseling based on the high incidence of gastric and breast cancer in the family. Specifically, his mother was diagnosed with gastric cancer and died of the disease at the age of 49, while his sister died of the same disease at the age of 25. Further inquiry revealed that the maternal grandfather had also succumbed to what was likely gastric cancer based on the disease course provided by our patient, although a definitive diagnosis was never made. Furthermore, two maternal aunts were diagnosed with breast cancer in their 50s and 60s. The strong prevalence of these two cancers within the patient’s maternal lineage raised suspicion for possible hereditary diffuse gastric carcinoma (HDGC) secondary to a genetic mutation in the CDH1 gene, particularly based on the recently updated guidelines []. Subsequent genetic analysis at our institution confirmed a monoallelic deletion of exons 1–2 of the CDH1 gene, further corroborating the clinical diagnosis. |
pmc-6046101-2 | Patient 2 is a 32-year-old male and a younger sibling of patient 1. Given the recently identified CDH1 mutation and HDGC diagnosis in his sibling, patient 2 had a 50% likelihood of being a CDH1 mutation carrier. Subsequent genetic screening at our institution confirmed that similarly to his older sibling, patient 2 had a monoallelic deletion of exons 1–2 of the CDH1 gene, predisposing him to the HDGC like several members of his family.
Initial CT scan of the chest, abdomen, and pelvis and EGD biopsy of gastric tissue indicated no sign of active malignancy. However, given the ~ 70% lifetime chance of developing HDGC, the patient was recommended prophylactic gastrectomy despite showing no signs or symptoms of disease. The patient agreed with the recommendation and underwent prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy and feeding j-tube placement. Immunohistochemical analysis of gastric and intestinal tissue identified three microscopic foci of signet ring cells in the lamina propria without invasion of the submucosa (Fig. a, b), consistent with poorly differentiated adenocarcinoma of the stomach. The rest of the intestinal tract showed no signs of malignancy, and 0 of 30 tested lymph showed positive for metastatic carcinoma. The tumor was pathologically staged as pT1aN0M0.
The patient recovered without complications and was discharged home on post-operative day 7. He returned to the emergency department 5 days later due to diffuse abdominal pain, dark-colored emesis, and no bowel movements for 2 days. Initial CT scan of abdomen and pelvis revealed dilated, gas-filled, small bowel loops. With the presumed diagnoses of ileus vs. partial small bowel obstruction, the patient was re-admitted to the surgical floor for further management. Subsequent tests were unremarkable except for elevated amylase of 286 U/L and lipase of 1153 U/L, suggesting pancreatitis as a more likely source for his abdominal pain. The patient was managed per pancreatitis protocol and recovered well. He was subsequently discharged from our institution and continues to do well without evidence of disease at the time of this manuscript. |
pmc-6046101-3 | Patient 3 is a 23-year-old female and youngest sibling of the two aforementioned patients. Her past medical history was relevant for generalized anxiety disorder and gastritis, while family history was relevant for an offspring with cleft lip, another condition associated with CDH1 mutations. Her genetic screening revealed presence of the same genetic mutation that afflicted her older siblings, namely, monoallelic deletion of exons 1–2 of the CDH1 gene. Initial CT scan of the chest, abdomen, and pelvis and EGD biopsy were unremarkable. Similarly to her older brother, she agreed to undergo prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy and j-tube placement despite exhibiting no active signs or symptoms of disease. Immunohistochemical analysis of gastric and intestinal tissue revealed multiple microscopic signet ring cell foci varying in size, with the largest measuring 1 mm at its largest diameter (Fig. a, b). The tumor was confined to the lamina propria without evidence of invasion into the submucosa. All 23 tested lymph nodes tested negative for metastatic disease, and no other organ revealed signs of malignancy, staging the tumor as pT1aN0M0.
The patient recovered without major complications and was discharged on post-operative day 7 after abdominal pain and nutrition were adequately managed. Furthermore, the patient was offered prophylactic bilateral mastectomy given the increased incidence of LBC in women with CDH1 mutations. Initially, the patient refused the procedure citing the desire to breastfeed her future children and the low incidence of the disease prior to the age of 30. However, she subsequently consented to the procedure and underwent successful prophylactic bilateral mastectomy. During her outpatient recovery, patient 3 developed symptomatic gallstones. She re-admitted for a third time to undergo elective cholecystectomy and recovered without complications. She continues to follow-up with our clinic and currently displays no evidence of disease. |
pmc-6046142-1 | A 23-year-old nulliparous woman was admitted to a state hospital in Ankara Hospital with regular uterine contractions at 40 weeks of her pregnancy. She had no known prenatal risk factor except a history of a splenectomy, which was performed because of trauma-related hemorrhage according to her statement. Cesarean section (CS) was performed for obstructed labor without any complication, and severe PPH was diagnosed sixteen hours after the surgery. A postpartum hysterectomy was performed urgently because of uncontrolled bleeding. Persistent tachycardia and hypotension were recorded during the surgery and prehysterectomy hemoglobin value of 4 mg/dl was reported. Six units of erythrocyte suspension and four units of fresh frozen plasma were given during the surgery for replacement of the lost blood. Unfortunately, cardiopulmonary arrest (CPA) developed in the last stages of the surgery, and cardiopulmonary resuscitation (CPR) was performed for 40 minutes until spontaneous heart beats began. The patient could not be extubated after the surgery and neurological examination revealed early signs of cerebral ischemia. Then, the patient was taken to Hacettepe University Hospital for intensive care and further evaluation.
She had fixed bilateral dilated pupils, her Glasgow Coma Scale (GCS) was three, her body temperature was 33 centigrade degrees, her blood pressure was 143/70 mmHg (MAP=97), her heart rate was 120 beats per minute, and arterial pH was 6.81. Extensive periphery edema was observed, and moist rales were auscultated, which indicated the onset of pulmonary edema. Pneumothorax in the apical lobe of right lung, interlobular septal thickening, and ARDS findings were detected in thorax CT. Mechanical ventilation was applied with positive pressure and positive end-expiratory pressure (PEEP). Complete blood count, blood biochemistry, arterial blood gas, coagulation profile, C-reactive protein (CRP), disseminated intravascular coagulation (DIC) panel, cardiac enzymes, electrocardiography (ECG), and posteroanterior chest X-ray were evaluated. Multiple organ failure due to hypovolemic shock was diagnosed. Central vascular access was established. Fluid replacement and inotropic support with noradrenaline and dopamine were applied. The patient began to have treatment-resistant tonic-clonic seizures; antiepileptic and anesthetic drugs were given to stop the seizures. Targeted temperature management was started with surface temperature-management device. Hypothermia (34°C) was applied for the first 24 hours. Then normothermia (36°C) was applied for the next three days. The seizures were stopped after three days. Broad spectrum antibiotics (meropenem and colistin) were administrated. Cranial magnetic resonance imaging (MRI) revealed severe hypoxic ischemic encephalopathy and bilateral cerebellar herniation.
During the search for the possible medical cause of the severe bleeding the patient's past medical record was evaluated, and it was found out that the patient had splenectomy at the age of sixteen. To our surprise, the consultation reports seven years ago revealed the diagnosis of NPD B. She received reconsultation from the pediatric metabolism and pediatric gastroenterology divisions which revealed that her parents had a consanguineous marriage, and she also had an older brother with NPD B.
There was no sign of gaining consciousness one week after cessation of the sedative drugs and no brain stem reflexes were obtained. Apnea test was positive and cerebral CT angiography was compatible with brain death. On the 14th day at the intensive care unit, brain death was confirmed. Brain death was declared to the patient's relatives but they did not donate the organs of the patient. Two days after the patient was pronounced as brain dead, the patient died after cardiac arrest. |
pmc-6046143-1 | A 73-year-old woman presented with pain, redness, and worsening vision in the right eye several months after uncomplicated cataract surgery. She had no medical history and her surgical history included Ex-PRESS glaucoma shunt of the right eye and radial keratotomy in both eyes. She was found to have postoperative cystoid macular edema (CME) and was started on topical prednisolone acetate and diclofenac, a topical nonsteroidal anti-inflammatory drug (NSAID). After being lost to follow-up for two months, she returned with a decline in BCVA of 20/20 soon after cataract surgery to 20/60. Her CME had resolved, but she now had superonasal corneal thinning in the right eye with an overlying epithelial defect that stained with fluorescein and was 4 mm vertically and 2 mm horizontally in size. She also had pigment epithelial erosions more prominent inferiorly throughout her corneas in both eyes. Her radial keratotomy incisions were intact, and central corneal tomography was stable based on Scheimpflug imaging (Pentacam, Oculus Inc., Lynnwood, WA). PUK was diagnosed; moxifloxacin, doxycycline 100 mg bid, vitamin C 1 g bid, and artificial tears were started and prednisolone and diclofenac were discontinued.
Lab workup for systemic inflammatory and infectious conditions revealed a positive QuantiFERON gold but was otherwise negative. Chest x-ray was negative. In collaboration with the patient's internist, oral prednisone was deemed safe and a moderate dose was added to the patient's treatment regimen for PUK.
In this case, the patient's PUK was attributed to long-term use of a topical NSAID. After this was discontinued and prednisone was used for three months, she improved and has been stable with a BCVA of 20/25. demonstrates a slit-lamp photograph of the case at presentation and AS-OCT images before and after treatment. |
pmc-6046143-2 | A 76-year-old man was referred to our service for progressive redness and pain in the right eye. Six months earlier, his disease had been diagnosed as conjunctivitis, episcleritis, and senile furrow degeneration and he had been unsuccessfully treated with topical tobramycin/dexamethasone. His ocular and medical history and review of systems were unremarkable. BCVA in the right eye was 20/25 and slit-lamp examination revealed limbal injection, fine inferior keratic precipitates, and temporal corneal thinning with an overlying epithelial defect that measured 5 mm vertically and 2 mm horizontally and stained with fluorescein. The presumptive diagnosis of PUK was made and the patient was started on moxifloxacin q.i.d., doxycycline 100 mg bid, vitamin C 1 g bid, and topical lubricants.
Lab workup was notable for positive purified protein derivative (PPD) and QuantiFERON gold. Cyclic citrullinated peptide antibody test, a marker for rheumatoid arthritis, was also positive. All other laboratory assays were unremarkable and chest x-ray was normal. An infectious disease specialist was consulted at this time who recommended isoniazid, pyridoxine, and rifampin for the treatment of latent tuberculosis. We also consulted the rheumatology service that recommended we proceed with immunosuppression using prednisone 1 mg/kg and mycophenolic acid.
His condition improved after one month and a prednisone taper was initiated. However, PUK recurred, at which point oral prednisone was restarted at the original moderate dose and amniotic membrane was placed via a PROKERA lens (Bio-Tissue, Doral, FL) to promote epithelial corneal healing. He returned two weeks later with worsening keratitis at which point the lens was removed and topical prednisolone acetate t.i.d. was initiated. Symptoms stably improved for three months, after which he was very slowly tapered off topical and systemic prednisone. At his last visit, 16 months after presentation, he remains asymptomatic with a BCVA of 20/30. demonstrates a slit-lamp photograph taken at presentation and AS-OCT images taken before and after treatment. The etiology for this patient's PUK was deemed related to his autoimmune disorder with possible rheumatoid arthritis. Given the need for immunosuppression, antituberculosis medications were initiated under the care of an infectious disease specialist. |
pmc-6046149-1 | An 11-year-old female with Turner syndrome (45, X) presented to the eye clinic with strabismus and poor vision in the right eye. The patient was of short stature and had a webbed neck. Ophthalmic examination was remarkable for a visual acuity of counting fingers in the right eye and 20/20 in the left eye, 1+ right afferent pupillary defect, and having a constant esotropia of 15 prism diopters. Stereopsis was absent. Hypertelorism was present. The anterior segment was unremarkable. The optic nerve in the right eye was large in appearance with central excavation and extensive peripapillary pigmentation; some straightening of the retinal vessels arising from the disc margin was present (). The left optic disc appeared normal in size and was pink with a normal appearing cup and sharp disc margins (). |
pmc-6046157-1 | A 54-year-old previously healthy Caucasian female with otherwise unremarkable past medical history presented to emergency department with one-day history of hematochezia and abdominal pain. The patient described crampy left lower quadrant pain with no aggravating or relieving factors. She had a total of five bowel movements since symptom onset with the first bowel movement containing stool mixed with bright red blood followed by predominantly bloody stools. She took no medications on a regular basis and denied having a screening colonoscopy for colorectal cancer at age 50. She reported symptoms of upper respiratory tract infection (cold, sneeze, and cough) for which she took three doses of 120 mg pseudoephedrine purchased from a local grocery store for 1 day prior to symptom onset. Her maternal grandfather had prostate cancer but there was no significant gastrointestinal tumor history in the family. She was a nonsmoker and reported drinking socially (roughly one standard drink) once a week.
Her admission vitals were within normal limits. Physical examination was consistent with mild tenderness on the left side of abdomen and hypoactive bowel sounds. Rectal examination showed bright red blood without any stool in the rectal canal. Her laboratory values were significant for mild anemia with hemoglobin of 11.5 mg/dl, hematocrit of 34.5%, erythrocyte sedimentation rate 31 mm/hr, and C-reactive protein 2.15 mg/dl. A computed tomography scan revealed mild to moderate mural thickening of the descending/sigmoid colon consistent with colitis without pericolonic abscess, ascites, or free air (). An infectious workup was obtained including blood cultures, stool cultures, gastrointestinal panel for Clostridium difficile, and gastrointestinal viruses but was negative. She was resuscitated with intravenous fluids.
The patient underwent colonoscopy which demonstrated segmental moderate inflammation in the sigmoid colon, descending colon and splenic flexure along with internal and external hemorrhoids. There was evidence of submucosal hemorrhages with mild edema in the aforementioned segments of the colon (). Endoscopic findings were highly suspicious of ischemic colitis. Several biopsies were obtained from the inflamed areas which exhibited focal lamina propria eosinophilic change with mild crypt attenuation and loss of goblet cells consistent with mild ischemic changes. There was no evidence of chronic inflammation.
She was observed in the hospital for 3 days and her diet was progressed slowly. Her bloody bowel movements ceased after 1 day in the hospital and patient was counseled and educated regarding avoidance of pseudoephedrine and over the counter medications for symptomatic management. |
pmc-6046159-1 | The patient was a 65-year-old man with a prior history of repeated plastic surgery for scar contracture of the hands and fingers, ablation surgery for idiopathic ventricular tachycardia, and diabetes. There was no family history of no consanguineous marriage or EB.
He had experienced recurrent blistering of the skin that was readily caused by an external force since the time shortly after birth, which had been treated symptomatically. He was diagnosed with EB during a genetic consultation that he had received before getting married at the age of 28 years. Subsequently, he was diagnosed with RDEB at the age of 38 years. Application of a strong external force to the skin results in blister formation as early as 15 min. In June 2012, he presented to a nearby hospital with epigastric pain, where he was diagnosed with cholelithiasis and cancer in the transverse colon and was referred to our hospital. In September 2012, transverse colectomy and cholecystectomy were performed via laparotomy, followed by an uneventful postoperative course. In April 2013, a liver metastasis (S2) was detected. The lesion was a solitary tumor measuring ≤2 cm and was treated by radiofrequency ablation (RFA) in June 2013, again followed by an uneventful postoperative course. In September 2015, a recurrent tumor was detected at the site of RFA, with suspected invasion into the diaphragm. He was then admitted to our hospital for curative open surgery. On admission, although no active blistering was noted, pigmentation and scars due to recurrent blistering were noted especially in the extremities and back. Most fingers in both hands were club-shaped, with a few intact fingers. Blood test showed a mild increase in glucose to 123 mg/dl and increases in tumor markers, including mean levels of CEA and CA19-9 of 25.0 (0–5) ng/ml and 62.1 (0–37) U/ml, respectively.
Abdominal CT/MRI revealed a 3.5 cm metastatic liver carcinoma with diaphragmatic invasion in the lateral segment of the liver. In January 8, 2016, open partial hepatectomy of the lateral segment with combined diaphragmatic resection was performed.
The patient was asked to climb on the operating table on his own to minimize application of an external force to the skin. Epidural anesthesia was achieved by just one injection of 5 ml of 0.5% procaine into the epidural space. For endotracheal intubation, due to a difficulty in manually fixing a mask and lifting the lower jaw, the patient was asked to open his mouth and intubation was performed while the patient was conscious using intravenous injection of 1% propofol and intratracheal spraying of 1% xylocaine, under bronchoscopic guidance using a McGRATH™ MAC video laryngoscope (Covidien). Isodine disinfectant was used for skin disinfection of the surgical site, as the patient was tolerant of chemical stimulations. A skin incision was made sharply with a scalpel, with particular care taken to avoid contact of a steel instrument with the skin. Partial hepatectomy of the lateral segment with combined diaphragmatic resection was performed. The diaphragmatic defect was closed with a 2-0 nonabsorbable suture while the lung was compressed, without chest tube placement. A 19 Fr closed low-pressure continuous-suction drain was placed on the liver resection surface. A block catheter was also placed on the bilateral rectus sheaths in case of postoperative wound pain. The wound was closed by two-layer suturing with a 0 monofilament absorbable suture for the peritoneal muscle layer and a 4-0 monofilament absorbable suture for dermal closure. The wound was covered with a Mepilex® Border Ag dressing (Mölnlycke Health Care). The drain was fixed with a needle and a suture and then with a Mepitac® tape (Mölnlycke Health Care). The operative and anesthetic times were 346 and 457 min, respectively.
The patient was discharged from the hospital on day 9. He had an uneventful postoperative course with no abnormality of the wound in postoperative outpatient examination. |
pmc-6046164-1 | A one-year-old male patient referred to the Gastroenterology Clinic due to an unusual chronic constipation, associated with abdominal distension, since six months of age.
He was born full term, weight 3.2 kg and length 49 cm, presented meconium elimination within the first 24 hours of life, and neonatal screening was considered normal for hemoglobinopathies, phenylketonuria, and CH (filter paper thyroid-stimulating hormone, TSH < 10 mIU/mL). He was exclusively breastfed during the first six months, bowel habit was three times a day with normal stools, and no blood or mucus was ever noticed. While he started complementary feeding at this age (pureed fruit, vegetables, potatoes, and meats), bowel movements became once a week, being stools like separate hard lumps, with no blood, and requiring additional force to be eliminated. Even though he received laxative conventional therapy from six to twelve months of age, comprised by lactulose 2 mL/kg/day and glycerol suppositories 1g each five days, he showed no clinical improvement. Stools only occurred while taking suppositories.
Along with chronic constipation and abdominal distension, he also presented with failure to thrive, severe developmental delay, bradycardia, rarefied hair and eyebrows, hoarse cry, and macroglossia (Figures and ). Abdominal distension was mostly due to massively air-filled bowel (tympanism), with no palpable mass of stools. At one year of age, he was able to hold up his head (since eight months) but was unable to sit with support or say simple words. All growth standards are according to 2006 World Health Organization (WHO) []: weight 5.07 kg (<3rd percentile) and height 63.5 cm (<3rd percentile) (Figures and ).
Anorectal manometry (ARM) tracings showed a great variation in internal anal sphincter resting pressure, with some transitory relaxation along with the insufflation of the rectal balloon, showing the presence of the rectoanal inhibitory reflex. Nonetheless, there were many transitory relaxations in the resting pressure simulating rectoanal inhibitory reflex without rectal stimulus, which ended up as an inconclusive test (). Intestinal transit showed a massively dilated stool-filled colon, although small bowel was not dilated. Contrast took nine hours to travel from the stomach to the cecum, which presented a marked distention that reached a diameter of 12.5 cm (), along with a dilatation of the whole colon (). Contrast only reached sigmoid colon and rectum after six days through a colonic cleansing (). Thus, intestinal transit evaluation was compatible with motility disturbance and a massively dilated stool filled colon that brought up the hypothesis of Hirschsprung disease.
Although neonatal screening for CH was normal, considering his clinical appearance, the history of chronic severe constipation, abdominal distension, and bradycardia, as well as the poor growth and development, thyroid retesting was indicated and revealed a high TSH (>100 mcIU/mL; normal range: 0.27–4.2) and a low free thyroxine (free T4, <0.15 ng/dL; normal range: 0.93–1.70). Levothyroxine sodium (LT4) replacement therapy was started immediately. After one month of adequate LT4 therapy, bowel movements were recovered, and intestinal habit became once a day with normal aspect stools. After six months of adequate LT4 therapy, laxative therapy was discontinued, and he recovered clinical aspect, with no abdominal distension (Figures and ), showing a rapid catchup in both weight and growth velocity (Figures and ). ARM was repeated and considered completely normal (). At 1.6 years of age, he was able to sit without support, and at 1.9 years, he started walking with support and saying simple words.
At five years of age, he showed no physical delay, with normal language and communication, socially and emotionally adequate, with satisfactory LT4 replacement. Weight was 16.4 kg (15–50th percentile) and height was 110.7 cm (50th percentile) (Figures and ). So far, the etiology of primary CH was defined as a thyroid hypoplasia through ultrasonography.
At eight years of age, he was euthyroid, with appropriate weight and height, respectively, 21.6 kg (50th percentile) and 128.6 cm (50th percentile). Nonetheless, despite normal thyroid function, he presented with a relapse of constipation, being bowel movements once or twice a day with scybalous stools, associated with a discrete abdominal distension (TSH 1.66 mcIU/mL; free T4 1.22 ng/dL). Laxative diet and medications (macrogol 1.5 g/kg daily) were reintroduced with poor clinical response. Serological testing for celiac disease was performed, with normal results of total immunoglobulin A (IgA) and tissue transglutaminase (tTG)-IgA antibodies. Rectal mucosal and submucosal biopsies were performed and showed the presence of normal ganglion cells (at 2, 4, and 6 cm above the dentate line). He started sacral transcutaneous electrical nerve stimulation (TENS), whose parameters were 20 Hz and 200 µs, during 30 minutes weekly, with electrodes placed in the corresponding S2 and S3 dermatomes. After four sessions, he presented with improvement of bowel habit.
The mother provided written consent and permission to publish this case. |
pmc-6046166-1 | A four-year-old girl presented to the emergency service with painful left hip and fever. There was no previous relevant medical history. There were no other local or systemic symptoms, except for a cervical adenopathy. On physical examination, she walked with a limp, and movements of the left hip were painful (mainly external rotation), but not restricted. Blood exam revealed anemia (Hb 8.7 gr/dL), normal WBC, ESB of 123 mm, and reactive C protein of 149.7 mg/L. An initial X-ray to the pelvis revealed no changes. An ultrasound of the left hip was performed revealing small infusion and synovitis. Guided puncture was then performed being macroscopically compatible with reactive arthritis, and general and bacteriological tests were demanded. Because of the unusual characteristics of the pain, a CT scan to the abdomen and pelvis was performed revealing a left adrenal mass and retroperitoneal adenopathies in the celiac trunk and superior mesenteric artery ().
Despite the painful complaints of the patient, no bone or articular involvement was found in the CT scan. No further alterations were reported in the thoracic CT scan or in peripheral blood smears. Bacteriological examination of the hip effusion was negative. MRI was also performed. The direct myelogram was compatible with infiltration from neuroblastoma. Bone marrow biopsy and cervical adenopathy specimens were collected to perform histological diagnosis. Skeletal scintigraphy demonstrated numerous points of osteoblastic activity compatible with metastatic activity, and the 12 iodine-123 metaiodobenzylguanidine scintigraphy concluded the following: “Abdominal mass with low expression of noradrenergic transporters. Diffuse bone metastasization with high expression of noradrenergic transporters. No other soft tissue involvement was detected.” In the histological report of the cervical adenopathy, the diagnosis of neuroblastoma NOS was performed. Immunohistochemistry revealed extensive expression for synaptophysin and CD56 (NCAM) and absence of expression of myogenin. ().
Bone marrow biopsy revealed extensive metastatic involvement. The patient started chemotherapy two weeks after admission, with 8 cycles of rapid COJEC protocol. After six months of follow-up, the primary tumor was still without criteria for resection, despite a decrease in the metastatic involvement. Given the chemotherapy-related renal toxicity, it was decided to proceed with irinotecan in combination with temozolomide (TEMIRI). After thirteen months of follow-up, no significant regression of the primary tumor occurred, so surgery was contraindicated and the patient was proposed for stem cell treatment. |
pmc-6046172-1 | Patient A presented as a mostly healthy 15-year-old Caucasian female with some developmental disabilities and ADHD, characterized by poor attention span, poor attention to details, poor organization, forgetfulness, excessive talking, impulsivity, and distractibility since age seven. Her father reported two severe brain injuries around the age of five. Over the course of one year at age 15, she required four inpatient psychiatric hospitalizations and numerous outpatient and medication management appointments due to an acute onset of “seizure-like” spells, psychotic thinking, and seemingly schizophrenic symptoms, manifesting as auditory hallucinations (AH) and catatonic movements. The differential diagnosis included schizophrenia, severe Tourette syndrome, Major Depressive Disorder, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder.
Over time, Patient A had several strange physical symptoms including dysphonia, mouth twitches, echolalia, frequent pacing, frequent cussing, holding her breath, repeatedly asking the same questions, crying and laughing for no reason, staring, outstretching of her arms for 30 minutes, stumbling, worsening dysgraphia, unable to solve math problem, and worsening reading skills.
Initially, the change in her behavior was thought to be a neurologic issue due to the “seizure-like” spells, characterized by uncontrollable mouth twitching, eye rolling, and staring into space. However, after an unrevealing neurology evaluation she was referred to psychiatry. Mood and anxiety disorders were also suspected due to fears of social situations, making mistakes, and trying new things in conjunction with irritability, muscle tension, insomnia, self-consciousness, stomachaches, and feelings of worthlessness resulting in self-blame.
After a few months of declining mental health, patient A began outpatient psychotherapy sessions, where she discussed issues with being bullied and social anxiety at school. During these sessions, patient A's professional clinical counselor (LPCC) consistently noted she was zoning out, mouthing words silently, seemingly in response to internal stimuli, and exhibiting unilateral catatonic right arm movements.
Due to the lack of outpatient success, patient A was admitted to a partial hospitalization program (PHP). There, she displayed symptoms of mouthing words and laughing as a response to internal stimuli, outbursts of cussing at friends not present, leaving food in mouth for hours before swallowing, and deterioration of handwriting. Due to the severity of symptoms, patient A was admitted to an inpatient psychiatry unit, where she was diagnosed with a psychotic disorder. Interestingly, she had experienced a Streptococcus infection one month prior to this first admission. While on the inpatient unit for eight days, risperidone 0.25 mg BID was started and sequentially increased to 0.5 mg QAM and 1.0 mg QPM, which caused enough improvement for patient A to return to the PHP. All neuroleptic trials for this patient lasted for about six to eight weeks.
The prevalence of her auditory hallucinations (AH's) increased in quantity and severity while in the PHP, so she was admitted a second time to inpatient psychiatry, where she began treatment for psychosis and schizophrenia. During this admission, she admitted that some of the voices in her head were her own and another voice was a male bully from school telling patient A to kill herself, raising questions as to whether these were actual AHs or flashbacks from past traumatic experiences.
Unfortunately, patient A continued to have difficulty with chewing and swallowing food, which led to gagging, choking, and emesis, as well as echolalia, restlessness, inappropriate smiling, and irregular arm movements. Her medication regimen was further altered to include benztropine 0.5 mg BID, ziprasidone 20 mg BID, and trazodone 25-50 mg at night for sleep. On this medication regimen, patient A showed improvement for the first few days before the AHs and other symptoms began to once again hinder her daily function.
After almost two weeks of crisis stabilization, patient A was discharged and sent back to the PHP, where thought blocking, flat affect, responding to internal stimuli, anxiety, and jerking movements persisted. She then began having self-harm and suicidal thoughts. Ziprasidone was increased to 40 mg QAM and 80 mg QPM with the goal of relieving the AHs while minimizing psychotic and seemingly schizophrenic symptoms. Propranolol 10 mg was introduced as needed for agitation. After little improvement, she was admitted to inpatient for a third time for a higher level of care.
During this hospitalization, ziprasidone was cross-tapered with aripriprazole with little benefit. Aripriprazole was then cross-tapered with lurasidone up to a dose of 40 mg QAM. Benztropine was increased to 0.75 mg BID and lorazepam to 0.25 mg BID and 0.5 mg QHS was also started. The as needed trazodone and propranolol were discontinued. With this regimen, AHs were only reported every other day, and activities of daily living (ADL) were able to be completed with less anxiety and prompting from staff, allowing her to be discharged from her third inpatient hospitalization. |
pmc-6046173-1 | A 13-year-old female patient was presented for consultation to the Department of Orthodontics and Dentofacial Orthopedics, School of Dentistry, Lebanese University. Her chief complaint was the crowding of her anterior teeth. Her medical and dental histories were noncontributory, and the patient did not mention any previous or recent habit. On physical examination, no swelling or tenderness was documented.
Upon clinical examination, the patient had all her permanent teeth and a retained mandibular left second primary molar. Radiographic records consisted of an orthopantomogram, a lateral cephalogram, a posteroanterior cephalogram, and a hand wrist radiograph. The orthopantomogram revealed a well-defined radiolucent lesion on the mandibular left side surrounding the unerupted mandibular left second premolar which appeared to be mesially tipped below the retained primary second molar. The root of the adjacent premolar was included in the lesion but did not reveal any root resorption (Figures and ).
Going back to the old orthopantomogram (OPG) of the patient collected by the Pediatrics Department, it was noted that no lesion was visible at that time (). The patient was referred to the Oral Pathology Department in order to obtain a meticulous diagnosis concerning the radiolucent lesion that was detected on the orthopantomogram during the initial diagnosis. The differential diagnosis for the lesion included a DC, an odontogenic keratocyst, and an ameloblastoma. Histologically, a thick epithelial lining with rete ridges was present. Moreover, chronic inflammatory cellular infiltration appeared in the capsule of the cyst. All these findings confirmed that the diagnosed cyst is a DC. The major objective of initiating the treatment as early as possible in this patient was to hinder the progression of the DC prohibiting its destructive consequences. Moreover, the aim of initiating a nonaggressive (marsupialization) treatment was to save the involved tooth, allowing its healthy eruption.
Several treatment modalities of a DC have been reported in the literature ranging from marsupialization to enucleation. The common treatment for DC is enucleation followed by extraction of the involved tooth. When the cyst is large, the first approach is marsupialization to decrease the size of the osseous defect and then enucleation and tooth extraction are performed afterwards [–].
Enucleation is the chosen treatment plan whenever the cyst is small and saving the involved tooth is impossible. This treatment modality should be avoided in large cysts since it is usually accompanied by facial, esthetic, and functional defects [].
Other approaches are considered when the cyst is small and when the patient is young. In cases of enlarged follicles of impacted canines, exposing the affected tooth surgically and the traction of the tooth by orthodontic means leads to the cessation of the cystic lesion and the preservation of the affected tooth [].
Taking into consideration that the diagnosed cyst can potentially become an aggressive lesion with a bone destructive ability that might lead to loss of the involved teeth, root resorption, pain, and facial asymmetry, and considering the age of the patient, a primary approach by marsupialization was initiated ().
After the surgery, the patient was instructed to wear the acrylic resin obturator that was previously fabricated to maintain the surgical opening during healing and assure success of the surgery (). The patient was asked to eat with the obturator in place and remove it only for cleaning. Follow-up appointments were scheduled every three months postsurgery to assure the eruption of the second premolar and the absence of any recurrence.
The postsurgical orthopantomogram (OPG) that was taken 6 months after the surgery revealed the absence of any radiolucent lesion and the successful eruption of the mandibular left second premolar (Figures and ). |
pmc-6046175-1 | An 85-year-old woman presented to the emergency department with sudden onset of paraparesis, numbness of the legs, and inability to void. She reported having experienced diaphoresis before presentation. She was transferred to our hospital 4 h after onset.
Her medical history was unremarkable apart from hypertension. Her blood pressure was 160/90 mmHg, and her heart rate was regular at 80 bpm. She was alert and oriented but had difficulty standing up. Physical examination revealed dissociated sensory loss below T4 in which sensory perception of vibration and touch was preserved. Muscle function was completely impaired in the left lower extremity globally but somewhat preserved on the right side with a power of 0/3 on the Medical Research Council (MRC) scale. The deep tendon reflex was absent on both sides. Based on these findings, we graded her condition as ASIA grade C. The NIH stroke scale (NIHSS) score was 6 on admission. Six hours after onset, we performed enhanced computed tomography of the whole body and magnetic resonance imaging (MRI) of all spinal lesions. MRI revealed no abnormality, such as ossification, stenosis, a mass, or intramedullary signal changes (). CT revealed a thrombosed aortic dissection in the descending aorta (Stanford type B) and severe arteriosclerosis ().
Two days after admission, repeat MRI revealed a linear high signal intensity area on T2-weighted images in the ventral parts of the spinal cord at T3–T10. These areas were confined to the anterior horn in the axial plane. Diffusion-weighted MRI showed slight abnormality on day 5 (). Therefore, we made a diagnosis of spinal cord infarction manifesting as sulcal artery syndrome.
Antihypertensive therapy was started. After intensive rehabilitation, her paralysis gradually improved to the point that she was able to walk with the aid of a T-cane and catheter could be removed. |
pmc-6046175-2 | The patient was a 68-year-old man who presented to the emergency department after developing sudden complete paraplegia with mild neck pain. He was transferred to our hospital 11 h after onset.
On examination, his blood pressure was 149/74 mmHg and his heart rate was regular at 70 bpm. Complete flaccid paralysis was noted in both lower extremities with a power of 0/0 on the MRC scale as well as loss of all sensation below L1. A digital rectal examination revealed no sensation with absent anal tone. Urinary retention was also present. Based on these findings, we graded his condition as ASIA grade A. The NIHSS score on admission was 10.
MRI performed 24 h after onset showed high signal intensity in the conus medullaris on T2-weighted images but no compression. Axially, the abnormal signal extended throughout the affected area of the spinal cord. We then performed diffusion MRI, which showed the abnormality more clearly (). Spinal fluid was examined, but no abnormality was detected.
Enhanced computed tomography revealed aortic dissection with an aortic aneurysm in the distal arch. The aneurysm had a diameter of 61 mm, which is an indication for surgery ().
Antiedema therapy was started, and rehabilitation was undertaken, during which the patient was monitored carefully. Unfortunately, his physical dysfunction did not improve after 3 months of hospitalization. The patient was finally transferred to another hospital for surgical repair of the aortic aneurysm. |
pmc-6046177-1 | A 48-year-old male presented in surgery clinic with a clinical history of benign prostatic hyperplasia and a 6-year history of an enlarging right inguinal hernia, with associated increase in discomfort. On physical examination, a cystic mass was palpated on the superior right testicle, and a firm, solid mass was found in the right groin. The testicular mass was fully mobile within the subcutaneous space and minimally tender and did not appear to be connected to the external ring. The patient had no other complaints, and the rest of his physical examination was unremarkable. A follow-up computed tomography (CT) scan revealed a partially visualized, heterogenous, and enhancing right inguinal mass, raising the concern for a peripheral nerve sheath tumor or sarcoma of the spermatic cord ().
The mass was surgically excised from the spermatic cord. During surgery, it was noted that the mass was located inside the external cord, but outside of the internal spermatic fascia. It had eroded through the aponeurosis of the external oblique muscle. Nonetheless, the mass could easily be separated from the spermatic cord and was submitted to pathology for evaluation. Macroscopically, the mass weighed 67.5 grams and measured 7 x 5.5 x 2.5 centimeters. Its outer surface was smooth, pink/white in color and covered by a thin membrane. The cut surface of the mass was white and firm and had a whorled texture containing occasional small cysts (). The tumor border is well delineated. The margin is inked green ().
Microscopically, the tumor had a heterogeneous pattern-less architecture with alternating hypocellular and hypercellular areas, interstitial hyalinization, and intermixed with ropy collagen bands (). The most prominent feature of the tumor was found within the vascular compartment. Numerous small- to medium-sized vessels were present and showed a continuum of changes, ranging from thick-walled vessels showing proliferation of myocytes, to vessels revealing intimal thickening, to vessels with circumferential prominent mural hyalinization (). Some of the larger vessels displayed subendothelial mucoid degeneration resembling vascular changes observed during accelerated hypertension (). When the course of one of the vessels was followed, the vessel was found to have cellular myocytic proliferation in some segments followed by hyalinization in other segments. Occasional individual exuberant hemangiopericytoma-like vascular channels were also present ().
The neoplastic cells were ovoid to spindle-shaped with scanty pale cytoplasm and oval to fusiform nuclei (). Mitosis was scarce and at less than one per 10 high power fields, and the margins were free of tumor. Immunohistochemical results for the patient are listed in . The tumoral cells expressed CD34, BCL-2, and CD99. They were also focally positive for Estrogen Receptor (ER) and Progesterone Receptor (PR) and negative for Smooth Muscle Actin (SMA) and S100. A STAT6 stain was ordered and revealed nuclear positivity in the tumoral cells but negative staining in the vascular myocytes (). No follow-up data is available due to the recent removal of the tumor at the time of writing of this case report. |
pmc-6046178-1 | A 55-year-old Caucasian male was admitted to our hospital with a history of biventricular systolic heart failure due to ischemic cardiomyopathy and chronic stage IV kidney disease due to diabetic nephropathy; one month earlier, he had been approved for combined heart-kidney transplant. He recently had increased fatigue and dyspnea, weight gain of 8 kg, and serum creatinine that increased from 2.3 mg/dL to 3.7 mg/dL despite outpatient inotropic and diuretic therapy. Other comorbidities included antiphospholipid syndrome under warfarin management, multiple myocardial infarctions, with 2 coronary artery bypass grafting procedures, placement of biventricular automated implantable cardioverter-defibrillator, and placement of left ventricular assist device (HeartWare) 5 months earlier.
On hospital day (HD) 14, after optimization of hemodynamics with diuretics and inotropic support, the patient was listed for heart-kidney transplant and transferred to the intensive care unit. On HD 24, the patient was taken to the operating room for combined heart-kidney transplant; however, only orthotopic heart transplantation (OHT) was possible. During the OHT, acute right ventricular graft dysfunction developed, resulting in cardiogenic shock, requiring placement of VA-ECMO support through central cannulation and withholding of the single-kidney transplantation. VA-ECMO was utilized to allow the newly transplanted heart to rest and recover and to optimize hemodynamics and volume status in order for the patient to eventually receive the single-kidney transplantation. Simultaneously, he received support with vasopressin 0.04 U/min, dobutamine 10 mcg/kg/min, epinephrine 0.01 mcg/kg/min, and full-dose anticoagulation with heparin 9.5 U/kg/hour. Tables and show the initial and subsequent laboratory results and ECMO parameters.
On post-OHT day 1, after the patient had improved volume and cardiovascular status, adequate urine output (1,660 mL/24 hours), and stable laboratory testing parameters, the heparin infusion was reduced to 5.5 U/kg/hour (i.e., low dose) and the patient underwent deceased-donor renal transplantation (DDRT). During the DDRT procedure, the patient received 1 unit of packed red blood cells and had no complications. After DDRT, the patient required epinephrine at 0.03 mcg/kg/min, dobutamine at 10 mcg/kg/min, and heparin at 5.5 U/kg/hour.
During the first 48 hours after DDRT, the patient's urine output was adequate (1,900 mL in 24 hours) and his serum creatinine concentration decreased to 2.0 mg/dL. On post-DDRT day 2 (post-OHT day 3), after repeated transesophageal echocardiography showed improved right ventricular function and optimal volume status, the patient underwent ECMO decannulation, chest washout, and sternal closure without complication. His renal function continued to improve, and his anticoagulation was discontinued. The only inotropic support needed was dobutamine at 7.5 mcg/kg/min. On post-DDRT day 5 (post-OHT day 6), the patient was successfully weaned from mechanical ventilation and on post-DDRT day 18 (post-OHT day 19) was transferred to the posttransplant care unit for further care. |
pmc-6046180-1 | A young man in his early twenties with no prior history of medical treatment started experiencing stiffness in his left leg during physical activity when he did his mandatory military service. A few years later, after a short stay in hospital, he was diagnosed with a functional movement disorder. He had an older sister affected by PD with disease onset in her late forties. Between age of 30 and 40 he was seen by several neurologists as he experienced worsening of asymmetric stiffness, pain, and sensory symptoms in his lower extremities. He was finally diagnosed with PD around age 40. He responded well to levodopa treatment and after many years on levodopa he developed increasing dyskinesias. He managed to stay in his academic position up in his midsixties and underwent STN DBS at age 65 because of medically intractable dyskinesias. He lived at home with support of health care assistance until his death at age 79. He did not show any sign of dementia.
Multiplex ligation-dependent probe amplification (MLPA) analysis revealed a homozygous deletion of exons 3-4 in the Parkin gene []. |
pmc-6046181-1 | A 63-year-old female sought medical intervention for a painless, firm, mobile mass within her right cheek. For the previous year-and-a-half, she had experienced right facial nerve paralysis, which progressed to facial numbness and progressive hearing loss. A PET-CT scan showed an FDG-avid 2.2 x 2.0 cm mass centered along the anterolateral aspect of the right masseter muscle without parotid gland involvement (). An MRI of the lesion indicated enhancement of the right trigeminal nerve from its origin to the point where it entered Meckel's cave along with enhancement of the right facial nerve from the internal auditory canal to the middle ear. A fine needle aspiration of the mass showed clusters of atypical spindled cells with elongated, irregular nuclei; the tumor was diagnosed as a malignancy consistent with neural or mesenchymal origin (Figures and ). A total right parotidectomy with selective resection of the facial and trigeminal (mandibular division) nerves was performed. Histopathologic review showed a tumor adjacent to, but not primarily involving, the parotid gland, characterized by a proliferation of spindle cells, many with multiple nuclei, grouped in interwoven fascicles and heavily interwoven with lymphocytes (). Nuclei were prominent and markedly pleomorphic, and the mitotic index was high (28/10 high-power fields; ). Immunohistochemical stains showed S100 to be strongly and diffusely positive (); collagen IV was 2+ positive around individual tumor cells (); Mart1/MelanA and HMB-45 were negative (not shown). Pancytokeratin, CK5/6, p63, desmin, CD34, and the mutant protein BRAF V600E also were negative. The tumor was diagnosed as a poorly differentiated MPNST. There was no evidence of metastatic tumor in the additionally submitted lymph nodes. The patient subsequently completed radiation therapy.
Approximately eight months after the initial resection, the patient presented with severe hearing loss in her right ear and difficulty with walking and balance. An MRI revealed a 6.4 mm, contrast-enhancing lesion at the right cerebellopontine (CP) angle () and a similar 3.8 mm lesion slightly distal running along the 7th cranial nerve. At this time, a 1.5 x 1.5 cm irregular pigmented lesion also was noted on her right cheek. A punch biopsy of this lesion revealed LMM (). In this biopsy, the Breslow depth was 0.25 mm; neither ulceration nor dermal mitotic activity was noted. Additionally, although neither lymphovascular nor perineural invasion was identified, the possibility was raised that the original parotid-region mass represented a metastatic melanoma instead of a separate primary MPNST.
The patient then underwent resection of the CP angle tumor as well as cranial nerve 7 approximately 23 months after the parotid-region mass was resected. Histopathologic review demonstrated spindled-to-epithelioid cells with pleomorphic nuclei (). In several areas, fine, golden-brown pigment was observed. The mitotic index was 4/10 high-power fields, and a Ki-67 immunostain showed an 18% index of proliferation. Similar to the original parotid-region mass, the tumor showed strong and diffuse positivity for S100 (), and there was weak focal reactivity for collagen IV (). Unlike the originally resected parotid-region mass, the CP angle lesion exhibited strong and diffuse positivity for Mart1/MelanA and HMB-45 (Figures and ) and was diagnosed as malignant melanoma.
She also underwent a wide excision of her right cheek melanoma, which revealed residual melanoma with a Breslow depth of 0.55 mm. Again, no dermal mitotic activity, ulceration, lymphovascular, or perineural invasion were noted. The tumor was again positive for Mart1/MelanA, as was demonstrated in the original biopsy.
Given the uncertain relationship between the original parotid-region and the CP angle masses, next-generation sequencing of a panel of 300+ genes was performed on both the parotid-region mass and the CP angle lesion (Foundation Medicine; Boston, MA). Both tumors showed high tumor mutation burden (TMB), and each showed over twenty potentially clinically significant genomic alterations; among these, they shared nineteen (). |
pmc-6046184-1 | A 63-year-old male presented to a private hospital complaining of asymptomatic gross hematuria. Computed tomography (CT) showed a hypervascular tumor affecting the right kidney. The tumor measured 10 cm in diameter with tumor thrombus toward the inferior vena cava (IVC) (). In addition, direct infiltration to the liver was observed (). Regional lymph node metastasis, multiple lung metastasis (), and intramuscular metastasis of left femoral muscle () were also observed (clinical staging of T4N1M1). The patient was referred to our hospital for treatment. Initially, indication of cytoreductive nephrectomy was questionable; therefore, we administered presurgical axitinib treatment according to our previously described protocol []. One-month treatment achieved shortened tumor thrombus and shrinkage of the primary site (); however, liver invasion had progressed (). Lung and intramuscular metastases were controllable (Figures and ). In spite of an increase in the dose of axitinib, liver infiltration was revealed to be worsening at 2 months from initial treatment (). Therefore, we considered immediate surgical intervention with en bloc right nephrectomy and hemihepatectomy. After discussion with liver surgeons, we attempted a perioperative PVE to preserve residual liver volume and function after right lobectomy (including invaded tumor) in consideration of chemotherapy-induced liver functional deterioration and high risk of major hepatectomy.
Department of Surgery policy at our institute requires that indocyanine green retention rate at 15 minutes (ICGR15) be determined preoperatively for the liver to be resected using the formula described by Takasaki et al. []. The estimated resected liver volume, excluding tumor volume (cm3), is measured by computed tomography volumetry []. The present volumetric analysis was conducted using Synapse Vincent Work Station (Fujifilm Medical Co., Tokyo, Japan). Essentially, in cases where the permitted resected volume is less than the estimated volume, or the estimated volume is greater than 65% in normal liver, preoperative PVE is selected []. In the present case, ICGR15 was 5.7% and the comprehensive evaluation of liver function was Child-Pugh grade A. The estimated resected liver volume was 921 cm3 (71% of the whole liver) (). PVE was performed by 2 interventional radiologists. Substances used for embolization were 4 sheets of gelatin lipiodol, Serescue (Nihon-Kayaku Co., Tokyo, Japan), mixed in contrast media, and 2 permanent microcoils were subsequently placed in the right portal veins. The post-PVE coarse was uneventful, resected volume was reduced from 921 cm3 to 599 cm3 (53.4 % of the whole liver), and an increase in remnant left liver volume of 523 cm3 (46.6 %) was achieved on day 14 after PVE (Figures and ). Preoperative ICGR15 was mildly worsened at 18%; however, the permitted resected volume by Takasaki's formula was maintained. The scheduled operation was performed on day 35 after PVE following a 3-day drug-off period.
The patient was placed in the left hemilateral position. Thoracoabdominal incision was made via the 9th intercostal space accompanied by upper abdominal midline incision. The urological surgeons first mobilized the ascending, transverse colon, and duodenum, and the right renal artery was dissected at interaortocaval region. Intraoperative ultrasound examination revealed that a shortened tumor thrombus remained within the renal vein and right renal vein dissection. Because of the tight connection between the kidney and liver and confirmation of tumor connection to the right side of vena cava, we were unable to perform ordinary liver mobilization at this stage. At this point liver surgeons were deployed. Placement of nasogastric tube in the retrohepatic space for LHM was performed according to the original Belghiti's maneuver () []. Prior to the transection, the right hepatic artery and portal vein were ligated and divided after confirmation of tumor invasion into the liver. Liver transection at the midline of the liver was easily achieved under intermittent hepatic inflow occlusion (three sessions at 15-minute intervals) and continuous hemiclamp of the infrahepatic vena cava through the maintenance of central venous pressure at 8 mmHg. After hepatic parenchymal transection exposing vena cava, the right hepatic veins were safely transected using vascular stapler. Finally, urological surgeons performed partial resection with direct closure of vena cava infiltrated by the tumor under good operative view and eventually achieved combined resection of right kidney and right liver. Apparent invasion to other retroperitoneal tissue was not observed except for right adrenal gland. Total operation time was 8 hours and 47 minutes, and total bleeding volume was 2370 ml. The patient recovered without postoperative hepatic or urinary complications and has remained free of local recurrence and any de novo metastasis for 18 months (Figures and ). Tyrosine kinase inhibitor treatment was initiated one month after surgery.
The tumor was composed of atypical polygonal cells (Fuhrman grade 2) with clear cytoplasm proliferating mainly in solid or nested fashion (), and papillary architecture was also observed in part of the tumor. The pathological findings were compatible with clear cell RCC. The tumor cells infiltrated directly to the renal vein, renal pelvis, right adrenal gland, and the liver (Figures -). Apparent pathological difference between primary site and invasion front was not confirmed (). Necrosis was observed in approximately 50% of the tumor with organization of obstructed medium-sized vessels, suggesting the effect of presurgical treatment (). Apparent infiltration of cancer cells to vena cava was not observed. |
pmc-6047104-1 | A 22-year-old man with a history of AU and moderately severe AD (Investigator's Global Assessment score of 3) presented to the clinic for treatment. The patient had a history of AD since childhood with more recent onset AU that progressed in the last 5 years. Physical examination at presentation demonstrated multiple eczematous patches affecting his face, back, chest, and bilateral upper and lower extremities (, A-D). The patient's itch severity based on the numerical rating scale itch score was 8 (of 10). He also exhibited patches of hair loss on the scalp, eyebrows, eyelashes, face, chest, and bilateral upper and lower extremities (, A-D). Skin biopsy results of the scalp were consistent with those of AU, which was previously treated with intralesional steroids, methotrexate, and mycophenolate mofetil with minimal improvement. Despite treatment with topical steroids, H1 and H2 antihistamines, and phototherapy for his AD, his condition remained refractory. Additionally, his AD also did not improve while receiving methotrexate and mycophenolate mofetil for his AU. Because of the lack of response of both AU and AD to multiple systemic therapies, the patient was started on off-label tofacitinib at a dose of 5 mg orally, twice daily. After 10 months of treatment, the patient experienced hair regrowth on all of the affected body parts with subsequent improvement of his AD (, E-H). After treatment, the patient reported a numerical rating scale itch score of 3. Importantly, no adverse effects were reported in terms of clinical symptoms and abnormal laboratory tests. |
pmc-6047112-1 | Case 1 involved a 6-year-old boy with bronchial asthma and delayed language development. He had experienced a total of three episodes of hypoglycaemia and convulsions during a common cold at 3 years of age. Acylcarnitine analysis of dried blood spots (DBSs) revealed an elevated tetradecenoylcarnitine concentration (C14:1 7.42 μM, cut-off < 0.4 μM) that was highly suspicious of VLCAD deficiency. ACADVL gene analysis revealed two novel mutations, L243F and V547M. Additionally, VLCAD enzyme activity in fibroblasts derived from this patient was 30% of normal, leading to a definite diagnosis of VLCAD deficiency. l-Carnitine supplementation was initiated at a dose of 600 mg/day (37.5 mg/kg/day) because the patient presented with a low free carnitine concentration (C0 7.45 μM, reference value 20–60 μM) at 3 years and 6 months of age. The dose was increased to 900 mg/day two months later. One month after beginning l-carnitine treatment, the patient presented with more frequent recurrent episodes of rhabdomyolysis, particularly when suffering from a common cold or an asthma attack or on sick days characterised by general fatigue. He ultimately experienced 11 episodes of rhabdomyolysis and was hospitalised 10 times during the 15 months of l-carnitine administration (). His C0 concentration was elevated (C0 44.3 μM) during the course of l-carnitine treatment; however, his C14:1 concentration did not decrease during his rhabdomyolysis episodes. It was suspected that the patient's rhabdomyolysis was triggered by l-carnitine supplementation; therefore, l-carnitine supplementation was stopped when the patient was 4 years and 9 months of age. The patient subsequently experienced rhabdomyolysis with acute bronchitis only once during the next 15 months despite a lack of specific changes in his lifestyle. |
pmc-6047112-2 | Case 2 involved an 8-year-old boy, the elder brother of case 1. These siblings did not undergo expanded newborn screening. He exhibited developmental delay but no respiratory problems. No abnormalities were observed in the acylcarnitine analysis of DBSs (C14:1 0.28 μM, cut off < 0.4 μM) at 1 year of age. Although the patient caught up with respect to his developmental milestones, he exhibited autistic behavioural characteristics. When he was 5 years old, he was diagnosed with VLCAD deficiency via genetic testing conducted after his brother was diagnosed. Genetic analysis revealed that he had the same compound heterozygous mutation as his brother. Because this patient's free carnitine concentration was close to the lower limit of the normal range (C0 23.7 μM, reference value 20–60 μM), l-carnitine treatment (900 mg/day; 45 mg/kg/day) was started. Two months later, the patient developed rhabdomyolysis for the first time in his life when he was suffering from a common cold. l-Carnitine supplementation was subsequently ceased, and the patient experienced no additional rhabdomyolysis episodes, even when suffering from influenza. |
pmc-6047121-1 | Our patient was a 9-year-old Arab boy who had had SDNS since the age of 5 years. Because of several relapses over the previous 4 years, and in an effort to spare steroid use and its long-term use complications, the patient was treated with levamisole. His family history revealed that his parents are nonconsanguineous and his father works as a taxi driver. Levamisole was initially well tolerated except for mild isolated and persistent neutropenia (absolute neutrophil count of 1400 cell/mm3), which had occurred 6 months after levamisole introduction. The patient had no history of cocaine exposure. Viral infections were ruled out (cytomegalovirus, Epstein-Barr virus, and parvovirus B19). Because the patient’s neutrophil count remained stable and he was in sustained remission, levamisole was maintained at the same dosage (2.5 mg/kg every other day). Six months later, he developed nonspecific lichenoid eruptions on both ears and the left cheek, compatible with cutaneous vasculitis [Fig. ]. Upon a physical examination, the patient was found to be alert, with vital signs of blood pressure 100/50 mmHg and body temperature 36.7 °C. His heart sounds were regular and rhythmic with a heart rate of 80 beats/min. The result of a neurological examination including sensory and motor responses, especially reflexes, was normal. The boy’s lungs were clear and resonant. His liver and spleen were moderately enlarged. He had lichenoid eruptions on both ears and his left cheek. Ultrasound of the abdomen revealed HSM with liver and spleen lengths of 14 cm and 13 cm, respectively. Mild anemia (hemoglobin 9.7 g/dl) was detected 3 months prior to the appearance of skin lesions. The patient’s kidney function was normal with a creatinine level of 60 μmol/L. Liver function tests reflected by aspartate aminotransferase and alanine aminotransferase showed slightly elevated levels of 120 IU/L (normal range 5–60 IU/L) and 50 IU/L (normal range 7–40 IU/L), respectively, and a normal alkaline phosphatase level of 60 IU/L.
Immunological investigation revealed an increased positive ANCA count of > 1/640, with negative antinuclear antibodies. Serum complement levels (C3, C4, and CH50) were normal. At this point, levamisole was discontinued. He remained in remission, and his skin lesions disappeared 1 week later. His neutrophil count and hemoglobin levels normalized concomitantly. Furthermore, HSM decreased within 1 month following the withdrawal of levamisole, with liver and spleen lengths becoming 11 cm and 8 cm, respectively. His ANCA levels, however, remained positive (> 1:640) for 12 months after drug cessation. Six months after levamisole withdrawal, the patient remained in remission, with normal white and red blood cell counts and absence of HSM (Fig. ). One year after levamisole withdrawal, the patient started to develop frequent relapses requiring the combination of steroids and mycophenolate mofetil (MMF) to ensure remission. The patient was never hospitalized and had ambulatory management. Our patient’s clinical course is illustrated in Fig. , denoting the relationship between levamisole use, discontinuation, and its marked effect on the neutrophil/hemoglobin levels. |
pmc-6047589-1 | A 3-year-old boy born to non-consanguineous parents of Chinese/Malaysian ethnicity presented at 2 months of age with acute respiratory distress requiring mechanical ventilation and an interstitial pneumonitis on X-ray (Figure A). Bronchoalveolar lavage identified Pneumocystis jirovecii by both PCR and immunofluorescence. He was treated with co-trimoxazole and made a full recovery (Figure B). Immunological work up performed at the time revealed normal immunoglobulin levels, with CD4+ and CD8+ lymphopenia (Table ). The CD8+ count normalized rapidly but his CD4+ lymphopenia persisted until he was 5 months of age. CD19+ B cell and NK cell numbers were normal; however, the B cell numbers climbed and have remained high (range 2.5–6.0 × 109/L—reference range 0.2–2.1 × 109/L). T cell immunophenotyping identified no abnormality (Table ). Mitogen-specific T-cell blastogenesis with phytohemagglutinin (PHA) was preserved; however, T-cell stimulation with anti-CD3 in early life was absent, and stimulation with anti-CD3/anti-CD28 at 9 months of age was reduced threefold compared with a control sample (Table ). He displayed features of global developmental delay at 7 months and was noted to be hypertonic floppy with normal deep tendon reflexes and a normal MRI of the brain. These features improved slowly and required intensive allied health (physiotherapy, occupational therapy, and dietician) support that is ongoing. He had failure to thrive complicated by frequent vomiting necessitating insertion of a gastrostomy at 10 months of age. Endoscopy revealed a thickened (but non-occlusive) pyloric antrum. He developed acral erythematous papules and vesicles on his upper and lower limbs. Skin biopsy revealed superficial subcorneal neutrophil microabscess formation with superficial and deep dermal and subcutaneous neutrophilia (Figure C). Neutrophils were also present within the lumen of a sweat duct. There was no evidence of vasculitis, although interstitial leukocytoclasis was present. The acral papules (Figure D) gradually resolved around 9 months while the skin of his extremities demonstrated a livedo racemosa pattern (Figure E). Notably, at the time of presentation he had raised inflammatory markers; however, these decreased to within normal range when tested during a routine follow-up (CRP < 3 mg/L, erythrocyte sedimentation rate < 14 mm/h) (Table ).
The patient was managed as a primary immunodeficiency with prophylactic co-trimoxazole and immunoglobulin replacement. He did not suffer from any further significant infections. Co-trimoxazole was ceased at 2 years of age and immunoglobulin replacement ceased at 21 months of age, since when he has remained free of infections. The patient underwent routine immunization and demonstrated adequate post vaccination serological responses.
At 33 months, the patient developed a pulmonary hypertensive crisis episode characterized by hypoxia following minor stimulation. Electrocardiogram suggested right ventricular (RV) hypertrophy, subsequently confirmed by echocardiogram which demonstrated suprasystemic pulmonary hypertension and a pressure loaded RV. Notably cardiac echocardiogram performed at age 21 months was normal. High resolution computed tomography of the chest to identify a pulmonary cause was abandoned due to hypertensive crises on stimulation. He was subsequently started on the pulmonary specific vasodilator, sildenafil.
To establish if there was a genetic cause of this disease, whole genome sequencing (WGS) was performed on the family trio. This identified a novel de novo missense variant c.852G>T in exon 7 of 8 in the gene TMEM173, encoding p.Arg284Ser in the protein STING (Figure A). The variant was confirmed by Sanger sequencing, and is not present in the Exac database (). In silico analysis predicted the mutation to be pathogenic based on; the physiochemical difference between arginine and serine (Grantham score 110); SIFT prediction (deleterious), PolyPhen (probably damaging), CADD (scaled = 26.7), mutation taster (disease causing), and Provean (deleterious). Interestingly, a previous case report documented a different de novo change in the same amino acid residue; c850A>G (pArg284Gly, R284G) in a patient suffering from SAVI with upregulation of IFN genes secondary to constitutive STING activation ().
We hypothesized the substitution of a serine for an arginine at position 284 in TMEM173 would result in constitutive activation of STING and consequently, autoinflammatory disease charactered by IFNαβ and NF-κB activation. To investigate this, peripheral blood mononuclear cells (PBMCs) were isolated from patient blood samples and analyzed for mRNA expression of ISGs and inflammatory cytokines by quantitative polymerase chain reaction (qPCR). Compared to healthy controls (HCs) our patient showed an IFN-gene signature with markedly raised levels of IFNB1 and the ISGs IFNA1, ISG15, IRF7, and MX1 supporting the diagnosis of an interferonopathy (Figures B–F). We also interrogated the mRNA expression of several NF-κB-dependent inflammatory cytokines: TNF, IL6, and IL1B. Interestingly, while TNF was not elevated, IL6 and IL1B were significantly upregulated (Figures G–I).
We next sought to directly determine if R284S triggers STING activation. STING expression plasmids encoding R284S and other known SAVI mutations (Figure A) were created by site-directed mutagenesis for in vitro studies. We then transfected HEK293T cells with wild-type (WT) and mutant versions of STING before assessing IFNβ and NF-κB activation using luciferase reporter systems. The R284S mutant STING induced high IFNβ activity compared to WT STING, similar to the previously published STING GoF mutants (Figure J). We further found that all SAVI mutants assayed, including R284S, induced markedly enhanced NF-κB activation compared to WT STING (Figure K). Therefore, in vitro analysis confirms R284S as a pathogenic GoF STING mutation.
After confirming the diagnosis of an interferonopathy, the patient was treated with a combination of oral prednisolone (2 mg/kg/day) and the JAK 1/2 inhibitor Ruxolitinib (5 mg daily) () which was well tolerated. His mobility and demeanor improved within days of steroid therapy including quality of sleep, respiratory effort, and cessation of his frequent vomiting episodes. His appetite improved, with weight gain of approximately 1.5 kg in 4 weeks. Serial weight velocity has subsequently increased from <3rd to 20th percentile in 5 months. His pulmonary pressures became sub-systemic within 8 weeks of sildenafil, steroids, and Ruxolitinib therapy. Initial steroid therapy coincided with a notable neurodevelopmental improvement. He made rapid gains in mobility (gross motor), self-feeding (fine motor), sleep/social interactions (personal social), and receptive speech (communication) compared to previous years while on intensive support. This correlated with a reduction in ISGs and inflammatory cytokines in the patient PBMCs following 6 months of treatment (Figure L). However, the lividinous rash persisted, and 6 months later the patient developed complete loss of his nasal septum while continuing on Ruxolitinib therapy. There was partial recrudescence of his gastrostomy feed related vomiting when his steroids were weaned. In summary, the treatment regime resulted in an excellent systemic response; however, it is possible that some tissue specific processes may remain uncontrolled. |
pmc-6047674-1 | A 53-year-old man with no medical history of arrhythmia, diabetes mellitus, coagulation disorder, or stroke consulted our hospital complaining of back pain. Contrast-enhanced computed tomography (CT) showed a 21-mm-diameter nodule in the lower left lung as well as multiple liver and bone metastases (Figure ), but no abnormalities in the brain. Percutaneous needle biopsy of the liver led to a diagnosis of adenocarcinoma of the lung (T1bN3M1c, cStage IVb) positive for an exon 19 deletion of the EGFR gene.
Before initiation of treatment with gefitinib, the patient was admitted to the hospital because of a disturbance of consciousness and malaise. His ECOG PS was 4. A brain CT scan again showed no abnormalities, whereas laboratory tests revealed a decreased platelet count of 59,000/μl (normal range, 158,000 to 348,000/μl), an increased prothrombin time/international normalized ratio (PT-INR) of 1.35 (normal range, 0.90 to 1.10), and an increased fibrin degradation product level of 174.3 μg/ml (normal range, 0 to 8 μg/ml), suggestive of cancer-associated disseminated intravascular coagulation. Anticoagulant therapy with thrombomodulin alfa (380 U/kg) was initiated. Transthoracic echocardiography revealed no findings of valvular disease or intracardiac thrombus. On his second day in hospital, the patient was started on gefitinib at 250 mg/day, given that this drug has been shown to be safe and effective in EGFR mutation–positive NSCLC patients with a poor PS []. After 2 days of treatment with gefitinib, the patient presented with right hemiplegia, aphasia, and cognitive dysfunction. Diffusion-weighted magnetic resonance imaging (DW-MRI) revealed multiple acute cerebral infarctions (Figure ) and the patient was diagnosed with Trousseau syndrome. He received intravenous unfractionated heparin with a target activated partial thromboplastin time of 40 to 60 s (normal range, 26 to 35 s) for 7 days, and he was treated with warfarin to maintain his PT-INR between 1.5 and 2.5. The hemiplegia, aphasia, and cognitive dysfunction were gradually ameliorated. After 11 days of treatment with gefitinib, laboratory data showed an improvement in the platelet count from 48,000 to 480,000/μl, CT revealed a partial tumor response according to RECIST criteria (Figure ), and DW-MRI detected no further cerebral infarction (Figure ). After treatment with gefitinib for 7 months, the patient showed disease progression with regard to the liver metastases (Figure ) without worsening of his coagulant profile. Rebiopsy of liver metastases to examine status for the T790M resistance mutation of EGFR was difficult because of the small lesion size and the continuation of anticoagulant therapy. We were able to detect the T790M mutation by analysis of plasma cell-free tumor DNA with the cobas EGFR Mutation Test (Roche), however, allowing a switch to osimertinib only 5 days after disease progression during gefitinib treatment. Exacerbation of the coagulation abnormality did not recur during treatment with osimertinib. Although shrinkage of the primary lung lesion and liver metastases was maintained during treatment with osimertinib (Figure ), the patient showed leptomeningeal disease progression 3 months after initiation of this therapy. No further chemotherapy was administered because of his poor ECOG PS associated with disease progression, and he died 1 month after discontinuation of osimertinib. |
pmc-6047835-1 | A 48-year-old, previously healthy male was admitted to the hospital with altered mental status of one day duration. The patient was confused and was not answering questions appropriately. Vital signs were remarkable for low-grade fever of 100.7 ºF and tachycardia. His physical exam was remarkable for a holosystolic murmur at the apex, radiating to the axilla. He was alert and oriented to self, but not to place or time. Cranial nerves were grossly intact with no focal neurological deficits. Laboratory evaluation revealed leukocytosis and mild hyponatremia. A computed tomography scan of the head did not show any acute intracranial hemorrhage. A lumbar puncture was performed and cerebrospinal fluid analysis did not suggest meningitis; however, the patient was started empirically on vancomycin, ceftriaxone, ampicillin, acyclovir, and dexamethasone. Magnetic resonance imaging of the brain showed large area of infarction in the left frontal, left parietal, and left caudate body, suggestive of a cardio-embolic source (Figure ). An echocardiogram revealed a large, mobile, vegetation (1.5 x 1.5 cm) on the mitral valve likely affecting the anterior and posterior leaflets with mild to moderate mitral regurgitation (Figures -). Blood cultures were sent to the lab, which later grew Streptococcus agalactiae. An infectious disease team was consulted and antibiotics were switched to penicillin G and gentamicin.
A cardiothoracic surgery team was consulted and he was not deemed a surgical candidate as it was thought it would be unlikely that the patient will have a meaningful recovery, and the risks outweighed the benefits of surgery. The patient’s mental status remained the same; he remained alert and oriented to self only despite several days of antibiotics. His repeat blood cultures remained negative.
In the third week of his hospitalization, the patient experienced worsening of his altered mental status and he was not responding to questions. An MRI of the brain showed hemorrhagic transformation of embolic infarcts with moderate cerebral edema and midline shift. He was transferred to the intensive care unit (ICU) for close monitoring. On the following day, he became unresponsive and was found to be in pulseless electrical activity. Emergency resuscitation efforts were unsuccessful. The family elected to withdraw care and the patient expired. |
pmc-6047836-1 | Our first patient was a 76-year-old Caucasian female with skin color changes on her back which were noticed by her husband a few weeks prior to presentation. The patient had a history of generalized pain with no identifiable etiology and had been using an electrical heating pad for 12 months for pain alleviation. As she became bedridden due to her intractable pain, she often laid on the electrical heating pad for at least six consecutive hours for several months and denied any associated burning or discomfort. Physical examination revealed reticulated, ill-defined, reddish-brown patches in a cape-like distribution down the patient’s back (Figure ).
The patient was informed that her lesions were due to chronic heat exposure and was advised to discontinue using her heating pad. At a follow-up visit 18 months later, her lesions had resolved. |
pmc-6047836-2 | Our second patient was a 52-year-old Caucasian female seen as an inpatient consult due to the presence of hyperpigmented lesions on her abdomen and upper thighs. She had been admitted to the hospital due to a brain abscess and had undergone a craniotomy for abscess drainage. The patient’s mental status was impaired and a history could not be taken. The primary team stated that the patient’s skin lesions had been present since admission; however, their exact duration was unknown. On examination, the patient had lace-like hyperpigmented patches on the lower abdomen and upper thighs (Figure ).
The diagnosis of erythema ab igne was given, and the care team was reassured of the benign nature of this condition. Several days later, additional history was obtained from the patient’s husband when he became available. He reported that the patient had uterine fibroids and had been using a heating pad for more than eight hours daily for the past three years to alleviate lower abdominal pain. The husband was informed that the heating pad was the culprit of the patient’s hyperpigmented skin and was instructed to discontinue its use. |
pmc-6047836-3 | Our third patient was a 50-year-old Caucasian female seen in our clinic for a full body skin examination. Hyperpigmented reticulated patches on the lower back were noted incidentally during her physical examination (Figure ).
The patient was not aware of the lesions but reported that she had used a heating pad weekly for lower back pain for at least six months until the pain resolved a few months prior to her visit. The patient was informed that she had erythema ab igne due to chronic heat exposure and was counseled on its benign course. |
pmc-6047837-1 | A 38-year-old man presented to the emergency room with complaints of anterior neck pain. He was playing with a paintball gun when he tripped and fell, landing on the back of the paintball gun and impacting his anterior neck, leaving him with difficulty in breathing, swallowing, and with severe neck pain. On arrival to the emergency room, his pain had improved, and he had no difficulty breathing. When he spoke, his voice was hoarse with some irritation evident. He felt a globus sensation each time he swallowed. On physical examination, a small bruising on the anterior neck at the thyroid cartilage was noted. Additional observations included mild tenderness to palpation, a full range of motion of his neck with no crepitus, no bleeding, no significant swelling of his neck and no palpable cervical lymphadenopathy. Computed tomography (CT) scan of his neck showed a thyroid cartilage fracture with a pharyngeal hematoma on the hypopharyngeal wall on the left effacing the piriform sinus (Figure ). Upon re-examination, he was in no distress; however, he was admitted to the surgical intensive care unit for close monitoring. Otolaryngology service was consulted, and a flexible nasal laryngoscopy was performed via left nasal cavity. The procedure included advancing a scope down into the nasopharynx; hyperemia of the vocal cords was observed, both vocal cords were mobile, though the left was slightly sluggish. In addition to this, a hematoma on the posterior portion of the left arytenoid into blunting of the left piriform sinus was noted; the rest of the exam was within normal limits. After the procedure, the patient was diagnosed with a closed fracture of the thyroid cartilage with a hematoma to the left piriform sinus and aryepiglottic fold without compromise to the airway. The patient continued to be observed in the surgical intensive care unit and was started on a full liquid diet day one; he advanced as tolerated and was discharged home on hospital day two without any airway issues. He came to out-patient follow-up and reported doing well. |
pmc-6047838-1 | A 71-year-old male patient, an ex-smoker, underwent a right-sided renal biopsy for an acute kidney injury and the derangement of renal function (creatinine: 8.1 mg/dL and blood urea nitrogen: 74 mg/dL). The derangement of renal function was believed to be secondary to vasculitis as his peripheral anti-neutrophil cytoplasmic antibodies (P-ANCA) levels were positive and, therefore, crescentic glomerulonephritis was suspected. Post-procedure, the patient became hemodynamically unstable within the first 24 hours and dropped 3 grams of hemoglobin. Hemoglobin/hematocrit before the procedure was 10.7 gm/dL/30.4%. Hemoglobin/hematocrit after the biopsy was 6.5 gm/dL/19.2%. His coagulation profile was normal. The patient had a contrast-enhanced computed tomography (CT) angiogram (CTA) for a suspected post-biopsy hemorrhage, which showed no active contrast extravasation from the native kidneys. Instead, a large retroperitoneal hematoma was seen in the right posterior lumbar and iliac fossa region, which was separate from the lower pole of the right kidney (Figure ).
The hematoma was measuring 11 cm in craniocaudal dimensions. On the arterial phase, a small saccular pseudoaneurysm measuring 3 mm was seen arising from the right second lumbar artery posterior to this hematoma (Figure ).
Subsequently, conventional angiography was performed. An initial abdominal aortogram was performed via a right common femoral arterial approach. Catheterization of the second left lumbar artery was performed with a 4 Fr Cobra catheter. Selective catheterization of the branch with the pseudoaneurysm was done with a microcatheter. Subsequently, coil embolization was done with three coils (one distal and two proximal to the pseudoaneurysm) followed by Gelfoam pledget embolization. The final angiogram demonstrated the successful exclusion of the pseudoaneurysm with a preserved flow in the main trunk of the lumbar artery (Figure ).
A selective renal angiogram was then performed that showed no evidence of renal vascular injury. Post-embolization, the patient had no further episodes of bleeding and was discharged in a stable state. |
pmc-6047839-1 | A 65-year-old African American male with past medical history of hypertension and chronic obstructive pulmonary disease (COPD) presented to the emergency department with the complaints of hemoptysis, hematuria, and mild midsternal chest pain for one week. He described his sputum as intermittent, mild/moderate in volume, and comprised of mucus mixed with blood. Chest pain was described as mild, pressure-like, non-progressive, non-radiating, worse with exertion and cough with no relieving factors. He reported gross painless hematuria throughout the urinary stream without clots. He is a chronic smoker with more than 40 pack years smoking history but denied alcohol and illicit drug use. He also denied fever, weight loss, night sweats, chills, hematemesis, melena, other genitourinary symptoms, incarceration, tuberculosis exposure, any recent travel, history of coagulopathy, and genetic disorders. Medication history included amlodipine for hypertension but no medication for COPD. The patient had no significant past surgical history and family history was noncontributory.
Pertinent findings during physical examination included the blood pressure of 135/80 and bilateral wheezing in the recumbent position. Rest of the physical examination was unremarkable.
The baseline investigations were unremarkable except serum creatinine at 1.81 mg/dl, blood urea nitrogen (BUN) 26 mg/dl with estimated glomerular filtration rate (EGFR) of 48.63 mL/min/1.73m². Urinalysis was positive for 3+ blood, 2+ protein, red blood cells (RBCs) >100/hpf and white blood cells (WBCs) 50-100/hpf. Urine sediment was positive for numerous dysmorphic RBCs. Chest X-ray showed emphysematous changes in lungs with no focal consolidation or pulmonary vascular congestion. Electrocardiogram (EKG) and transthoracic echocardiogram (TTE) did not reveal any abnormality. Computed tomography (CT) scan of the chest with intravenous (IV) contrast done in emergency department showed left lower lobe nodules (largest ~2x1 cm) with surrounding ground-glass opacities and general emphysematous changes. He was admitted for further evaluation of hemoptysis, hematuria, and lung nodule. During his course of hospital stay, serum creatinine increased to 3.12 mg/dl. C3 and C4 were within normal limit. Ultrasound showed normal-sized kidneys without hydronephrosis. Renal biopsy showed focal necrotizing glomerulonephritis with more than 40% cellular crescents. He was treated with IV methylprednisolone burst for three days and prednisone 60 mg daily.
Six days later, he received one dose of IV cyclophosphamide 793 mg. On the same day, he developed tachycardia at the rate of 130-140bpm (Figure ). EKG showed tachycardia due to atrial fibrillation with rapid ventricular rate (RVR) that was initially treated with a Cardizem® drip in the medical intensive care unit (MICU). The patient reverted to sinus rhythm after 10-15 minutes of the treatment. TTE showed normal ejection fraction, trace regurgitation of mitral and tricuspid valves, but no vegetations. Anticoagulation was not started due to hemoptysis and hematuria (CHADS Vasc score=2).
The patient was transferred to the floor after weaning off the drip and transitioned on oral Cardizem® 240 mg daily. The patient was further evaluated to rule out other causes of atrial fibrillation including complete blood count (CBC), serum electrolytes, thyroid function tests, cardiac enzymes and chest X-ray, which were all within normal limits. During the rest of his hospital stay, the patient remained hemodynamically stable and did not develop another episode of atrial fibrillation. An echocardiogram was repeated before discharge which remained unchanged from his previous echocardiogram.
Given the associated onset of symptoms following the use of cyclophosphamide, normal investigations were performed to rule out other causes, and with no recurrence of atrial fibrillation following cessation of cyclophosphamide, the diagnosis of cyclophosphamide-induced atrial fibrillation was made. |
pmc-6047840-1 | This case details the history of an 18-year-old Caucasian male, with a past psychiatric history of ASD, who initially presented to the psychiatric emergency service with complaints of depressed mood, and suicidal ideation with a plan to hang himself. The patient reported that he put a rope around his neck, and was about to kill himself, however, he had second thoughts, and walked into the hospital asking for help. The patient reported having these thoughts after experiencing sexual fantasies. These fantasies included being aroused by "anthropomorphic animal characters" and were self-described as "furry". He had a self-reported history of having a violent sexual fantasy in which he "had sex with a girl and then cut off her head." The patient reported two previous suicidal attempts, the first being when he was 16 years of age. The patient described trying to strangle himself with his hands, but denied seeking any medical attention. The patient's second and most severe suicide attempt occurred a few weeks prior to his presentation at the psychiatric emergency service, after having a violent sexual fantasy in which he "had sex with a girl and cut off her head." The patient was deeply disturbed by this fantasy, and he experienced intense fear, anxiety and guilt as a result. These intense feelings led to his suicide attempt in which he tried to suffocate himself with a plastic bag.
On psychiatric review of symptoms, the patient endorsed the following neurovegetative symptoms of depression including poor sleep, a recent loss of interest, difficulty concentrating, guilt over a recent sexual fantasy and his perceived inability to socialize like his peers. He denied loss of energy, change in appetite, psychomotor retardation and feeling hopeless, or helpless.
The patient had a significant past medical history for sinusitis at the age of ten complicated by a brain abscess that required a computed tomography (CT) guided craniotomy for drainage of the abscess. The patient had a repeat CT scan without contrast that showed encephalomalacia on the axial section located in the right frontal lobe as indicated by the yellow circle in Figure . Figure is a corronal CT scan without contrast that showed encephalomalacia located in the right temporal lobe. |
pmc-6048239-1 | A 36-year-old Italian woman, gravida 3 para 1, was admitted to the emergency department of the University Hospital “San Giovanni di Dio e Ruggi d'Aragona,” Salerno-Italy with a history of declared 5 weeks amenorrhea and lower abdominal pain.
At the age of 32, she underwent conization for cervical intraepithelial neoplasia, Human Papilloma Virus (HPV) positive. At hysterosalpingography, tubes were not occluded.
At admission, her serum β-hCG was 35,993 IU/L. Transvaginal ultrasonography revealed an empty uterine cavity but a mass of 35.7 mm in diameter characterized by a hypoechoic central area was seen in the interstitium (Figure ). Both ovaries appeared normal and there was no free fluid in the Pouch of Douglas. The ectopic interstitial pregnancy localized in the left tubaric corner was confirmed by the hysteroscopy (Figure ).
After careful evaluation of the available literature data on the management of EP, a pharmacological approach was preferred to a surgical one. The decision was made taking into account the pros and cons of the surgical approach and in consideration of the ACOG () and RCOG () guidelines justifying the use of the medical therapy with MTX instead of the surgery.
The administration of MTX was legitimated by the patient's stable haemodynamic condition, and the absence of haematologic, renal and hepatic impairments.
As the patient showed very high serum β-hCG levels that have been associated to the risk of treatment failure or the need for supplemental MTX dosage, a multiple-dose intramuscular administration of MTX in a daily dose of 1 mg/Kg alternated with 0.1 mg/kg folinic acid for 5 days was preferred to a single dose regimen. The patient provided her written informed consent. The therapeutic scheme was shown in Figure .
The patient remained hospitalized for 20 days after the first MTX injection. A progressive decrease of the β-hCG serum levels was monitored during hospitalization. Notably, more than β-hCG 15% reduction was detected between the 4th (30,831 IU/L) and the 7th (21,844 IU/L) day after the beginning of the treatment (Figure ). The serum β-hCG became undetectable 35 days after the first MTX injection. |
pmc-6048603-1 | A 23-year-old African American female with no known past medical history presented to
the emergency department with 3 days history of nonproductive cough and runny nose.
Review of systems was otherwise negative denying chest pain, dizziness, palpitation,
or syncope. The patient was not taking any medications. She had no recent travel or
positive family history. On physical examination, the patient appeared comfortable.
She was afebrile with blood pressure of 107/74 mm Hg, heart rate of 45/minute, and
oxygen saturation of 99% on ambient air. The patient had mild pharyngeal edema but
no jugular venous distension. Auscultation of the heart revealed slow heart rate,
but it was regular with normal first and second heart sounds having no murmurs.
Auscultation of bilateral lungs revealed clear breath sounds. There were neither
skin rash nor pedal edema.
Admission electrocardiogram (ECG; ) showed CHB characterized by AV dissociation with narrow QRS
escape rhythm, atrial rate of 90/minute, and ventricular rate of 45/minute. Chest
X-ray was unremarkable. Complete blood count and chemistry panel were within normal
limits. Troponin, erythrocyte sedimentation rate, and thyroid panel were also within
normal limits. Urine toxicology was negative. Lyme IgM antibody, antinuclear
antibody, and rheumatoid factor were also negative.
The patient was admitted to the cardiac care unit in the diagnosis of CHB with
profound bradycardia at rest. Throughout her hospital stay, the patient remained
asymptomatic. She occasionally switched to apparent 2:1 heart block on the
telemonitor as shown in . Her average systolic blood pressure was around 100 mm Hg, and her
average heart rate was 40 to 50 beats per minute. The patient’s heart rate
fluctuated along with her physical activity, the lowest being 32/minute during sleep
and the highest being 116/minute during exertion. Transthoracic echocardiogram
revealed normal left ventricular systolic and diastolic function without major
valvular or structural abnormalities. Exercise stress test was performed to assess
the patient’s chronotropic competency to physical activity. The patient achieved
Bruce protocol stage 3 without any symptoms. She exercised for 10 minutes and
achieved metabolic equivalent 12.4. The maximum heart rate during exercise was
139/minute, and she remained in junctional escape rhythm with CHB throughout the
exercise and recovery. is her resting ECG showing CHB with isorhythmic AV dissociation
mimicking 2:1 block, atrial rate being around 80/minute, and ventricular rate being
around 40/minute.
Her hospital course was uneventful, and the patient was discharged with an outpatient
cardiology appointment. She was also scheduled to receive a loop recorder
implantation. |
pmc-6048751-1 | A 42-year-old white man was referred to neurosurgery due to a non-functional pituitary macroadenoma with bitemporal hemianopsia associated. Pituitary magnetic resonance imaging showed a large sellar and suprasellar mass with invasion of cavernous sinuses bilaterally and with superior stretching and bulging of the optic chiasm (Fig. ). His past medical history included depression, but he was not medicated for this.
He was admitted to our neurosurgery department and underwent partial resection of the tumor by subfrontal approach on July 2, 2015. The tumor was large, but the surgery was no more invasive than the usual pituitary surgery, and there was no section of the pituitary gland.
On the first postoperative day, he presented polyuria of 200 mL/hour with Na 149 mEq/L, plasma osmolality (pOsm) 301 mOsm/kg, uOsm 293 mOsm/kg, and complained of being thirsty. He was receiving an intravenous infusion of 150 mg of hydrocortisone, dexamethasone 4 mg every 8 hours over 24 hours, 1500 ml of intravenously administered isotonic saline, and free water ingestion (Table ). His plasma glucose levels were between 113 and 138 mg/dL, and his spot analysis did not show glycosuria. His condition was interpreted as DI, and he started nasal desmopressin 0.05 mg/day with good response. On July 5 his Na was 142 mEq/L with resolved polyuria.
On the sixth postoperative day he was transferred to our neurosurgery ward, and medicated with desmopressin 0.05/day, levothyroxine 75 μg, hydrocortisone 30 mg/day, and 1000 mL of isotonic fluid. He was started on levothyroxine because his blood tests after surgery revealed hypopituitarism: thyroid-stimulating hormone (TSH) 0.08 uUI/mL, Free T4 1.23 ng/dL (0.7–1.48), free testosterone 1.47 pg/mL (7.20–23), plasma cortisol 0.80 μg/dL, and adrenocorticotropic hormone (ACTH) < 1.0 ng/dL.
On the seventh postoperative day, he became confused and complained of headache. A cerebral computed tomography (CT) scan was performed with no significant changes. His blood tests showed that natremia dropped from 137 mEq/L to 128 mEq/l, with development of polyuria of 4320 mL/day, despite the maintenance of desmopressin dose. His hemoglobin and hematocrit rose from 9.1 g/L to 11.6 g/L and 27.5% to 32.5% (reference value 43–55), respectively. His thyroid function was normal, and he had taken the prescribed hydrocortisone dose. His plasma glucose level was 89 mg/L, blood urea nitrogen (BUN) 28 mg/dL, creatinine 0.51 mg/dL, potassium 3.7 mEq/L, and chloride 93 mEq/L. At 12 p.m. he initiated 150 mg of hydrocortisone infusion, but his Na level did not increase. Plasma and uOsm were 264 mOsm/kg and 679 mOsm/kg, respectively. At 4 p.m. hydrocortisone infusion was increased to 200 mg in 500 mL of sodium chloride (NaCl) 9 mg/mL (0.9%), and hypertonic saline replacements were started with infusion of hypertonic Na over 20 minutes. Desmopressin was removed from the prescription. Despite these medications his natremia dropped even more, to 124 mEq/L. The hydrocortisone infusion was replaced with intravenously administered hydrocortisone 50 mg four times a day, and another infusion of hypertonic Na was performed. In the evening his Na was 123 mEq/L and he was dehydrated, with reduced turgor, dried oral mucosa, persistent polyuria and vomiting, normal heart rate, and blood pressure of 96/58 mmHg. Hyponatremia was very resistant to treatment despite hypertonic saline replacements, without improvements of serum Na levels. We opted to start a continued infusion of three ampoules of 20% hypertonic saline diluted in 1000 mL of isotonic saline with an infusion rate of 42 mL/hour, and he was transferred to an intermediate care unit for proper surveillance. Given this clinical picture, the association of DI and CSWS was considered. On the ninth postoperative day, urine spot analysis showed that natriuresis was 63 mEq/L, even in the face of decreased serum Na of 132 mEq/L, representing another clue to the confirmation of the CSWS diagnosis.
On the eight postoperative day our patient’s Na was 129 mEq/L, and we started fludrocortisone 0.1 mg/three times a day because it is a known effective adjunct treatment of CSWS. His Na increased to 132 on the following day. As an adverse effect of fludrocortisone, he developed hypokalemia, which we controlled with potassium supplements.
Over the following days, his Na level was stabilized and desmopressin was restarted. His urine volume subsequently decreased to a normal diuresis. He was managed with intravenously administered fluids and hypertonic saline. The hypertonic saline dose was gradually decreased and switched to NaCl tablets.
He was discharged on postoperative day 27, medicated with fludrocortisone 0.1 mg/twice a day, orally administered NaCl 16 g/day, orally administered desmopressin 0.1 mg/twice a day, hydrocortisone 20 mg/day, levothyroxine 100 mg/day, and potassium chloride supplements. On follow-up as an out-patient, fludrocortisone and potassium were reduced and then discontinued. Two months later he was only taking hydrocortisone, desmopressin, and levothyroxine, and testosterone replacement was prescribed. The dose of desmopressin had to be increased to 0.5 mg/day to control diuresis, which indicated persistent DI in our patient.
Regarding the adenoma, the histological result was revealed to be a gonadotropinoma. He underwent another neurosurgery on February 4, 2016; he also underwent external radiotherapy with a total dose of 52.2 Gy in 29 fractions and with photon energy of 18 MV, according to the computerized dosimetry planning. He is now clinically well, with his hypopituitarism and permanent DI controlled. |
pmc-6048768-1 | A 46-year-old female with a past medical history of SLE and associated Sjögren syndrome, usual interstitial pneumonia and migraine, medicated with prednisolone 5 mg and hydroxicloroquine 400 mg, with a recently worsened asymptomatic hypogammaglobulinemia (IgG of 297 mg/dL and IgA < 8 mg/dL) secondary to rituximab (taken 4 years earlier), was proposed for replacement therapy with IVIG. She had no previous history of therapy with IVIG. She was started on IVIG 10%, 2 g/Kg over 5 consecutive days. She was given two doses of IVIG in two consecutive days without any immediate reaction.
The patient presented to the emergency department, 36 h after the first infusion, with headache, photophobia, nausea, vomiting and fever. On examination, she was prostrated and had neck stiffness without focal neurological signs. Blood work showed low inflammatory parameters. The brain CT was normal. The CSF analysis showed neutrophilic pleocytosis with 1547 cells/mm3 (87.5% neutrophils), hyperproteinorrachia (15.3 mg/dL) and mildly reduced glucose (50 mg/dL in CSF and 113 mg/dL in plasma). The patient was admitted to the Infectious Diseases Department with the diagnosis of meningitis and given ceftriaxone 2 g every 12 h and ampicillin 2 g every 4 h.
Blood cultures were negative as well as Gram stain, India ink smear, CSF culture for bacteria and fungus and Nucleic Acid Amplification Test (NAAT) for Listeria monocytogenes in the CSF. The urinary pneumococcal antigen was also negative.
The patient was asymptomatic after 2 days of therapy. The lumbar puncture was repeated after 5 days of therapy. The CSF analysis showed 0 cells, normal glucose (67 mg/dL in CSF and 91 mg/dL in plasma) and normal proteins (3.5 mg/dL). Accordingly, the antibiotics were withdrawn and the patient was discharged.
Drug-induced aseptic meningitis usually manifests as meningismus within 48 h after drug exposure. Typically, CSF examination reveals neutrophilic pleocytosis (median 147, range 8–19,000 cells/mm3), protein elevation (median 1.20, range 0.04–3.90 g/L) and normal levels of glucose (median 61.64 mg/dL, range 43.45–157.45 mg/dL). Eosinophilic pleocytosis has been reported in some patients. CSF culture is necessarily negative.
In our case, the diagnosis was based on the presence of risk factors for IVIG associated meningitis (migraine, SLE, first infusion and high dose IVIG), the strong temporal relationship between administration of IVIG and onset of symptoms, the typical CSF characteristics, the exclusion of alternative causes and the quick improvement within a few days. |
pmc-6048798-1 | A 4-year-old boy was referred to our hospital because of respiratory tract infection, splenomegaly, and thrombocytopenia. The mother was 26-year-old, and the father was 31-year-old; both were of Chinese origin, non-consanguineous and healthy. The patient had two healthy sisters. The prenatal history was unremarkable, and the patient was born via a normal delivery at term. His birth weight was 3000 g, height 50 cm, and occipitofrontal circumference 36 cm. Family history did not show any congenital malformations.
On admission, the patient showed distinct facial features, including low nasal bridge, prominent epicanthic fold, hypertelorism, and low-set ears (Fig. ). Enlargement of the liver and spleen was also observed. Furthermore, he had congenital bilateral club feet and cryptorchidism, as well as delayed speech and motor development. A routine blood test indicated an abnormal increase of white blood cell count and hypochromic anemia. As a common symptom of JMML patients, anemia occurs when bone marrow is overcrowded by leukemia cells. Bone marrow aspiration smear revealed trilineage myelodysplasia and decreased platelet production from megakaryocyte. The diagnosis of juvenile myelomonocytic leukemia (JMML) was based on the fulfilling these criteria: (1) absence of Philadelphia chromosome or BCR/ABL fusion gene; (2) peripheral blood monocytosis > 1× 109/L (peripheral blood monocyte count: 9.2×109/L, peripheral blood lymphocyte count: 8.2×109/L); (3) less than 20% blasts (including promonocytes) in the blood and bone marrow; (4) immature granulocytes and nucleated red cells in the peripheral blood; (5) white blood cell count > 10×109/L (peripheral white blood cell count: 23.9 × 109/L); (6) splenomegaly. The patient died before chemotherapy could be started and bone marrow transplantation performed due to severe infection. The CARE guidelines were followed in reporting this case.
Patient’s peripheral blood DNA was subjected to whole-exome sequencing to screen for causal variants. Briefly, 3 μg DNA was sheared to create fragments of 150–200 bp in size. An adaptor-ligated library was prepared using the paired-end sequencing library prep kit (Agilent Technologies, Santa Clara, CA, USA) and both the coding exons and flanking intronic regions were enriched with SureSelect XT Human All Exon V5 (Agilent Technologies). Then, clusters were generated by isothermal bridge amplification with an Illumina cBot station, and sequencing was performed with an Illumina HiSeq 2500 System (Illumina, San Diego, CA, USA). The Burrows Wheeler Alignment tool (BWA) v0.2.10 was employed for sequencing data alignment to the Human Reference Genome (NCBI build 37, hg 19). All data were assessed using FastQC (version 0.11.2) for quality. In addition, all single-nucleotide variants (SNVs) and indels were saved in VCF format and uploaded to Ingenuity Variant Analysis (Ingenuity Systems, Redwood City, CA, USA) for biological analysis and interpretation. Chromosomal microarray analysis (CMA) was performed using SurePrint G3 customized array (Agilent Technologies, Santa Clara, CA, USA). Previously validated platform settings were consistently utilized for CNV detection and filtering. CNVs within the size range 2–400 kb were detected via CMA and were further confirmed by manual inspection.
Using WES, we detected a heterozygous missense mutation (c.34G > A, p.Gly12Ser) in the KRAS gene in DNA extracted from peripheral blood of the patient, which could be categorized as pathogenic (Fig. ). Sanger sequencing was applied to confirm the missense mutation. Further analyses of the parental blood sample and patient’s buccal swab sample revealed that the KRAS mutation was absent, which indicated the presence of a somatic mutation. A pathogenic deletion encompassing 7311 kb (arr[GRch37] 10q22.3q23.2 (81628905_88940359)× 1) was detected by CMA from the proband but not from his parents. The deleted region involved the OMIM genes, including NRG3, CDHR1, RGR, LDB3, BMPR1A, and GLUD1. |
pmc-6048844-1 | This 42-year-old male patient was a HBV carrier with regular follow-up. He had no symptoms, but abdominal sonography in a routine examination revealed a liver tumor. His blood pressure was 123/86 mmHg, and heart rate (HR) 84 bpm. Laboratory data revealed AST/ALT = 58/58 U/L, total bilirubin = 1.2 mg/dL, albumin = 4.3 g/dL, HBV DNA titer 37,600 copies, and AFP level = 121 ng/mL. Abdominal computed tomography (CT) showed a large tumor (13.0X7.0 cm) and several adjacent small nodules with typical arterial enhancement and portovenous washout. The patient was diagnosed with hepatocellular carcinoma (HCC), Barcelona clinic liver cancer (BCLC) stage B, and then underwent extensive left lobectomy. The pathology report revealed metastatic lymphadenopathy; thus, his cancer stage was revised to BCLC stage C.
This patient started treatment with sorafenib 400 mg twice per day for his metastatic HCC. However, grade 3 hand-foot syndrome developed, and then sorafenib was gradually titrated to 200 mg once daily. Two months after initiation of sorafenib, his AFP level increased from 121 to 1152 ng/dL, and follow-up CT scan showed an increase in the size of the intra-abdominal lymph nodes; therefore, progressive disease was confirmed. With a thorough evaluation and having obtained the patient’s informed consent, an off-label treatment with pembrolizumab at a reduced dose of 100 mg (due to his financial situations) every three weeks was administered.
The patient did not experience an irAE until after six cycles of pembrolizumab had been prescribed. Grade 2 fatigue, dizziness and anorexia were complained. The systolic blood pressure declined to 90 mmHg. After fluid resuscitation, his symptoms and hypotension were partially improved. However, his HR dropped with the slowest 38 bpm few days later. He denied chest tightness/pain, cold sweating, palpitation and dyspnea. Physical examination disclosed regular and slow heart beats without murmur, no engorged jugular vein and no leg edema. Electrocardiography (ECG) showed sinus bradycardia (Fig. ). Laboratory data revealed CPK = 19 U/l, Troponin-I < 0.4 ng/ml, Na = 140 mEq/L, K = 4.6 mEq/L, Ca = 8.1 mg/dl and Mg = 1.9 mg/dl that were all within a normal range. A cardiologist was consulted for the symptomatic bradycardia. The 24-h Holter Monitoring was performed which revealed marked sinus bradycardia (minimal heart rate < 40 bpm at day time) with intermittent atrial and ventricular premature contractions. There was no long pause more than 2 s on Holter, but chronotropic incompetence with easily fatigue and light-headedness during moderate physical activity was noted. Cortisol level maintained in the normal range in regular check-up, but dropped to 3.1 (3.7–19.4) mcg/dl after six cycles of pembrolizumab. ACTH level declined to 6.4 (7–46) pg/ml at the same time (Fig. ).
Backtracking his medical records, his HR gradually slowed down while the systolic pressure and cortisol level remained normal. Both immune-mediated sinoatrial node dysfunction and adrenal insufficiency were suspected. Since systemic steroids could treat both irAEs, a low dose of cortisone (12.5 mg) was prescribed orally once daily. His symptoms, bradycardia and hypotension improved immediately after one dose of cortisone. Three weeks later, cortisone was discontinued without symptoms relapse. Pembrolizumab was also discontinued due to the progressive status of his HCC. |
pmc-6048891-1 | A 14-year-old Thai girl was born via cesarean section due to premature rupture of the membrane with a birth weight of 2500 g. She is the first child of a consanguineous (second-degree relatives) couple. Both parents are healthy and have never had fractures. During her first year of life, she had delayed motor development and growth failure. At one year of age, she could not sit by herself and weighed 7.5 kg (< 3rd centile). She presented to our hospital at 14 months of age with fractures of both femora without a history of significant trauma. She was found to have ptosis of both eyes with normal teeth but no blue sclerae. She was small for her age. Her weight was 7.8 kg (3rd centile) and her length was 68 cm (< 3rd centile). Skeletal survey showed diffuse osteopenia, multiple healed fractures of the right humoral shaft, both tibiae and fibulae. Spine radiograph showed flattening and indentation of vertebral bodies (Fig. ). A diagnosis of OI was made and intravenous bisphosphonate therapy (pamidronate 1 mg/kg/dose for 3 days) was initiated and given every 3 months. However, she sustained 1–2 long bone fractures per year from minor trauma. She required multiple corrective osteotomies to correct her deformities. At the last follow-up, she was 14 years old, weighing 20 kg. She could not walk due to her long bone deformity (Fig. ). Remarkably, although she was in a special education class due to physical disabilities, her cognition was appropriate for age. She could talk fluently and do mathematics properly.
Prenatally, her younger sister was found to have a dilated fourth ventricle by an ultrasonography. She was born at term via cesarean section because of previous cesarean section and was diagnosed with hydrocephalus at birth. At 4 months of age, she had her first fracture without a history of a significant trauma, leading to a diagnosis of OI. Physical examination revealed a head circumference of 38 cm (> 95th centile) with a wide anterior fontanelle (3 × 3 cm.) and blue sclerae. She had global developmental delay (could not hold her head) and hypotonia. MRI of the brain demonstrated a large posterior fossa cyst connecting with the fourth ventricular system, moderate hydrocephalus, hypoplasia of cerebellar hemisphere with absence of cerebellar vermis, and hypoplasia of corpus collosum. She was also diagnosed with vesicoureteral reflux grade V and gastroesophageal reflux requiring tube feeding. The patient had multiple hospitalizations because of recurrent urinary tract infections and pneumonia. She expired at the age of one year.
Sixteen known OI genes, BMP1, COL1A1, COL1A2, CREB3L1, CRTAP, FKBP10, IFITM5, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, TMEM38B, WNT1, and MBTPS2, were amplified from 200 ng of genomic DNA using the Truseq Custom Amplicon Sequencing kit (Illumina, San Diego, CA). 286 amplicons which covered all the 226 exons (28 kb) of the target genes were sequenced by Miseq (Illumina, San Diego, CA) using 2 × 250 paired-end reads. SNVs and Indels were detected by Miseq reporter software. The proband was found to harbor a homozygous mutation, c.6delG, p.Leu3Serfs*36 in WNT1. The mutation has never been reported in Human Gene Mutation Database (HGMD; ) (Fig. ). The mutation was subsequently confirmed by PCR-Sanger sequencing. Segregation analysis was performed by using primers, WNT1-E1F: GGT TGTTAAAGCCAGACTGC and WNT1-E1R: ACCAGCTCACTTACCACCAT. The results revealed that the patient was homozygous, while her mother was heterozygous for the mutation (Fig. ). |
pmc-6048909-1 | A 35-year-old woman was evaluated in clinic with progressive fatigue, pre-syncope, upper respiratory symptoms, pallor, and low-grade fevers over the preceding week. She had been diagnosed with locally advanced malignant melanoma of her left upper extremity 10 months prior, in March 2016. The patient had undergone a complete surgical resection with sentinel lymph node biopsy, which showed melanoma with a Breslow depth of 2.2 mm. One of three sentinel nodes was positive for metastasis and the tumor was negative for BRAF or KIT mutations. This resection was followed by a complete level three axillary lymph node dissection, which was negative for further metastasis. She then received 4 cycles of adjuvant ipilimumab, which was complicated by panhypopituitarism. Two months after completing adjuvant treatment she reported a dry cough and fatigue. Computed tomography showed widespread metastatic disease in the bilateral lungs and axial skeleton, including a sternal mass with soft tissue extension. Three weeks before presentation she was given her first doses of combination immunotherapy with ipilimumab and nivolumab.
On examination, she was pale and slightly jaundiced. Cardiac exam revealed a regular, tachycardic rhythm and her lungs were clear to auscultation. She had a benign abdominal exam but exhibited palpable splenomegaly below the left costal margin. There were no ecchymoses or petechiae. Her heart rate was 121 BPM and her blood pressure was 82/45 mmHg. Her hematologic work up revealed a hemoglobin of 2.9 mg/dL and a platelet count of 79 × 10^3/uL, both decreased from values of 8.0 mg/dL and 119 × 10^3/uL, respectively, 2 weeks prior. Her bilirubin was elevated to 2.9 mg/dL, of which 1.7 mg/dL was unconjugated. Her prothrombin and partial prothrombin times were normal and the patient denied any recent history of bleeding. She was given intravenous fluid boluses and admitted to the hospital for further work-up.
In the hospital, her hemoglobin level increased to 7.0 mg/dL after being transfused with 4 units of packed red blood cells. It decreased again below 7.0 mg/dL on hospital days two and three, prompting two more units of blood. Further laboratory testing revealed a lactate dehydrogenase level of 1029 U/L, a C-reactive protein of 202 mg/L, and a haptoglobin of < 20 mg/dL. Her direct Coombs test was negative and glucose-6-phosphate dehydrogenase level was normal. Bilirubin increased to 8.5 mg/dL, of which 5.4 mg/dL was conjugated. Her ferritin level was elevated to 5474 ng/mL and fasting triglyceride level was 336 mg/dL. The reticulocyte production index was 0.6. An ADAMTS13 function was normal and an inhibitor was not found. Her cortisol level was 42.7 μg/dL, thyrotropin was reduced at 0.07 mcU/mL, and free thyroxine was 1.65 ng/dL. An infectious work up, including blood and urine cultures, parvovirus, EBV, and CMV serology was negative. An MRI of her liver showed a stable hemangioma and stable metastatic deposits were noted in the incidentally visible lung. Trends in the patient’s laboratory values can be seen in Fig. .
A hematopathology review of the peripheral blood showed a marked reduction in red blood cells with the remainder displaying spherocytosis, ansiopoikilcytosis, and rare teardrop forms. The granulocytes and lymphocytes appeared mature and normal. A bone marrow biopsy of her posterior iliac crest was performed. The core biopsy sections (Fig. ) revealed a hypercellular bone marrow (approximately 85% of total area) with large sections of tumor cell necrosis. Occasional positive S100 and Melan A immunostains were noted within the dead tumor debris. CD3+ T cells were abundant, the majority of which were CD8+ (Fig. ). Moderate serous atrophy and MF-2 fibrosis was noted on reticulin staining. Unexpectedly, it also revealed increased histiocytes throughout the marrow with active hemophagocytosis (Fig. , blue arrows). Soluble CD25 levels were significantly elevated at 2840 U/mL.
Given these laboratory results, in combination with the patient’s clinical signs and symptoms, HLH was considered. The patient met HLH-2004 criteria with her splenomegaly, cytopenias, hypertriglyceridemia, hemophagocytosis, elevated ferritin, and elevated soluble CD25 levels establishing the diagnosis. The patient was started on 1.5 mg/kg of methylprednisone every 8 hours on hospital day four and her hemoglobin began to improve; further transfusions were not required. She was monitored in the hospital for 4 days and the steroid dose was decreased to 1 mg/kg of oral prednisone. On discharge, her hemoglobin had increased to 9.1 mg/dL without further transfusion. The use of additional treatment, per HLH-2004 guidelines, was considered but was decided against given her marked improvement and with consideration of the etiology of her presentation.
Over the course of the next 2 months, her bilirubin decreased to 0.2 mg/dL, ferritin to 651, CRP to < 3 mg/L, and lactate dehydrogenase to 253 U/L (Fig. ). She remained on high-dose steroids for 1 month before being tapered slowly down to her prior replacement dose regimen for panhypopituitarism. On a follow up clinic visits in 2017, the hemoglobin was maintained above 14 mg/dL and a computed tomographic scans revealed a resolution of both her previous metastatic lung nodules and sternal mass. A repeat bone marrow biopsy was performed due to a residual abnormal bone marrow intensity noted by CT imaging. This demonstrated focal bone marrow remodeling with trilineage hematopoiesis, no hemophagocytic activity, and no morphologic or immunohistochemical evidence of involvement by metastatic melanoma (Fig. ). The patient remains off treatment and in complete remission 12 months later. |
pmc-6050164-1 | The patient was a 70-year-old man who presented with exertional dyspnea, which had persisted for one week and aggravated dyspnea, which had persisted for two weeks. He had been diagnosed with asthma two years previously and had regularly used inhaled corticosteroids since then. He had a 48 pack-year smoking history. On admission the patient had decreased breath sounds and coarse crackles in the left lower lung field. A laboratory test showed a normal blood leukocyte count and abnormal partial pressure of oxygen (59%) and oxygen saturation (88%) values. Chest radiography revealed an area of high density in the left lower lung, which led to a diagnosis of obstructive pneumonia and atelectasis (Fig. A). Computed tomography (CT) revealed a mass of 20-mm in diameter with smooth edges and a uniform density in the left main bronchus (Fig. B). Magnetic resonance imaging (MRI) revealed water signal intensity with low signal intensity on T1-weighted imaging (Fig. C) and high signal intensity on T2-weighted imaging (Fig. D), further suggesting a cystic lesion.
Flexible bronchoscopy revealed a shiny mass with a smooth surface and abundant blood vessels blocking the left main bronchus (Fig. A). When grasped by forceps, the cyst wall was easily broken and a sticky transparent secretion flowed out of the cyst. Polypectomy through bronchoscopy was finally performed. Histopathology confirmed a cystic lesion that consisted of ciliated columnar epithelium lining cells covering the lumen and collagenous fibres with a bronchial gland covering the wall (Fig. B). The cyst was not infected and nor malignant. The patient underwent follow-up examinations at six and 16 months after polypectomy. The remaining part did not grow in size. The detailed examination of the lesion by CT showed the oesophagus running on the dorsal side of the rear wall of the left main bronchus, which was the site of occurrence. We understood that the lesion was entering the gap between the two. This finding was suggestive of Foregut’s migration disorder (Fig. C, D). |
pmc-6050165-1 | A 59-year-old man with a history of non-melanoma skin cancer was followed by his dermatologist every six months for skin checks. His prior skin lesions included a basal cell carcinoma on the back, squamous cell carcinomas on the cheek and antihelix, and multiple actinic keratoses. Benign lesions included lipomas on his upper extremities. Four years ago, he developed an asymptomatic lesion on his distal flexor right forearm overlying his wrist. There was no history of trauma to the site.
Cutaneous examination of his right forearm showed a soft, 10 x 10 mm, compressible blue subcutaneous nodule that was most prominent when his arm was held in a dependent position (Figure ). When he would raise his arm above the level of his heart, the nodule would spontaneously flatten.
Correlation of the history and clinical morphology established the diagnosis of a superficial venous aneurysm. The aneurysm did not interfere with the patient’s activities of daily living. Therefore, he declined any additional evaluation and no therapeutic interventions were initiated. |
pmc-6050167-1 | We report a case of a 21-year-old male with a history of WPW syndrome who had undergone a prior electrophysiology study in 2010 at an outlying facility, documenting an anteroseptal accessory pathway near the His bundle along with an unsuccessful attempt at radiofrequency ablation at that time. No supraventricular tachycardia was induced at that previous study. The surface ECG, at this time, was consistent with the anteroseptal WPW pattern, as shown in Figure .
The patient now presented with a complaint of intermittent palpitations with no definitive trigger. He also described a recent syncopal episode while walking inside his home. His physical exam and all lab work were within normal limits for his age. He underwent a repeat EP study where the baseline PR interval was 62 milliseconds and the QRS duration was 172 milliseconds in a pre-excited pattern. There was found to be an antegrade-only conducting accessory pathway at the anteroseptal region near the His bundle. Antegrade AVRT was induced with a single ventricular extra stimulus while on 2 mcg/min of isoproterenol, as shown in Figures -.
Cryoablation was performed in a position slightly posterior to the His bundle, which successfully resolved the accessory pathway conduction. A first-degree AV block was noted in a sinus rhythm with a PR interval of 226 milliseconds post-cryoablation. There was no recurrence of accessory pathway conduction on follow-up ECG 24 hours post-cryoablation, as shown in Figure . |
pmc-6050547-1 | A 67-year-old man was transferred to our hospital, a large academic medical center, for work-up of persistent gross hematuria. The patient first presented to his local hospital eight days prior with the complaint of gross hematuria and left flank pain. A computed tomography (CT) scan was obtained, revealing an obstructing 2-3 mm left ureteropelvic junction (UPJ) stone and associated hydronephrosis. Physical exam also showed a fever of 102F. Urologic evaluation was not available so he was subsequently transferred to a different outside hospital for management, where he was admitted to the medical intensive care unit (MICU) and taken to the operating room (OR) for ureteral stent placement. A retrograde pyelogram was normal without filling defects, however urine from his left ureteral orifice was noted to be bloody and there was a hydronephrotic drip reported. A postoperative abdominal and pelvic CT with and without contrast showed clot in the left collecting system and hydronephrosis with a 3 mm lower pole stone. His hematuria persisted, though his vital signs and hemoglobin were stable. He was ultimately discharged home on hospital day 5 with an indwelling Foley catheter and plans to follow-up with his primary urologist. He returned to his primary urologist several days later with persistent gross hematuria and passing clots through his Foley catheter, for which continuous bladder irrigation (CBI) therapy was initiated. His hemoglobin was noted to have fallen to 8.6mg/dL from 10.8mg/dL in the past week. At this time, he was transferred to our hospital for further work up and management.
Notable past medical history for this patient includes acute lymphocytic leukemia (ALL) diagnosed 4 years prior to this current admission, for which he received an allo-stem cell transplant. He subsequently developed graft versus host disease (GVHD), but otherwise did well and maintained his immunosuppression on mycophenolate and prednisone without any issues. Labs on presentation were normal except for hemoglobin of 8.5mg/dL and PTT of 98 (normal range 25 - 35 seconds). His WBC was 6.2, platelet count was 217, creatinine was 1.05 mg/dL, PT was 15.4 (normal range 12 - 15 seconds) and INR was 1.2. Given his elevated PTT the Hematology service was consulted. They ordered further blood work that demonstrated normal fibrinogen and thrombin time levels. On mixing studies, he was found to have a Factor 8 inhibitor level of 384 (normal range 0.0 - 0.4).
Our patient was subsequently diagnosed with acquired hemophilia A and transferred to the hematology service for further management. He continued on CBI and conservative management for his hematuria. Therapy was initiated with Novo-7 and FEIBA (activated prothrombin complex concentrate or aPCC, dosed at 70 units/kg) daily until resolution of hematuria, and five weekly doses of Rituximab. During his hospitalization, he required one transfusion of pRBCs. His hematuria improved enough that his CBI was stopped and then his Foley catheter was removed. He was discharged home with continued follow-up and infusions per the Hematology team. |
pmc-6050556-1 | A 73-year-old man with progressive lower urinary tract symptoms for five months was referred to our service for evaluation of prostatic enlargement. During this period, he was using indwelling bladder catheter. He denied any known epidemiological history or respiratory symptoms.
PSA levels were 6.54ng/mL and digital rectal examination showed a diffusely enlarged prostate without focal nodulations. He was submitted to prostatic multiparametric MRI to exclude a concomitant neoplasia that demonstrated an enlarged prostate () with increased vascularization on perfusion map (). A small nodule of abnormal diffusion restriction in the left posterior mid-third of the transition zone, with intense peripheral post-contrast enhancement and a liquefied center was also identified, suggestive of a microabscess (). Despite the focal lesion, final PI-RADS score was 2 (a score used to predict the risk of malignancy on multiparametric MRI-()), indicating low probability of a significant prostatic neoplasia. Ultrasound-guided biopsy was performed after multiparametric MRI due to PSA levels, including a targeted biopsy on the area described.
The histopathological analysis of the fragments on the targeted area (suggestive of abscess) evidenced a chronic granulomatous inflammatory process and the specific test for acid-alcohol resistant bacilli (BAAR) confirmed mycobacterial etiology. |
pmc-6050558-1 | Intraoperative consultation was requested by proctology. During left colectomy for adenocarcinoma, the left uppper-mid ureter of a 69-year old man was resected, leaving a 12cm gap. To spare the patient of another enteroenterostomy, antiperistaltic ureteroappendicoureterostomy was performed over a double-J stent (, upper left). The patient was discharged from the hospital at the 17th postoperative day (POD). We removed the double-J stent at the 53th POD, and left pyeloureterectasis with obstruction at the proximal anastomosis was seen on an intravenous pyelogram performed at the 82th POD (, right). A 99TcDTPA nephrogram immediately followed, which showed adequate emptying (, lower left). After 2 years the patient remains assymptomatic, with symmetric renal function (glomerular filtration rate: left=36.52, right=37.16mL/min/1.73m2). Computed tomography revealed mild-moderate left pyeloureterectasis, with good cortical uptake (). displays both left and right urinary tracts as well as proximal and distal ureteroappendiceal anatomoses. |
pmc-6050648-1 | A 35-year-old male presented with constant blurry vision in his left eye for 6 weeks. His past medical history was significant for CF complicated by chronic pancreatic insufficiency leading to insulin dependent diabetes mellitus, chronic sinusitis, hypertension, iron deficiency anemia, and obstructive sleep apnea. His only previous surgery was a combined sinus surgery consisting of bilateral maxillary antrostomies, ethmoidectomies, sphenoidectomies, and frontal sinusotomies performed 7 months prior to presentation. Medications at the time of presentation included albuterol, azithromycin, itraconazole, insulin, lisinopril, pancreatic enzymes, and sulfamethoxazole-trimethoprim. He denied any tobacco or drug use. His visual acuity at presentation was 20/20 in both eyes, intraocular pressure was 18 OD and 16 OS, and his pupils were 4 mm and reactive in both eyes. His anterior exam was unremarkable, but his posterior exam in the left eye was significant for intraretinal hemorrhages along the nerve fiber layer with associated retinal thickening in the inferior macula consistent with a BRVO (Fig. ). Optical coherence tomography revealed mild intraretinal and trace subfoveal fluid in the left eye (Fig. ). The findings were confirmed with fluorescein angiogram which revealed delayed venous filling in the inferior venous arcade (Fig. ).
His blood pressure readings had been consistently between 110 and 145 systolic over 70–85 diastolic in the past year, and his most recent hemoglobin A1c was 6.9% 4 months prior to presentation. Laboratory workup revealed normal complete blood cell count, Vitamin A and D levels, prothrombin time, thrombin time, antithrombin activity, Protein C and S activity, cardiolipins, dilute Russell’s viper venom time, homocysteine level, and a negative prothrombin G20210A mutation. A complete metabolic panel was notable for a mild elevation in glucose of 121 mg/dL (70–100 mg/dL). Antinuclear antibody was weakly elevated at 2.1 units (≤ 1 unit), and sedimentation rate was 24 mm/h (0–22 mm/h) with normal C-reactive protein. The only significantly abnormal lab was a fibrinogen level of 479 mg/dL (200–375 mg/dL).The patient was observed without treatment given his visual acuity was 20/20 and the macular fluid did not involve the fovea (Fig. ). Six months after presentation he remained 20/20 in both eyes and the macular fluid had resolved (Fig. ) with careful observation. |
pmc-6050669-1 | A Hispanic male infant was born large for gestational age (LGA) (birth weight 4.11 kg, above 100th percentile and length 51 cm, 98.6th percentile) at 34 weeks to a 17-year-old mother with uncontrolled gestational diabetes and pre-eclampsia. No family history iof hypoglycemia was reported. He was born by emergency C-section at an outside medical center when fetal monitoring revealed a flat strip. At the time of delivery, his APGAR scores were 2 at 1 min, and 6 at 5 min. His initial arterial blood gas was pH 7.13, pO2 65, pCO2 40 mmHg, base excess (− 9.2). His initial plasma glucose level was 7 mg/dL. He received an IV bolus with D12.5%, followed by IV fluids (IVF) with a glucose infusion rate (GIR) of 6.9 mg/kg/min. The infant was transferred to our hospital at day of life (DOL) 2 for respiratory distress syndrome (RDS), supraventricular tachycardia, and hypoplastic aortic arch as well as persistent hypoglycemia.
During his hospital stay, the GIR was gradually increased to 16 mg/kg/min. Polycose supplement was added to his feeds with the goal of maintaining plasma glucose levels close to 70 mg/dL when titrating IV dextrose. However, on DOL 21, he developed hypoglycemic episodes (BG below 50 mg/dL) after IV dextrose was weaned off and despite consuming 26 cal/oz. of formula. Extensive workup for CHI was initiated on DOL 25, and the results revealed an elevated insulin level of 16.3 mcIU/mL coincident with a plasma glucose level of 48 mg/dL and beta hydroxybutyrate level of less than 100 mcmol/L. Ammonia, pyruvic acid, cortisol level,, serum amino acids, acyl carnitine profile, and urine organic acids were all in the normal range (Table ). A pediatric endocrinology consultation was performed and DNA sequencing for CHI was ordered, revealing a heterozygous maternally-inherited likely pathogenic variant in KCNJ11, c.616C > T (p.Arg206Cys). This variant has been previously reported in a family where it segregated with several affected individuals with CHI. It is rare in population databases (ExAC and gnomAD; 3/242,646 alleles) [] and predicted by in silico tools (GERP, SIFT, PolyPhen) to be damaging []. Diazoxide was started and plasma glucose levels stabilized above 70 mg/dL at the dose of 15 mg/kg/day on DOL 30. The patient was discharged home at DOL 71 with diazoxide at 10 mg/kg/day. His plasma glucose was stable on a similar dose at the time of his last visit when he was 11 months old. |
pmc-6050669-2 | A male infant was born small for gestational age (SGA) [birth weight 1.45 kg (4.7th percentile), and birth length, 40 cm (3.5th percentile)] at 33 weeks of gestational age to a 35-year-old mother with gestational diabetes and pregnancy-induced hypertension (PIH) at a local medical center. His mother managed her gestational diabetes with diet control only. Family history was remarkable for type 2 diabetes in the maternal grandmother. No family history of hypoglycemia reported. Paternal history was unknown. His APGAR scores were 1, 6, and 10 at 1, 5, and 10 min, respectively. He developed persistent hypoglycemia on DOL 5 (Plasma Glucose = 43 mg/dL) and also had transient RDS.
Treatment for hypoglycemia was started with dextrose 10% IVF with GIR at 6–10 mg/kg/day in addition to increased oral feeds. He also received hydrocortisone treatment (30 mg/m2/day) secondary to low cortisol level during a prior hypoglycemic event (4.3 mcg/dL) from DOL 12 to DOL 20. Hypoglycemia recurred after discontinuing hydrocortisone therapy as well as dextrose containing IVF, and then our pediatric endocrinology team was consulted. Critical labs were obtained on DOL 21 (Table ). Urine ketones were negative but the beta hydroxybutyrate was not obtained at outside hospital. The physical exam of this infant was negative for concerning findings for hypopituitarism.
High-dose ACTH stimulation testing (abbreviated) was performed due to random low cortisol level and the infant responded adequately with a stimulated cortisol level at 29.7 mcg/dL and baseline cortisol level at 10.4 mcg/dL. Serum ammonia and lactic acid levels were normal. A glucagon challenge test was recommended by the pediatric endocrine team but was not performed. The infant was started on diazoxide at 15 mg/kg/day with good response. DNA sequencing for CHI revealed a heterozygous pathogenic missense variant in exon 7 of HNF4A,( p.Arg267Cys; c.799C > T; legacy Arg245Cys). This variant affects a highly conserved amino acid and is predicted to be deleterious by in silico tools. It has been previously detected in patients with MODY 1 [], and different substitutions affecting this same codon (p.Arg267Ser and p.Arg267Gly) have been reported []. This variant is absent from population databases including GnomAD, ExAC and Leiden Open Variation Database. Parental testing was not performed due to maternal refusal and unavailability of father. Renal ultrasound, liver function tests, and urinalysis of this patient were normal. The patient responded well to diazoxide, which was gradually tapered based on POC home glucose values in the range of 70–100 mg/dL and hemoglobin A1C, and eventually discontinued at 6 months of age. Fasting challenge test was not performed before total discontinuation of diazoxide. Infant remained euglycemic at the time of his last visit in clinic (2 years 9 months of age). |
pmc-6050682-1 | In June 2013, a 19-year-old male patient underwent SMILE for myopia in both eyes. He had a history of eye rubbing and allergic conjunctivitis, and before SMILE he had no history of pellucid marginal corneal degeneration and no family history of keratoconus or high myopia. Preoperative characteristics and parameters are summarized in Table . Preoperative topographies are presented in Fig. . The manifest refraction values were − 6.75 DS with 1.00 DC × 45 in the right eye and − 6.75 DS with 0.75 DC × 140 in the left eye, and corrected distance visual acuity (CDVA) was 20/20 in both eyes.
At 1 month after SMILE, uncorrected distance visual acuity (UDVA) was 20/20 in both eyes. The patient had no complaints of a decline in vision. Corneal topography revealed corneal ectasia. Posterior elevation was + 21 μm in both eyes, and respective thinnest corneal thicknesses (TCTs) were 433 mm and 429 mm in the right and left eyes. The patient’s characteristics, parameters and topographies are presented in Table and Fig. . Pachymetry examination showed a decentred elevation coincident with the thinnest point on the posterior surface.
At 7.5 months, topography indicated posterior elevation of + 29 μm in the right eye and + 31 μm in the left (Table , Fig. ). Respective TCTs were 445 mm and 426 mm in the right and left eyes. At 14 months after SMILE, UDVA had reduced to 20/32 in the right eye and 20/40 in the left (Table , Fig. ). The patient still exhibited eye rubbing and intermittent episodes of allergic conjunctivitis after SMILE. Simultaneous PTK and CXL (PTK + CXL) was performed in both eyes. Before CXL, the central 9.0-mm diameter epithelium with a 50 μm depth was removed via PTK using the excimer laser system (EX500, Wavelight Technologies, Germany). The general CXL technique used was based on the original CXL procedure described by Wollensak et al. []. riboflavin solution (0.1%)was administered topically every 2 min for a total of 30 min. The cornea was then irradiated with ultraviolet A light (370 nm, 3.0 mW/cm2) (UV-X illumination system version 1000, UVXTm, IROCAG, Zurich, Switzerland) for 30 min at a distance of 5 cm, with continuous application of the riboflavin solution every 2 min. At the end of the procedure, a soft bandage contact lens was placed until corneal reepithelialisation had occurred. Antibiotic eye drops were administrated 4 times daily for 1 week, and fluorometholone eye drops 0.1% were administrated 4 times daily for 4 weeks. No intraoperative or postoperative complications occurred. The follow-up keratometry values and TCT, spherical equivalent and UDVA measurements at 6, 12, 24 and 36 months after PTK + CXL are summarized in Table .
At 36 months, in the right eye maximum corneal keratometry (Kmax) and mean corneal keratometry (Kmean) were decreased by 2.6 D and 1.5 D, respectively, while in the left eye the corresponding reductions were 4.0 D and 1.6 D. TCT had decreased from 432 μm to 412 μm in right eye, and had not changed in the left eye. Spherical equivalent improved significantly over the course of the study, from − 4.25 D to − 2.75 D in the right eye and from − 5.25 D to − 3.5 D in the left eye at 36 months. UDVA increased over time, and did not require glasses or enhancement. |
pmc-6050690-1 | This is a case of a 37-year-old, right-hand dominant, Malay man who presented to our Emergency Department 6 hours after he had fallen approximately 6 meters from a rambutan tree where his left arm hit the tree trunk on his way down to the ground. Post trauma, he complained of pain and swelling over his left antecubital fossa. There was no wound over his left upper limb. He had no history of trauma to his left upper limb and no significant past medical history. He did not take any medications. He was an army officer and had been an army officer for 16 years. Two years prior to the current accident, he was transferred to the administration unit of the Ministry of Defense. His job scope was mainly office work. He lived with his wife and three children in a small suburban home. He was an active tobacco smoker with a 20 pack year smoking history. Currently he smoked 10–15 cigarettes a day. He did not consume alcohol.
In our Emergency Department, his vital signs were stable with blood pressure 132/80, pulse rate 79/minute, and temperature 37 °C. A physical examination of his left upper limb revealed a tender, fluctuant swelling over the left antecubital fossa with slight limitation in his left elbow range of motion due to pain. There was ecchymosis over the lateral aspect of his left elbow joint but his left elbow was not deformed. His left radial pulse was feeble and his left ulnar pulse was not palpable. Capillary refill times of all fingers were more than 2 seconds. Sensation over left upper limb was normal. Doppler signal of brachial artery proximal to cubital fossa was triphasic, radial artery was monophasic, and ulnar artery was absent. Radiographs of his left elbow showed chip fracture over the left lateral epicondyle of the humerus (Figs. and ). Subsequently an urgent computed tomography angiogram of his left upper limb was done which showed a segment of non-opacification of contrast at the distal left brachial artery measuring 3.3 cm with distal reconstitution of the left brachial artery by collaterals just before the bifurcation of the left brachial artery at the left elbow joint (Figs. and ). The computed tomography scan also showed minor fractures of left lateral epicondyle and left radial head (Fig. ). Laboratory investigations (full blood count and renal function test) were all normal.
He was seen by general surgery and orthopedics teams. Our hospital did not have vascular expertise; hence, he was referred and transferred to a vascular surgeon in another hospital for surgery. He underwent emergency left brachial artery exploration surgery 15 hours after his fall. On intraoperative examination, his distal left brachial artery was contused. Therefore, a left brachial to brachial artery bypass was done using reversed saphenous vein graft. Intravenously administered antibiotics (cefuroxime 750 mg three times a day) were given before induction and for 3 days postoperatively. Postoperatively, Doppler signals of left radial and ulnar arteries had improved. He did not develop reperfusion syndrome requiring fasciotomy. The vascular repair was successful and he was discharged 4 days after surgery. On discharge, his bilateral radial pulses were symmetrical and strong. Fractures over left lateral epicondyle and left radial head were treated conservatively using a 90 degrees posterior splint for 2 weeks. The plan was to immobilize these fractures for a short duration followed by early range of motion exercises.
This patient was followed up in orthopedic and vascular out-patient clinics. Six weeks post trauma, his left elbow was noted to be dislocated in an out-patient clinic (Fig. ). Closed manipulative reduction was attempted but unsuccessful. His left elbow was still subluxed (Fig. ). There was probably soft tissue interposition in the left elbow joint. His left upper limb neurovascular examination was intact. He was counselled for surgery to reduce the elbow joint with vascular team standby. However, he was not keen for surgery at that time. At the last clinic follow-up around 6 months post trauma, his left elbow joint was still subluxed, his left triceps was shortened, and left elbow range of motion was reduced (extension 0 degrees, flexion 45 degrees, and pronation and supination normal). His radial pulses were strong and equal bilaterally. Functionally, he was able to cope with light duties. He used his left shoulder to compensate for the reduced range of motion of his left elbow. However, he was unable to carry weight > 2 kg using his left upper limb. He was still not keen for any surgical intervention to stabilize his elbow joint due to the risk of vascular graft thrombosis and injury. |
pmc-6050796-1 | A 78-year-old female was referred to our clinic for evaluation of anemia and
thrombocytopenia. She complained of fatigue, early satiety, and had an unintentional
weight loss of 80 pounds over the past 2 years. She denied fevers, night sweats,
nausea, vomiting, or abdominal pain. Physical examination revealed massive
splenomegaly, but no hepatomegaly or lymphadenopathy. A complete metabolic profile
and lactate dehydrogenase were normal. Her hemoglobin and platelet counts were 10.0
g/dL and 91 × 109/L, respectively. Her white blood cell count was 8.7 ×
109/L with 67% lymphocytes and 5% atypical lymphocytes. The
peripheral smear showed abundant prolymphocytes (). A bone marrow aspirate and biopsy
revealed a marrow that was diffusely infiltrated by atypical, homogenous lymphocytes
with medium to large size moderately condensed chromatin and prominent nucleoli.
These lymphocytes accounted for about 50% of marrow cellularity, with B- and
T-lymphocyte ratio estimated to be 2:1 (). Flow cytometric analysis of the
bone marrow aspirate with additional markers revealed that B cells were positive for
CD20 and FMC7 (relatively dim and variable) and negative for CD23 and surface
immunoglobulin M and immunoglobulin D. The bone marrow pathology and immunophenotype
was consistent with a diagnosis of B-PLL. Cytogenetic analysis of the bone marrow
aspirate revealed no chromosomal abnormalities. A positron emission tomography (PET)
scan revealed the spleen to be massively enlarged measuring 29 × 12 × 8 cm with
significant mass effect on the intra-abdominal contents, with displacement of the
left kidney to the midline and compression of the colonic splenic flexure (). There were also a
few scattered mildly hypermetabolic lymph nodes throughout the body. Her initial
ECOG (Eastern Cooperative Oncology Group) performance status was 1.
The patient was started on treatment with rituximab and bendamustine; however, she
experienced recurrent infusion reactions with rituximab, which worsened with every
treatment. Rituximab was stopped after the third cycle. After receiving 3 cycles of
treatment, a repeat PET scan showed interval development of bilateral cervical
hypermetabolic lymphadenopathy, persistent mediastinal, periportal hypermetabolic
lymph nodes, and persistent splenic enlargement. She also developed bilateral
pleural effusions (). Her posttreatment hemoglobin and platelet counts were 10.0 g/dL and 50 ×
109/L, respectively. Her white blood cell count decreased to 5.3 ×
109/L but consisted predominantly of lymphocytes and prolymphocytes.
She was therefore considered to have disease progression because of her persistent
cytopenias, the progressive worsening of her lymphadenopathy and splenomegaly, and
overall decline in her performance status to an ECOG of 2. She expressed a desire to
continue treatment for her B-PLL, so it was decided to change therapy to a
combination of obinutuzumab and chlorambucil. This regimen entailed the
administration of obinutuzumab 1000 mg on day 1 of every cycle and chlorambucil 0.5
mg/kg on days 1 and 15 every 28 days. She demonstrated greater tolerability to this
regimen and did not experience any infusion reactions. After 4 cycles of
obinutuzumab-chlorambucil, she had gained weight with improved appetite and energy
level. On physical examination, her spleen was no longer palpable. A repeat
posttreatment PET scan showed a decreased spleen size, which measured approximately
18.5 × 10.0 × 7.3 cm, and her lymphadenopathy and pleural effusions had resolved
(). She also had
an improvement in her anemia and thrombocytopenia posttreatment with normalization
of the lymphocyte count. Prolymphocytes were no longer noted on the peripheral
smear. She achieved a clinical partial remission and was then placed on maintenance
obinutuzumab 1000 mg monotherapy every 2 months. In total she completed 8 cycles of
treatment with obinutuzumab. Therapy was held thereafter as she had no evidence of
active disease and she was switched to surveillance. No major adverse events
occurred during her treatment with obinutuzumab and chlorambucil or while on
monotherapy with obinutuzumab. At the time of this report, she was still alive at 81
years old with no evidence of disease progression and has been off treatment for
greater than a year. |
pmc-6051074-1 | A 52-year-old female with no known past medical history was evaluated for a 3-year history of abdominal pain. Pain was sharp, primarily located in the lower chest and subcostal region left more than right, waxing and waning, nonradiating, and aggravates with certain nonspecific movements including forward lean. She was an accountant by profession and was never involved in any athletic activities. Her medications included over-the-counter acetaminophen and cyclobenzaprine. She underwent frequent physical therapy sessions and was treated with different analgesics with minimal improvement.
Complete physical examination was unremarkable except for mild to moderate tenderness in the left more than the right subcostal area which was reproduced on hooking maneuver.
Prior to presentation, she underwent frequent imaging modalities on multiple occasions including CT chest, CT abdomen and pelvis, MRI abdomen and pelvis, and plain X-rays. All these modalities failed to identify any significant underlying abnormality. EGD was also performed twice and was unremarkable on both occasions. Dynamic flow ultrasound of the lower chest was performed to potentiate the diagnosis and revealed slipping of the lowest rib over the next lowest rib bilaterally left worse than right, findings consistent with bilateral slipping rib syndrome.
Reassurance about the benign nature of disease was provided, and avoidance of pain-inciting postures was recommended. Her symptoms persisted despite conservative management, and intercostal nerve block was planned. Patient's symptoms remarkably improved with nerve block without requiring any surgical intervention. |
pmc-6051076-1 | A 42-year-old woman with history of hypertension and diabetes mellitus presented to the outpatient clinic with abdominal pain and diarrhea for two weeks. The patient was recently treated with clindamycin for sinusitis. On examination, the patient appeared comfortable, afebrile, and had normal vital signs. There was mild tenderness reported on abdominal palpation, and the remainder of the physical examination was unremarkable. Clostridium difficile infection was confirmed by a positive stool toxin B PCR, and the patient was started on treatment with metronidazole. Due to complaints of nausea on day three of metronidazole use, the treatment was changed to oral vancomycin at 125 mg every 6 hours. At the time of initiation of therapy, the patient had creatinine of 0.6 mg/dL. After the third day of oral vancomycin, the patient reported new symptoms of lightheadedness, sensations of “buzzing and whistling” in both ears, as well as decreased perception of hearing described as “clogged ears.” The patient presented to the emergency department (ED) due to worsening of these symptoms, and the vancomycin dose was reduced to 125 mg every 8 hours. However, the reported symptoms persisted, and on day 5 of therapy, vancomycin was discontinued in the outpatient clinic. A random vancomycin level obtained 24 hours after the last dose of vancomycin, resulted as 2 mcg/mL. The patient's symptoms were also reported to be resolved within 24 hours after discontinuation of therapy. The temporal association of the patient's symptoms and improvement with cessation of therapy along with a detectable vancomycin level indicates systemic absorption of oral vancomycin with associated ototoxicity. |
pmc-6051090-1 | An 18-year-old female without significant past medical history initially presented to urgent care with complaints of a sore throat, swollen neck, fevers, and chills for 5 days. At the urgent care, the rapid strep test came back negative. She was then sent home on steroids and azithromycin. She presented to the emergency department two days later with progressively worsening shortness of breath along with sudden onset pleuritic chest pain. Review of systems was remarkable for shortness of breath and chest pain. Vitals showed temperature of 99 °F, blood pressure of 107/66 mm Hg, a pulse of 138/min, respiratory rate of 28/min, and SpO2 of 97%. Physical examination was remarkable for tenderness in the neck, pus formation on the tonsils, and decreased breath sounds. Labs were remarkable for severe thrombocytopenia, leukocytosis with left shift, granulated polymorphonuclear leukocytes (PMNs), and acute kidney injury (AKI).
Initial chest X-ray showed bilateral pleural effusions (). Computed tomography (CT) chest without contrast showed bilateral lung nodules and pleural effusions (). Echocardiogram demonstrated small pleural effusion with normal ejection fraction. Bilateral neck ultrasound and computed tomography (CT) neck without contrast did not show jugular vein thrombophlebitis or peritonsillar abscess, although the study was limited due to insertion of bilateral internal jugular (IJ) catheter insertions. Blood cultures were obtained, intravenous fluids were given, and empiric antibiotic therapy was started with intravenous (IV) vancomycin, IV cefepime, and IV doxycycline. The patient became more hypoxic requiring intubation and mechanical ventilation and went into septic shock requiring pressors. An interval chest X-ray demonstrated worsening bilateral effusions (). Her renal function deteriorated requiring continuous renal replacement therapy (CRRT). She then developed cardiac arrest due to pulseless electrical activity (PEA) following chest compressions, and there was a return of spontaneous circulation (ROSC). Blood culture grew Fusobacterium, and antibiotics were changed to IV meropenem. To drain the empyema, bilateral chest tubes were placed, the sample was cultured, and it was negative for bacterial growth. The patient also had a left-sided pneumothorax, and it was unsure if the cause was secondary to the underlying infection or iatrogenic. She was placed on acute respiratory distress syndrome (ARDS) net protocol following which there was an improvement, and she was eventually weaned off the ventilator. A repeat CT chest abdomen pelvis with contrast 5 days later was ordered which showed septic emboli in the lungs bilaterally, splenic emboli, bilateral loculated empyema, and left adrenal gland hemorrhage ().
The patient responded to antibiotics, and she required long-term care at LTACH where she recovered completely. |
pmc-6051095-1 | A 29-year-old man with no significant past medical history presented to emergency department with 2 days of epistaxis and petechiae. The patient experienced upper respiratory infection symptoms 5 days prior to presentation. He was not taking any home medication. His family history was not significant. His vital signs were stable. Physical exam was notable for oral blisters and petechial rash over extremities. He was found to have a platelet count of 1 × 109/L. The rest of CBC was normal. Peripheral blood smear confirmed profound thrombocytopenia with normal platelet size and no platelet clumping. TSH, hepatitis C antibody, HIV antibody, H. pylori stool antigen, CMV PCR, and EBV PCR were all negative. Coagulation function and ADAMTS13 activity were normal. The respiratory viral panel was positive for rhinovirus. Bone marrow biopsy showed trilineage maturing hematopoiesis with markedly increased megakaryocytes. Bone marrow flow cytometry and cytogenetic analysis were unremarkable. He was diagnosed of ITP possibly triggered by rhinovirus infection.
After admission, the patient was immediately started on IV dexamethasone 40 mg daily for 4 days. IVIG 1 g/kg/day was administered on hospital days 4 and 5. The patient developed severe headache on hospital day 5. Head CT followed by sella MRI demonstrated a small focus of hemorrhage into a pituitary macroadenoma consistent with pituitary apoplexy. At this time, he was started on intravenous aminocaproic acid. He received daily platelet transfusion with no response in platelet count (). Romiplostim was administered on hospital day 7 (6.5 μg/kg) and day 14 (10 μg/kg). Anti-D could not be used given his Rh-negative blood type. Dexamethasone was transitioned to prednisone 1 mg/kg/day and then gradually tapered down. His platelet count was refractory to all treatments above and remained at a single-digit level. Eventually, he underwent uncomplicated laparoscopic splenectomy on hospital day 18. He was discharged on postoperative day 2 with the maintenance dose of corticosteroids as his platelet count rose to 215 × 109/L.
On postoperative day 7, he was found to have a platelet count of 8 × 109/L during clinic follow-up. He was subsequently started on rituximab 375 mg/m2 weekly, romiplostim 10 μg/kg weekly, and mycophenolate 500 mg twice daily. On postoperative day 20, his platelet count increased to 60 × 109/L. On postoperative day 27, he developed a mild headache, and his platelet count was found to be 2424 × 109/L (). A head CT was done which showed no acute process but findings compatible with resolving pituitary apoplexy. He was admitted to hospital for urgent plateletpheresis given extreme thrombocytosis (>1000 × 109/L) associated with headache and started on aspirin 81 mg q.d. for thromboprophylaxis. The plateletpheresis was performed with whole blood daily for three consecutive days. Platelet count immediately after last plateletpheresis was 1012 × 109/L. Platelet count remained elevated in the 1000–1400 × 109/L range for the first week after discharge before it started to normalize (). All ITP treatments were discontinued. Platelet count was 288 × 109/L at postoperative week 8 and 477 × 109/L at postoperative week 39. |
pmc-6051099-1 | A 71-year-old female with multiple myeloma status after 5 cycles of ixazomib, lenalidomide, and dexamethasone, chronic kidney disease stage III, previous stroke, hypertension, gout, and peripheral arterial disease presented to the hospital with generalized weakness, vomiting, and diarrhea as well as acute on chronic kidney injury in which serum creatinine and creatinine clearance (CrCl) were 3.3 mg/dl and 15 ml/min, respectively (baseline creatinine of 1.9 mg/dl with CrCl of 30 ml/min). Blood test showed thrombocytopenia with a platelet count of 84000/dl and anemia with hemoglobin of 12 g/dl. Regarding multiple myeloma, she was diagnosed with kappa light chain multiple myeloma with extensive lytic lesions in bones as well as renal dysfunction a few years ago. Diagnosis was made by bone marrow biopsy which demonstrated 80%–90% cellular marrow with 61% plasma cells. FISH study was abnormal for chromosome 1q, chromosome 13q, and 17p deletion. Based on patient's average CrCl of 30 ml/min, ixazomib was started at a dose of 3 mg on days 1, 8, and 15 of a 28-day treatment cycle along with lenalidomide and dexamethasone. After the second cycle of ixazomib, the patient had been having intermittent GI disturbances including diarrhea, and biweekly blood test revealed thrombocytopenia with a nadir of about 75000/dl (), which were both attributed to ixazomib. Ixazomib was held on admission due to significant vomiting, abdominal pain, and diarrhea. Clostridium difficile toxin and stool culture were negative, ruling out infectious causes. One week after admission, the platelet count decreased dramatically to 9000/dl from 84000/dl on admission. The patient also developed intravascular hemolysis evident by an elevated LDH level (1366 units/L), decreased haptoglobin level (10 mg/dl), elevated total bilirubin (1.6 mg/dl), and indirect bilirubin (1.3 mg/dl). Peripheral blood smear also showed profound schistocytes. Coomb's test was negative, and DIC was ruled out as the fibrinogen level was normal (521 mg/dl). Acute thrombocytopenia, Coomb's negative hemolytic anemia with profound schistocytes, and acute renal injury raised the concern for TMA. Given the high morbidity of TMA, the patient received fresh frozen plasma and underwent plasmapheresis while further workup was in progress. Normal ADAMTS13 activity ruled out TTP. Normal complement levels and negative stool culture made atypical HUS and HUS less likely. Plasmapheresis was stopped after 5 days due to lack of clinical improvement and negative workup for TTP. Approximately three weeks after the onset of TMA, the platelet count started to improve spontaneously with supportive management. The gradual and spontaneous improvement in the platelet count pointed suspicion away from malignancy-induced TMA and favored DTMA caused by cumulative toxicity of ixazomib, likely precipitated by acute renal dysfunction and hypoproteinemia from malnutrition and chronic diarrhea related to ixazomib side effect. The presentation of this patient was consistent with ixazomib-induced DTMA from cumulative toxicity as the clinical picture of TMA improved after stopping ixazomib, independently of plasmapheresis. Also, the lack of recurrence of TMA after stopping ixazomib supported the diagnosis in our case. |
pmc-6051101-1 | A 67-year-old female with past medical history of congenital deafness presented to the emergency room with complaints of right-sided facial droop and right upper extremity weakness, tingling, and numbness. These symptoms were sudden in onset and lasted for a few minutes. Symptoms had completely resolved at the time of presentation. She did not have a history of any atherosclerotic risk factor including hypertension, diabetes, or hypercholesterolemia. The initial set of vital signs were normal; routine laboratory tests including complete blood count and basic metabolic panel were unremarkable. A computed tomography (CT) of the head without contrast as well as a magnetic resonance imaging (MRI) of the brain with and without contrast did not show any acute intracranial hemorrhage or infarction.
The patient was diagnosed with TIA, and further investigations were planned to determine the etiology. A magnetic resonance angiogram (MRA) of the head and neck with and without contrast did not show any arterial flow limiting stenosis or occlusion. A transthoracic echocardiogram (TTE) with bubble study using agitated normal saline contrast was performed and was found to be normal. Patient's heart rhythm was monitored with continuous cardiac monitoring, and no arrhythmias were noted during her stay at the hospital. At this point, the patient was identified as having cryptogenic TIA, having failed to determine the precise etiology from routine workup. Patient was started on aspirin therapy and discharged from the hospital on day 3 with further outpatient workup planned. Outpatient workup for hypercoagulability showed a high factor VIII activity of 153%, which potentially put her at increased risk of venous thromboembolism. However, this test was performed just one week after the thrombotic event and was hence difficult to interpret. Subsequently, a transesophageal echocardiogram (TEE) was performed that revealed a patent foramen ovale with right-to-left shunt. This raised the concern for paradoxical embolism as the cause of patient's TIA. Lower extremity duplex venous ultrasound showed no evidence of deep vein thrombosis. However, magnetic resonance venogram (MRV) of pelvis showed compression of the left common iliac vein just after its origin, which was suggestive of May-Thurner syndrome (). There was no evidence of venous thrombosis on the MRV. May-Thurner syndrome was recognized as the probable source of paradoxical embolism causing TIA in the patient. The patient was eventually referred for percutaneous PFO repair, which was performed without any complications. The patient had been regularly followed yearly at the cardiology clinic for 5 years now. She remains in good health with no further episodes of TIA. |
pmc-6051109-1 | A 76-year-old male with past medical history of grade 3 RCC on day 24 of pazopanib after a left radical nephrectomy, atrial fibrillation, coronary artery disease, hyperlipidemia, obesity, and obstructive sleep apnea presented with fatigue, dyspnea, hematuria, and confusion.
He initially was diagnosed with RCC four months prior to admission (PTA) in the setting of hematuria. Two days PTA, he presented to an outside hospital emergency department with complaints of nausea and emesis and was admitted overnight for intravenous hydration and discharged with mild improvement in symptoms. He subsequently presented to his medical oncology clinic for an acute visit on the day of admission with progressive symptoms and new confusion and was admitted to the inpatient hematology service.
Upon admission, the patient was found to be hemodynamically stable and febrile with temperature of 37.8°C on admission and 38.3°C on hospital day 3. Exam was significant for drowsiness, irregularly irregular heart rhythm, and bilateral lower extremity venous stasis changes.
Labs were significant for acute thrombocytopenia (32 × 109/L, anemia (hemoglobin 12.6 gm/dL)), LDH 2001 U/L, fibrinogen 652 mg/dL, normal INR/PTT, elevated transaminases (AST 113 U/L and ALT 147 U/L), acute kidney injury (creatinine 1.59 mg/dL from baseline of 1.19 mg/dL), hyperbilirubinemia (2.2 mg/dL), and elevated LDH (2001). Haptoglobin was noted to be normal (135) on admission but was noted to downtrend to lower limit of normal (41) on day two of admission.
Scattered schistocytes were seen on peripheral smear, and he was diagnosed with thrombotic microangiopathy (TMA). Pazopanib was held, and he was subsequently started on daily, one-volume plasma exchange with rapid improvement in thrombocytopenia.
The platelet count normalized (), and ADAMTS13 activity returned as undetectably low with no inhibitor detected by mixing studies (ADAMTS13 assay FRETS-VWF73 via the Blood Center of Wisconsin) []. Plasmapheresis was continued for 19 days, as he had become febrile and confused on days when plasmapheresis was held. Repeat ADAMTS13 activity level two days after plasmapheresis was stopped and returned as normal. Platelet count initially remained stable after stopping plasmapheresis, but then started to downtrend within four days. He developed arrhythmias and catheter-related septicemia. Following discussion with family, care was transitioned to comfort-directed treatment plan. An autopsy listed the major cause of death as metastatic renal cell carcinoma. |
pmc-6051112-1 | A 76-year-old male was referred to the emergency department in May 2016 for significant unintentional weight loss of approximately 57 kg and associated chronic nonbloody watery diarrheal illness in the preceding 18 months. Medical history was notable for prostate cancer curatively treated in 2012, gout, a remote transient ischemic attack, osteoarthritis, and bilateral cataracts. In the months prior to presentation to Gastroenterology, an extensive medical workup performed as an outpatient was negative for prostate cancer recurrence, new malignancy, autoimmunity, or an identifiable malabsorption syndrome including celiac disease and pancreatic insufficiency.
The patient also noticed onycholysis in both his hands and feet (), followed by hyperpigmentation of his hands (), soles of his feet and legs, and abdomen. In addition to the nonbloody diarrhea, the patient reported a severe change in taste, early satiety, chronic heartburn, and nonspecific abdominal pain. He denied a history of fever, cough, night sweats, or abdominal pain. There was no family history of gastrointestinal malignancy or similar disorder.
Physical examination demonstrated profound cachexia with a weight of 50.9 kg and a BMI 16.5. Generalized sarcopenia was noted. The abdomen was scaphoid and nontender with no hepatosplenomegaly. Nonscarring alopecia was seen on the scalp, dystrophic nail changes were identified in both the hands () and feet, skin hyperpigmentation was noted primarily involving the palms (), dorsal aspects of fingers, face, and limbs, as well as sexual pattern hair loss of the abdomen, groin, and axillary hair. No cervical, inguinal, or axillary lymphadenopathy was identified. The rest of the physical exam was unremarkable.
Complete blood count was notable for a mild normocytic anemia (hemoglobin 119 g/L (reference range, 130–175 g/L) and mild eosinophilia of 0.82 g/L (reference range, 0–0.35 g/L)). Serum albumin was low at 28 g/L (reference range, 35.0–55.0 g/L). Serum electrolytes platelet count, white count, renal, liver enzyme and function tests, lipase and total protein, serum immunoglobulins, CRP, and TSH were normal. PSA was undetectable. Autoantibodies, including antinuclear antibody, antineutrophil cytoplasmic antibody, and rheumatoid factor (RF) were undetectable as were serologic tests for HIV, hepatitis, syphilis, and Lyme disease. Serum protein electrophoresis exhibited a modest elevation in kappa free light chains (23.0 g/L) but a normal kappa/lambda ratio was not consistent with a monoclonal gammopathy. There were no extended nutrient deficiencies with lead, copper, zinc, B12, or iron. Fecal elastase, stool culture, C. difficile, ova and parasites, and fecal leukocytes were negative. Stool for occult blood was positive.
Abdominal computed tomography (CT) demonstrated extensive gastric and duodenal mucosal fold thickening ().
Upper endoscopy demonstrated florid gastric and duodenal polyposis, with thickening of gastric folds and “carpet-like” semipedunculated gastric and duodenal polyps ranging from 5 mm to 20 mm (Figures and ). Histologically, the duodenal polyps showed edematous mucosa with variably dilated and branching glands, foci of gastric foveolar metaplasia, and blunted or absent intestinal villi. The inflammatory cell content of the lamina propria was mildly increased with prominent eosinophils.
Where native intestinal-type surface epithelium remained, it showed a mild increase of intraepithelial lymphocytes and an occasional intraepithelial eosinophil. There was no subepithelial collagen deposition. The gastric polyps were also a characteristic of Cronkhite-Canada syndrome. The foveolar glands were elongated, irregular, and focally dilated. The lamina propria was widely expanded by edema with an infiltrate of eosinophils and mononuclear cells (Figures and ). Helicobacter organisms were not identified in gastric or duodenal specimens. The involvement of the duodenum and gastric antrum in this process ruled out Menetrier's disease which is typically confined to the gastric body.
Based on these clinical, endoscopic, and histopathologic features, a diagnosis of Cronkhite-Canada Syndrome was made.
Due to near complete inability to take in enteral intake from severe early satiety and subjective global assessment of severe malnutrition, TPN was initiated in conjunction with a short course of methylprednisolone, followed by a tapering prednisone regimen starting at 50 mg per day. Azathioprine was also initiated at 75 mg daily. A jejunostomy tube was placed under radiological guidance to provide enteral nutrition, and a high protein formula was used for caloric requirements, as the patient was unable to take in more than a few tablespoons at a time.
Approximately six weeks after discharge, during the course of continued outpatient evaluation, the patient exhibited a worsening of his diarrheal illness accompanied by fever and progressive abdominal pain. Stool testing was positive for C difficile, and oral vancomycin was initiated with satisfactory clinical response. After several clinical relapses on vancomycin taper, the patient was advised by infectious diseases to continue suppressive vancomycin 125 mg PO daily.
Several months into steroid taper, the patient developed polyuria, polydipsia, and hyperglycemia which had not been present at higher steroid doses. Insulin was initiated with reversion to normoglycemia.
Despite adequate enteral caloric intake and immunosuppression, the patient continued to experience progressive weight loss, failure to thrive, and ongoing diarrhea (C. difficile toxin-negative). Based on a successful recent case report, off-label infliximab was employed []. Typical induction and maintenance infusions of infliximab were initiated with a regimen of 5 mg/kg at weeks 0, 2, and 6 followed by maintenance regimen of 5 mg/kg every 8 weeks thereafter. Remicade level was within the accepted range at week 14. Azathioprine was initiated with infliximab, at the beginning of therapy to prevent antibody formation to the anti-TNF.
The patient did not have an immediate initial response, and due to nausea, azathioprine was discontinued after 3 months. Azathioprine metabolites showed a 6-thioguanine of 106 pmol/8 × 108 RBC in the nontherapeutic range (230–400) and an undetectable 6-methyl mercaptopurine, appropriate for combination therapy with infliximab. Therefore, azathioprine was discontinued.
At 4 months from induction, the patient began to have nail regrowth, improvements in taste, and a modest improvement in diarrhea and weight.
Eight months following induction therapy with infliximab, bowel hygiene was significantly improved with approximately two formed movements daily. The patient was able to resume eating and drinking, and weight had increased by 10 kg. The patient also noted an improved sense of taste. Physical examination showed hair regrowth on the scalp, abdomen, and axillary and pubic regions in addition with improved proximal nail bed health. Hyperpigmentation was globally improved (). Laboratory values were within normal range.
Repeat upper endoscopy 9 months after initiation of anti-TNF showed notable improvement in gastric distention; however, there was persistent polyposis and no obvious pathological improvement in inflammatory cell infiltrate. |
pmc-6051115-1 | The patient was a 38-year-old nulliparous woman who suffered from infertility of unknown origin. She had been treated with assisted reproductive technologies including artificial insemination and in vitro fertilization for over four years. During her treatment for infertility, cytological review followed by colposcopic biopsy revealed an invasive nonkeratinizing squamous cell carcinoma (SCC). A 1 cm mass was identified in the uterine cervix, but a pelvic MRI did not describe the cervical mass or parametrial invasion. Additionally, a submucosal leiomyoma of 15 mm in diameter was found in the uterus (). CT scans showed no signs of lymph node swelling or distant metastases. Based on these findings, she was diagnosed with stage IB1 cervical squamous cell carcinoma. We offered radical hysterectomy and pelvic lymphadenectomy as standard treatment although she strongly desired fertility preservation. The submucosal leiomyoma may have been the cause of her infertility, and she was keen to resect the myoma during the same procedure. Submucosal leiomyomas can usually be resected with hysteroscopy but was not advised in this case from the oncological viewpoint. As such, we obtained informed consent and performed an abdominal radical trachelectomy followed by abdominal myomectomy.
During the surgery, we first drained the ascites in the pelvic cavity, resected bilateral pelvic lymph nodes, and sent them for intraoperative pathology. They were reported to be negative. The paravesical and pararectal spaces were then developed. The ureters on either side were resected to their insertion into the bladder. The uterine arteries were ligated and cut at the origin where they branched from the internal iliac arteries. Next, the uterosacral ligaments were divided. A colpotomy was performed circumferentially, and the cervical specimen was excised together with the parametrium at least 2 cm below the internal os. During the surgery, a frozen section procedure was performed for histology. The patient was found to have a 5 mm free cervical margin. A permanent cerclage was placed at the level of the isthmus. The uterus was then reanastomosed to the vagina. We then performed resection of the submucosal myoma via a uterine vertical incision. An intrauterine device (FD-1; Fuji Latex Co., Tokyo, Japan) was placed in the uterine cavity. The operation duration was 339 min, and blood loss was 500 ml. The surgery was completed with no complications.
The final histological specimen confirmed the diagnosis of squamous cell carcinoma, keratinizing type of cervix uteri, pT1B1. Exocervical, endocervical, and deep margin regions were negative. There was no metastatic lesion in the lymph nodes or lymphovascular space invasion. Leiomyoma of the corpus uteri showed no malignancy. No adjuvant treatment was administered, and no recurrence has been reported for at least 18 months postoperatively.
Six months after the surgery, she became pregnant following the postoperative first embryo transfer. The fetus was appropriate for gestational age. At 21 weeks of pregnancy, she claimed vaginal bleeding, and her lower uterine segment lengths were shortened from 23 mm to 13 mm. She was diagnosed with threatened abortion, and tocolysis was started. At 25 weeks, preterm premature rupture of membranes occurred. She received antibiotics, and intramuscular betamethasone was administered. At 26 weeks, a male baby weighing 980 g was delivered with an Apgar score 3/5/7 by caesarean section due to chorioamnionitis. The baby received general care in a neonatal intensive care unit for four months and weighed 4520 g when discharged. He is now 6 months old and is well. There has been no recurrent disease of her cervical cancer for 18 months from the trachelectomy and myomectomy. |
pmc-6051118-1 | Our patient is a 24-year-old nulligravid female with uncertain last menstrual period who presented to the emergency department (ED) with 12 hours of diffuse abdominal pain, worse in the left lower quadrant. She had intermittent nausea with one episode of emesis. She denied fevers or chills. She noted intermittent vaginal spotting, but no abnormal vaginal discharge. She had been seen two months previously for menorrhagia and was told at that time she had a possible fibroid; she was started on Depo-Provera for her menorrhagia. She denied any significant medical or surgical history. She denied any history of diabetes, HIV, or other immunocompromise. She denied any history of IUD placement or other uterine instrumentation. She had not been sexually active in several months and had no history of sexually transmitted infections.
She was initially febrile to 100.9F in the ED; within a few hours her temperature increased to 103.6F, she became tachycardic to the 140s, and was hypotensive to the 80s/50s. Her WBC count was 17.8. Urine pregnancy and HIV tests were negative. Blood glucose was 164 on admission. She was started on IV fluids and pressors and was given doses of cefepime, ceftriaxone, doxycycline, and metronidazole. CT abdomen/pelvis with contrast showed an 8.1 x 5.5 x 5.6 cm heterogeneous mass in the deep left pelvis that was inseparable from the uterus and broad ligament; it had an incomplete solid ventral surface and was thought to represent a hemorrhagic or infarcted fibroid (). No internal calcifications or fat was seen. Fat stranding and fluid were visible surrounding the mass. There was no pneumoperitoneum. Given the severity of the patient's condition and her hemodynamic instability, she was taken to the operating room for an exploratory laparoscopy.
Intraoperatively, pus was noted throughout the abdomen and the patient's bowel was edematous and filled with gas. Multiple pus pockets were seen in the patient's pelvis. A large left broad ligament leiomyoma was noted and appeared to be leaking pus (Figures and ). A myomectomy was performed laparoscopically, and the patient's abdomen was washed out.
She was then taken to the ICU intubated on pressors. She was kept on tobramycin and clindamycin for a presumed tuboovarian abscess. She was extubated on postoperative day 2 but continued to require supplemental oxygen and pressors. She also continued to spike fevers to 101.3F and was persistently tachycardic to the 140s. Infectious disease recommended switching to ceftriaxone and metronidazole at that time. She was afebrile by postoperative day 4 and remained afebrile with the exception of one isolated elevated temperature on postoperative day 8. Her tachycardia resolved. Blood glucose remained within normal limits. She was transitioned to oral antibiotics and discharged home in good condition on postoperative day 10.
Pathology showed a 128-gram leiomyoma with partial ischemic changes and nonspecific inflammation. A gram stain of the pus showed many neutrophils and gram-negative rods; a culture of the purulent fluid showed no growth, indicating an anaerobic infection. |
pmc-6051120-1 | A 32-month-old Middle Eastern boy was born full term at a community hospital in Michigan with birth weight of 3135 g (15.0 percentile). He had normal prenatal ultrasounds. He passed meconium at birth and had no other complications including prolong neonatal jaundice or dehydration. His CF NBS showed serum IRT 139 ng/ml and was negative for the 40 gene mutations panel. At 1 month of age, he developed a wet cough without any other symptoms. He was followed by his primary care provider (PCP), and no treatment was given at the time. His symptoms continued on and off until 1 year of age. At 1 year, the mother noticed increased frequency of productive cough, lack of appetite, and poor weight gain. His weight-for-age percentile ranged from 0.3 to 5.0. His stools were reportedly normal. He had no excessive sweating. He was referred to an outside asthma/allergy specialist for evaluation of asthma. He was prescribed budesonide without any improvement. He had frequent pharyngitis and otitis media that were treated with oral antibiotics that reportedly helped treat acute infection, but the cough persisted. He was also prescribed a H2 blocker for possible gastroesophageal reflux disease, but no improvement in symptoms was noted. Family history was negative for CF.
At 30 months of age, he was seen by his PCP for one week of cough and fever. He was treated with amoxicillin. His symptoms continued to worsen despite oral antibiotics, and he had two episodes of small-volume hemoptysis. He was subsequently admitted for community-acquired pneumonia and influenza B. Chest X-ray showed diffuse ill-defined opacities in the perihilar area and diffuse bronchiectasis. During the hospitalization, pediatric pulmonary consult was obtained. Given the negative NBS, it was stated that CF was unlikely and no sweat chloride test was recommended. He had a normal videofluoroscopic swallow study. Immunodeficiency workup revealed elevated immunoglobulin levels, protective vaccine titers, and normal lymphocyte counts and response to phytohaemagglutinin, concanavalin A, and pokeweed mitogen. HIV test was negative. Pediatric gastroenterology was consulted for failure to thrive and recommended to continue high-calorie diet. He was discharged home on augmentin.
Ten days following discharge, he was seen at the immunology clinic. He was noted to have digital clubbing, worsening tachypnea, and crackles. With the concerning physical exam findings, a sweat chloride test was done with a result of 90 mmol/L (normal 0–29 mmol/L; intermediate 30–59 mmol/L; abnormal ≥60 mmol/L) []. He was referred to pediatric pulmonary clinic the same day. He was then admitted and treated for a CF exacerbation. Throat culture grew Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus (MSSA). Fecal elastase-1 was <50 mcg E/g stool (normal >200 mcg E/g stool). Lab results including comprehensive metabolic panel and vitamin A and E levels were normal. He completed two weeks of cefepime and tobramycin.
After notifying MDHHS with the false-negative NBS results, the blood spot that was available at the NBS lab was retested using the new and expanded mutation panel (60 mutations). He was found to be homozygous for R1066C (c.3196C > T; p.Arg1066Cys) mutation. His care was transferred to our CF center, as per parents' request. Two weeks later, he was admitted for worsening respiratory symptoms and treated for a CF exacerbation. Vitamin D level was low at 25 ng/ml (normal ≥30 ng/ml). High-resolution computed tomography of the chest showed diffuse bilateral bronchiectasis (). Flexible bronchoscopy showed airway erythema and significant thick green secretions () that was positive for MSSA. |