A 30-year-old male, with no significant past medical history, came to the emergency department with complaints of fever and chills for a duration of 3 days. He also complained of myalgia and abdominal pain for the same duration. He reported diffuse abdominal pain, which was 6/10 in severity, nonradiating, and not related to food. He also reported 2 episodes of diarrhea without any blood or mucous, brown in color. He denied cough, shortness of breath, chest pain, night sweats, weight loss, history of trauma, extreme exercise, or any history of travel.
His abdominal examination was significant for abdominal tenderness in all four quadrants, but was soft and nondistended and bowel sounds were present. The rest of his examination was unremarkable. Triage vitals were significant for a temperature of 103.3°F, heart rate of 88 beats per minute, respiratory rate of 18 breaths per minute, blood pressure of 109/49, and pulse oximetry of 99% on room air.
Admission laboratory workup revealed leukocyte count of 6.1 × 103 µL (reference range 4.5–11.0 × 103) with 72% neutrophils, hemoglobin of 16.2 g/dL (reference range 13.0–17.0), hematocrit of 48.2% (reference range 39–53), platelet count of 149 × 103 µL (reference range 130–400 × 103), ESR of 4 mm/hr (reference range 0–20), BUN of 34 mg/dL (reference range 8–20), creatinine of 1.8 mg/dL (reference range 0.4–1.3), potassium of 4.7 mmol/L (reference range 3.6–5.1), phosphorous of 3.0 mg/dL (reference range 2.4–4.7), aspartate aminotransferase of 1,146 IU/L (reference range 15–41), alanine aminotransferase of 243 IU/L (reference range 17–63), and creatinine kinase of 39,125 IU/L (reference range 38–398). Urinalysis was significant for large blood, and urine red blood cells were 0–2.
In view of the high-grade fever, we attempted to find an infectious source to explain his history and presentation. Chest X-ray () and CT scan were obtained and showed no signs of pneumonia. Urinalysis and influenza rapid antigen test were performed and did not reveal any abnormalities. CT of the abdomen and pelvis was obtained and did not reveal any focal sources. Stool culture with ova and parasites, blood cultures, urinary toxicology including synthetic THC (K2), HIV, herpes simplex virus, hepatitis panel, Mycoplasma pneumoniae IgM antibody, urine Legionella antigen, QuantiFERON® test for tuberculosis, and TSH were all performed as well. All the test results were negative except immunoglobulin M antibodies for Mycoplasma pneumoniae that were detected by enzyme-linked immunosorbent assay. The antibodies were initially 781 U/mL, which is considered a low positive (reference range 770–950).
Our patient was empirically started on levofloxacin and metronidazole for possible gastroenteritis initially while culture and laboratory results were pending. He was managed for his acute renal failure and rhabdomyolysis with aggressive parenteral hydration. However, he continued to spike fevers during days 1–4 of the admission, but his diarrhea, abdominal pain, and myalgia resolved by day 3. One week later, mycoplasma antibody was recorded again and it was 976 U/ml, which is considered a true positive (reference range 950+). The fact that the antibody titer was trending up was clinically significant for a recent Mycoplasma pneumoniae infection. After mycoplasma was found to be positive, metronidazole was discontinued and he was continued with levofloxacin. His creatinine, liver function tests, and CK trended down to normal reference ranges (), and he was discharged on day 9 with planned outpatient follow-up.


A 35-year-old Caucasian male presented during February 2012 with a three-month history of progressive lower back pain radiating to the left leg. Dorsal spine magnetic resonance imaging (MRI) revealed a mass involving the left ilium, sacrum, and left sacroiliac joint. It was also invading the S1-S2 left neural foramen and superior sciatic notch (Figure ). Biopsy of the mass showed a small round blue cell malignant neoplasm, having a uniform site of morphology with a lobulated growth pattern with some of the cells having limited amounts of amphophilic cytoplasm. There was a strong immune positivity for CD99 but negative for desmin CD 163 and CD68. He was diagnosed with primary localized ES. The patient received neoadjuvant chemotherapy and adjuvant radiation therapy according to the VIVA (vincristine + ifosfamide + doxorubicin + actinomycin D) regimen. He completed radiotherapy to the primary site in August 2012 with concurrent ifosfamide and etoposide. All planned treatment was completed in January 2013. The patient was under close follow-up, and in May of 2014, he presented with multiple lung and two pleural lesions. Biopsy confirmed the lesions to be a relapse of ES with metastasis to lungs (Figures , ). In addition, pleural fluid immunohistochemical stains demonstrated the neoplastic cells to be positive for CD99 and negative for MAK-6, synaptophysin, neuron-specific enolase (NSE), and CD56, consistent with metastatic ES. The patient received five cycles of topotecan and cyclophosphamide. A follow-up computed tomography (CT) of the chest in July 2014, before cycle 3, showed interval decrease in the metastatic lesions, consistent with chemosensitive disease. A positron emission tomography/computed tomography (PET/CT) scan during August 2014, after five cycles of topotecan/cyclophosphamide, showed stable metastatic disease in the form of pulmonary nodules and pleural involvement. Autologous stem cells were collected during a single leukapheresis session before the first high-dose chemotherapy (HDCT). The patient received high-dose chemotherapy in October of 2014 (busulfan, 0.8 mg/kg IV (intravenous) q six hours x 16 doses; melphalan, 140 mg/m2) and received CD34+ cells 4.24 x 10 e6/kg infused as an autologous stem cell rescue. The second round of planned consolidative high-dose chemotherapy was given during July 2015 (etoposide/melphalan regimen - etoposide, IV 400 mg/m2, total three doses (Days 2, 3, 4) and melphalan, IV 100 mg/m2, one dose (on Day 1)) followed by autologous peripheral blood stem cell rescue. During the first cycle of chemotherapy, the patient developed mucositis, neutropenic fever, and diarrhea secondary to Clostridium difficile colitis. After the second cycle of HDCT, the patient developed mucositis and transient elevation of liver function tests but these abnormalities resolved over a few weeks.
HDCT achieved 12 months of progression-free survival (PFS); however, on a subsequent PET scan performed during October 2015, the patient showed disease progression. An increase in the size of the metastatic lesions was noted, along with new areas of involvement of malignancy. The patient subsequently received six cycles of pembrolizumab, an antibody against programmed cell death 1 (PD-1) receptor. Subsequent imaging studies showed a progression of the disease, and the patient subsequently received cyclophosphamide, vincristine, dactinomycin (alternating with ifosfamide), and etoposide during March of 2016. The patient developed significant toxicities, bone marrow suppression, and in the presence of progressive disease during June 2016, he chose hospice care (Figure ).


A 54-year-old postmenopausal woman from Casablanca (Morocco), presenting episodic abdominal complaints, was referred to our outpatient institution for laboratory testing as part of a routine checkup in May 2011. Her medical history was significant for extensive endometriosis confirmed by the laparoscopy procedure and infertility. The patient had surgery followed by hormonal therapy in 2003. At initial blood testing, the results indicated normal cell count with a hemoglobin of 14 gm/dl, a total leukocyte count of 8,200/mm, and a platelet count of 3,44,000/mm. Serum urea, creatinine, bilirubin, transaminases, total cholesterol, triglycerides, calcium, fasting blood glucose, C-reactive protein, gamma-glutamyl transpeptidase, alkaline phosphatase levels, and other electrolytes were normal (). However, the serum amylase level was 198 IU/L (reference range 30–110), and serum lipase increased to reach 1461 IU/L which is fivefold over the upper limit (reference range 27–280). Blood pancreatic isoamylase values were also abnormal. As the abnormal pancreatic enzyme secretions usually denote pancreatic pathology, a deep screening for pancreatic alterations was done to find out the possible causes of the elevated levels of lipase and amylase. Serological tests for hepatitis A, B, and C viruses and human immunodeficiency virus (HIV) were negative. The tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetal protein, and carbohydrate antigen 125) showed normal ranges (). To exclude the common sources of hyperlipasemia and hyperamylasemia such as macroamylasemia, autoimmune diseases like systemic lupus erythematosus, celiac disease, and inflammatory bowel, investigations were done and all were absolutely normal. Abdominal ultrasonography and magnetic resonance imaging scans were performed in 2011 and showed normal pancreas, liver, and biliary tree (). The patient denied weight loss, diarrhea, vomiting, cigarette smoking, or alcohol drinking. The biochemical screening of pancreatic hyperenzymemia was negative in the patient's family members. Given the interest of this case, we decided to follow-up the patient with blood and imaging tests as long as possible. Five years after the first medical consultation, the patient remained asymptomatic although the serum lipase and amylase values fluctuated widely. The amylase and lipase median values were 205.5 and 831.5 U/L, respectively (). Interestingly, the lipase concentration never exceeded the value of 2,000 U/L. In the light of these observations, we hypothesized that hyperenzymemia in this situation may be considered as a true Gullo's syndrome case.


A 61-year-old male patient presented to the emergency room (ER) on account of a 3-month history of hemoptysis as well as a 2-week history of right upper extremity weakness and numbness.
Hemoptysis was associated with pleuritic right-sided chest pain as well as orthopnea and had been previously treated with two courses of empiric antibiotics and steroids at an outside hospital without improvement prompting his presentation to our emergency room.
Weakness and numbness of the right upper extremity were initially associated with a painful right palmar rash which was resolved with self-administered topical corticosteroids at home.
Past medical history was significant for untreated latent tuberculosis (TB) diagnosed about forty years prior to this presentation as well as coronary artery disease requiring stent placement twice in the past.
On presentation, the patient was not in acute distress but was tachycardic at 100 beats per minute, with a respiratory rate of 16 cycles per minute and an oxygen saturation of 100 percent on room air. Blood pressure was 144/87 millimeters of mercury, and temperature was 99 degrees Fahrenheit.
On physical examination, he was afebrile and had normal breath sounds and heart sounds without murmurs. Neurological examination was notable for reduced sensation to light but not crude touch over the right hand with reduced strength of 4/5 in that in same extremity. Laboratory studies were significant for a white blood cell count of 18,400 per microliter with 76.3 percent neutrophils, an erythrocyte sedimentation rate of 90 millimeters per hour, and a C-reactive protein level of 167 milligrams per liter.
Imaging done on admission revealed multifocal lung opacities () concerning for community-acquired multifocal pneumonia (possibly secondary to a resistant organism as patient had completed courses of cefdinir and levofloxacin at the outside hospital without resolution of his symptoms). Other considerations were for possible septic emboli of undetermined source as well as reactivated pulmonary tuberculosis given his long-standing history of latent TB with multiple positive skin purified protein derivative tests in the past.
CT scan of the head without contrast was concerning for a possible infarct of unclear age, and a follow-up MRI revealed possible abscess collection (Figures and ).
He was initially placed on airborne isolation with empiric first-line antituberculosis agents (which were discontinued after 6 negative acid-fast bacilli sputum samples were obtained) as well as empiric antibiotics (vancomycin and piperacillin/tazobactam) for possible multifocal pneumonia, based on recommendations of the infectious disease consultants. Two blood cultures, obtained on admission, returned positive and grew Streptococcus intermedius sensitive to ceftriaxone, levofloxacin, tetracycline, erythromycin, clindamycin, and vancomycin. A transthoracic echocardiogram showed normal left ventricular systolic function and normal valves without regurgitations, stenosis or, vegetations.
A subsequent transesophageal echocardiogram (TEE) revealed an 8.3 × 4.6 mm oscillating dumbbell-shaped vegetation arising from the Chiari network, close to the os of the right atrial appendage (), without evidence of valvular vegetations, insufficiency, or a patent foramen ovale.
A diagnosis of infective endocarditis was made based on the modified Duke criteria with two separate blood cultures positive for Streptococcus intermedius, echocardiographic findings of an oscillating intracardiac mass, consistent with a vegetation, and septic pulmonary and intracranial lesions []. Medical management was chosen at the time of the diagnosis of this Chiari network endocarditis with septic emboli to the lungs and brain, with plans for repeat imaging with a transesophageal echo after six weeks of appropriate antibiotic therapy.
Antibiotic coverage was thus narrowed and tailored to the culprit organism with ceftriaxone, and gentamycin was added for endocarditis synergy per infectious disease team recommendations. Clinical and laboratory evidences of improvement including resolution of the hemoptysis and right upper extremity weakness as well as reduction in the white blood cell count from 18,400 per microliter on admission to 6400 per microliter and in the erythrocyte sedimentation rate from 90 millimeters per hour to 28 millimeters per hour as well as the C reactive protein from 167 milligrams per liter to 0.9 milligrams per liter were documented.
Interval reduction in the size of the lung lesions but not the brain lesions was noted after four weeks of parenteral antibiotic treatment, and neurosurgical evaluation for possible evacuation of the abscess was thus recommended. The patient was transferred to an outside hospital where those services were readily available. He had an image-guided stereotactic drainage of the abscess via a left parietal burr hole, with initial gram stain of the fluid showing gram-positive cocci, but the culture had no growth after 5 days probably because the patient had been on appropriate antibiotics for four weeks prior to the drainage procedure.
The patient completed six weeks of antibiotic therapy at the outside hospital and was discharged home in a stable clinical state but did not follow up as recommended.


We report the case of a 28-year-old female patient who presented with a 4-year history of almost daily episodes of urticarial skin lesions. She reported to not yet be suffering from angioedemas. The patient suspected that the skin reactions were triggered by exposure to the sun. Furthermore, the intake of cetirizine tablets had led to a worsening of the urticaria in the past, and sometimes she had experienced episodes of vertigo and nausea after intake. Thus, the patient had self-tested the tolerability of several antihistamines during symptom-free periods. She reported always having developed urticarial lesions approximately 2 hours after intake. The triggering drugs were Rupafin® (rupatadine), Telfast® (fexofenadine), Atarax® (hydroxyzine), Lorano® (loratadine), Wick Medi Nait® (among others, doxylamine succinate), and Grippostad® (among others chlorpheniramine maleat). Furthermore, the patient indicated that Livocab® (levocabastine) eye and nose drops, used for the treatment of rhinoconjunctival conditions, had also led to urticarial lesions in the entire integumentary system, mostly in the face. Her patient history included neurodermitis in childhood, rhinoconjunctival symptoms in the months of April to October, oral allergy syndrome after ingestion of apples and various nuts as well as perennial bronchial asthma. Due to migraines, she took acetylsalicylic acid and ibuprofen as needed, the latter twice a week. Due to relapsing tonsillitis, a tonsillectomy had been carried out, but after that, increased CRP levels had still repeatedly been measured. On the day of first presentation, the skin symptoms were weak, no urticarial lesions or red dermographism were detected. The physical examination revealed remnants of the tonsils at the soft palate.


A 55-year-old woman without relevant medical history was referred to our burn center with 35% total body surface area full thickness thermal burns (third degree) from flames on her lower limbs, hands and face (UBS 110, ABSI 9) (Fig. ). The burns on her right ankle and foot and left knee seemed to be deeper (fourth degree). Initial surgical treatment occurred 2 h after the burns (Day 0) and included releasing incisions from knee to toes in both her lower limbs. The initial dressing was composed of silver sulfadiazine 1% and general resuscitation included fluid resuscitation and invasive monitoring. Then, three surgical procedures were required to excise the devitalized tissues, including muscles and tendons of both lower limbs. Thighs and upper third of her legs were covered with skin autografts. Tibia and fibula were exposed on the right limb. Toes were amputated through the metatarso-phalangeal joints. Ankle, mediotarsal and tarso-metatarsal capsules were burnt, some joints were open (Fig. ) and vasculo-nervous pedicle was at high risk of exposure. Consequently, the lower extremity required covering with vascularized tissues. Local pedicled flap was not an option for the ankle and foot; therefore, we opted for a latissimus dorsi musculo-cutaneous flap with vertical skin paddle (4 × 20 cm) centered on the main perforator of the anterior branch of the thoraco-dorsal pedicle, identified with an echo-doppler. The flap was performed on day 27 post-burn. On the pre-operative CT-angiogram of the lower limb, we noticed that the anterior tibial artery was thrombosed just at the second third of the leg. The posterior tibial pedicle was preserved to ensure the vascularization of the remaining tissues of the foot. The thoraco-dorsal pedicle was end-to-end anastomosed to the anterior tibial artery. The anastomoses were difficult to perform because inflammatory tissues, full of oedema, surrounded the vessels. The skin paddle of the latissimus dorsi flap was originally intended for flap monitoring (Fig. ). The free flap was a success, and 3 weeks later, the right limb was almost totally covered either with skin graft or with the flap. Nevertheless, the left patellar tendon was still exposed and needed to be covered with a flap (Fig. ). The options discussed were to perform a pedicled flap, to perform a second free flap or to recycle tissues from the previous flap. We performed a vascular mapping of the flap with the use of an echo-doppler. The main pedicle of the flap was divided into two branches. The skin paddle was vascularized by this anterior branch from which a main perforator was identified. The choice between a musculo-cutaneous flap and a perforator flap was discussed. As a cross-leg had to be performed, the risks of rupture due to excessive tension or of thrombosis due to desiccation of the perforator were considered as too high. Consequently, a musculo-cutaneous cross-leg flap was harvested from the previous flap. The flap was partially raised from the right limb including the anterior branch of the thoraco-dorsal pedicle and a cross leg was performed to cover the left patellar tendon. Both legs were immobilized together using an external fixation (Hoffmann apparatus, Fig. ). The donor site was covered with a skin graft. After a period of 3 weeks, the skin paddle was progressively cut from the previous flap after partial occlusion clamps were tested. One week later, the patient was discharged to a rehabilitation center for further treatment. The wounds were completely healed 9 weeks after the burns. At 6 months post-burns, the patient was able to walk and left the rehabilitation centre (Fig. ).


A 15-year-old male sustained a grade IV liver laceration (
) during an all-terrain vehicle accident. He was hemodynamically stable and treated nonoperatively with intensive care unit (ICU) observation for 24 hours and bed rest for a total of 5 days. On hospital day 6, he developed abdominal distension and a high-grade fever. Chest radiograph showed bilateral atelectasis and a right-sided pleural effusion. Abdominal ultrasound (US) revealed a small collection on the right lobe of the liver within the hematoma. Broad-spectrum antibiotics were started, and US-guided drainage of the pleural fluid was performed. The fluid was serous without evidence of infection or bile. The patient developed a worsening ileus and abdominal tenderness a few days later. Repeat abdominal US showed an increase in the amount of free fluid in the right upper quadrant. In addition, his serum conjugated bilirubin was elevated; therefore, suspicion of an ongoing bile leak was high. On hospital day 10 after injury, the patient underwent ERCP (
), which demonstrated a leak from one of the secondary bile ducts in the right lobe. Sphincterotomy was performed with insertion of a transampullary stent. Two days later, his ileus resolved. He was started on oral diet, antibiotics were stopped, and then he was discharged home 5 days following the ERCP and stenting. At his 6-week follow-up, the patient had resumed normal physical activity, his bilirubin had normalized, and repeat abdominal US showed complete healing of the liver injury. Biliary stent was removed 8 weeks after placement.


A 12-year-old female pedestrian suffered multisystem blunt trauma on the right side of her abdomen after being struck by a sports utility vehicle. The patient suffered a closed head injury, bilateral pulmonary contusions, and grade IV liver laceration. Because the patient was vitally stable, she was observed in the ICU. Seven days after the initial injury, the patient's abdomen became markedly distended and caused respiratory compromise requiring reintubation. Repeat computed tomography (CT) scan of the abdomen (
) showed a significant amount of free fluid in the peritoneal cavity. An abdominal drain was inserted under US guidance, and several liters of bloody fluid and bile were removed. Despite the drain, the patient went on to develop infected bile peritonitis (peritoneal culture grew pseudomonas aeruginosa) showing signs of severe sepsis requiring laparotomy and washout, as well as extensive abdominal drainage. Ten days after the laparotomy and 4 weeks after the initial injury, bile leak was persistent and the patient underwent ERCP (
), which demonstrated bile leakage from a left second biliary radicle. A transampullary stent was placed. Shortly thereafter, she improved dramatically and was discharged home after a 7-week hospital stay. Bilirubin had returned to normal prior to discharge. A follow-up US 6 weeks later showed no fluid collection or vascular abnormality. The stent was removed 8 weeks later. At her 12-month follow-up, the patient had resumed her normal activity with no residual symptoms.


A 10-year-old boy sustained a handlebar injury while riding a snowmobile. He suffered a grade IV liver laceration with a vascular injury to segment 4 that necessitated emergency angiogram and embolization. Postembolization he developed respiratory distress secondary to increasing abdominal distention. On postinjury day 5, a drain was inserted into the peritoneal cavity which drained approximately 1.5 L of bile. This resulted in clinical improvement, but an HIDA scan postinjury day 8 demonstrated ongoing bile leak from the laceration site. And ERCP demonstrated a leak just distal to the bifurcation of the right hepatic duct. This was treated with stenting and sphincterotomy on postinjury day 10. Unfortunately, the patient continued to have abdominal distention and discomfort and on postinjury day 12, he started deteriorating clinically necessitating an urgent laparotomy and drainage of multiple infected bile and blood collections. Postoperatively he continued to improve slowly until discharge home with close follow-up.
His biliary stent was removed 3 months after insertion. At his 6-month follow-up, he was doing well and had resumed all of his physical activities.


An 80-year-old lady suffered a comminuted intratrochanteric fracture following a mechanical fall, with an AO classification of 3.1A2.3. After we excluded all contraindications, drew up a series of preoperation plans, consist of measure medullary cavity diameter, anterior femoral arch angle and the optimal entry point and so on. We treated with satisfied close reduction with traction on a traction operating table, and then captured the best point to insert the guide needle (). In sequence, reamed medullary cavity was performed step-by-step. Unfortunately, the reamer was stuck into femoral medullary cavity tightly at last, we could not move out by traction or rotation. What's the worst, the reamer head was ruptured completely finally, and remained in femoral shaft isolated (). The broken reamer located much more distal to the femoral intertrochanteric fracture site and jammed with cortex of bone firmly. So an extreme tough challenge for removal was in front of us.
The guide needle was removed easily, on account of less experience to refer, and no instrument to use. Therefore we performed an open technique and created a 2.0 cm ×0.4 cm long strip bony window by using an osteotome, which is just right for inserting a bone detacher, then put the detacher head adjoin the reamer, we moved out the broken reamer head by knocking back the inserted detacher and pulling out through the medullary cavity using a Kocher's clamp (). A set of PFNA was inserted to fixation and the bony window was full with bony bar taken down before, and the fracture got a good bone union after 2 months ().


A 23-year-old nulliparous woman was admitted to a state hospital in Ankara Hospital with regular uterine contractions at 40 weeks of her pregnancy. She had no known prenatal risk factor except a history of a splenectomy, which was performed because of trauma-related hemorrhage according to her statement. Cesarean section (CS) was performed for obstructed labor without any complication, and severe PPH was diagnosed sixteen hours after the surgery. A postpartum hysterectomy was performed urgently because of uncontrolled bleeding. Persistent tachycardia and hypotension were recorded during the surgery and prehysterectomy hemoglobin value of 4 mg/dl was reported. Six units of erythrocyte suspension and four units of fresh frozen plasma were given during the surgery for replacement of the lost blood. Unfortunately, cardiopulmonary arrest (CPA) developed in the last stages of the surgery, and cardiopulmonary resuscitation (CPR) was performed for 40 minutes until spontaneous heart beats began. The patient could not be extubated after the surgery and neurological examination revealed early signs of cerebral ischemia. Then, the patient was taken to Hacettepe University Hospital for intensive care and further evaluation.
She had fixed bilateral dilated pupils, her Glasgow Coma Scale (GCS) was three, her body temperature was 33 centigrade degrees, her blood pressure was 143/70 mmHg (MAP=97), her heart rate was 120 beats per minute, and arterial pH was 6.81. Extensive periphery edema was observed, and moist rales were auscultated, which indicated the onset of pulmonary edema. Pneumothorax in the apical lobe of right lung, interlobular septal thickening, and ARDS findings were detected in thorax CT. Mechanical ventilation was applied with positive pressure and positive end-expiratory pressure (PEEP). Complete blood count, blood biochemistry, arterial blood gas, coagulation profile, C-reactive protein (CRP), disseminated intravascular coagulation (DIC) panel, cardiac enzymes, electrocardiography (ECG), and posteroanterior chest X-ray were evaluated. Multiple organ failure due to hypovolemic shock was diagnosed. Central vascular access was established. Fluid replacement and inotropic support with noradrenaline and dopamine were applied. The patient began to have treatment-resistant tonic-clonic seizures; antiepileptic and anesthetic drugs were given to stop the seizures. Targeted temperature management was started with surface temperature-management device. Hypothermia (34°C) was applied for the first 24 hours. Then normothermia (36°C) was applied for the next three days. The seizures were stopped after three days. Broad spectrum antibiotics (meropenem and colistin) were administrated. Cranial magnetic resonance imaging (MRI) revealed severe hypoxic ischemic encephalopathy and bilateral cerebellar herniation.
During the search for the possible medical cause of the severe bleeding the patient's past medical record was evaluated, and it was found out that the patient had splenectomy at the age of sixteen. To our surprise, the consultation reports seven years ago revealed the diagnosis of NPD B. She received reconsultation from the pediatric metabolism and pediatric gastroenterology divisions which revealed that her parents had a consanguineous marriage, and she also had an older brother with NPD B.
There was no sign of gaining consciousness one week after cessation of the sedative drugs and no brain stem reflexes were obtained. Apnea test was positive and cerebral CT angiography was compatible with brain death. On the 14th day at the intensive care unit, brain death was confirmed. Brain death was declared to the patient's relatives but they did not donate the organs of the patient. Two days after the patient was pronounced as brain dead, the patient died after cardiac arrest.


A 55-year-old Caucasian male was admitted to our hospital with a history of biventricular systolic heart failure due to ischemic cardiomyopathy and chronic stage IV kidney disease due to diabetic nephropathy; one month earlier, he had been approved for combined heart-kidney transplant. He recently had increased fatigue and dyspnea, weight gain of 8 kg, and serum creatinine that increased from 2.3 mg/dL to 3.7 mg/dL despite outpatient inotropic and diuretic therapy. Other comorbidities included antiphospholipid syndrome under warfarin management, multiple myocardial infarctions, with 2 coronary artery bypass grafting procedures, placement of biventricular automated implantable cardioverter-defibrillator, and placement of left ventricular assist device (HeartWare) 5 months earlier.
On hospital day (HD) 14, after optimization of hemodynamics with diuretics and inotropic support, the patient was listed for heart-kidney transplant and transferred to the intensive care unit. On HD 24, the patient was taken to the operating room for combined heart-kidney transplant; however, only orthotopic heart transplantation (OHT) was possible. During the OHT, acute right ventricular graft dysfunction developed, resulting in cardiogenic shock, requiring placement of VA-ECMO support through central cannulation and withholding of the single-kidney transplantation. VA-ECMO was utilized to allow the newly transplanted heart to rest and recover and to optimize hemodynamics and volume status in order for the patient to eventually receive the single-kidney transplantation. Simultaneously, he received support with vasopressin 0.04 U/min, dobutamine 10 mcg/kg/min, epinephrine 0.01 mcg/kg/min, and full-dose anticoagulation with heparin 9.5 U/kg/hour. Tables and show the initial and subsequent laboratory results and ECMO parameters.
On post-OHT day 1, after the patient had improved volume and cardiovascular status, adequate urine output (1,660 mL/24 hours), and stable laboratory testing parameters, the heparin infusion was reduced to 5.5 U/kg/hour (i.e., low dose) and the patient underwent deceased-donor renal transplantation (DDRT). During the DDRT procedure, the patient received 1 unit of packed red blood cells and had no complications. After DDRT, the patient required epinephrine at 0.03 mcg/kg/min, dobutamine at 10 mcg/kg/min, and heparin at 5.5 U/kg/hour.
During the first 48 hours after DDRT, the patient's urine output was adequate (1,900 mL in 24 hours) and his serum creatinine concentration decreased to 2.0 mg/dL. On post-DDRT day 2 (post-OHT day 3), after repeated transesophageal echocardiography showed improved right ventricular function and optimal volume status, the patient underwent ECMO decannulation, chest washout, and sternal closure without complication. His renal function continued to improve, and his anticoagulation was discontinued. The only inotropic support needed was dobutamine at 7.5 mcg/kg/min. On post-DDRT day 5 (post-OHT day 6), the patient was successfully weaned from mechanical ventilation and on post-DDRT day 18 (post-OHT day 19) was transferred to the posttransplant care unit for further care.


The 31-year old male proband presented with symmetrical scaling when he was young, which was more prominent on the extensor surfaces of the limbs, along with dark brown, tightly adherent polygonal scales (Fig. ). The soles and palms were unaffected. The proband is the fourth child, and his mother had a similar but less severe phenotype. His father was unaffected. Two of the elder sister had similar phenotype with their mother, and one of them had a 4-year old boy without phenotype. Another elder sister presented slight scaling, whose 12-year old boy presented slight phenotype. In the extended family, 4 affected females had a slight phenotype. The family tree was drawn (Fig. ).
To investigate the genetic defects for patients with ichthyosis, a panel of 25 genes (ABCA12, ALOX12B, ALOXE3, CLDN1, COL17A1, COL7A1, CYP4F22, FLG, ITGA6, ITGB4, KRT14, KRT5, LAMA3, LAMB3, LAMC2, MBTPS2, NIPAL4, PLEC, PNPLA1, SLC27A4, SNAP29, SPINK5, ST14, STS, and TGM1) underlying the most common genetic defects for ichthyosis was detected by NGS (BGI-Wuhan). Briefly, all exons with the adjacent 10 bp introns of the 25 genes covering 100,596 bp in length listed above were captured by using a microarray chip, and were further sequenced with Illumina HiSeq2000. Base calling was performed with the Illumina Pipeline. Mutations were identified using the BWA (Burrows Wheeler Aligner) software package against the hg19 human genome reference. The average sequencing depth for target region was 272.2 -fold, and the average coverage was 98.84%. 97.02% of the target region was sequenced for more than 30-fold. Mutation identified by NGS was validated by Sanger sequencing. The detection of exonic deletions using target capture and deep sequencing data was performed using the script for the detection of exonic deletions as previously described []. Deletion of STS gene was further validated by real-time quantitative PCR of genomic DNA isolated from peripheral blood.
A total of 153 mutations were identified by NGS in the proband. After data processing and filtering referred to inherited model, minor allele frequency (MAF) in 1000G, ExAC, and gnomAD databases, splice effect, computer prediction and so on, hemizygous STS deletion of exon 1–10 (NM_000351) and heterozygous FLG NM_002016: c.3321delA (p.Ser1107SerfsTer15) frameshift mutation were identified as pathogenic mutations in the proband. The deletion of STS gene was confirmed by real-time quantitative PCR using a healthy female and a male subject as control. FLG c.3321delA mutation was confirmed by Sanger sequencing.
Several family members were included. STS deletion of exon 1–10 and FLG c.3321delA mutation were validated in these included family members (Figs and ).
In this family, the male proband presented the most severe scaling (Table ). He carried hemizygous STS deletion of exon 1–10 and heterozygous FLG c.3321delA mutation. His mother and one elder sister showed obvious but less sever symptom than the proband harbored heterozygous STS deletion of exon 1–10 and heterozygous FLG c.3321delA mutation. Another elder sister and 12-year old nephew showed slight phenotype carried only heterozygous FLG c.3321delA mutation. Another 4-year old nephew carried only heterozygous FLG c.3321delA mutation had no clinical symptom yet. The proband’s father was unaffected and neither mutation was detected.


A 32-year-old G2P0020 healthy Caucasian female initially presented to our institution for outpatient evaluation and management of secondary infertility. Her obstetric history was notable for two first-trimester miscarriages that were both managed expectantly. The couple's infertility evaluation revealed normal ovarian reserve testing and semen-analysis parameters with an unremarkable hysterosalpingogram (HSG) study, and they were diagnosed with unexplained infertility. The patient underwent ovulation induction with clomiphene citrate and HCG trigger with timed intrauterine insemination (IUI) using her partner's sperm. In the weeks following IUI, the β-hCG level rose appropriately from 641 to 971 in 48 hours. One week later, the β-hCG level rose to 3,448 and TVUS revealed a small, irregularly shaped gestational sac in the uterus without a clear yolk sac or evidence of a fetal pole. The right adnexa appeared to have two corpus luteal cysts. Of note, no free fluid was identified in the cul-de-sac and the patient was asymptomatic at that clinic visit. The plan was for a repeat β-hCG level and TVUS in 48 hours.
The patient subsequently presented to the emergency room the following morning with diffuse lower abdominal pain and vaginal bleeding. TVUS identified what appeared to be a corpus luteal cyst in the right ovary () and a likely ectopic pregnancy in the left adnexa () with a small amount of complex free fluid within the cul-de-sac. Her abdominal exam was significant for involuntary guarding of the lower quadrants bilaterally with diffuse tenderness. After discussion with the patient regarding our concern for ruptured ectopic pregnancy, the patient was amenable with the plan of proceeding with a laparoscopic unilateral salpingectomy.
A diagnostic laparoscopy was performed which revealed moderate hemoperitoneum upon abdominal entry. On pelvic survey, the left fallopian tube was noted to have a dilated distal portion, approximately 2cm in diameter with active bleeding, consistent with a ruptured left ectopic versus tubal abortion (). Notably, the mid-portion of the right fallopian tube appeared dilated at the junction between the isthmus and the ampulla, about 3cm in diameter, without evidence of rupture or bleeding, which was concerning a concurrent second ectopic pregnancy ().
The surgeons were then faced with a difficult decision regarding management of the unruptured contralateral tube. The patient's husband (and power of attorney) subsequently became involved with all decisions regarding the patient's plan of care. A left salpingectomy was essential given the abnormal left fallopian tube with active bleeding. Options for management of the contralateral tube were presented: right salpingectomy, right salpingostomy with Methotrexate (MTX) administration, or MTX administration alone without surgical intervention on the right fallopian tube. After thorough risk-benefit consideration, as well as intraoperative consultation with the patient's Reproductive Endocrinologist, the decision was made to retain the right fallopian tube and proceed conservatively with MTX administration (single-dose regimen of 50 mg/m2) due to the patient's likely desire to preserve her fallopian tube.
The patient had an uneventful recovery and her day 4 and day 7 β-hCG values confirmed an appropriate decline in β-hCG levels after MTX injection. The β-hCG level had dropped to a nonpregnant level by approximately three weeks following MTX administration. Histology of the left fallopian tube included the presence of chorionic villi, which confirmed the diagnosis of a left ectopic pregnancy. Repeat TVUS one-month following the surgery was normal without evidence of right tubal dilatation. Approximately 14 weeks after surgery, the patient had a repeat TVUS which revealed a single viable intrauterine pregnancy, which was conceived spontaneously.


A 30-year-old Caucasian female consulted her physician after being subject to lethargy, night sweats, weight loss, and dry cough with dyspnea upon heavy exercise for one month. She was previously healthy, occasional smoker with no previous surgeries or any known allergies.
Series of lab tests showed a mild normocytic anemia with mild lymphocytosis, while a preoperative chest computed tomography scan, showed a 15 cm anterior mediastinal mass with no involvement of the adjacent structures: superior vena cava, pericardium, or pleura. Following that, the thoracic surgeon scheduled a diagnostic mediastinoscopy.
The implicated surgeon described the procedure to the anesthesiologist in charge of the patient as being risk-free, and that he needs general anesthesia due to the difficulty in accessing the mediastinal mass. Anesthetic induction was uneventful. The patient was easily ventilated and after reaching a proper anesthetic depth, she was intubated via uncomplicated direct laryngoscopy with a French endotracheal tube (ETT) 7.5 cm. Bilateral breath sounds were checked and even chest expansion were noticed. Pulse oximetry showed an arterial oxygen saturation of 99% with an end-tidal CO2 within the normal range.
Few minutes later, the patient developed a sudden airway collapse where end-tidal CO2 dropped significantly, and desaturation was noted with no chest expansion. The anesthesiologist directly extracted the tube, but the mask ventilation was unsuccessful; so he decided to immediately reintubate the patient to secure the airway. Then, the ventilation was regained, saturation increased, and CO2 curve reappeared. So as a result, airway collapse was reported and/or ETT displacement.
Later, the patient developed another airway collapse, so bronchospasm was suspected. Based on this suspicion, albuterol and Solu-Cortef were given. As a result, ventilation was regained, but with high inspiratory and positive end expiratory pressures and with an increase of the end-tidal CO2 to a critical level.
The anesthesiologist then performed a fiberoptic tracheal exploration, it showed a narrowed trachea just distal to the ETT due to an extrinsic mass obstructing the tracheal lumen and extending down the carina. Due to this new finding, he decided to postpone the procedure until the stabilization and the management of the airway stenosis. However, the surgeon insisted to proceed with this elective surgery.
Under diagnostic biopsy performance and mediastinoscope insertion, she developed another airway collapse while the patient was sedated, but ventilation was maintained at high inspiratory pressures and the patient was monitored for a consecutive of 15 minutes.
Biopsy from the anterior mediastinal mass was taken and sent to the anatomopathologist. Then, mediastinoscope was retracted, auscultation revealed bilateral minimal air entry. Propofol and sevoflurane used for maintenance of anesthesia were discontinued and 15 min later, the patient was breathing spontaneously but with some retractions. Upon giving Prostigmin, she developed another airway collapse with severe oxygen desaturation. The anesthesiologist decided to keep the patient intubated; she was transferred to the intensive care unit for observation and evaluation of her airway obstruction.
In the intensive care unit, thorough laboratory and radiology revealed a severe distal extrinsic tracheal compression and left main bronchus compression of more than 80% by the anterior mediastinal mass, with no involvement of the adjacent vascular structure. They also showed a left lower lobe consolidation in favor of a pneumonia and minimal bilateral pleural effusion. Meanwhile, she kept developing airway collapse with severe arterial oxygen desaturation.
She was treated with an empiric antibiotherapy, with intravenous steroids and nebulizers. A multidisciplinary team decided to begin chemotherapy after the anatomopathologist result came as a non-Hodgkin's lymphoma.
Subsequent to treatment, lymphoma size decreased progressively, relieving the airway compression, and extubation was performed after one week from undergoing the mediastinoscopy. After three days of observation, she was discharged home, with scheduled outpatient chemotherapy sessions and later possible surgical management.


A 71-year-old woman with a past medical history of uterine cancer 25 years before, herpes-zoster infection two years before, recent diagnosis of human immunodeficiency virus (HIV) infection, and cervical adenopathies under investigation presented at the first medical appointment at the Infectious Diseases Unit referring a 3-week history of fever, weight loss of 20 kg, and hemoptoic cough, as well as diarrhea with one year of evolution. On physical examination, she was cachectic and weak, had axillary temperature of 38°C, blood pressure of 112/80 mmHg, respiration rate of 40 per minute, heart rate of 142 beats per minute, and oxygen saturation of 95% in room air. She also presented with pain and tenderness at the palpation of the hypogastric region, and during the consultation, she presented cardiorespiratory arrest. Advanced life support with favorable response was performed, and she was subsequently transferred to the emergency room where it was necessary to initiate aminergic support and proceed to orotracheal intubation and mechanical invasive ventilation. The complementary diagnostic exams revealed white blood cell count 14,740/μL with absolute neutrophil count 13,180/μL (89.4%) and absolute lymphocyte count 970/μL (6.6%) with 113 CD4+/μL cells, hemoglobin level 11.3 g/d, and platelet count 2,33,000/μL. She presented with blood creatinine 1.34 mg/dL, pancreatic amylase 222 U/L (4 times above the upper limit of normal), pancreatic lipase 174 U/L (3 times above the upper limit of normal), and seric lactates 6.5 mmol/L. Viral load of HIV by polymerase chain reaction was 2,330,220 copies/mL. Thoracic, abdominal, and pelvic computed tomography (CT) revealed pneumoperitoneum, peritonitis, diffuse parietal thickening, and dilatation of the intestinal loops of the jejunum with splenic infarction ().
An emerging surgery exploratory laparotomy was performed having been found enteric peritonites of the large cavity, occlusion with transition point at the level of the distal jejunum and poor perfusion, and thickening of the distal loops and perforation at the level of the distal ileum. Segmental enterectomy of approximately 35 cm of jejunum/ileum has been performed, including ischemic loop and ileal perforation. In the postoperative period, she was admitted to the intensive care unit, and broad-spectrum antibiotic therapy has been initiated. Nevertheless, she evolved with progressive clinical deterioration with increasing need of amines and without favorable hemodynamic response. The patient passed away the same day. The histological examination of the segmental enterectomy piece and available postmortem revealed acute transmural inflammation of the enteric wall, with suppuration and necrosis and extensive lesions of acute fibrinoexudative serositis with fungal hyphae of the Aspergillus spp. type. There were no images of angioinvasion, epithelioid granulomas, or signs of malignancy. The culture of peritoneal fluid obtained during surgery revealed polybacterial and fungal overinfection with Enterococcus faecium, Escherichia coli, and Candida albicans.


A 28-year-old lady was referred to the neuro-ophthalmology clinic of Hospital Universiti Sains Malaysia for progressive bilateral visual disturbances over a period of three months. The patient was diagnosed to have diffuse large B-cell lymphoma stage IV with metastases to the breast, pancreas, lungs, and ovaries. The diagnosis was made a year before when she presented with right breast lumps, which were subsequently biopsied.
She completed six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) together with intrathecal methotrexate, dexamethasone, and cytosine arabinoside over a period of five months after the diagnosis. Four months later, she developed right upper limb neuropathic pain and was diagnosed with peripheral neurolymphomatosis of the right brachial plexus. Positron emission tomography with fluoro-D-glucose integrated with computed tomography (FDG-PET/CT) showed no central or peripheral nervous system involvement. She was initiated on methotrexate, but defaulted after the eighth cycle.
Three months later, she developed gradual onset of visual disturbances in both eyes, described as a loss of the left visual field in both eyes. She denied seeing any floaters or flashes of light. The symptoms worsened a month prior to presentation, associated with short-term memory loss and emotional lability. There was no history of fits, body weakness, or sensory deficits. There were also no symptoms of high intracranial pressure such as headache, nausea, or vomiting. She had no diplopia, dyschromatopsia, or metamorphopsia. She denied any recent trauma.
On examination, best-corrected visual acuity was 6/9 in both eyes. Confrontation visual field testing showed left homonymous hemianopia. Ishihara color vision testing was normal. There was no afferent pupillary defect. Both anterior and posterior segments were unremarkable. Humphrey automated visual field confirmed a dense left homonymous hemianopia (Figure ).
Magnetic resonance imaging (MRI) of the brain revealed a well-defined mass in the splenium of corpus callosum associated with white matter oedema, suggestive of metastases (Figure ).
She was diagnosed with secondary central nervous system neurolymphomatosis and started on a regime of rituximab, ifosfamide, carboplatin, and etoposide. She was also given another cycle of intrathecal methotrexate, steroid (dexamethasone), and cytarabine. After completion of three cycles of chemotherapy over a period of two months, her visual field improved significantly (Figure ).
MRI after completion of chemotherapy showed that the mass in the splenium of corpus callosum had reduced markedly in size (Figure ).


A 65-year-old female was transported to the emergency department (ED) at approximately 2:00 AM following a witnessed cardiac arrest. According to the patient’s husband, she had been asleep in bed when she awoke suddenly, sat upright, and reached for her albuterol inhaler before “collapsing.” He found her to be pulseless and initiated cardiopulmonary resuscitation (CPR) while placing a call to emergency medical services (EMS). On EMS arrival, the patient was unresponsive and continued to receive CPR. She was intubated in the field using a size 7.0 endotracheal tube. Her initial rhythm was pulseless electrical activity (PEA), but she converted to normal sinus rhythm after receiving 1mg of epinephrine intravenously and 15 total minutes of CPR. No further history was available.
Per her husband, her past medical history was notable for “thyroid problems.” Her only medications were an albuterol inhaler, recently prescribed by her primary physician, and a multivitamin. She had no known drug allergies. On social history, the patient was not known to drink alcohol, smoke cigarettes, or use other substances. A family medical history and review of systems could not be obtained due to the acuity of her condition.
On examination, the patient was an obese female, intubated, and unresponsive. Her temperature was 37.1 degrees Celsius, blood pressure was 97/65 millimeters Hg, heart rate was 75 beats per minute (bpm). Her body mass index was estimated at 32. She was initially receiving assisted ventilation by EMS, but on examination in the ED she was found to have a spontaneous respiratory rate of 12 breaths per minute with an oxygen saturation of 98% on 40% fraction of inspired oxygen. Her head was atraumatic and normocephalic. Her pupillary exam showed mid-dilated symmetric pupils with sluggish reactivity to light. There was no hemotympanium or Battle’s sign. She had no apparent facial droop. An oral endotracheal tube was in place, confirmed with radiography and audible bilateral breath sounds. She had a full, supple neck without palpable masses, but additional exam was limited by body habitus. On cardiopulmonary exam, her lungs were clear to auscultation bilaterally and her heart had a regular rate and rhythm with no murmurs, gallops, or rubs. The patient’s abdomen was soft and nondistended with normal bowel sounds. On neurologic exam, her Glascow Coma Scale was 3T. She had diffusely decreased muscle tone, and 1+ patellar and brachioradialis deep tendon reflexes. Her musculoskeletal exam was unremarkable for deformity, erythema, or edema. Skin exam did not show any rashes, wounds or other lesions.
Initial electrocardiogram (ECG) () showed normal sinus rhythm at a rate of 70 bpm, normal axis, normal intervals and no pathologic t-wave inversions or ST-segment changes. A complete blood count and complete metabolic panel were done (). Additional laboratory tests, including thyroid studies, were unremarkable except for an elevated lactic acid of 6.9 millimoles/liter (L) (). A point-of-care echocardiogram was performed, which demonstrated grossly normal heart chamber sizes and systolic function with no pericardial effusion (). A point-of-care ultrasound of the abdomen and thorax was negative for any intra-abdominal free fluid. There was bilateral lung sliding present and no B lines. An anterior to posterior chest radiograph (CXR) is shown in .
The etiology of the patient’s cardiac arrest was unknown until a further diagnostic test was performed that revealed the diagnosis.


We present the case of a 76-year-old male with history of hypertension and deep vein thrombosis. He initially presented to the oncology clinic in June 2016 with a low white blood cell (WBC) (2,700 cells/microliter) and platelet counts (58,000 cells/microliter), which was found during routine blood work. Initial bone marrow biopsy performed in June 2016 showed normocellular marrow with no evidence of blasts. Fluorescence in situ hybridization (FISH) did not show evidence of myelodysplastic syndrome (MDS). The patient was treated conservatively and was given a trial of steroids. He did not respond to these treatments, and blood tests performed in February of 2017 showed a platelet count of 39,000 cells/microliter, a hemoglobin level of 7.8 gm/dl, and a WBC count of 2,000 cells/microliter. In view of the persistent trilineage depressed blood counts, a second bone marrow biopsy was performed in March of 2017, which revealed 20.8% blasts with hypercellular bone marrow. Therefore, he was diagnosed with AML. He underwent additional cytogenetic testing, which showed that he did not have any of the favorable cytogenetics, including mutations of the CCAAT/enhancer-binding protein alpha (CEBPA) gene or nucleophosmin (NPM) 1 gene. Unfavorable FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was detected with a polymerase chain reaction (PCR) product of 327 base pairs (bp). In addition, another poor prognostic marker, trisomy of the 21st chromosome, was detected. We administered the standard first-line induction chemotherapy regimen to the patient, including cytarabine (100 mg/m2) and daunorubicin (60 mg/m2), in March 2017. Unfortunately, a bone marrow biopsy performed 14 days after chemotherapy initiation showed AML with 72% blasts (Figure ). At that time, the patient decided that he did not want to continue with re-induction attempts involving intensive chemotherapy. After detailed discussions with the patient and a literature review, we presented the option of salvage chemotherapy with the less-toxic AZA for the treatment of his refractory AML. He agreed to this treatment, and we administered AZA (75 mg/m2) for seven days in the second half of March 2017. A subsequent bone marrow biopsy performed in April 2017 showed a positive response with no morphologic or immunophenotypic evidence of increased blasts. Subsequently, he received nine more cycles of AZA, which he tolerated very well. A repeat bone marrow biopsy performed in January 2018 revealed no blasts (Figure ). The patient continues to be in complete remission with incomplete hematologic recovery (low platelet counts - 44000 cells/microliter) after 10 cycles of treatment with AZA.


A 48-year-old man presented at the ophthalmologic out-patient department with a 3-day mild horizontal diplopia in the left direction followed by the onset of headache 17 days later. He denied nasal obstruction, epistaxis, nasal discharge, pain, hyposmia, and nasal swelling. There was no history of fever, weight loss, or nocturnal sweating. He had no history of diabetes, hypertension, or any neurological disease. On physical examination, cardiopulmonary examination was normal and neither lymphadenopathy nor hepatosplenomegaly was observed. Neuroophthalmologic examination revealed normal visual acuity, fields, and fundi. The pupils were equal and reactive to light and near stimuli. There was no ptosis, but there was limitation of movement of the left eye when he gazed to the left side. Function of the remaining cranial nerves was normal. There were no sensory or motor deficits in the upper and lower extremities; all tendon reflexes were normal. He was found to have isolated left abducens nerve palsy. Computed tomography (CT) scanning revealed soft-tissue density neoplasms filling the sphenoidal sinus (). Magnetic resonance imaging (MRI) scanning with gadolinium injection was performed and revealed a homogeneous mass lesion (2.8cm x 2.3cm x 2.9cm) occupying the sphenoidal sinus and invading and destroying the clivus (). Rhinoendoscopy revealed a mass at the sphenoidal sinus which was biopsied and histological examination revealed a malignant lymphoma. The immunohistochemical staining of tumor tissues showed CD3+, CD56+, Ki67>80%, LCA+, CD38+, and CD20− (). The lymphoma cells were positive for EBER in situ hybridization. The pathological diagnosis was ENKL. Plasma EBV PCR yielded 1.18 x 106 copies/ml. Ten days later the patient had the B symptom (fever, night sweats). The enlarged lymph nodes were checked in the neck, bilateral subclavian, alar, and inguinal. Contrast enhanced CT showed renal metastases. Bone marrow smear and biopsy showed active hyperplasia, immature lymphocytes accounting for 3%, and heterotypic large cells having a scattered distribution (). Flow cytometry analysis showed lymphocytes accounting for 6.8% and suggested phenotypic abnormal NK cells in the bone marrow. Cerebrospinal fluid analysis showed glucose (2.87mmol/L) and protein content (0.22g/L) with normal cell count and no malignant cells. Blood analysis showed complete blood cell reduction. The second bone marrow biopsy suggested hemophagocytic syndrome []. The clinical diagnosis was stage IV of ENKL. The patient asked to be transferred to the community hospital.


A 54-year-old Caucasian male with past medical history of profound intellectual disability, schizophrenia, posttraumatic stress disorder, Parkinson's disease, gastroesophageal reflux disease, and seizure disorder initially presented to the emergency department (ED) from an assisted living facility with fever, tachycardia, nausea, and vomiting of three days duration. The patient was diagnosed with sepsis of unknown origin and admitted to the hospital for further workup and treatment. On admission, vitals showed the following: temperature of 102.5F, pulse 123 beats per minute, respiratory rate 40 breaths per minute, O2 saturation of 96% on room air, and blood pressure 154/84 mm/Hg. On imaging, chest X-ray showed no evidence of acute cardiopulmonary disease. Electrocardiogram showed sinus tachycardia with possible right atrium enlargement and ventricle hypertrophy. Laboratory studies showed the patient had no leukocytosis; however, segmented neutrophil was 92.8% and absolute neutrophil count was 9.19 k/cmm. Hemoglobin and hematocrit were decreased at 12.8 and 38.0%, respectively. Atrial blood gas was unremarkable. Lactic acid sepsis was initially 1.96 mmol/L and later increased to 2.63 mmol/L. Procalcitonin was 0.32 ng/ml. Metabolic panel showed sodium was 149, chloride 114, BUN 37 mg/dL, AST 136, ALT 43. Urinalysis showed trace blood likely secondary to catheterization and urine ketones of 40 mg/dL. Urine culture was negative after 48 hours. Blood cultures from admission were negative after five days. Influenza screen was negative. Viral PCR was negative. Physical examination at admission showed the patient was in moderate distress, diaphoretic, agitated, tachycardic, and tachypneic. The patient was started on antibiotic therapy with vancomycin, levofloxacin, and piperacillin/tazobactam for sepsis of unknown origin and given fluid resuscitation. Home medications included the following: paliperidone 3mg daily, haloperidol 2.5mg twice daily as needed, citalopram 40mg daily, carbidopa/levodopa 25-100mg three times daily, and carbamazepine ER 200mg twice daily.
On hospital day 2, the patient developed increased muscle rigidity, tremors, hypoxemia with O2 saturation in the 70s on room air, increasing temperature (102.9F), tachypnea (max respiratory rate 45), and worsening tachycardia (max heart rate 130). Repeat labs revealed leukocytosis with a white cell count of 11.9 k/cmm and neutrophil count of 89.6 k/cmm. Patient also developed acute renal insufficiency with BUN and creatinine of 52 mg/dL and 1.53 mg/dL, respectively. Lactic acid further increased to 4.3 mmol/L. Total creatine kinase was 2249 u/L.
The patient was transferred to intensive care unit (ICU), intubated, and ventilated for airway protection. Close review of medical records from his assisted living facility indicated that the patient had received intramuscular injections of haloperidol 2.5mg seven times over the previous three weeks to help with behavioral agitation. The last dose was administered on the day of admission. Over the same period of time, it also appeared that the patient had been refusing many of his scheduled medications to include carbidopa/levodopa. The patient's history, examination, and laboratory findings strongly suggested a diagnosis of NMS and treatment was initiated accordingly. A one-time dose of dantrolene 125mg IV was given. Additionally, the patient received supportive care measures including application of a cooling blanket and infusion of cooled normal saline provided for hyperpyrexia. Intravenous vecuronium was started for severe muscle rigidity. All psychotropic agents were held.
Neurology recommended video electroencephalography (VEEG) due to the patient's history of seizures. VEEG showed no epileptiform activity and mild nonspecific encephalopathy. Neurology recommended the resumption of carbidopa/levodopa 37.5-150mg three times daily and carbamazepine 200mg twice daily with titration to a final dose of 500mg twice daily with a target carbamazepine level of 10-12. Throughout the ICU stay, the patient's total CK level trended downward, decreasing from 2249 u/L to 535 u/L. BUN and creatinine trended down to 23 mg/dL and 0.85 mg/dL.
As the patient's condition improved, he was extubated and transferred to the general medicine unit. However, with resumption of carbidopa/levodopa, the patient's untreated psychotic symptoms exacerbated and included audio-visual hallucinations and delusional paranoia. He was also intermittently agitated and not sleeping well. Psychiatry was consulted for recommendations regarding treatment of psychosis in the setting of resolving NMS. Carbamazepine and lorazepam were recommended for management of agitation, and trazodone 100mg at bedtime was started for sleep. Psychotic symptoms and agitation persisted despite being on lorazepam 2mg three times daily as well as being on a therapeutic dosage of carbamazepine. The decision was made to start low dose quetiapine at 12.5mg at bedtime and titrated up to 12.5mg twice daily after four days, at which point the patient's psychosis diminished. The patient was monitored closely throughout for recurrence of NMS symptoms. Quetiapine was well-tolerated and the patient demonstrated improvement in psychosis, agitation, sleep, and appetite. After X days, the patient returned to his baseline mentation and was successfully discharged back to his assisted living facility.


A 59-year-old male was scheduled for elective open retropubic prostatectomy for a benign enlarged prostate weighing approximately 65 grams. The patient's weight was 89 kg, ASA physical status II, diagnosed with essential hypertension two years ago, and controlled with ACE-I, Ramipril 10 mg once daily. No other morbidities were associated and no other medications were taken by the patient. The preoperative assessment did not reveal any other abnormality related to anaesthesia with normal vital signs, omitting Ramipril for 48 hours before the operation and normal baseline laboratory results including renal profile (creatinine 87 micromole/L, urea 7.9 mmol/L, Na 140 mmol/L, and K 4.1 mmol/L).
Following discussion with the patient and the surgical team, the anaesthetic plan was general anesthesia (GA) with postoperative patient-controlled analgesia (PCA) with morphine. Relatively uneventful induction of GA by propofol (2mg/kg), fentanyl (100 micrograms), and rocuronium (0.6 mg/kg) with endotracheal intubation, radial arterial cannulation for IBP monitoring, and two wide-bore peripheral cannulas (18G) were inserted. Induction was accompanied by hypotension (BP dropped from 112/68 to 73/46) and bradycardia (HR dropped from 78/min. to 38/min.) that required two successive doses of ephedrine each 6 mg were followed by restoration of BP and HR. Baseline arterial blood gas (ABG) after positioning was normal (). At 2 hours after the start of surgery, the estimated blood was about 350 ml and the urinary output (UOP) was 120 ml (over 2 hours) with mean arterial pressure (MAP) being maintained above 70 mmHg without further vasopressors required other than the initial 12 mg of ephedrine required immediately after induction. An arterial blood gas (2 hours after start of surgery) was initially performed for monitoring haemoglobin level showed hyperkalaemia (6.1 mmol/L) with acidosis (pH 7.33 and PCo2 6.2 kPa). The initial explanation was respiratory acidosis, and ventilation parameters were increased. Twenty-five minutes later ABG showed a decrease of PCo2 to normal with normal anion gap acidosis and increasing potassium to 6.5 mmol/L. Hyperkalaemia was treated with glucose-insulin (10 units of insulin added to 1 litre of glucose 10%) and mild hyperventilation and furosemide (20 mg bolus) with a change of the maintenance fluid from compound lactate solution to normal saline with the same rate (225ml/h). Forty minutes later, these measures had reduced potassium from 6.5 mmol/L to 4.1 mmol/L.
Despite normalization of potassium level (k 4.1 mmol/L) following the measures mentioned above, the acidosis persisted with maintained normal bicarbonate level and normal PCo2 (). From the time of normalized potassium, the acidosis required three hours to normalize which was two hours after recovery from GA. The presence of acidosis did not affect emergence from anaesthesia or recovery of the patient.
Postoperative follow-up of the renal function tests and electrolytes () revealed normalization over a period of two days postoperatively with the patient restored intake of ACE-I on day one postoperatively with no effect on potassium level.
At the end of surgery, the estimated blood loss was about 635 ml, UOP was 700 ml (over an operative time of 4 hours), and the infused fluids included 450 ml of Hartman's solution (over the first 2 hours), 950 ml of 0.9% normal saline, and 500 ml of Gelofusine 4% (over the second 2 hours) in addition to 1 litre of glucose 10% with insulin. No blood transfusion was required and no MAP <70 mmHg was recorded.


We report the case of a 37-year-old gentleman who presented on a Sunday to the general surgical on-call with a four-day history of generalised abdominal pain postcolonoscopy. He had associated nausea and slightly reduced stoma output.
Past medical history includes asthma and Crohn's disease which had settled at the time leading up to the colonoscopy. There were no known drug allergies, and the patient takes azathioprine, salbutamol, and beclometasone. He is a nonsmoker and drinks minimal alcohol.
Past surgical history includes a complicated appendicectomy in 2007 resulting in a colostomy; a colonic perforation and retroperitoneal abscess secondary to Crohn's disease led to an ileostomy in 2010, and the ileostomy was reversed with an ileocolonic anastomosis formed in 2012. Anastomotic dehiscence occurred leading to major sepsis with abdominal wall breakdown and abdominal compartment syndrome. A debridement of the area was performed and left as a laparostomy, and an ileostomy was reformed. The area was later covered by a large skin graft in 2012. His colonoscopy was part of a preoperative workup for a procedure in a quaternary centre to assess his viability to repair his complex hernia.
On examination, his heart rate was 117 beats per minute (bpm), blood pressure 128/81 mmHg, respiratory rate 15, and oxygen saturation 98% on air. There was a large mass overlying the hernia to the left of the midline and on abdominal palpation; the mass was ballotable with crepitus, was slightly tender, and had a cough impulse (Figures –). In addition, a stoma was present. The chest was clear to auscultation, and GCS was 15/15.
Bloods on admission revealed a C-reactive protein of 219 mg/L (0–5 mg/L) and were otherwise unremarkable.
There is a huge amount of free air, which is most likely secondary to a recent colonoscopy that has probably blown off the ascending colon stump. The colon cannot be traced beyond the midtransverse colon in the current scan (). A large midline abdominal wall hernia containing several bowel loops with most of the gas seeping into the mesentery within the hernia can be seen. Part of the gas is also seen in the intrahepatic and right perinephric space.
The patient was managed with an ABCDE approach. Tazobactam with piperacillin (Tazocin) was administered as per local guidelines. Intravenous fluids, analgesia, and monitoring of output were commenced.
Given the result of the computed tomography scan, the surgical registrars had consented the patient for a laparotomy plus proceed as necessary. This was halted when the consultant on-call reviewed the patient an hour later.
A conservative approach was adopted, and the patient was discharged just days following admission. He did very well and is currently undergoing review at one of our quaternary centres for his abdominal wall reconstruction.
Following his admission and conservative management, contact was made with the quaternary centre and they reported that the colonoscopy had gone to plan and was carried out meticulously and there was no evidence of a perforation; it was noted that there was evidence of inflammation macroscopically and microscopically and this was determined to be nonspecific.


A 38-year old male presented with a chief complaint of chronic and worsening left hip pain. The patient reported a lifelong history of pain and disability and described his current pain as sharp, aching, burning, severe, and constant, occurring daily. Relevant history included a diagnosis of hip dysplasia at age 1 year and confirmation of Legg-Calve-Perthes disease at age 18. The patient walked with a significant limp and reported difficulties with activities of daily living such as putting on socks and shoes and pain on getting out of bed. He also reported the use of a heel lift to equalize his leg lengths and expressed frustration at his daily pain. He had attempted to manage his pain with home exercise, activity modification, strengthening, anti-inflammatories, ice, and rest at length, all without success.
On physical examination, the left leg was significantly shorter, with the leg length discrepancy measured grossly at approximately 2.5–3.0 cm. Range of motion (ROM) of left hip was decreased and measured as follows: 0–85° of flexion, 5° of internal rotation in flexion (IRF), 5° of external rotation in flexion (ERF), 30° of abduction, and 5° of adduction. Abductor strength was 4/5 bilaterally. Neurological examination was unremarkable.
Radiographs revealed left hip dysplasia with upsloping of the acetabular socket. LCPD affecting the femoral head was confirmed, with an incompletely formed femoral head noted and a leg length discrepancy measured at 2.5 cm.
The preoperative plan included left hip total hip arthroplasty. Imageless, computer-assisted navigation was used during surgery to assist with leg length equalization and component placement (off-label use).
Surgery was successful and at three weeks postprocedure, the patient was progressing well, had experienced significant pain relief, and was satisfied with his surgery. Left hip range of motion was improved, most notably in flexion and ERF. Postoperative ROM was measured at 0–95° flexion, 5° IRF, 30° ERF, 30° abduction, and 10° adduction. Radiographs revealed that the left hip was well aligned and concentrically reduced. The left leg was lengthened by 2.5 cm, and leg lengths were even ().


A 47-year old female presented with a chief complaint of severe right-sided hip pain that was chronic in nature. Relevant history included right hip surgery at 10 years of age to address symptoms of Legg-Calve-Perthes disease. She reported no relief from this procedure and in the interim, had sought relief through multiple conservative treatments without success. The patient also reported chronic low back pain, contralateral knee pain, and right-sided groin pain and thigh pain which she attributed to a significant LLD.
On physical examination, the right leg was significantly shorter, with a noticeable LLD present. Range of motion of right hip was decreased and measured as follows: 0–80° flexion with significant pain at end range, 5° IRF with significant pain, 5° ERF, 20° abduction, and 10° adduction. Abductor strength was 4/5 bilaterally. On orthopedic testing, anterior impingement test, Patrick-FABERE, and lateral impingement tests were all positive on the right. Neurological examination was unremarkable.
Radiographic examination revealed a 3.5 cm LLD with the right leg shortened, ovoid femoral head, joint space narrowing, sclerosis, osteophytes, acetabular dysplasia, shortened femoral neck, and trochanteric overgrowth. Diagnoses of Legg-Calve-Perthes disease and secondary osteoarthritis were confirmed.
The preoperative plan included a right hip total hip arthroplasty. During surgery, computer-assisted navigation was again used to assist with component placement and monitoring of changes in leg length (off-label use).
Surgery was successful and at three weeks postprocedure, the patient reported significant pain relief and was satisfied with the outcome of her surgery. She reported the use of a cane when walking long distances but was otherwise ambulating without the use of assistive devices and was progressing well in physical therapy. Range of motion had improved, most significantly in flexion, ERF, and abduction, and was measured at 0–95° flexion, 5° IRF, 30° ERF, 35° abduction, and 5° adduction. Radiographs revealed equalized leg lengths and implants that were well aligned and concentrically reduced ().


An 88-year-old male presented to a large community teaching hospital with a primary complaint of an irritating, generalized skin rash. The patient was afebrile. He reported recently receiving vancomycin and piperacillin-tazobactam at another area hospital for lower extremity cellulitis. Due to the extensive nature of the skin rash, he was admitted for further clinical assessment.
The patient's past medical history was significant for hypertension, benign prostatic hyperplasia (BPH), stage 3 chronic kidney disease (CKD) (baseline serum creatinine, 1.8 mg/dL), class 3 obesity (BMI 43), cholecystectomy, and left knee replacement surgery. Due to BPH progression, the patient had been using a Foley catheter for the past year which was changed monthly.
Initial laboratory results were unremarkable except for a slightly decreased red blood cell (RBC) count of 3.97 × 106/µL, hemoglobin 11.9 g/dL (reference range, 13.5–8.0 g/dL), and hematocrit 36.5% (40.5–54.0%). His serum creatinine was 2.02 mg/dL with an estimated glomerular filtration rate of 31 mL/min/1.73 m2 and elevated blood urea nitrogen (BUN) of 37 mg/dL (7–18). Urinalysis revealed a clear, yellow appearance, trace leukocyte esterase, 2+ white blood cell (WBC) count, 2+ RBC, occasional bacteria, and <1 squamous epithelial cells. An initial urine culture produced no growth after 24 hours.
The patient's skin rash, which covered more than fifty percent of his body, was treated with intravenous methylprednisolone 60 mg every 8 hours along with diphenhydramine 25 mg every 8 hours as needed. As the rash improved, the methylprednisolone was changed to oral prednisone (40 mg/day). During treatment, the patient experienced an increase in serum creatinine to 2.49 mg/dL and a BUN of 100 mg/dL. Oral prednisone was tapered to 20 mg/day, and the patient's rash improved with treatment.
During hospitalization, the patient's WBC count became elevated to 12.6, but he remained afebrile. His Foley catheter was changed, and urinalysis from the catheter was performed. Urinalysis demonstrated a cloudy, yellow appearance, 3+ leukocyte esterase, 1+ RBC, 4+ WBC clumps, and 2+ bacteria. Urine Gram stain and culture results revealed catheter colonization by Gram-negative rods with a final result of >100,000 colony-forming units/mL of Cedecea neteri. No other microorganism was identified from the catheter. The patient received empirical therapy of intravenous aztreonam (500 mg/8 h) until antibiotic susceptibility evaluations performed using the MicroScan WalkAway 96 Plus (Beckman Coulter) enabled de-escalation of therapy. MIC determination revealed that the C. neteri isolate was sensitive to piperacillin-tazobactam, ceftazidime, ceftriaxone, cefepime, aztreonam, gentamicin, tobramycin, nitrofurantoin, ciprofloxacin, and sulfamethoxazole-trimethoprim, but resistant to ampicillin, ampicillin-sulbactam, cefazolin, and cefoxitin, and intermediate to cefuroxime. The patient's WBC count returned to normal range, and therapy was de-escalated to ciprofloxacin 250 mg twice daily for 5 days prior to the patient's discharge to a rehabilitation facility.


A 48-year-old man with no apparent past medical history initially presented with abdominal pain associated with nausea and vomiting. Physical examination was unremarkable. Lab results were significant for anemia, with a hemoglobin level of 11.6 g/dL (14–18), hematocrit 32.2% (42–52), and lipase 164 U/L (13–60). His comprehensive metabolic panel was unrevealing. A CT of the abdomen and pelvis with contrast was performed, which revealed an enlarged pancreas without a focal mass, diffuse surrounding mesenteric edema, mild retroperitoneal lymphadenopathy, mild mesenteric lymphadenopathy, rectal wall thickening with perirectal lymphadenopathy, left renal mass measuring 3.7 × 1.4 × 1.4 cm, right renal mass measuring 2.3 × 4.3 × 5.2 cm, marked diffuse urinary bladder wall thickening, and trace pericardial effusion (). The concern at the time was for peritoneal carcinomatosis and/or mesenteric tumor. Urology and oncology services were invited to evaluate the patient, both in agreement for a biopsy of the lymph node; in addition, urine cytology and HIV were tested.
Urine cytology revealed atypical lymphocytes. Renal biopsy revealed diffuse large B-cell lymphoma (DLBCL). Bone marrow biopsy was consistent with involvement of B-cell lymphoma. HTLV-I/II antibody was negative. HIV screening returned with a positive result. Initial CD4 was 440/μl with a percentage of 14%, and HIV RNA viral load by PCR was 61800 copies/mL. Hepatitis C virus screening was negative; hepatitis B screening was positive for the core antibody and surface antibody but negative for surface antigen. His lactate dehydrogenase (LDH) was above the upper limit of the detection for our lab, >2500 U/L (135–225). Cerebrospinal fluid at the time revealed atypical lymphocytes.
Biopsy of the kidney mass revealed atypical lymphocytes positive for CD45, CD20, PAX-5, and CD10, while negative for CD5, CD30, MUM-1, BCL-1 (cyclin D1), BCL-2, BCL-6, c-myc, CD68, CD34, CD117, and MPO, with a high proliferation index (Ki-67) of 80% approximately. The morphology was consistent with diffuse B-cell lymphoma (DLBCL), NOS, and germinal center B-cell subtype involving the kidney. A subsequent bone marrow biopsy revealed involvement by DLBCL ().
His Revised International Prognostic Indicator (R-IPI) was calculated to be 4, NCCN-IPI of 5, and CNS-IPI of 4. Decision was made to offer him dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) to treat his disease. For HIV, he was treated with raltegravir, tenofovir, and emtricitabine, with a subsequent decrease in viral load to our laboratory's threshold for undetectable. This regimen was chosen specifically for the tenofovir to act as prophylaxis to suppress hepatitis B virus reactivation. In addition, he was treated with fluconazole and acyclovir for antimicrobial prophylaxis. He received 3 cycles of chemotherapy and 1 dose of intrathecal methotrexate, with initial improvement in renal lesions. However, after the third cycle, he presented with dysphagia, Bell's palsy, and diffuse bone pain. Neurology service was consulted recommending MRI of the brain without contrast, which was unremarkable. Subsequent CSF flow cytometry was positive for CD10+ B-cells, with a conclusion of DLBCL infiltrating the CNS. Gastroenterology service was consulted, who performed an EGD but found no explanation for dysphagia. ENT service found mucous in the postcricoid region but had no acute interventions to offer, and evaluation by the speech and language pathologist revealed marked pharyngeal dysphagia, with high risk for aspiration.
A repeat CT of the chest without contrast revealed a right pericardial mass with mediastinal lymphadenopathy. At that time, he did not report any chest pain, dyspnea, or cough. His vital signs were remarkable only for sinus tachycardia of 110 beats per minute, and he was normotensive, tolerated room air, and maintained good mentation. A subsequent echocardiogram revealed a large loculated pericardial effusion near the right ventricle, with echocardiographic evidence of tamponade. A large mass could be appreciated in the right atrium in the lateral wall, possibly obstructing the IVC. Cardiac mass size was 2.1 cm × 2.5 cm (). This was concerning for disease recurrence. He was transferred to the coronary care unit for monitoring but did not show any clinical signs of cardiac tamponade. Treatment options were discussed with the patient, who opted for palliative care measures and a transfer to hospice care.
The patient's wishes were followed. A PEG tube was placed for nourishment, and his pain was controlled with opioid analgesics. Plans to transfer him to inpatient hospice care were put in place. Unfortunately, the patient expired before he could be discharged, 5 months following initial diagnosis of DLBCL, and within 3 weeks of pericardial involvement being discovered. His dysphagia never resolved and was likely related to the discovered cardiac mass.


A 23-year-old man presented in 2014 with a white blood cell count of 34 × 109/L with 87% circulating blasts by manual differential count. Flow cytometric analysis on the peripheral blood (PB) revealed 89.6% blasts by CD45/SSC gating. The blasts expressed CD10, CD19, CD34, HLA-DR, and CD20 (dim); partially expressed CD13, CD15, and CD33; and did not express CD2, CD7, CD56, and CD117. A subsequent bone marrow (BM) biopsy was done the next day but was a dry tap; therefore, flow cytometry and other cytogenetic studies were not performed on the BM sample. Immunohistochemistry (IHC) studies were performed on the BM biopsy showing 95% blasts positive for CD79a, PAX-5, and TdT, and negative for CD20 and myeloperoxidase (MPO). The morphology and immunophenotype of the blasts in the peripheral blood and bone marrow biopsy were consistent with B-lineage lymphoblastic leukemia. We did perform FISH analysis with a B-ALL panel on the peripheral blood specimen which revealed CDKN2A (p16 at 9q21) gene deletion on one or both chromosomes 9. Fusion of BCR and ABL1 was not detected. Intensive chemotherapy was initiated according to the CALGB 10403 “Adolescent Young Adult” regimen [], and the patient achieved complete remission. He then proceeded to consolidation without consideration of allogeneic hematopoietic cell transplantation (allo-HCT) based on standard of care for B-cell ALL with favorable cytogenetic and molecular profile.
However, the patient had prolonged cytopenias during consolidation therapy culminating in treatment delay. In early January of 2015 (approximately 24 weeks after initial diagnosis), the patient's complete blood count revealed 27% blasts. Flow cytometry analysis was performed on the PB; the blasts expressed HLA-DR, CD15, CD33, and CD117; partially expressed CD13 and CD56; and did not express CD2, CD3, CD5, CD7, CD10, CD19, CD20, or CD34. A restaging BM biopsy was performed the same day; unfortunately, it was again a dry tap, so flow cytometric analysis could not be performed. The histology examination of the BM biopsy revealed a hypocellular (30%) marrow with 85% recurrent leukemic blasts. IHC showed the blasts were now positive for MPO, while CD10, PAX-5 CD20, CD79a, and TdT were negative. The overall findings on PB and BM biopsy were consistent with a lineage switch to acute myeloid leukemia (AML) (). Although it was a dry tap, a very small amount of aspiration specimen was obtained in the EDTA tube. Despite few marrow spicules on the aspiration smear, cytogenetic analysis and FISH studies were performed. FISH analysis with both B-ALL and AML panels showed persistence of a heterozygous CDKN2A deletion, plus the acquisition of a TP53 deletion, and 7q and 17q duplications. Cytogenetic studies now showed a complex karyotype in 18/20 metaphases, 47,X,-Y,add(1)(p36.1),+18,+add(18)(q23) [12]/47–48,X,−Y,del(1)(p32p36.1),add(11)(p11.2),+18,+18[cp6]/46,XY [].
Intensive salvage chemotherapy was initiated with the MEC regimen [], and nadir BM evaluation was hypocellular without blasts, although FISH demonstrated low-level CDKN2A deletion, consistent with minimal residual disease. Ten days later, a rising PB blast percentage prompted another BM biopsy which showed persistence of AL with the same phenotype and FISH with CDKN2A deletion. Further intensive chemotherapy was initiated, but the patient ultimately died of respiratory failure and refractory AL.


In September 2015, a middle age woman (44 years old) resident from Recife, northeast Brazil, gave birth to a male in a local public hospital. At birth, the neonate had 2580 g, 45.5 cm in length and head circumference of 29.5 cm (suspected case of microcephaly). The child was born after a 38 weeks single-gestation period (full-term), during the first trimester of pregnancy the mother reported a febrile episode followed by headache, joint pain, and rash, the symptoms described did not last more than 3 days and no other symptoms were reported, dengue virus (DENV) IgM serology was negative. At 20 weeks of the gestational age, a prenatal intrauterine ultrasound was performed and the diagnosis was consistent with congenital microcephaly. After birth, during the first month of life, a complete brain imaging examination of the infant evidenced the findings consistent with severe microcephaly, following the protocol of the Brazilian Ministry of Health for Microcephaly Investigation. Brain imaging (magnetic resonance) demonstrated the presence of lissencephaly, decreased brain parenchymal volume, decreased cortical mantle and white matter together with hypoplasia of the corpus callosum. Computed tomography and transfontanellar cranial ultrasound evidenced the presence of multiple brain calcifications, colpocephaly and gliosis in the left cerebellar hemisphere were also documented (Fig. ). Serological tests were performed on the mother (18 days after she gave birth), the results for STORCH laboratory screen (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus), Parvovirus B19 IgM and chikungunya virus (CHIKV) IgM were all negative (Fig. ), no ZIKV serological (ELISA or PRNT50) or molecular tests (rRT-PCR) were performed during pregnancy since these tests were not available at that time, being implemented in Brazil only later in 2016.
Laboratory STORCH tests were also performed in the child with 1 month of life, the results were all negative, including chikungunya IgM and anti-Epstein-Barr virus (EBV) IgM (Fig. ). No Zika virus serology or molecular tests were performed on the child and no samples were stored for later investigations. After 1 month of life, a detailed neurological examination in the infant evidenced upper and lower limb spasticity (mainly on upper limbs), extreme irritability, continuous cry and head circumference measurement of 31 cm was consistent with severe microcephaly (< 3 SD on the Fenton growth chart).
With approximately 6 months of life, the child was admitted to a local hospital after presenting several recurrent seizure episodes. Electroencephalographic (EEG) examination evidenced the presence of focal frontal epileptiform discharges. At the hospital, a blood and a cerebrospinal fluid (CSF) samples were collected. Laboratory results of serum and CSF confirmed the presence of ZIKV viral RNA on both samples, analyzed by rRT-PCR following a well-established laboratory protocol []. Additionally, rRT-PCR for chikungunya (CHIKV) and ELISA tests were all negative in serum and CSF as follows anti-ZIKV IgM, anti-DENV I, M and IgG, anti-CHIKV IgM and IgG (Fig. ). To confirm ZIKV infection a plaque reduction neutralization test (PRNT50) was performed from the CSF sample, a ZIKV positive neutralization titer of 99 confirmed the previous infection, no neutralizing DENV antibody titers were observed (Table and Fig. ).
The interesting presence of ZIKV RNA previously identified at 6 months of life prompted us to investigate ZIKV persistence in a second sample collected with the age of 1 year and 5 months (here denominated 17 months for a better understanding). Given the risk of an invasive lumbar puncture, only a blood sample was collected from the child following a regular visit to the pediatrician, on the same occasion, a blood sample from the mother was also requested. On child serum, after 17 months of life, ZIKV rRT-PCR was still positive. Serology was negative for the tested arboviruses as follows anti-ZIKV IgM, anti-DENV IgM and IgG, anti-CHIKV IgM and IgG (Fig. ). A plaque reduction neutralization test (PRNT50) was again performed on child serum, ZIKV positive neutralization dilution titer of 527.9 reinforced our previous result of ZIKV infection, and again no neutralizing DENV antibody titers were observed. Moreover, the presence of a high titer of ZIKV neutralization antibodies (titer of 972) on mother’s serum confirms Zika virus infection (Table and Fig. ). On mother’s serum the presence of positive DENV neutralization titer is not surprisingly since dengue virus is endemic in Brazil, especially in the northeast region.
It’s intriguing the presence of ZIKV RNA for such a long time and since samples were stored with RNA preservative solution viral isolation was not attempted. Thus, to further confirm the presence of ZIKV on child CSF and serum we performed genome sequencing direct from blood and CSF positive samples, employing a previously published protocol []. We obtained two partial ZIKV genomes from samples CSF-six-months and serum-17-months of 6653 and 5292 base pairs, respectively, corresponding to 60.6 and 48.9% of genomic coverage (Fig. ). Phylogenetic analysis showed that these two draft genomes belong to the Asian genotype and clustered closely with a ZIKV isolate from Paraíba/Brazil (Fig. ), located around 120 km from where the mother gave birth. Since six-months-CSF sample differs from Paraiba_01 ZIKV strain by two single nucleotide polymorphisms (SNPs) in the envelope gene (E) and serum-17-months sample differs from Paraíba_01 by three SNPs, these results are consistent with a single ZIKV infecting strain. The child is being followed in a local hospital. Clinical evolution consists mainly in delayed neuropsychomotor development, dysphagia (difficulty swallowing), visual impairment, and double spastic hemiplegia. Treatment consists of clobazam (antiepileptic drug). After almost 2 years of life, the child presents controlled structural epilepsy.
CSF and blood were collected through standard procedures. Anti-dengue and anti-chikungunya virus IgM and IgG antibodies were detected by commercially available capture ELISA kits (Anti-Dengue Virus ELISA IgM/IgG and Anti-CHIKV IgM/IgG from EuroImmun AG, Luebeck - Germany), following manufacturers instructions. Serotype-specific anti-DENV and anti-Zika antibodies were assessed by plaque reduction neutralization test (PRNT). The antibody titer was determined as the serum dilution that inhibited 50% of the tested virus inoculum (PRNT50). Anti-Zika IgM antibodies were detected by Capture Enzyme-Linked Immunosorbent Assay (MAC-ELISA). Viral RNA was extracted by the use of a QIAamp Viral RNA kit (Qiagen, Hilden - Germany), following manufacturers instructions and rRT-qPCR reactions were performed from purified RNA serum samples accordingly to Lanciotti et al.[], with modifications. Briefly, reactions were performed with the kit GoTaq® Probe 1-Step RT-qPCR System (Promega, Fitchburg, USA) in a 20 μl final volume, primers and probes employed were as follows: Zika 1087 5’-CCGCTGCCCAACACAAG-3′, Zika1163c 5’-CCACTAACGTTCTTTTGCAGACAT-3′ and Zika 1087 VIC (probe) 5’-AGCCTACCTTGACAAGCAGTCAGACACTCAA-3′. Samples with a Ct value < 38 in duplicate wells were considered to be positive for ZIKV. For sequencing, total RNA extracted as above was converted to cDNA and amplified, PCR products were then quantified and libraries were prepared with Nextera XT Library Prep Kit (Illumina, San Diego - USA), MiSeq Reagent Kit V3 of 150 cycles was used to sequence employing a paired-end strategy. Mapped reads were visualized and majority rule consensus genomes were extracted with Integrated Genome Viewer (IGV) and carefully checked on the mapping results. Phylogenetic reconstruction was performed on an alignment of the coding region of all ZIKV genomes available by maximum likelihood. All sequences were aligned with Mafft v 7.


An 80-year-old Arabian female presented to our hospital with a 2–month history of swelling over the right eyebrow, pain, proptosis of the right eye and diplopia (Fig. ). Physical examination revealed a 2 cm ill-defined painful mass over the right eyebrow. The patient complains of double vision looking to the left. Computed tomography (CT) of the right orbit demonstrated an ill-defined, homogeneous, contrast-enhancing mass attached to the medial rectus. As a space-occupying orbital lesion, a lymphoma or a sarcoma was suspected. As a result, a biopsy was performed. On microscopic examination, the tumour was composed of interlacing bundles of spindle cells with anisokaryosis and hyperchromatic nuclei (Fig. ). Some mitotic figures were observed. Immunohistochemical study was not possible because neoplastic material has been exhausted. The conclusion was malignant spindle cells tumour, most consistently to sarcoma or sarcomatoid carcinoma. No lymph node or distant metastases were found. Subsequently, total exenteration of the right orbit was performed under general anaesthesia. Dilute adrenaline was injected to lessen bleeding generally abundant in this type of excision. Periosteum was incised right around the orbital rim and separated from the bone passing back towards the orbital apex. The eyeball, eyelids, appendages of the eye and periosteum were removed. Surgical specimen was addressed for pathological examination. At gross examination, the tumour appeared ill-defined, whitish and firm. It measured 4/2.5/1.5 cm. It was attached to the sclera without infiltration into eyeball. It infiltrated the upper eyelid (Fig. ). Microscopic examination revealed spindle cells forming disorganized fascicles. They have an irregular nucleus with vesicular chromatin and an eosinophilic cytoplasm. The mitotic index was 18 per 10 high-power fields. Adipose tissue and striated muscle infiltration was observed (Fig. ). Immunohistochemical panel used for initial work up of this high grade spindle cell neoplasm was desmin, smooth muscle actin (SMA), pancytokeratin AE1/AE3, epithelial membrane antigen (EMA), S100 protein and CD34. This panel served to rule out first leiomyosarcoma, rhabdomyosarcoma, sarcomatoid carcinoma and spindle cell melanoma. It revealed diffuse positive staining for pancytokeratin AE1/AE3, EMA and SMA and focal positivity for S100 protein (Fig. ). The lesion was immunonegative for desmin and CD34 (Fig. ). As pancytokeratin AE1/AE3, EMA, SMA and S100 protein staining was positive, we completed by second panel. It showed h-cladesmon, Melan-A and HMB-45 negative staining. These pathological and immunohistochemical findings suggested the diagnoses of myoepithelioma, epithelial myoepithelial carcinoma and myoepithelial carcinoma. Myoepithelioma was excluded because the tumour borders were infiltrative. Epithelial myoepithelial carcinoma is by definition composed of a biphasic arrangement of inner luminal ductal cells and outer myoepitheliaI cells. However, the tumour did not show bi-layered duct-like structures. The most appropriate diagnosis was myoepithelial carcinoma. The tumour was extending to upper and posterior surgical margins. Radiotherapy was then indicated. The patient was lost to follow-up until she developed local tumour progression 3 months after removal. The patient was again lost to follow-up and therefore did not receive any other treatment in our hospital.