A 60-year-old North African man presented to a primary care hospital with chest pain and an altered mental status. He had a 12-year history of type 2 diabetes and hypertension. His history also included ischemic stroke 4 years ago and he was allergic to penicillin. His medication included captopril, furosemide, and metformin. He was a non-tobacco smoker and had no family history of coronary artery disease.
He took 1000 mg of amoxicillin in automedication for a dry cough. He immediately experienced discomfort and chest pain. He presented to our emergency department 30 minutes later with dizziness, pruritus, warmth, flushing, and dyspnea associated with retrosternal oppression graded 7/10 on a pain scale.
At presentation, he had an altered mental status with a Glasgow Coma Scale (GCS) of 14/15 and had generalized urticaria. His vital signs were stable. An electrocardiogram (ECG) showed sinus rhythm and signs of myocardial injury with significant ST segment elevation of 3 mm in II, III, aVF, V7, and V8 leads and a reciprocal change in the anterolateral wall (Fig. ).
In the light of these clinical and electrical findings, the diagnosis of ST segment elevation myocardial infarction concomitant with anaphylactic reaction was strongly suspected.
Dexamethasone and diphenhydramine were intravenously administered in association with anti-ischemic treatment: heparin (50 mg intravenously administered), aspirin (250 mg intravenously administered) and clopidogrel (300 mg administered orally). Fibrinolysis was performed successfully using intravenously administered streptokinase. Our patient’s symptoms gradually improved and his ECG showed that the ST segment elevation returned to normal during transfer to the nearest cardiology department (Fig. ).
Transthoracic echocardiography showed severe hypokinesis of the posteroinferior wall from base to apex with altered left ventricular systolic function (ejection fraction = 30%) and moderate ischemic mitral insufficiency.
Laboratory tests showed the following: serum troponin I, 4.7 ng/l; creatine kinase–myocardial band (MB), 2096 mmol/l; brain natriuretic peptides (BNP) 110 ng/ml; and no abnormalities in electrolytes, renal function, and routine blood tests.
Coronarography was performed 24 hours later and showed mild and proximal stenosis of his left anterior descending artery (LAD) without evidence of ruptured vulnerable plaque, and severe proximal circumflex artery occlusion that required balloon dilatation and artery stenting. The result was middling with low coronary blood flow after percutaneous transluminal angioplasty: Thrombolysis in Myocardial Infarction Grade (TIMI) Flow II.
On the second day of hospitalization, he presented a cardiogenic shock concomitant with severe ventricular arrhythmia. The rhythm disorder was reduced by external electric shock. The reappearance of the ST segment elevation in lateral territory with persistent hemodynamic instability imposed treatment by a dobutamine infusion and urgent coronarography which revealed circumflex artery in-stent restenosis. An attempt to open the artery by balloon angioplasty was unsuccessful. A systolic electro drive probe was placed. On day 4, he presented an altered neurological status requiring intubation, mechanical ventilation, and sedation. Cerebral imaging showed massive inoperable intraparenchymal hemorrhage. The outcome was fatal on the sixth day of hospitalization (Additional file ).


A previously healthy 45-year-old North African man was brought to our emergency room complaining of generalized rash a few minutes after manipulating some plants in his garden. He immediately received 4 mg of dexamethasone intravenously for suspicion of anaphylactic reaction. Half an hour later, he developed severe retrosternal pain radiating to his left arm accompanied with epigastric discomfort. His vital signs were stable: his systolic blood pressure was 110 mmHg, his heart rate was 98 beats per minute, and his oxygen saturation was 99%.
An ECG showed ST elevation in anterior leads with ST depression in inferior wall (Fig. ). Upon arrival of the Emergency Medical Service (EMS) team, he was conscious and hemodynamically stable with regression of the hives. KS was immediately suspected. Anti-ischemic treatment was administered: heparin (50 mg intravenously administered), aspirin (250 mg intravenously administered) and clopidogrel (600 mg administered orally). He was transferred to the nearest catheterization room for primary angioplasty.
A coronary angiogram revealed total occlusion of his mid-LAD. His left circumflex artery and his right coronary artery were normal (Fig. ). Balloon inflation at the occlusion site allowed restoration of blood flow (TIMI Flow I; Fig. ). The lesion was very thrombotic, so the interventional cardiologist performed thrombo-aspiration and intracoronary abciximab injection, which was completed by a bare metal stent (3×18 mm) implantation. The final angiography result was good with TIMI Flow III (Fig. ).
The outcome was favorable and he was discharged from hospital 5 days later on adequate treatment with close follow-up (Additional file ).


A 57-year-old woman presented with 4 weeks of shortness of breath, dyspnea on exertion, and nonproductive cough. Imaging studies revealed a lung mass extending into the mediastinum with narrowing of the left pulmonary artery and total left upper lobe collapse. Patient was diagnosed with limited stage small cell carcinoma of the lung (SCCL). Initial therapy included cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 3 with plan to include radiation at cycle 2. Prior to the administration of cisplatin, patient's serum sodium (SNa) was 134–137 mEq/L. Following the first cisplatin dose, her SNa decreased to 133 mEq/L and 125 mEq/L by 24 and 48 hours, respectively. The acute hyponatremia was initially attributed to the continuous infusion of 5% dextrose half-normal saline in association with presumed lung cancer induced SIADH. However, despite empirical free water restriction, her SNa decreased to 119 mEq/L within 72 hours. Patient developed acute headache, nausea, and fatigue. Renal service was consulted.
Medications included fluticasone nasal spray twice daily, amoxicillin-clavulanic acid 875 mg twice daily, omeprazole 20 mg daily, and empirical intravenous stress dose of hydrocortisone 100 mg q 8 h. As needed medications included metoclopramide 10 mg q 6 h and albuterol 2.5 mg nebulizer treatment q 4 h.
Physical exam revealed blood pressure 123/76 mmHg, heart rate 70 beats per minute, and respiratory rate 18 per minute. Patient was uncomfortable with generalized headaches and nausea but alert and oriented to situation, person, place, and time. Oral mucosa was dry. Heart, lungs, abdomen, and extremities were unremarkable. Neurological exam was nonfocal.


A 65-year-old African American female presented with 4-month history of intermittent dysphagia, diplopia, fatigue, and muscle weakness which was more prominent in upper extremities.
Examination of cranial nerves revealed diplopia on right gaze, bilateral ptosis on sustained upward gaze, and mild lower facial muscle weakness. Motor examination showed decreased muscle strength of 4/5 in proximal and distal musculature of all extremities and neck flexors. Sensory system was intact and reflexes were normal.
In view of the above clinical presentation, MG was suspected and serological workup for MG was obtained which was positive for antibodies to acetylcholine receptor (AChR) with a titer of 14.6 nanomole/liter (0.0–0.4 nanomole/liter). Once diagnosis of MG was confirmed, she was started on pharmacological treatment with oral pyridostigmine (60 mg Q8 hours) and intravenous (IV) methylprednisolone (125 mg daily). Computerized Tomography (CT) of chest was done to exclude thymoma.
On 2nd day of treatment patient developed bradycardia with heart rate ranging from 40 to 50/min and frequent sinus pauses lasting from 1 to 3 seconds (). She then developed an episode of asystole lasting 16 seconds (), which was picked up by telemetry. Patient was asleep during this period and reported no symptoms. The etiology of this prolonged asystole was attributed to high grade SA node block caused by pyridostigmine. The dose of pyridostigmine was decreased to 30 mg q8 hours orally; however, patient continued to have sinus pauses and bradycardia. Therefore, treatment with oral muscarinic antagonist hyoscyamine (0.25 mg q6 hours) was initiated, which resulted in improvement in bradycardia and sinus pauses. Patient did not have any known history of bradyarrhythmias or dysautonomia. She did not report any symptoms (postural dizziness, syncope, or transient weakness) concerning for primary or secondary autonomic dysfunction. On reviewing the medications, no other drug besides pyridostigmine that can cause severe bradycardia or asystole was found. She was on continuous telemetric monitoring for 72 hours after starting treatment with hyoscyamine and no further episodes of bradycardia or asystole were reported. At 1-month follow-up after discharge, patient did not complain of any symptoms of dizziness or syncope. An electrocardiogram done at the follow-up visit showed normal sinus rhythm.


A 35-year-old right-handed Japanese man presented with a 1-month history of limited flexion and radiated pain in the left middle and ring fingers. He discontinued his work as a dentist because of the symptoms. A physical examination demonstrated an elastic hard nodular mass in his left palm with radiating pain. The active motion of the middle and ring fingers revealed loss of full flexion. The finger-to-palm distance was 10 mm. The passive motion was not restricted in all of the joints of the fingers. The left hand function was also reduced, with a grip strength of 35 kg in the right hand and 5 kg in the left. The Disabilities of the Arm, Shoulder and Hand (DASH) score was 14.5. The box and blocks test (BBT) score was 75 in the right hand and 55 in the left.
The laboratory test findings, including blood cell count and blood chemistry, were all within normal ranges. Radiographs of the hand revealed no remarkable findings. Magnetic resonance imaging (MRI) revealed a 2 × 1.5 × 1 cm mass of low intensity on T1-weighted images and high intensity compared with normal muscle on T2-weighted images and gadolinium enhancement (). 2-[18F]-Fluoro-2 deoxy-D glucose positron emission tomography revealed increased uptake with a maximum standardized uptake value of 3.73 in the mass.
After biopsy, he underwent resection of the tumor. The tumor had adhered to the flexor digitorum profundus of both the third and fourth fingers (). From which tendon the tumor arose could not be determined from the operative findings. The tumor, which was grossly firm and white-colored, was carefully dissected from the flexor tendons and neurovascular structures.
The external surface of the mass was smooth and glistening without any gross abnormalities or disruption and measured 2.0 × 1.3 × 0.9 cm (). The lesion was well circumscribed and contained fibroblastic spindle cells in a collagenous background, and some inflammatory cells were seen. There was generally no atypia. Elongated, slit-like spaces were prominent (). β-Catenin immunohistochemistry showed no nuclear staining. The histological diagnosis was fibroma of tendon sheath.
Immediately after the surgery, the limited flexion of the fingers was improved. The patient achieved full range of motion of all of the fingers with no pain or tenderness by two months after the surgery. The left hand function was also improved, with a postsurgery grip strength of 24 kg. His DASH score was 0.75, and his BBT score was 73 in the left hand. His International Society of Limb Salvage (ISOLS) score was 30. He returned to his dental practice, and no recurrence has been observed in the two years since the surgery.


A 50-year-old male patient suffering from the tenesmus and the presence of the blood in his stool, was admitted to the Gastroenterology and Liver Disease Research Institute, Taleghani Hospital, Tehran, Iran in January 2013. He referred with no personal or family history of the colorectal carcinoma or other related gastrointestinal diseases. Following the colonoscopy procedure, a hyperemic and flat lesion in the descending colon was discovered. The colon biopsy was performed to evaluate the depth of invasion in colon carcinoma in combination with the clinical examination by computed tomography scan. The final diagnosis was advanced colon cancer with liver metastases T3N2M1, stage IV.
After obtaining informed consent from patient, the EGFR immunohistochemical expression profile was investigated by anti-EGFR monoclonal antibody according to the manufacturer’s descriptions. The paraffin-embedded tissue sections were collected on microscopic slides. Tumor and tumor-free areas of the samples were identified within 15 μm thick deparaffinized, lightly hematoxylin-counterstained sections and subjected to the pathological studies. Each microdissected area was applied to the DNA extraction followed by the mutational analysis of KRAS (exons 2 and 3) and BRAF (exon 15) by using polymerase chain reaction (PCR) and direct sequencing. PCR cycling conditions were performed according to the manufacturer’s instruction. The ABI 3130 genetic analyzer (Applied Biosystems, USA) and the Big Dye Terminator (Applied Biosystems, USA) were used for the sequencing reactions of this study.
To investigate microsatellite instability (MSI), the DNA samples from the blood and microdissected tumoral areas of the patient were examined by using the BAT26, BAT25, NR24, NR21 and NR27 mononucleotide microsatellite markers. These markers are known to be the most sensitive markers of MSI status and widely uses for identification of the CRC cases with the concomitant mismatch repair (MMR) defects.
KRAS and BRAF mutational status analysis was performed on the representative lesion of the colon, using the PCR-sequencing method and MSI analysis. The identified mutations in KRAS and BRAF genes were a mutation in codon 12 of exon 2 and a missense nucleotide base change in codon 600 of exon 15 (GTG to GAG), respectively. However, MSI was not detected.


A 68-year-old man presented with a 7-month history of progressive multiple abscesses, followed by fever, lower extremity weakness and urinary retention. Seven months before, he occasionally found a bean-size lump with slight tenderness on the left side of the lower back. One month later, the lump increased to the size of an egg (Fig. ). Computed tomography (CT, for short) scan revealed an abscess inside the fascia. Chest CT scan showed pulmonary abscess formation (Fig. ). Repeated cultures of blood and percutaneous aspiration were constantly negative. Abscess incision and drainage were performed and empirical antibiotic treatment was given. Three months later, chest CT revealed the unresolved pulmonary abscess and additional multiple destructions of vertebral bodies, especially T5 and T11 (Fig. ). Empirical anti-tuberculosis drugs were administrated for 2 months. Instead of improvement, the patient became febrile to 38.4 °C, and developed weakness and numbness in both legs and urinary retention. The patient reported no significant past medical history, and he denied any exposure to bird droppings.
On examination, physician identified a skin lesion with draining sinus on the left side of the lower back. He had grade 0 muscle strength of both legs and slightly increased muscle tone. There was slight tenderness on the T4 and T5 vertebrae bodies, with hypoesthesia below T4 level. Laboratory testing revealed a leucocyte count of 16.55 × 103 cells/μL, a C-reactive protein concentration of 128 mg/L, an erythrocyte sediment rate of 120 mm/h and a negative result of HIV serology test. CD4+ T cell count was normal and the levels of serum globulins including IgG, IgA, IgM and total IgE were within normal range. T-SPOT. TB was negative. The (1, 3)-β-D-glucan test (or G test) and repeated SCLATs were all negative. Other laboratory results were unremarkable.
Spinal magnetic resonance imaging (MRI, for short) and subsequent CT revealed multiple bone destruction of thoracic and lumber vertebrae and ribs, with spine compressed at T4 and T5 level (Fig. ). Surgical excision of paravertebral abscess at T4-T5 level was performed and pathological examination of the excisional biopsy specimen found nothing but inflammatory changes. Specimen cultures were negative for bacteria, tuberculosis and fungi. Anti-mycobacterial treatment was ceased and the antibiotics changed to intravenous sulfamethoxazole-trimethoprim compound and oral doxycycline. Gradually, his temperature returned to normal and abscesses regressed. The patient was discharged on oral maintenance therapy.
Two months later, the patient presented to hospital again with a complaint of fever and a 50 × 60 mm new-onset lump with slight tenderness in the right groin. CT and MRI revealed a large right iliac abscess (Fig. ). Repeated cultures were negative and laboratory tests revealed no specific findings. The abscess increased in size gradually. Surgical drainage yielded 700 ml of coffee ground pus. Bedside inoculation of the pus was carried out and the result of culture revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction (PCR, for short) (Fig. ). The contrasted brain MRI found no evidence of central nervous system involving and so did the lumbar puncture. Liposomal amphotericin B and itraconazole were given. The fevers resolved when the accumulated dose of amphotericin B reached 2.5 g, and then itraconazole was replaced by fluorocytosine. We withdrew liposomal amphotericin B when its accumulated dose reached 3.0 g. The patient discharged with 4 months fluorocytosine plus fluconazole and regular follow-up. At 18-month follow-up, the patient was afebrile, with no new-onset abscess, and he could walk slowly. A Gantt chart was used to summarize the presentation and management of the patients (Fig. ).


A 23-year-old African American male presented two months after an injury from a motor vehicle collision where he sustained bilateral femoral fractures and a cervical spine injury. The patient had undergone a prior occipital to cervical level five posterior fusion and bilateral femur fracture fixation under general anesthesia without anesthetic complication. Other than the trauma, he had no significant past medical history. The patient’s family history was not significant for cancer, hypertension, endocrine, neurologic, or renal issues. He also reported he had no history of alcohol, smoking, and drug use. The patient was not currently taking any medication and reported he had no drug allergies.
On the day of surgery, the patient presented with a stabilizing halo fixation device in place and underwent an anterior cervical discectomy and fusion of cervical levels five through seven and a posterior spinal fusion of cervical levels five through thoracic level two.
The patient was premedicated with 2 mg intravenous midazolam. All standard American Society of Anesthesiologists-required monitors were placed, and an infusion of dexmedetomidine was initiated at 1 mcg/kg for 10 minutes as a loading dose, per dexmedetomidine drug protocol. After 10 minutes, the infusion rate was decreased to 1 mcg/kg/hour. The dexmedetomidine infusion was then stopped after intubation, and general anesthesia was initiated with a propofol drip at 100 mcg/kg/minute, and a remifentanil drip was initiated at 0.3 mcg/kg/minute; both drips were continued throughout the procedure as a general anesthetic. A bispectral index monitor was placed to monitor sedation levels. The anterior portion of the operation took approximately four hours, after which the patient was moved prone with appropriate spine stabilization.
The patient’s urine output was 150 mL one hour into the procedure. The patient’s urine output began increasing in the second hour until the completion of the nine-hour, 20-minute operation, reaching 750 mL/hour. During the surgical procedure, the patient received maintenance fluid as well as fluid to replace a presurgical deficit and blood loss, totaling 4.5 L of crystalloid. Blood loss was measured at 200 mL, and total urine output by the end of the procedure had reached 3065 mL (Table ).
The patient was hemodynamically stable throughout the procedure without significant episodes of hypotension or tachycardia, with a mean arterial pressure steady at approximately 65 mmHg. Due to the patient’s unexplained polyuria, a polyuric workup was initiated including urine and serum electrolytes and osmolalities. The patient’s initial serum sodium was 136 mmol/L, which was measured four days prior to the surgery. During the procedure, his sodium increased to 148 mmol/L, and, one hour following surgery, his serum sodium was 149 mmol/L. The patient’s intraoperative serum osmolality was within normal limits (294 mOsm/kg). However, his urine osmolality was as low as 55 mOsm/kg, and upon subsequent lab analysis, it increased to 127 mOsm/kg. The patient was extubated following a return to supine position, and he was monitored in the postanesthesia care unit for neurologic changes. The patient was then followed on the medical surgical unit. The patient’s urine output and laboratory values returned to baseline levels the following morning, and the patient was discharged home the following day without sequelae.


A 19-year-old married, Asian female, with a strong history of tuberculous contact, presented in a clinical set-up with a headache, backache, and mild lower limb weakness for four months. She was diagnosed as a case of TBM based on cerebrospinal fluid (CSF) detailed report. Her initial CSF report showed lymphocyte predominance, high protein, low glucose, and positive mycobacterial culture on BACTEC medium. She was started on isoniazid 250 mg, rifampin 450 mg, streptomycin 750 mg, and pyrazinamide 1000 mg once daily. After getting discharged her bilateral lower limb weakness progressed and worsened. she had become unable to even stand independently. There were associated high-grade fever, headache, and vomiting. She had no complaints of numbness, paresthesia, bowel or bladder incontinence or retention, diplopia, facial weakness, or dysphagia. Also, she did not report any trauma or fall. There was no history of cardiac, respiratory, genitourinary, gastrointestinal, or musculoskeletal abnormality. Both her parents had TB and completed treatment for it.
On admission, she was pale-looking but was vitally stable. On neurological examination, she was conscious and alert with a GCS of 15/15. Her higher mental functions and cranial nerves were intact. Signs of meningeal irritation were not present. Her sensory examination was completely normal. However, on motor examination, there was decreased bulk globally and flaccid paralysis in both lower limbs. Cerebellar signs (dysdiadochokinesia, scanning speech, intention tremors, past pointing, nystagmus) were not there. Other systemic examination findings were normal.
Initial investigations showed a normal leukocyte count. Renal function tests, electrolytes, and liver function test were within normal ranges. Erythrocyte sedimentation rate was 6 mm. Her chest x-ray (CXR) did not show any abnormality. Enzyme-linked immunosorbent assay (ELISA) for HIV came back negative. The CSF examination revealed raised CSF protein of 351 mg/dl (reference range is 15 to 60 mg/100 ml) and normal glucose of 59 mg/dl (reference range is 50 to 80 mg/100 ml). Random blood sugar (RBS) was normal (90 mg/dl) with a CSF to RBS ratio of 0.66. A lymphocytic pleocytosis was also seen. These findings except culture were quite like the prior CSF analysis based on which she was started on antituberculous therapy (ATT). The CSF microscopy, culture, and sensitivity were negative for Mycobacterium tuberculosis (MTB). Similarly, CSF polymerase chain reaction (PCR) could also not detect MTB DNA. Apart from this CSF oligoclonal bands were detected, indicative of intrathecal immunoglobulin G (IgG) synthesis. Magnetic resonance imaging (MRI) brain had no remarkable findings.
Electromyography and nerve conduction studies were suggestive of bilateral lumbosacral polyradiculopathy likely secondary to spinal arachnoiditis. MRI dorso-lumbar spine (with contrast) revealed abnormal signal intensity area seen within the spinal cord extending from the lower dorsal level up to D10 appearing iso-intense to low-intense on T1W and high-intense on T2W images showing no significant post-contrast enhancement. The cord appeared irregular in outline representing syringohydromyelia involving the long segment. There was associated clumping of peripheral nerve roots seen in the lower lumbar spine representing arachnoiditis with syrinx formation (see Figure ).
We started her on a tapering dose of intravenous dexamethasone 0.4 mg/kg along with ciprofloxacin 750 mg twice a day while continuing oral first line ATT []. Her steroid dose was tapered. Over the period of one month, she showed marked improvement in power from 1/5 to 4/5 bilaterally and she could walk with support.


A 10-year-old healthy Indian boy presented to the Department of Oral Medicine and Radiology with a complaint of a small swelling in the roof of his mouth. His parents reported that the swelling was noticed 10 days earlier and he had no prior complaints. The onset was spontaneous with no history of trauma due to any cause. It was associated with minor bleeding and mild pain on chewing food. He did not report any nasal block or epiphora. His past medical history (immunized for age), social history, family history, and environmental history were noncontributory. General examination revealed normal vital signs (afebrile, heart rate of 100 beats/minute) with no signs of pallor, cyanosis, or icterus. His height was 108 cm and his weight was 18 kg. He was conscious, cooperative, and well oriented to time, place, and person. There were no demonstrable neurological deficits. Intraoral examination revealed a well-circumscribed growth along the midline on the posterior aspect of his hard palate, approximately 2 cm in diameter, dark purple in color with overlying whitish-yellow pseudomembrane (Fig. ). The surface over the growth appeared slightly irregular. On palpation the lesion was sessile and soft-to-firm in consistency with tenderness. There was no bleeding on manipulation and a diascopy test showed mild blanching. Taking his young age and clinical presentation into account, hemangioma/vascular malformation, pyogenic granuloma, and angina bullosa hemorrhagica were considered for clinical differential diagnoses. Contrast-enhanced Magnetic resonance imaging revealed that the oral lesion was well encapsulated with thinning of the floor of his nasal cavity (Fig. ), which indicated the possibility of a hemangioma. Considering the clinical and radiological investigatory findings, the differential diagnoses that were taken into account were encapsulated vascular lesions and palatal minor salivary gland tumors. His preoperative laboratory values were all within the normal range: hemoglobin 10 g/dl; hematocrit 32%; mean corpuscular hemoglobin (MCH) 17.6 pg; mean corpuscular hemoglobin concentration (MCHC) 31.2 g/dl; mean corpuscular volume (MCV) 56.3 fl; platelet count 285×103/μl; red blood cell (RBC) count 5.68×106/μl; total white blood cell (WBC) count 14×103/μl; activated partial thromboplastin time (APTT) 28.5 seconds; serum urea 18 mg/dl; and serum creatinine 0.5 mg/dl. Serological tests were non-reactive for human immunodeficiency virus and hepatitis B. Following this he was posted for elective surgical excision of the lesion. Complete removal of the growth was done under general anesthesia and the specimen was sent for histopathological examination.
Histopathological examination revealed a tumor with surface ulceration and inflammation, composed of bland spindle-shaped cells that had ovoid-shaped to spindle-shaped tumor cells arranged in a fascicular pattern and swirls with intervening pale mucoid to myxoid stroma. No areas of increased mitosis, necrosis, or pleomorphism were noted. As the tumor tissue was received in multiple bits, the marginal clearance could not be commented upon. However, the tumor lacked features such as infiltrative growth pattern, necrosis, or perineural invasion owing to which a diagnosis of benign myoepithelioma was considered. Differentiating features between benign and malignant counterparts of myoepithelioma are cytological atypia and mitosis. The tumor cells on immunohistochemistry stained positive with S100, CK5/6, and p63 (Fig. ). A diagnosis of palatal myoepithelioma (benign spindle cell variant) was made based on the above features.
His postoperative recovery was uneventful with complete healing of the palatal area and no clinical evidence of recurrence (7 months postoperation). He was advised to have clinical/ radiological follow-ups on an annual basis.


A 38-year-old gravida 7 para 5015 patient with Class C diabetes and singleton pregnancy presented at 36 + 4/7 weeks of gestation for scheduled nonstress testing with the additional report of decreased fetal movement for the last day. The patient's blood glucose logs indicated sufficient glucose control and her hemoglobin A1c one month prior to presentation was 7.1%. Fetal growth was greater than the 98th percentile with an estimated fetal weight of 3616 grams and an amniotic fluid index of 22.1 cm nineteen days prior to presentation at 33 weeks and 6 days of gestation. Fetal umbilical Doppler studies were not indicated and patient was monitored with twice weekly nonstress tests, which were within normal limits. She was a nonsmoker and had an overweight BMI of 28.47 kg/m2. On presentation, bedside ultrasonography identified amniotic fluid level of 4.75 cm and the fetal heart rate tracing indicated irregular contractions with recurrent late-pattern decelerations from a baseline of 150 with moderate variability to 90 beats per minute lasting about one minute. Due to nonreassuring fetal status with oligohydramnios, delivery was affected by repeat low transverse cesarean section. At delivery, the umbilical cord was dusky and thrombus was palpable (). The male infant weighed 4015 g. Resuscitation was rapid with Apgar scores 8 and 9 at 1 and 5 minutes, and other than transient hypoglycemia, the neonatal course was uneventful. The maternal postpartum course was also uncomplicated.
The placenta weighed 501 grams and the disc grossly appeared normal; however, the entire length of the cord appeared dark and mottled, showing signs of thrombosis. The pathological report described a three-vessel umbilical cord with subocclusive thrombosis of the umbilical vein, narrowing the vascular lumen by 40% (). The fetal membranes were unremarkable. There were vascular congestion of the chorionic plate and a small 10 mm diameter area of subchorionic hemorrhage. Due to greater than the 10 capillaries per high power field of the chorionic villi, chorangiosis was identified ().


A 74-year-old Maltese female was transferred to our hospital from a rural emergency department following an unwitnessed collapse preceded by several days of generalized weakness. Her significant past medical history included ST elevated myocardial infarction, hypertension, depression, osteoarthritis requiring a total hip replacement, and osteoporosis. Her weight was stable at 51 kg with a body mass index of 22.5. She was a nonsmoker and she consumed on average one unit of alcohol per day. Her admission medications included amlodipine, atorvastatin, ticagrelor, metoprolol, aspirin, amitriptyline, perindopril, and weekly risedronate. She had been treated with a combination product of amlodipine and atorvastatin for several years. Two and a half months prior to her admission, she was diagnosed with ST elevation myocardial infarction, which was medically managed due to unsuccessful percutaneous coronary intervention to reopen a blocked artery. Her management included an increased dose of amlodipine/atorvastatin combination from 5/20 mg to 5/80 mg and antiplatelet therapy of low-dose aspirin in addition to ticagrelor 90 mg twice a day as per treatment guidelines.
In the rural emergency department, the patient was hypotensive and had minimum urine output. She received fluid resuscitation of 4 litres and was commenced on noradrenaline infusion at 10 micrograms per minute. The initial diagnosis was septic shock and acute kidney injury with a creatinine level of 404 μmol/L and urea of 17 mmol/L. She had mild neutrophilia. The chest X-ray and computed tomography of the brain and the cervical spine were reported as unremarkable. She was then transferred to our intensive care unit (ICU) due to lack of ICU services at the referring hospital.
Upon admission to ICU, the patient appeared confused, but cooperative. She was moving her 4 limbs. Her heart rate, blood pressure, respiratory rate, and temperature were 86 beats per minute, 102/42 mmHg, 15 breaths per minute, and 35.7°C, respectively, while receiving 10 micrograms per minute of noradrenaline. She was well oxygenated on 2 litres per minute of oxygen. She was tender on her right lumber region, while the rest of the physical examination was unremarkable. The liver function was significantly deranged, with alteration in the coagulation profile and worsening renal function ().
The computed tomography and the ultrasound of the abdomen revealed a calculus thickened gall bladder with pericholecystic fluid and free fluid in the abdomen. The diagnosis of acute cholecystitis that resulted in multiorgan failure was affirmed. On subsequent assessment however, the abdominal symptoms and signs had dissipated, and surgery was no longer indicated. Continuous venovenous haemodialysis and filtration (CVVHDF) was commenced due to worsening metabolic acidosis and acute anuric renal failure.
On day 2, the patient developed worsening muscle pain and progressive weakness in the upper and lower limbs with diminished tendon reflexes. The creatinine kinase (CK) was profoundly elevated approaching 100000 U/L () and there was a progressive deterioration in the liver function (). On further microbiological, biochemical, and serological assessment, sepsis, haemolysis, vasculitis, thyroid disorders, and paracetamol toxicity were excluded. A provisional diagnosis of autoimmune myositis or SAR was suggested. On day 7 magnetic resonance imaging (MRI) of the musculoskeletal system revealed features consistent with upper and lower limbs proximal myositis. MRI targeted muscle biopsy was also performed. CK was persistently elevated with worsening liver function; disseminated intravascular coagulation developed leading to epistaxis, upper gastrointestinal bleeding, and subcutaneous haemorrhage. She continued to have moderate neutrophilia, modest increase in the C-reactive protein.
The disseminated intravascular coagulopathy was treated with platelets and clotting factors replacement and with Vitamin K. A presumed diagnosis of autoimmune myositis was made. Further deterioration in the patient state, while waiting for the biopsy results, prompted treatment with 1 gram of intravenous methylprednisolone daily for 3 consecutive days for the potential autoimmune aetiology of her presentation. The patient was more fatigued, becoming drowsy and hypoxic and requiring endotracheal intubation and ventilation. The muscle biopsy revealed extensive myonecrosis of similar age and scant regeneration, consistent with toxin induced necrotising myositis.
Her condition gradually improved and CK levels gradually returned to within the normal range (). Due to profound weakness, she was rendered difficult to be weaned off mechanical ventilation and subsequently received percutaneous tracheostomy. The renal and liver function gradually improved and CVVHDF was discontinued. The renal biopsy confirmed acute tubular necrosis with extensive myoglobin-related cast formation. She was gradually weaned off the ventilator and the tracheostomy tube was removed in the ICU. She was mechanically ventilated for a total of 1041 hours and she stayed in ICU for 69 days. She was discharged to the medical ward and subsequently discharged to a rehabilitation centre.


We present the case of a term baby girl born to a healthy 38-year-old mother. Pregnancy was uneventful until a fetal ultrasound revealed subependymal cysts at 26 weeks of gestation. Prenatal magnetic resonance imaging (MRI) confirmed bilateral intraventricular cysts and mild dilation of both posterior horns of the lateral ventricles (Figure A). At 36 weeks of gestation, a second MRI revealed additional diffuse white matter hyperintensities (Figure B). While the mother had documented CMV IgG serum antibodies prior to pregnancy, amniocentesis was performed subsequent to MRI and CMV PCR from amniotic fluid was positive (8.96 log GEq/ml). Therefore, maternal recurrent CMV infection during pregnancy was diagnosed.
The girl was born by spontaneous vaginal delivery at 40 weeks and 1 day gestation. During delivery, meconium staining of the amniotic fluid was noted and Apgar scores were 8, 8, and 10 at 1, 5, and 10 min, respectively. Umbilical cord pH values were 7.20 (arterial) and 7.34 (venous). Signs of mild respiratory distress disappeared at 10 minutes of life, and no further respiratory support was required. Her birth weight was 3,140 g [Percentile (P) 19], length 50 cm (P29), and head circumference was 33 cm (P8). Upon physical examination, extensive petechiae, hepatosplenomegaly, and jaundice were found.
Congenital CMV infection was suspected and confirmed within the first days of life by serology (CMV IgG 1,473.4 AU/ml, IgM 0.95 TW), and PCR in infant blood and urine samples (9,710 and 7.09 log GEq/ml, respectively). After informed consent to administer antiviral therapy was obtained from the parents, intravenous (i.v.) ganciclovir (7.5 mg/kg/dose 12 h) therapy was initiated. Postnatal MRI on day 5 of life revealed bilateral subependymal cysts, mild dilatation of both lateral ventricles and white matter hyperintensities (which had already been detected during fetal imaging), but neither calcifications nor polymicrogyria were observed (Figures A,B). Severe thrombocytopenia (5 × 109/l minimal count) required repeated platelet transfusions. Profound hepatopathy (ALAT 369 U/l and ASAT 863 U/l maximal count, respectively) led to conjugated hyperbilirubinemia (257.6 µmol/l maximal count), coagulopathy, and progressive cholestasis within the first 2 weeks of life. Otoacoustic emissions and acoustic-evoked potentials, performed on days 4 and 21 of life, were abnormal on the right side. Eye examination was unremarkable except for preretinal bleeding spots and EEG was normal.
Over 3 weeks of i.v. ganciclovir therapy, liver dysfunction improved, and CMV viral load in the plasma decreased significantly, from maximal values of about 10,000 GEq/ml to minimal 1,000 GEq/ml. Therapy was changed to oral valganciclovir (18 mg/kg/dose 12 h), and the girl was discharged with close interdisciplinary follow-up.
The child was regularly seen in our outpatient clinic and viremia persisted with viral loads between approximately 1,000 and 3,000 GEq/ml. Oral valganciclovir was stopped after a total of 6 weeks of antiviral treatment. She exhibited normal neurological development apart from mildly reduced muscle tone and suspected sensorineural hearing loss (SNHL) on the right side. The latter was confirmed by electric response audiometry at the age of 1 month. At the age of 12 months, she still showed normal neurological development. In addition, muscle hypotonia had disappeared, but hearing loss on the right side was still detectable. Unfortunately, no serum viral load was determined.
At the age of almost 4 years, the girl presented with acute unsteadiness (mild ataxia) at our emergency department. Multiple laboratory examinations, including cerebrospinal fluid and blood tests for viral or bacterial infections revealed negative results. Unfortunately, no CMV diagnostic was made when the child underwent a thorough workup for her disorder. A cranial MRI showed regressive cerebral abnormalities (periventricular white matter lesions on both sides due to demyelination and gliosis, and intraventricular occipital adhesions, Figures A,B) without any signs of intracranial bleeding, infection or tumor. During hospitalization, she developed discrete signs of an upper respiratory tract infection while neurological symptoms slightly decreased. Symptoms were interpreted to be of parainfectious origin, and there was no evidence of a relationship with cCMV.
The girl was last seen for follow-up at 4.5 years of age. She still exhibited normal neurological development. As a residuum of cCMV infection, deafness on the right side persisted [hearing threshold level >90 dB, defined as severe hearing loss ()]. Further auditory follow-up until the age of 6 years was recommended.


A 62-year-old man presented to the hospital for evaluation of progressive vision loss and back pain. His past medical history was significant for plasma cell leukemia-multiple myeloma since September 2015. His treatment regimen was as follows: VCD (bortezomib, cyclophosphamide, and dexamethasone), RVD (lenalidomide, bortezomib, and dexamethasone), Kyprolis-dex (carfilzomib and dexamethasone), pomalyst (pomalidomide), hyper CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and autologous stem cell transplant.
He developed asymptomatic cutaneous nodules on the arms and legs 50 days after stem cell transplant. Cutaneous examination revealed erythematous, firm, non-tender, and smooth nodules, which ranged from 8 mm to 2 cm in diameter on the proximal upper arms (Figure ) and bilateral lower extremities (Figures -). One nodule was on each proximal arm, 10 were on the right upper leg, and two were on the left upper leg.
His laboratory studies from 11/14/2016 showed a total leukocyte count of 3.1 × 109/L with 45% polymorphonuclear cells and 30% lymphocytes. His hemoglobin was 8.1 gm/dL and the platelet count was 62,000. Monoclonal kappa light chain bands were noted in the blood and urine. Biochemical parameters were: serum creatinine 0.66 mg/dL, serum calcium 8.3 mg/dL, total serum proteins 6.3 g/dL, and alkaline phosphatase 36 U/L. His serum bilirubin and liver enzymes were within normal limits.
Magnetic resonance imaging of his brain (11/11/2016) and spine (11/13/2016) showed leukemic involvement of the brain and lumbar intrathecal space. The patient’s cerebrospinal fluid was found to have large, immature plasmacytoid cells. Flow cytometry revealed clonal, kappa-restricted plasma cells.
A punch biopsy for pathology and tissue culture (bacterial, fungal, and mycobacteria) was performed on the right upper leg on 11/11/2016. The biopsy showed sheets of plasmacytoid cells arranged in a nodular aggregate with pronounced atypical nuclei (Figures -). Immunohistochemistry was performed with CD20 (B-lymphocyte antigen), PAX-5 (B-cell-specific activator protein), CD138 (syndecan-1, a plasma cell marker), and kappa/lambda chromogenic in situ hybridization. The cells of interest were negative for CD20 and PAX-5. Plasma cell lineage was confirmed with CD138 immunolabeling of the neoplastic cells (Figure ), and clonality was demonstrated with kappa-light chain restriction (Figures -). These results corresponded to previous characteristics of the patient’s myeloma. Tissue cultures were negative.
Correlation of the history, clinical presentation, and histopathology/immunohistochemical studies confirmed the diagnosis of plasma cell leukemia. The patient’s progressive vision loss and back pain was attributable to central nervous system involvement of his plasma cell leukemia. The patient received dartumumab (monoclonal CD38-inhibitor) for his systemic disease. He also received intrathecal cytarabine before and after radiation to treat his central nervous system relapse.
The patient was later admitted for failure to thrive and shortness of breath, with concern of a possible lung infection []. He was then transferred to hospice care and succumbed to his underlying disease and sepsis. The patient died at day 75 post-transplant, 25 days after his diagnosis of leukemia cutis.


A 72-year-old male presented to the emergency department complaining of 6-week history of intermittent hematuria. He was diagnosed with prostate cancer thirteen years prior to this presentation and was treated with external beam radiation therapy. His cancer recurred six years later and he was treated with high dose brachytherapy. Five-year posttreatment follow-up with computed tomography (CT) scans and prostate specific antigen (PSA) levels (range 0.63–0.8 ng/mL) revealed no evidence of disease. He had a past medical history of coronary artery disease status after percutaneous intervention with drug-eluting stent to the right coronary artery, diabetes mellitus type 2, hypertension, obstructive sleep apnea, and complicated necrotizing pancreatitis with walled-off necrosis. He had a past surgical history of cardiac catheterization, distal pancreatectomy, and brachytherapy seeds implantation. He denied any previous history of smoking and alcohol or illicit drug use. He has a family history of diabetes and hypertension, but no history of malignancy. His home medications included aspirin, clopidogrel, atenolol, lisinopril, simvastatin, insulin, and as needed acetaminophen-oxycodone for pain. He has no known allergies. On physical examination he was alert, oriented, and not in acute distress. His vital signs were as follows: temp 36.4°C; blood pressure 134/75 mmHg; respiratory rate 16 bpm; pulse 116 bpm; and oxygen saturation 97% on room air. Abdominal examination revealed normal active bowel sounds, which was soft and nontender to palpation, no evidence of organomegaly, left-side nephrostomy tube with clear urine, and an indwelling urinary catheter with gross hematuria. Digital rectal exam revealed normal sphincter tone, with the prostate being smooth, symmetric, and measuring 4 × 5 cm. Fecal occult blood test (FOBT) was negative.
The patient presented to another hospital with same complaint of hematuria two months prior to this admission. At that time workup revealed left sided hydronephrosis due to obstructive ureteric stones. Urgent cystoscopy with ureteric stent placement was performed which failed to relieve the obstruction. So, an emergent nephrostomy tube was inserted and he was discharged with indwelling urinary catheter and follow-up plans for revision and placement of another anterograde ureteric stent.
Upon admission to our hospital, the urinary catheter was replaced with a three-way urinary catheter and bladder irrigation was initiated. Computed tomography (CT) scan of abdomen and pelvis revealed no evidence of obstructive uropathy, diffuse thickening of the wall of the urinary bladder, and brachytherapy radiation seeds in the prostate (). Cystoscopy revealed edematous mass over the left wall of the bladder. Transurethral resection of bladder tumor (TURBT) was performed and histopathology revealed invasive poorly differentiated carcinoma infiltrating lamina propria and muscularis propria, with foci suspicious for angiolymphatic invasion. Immunohistochemical stains were positive for Ber EP4, pankeratin, AE1/AE3, chromogranin, and TTF-1 and negative for CK-7, CK-20, PSA, and PAP (). This carcinoma was histologically distinct from the previous prostate adenocarcinoma and consistent with large cell neuroendocrine carcinoma (LCNEC).
Further workup for staging of the disease was performed. Computed tomography (CT) scan of the chest revealed multiple bilateral pulmonary and pleural-based nodules suggestive of metastasis (). Magnetic resonance imaging (MRI) of the brain and bone scan were both negative for metastatic disease.
Considering the rarity of the disease and unclear treatment guidelines a multidisciplinary team discussed the best treatment approach. The consensus was treatment with neoadjuvant chemotherapy using carboplatin and etoposide for five cycles followed by radical cystectomy. After completion of his fifth cycle of chemotherapy, a follow-up CT scan of the chest/abdomen/pelvis revealed interval increase in the size and number of bilateral pulmonary nodules and development of new liver lesions consistent with metastasis. He was started on anti-PD-1 immunotherapy with pembrolizumab “as an off-label prescription.” Nevertheless, he was readmitted to the hospital due to intractable shoulder and back pain. Palliative care team met with the patient and his family. He stated his wishes to be transferred to hospice with comfort care due to his significant declining performance status and quality of life.


A 39-year-old female presented as a transfer from outside hospital for management of peritonitis and peritoneal abscess following colon perforation which occurred as a complication from oophorectomy and ventral hernia repair. Patient underwent exploratory laparotomy and diverting colostomy and a drain was placed for drainage of peritoneal abscess. Electrocardiogram (ECG) () at admission demonstrated normal QT interval and serum potassium was 5.2 mEq/L. No structural abnormalities were noted on echocardiogram.
After 6 days of treatment with intravenous IC, she developed hypokalemia of 3.1 mEq/L, metabolic alkalosis, and prolongation of QT interval (QTc 533 ms). The rest of the electrolytes including magnesium and serum calcium were normal. Potassium was replaced and the antibiotic was switched to PT based on cultures after 2 days. Hypokalemia worsened to 2.9 mEq/L and continued to remain low despite replacement of potassium of 80–120 mEq/day. QTc further increased to 632 ms (). No QT prolonging drug was administered in the previous 48 hours (see the following list).
List of medications administered before the episode of Torsades de Pointes (TdP):Acetaminophen Amlodipine besylate Calcium gluconate Chlorhexidine gluconate (last administered 5 days before episode of TdP) Dexmedetomidine hydrochloride (last administered 5 days before episode of TdP) Divalproex sodium Docusate sodium with senna Enoxaparin injection Fentanyl citrate in 0.9% NaCl (last administered 5 days before episode of TdP) Furosemide injection (last administered 5 days before episode of TdP) Hydromorphone hydrochloride injection (last administered 5 days before episode of TdP) Imipenem-cilastatin (last administered 2 days before episode of TdP) Lisinopril Lorazepam injection (last administered 9 days before episode of TdP) Metoclopramide hydrochloride (last administered 6 days before episode of TdP) Micafungin sodium (last administered 13 days before episode of TdP) Midazolam hydrochloride (last administered 5 days before episode of TdP) Morphine sulfate (last administered 10 days before episode of TdP) Olanzapine injection (last administered 4 days before episode of TdP) Pantoprazole sodium (last administered 4 days before episode of TdP) Piperacillin-tazobactam Potassium chloride Potassium phosphate Sertraline hydrochloride (last administered 3 days before episode of TdP) Vancomycin hydrochloride (last administered 5 days before episode of TdP).
Three episodes of self-terminating TdP were noted on telemetry, with approximately ten seconds being the longest duration (). During these episodes, the patient experienced palpitations, dyspnea, and lightheadedness. Multiple episodes of nonsustained VT were also noted on telemetry. Intravenous magnesium was administered and potassium replenishment continued. Transtubular potassium gradient was calculated to be 6.5 indicating renal loss of potassium. Renin and aldosterone levels were normal. Repeat cultures demonstrated Enterobacter cloacae which was resistant to PT in addition to Proteus mirabilis and Enterococcus faecalis. PT was switched back to IC as per recommendations by infectious disease specialist. Hypokalemia now responded to potassium replacement and improved to 4 mEq/L from 3.3 mEq/L and remained in normal range. QTc improved to 487 () and patient had no more events on telemetry. It has to be noted that during her entire hospitalization she did not develop diarrhea or vomiting to suspect gastrointestinal loss of potassium or acid.


Mr. F. is a 52-year-old man, single, and employed. He had no a personal or familiar history of OCD or HYPO. At 31 years, he developed schizo-affective disorder (SA) (DSM-IV criteria), successfully treated () with clozapine (200 mg/day), lithium salts (serum level 0.60 mEq/l), and valproate (600 mg/day, serum level 50 μgr/ml). After 5 years of remission, we discontinued valproate and reduced clozapine to 150 mg/day. When F. was 47 years old, he developed severe HYPO (DSM-IV criteria) () with headache, dizziness, fear of having a neurological disease, and reassurance seeking (frequent neurological visits and calls). We treated unsuccessfully HYPO: (a) adding sertraline (150 mg/day) and discontinuing it after 3 months for psychotic symptoms reactivation (the Positive and Negative Symptom Scale total score increased from 44 to 72); (b) adding valproate (900 mg/day, serum level 78 μgr/ml) (4 months); (c) adding aripiprazole (20 mg/day) (2 months). The combination of pharmacotherapy and CBT (37 sessions) partially improved HYPO. Lastly, we reduced the clozapine dosage from 150 to 75 mg/day (25 mg for month) and HYPO gradually remitted (). HYPO remission, as well as SA remission, continued for 3 years.


Mr. B. is a 48-year-old man, single, and employed. He had a personal history of panic attacks but not a personal or familiar history of OCD or HYPO. When he was 19 years old, he developed SCH successfully treated with clozapine (500 mg/day) in combination with valproate (1000 mg/day, serum level 86 μgr/ml) (). Seven years ago, we discontinued valproate and reduced clozapine (400 mg/day). When B. was 45 years old, he developed a very severe HYPO disorder (DSM-IV criteria) () with dyspnea, fear of having a cardiac disease, and reassurance seeking (frequent medical visits and hospital admissions). B. refused CBT and we treated HYPO unsuccessfully: (a) adding paroxetine (30 mg/day), sertraline (150 mg/day), and clomipramine (50 mg/day) (resp., 2, 3, and 2 months); (b) adding valproate (1500 mg/day, serum level 94 μgr/ml) (3 months); (c) adding valproate (1500 mg/day, serum level 91 μgr/ml) plus amisulpride (600 mg/day) (4 months). Lastly, we reduced clozapine dosage (100 mg/die) without changing valproate and amisulpride doses and HYPO dramatically improved (). HYPO improvement, as well as SCH remission, continued for 2 years.


A 34-year-old North African woman with no specific past medical history was hospitalized, initially in another hospital, for the management of obstructive jaundice with a hepatic cystic lesion of segment I taken for a hydatid cyst that compressed the biliary convergence. She had undergone a resection of the protruding dome by laparotomy. Two months later, she was admitted for angiocholitis due to a probable recurrence of the hydatid cyst complicated by compression or rupture in the bile ducts. She was febrile 38.5 °C with mucocutaneous jaundice, dark urine, and discolored stools. A clinical examination found neither defense nor hepatomegaly or palpable mass.
Biological examinations revealed moderate cytolysis and cholestasis. Hydatid serology and serum tumor markers were negative: carcinoembryonic antigen (CEA) and carbohydrate antigen (CA).
A computed tomography (CT) scan showed a hepatic cystic lesion of segment I, with parietal and septal enhancement after agent contrast injection; this lesion was ruptured in the biliary convergence.
Magnetic resonance imaging (MRI) showed a partitioned lesion, hypointense in T1 and hyperintense in T2, ruptured in the biliary bifurcation and causing dilatation of intrahepatic bile ducts, especially on the left side; the common bile duct (CBD) was also dilated with heterogeneous signal content (Figs. and ). She underwent laparotomy by subcostal incision; the exploration noted a micronodular liver and the opening of her CBD allowed the extraction of membranes with a mucinous fluid issue, which raised questions about the diagnosis of hydatid cyst (Figs. and ). A t-tube was placed in the CBD at the end of the operation. A histological study of the membranes as well as liver biopsies indicated a biliary cystadenoma without signs of malignancy associated to biliary cirrhosis. Postoperative cholangiography performed 1 month later revealed the persistence of the biliary cystadenoma (Fig. ).
Three months after this second surgery, we decided to perform radical excision after regression of jaundice and amelioration of blood tests. In fact, she underwent a left hepatectomy enlarged to segment I by laparotomy, because the cyst was ruptured in the posterior wall of the left hepatic canal, with large fistula, near the biliary convergence; a simple enucleation was impossible due to posterior location of the cyst and the adhesions of anterior surgeries. Her postoperative follow-up was simple and a histological study of the specimen confirmed the diagnosis of biliary cystadenoma without signs of malignancy.


A 79-year-old man presented with a transient ischemic attack of the posterior circulation. He had no complaints at that time. On neurological examination, he had a non-symptomatic, pulse-synchronous pulsatile proptosis of the left eye (see Video in Supplementary Material). According to the patient, this was present since childhood or even birth. There was no complaint of oscillopsia. He denied a history of birth trauma or head injury. He had no history of congenital anomalies, bone dysplasia, or neurofibromatosis. The neurological examination was otherwise normal and no bruit was heard. There was 4 mm proptosis of the left eye. Visual acuity without correction was for OD 1.0 and for OS 0.4. Intraocular pressure was 9 mmHg in OD and 10 mmHg in OS. Direct and indirect pupillary responses were normal. OD showed pseudophakia. OS had cataract. There was no conjunctival venous congestion nor venous congestion of the posterior poles of the eyes. Arterial abnormalities were absent in the posterior pole of the eye. He had full range eye movements without double vision. Examination of the eyes was further unremarkable. Computed tomography and MR imaging (see Figure ) revealed a meningocele into the left orbit due to a bony defect in the orbital roof (42 mm × 37 mm). He was not bothered by the proptosis and declined surgical correction of the orbital roof.


A 1.5 year-old male German Pointer dog weighing 27 kg was referred to the VTH UT for a protrusion of the right third eyelid, and a locked-jaw syndrome associated with extreme pain when the dog tried to open his mouth. These signs had appeared 10 days earlier, after the dog was hit on the head by a ball. The dog had remained stable since then. History revealed a strong suspicion of snake envenomation 3 months earlier. At that time, the dog was presented in shock to a veterinarian with marks on the head suggestive of a snake bite. The laboratory workup revealed markedly increased prothrombin time (PT) and activated partial thromboplastin time (aPTT). The veterinarian started a symptomatic treatment [fluid-therapy (Ringer Lactate), corticosteroids (prednisolone, 1 mg/kg, IV, q 12 h), antibiotics (marbofloxacin, 4 mg/kg, IV, q 12 h) and K1 vitamin] and clinical signs improved within a few days. However, the PT and aPTT remained moderately increased after this suspected envenomation. One month later, a gingival wound appeared, requiring a surgical suture to stop the bleeding. On this occasion, PT and APPT were still markedly increased (PT >35 s, RI [12–19 s] and aPTT >200 s, RI [75–105 s]).
Upon admission at the VTH UT, physical examination showed an exophthalmia of the right eye associated with protrusion of third eyelid. The dog was reluctant to be touched on the head and opening the mouth elicited severe pain. Apart from this, clinical examination was unremarkable and a thorough ocular examination did not reveal any other abnormality. The ocular ultrasonography was consistent with a retrobulbar cellulitis with no image suggesting the presence of a foreign body. Because of the history of abnormal coagulation, the retrobulbar fine needle aspiration was postponed until the laboratory results were available.
An extensive laboratory profile, including complete hemostatic profile, was performed at the veterinary clinical pathology laboratory of the VTH UT. Severe hypofibrinogenemia (0.34 g/L, RI [1.30–4.80 g/L] assessed by Clauss’coagulometric method), increased PT (15.0 s, RI [7.10–9.00 s]) and aPTT (19.3 s, RI [12.8–17.2 s]) were observed. All other results including buccal mucosal bleeding time, complete blood count (CBC), D-dimers (DDi), and antithrombin (AT) were within reference intervals (Table ). The fibrinogen/fibrin degradation products (FDPs) value was however in the grey zone (between 5 and 20 μg/mL, RI [< 5 μg/mL]).
The hypofibrinogenemia was observed on repeated coagulometric measurements as well as by physical measurement using the Millar heat-precipitation method based on the ability of fibrinogen to precipitate at 56 °C []. This method confirmed the severe hypofibrinogenemia with an almost undetectable fibrinogen precipitation band.
A screening for possible causes of hypofibrinogenemia was performed. The normal liver profile, including a normal bile acid test, excluded liver failure (Table ). The absence of clinical signs of disease conditions that are associated with disseminated intra-vascular coagulation (DIC) together with the absence of any other laboratory signs of hemostasis system activation (normal platelet count, DDi and AT) was not consistent with DIC. Chronic bleeding was ruled out by clinical, diagnostic imaging and CBC findings. To rule out the hypothesis of circulating anticoagulant interfering with the fibrinogen determination, a 1/1 dilution of the dog’s citrated plasma with pooled healthy dog plasma (PHDP) was performed. PHDP was prepared by pooling identically prepared plasma samples from 9 clinically healthy dogs. The fibrinogen concentration assessed by coagulometric method in the mixture was consistent with the expected calculated result (Table ). This finding ruled out the presence of circulating anticoagulant with fibrinogen inhibitory properties. A congenital hypofibrinogenemia was hence diagnosed.
Retrobulbar fine needle aspiration was not performed due to the high risk of puncture-induced hemorrhage. In the hypothesis of a retrobulbar cellulitis, the following treatment was administered: antibiotics (gentamicin 6.6 mg/kg, IV, q 24 h for 6 days, and amoxicillin/clavulanic acid 20 mg/kg, IV, q 8 h for 6 days, then 12.5 mg/kg, PO, q 12 h for 6 weeks) and corticosteroid therapy (prednisolone 0.3 mg/kg, IV, q 24 h for 6 days then 0.3 mg/kg, PO, q 24 h for 3 weeks, and finally 0.3 mg/kg, PO, every other day, for 2 weeks).
After 2 days of treatment, the protrusion of the third eyelid and the pain associated with mouth opening decreased and resolved after 2 weeks. One month later, the dog was completely normal. Two months later, the dog was stable but fibrinogen remained persistently below the reference interval (Table ) and the FDP value was negative (< 5 μg/mL). Six months after the initial presentation, no clinical relapse was observed but plasma fibrinogen value remained low.
There is no specific treatment for congenital hypofibrinogenemia, other than plasma transfusion during acute bleeding crisis. It was therefore strongly recommended to avoid strenuous exercise or hunting with the dog to prevent trauma.


A 54-year-old woman presented to our department with a common toothache. She described a history of a neurological examination with a brain MRI, and the neurologist sent her to us due to the possibility of a dentally originating lesion. During the clinical examination, we noticed a palpable fluctuant swelling on the upper labial sulcus, beneath the right nasolabial fold. There were no bony changes in the orthopantomography and occlusal radiography examinations, and all of the associated teeth were shown to be vital using electrical pulp testing (). US was performed, and a well-defined, ovoid shaped, approximately 2-cm in diameter anechoic cystic lesion was observed (). The MRI revealed a well-defined, round, cystic mass in the right nasal alar region. The relevant cystic lesion exhibited a homogeneous hypoisointense (with adjacent soft tissue) appearance on the T1-weighted images and a homogenous hyperintense appearance on the T2-weighted images (Figures , , and ).
Based on the MRI, US, plain radiographic, and clinical findings, a preliminary diagnosis of a nasolabial cyst was made. The lesion was removed surgically with an intraoral approach under local anesthesia, and the surgical specimen was sent for a histopathological examination. The lesion was diagnosed as a nasolabial cyst.


A 48-year-old man with a controlled thyroid nodule and tobacco and cannabis abuse presented with ecchymosis in his limbs by August 2014. The laboratory test found isolated thrombocytopenia (platelet count 9 × 109/L) without atypical features. The bone marrow examination (aspiration and biopsy, April 2015) revealed results compatible with ITP.
He started prednisone (1 mg/Kg, daily). After 3 weeks of treatment, there was no response (platelet count 12 × 109/L). Aiming to perform the thyroid nodule extirpation, immunoglobulins were also administered (1 g/Kg daily for 2 days). After 5 weeks with no further response (platelet count 20 × 109/L), prednisone was tapered and romiplostim was started at 3 µg/Kg, observing a rapid response after two weeks (platelets 270 × 109/L). Steroids were discontinued and romiplostim was discontinued for one week, observing a new platelet decrease to 9 × 109/L after which romiplostim was rescheduled at 2 µg/Kg dose, achieving a stable platelet response and allowing the thyroid surgery (October 2014, follicular adenoma, nonmalignant). Romiplostim was maintained at 3 µg/Kg with stable platelet counts () until January 2015, when there was a platelet decrease (3 × 109/L) without hemorrhagic signs, managing titrating romiplostim to 4 µg/Kg. Helicobacter pylori was then eradicated after positive breath test.
Romiplostim continued at 3 µg/Kg thereafter with acceptable platelet counts (30–150 × 109/L) and was initially tapered to 2 µg/Kg (month 9 after diagnosis; platelet count: 270 × 109/L) and further decreased by 0.5 µg/Kg every two months while maintaining platelet response (). The treatment was finally discontinued 16 months after ITP diagnosis, achieving its current state of remission by June 2016 (platelet count ≥ 50 × 109/L for 24 consecutive weeks in the absence of any treatment for ITP). No adverse events were observed.


A 64-year-old male was assisted in emergency department because of melena, mild hemorrhagic lesions in thorax and abdomen, asthenia, and progressive adynamia in April 2015. He had a history of tobacco abuse, ischemic stroke, and arterial hypertension and was receiving acetylsalicylic acid, atorvastatin, rizatriptan, ferrous sulfate, and losartan-hydrochlorothiazide. The blood count showed hemoglobin 7.9 g/dL and platelet count 3 × 109/L. The diagnosis was ITP after excluding other possibilities including bone morrow study. A digestive endoscopy revealed hiatus hernia, Schatzki ring, and severe erythematous gastritis in body and fundus. Positive results for Helicobacter pylori in stool test were obtained.
After diagnosis, aspirin was stopped, and H. pylori eradication treatment and immunoglobulins (1 g/Kg daily for 2 days) were started. After 4 days without response (platelet count: 10 × 109/L), the patient initiated dexamethasone 40 mg daily for 4 days (without tranexamic acid) achieving 410 × 109/L platelets. Fourteen days after ITP diagnosis, the H. pylori test was negative and the platelet count decreased to 2 × 109/L. Five additional cycles of dexamethasone were administered (40 mg daily for 4 days every 15 days), not maintaining a stable response (platelet count: 1–10 × 109/L before dexamethasone cycles; 187–410 × 109/L one week after). During the fifth cycle, the patient was then hospitalized after blood transfusion due to digestive bleeding with hemodynamic angina.
Romiplostim treatment was then started at 3 µg/Kg. High platelets response was observed after one week (platelets 649 × 109/L). Platelet count decreased to 2 × 109/L after 1 week without romiplostim being administered. It was reinitiated at 4 µg/Kg since the first platelet response was assumed to be caused by the combination of steroids and romiplostim. A new increase in platelet count (528 × 109/L) was observed. After 6 weeks of intermittent administration, the platelet count remained stable at 2 µg/Kg (), and the aspirin treatment was restored. Romiplostim intervals of administration were sequentially spaced and the treatment was finally discontinued after 14 weeks of romiplostim onset, achieving its current state of remission in May 2016. No new safety signals were observed.


A 21-year-old male was diagnosed of ITP in August 2008 after presenting sustained severe mucocutaneous manifestations (age at diagnosis: 13 years old). At diagnosis, the blood count showed platelet count 5 × 109/L and hemoglobin 11.2 g/dL with iron deficiency and negative direct Coombs test. After being treated with immunoglobulins and corticosteroids achieving limited response, the patient was splenectomized in July 2009 followed by a complete response, sustained for 30 months. After relapsing (severe asthenia, mucocutaneous manifestations, platelet count 12 × 109/L, and hemoglobin 11 g/dL), he refused to be treated with steroid and immunoglobulin treatment was indicated (1 g/Kg daily for 2 days) with short-term response (platelet count 296 × 109/L and 12 × 109/L after 4 and 10 days, resp.), followed by a second cycle (0.8 g/Kg single dose) 21 days thereafter achieving a similar response (platelet count 134 × 109/L and 3 × 109/L after 4 and 10 days, resp.) with presence of petechiae and ecchymosis. The patient was then treated with four 15-day cycles of dexamethasone (40 mg daily for 4 days) in monotherapy without observing further response (platelet count 9 × 109/L, without bleeding).
As he wanted to continue with an active life, at June 2013 (18 year-old; platelet count 2 × 109/L) he started romiplostim 3 µg/Kg, observing an increase in platelet count after 2 weeks to 378 × 109/L. The patient maintained stable values of platelets between 109 and 178 × 109/L for 12 months with a romiplostim dose of 2 µg/Kg (). At the 12-month visit romiplostim was interrupted for 2 weeks, followed by a decrease in platelet count observed in the third week without treatment (47 × 109/L). After romiplostim retreatment (2 µg/Kg every 3 weeks) the number of platelets steadily increased () and treatment was discontinued 18 months after romiplostim onset. After 20 months of treatment withdrawal the patient is still under clinical remission, with no safety signals observed.


A 67-year-old woman with history of hypercholesterolemia, cholecystectomy, and appendectomy was diagnosed with ITP in 2000. A bone marrow aspiration and biopsy were performed with results compatible with ITP. The patient was initially treated with prednisone (1 mg/kg), achieving a sustained complete response until 2006 when she relapsed presenting concomitant hemolytic anemia (Evans syndrome) unresponsive to corticoids. She regained full response after four weekly cycles of rituximab (375 mg/m2), maintaining adequate platelet counts (>100 × 109/L) during 9 years.
In July 2015, the patient presented a new episode of severe thrombocytopenia (platelet count 3 × 109/L) and epistaxis, starting biweekly dexamethasone (40 mg daily for 4 days). After 3 cycles without observing clinical response, eltrombopag was initiated at 50 mg/day and rapidly increased to 75 mg/day for 3 weeks. The platelet count remained low (6 × 109/L) and, in September 2015, the TPO-ra treatment was switched to romiplostim 3 µg/Kg, observing a reduction in cutaneous bleeding diathesis, but without platelet count increases after one week. Romiplostim was then titrated to 4 µg/Kg, with a discrete increase in platelet count observed after 2 weeks, achieving 219 × 109/L after 5 weeks. The dose was sequentially tapered to 3 µg/Kg, to 2 µg/Kg in alternate weeks one month thereafter, and to 1 µg/Kg in alternate weeks by December 2015 (). Romiplostim was finally discontinued in January 2016 (platelet count 379 × 109/L), achieving and maintaining remission with no new safety signals observed.


Patient PLTX_19, a three-year old boy suffering from progressive familial intrahepatic cholestasis, primary B19V infection occurred after liver transplantation. He underwent re-transplantation after 143 days due to acute refractory rejection. B19V IgG was lacking despite IVIG transfusion after first transplantation. He received high doses of prednisolone (≥60 mg/m2/day) and a tacrolimus-based maintenance therapy in temporal relation to re-transplantation.
Parvovirus B19 DNA (<600 geq/mL) was detected for the first time three days after re-transplantation. Unfortunately, neither the donor organ nor donor blood was available for testing, so it remains unknown if the organ was the source of infection. The patient developed an itching exanthema with target lesions and slapped cheeks two days after transplantation, consistent with the clinical manifestation of the fifth disease. The course of viremia and other markers are depicted in .


This is the case of a 33-year-old man without significant medical history who was incidentally diagnosed with a right neck cystic mass by computer tomography (CT) after a motor vehicle accident (). Patient denied diaphoresis, palpitations, diarrhea, constipation, mood changes, or any other symptoms. Physical exam revealed a right-sided tender neck mass, without any other remarkable findings. He did not have history of neck irradiation, thyroid disease, or family history of thyroid cancer. Thyroid function tests were within normal limits (TSH: 1.5 IU/mL). Excisional biopsy of the neck mass reported metastatic, well-differentiated, thyroid papillary carcinoma within lymph node tissue. Pathologic description consisted of a nodular segment, tannish, rubbery specimen with attached membranous cystic tissue. The pathological specimen (lymph node) was distorted and had a well-defined cystic structure within it. While the cystic structure measured 2 cm × 1.5 cm × 1 cm, the lymph node measured 1.5 cm × 1 cm (). Due to previous findings, he underwent total thyroidectomy with right neck dissection in order to rule out occult primary carcinoma of the thyroid. Histopathological findings revealed a normal thyroid gland without evidence of papillary thyroid carcinoma and sixteen right neck lymph nodes without evidence of metastasis. Thyroid pathology was meticulously reviewed, without any evidence of papillary thyroid carcinoma identified. After surgery, thyroid hormone replacement was started. One month after procedure, thyroglobulin was 133.61 ng/ml (1.15–130.77 ng/ml) and thyroglobulin antibodies were 11.8 uU/ml (negative, less than 45 uU/ml). Thyroid scintigraphy reported functional thyroid remnants at the right thyroid bed. Ultrasonography evaluation revealed hypoechoic foci within the thyroid beds bilaterally, likely secondary to postsurgical granulation tissue versus residual thyroid tissue. A right, level 2A lymph node seen measured 2.1 × 1 cm with loss of normal lymph node morphology, without microcalcifications or internal increase in vascularity. Another lymph node at level 3 measured 2 cm × 0.7 cm × 8.7 cm, without worrisome features. Fine needle aspiration biopsy of the aforementioned nodules showed papillary thyroid carcinoma. Final diagnosis was malignant transformation of heterotopic thyroid tissue. Whole-body scan showed functional thyroid tissue remnants in the thyroid bed with multiple enlarged neck lymph nodes (). At that time, TSH was elevated (44.3 IU/mL) and free T4 was suppressed (0.58 ng/dl; normal value: 0.75–1.54 ng/dl). The patient was referred to nuclear medicine for radioiodine therapy. Radioiodine ablation 142.2 mCi was given. After appropriate cessation of hormone replacement therapy, whole-body scan showed no nodules uptake.


A 75-year-old man with NYHA-II class systolic heart failure due to hypertensive cardiomyopathy (history of long-lasting arterial hypertension, concentric left ventricular hypertrophy with diffuse hypokinesia – LVEF = 40% in echocardiographic study and extreme coronary artery tortuosity without significant atheromatic disease in coronary angiography) underwent an ICD implantation in March 2013, after an episode of sustained VT with hemodynamic collapse, which required urgent cardioversion.
Soon after the implantation, ES occurred with multiple episodes of sustained VT, requiring either antitachycardia pacing (ATP) or shock therapy for sinus rhythm restoration (Fig. ). Intravenous amiodarone was administered acutely, followed by chronic per os intake. New episodes of ES occurred during the following period, with no detectable triggering condition. Two transvenous ablation procedures were performed within 6 months, both without success. In both electrophysiological studies, ventricular stimulation was characterized by the induction of at least five different morphologies of sustained VT. During follow-up, three different high-dose b-blocker agents were administered consecutively (carvedilol, metoprolol, or bisoprolol in combination with amiodarone), as well as sotalol, with no clinical response. Mexiletine was added for a period of only 2 months. It was prematurely discontinued due to severe central nervous system toxicity.
In summary, during the period of 16 months after implantation, 211 appropriate ATP and 91 appropriate shocks occurred (Fig. ), despite our attempts to reduce shock burden, through adequate adjustment of therapy-zone parameters. More specifically, the lower limit of VT zone was gradually elevated from 136 beats per minute (bpm) tο 162 bpm (detection: 20 beats, redetection: 12 beats), as even long-lasting slow VT episodes were well tolerated, with no obvious hemodynamic deterioration. Additionally, the application of burst sequences (three sequences, 88%, 10 pulses) of VT zone was proven to be (more or less) ineffective. Thus, burst sequences were replaced by a more aggressive (and more effective) protocol of 3 plus 3 Ramp+ sequences (84%/78%/75%, eight pulses and 75%/69%/66%, eight pulses, respectively). In general, ATP and shocks were distributed normally in time, without long periods of recession. As a consequence, energy depletion of the device occurred prematurely (September 2014, device replacement). The heart rate spectrum of VTs was wide (120–230 bpm) and many episodes of sustained VT were only monitored without any intervention, displaying R-R interval above the therapy zones (heart rate 120–162 bpm, monitor-only zone). During this period, the patient underwent multiple hospitalizations, mainly receiving I.V. amiodarone. His quality of life clearly deteriorated, with new-onset symptoms of anxiety and depression (psychiatric consultation was also performed). Despite multiple shock therapies, four consecutive echocardiographic studies were fortunately comparable to the initial one, with no clear deterioration of left ventricular systolic function.
After device replacement, new ES episodes occurred, as expected. The pattern of VTs and subsequent device interventions was somewhat different, with lower mean heart rate of VT episodes, many hundreds of ATP and only few shocks, always appropriate (Fig. ). Fifteen months after device replacement, subclinical hyperthyroidism was detected (December 2015, no previous history). Amiodarone was replaced by flecainide, with no clear clinical response (new episodes of VT occurred, with even lower mean heart rate, new therapeutic interventions – mainly ATP – were detected).
Three months after amiodarone discontinuation, in March 2016, ranolazine was added to the antiarrhythmic therapy (patient under carvedilol 12.5 mg × 3 and flecainide 100 mg × 2), with up-titration to the dose of 750 mg × 2. Surprisingly, during the following 7 months (March to October 2016), no VT or VF episode occurred, in complete contrast to the displayed history of the previous 3 years, since first ICD implantation, with a total burden of 2871 ATP and 109 shocks, all appropriate (Fig. ). It should be mentioned that no reversible underlying arrhythmogenic conditions (other than cardiomyopathy) were ever detected in our patient. Additionally, the patient's adherence to medical advisory was reliable and constant during the long period of 3.5 years of follow-up. Currently, the patient is under a good psychologic and a stable functional status (NYHA-II).


A two-month-old male was brought to the Infectology service of INP to seek medical care, because he had dysmorphias. Also, maternal acute toxoplasmosis was suspected at six weeks of gestation (WG) due to abnormal evolution and presence of IgM anti-T. gondii antibodies (abs). The nineteen-year-old woman harbored intrauterine dichorionic diamniotic twins of 7.4 (gestational sac of 2.4 cm) and 7.3 (2.3 cm) WG as calculated from the ultrasound (USG) (Fig. ). She had miscarriage threat at 11 WG. At the 14th WG, only one apparently normal fetus was apparent in the USG, so there was involution of the other twin (Fig. ). A unilateral complete palatal defect was seen in the USG performed during the last trimester. A male product was born by cesarean at 38 WG; with a weight of 2.78 kg (P10), a height of 48 cm (P10–25), an Apgar score of 8/9 and a Silverman score of 0 points. The newborn lacked the left eye and presented ipsilateral oblique oro-orbital cleft. The diagnostic approach began four days after birth with a TORCH profile. IgG was positive for T. gondii, Rubella and Cytomegalovirus, but IgM abs were negative against the three agents. The blood count was normal. The baby presented bilateral sensorineural hearing loss as demonstrated by auditive screening. The metabolic screening results were normal.
When the patient arrived to INP, no evidence of psychomotor retardation was found and the Ophthalmology service discarded alterations in the healthy eye. Cytomegalovirus and T. gondii infections were searched in blood by serology and real-time PCR. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neoabs in western blot, as well as by real time PCR in blood (Fig. ), with a parasite load of 6903 parasites/mL [, ].
In the cranial CT scan (Fig. ), the left oblique oro-orbital and parasagittal cleft defect were observed, as well as ipsilateral lack of osseous tissue and soft palate. Left choanal atresia and narrow-left vestibule were discovered in the nasal cavity. The right nasal cavity was communicated with the oropharynx through a narrow choanal passage. The left turbinates were hypoplastic. A nasal endoscopy was performed which confirmed CT scan findings. The left eyeball and the optic nerve were absent; however, hypoplastic extraocular muscles were present in the orbit. The brain parenchyma and the right side of the face were normal.
According to the data described above, diagnosis was type 3 left craniofacial cleft (Tessier classification), ipsilateral anophthalmia and congenital toxoplasmosis.
Anti-T. gondii therapy with pyrimethamine, trimethoprim/sulfamethoxazole and folinic acid was started according to the international recommendations []. At the beginning, the mother did not adhere to treatment, because as she argued, there was a long distance between her home and the hospital, but mainly because she had difficulty to understand the benefits of prophylactic chemotherapy; the physicians perseverated, so the second semester of life the baby received proper treatment.
Surgical management was focused in maximizing actual vision and improving aesthetics, through simultaneous stimulation of soft tissues and bony orbital growth. Anophthalmia requires additional remodeling by soft tissue reconstruction and endo-orbital volume replacement (with implants, expanders and dermis-fat grafts). A first surgery was performed to start correction of the anatomical defect. During the surgery, a biopsy containing mucosa and skin was taken from the anophthalmia site. Images compatible with T. gondii pseudocysts and free parasites were observed by histopathology, as well as an active chronic inflammatory reaction, composed by lymphocytes, plasma cells, eosinophils and neutrophils (Fig. ). Prognosis is favorable since the baby had no neurodevelopment disorders, no right eye or intracranial lesions and is following a protocol for reconstructive plastic surgery including eyeball prosthesis.


A 78-year-old G1P1001 woman with a history of hypothyroidism, hypertension, and stage III chronic kidney disease presented with a complaint of long-standing acne and alopecia. Her growth, developmental, and reproductive history were unremarkable; her complaints began in her seventies. On 6/18/13, her unstimulated serum 11-deoxycortisol concentration was impressively elevated at 91 ng/dL (<37 ng/dL) consistent with a nonclassic 11-hydroxylase deficiency. Serum 11-deoxycortisol concentration was determined by liquid chromatography/tandem mass spectrometry. Cosyntropin (ACTH) stimulation testing was considered superfluous in this setting, as the baseline serum 11-deoxycortisol concentration was already 2.5× the upper limit of the reference range and other adrenal steroid metabolites (17-OH-progesterone, 17-OH-pregnenolone, and deoxycorticosterone) were all within normal limits and because (unlike 17-OH-progesterone) there is no quantitatively important ovarian source for 11-deoxycortisol. The patient was not treated with metformin, which is usually effective in NCAH [, ], because of her stage 3b chronic kidney disease. Based on our experience with other forms of nonclassic congenital adrenal hyperplasia and honoring the patient's request to try a “natural” approach, after obtaining informed consent, treatment was initiated with a standardized preparation of Ashwagandha root, with a dosage of 400 mg twice daily, which is the starting dose recommended on the product label as well as the dose that we previously reported as effective in treating other forms of NCAH []. On 4/9/2014, her serum 11-deoxycortisol concentration declined to 64 ng/dL. The dosage was increased to 400 mg to be taken in the morning and 800 mg in the evening. On 12/12/2014, the serum 11-deoxycortisol level further declined to 46 ng/dL. We then increased the dosage to 800 mg twice daily. On 5/3/16, the serum 11-deoxycortisol was 33 ng/dL. We noted an apparent dose/effect relationship between the Ashwagandha dosage and serum 11-deoxycortisol concentration. After a period of three years on a gradually increasing dose of Ashwagandha root, her serum 11-deoxycortisol concentration had normalized (). Biochemical improvement has been accompanied by resolution of acne and reduction in hair loss. Since her acne was primarily facial, we chose not to photograph her, even with her eyes covered, to protect her privacy. For safety monitoring, we followed up the patient's vital signs, serum glucose, electrolytes, complete blood count, liver function tests, lipid profile, urinalysis, estimated glomerular filtration rate, and microalbumin, none of which changed appreciably.


A 61-year-old man underwent placement of a left superficial femoral artery stent without complications. His past medical history included war-related PTSD, diabetes, hypertension, and heavy smoking. Medications included aspirin, lisinopril, glyburide, metformin, and fentanyl patch. Shortly after his surgical procedure, the patient threatened to leave AMA unless he was allowed to “roll around” in a wheelchair “as he pleased.” He was permitted to briefly leave the ward with his peripheral intravenous (IV) catheter left in place. The next morning, the patient was awake, alert, and fully oriented. About two hours later, he was increasingly lethargic with apneic episodes and oxygen saturation 80–85%. Other vital signs were unremarkable. His glucose was 246 mg/dL and was treated accordingly. After he was given Narcan (0.2 mg IV), the patient became markedly more alert and was transferred to the Intensive Care Unit (ICU). He denied self-administration of medication. A urine toxicology test was positive for benzodiazepines (received during anesthesia the day before). His arterial blood gases demonstrated a hypercarbic respiratory acidosis with pH 7.32, PaCO2 68.3 mmHg, and PaO2 99 mmHg. After he received a second dose of Narcan (0.2 mg), he became agitated and wheeled himself out of the unit and eventually the hospital with IV still in place and his care team in pursuit. He got in his car and drove until he encountered a barricade set up by hospital police officers to stop him as he presented a potential danger to himself and to others. The patient agreed to return to the ICU but refused all tests. The next morning, despite his systolic blood pressure being 231 mmHg, the patient left the hospital AMA after removal of his peripheral IV catheter. He never returned to our facility for follow-up or medical care.


A 60-year-old man underwent an elective video-assisted thoracoscopic surgery for lung biopsy. His past medical history was significant for heavy smoking with chronic dyspnea and war-related PTSD. His medications included inhalers and prazosin. His surgery and postoperative course were unremarkable. Around 5:00 a.m. on the morning of postoperative day 2, the patient declared that he would be leaving the hospital at 7:00 a.m. and demanded removal of the peripheral IV catheter. Upon being informed that the removal can only occur with a written order by his doctor, the patient left the ward. The grounds were searched but he was unable to be located. Shortly thereafter, the patient returned to the unit and stated, “I want this IV out and I am leaving at 0700.” After the risks associated with leaving AMA were discussed (e.g., tension pneumothorax) and understood by the patient, his peripheral IV was removed, and he left the hospital AMA for a long distance drive home alone. Subsequently, he missed follow-up appointments and refused emergency treatment when he developed cardiac chest pain at home (unrelated to surgery).


A 57-year-old man was admitted to the hospital after being found at home lethargic and minimally responsive after a fall. The noncontrast computer tomography (CT) of the head showed a large, acute-on-chronic right subdural hematoma measuring up to 1.7 cm, with a 6 mm right-to-left midline shift and subfalcine herniation. The patient was admitted to ICU for assessment and urgent treatment. His past medical history was significant for diabetes, polysubstance abuse, war-related PTSD, and heavy smoking. The patient had a history of noncompliance. His medications on admission included metformin, trazodone, and methadone. Given the clinical presentation and head-CT findings, the neurosurgical team recommended proceeding emergently with evacuation of the subdural hematoma. However, the patient refused to consent stating that he would rather die than have surgery, stating “It would be fine [if he died]; it would relieve me of my pain”, but that he “will not die,” because he was a Navy Seal. Psychiatric consultation found the patient lacking in decision-making capacity. Given the danger to self and the potential threat he posed to others, they recommended holding the patient in the ICU and restarting his home medications. Psychiatric reassessment a day later determined that the patient had regained his decision-making capacity. His vital signs, mental status, and neurological exam results were stable. Following thorough presentation and discussion of the risks associated with leaving AMA and assertion by the patient that he understood, he left the hospital. Subsequently, he was difficult to contact and missed appointments.


A previously healthy 8-month-old female presented with three days of vomiting without diarrhea or an antecedent illness. At presentation she was severely hypertensive, volume overloaded, and oliguric. Laboratory workup revealed the triad of hemolytic anemia, thrombocytopenia, and AKI, consistent with TMA. Urinalysis was significant for 3+ hematuria and 4+ proteinuria. Serum chemistry was notable for hyponatremia, hyperkalemia, hyperphosphatemia, and metabolic acidosis. Serum complement C3 was decreased (52 mg/dL; normal value: 86–179 mg/dL), but C4 was normal (17 mg/dL; normal value: 14–45 mg/dL). Platelet activation studies demonstrated increased ATP secretion in response to adenosine diphosphate and arachidonic acid, but were otherwise normal. ADAMST13 activity was 59%, and therefore the diagnosis of atypical HUS was made.
Management included renal replacement therapy, plasma infusions/exchange, and eculizumab infusions. Figure shows the timing of infusions and eculizumab dosing relative to lab trends used to monitor disease activity. During the first week of admission the patient was treated with continuous renal replacement therapy and received daily plasma infusions. On hospital day 8, she was transitioned to intermittent hemodialysis and began a regimen of weekly eculizumab infusions, with all doses administered during the last hour of dialysis, as previously described. [] After the third eculizumab dose, renal biopsy was performed. Three of eight glomeruli present in the specimen were globally sclerotic. Non-globally sclerotic glomeruli showed mild mesangial cellularity with increased matrix and numerous platelet thrombi visualized within glomerular capillary loops, consistent with active TMA (Fig. ). Electron microscopy demonstrated podocyte foot process effacement (Fig. ). Due to continued evidence of hemolysis (anemia and thrombocytopenia in the setting of low haptoglobin and elevated LDH; Fig. ) and biopsy-proven active TMA, the patient underwent daily plasma exchange and post-exchange eculizumab redosing for three consecutive days, after which she was started on a regimen of twice weekly intradialytic plasma and eculizumab infusions. Six days after the initiation of combined therapy, hemolysis began to resolve, and complement C3 levels increased to the normal range (Fig. -, ). Therefore, the frequency of eculizumab dosing was reduced to every 14 days. However, the patient did not recover renal function, and she was eventually transitioned to chronic peritoneal dialysis (Fig. ).
We performed extensive diagnostic testing to identify the cause of our patient’s HUS. Workup for complement factor H autoantibodies was negative. Neutrophil and lymphocyte expression of membrane cofactor protein, the second most frequently mutated gene associated with atypical HUS, was at the lower limit of normal. [, ] We used a commercially available next generation sequencing assay (Machaon Diagnostics, Inc.) to test for mutations in the following twelve genes with known pathogenic mutations associated with atypical HUS: CFH, MCP, CFI, CFB, C3, CFHR1, CFHR3, CFHR4, CFHR5, thrombomodulin, plasminogen, and DGKE. DGKE sequencing included all exons plus 25 bp of flanking intronic DNA, as well as the previously reported c.888 + 40A > G intronic mutation. [] The patient was homozygous for the H3 haplotype, which comprises three non-pathogenic SNPs in the CFH gene that are associated with predisposition to atypical HUS: (i) c.1–332 C > T in the promoter; (ii) a silent mutation at Q672, and (iii) a E936D substitution. [, ] Additionally, our patient was heterozygous for a rare missense SNP in DGKE (c.1679A > G; p.Q560R) in the c-terminal low complexity region, which was not thought to be pathogenic since all reported cases of atypical HUS associated with DGKE mutations follow a recessive inheritance pattern. [, ] Finally, we performed whole exome sequencing using blood samples from the patient and her parents (Baylor Miraca Genetics Laboratories), which identified a de novo heterozygous c.1384C > T missense mutation in exon 9 of the WT1 gene, which was subsequently confirmed by Sanger sequencing. This mutation results in a p.R394W substitution in the third Zinc finger of WT1 protein (Fig. ), and it is the classic mutation associated with DDS. [, ].
DDS is characterized by abnormal genitourinary development in males, Wilms tumor, and diffuse mesangial sclerosis. [] Karyotyping confirmed that the patient was 46, XX. However, no ovaries were visualized on pelvic ultrasound. Due to the patient’s high risk of developing Wilms tumor, she underwent bilateral nephrectomy five months after initial presentation. Gross examination revealed small, sclerotic kidneys that weighed a combined 30.6 g (average combined weight for age is 71 g; Fig. ). Histologic lesions ranged from moderate to severe mesangial hypercellularity with mesangial sclerosis to global glomerulosclerosis (Fig. ). Arterioles had an “onion skin” appearance with intimal and mural thickening (Fig. ). There was no evidence of lesions associated with TMA. The histopathologic features were entirely consistent with the diagnosis of diffuse mesangial sclerosis, the glomerulopathy classically associated with DDS. As there was no evidence of diffuse mesangial sclerosis on the initial renal biopsy, these findings show that HUS manifested prior to the development of glomerulopathy in this patient.


Patient 1 is a 6-year old girl. She is the third child of healthy, non-consanguineous parents. Her family history is positive for intellectual disability (one brother). She has microcephaly and mild dysmorphic features. Neuropsychiatric evaluation revealed intellectual disability, psychomotor and language delay. EEG (electroencephalogram) and brain CT were reported normal.


Patient 2 is a 8-year old boy, the second child of non-consanguineous parents. He was born at term of gestation by cesarean delivery. He was referred to us because of learning disabilities and encopresis. Physical examination showed growth retardation (all growth parameters lower than 3° percentile) and dysmorphic features: dry hair with abnormal implant, hypotelorism, muscular hypotrophy and bilateral clinodactyly of I, II, IV, V fingers. Brain and pituitary MRI was reported normal.


Patient 4 is a 2-year old boy, the first child of non-consanguineous parents. His family history is positive for intellectual disability, congenital anomalies (first pregnancy: stillbirth with agenesis of the radius and thumb) and chromosomal abnormalities (trisomy 21). He was born at 39,1 WG by cesarean delivery. He was referred to us because of the presence of severe vesicoureteral reflux (VUR), with hydronephrosis detected prenatally, and dysmorphism. Physical examination showed growth retardation (all growth parameters lower than 3° percentile) and dysmorphic features: prominence of the metopic suture, plagiocephaly, hypotelorism, bilateral clinodactyly of IV and V fingers and toes. Brain and heart ultrasounds were reported normal.