A 3-year-old boy was admitted to Red Cross War Memorial Children's Hospital, Cape Town, South Africa, with acute gastroenteritis, pneumonia and herpes gingivostomatitis. Six months earlier, HIV infection was diagnosed at a primary health care clinic. Antiretroviral therapy (ART) was not initiated despite it being indicated for such patients by the South African ART guidelines. He was stunted (height 85 cm, height–age z-score – 3) but not wasted (weight 12.6 kg, weight-for-height z-score +1 [2006 WHO Child Growth Standards]). Blood results on admission showed a normocytic anaemia (haemoglobin 6.8 g/dL, reference range 10.7–13.1) and leucopaenia (white cell count [WCC] 2.71 × 109/L, reference range 6–18). The differential WCC showed that neutropaenia (1.22 × 109/L, reference range 2–5.5) and lymphopaenia (1.49 × 109/L, reference range 3.6–12) were present. A chest radiograph showed features of a bilateral pneumonia (), for which he was commenced on ampicillin and gentamicin, and acyclovir, for the pneumonia and herpes gingivostomatitis, respectively. No supplemental oxygen therapy was required at admission and empiric treatment for Pneumocystis jirovecii pneumonia was not initiated. However, cotrimoxazole prophylaxis was commenced on admission.
He experienced high fevers, peaking at 40 °C. On day 6 of admission, he developed diffuse abdominal tenderness and a generalised erythematous maculopapular exanthem. Liver function tests (LFTs) showed normal total bilirubin (2 µmol/L, ref. range 0–21) and alkaline phosphatase (ALP 268 U/L, ref. range 104–345) concentrations, and elevated γ-glutamyl transferase (GGT 120 U/L, ref. range 3–22), alanine transaminase (ALT 223 U/L, ref. range 5–30) and aspartate transaminase (AST 1304 U/L, ref. range 0–56) concentrations. The C-reactive protein (CRP) was 58.2 mg/L (reference range 0.1–7.5). Owing to the persistent fever, antimicrobial therapy was changed to ertapenem and fluconazole for presumed hospital-acquired infection. There was no growth on blood culture after 5 days of incubation, and a urine culture yielded mixed bacterial growth. Tuberculin skin testing (Mantoux method) and Xpert MTB/RIF (Cepheid, Inc., Sunnyvale, CA, USA) on induced sputum specimens were negative. Two days later, he had generalised tonic clonic seizures for which he received an intravenous loading dose of phenobarbitone. The antibiotic was empirically changed to meropenem for possible hospital-acquired meningitis. A cerebrospinal fluid specimen was bloodstained but there was no bacterial growth, and polymerase chain reaction (PCR) assays for entero- and herpesviruses were negative.
The fever and maculopapular rash persisted. Repeat CRP (88.4 mg/L), procalcitonin (5.3 µg/L, reference range 0.0–0.5), ferritin (91 705 µg/L, reference range 20–200) and triglyceride concentrations (4.7 mmol/L, reference range 0.3–1.1) were elevated. The differential diagnosis included haemophagocytic lymphohistiocytosis (HLH), disseminated tuberculosis and invasive fungal infection. The patient subsequently developed respiratory distress requiring supplemental nasal prong oxygen therapy. Repeat chest radiography was unchanged from admission with features not suggestive of tuberculosis or fungal infection. He was given packed red blood cell, platelet and cryoprecipitate transfusions for severe anaemia (Hb 5.6 g/dL), thrombocytopaenia (platelet count 52 × 109/L) and hypofibrinogenaemia (fibrinogen concentration 1.0 g/L, reference range 1.7 g/L – 4.0 g/L), respectively.
Skin and bone marrow biopsies were performed on day 10 in hospital. Skin histology showed extensive karyorrhexis and numerous dermal histiocytes containing cytoplasmic small fungal organisms. Grocott and Periodic acid–Schiff stains were positive and suggestive of dermal histoplasmosis (). Skin culture did not grow fungi or mycobacteria. Bone marrow histology revealed histiocytosis and haemophagocytosis consistent with a diagnosis of HLH. Fungal stains showed scanty structures 1.5 µm × 2.5 µm in diameter and morphologically compatible with Histoplasma capsulatum. A diagnosis of disseminated fungal infection with secondary HLH was made and intravenous amphotericin B deoxycholate 1 mg/kg/day commenced 14 days later.
Culture of the bone marrow aspirate in a BACTEC MycoF/lytic bottle (Becton Dickinson, New Jersey) flagged positive after 17.6 days of incubation, and small yeasts were seen on Gram stain. The isolate was submitted to the National Institute for Communicable Diseases for further identification. The fungus was converted from the mycelial to yeast phase on brain heart infusion agar with 5% sheep blood (Diagnostic Media Products, Sandringham) at 35 °C and morphologically characterised based on DNA sequencing of the internal transcribed spacer region of the isolate's ribosomal gene. The isolate was identified as the thermally dimorphic fungus Emmonsia species. The DNA sequence was the same as those of previously described isolates of a novel Emmonsia species. An investigational urine Histoplasma antigen test (ImmunoMycologics, Norman, OK) was negative.
ART, comprising abacavir, lamivudine and efavirenz, was commenced 3 days before amphotericin B was started. The LFT concentrations had marginally improved at this stage with an ALT of 156 U/L, AST 560 U/L and GGT 102 U/L. The baseline CD4+ T-cell count (percentage) was 12 × 106/L (0.45%) and HIV-1 viral load 2 149 305 RNA copies/mL. After ART and amphotericin B were commenced, he made a remarkable recovery. Within 3 days, supplemental oxygen was discontinued and, after 5 days, the skin lesions and fever had resolved. The abdominal tenderness and abnormal LFTs resolved on day 11 and 12 of amphotericin B, respectively.
Daily amphotericin B was continued for 6 weeks via a central venous catheter. Adverse effects were minimised through pre-emptive hydration before amphotericin B infusions, close monitoring of renal function, potassium and magnesium concentrations and, where necessary, electrolyte replacement. Itraconazole 100 mg daily orally was commenced once amphotericin B had been discontinued. Because of its potential for reducing the bioavailability of itraconazole, efavirenz was replaced with a lopinavir/ritonavir co-formulation. Six months after commencing ART, the patient was well, virologically suppressed (HIV-1 viral load < 40 RNA copies/mL), had a CD4+ T-cell (percentage) of 884 × 106 cells/L (17.9%) and normal LFTs. At last evaluation, there was no clinical evidence of active fungal infection. The intention is to maintain him on itraconazole for a minimum of 12 months and until his CD4 count reaches 25%, before considering discontinuation of antifungal therapy.


A previously healthy 35-year-old Swiss woman presented with fever, headache, and myalgia for three days. Symptoms began on the final day of travel in Colombia. Abdominal examination revealed a positive Murphy sign. Laboratory results at presentation are shown in . Abnormal findings included a thrombocytopenia (121,000/mm3), an elevated total bilirubin (48 μmol/liter), and high alkaline phosphatase (163 U/liter). Abdominal ultrasound showed signs of an acute acalculous cholecystitis (AAC) ().
At presentation, chest radiography showed no abnormalities (). On the third day of hospitalization, however, the patient developed a cough, dyspnea, and hypoxemia. A second chest radiography revealed a left-sided infiltrate (). Her traveling companion was admitted to the hospital with identical symptoms, including an AAC and development of pneumonia. What is your diagnosis?


A 72-year-old woman underwent esophagogastroduodenoscopy for the first time in her life, as part of a general health check-up. An endoscopic examination revealed a 16-mm submucosal tumor on the greater curvature of the gastric body on a background of chronic atrophic gastritis due to Helicobacter pylori infection. The tumor had a smooth surface with a central depression and a small erosion on top (Fig. a, b). An abdominal contrast-enhanced computed tomography (CT) scan demonstrated a 16-mm diameter low-attenuated tumor in the greater curvature of the stomach with slow enhancement (Fig. ). A CT scan of the abdomen and pelvis did not reveal any evidence of metastatic lesions. Endoscopic ultrasonography was not performed. Histological evaluation of the biopsy specimen revealed proliferation of small uniform cuboidal cells. The nuclei were monomorphic with inconspicuous nucleoli and cytoplasm was abundant. Immunostaining revealed that the tumor cells were positive for chromogranin A, synaptophysin, and CD56. The Ki-67 labeling index was < 2%. Therefore, based on the diagnosis of Grade 1 NET, laparoscopic and endoscopic cooperative surgery was performed. On gross examination, the mucosal aspect appeared slightly protuberant. An intramural, nodular solid mass measuring 16 × 12 × 6 mm was noted. Histological examination of the resected specimen revealed a cellular tumor primarily situated in the submucosa. The overlying mucosa was largely intact (Fig. a), except for a focal area where it was breached by the tumor. The mucosal surface showed focal ulceration. The tumor growth had a solid, nested, trabecular, and pseudoglandular pattern with delicate capillaries (Fig. b). There was minimal cellular pleomorphism. Mitotic counts were < 1 for each 10× high-power field. Tumor necrosis was not present. Aberrant exocrine acini were barely detected in the peripheral zone of the main tumor and in a duct penetrating the center of the tumor (Fig. c, d). Peripheral acinar cells were positive for trypsin (Fig. e). Although there were no islands of Langerhans, large duct and acini indicated the presence of ectopic pancreatic tissue. Ductular cells were negative for both neuroendocrine marker and trypsin. Immunohistochemical examination revealed that the tumor cells were positive for the neuroendocrine markers chromogranin A and synaptophysin and negative for gastrin, glucagon, somatostatin, VIP, insulin, and serotonin. The Ki-67 labeling index was 0.61%. These morphological features were typical of a well-differentiated Grade 1 NET. Adjacent gastric epithelium did not show evidence of endocrine cell hyperplasia.


A 64-year-old man was admitted to an outside hospital 6 months prior with a brain abscess and underwent surgery. He experienced recurrent epistaxis and was on anticoagulation therapy for chronic atrial fibrillation. During follow-up, he developed dyspnea, and chest CT showed a left-sided pleural effusion (Fig. a). Chest drainage revealed the collection to be a hemothorax, and the patient was referred to our hospital. Laboratory data showed slight anemia with a hemoglobin of 9.4 g/dl. Pulmonary function tests were within normal range. Chest CT after drainage revealed a solitary 15-mm nodule in the periphery of the left lower lobe, and identification of a feeding artery and draining vein on three-dimensional CT (3DCT) suggested that the node was a PAVM (Fig. b, c). The PAVM was adjacent to the diaphragm, and multi-detector CT (MDCT) and 3DCT demonstrated that the peripheral nodule slightly displaced the diaphragm, with the nodule protruding into the pleural cavity (Fig. ). After multidisciplinary conference, we believed that surgical therapy might be preferable to catheter embolization for the following reasons. Firstly, the patient had already developed a brain abscess and hemothorax, so definitive treatment without a chance for recurrence was paramount. The second reason was that the PAVM was a solitary, small nodule located in the periphery of the lung, with MDCT and 3DCT indicating that the nodule might be in close proximity to the visceral pleura protruding into the pleural cavity, making minimally invasive wedge resection straightforward.
The patient was placed in the right lateral decubitus position, and VATS with three ports was performed. The maximum incision length was 15 mm. The PAVM protruded from the periphery of the lung like a polyp, and wedge resection was easily performed after simple adhesiolysis (Fig. ). There were no complications, and the patient remained asymptomatic after 1-year of follow-up.


A 36-year-old woman who emigrated from the Ecuador in 2002 presented to the emergency department with a one-year history of intermittent abdominal pain, diarrhea, and a 70-pound weight loss. She had no reported medical history, recent travel outside of the US, or known sick contacts. She appeared cachectic with diffuse muscle wasting and had a body mass index (BMI) of 14. Initial labs were notable for a white blood cell count 4.5 k/mm3, hemoglobin 8.8 g/dL, iron 17 mcg/dL, TIBC 47 mcg/dL, ferritin 123 μg/L, C-reactive protein 9.4 mg/dL, HIV negative, anti-nuclear antibody screen negative, anti-myeloperoxidase antibody negative, anti-perinuclear-3-antibody negative, and albumin 1.8 g/dL. Computed tomography (CT) of the chest and abdomen showed several right-sided pulmonary nodules, a large left-sided pleural effusion, and diffuse small and large bowel wall thickening with enlarged mesenteric lymph nodes. EGD revealed atrophic mucosa throughout the stomach and proximal duodenum. Esophageal, gastric, and duodenal biopsies were unrevealing. Colonoscopy showed circumferential friable ulcerated mucosa in the descending colon (). The colonoscope was not advanced beyond this area. Biopsies showed necrotic tissue that was negative for acid-fast bacilli (AFB). Extensive autoimmune and infectious workup was unrevealing. Mycobacterium tuberculosis (MTB) polymerase chain reaction from an induced sputum sample was positive. Stool culture was positive for acid-fast bacilli. Soon after antituberculin therapy was initiated she developed a large bowel obstruction with segmental colitis and strictures at multiple areas including the splenic and hepatic flexures as seen on CT scan (Figures and ), and she required a subtotal colectomy with end-ileostomy. Pathology of the resected colon showed confluent necrotizing granulomatous inflammation with transmural colonic wall involvement and stricture at the splenic flexure, as well as necrotizing granulomas of the surrounding lymph nodes, consistent with tuberculosis (Figures and ). There was no inflammation or pathology in the terminal ileum. She was continued on antituberculin therapy and was discharged to a rehabilitation facility with improvement in her symptoms and malnutrition.


An 83-year-old female was referred to gastroenterologist by a cardiologist for a determination of her bleeding risk in the context of possible anticoagulation for atrial fibrillation. Her past medical history includedatrial fibrillation (not on anticoagulation or aspirin due to prior history of a gastrointestinal (GI) bleed), chronic obstructive pulmonary disease, pulmonary hypertension, chronic heart failure, and non-Hodgkin's lymphoma treated with chemotherapy twenty-two years earlier. The patient had been taking Xarelto for atrial fibrillation, but following an episode of gastrointestinal bleeding two years prior, the patient’s Xarelto was discontinued.
A cardiologist had recently evaluated the patient for atrial fibrillation and consulted gastroenterologist to determine the patient’s risk for GI bleeding before restarting anticoagulation therapy. The patient was noted to have normocytic, normochromic anemia with hemoglobin of 10 gm/dL and mean corpuscular volume of 82; however, additional findings were not consistent with iron deficiency anemia. As a result, the patient received a diagnostic endoscopy and colonoscopy to evaluate for any high-risk lesions. The endoscopy discovered patchy erythematous antral gastropathy and mucosal changes in the stomach and the duodenum that resembled melanosis gastri () and duodeni (). Pathology report of this stomach and duodenal biopsy ultimately determined that the specimen had normal villous architecture without diagnostic abnormality.
The colonoscopy also revealed severe diverticulosis and luminal distortion, to the extent that the scope could not be advanced safely beyond the distal descending colon, as well as non-bleeding small internal hemorrhoids. The patient was instructed to avoid NSAIDS and consume a high-fiber diet. Upon follow-up visit, she had no complaints but decided against receiving anticoagulation therapy due to a risk of bleeding.


A woman in her 40s, presented to the emergency department with complains of nausea, vomiting, and dizziness for the last 2 days. She was experiencing non-bilious, non-bloody, and non-projectile vomiting associated with diffuse abdominal pain and non-bloody watery diarrhea. Patient reported subjective fever associated with rigors and chills but denied diurnal variation, any sick contacts, uncooked/stale food consumption, recent travels, or any urinary symptoms. Her comorbid conditions included human immunodeficiency virus (HIV) infection with a recent CD4+ count of 810 cells/μL (acquired through unknown source, compliant on antiretroviral therapy), subclinical hypothyroidism, hypertension, and diabetes mellitus. She had tubal ligation done 5 years ago and did not report any family history of cancers, heart, or lung diseases. She was non-smoker, non-alcoholic, and had never used recreational drugs or herbal medications. She worked as a home attendant and had 3 children, lived in United States for the past 15 years with last travel to Africa 6 years ago.
On presentation to the emergency department, patient was found to be febrile with a temperature of 38 °C (Fig. ), tachycardia of 112 beats/min, blood pressure of 125/75 mmHg, and an oxygen saturation of 100% on room air. She was lethargic but alert and oriented and not in an acute distress. Cardiovascular exam was unremarkable except for tachycardia. Rest of the physical examination was unremarkable. Initial laboratory findings are shown in Tables and . Patient was started on intravenous fluids and intravenous antibiotics for suspected acute cholangitis. Computed tomography (CT) scan of the abdomen was performed to discern cause of sepsis, results of which were inconclusive. Advance imaging including magnetic resonance cholangiopancreatography (MRCP) was negative for any intrahepatic, biliary, or pancreatic ductal pathology. She continued to have persistent fevers despite sufficient antibiotics, and all cultures remained negative. Her liver function tests normalized within 3 days, without any intervention. Extensive work up for fever including testing for legionella, mycoplasma, leptospirosis, herpes simplex, Cytomegalovirus (CMV), strongyloides, stool ova and parasites were negative.
On day 7 of Intensive Care Unit (ICU) stay, patient became tachypneic and hypotensive, with oxygen saturation dropping to 88%. She was started on supplemental oxygen via nasal cannula and a bedside goal-directed echocardiography was performed by the ICU team. Echocardiography was significant for a right ventricular strain pattern. An emergent CT angiogram of the chest was done, eliciting a large saddle embolus (Fig. ). Ultrasound of the lower extremities showed right sided superficial femoral and popliteal vein deep vein thrombosis (DVT). Intravenous tissue plasminogen activator (t-PA) was administered and later the patient was started on intravenous heparin infusion. On day 9, Gallium scan was done (Fig. ) that showed uptake exclusively in the lungs, and confirmed suspicion of pulmonary embolism as the sole cause of her fever. All antibiotics were discontinued and patient eventually became afebrile on day 11 of ICU stay (3 days after initiation of anticoagulation). She was observed for continued stability and transferred to the floor for further care.


An 83-year-old male patient came to the Department of Hand and Reconstructive Surgery of the People's Hospital (Zhejiang Province, China) complaining of mild pain and swelling, and upon inspection a mass was found in his left upper abdomen. This mass had been slowly increasing in size for 2 years. Two years ago, the patient had undergone an operation to remove an abdominal soft tissue fibrosarcoma. The local general surgeon had used a mesh to repair the peritoneal defect and to close the abdominal wall directly. Unfortunately, the incision did not heal due to infection, and the mesh was soon taken out by operation. The incision resulted in a draining wound, and bacterial cultures eventually showed that the wound had a methicillin-resistant Staphylococcus aureus infection. The patient repeatedly came to the clinic to have his bandage replaced, but the masses in his abdomen gradually increased in size. The patient was referred to the Hand Department, and while laboratory tests were normal, further examination by computed tomography imaging revealed that the tumor had recurred, and that the patient also had a hernia in the upper abdomen along with the infected wound. Considering the patient's condition, the main purpose of the operation was to resect the tumor and treat the hernia. The surgical procedure was designed to resect the recurrent tumor using a left upper abdomen approach under general anesthesia, but a very large (15 × 8 cm) abdominal wall defect was found on peritoneum, which could not be directly sutured (Fig. ). In this case there was no obvious skin defect. Because of this defect, a right upper abdominal lateral approach for the operation was planned. The operation was planned to include a vascularized partial 9 to 10 ribs-pleural transfer (without a thoracic umbilical flap) by the vessel pedicle of the deep inferior epigastric artery (DIEA). The vascularized partial 9 to 10 ribs-pleural transfer material was first harvested so that it was connected only by the artery pedicle (Fig. ).
The vascularized partial 9 to 10 ribs-pleural transfer was translocated to the left abdominal wall defect site via subcutaneous tunnel. The composite tissue was used to fill in the abdominal wall defect (Fig. ). First, we sutured the broken peritoneum to the pleura, and then sutured the intercostal muscles to the abdominal muscles. Next, we closed the skin and the abdominal wall defect. Examinations after the surgery revealed that the right lung was not harmed. The right rib donor was wired closed using 1 mm steel wire, and the muscles, subcutaneous tissue, and skin were all sutured directly.
Three days after the surgery, the patient's basal temperature returned to normal and he began to eat a full liquid diet. Six days after the surgery, we pulled out a subcutaneous drainage tube and the patient was able to eat half liquid diet. The patient had been given an infusion of Claforan for 1 week (4 g every 12 h; North China Pharmaceutical Co. Ltd, China). Ten days after the surgery, we removed the abdominal cavity drainage tube and the patient had recovered to the point where he could eat a normal diet. Two weeks after the surgery the incision healed, sutures were removed, and the patient was discharged. One year after the surgery, no masses in his abdomen were evident, and magnetic resonance imaging scans revealed no evidence of tumor recurrence. The patient also reported no abdominal pain or swelling symptoms. The patients’ diet and breathing were normal and the patient was then able to be able to resume his daily activities. Nevertheless, we continued to observe and follow up with the patient (Fig. ).
These study protocols were approved by the medical ethics committee of the Zhejiang Provincial People's Hospital. Written informed consent for publication of clinical details and images was obtained from the patient. A copy of the consent form is available for review upon request.


A 45 year old Sri Lankan man presented to us with a 2 day history of fever, head ache, arthralgia, myalgia especially affecting the lower limbs and lower abdominal pain. In addition he had vomiting and passing of dark colored urine for one day. He said that there was an apparent reduction of volume of urine he passed. The day before he had taken treatment from a general practitioner and has been on oral amoxicillin, paracetamol (acetaminophen) and vitamin B complex tablets since then. As his symptoms got aggravated he was admitted to our hospital.
He is used to standing bare footed at the mouth of a large urban drain (polluted with animal excreta) discharging into a stream after the rains and catching fish because he noticed the fish of the stream concentrating there to eat matter flushed along the drain. The last time he did this was 6 days before admission. That indicates his exposure to leptospirosis. His past medical history and the family history were unremarkable except that there was a history of an allergic reaction to an unidentified agent 2 decades ago that needed hospitalization.
Upon examination there was a mild pallor and icterus but no conjunctival suffusion, no fever. His pulse rate was 88/min, blood pressure was 120/80 mm mercury, his lungs were clear to auscultation and his liver was felt 1 cm below the right costal margin. The results of his central nervous system examination were normal. There was neutrophilic leucocytosis. Leptospirosis was diagnosed and intravenous ceftriaxone and supportive therapy was initiated.
Upon the second assessment the patient was very pale and a sample of urine from him indicated hemoglobinuria as shown in Fig. .
Further details were asked and he revealed that he had eaten cooked leaves of Kuppameniya (Acalypha indica) 1 day before the onset of fever, but denied any diagnosed hematological disease affecting his brother or relatives from the maternal side of his family. He did not know about any illness during his neonatal period.
Hence we started a workup for the possibility of hemolytic anemia as well. Table summarizes his laboratory investigation results.
He denied ingestion of other drugs or food that may induce hemolysis. A hemolytic crisis triggered by Acalypha indica in a G6PD deficient person was diagnosed, antibiotic was stopped. Blood transfusions were given (700 ml packed cells during the day 3, 350 ml each on day 4 and day 6). A consultant hematologist’s opinion obtained. After his symptoms subsided on the fifth day after admission, he was sent home on ferrous sulfate 400 mg and ascorbic acid 100 mg thrice daily, folic acid 1 mg daily supplements with a list of drugs to be avoided. Reticular cell count was repeated 6 weeks after discharge. It has returned to normal (0.5%). Patient was again referred to the hematologist, a positive Brewer’s test confirmed the diagnosis. Brewer’s test [] is the only test available at Sri Lankan state hospitals like ours for confirmation of G6PD deficiency []. Later a G6PD qualitative reflex quantitative estimation was performed and level was 2.0 U/g Hb (reference range 4.60–13.5) and that further confirmed the diagnosis.


A 49-year-old Hispanic male with a past medical history of SCZ presented to the emergency room because of auditory hallucinations and aggressive behavior. The patient was admitted to the psychiatric unit with the chief complaint of a female voice telling him to hurt someone, seeing people hurting each other, and also because he couldn’t sleep well. Upon admission, his behavioral assessment findings were paranoia, withdrawal, depression, anxiety, auditory and visual hallucinations; he described seeing a woman stabbed to death by another woman at the assisted living facility where he resided, as well as seeing ghosts and a deity at his feet. During acute stay, the pharmacological agents administered upon admission were Risperdal 3 mg orally twice a day, haloperidol 5 mg/mL IM injection as needed, lorazepam 2 mg/mL IM injection as needed, and citalopram 40 mg orally daily.
In the inpatient unit, a monitoring biosignal device, a heart/respiration rate monitor (Zephyr Biopatch, Annapolis, MD) was placed on the chest of the patient overnight and the following day in the morning but removed at around 9:00 am. Thereafter, the physiological monitoring was repeated for two more consecutive days. Clinical improvement was observed on Day 2 after medication treatment began; the patient was cooperative and denied hallucinations and homicidal ideations. His attention, thought content, insight, and judgment also improved; however, his thought process was linear with a slow flow of thought.
For HRV, R-R intervals obtained on the monitoring device were subsequently analyzed using Kubios HRV® (Kubios, Kuopio, Finland) (see Figure ).
The time series between the times of 9:00 p.m. to 3:00 a.m. (~five hours duration for each day) results showed that the HRV basic heart rate (HR, meanNN = mean value of NN intervals) did not change over time, Day 2 showed the most prominent change in HRV (increased). Day 3 showed partly higher values of HRV in comparison to Day 1; in general, the variability standard deviation of normal R-R-intervals (sdNN) increased over time from Day 1 to Day 3, with the strongest reaction at Day 2 (Day 1 = 0.06 ms; Day 2 = 0.12 ms; Day 3 = 0.11 ms). With regard to respiration, the respiration mean rate (meanNN) did not change over time; respiratory variability (RESPV; sdNN) increased over time from Day 1 to Day 3 (day 1 = 0.10 ms; Day 2 = 0.18 ms; Day 3 = 0.19 ms). In CRC (normalized short time partial directed coherence (NSTPDC), 120 samples window length) the influence of heart rate (BBI) on respiration (RESP) increased from Day 1 to Day 3 (Area_BBI→RESP : Day 1 = 0.05; Day 2 = 0.08; Day 3 = 0.10) and the influence of RESP on BBI decreased from Day 1 to Day 3 (Area_RESP→BBI: Day 1=0.23; Day 2=0.18; Day 3=0.13). Considering the coupling direction, the normalized factor (NF) values showed an increase from Day 1 to Day 3. Day 1 (NF~ -1.3) pointed to a bidirectional coupling, with a driver-responder relationship from RESP→BBI, Day Two (NF~-0.8) pointed to a weak bidirectional coupling with a driver-responder relationship from RESP→BBI, and Day 3 (NF~-0.34) pointed to an equal influence in both directions (see Figure ) suggesting a more balanced autonomic cardiorespiratory modulation in response to the antipsychotic treatment where respiration still acts as the driver (respiratory sinus arrhythmia). The HRV analysis showed an increased variability and improved cardiovagal modulation over time (from Day 1 to Day 3), with strongest reaction at Day 2.
The respiration analysis showed an increased respiratory variability over time (from Day 1 to Day 3) suggesting improved autonomic modulation in response to the pharmacotherapy. The CRC showed that the influence of heart rate on respiration increased from Day 1 to Day 3. The numeric sequence test, used for testing attention, was '4' (higher values are associated with better attention) during Day 1. The attention span increased during Day 2 and Day 3 with scores of '8' and '9', respectively. Upon discharge on Day 4, improvement was observed in the patient's general psychiatric condition; he was calm, cooperative, and denied visual and auditory hallucinations.


The patient was a 52-year-old Italian woman with consanguineous healthy parents. Her medical history revealed recurrent headaches since puberty () and three previous acute episodes of altered consciousness, which resolved spontaneously. Two acute crises occurred at 20 and 24 years of age, both in postpartum periods on the fourth day after delivery, when the patient manifested psychomotor agitation, anxiety, and confusion. During the first episode, she also experienced severe visual impairment, accompanied by confusion and anxiety in the few hours after she was discharged from the Maternity Unit. For 10 days, she showed behaviour and mood changes and required sedation. After a 20-day hospitalization, a diagnosis of postpartum psychosis was made. During the second postpartum crisis, symptoms included disorientation, confusion, and mydriasis, causing a new 10-day hospital admission.
The third crisis occurred at 51 years of age when the patient suddenly became confused. She was admitted to the Emergency Department because of marked coordination difficulties, disorientation, and anxiety. Within a few hours, she also experienced severe headache, nausea, and vomiting. Video electroencephalogram (EEG) monitoring showed bilateral frontal epileptiform and slow activity. Brain MRI showed hyperintensities in the cortical frontal regions. A CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; OMIM #125310) was suspected but NOTCH3 gene testing was negative. Neurological and behavioural abnormalities spontaneously disappeared after a few days.
At 52 years of age she was admitted to the Neurology Unit with clinical features similar to the last episode. Her husband reported that she performed repetitive and senseless actions, such as undressing and dressing again or opening and closing the dishwasher. This crisis was preceded by a period of insomnia, severe headaches, low caloric intake, and dehydration. She reported she had never enjoyed meat and self-selected a low protein diet. Ammonia level on admission was 45 µmol/L (normal values:(n.v.) 11–32), but rapidly increased to a maximum of 330 µmol/L. EEG showed abnormalities which were consistent with non-convulsive status epilepticus. During the hospitalization, hyperammonemia associated with confusion, psychomotor agitation (i.e., echolalia and motor stereotypies), nausea, and vomiting was detected several times, mainly in the evening. Suspecting a UCD, protein intake was stopped and glucose intravenous infusion and oral supplementation with l-arginine (195 mg/kg/day) were started. Subsequently a low protein diet was introduced. Unfortunately, metabolic investigations were performed on samples collected after the initiation of arginine therapy and were inconclusive (). The patient’s clinical status gradually improved with normalization of plasma ammonia levels. However, ammonia concentrations fluctuated considerably over the follow-up period and sodium benzoate 160 mg/kg/day in 4 divided doses was introduced. After molecular confirmation of NAGSD, NCG treatment 16 mg/kg/day in 4 doses was started. Sodium benzoate was gradually reduced and then discontinued, as was the l-arginine. She did not experience further episodes of altered consciousness and headaches. She is currently treated with NCG 24 mg/kg/day. After 6 months of NCG treatment, plasma ammonia and amino acid levels are constantly normal.


A 4-year-old female presented with prolonged fever for 1month which was misdiagnosed as chicken-pox. She had non purulent conjunctivitis and peri-ungual desquamation. Echocardiography revealed coronary artery aneurysms; RCA and LCA measuring around 9 mm and 6 mm respectively. There was improvement of her clinical status and disappearance of fever after she received the second dosage of intravenous immunoglobulin (IVIG) on 2g/kg. During her follow-up by echocardiography for 4 years, there was mild regression of the coronary aneurysms compared to that of the initial measurements. Multi-slice CT angiogram showed regression of the LAD and RCA aneurysms with appearance of LAD and RCA stenosis ().
Coronary angiography, intravascular ultrasound (IVUS) and fractional flow reserve (FFR) were decided and revealed proximal RCA aneurysm partially occluded by organized thrombi with the inlet and outlet of the aneurysm showing 50% and 90% stenoses respectively, with significantly reduced FFR (0.78 resting gradient without giving adenosine) across both lesions. Proximal LAD smaller aneurysm and mid LAD lesion with a 50% stenosis, these findings are due to thrombi with adequate FFR (0.88 after intra-coronary adenosine).
This case underscores the following issues in the diagnosis of acute KD:
A long time between the onset of symptoms and diagnosis (1 month)
Persistence of 2 findings; non purulent conjunctivitis and peri-ungual desquamation
Delay in diagnosis led to large coronary aneurysms in both coronary arteries.


A 3-year-old boy was referred to our clinic because of high-grade fever and jaundice. The onset of fever was from 7 days followed by icteric tinge and dark urine manifested 2 days after the onset of fever and resolved after 3 days.
History obtained from the parents revealed no hepatotoxic drug consumption or maculopapular rash. On physical examination, body temperature was 39°C and desquamation on the tips of fingers and toes were seen. Eye examination showed bilateral bulbar conjunctival injection. Abdominal examination revealed no hepatosplenomegaly or tenderness. Abdominal ultrasonography revealed no hepatosplenomegaly with normal echogenecity, gallbladder and bile ducts were normal and ascites was not detected.
Laboratory findings showed elevation of ESR, CRP and liver transaminases with hyperbilirubinemia. There was no serologic finding compatible with viral hepatitis ().
According to clinical and laboratory findings of this patient, KD was suspected and echocardiography findings were normal. Intravenous immunoglobulin (IVIG) (2g/kg) and aspirin (80mg/kg/day) were given during hospital admission. Resolution of fever and conjunctival injection were achieved during 48 hours after initiation of IVIG. Liver enzymes normalized within 1 week from the start of the febrile illness and before IVIG. Platelets count rose to 900,000/mm3 after 2 weeks from the onset of the illness. His echocardiographic findings were normal during his follow-up visits and aspirin therapy was continued on 5mg/kg/day.
Why this presentation is an incomplete form of KD?
High-grade fever and jaundice were the main presentations
Clinical criteria were incomplete: the presence of only 2 clinical findings; desquamation on the tips of fingers and bilateral bulbar conjunctival injection.
Laboratory criteria helped to establish the diagnosis: evidence of hypoalbuminemia, elevated alanine aminotransferase and thrombocytosis.


A 57-year-old male with no prior medical history presented to an outside hospital with progressive fatigue, decreased exercise tolerance, and lower extremity edema of 3 months duration. No lymphadenopathy or hepatosplenomegaly was noted on exam. Laboratory tests were significant for a leukocytosis of 95 200/µL with 84% lymphocytes, smudge cells on peripheral smear, hemoglobin 13.2 g/dL, platelet count 177 000/µL, creatinine 1.2 mg/dL, serum albumin 2.1 g/dL, and hemoglobin A1c of 5.7% (). No prior laboratory tests were available for comparison, as the patient had not seen a physician in several years. Peripheral blood immunophenotyping showed a monoclonal population of cells positive for CD5, CD19, CD20, CD22, and CD23 and negative for CD38, an immunophenotype that is consistent with CLL. Peripheral blood fluorescent in situ hybridization was positive for trisomy 12 and negative for del(11p), del(13q), and del(17q). ZAP70 and immunoglobulin heavy-chain variable-region mutations were also negative. Serum β-2 microglobulin was elevated at 3.7 µg/mL (normal 0-3 µg/mL). The patient was diagnosed with Rai stage 0 CLL and was followed with a watch and wait approach until approximately 6 months afterward when a computed tomography (CT) scan reportedly showed a left lower quadrant mass concerning for possible Richter’s transformation to diffuse large B-cell lymphoma. He was subsequently referred to our institution for further evaluation.
On admission, physical exam was significant for bilateral axillary and inguinal lymphadenopathy, hepatomegaly, splenomegaly, and diffuse anasarca with pronounced scrotal edema. Laboratory tests were notable for a leukocytosis 77 000/µL with 93% lymphocytes, hemoglobin 11.5 g/dL, platelet count 174 000/µL, creatinine 1.3 mg/dL, estimated creatinine clearance (CrCl) of 95 mL/min, and serum albumin 1.4 g/dL (). Platelets, serum electrolytes, transaminases, alkaline phosphatase, total bilirubin, and international normalized ratio were within normal limits. Repeat peripheral blood flow cytometry confirmed CLL with a monoclonal population of cells with the immunophenotype previously noted along with negative expression of CD34, CD117, and FMC7. Urinalysis showed 3+ protein, and a 24-hour urine protein collection showed 11 g/24 h (normal <150 mg/24 h). The high-grade proteinuria, hypoalbuminemia, and anasarca confirmed the diagnosis of nephrotic syndrome. The patient also underwent a whole-body positron emission tomography/CT scan to evaluate for possible Richter’s transformation. Diffuse mesenteric, inguinal, and retroperitoneal lymphadenopathy was noted consistent with Rai Stage II, but there was no evidence of hypermetabolic masses concerning for diffuse large B-cell lymphoma. However, an acute right pulmonary embolus () and a left renal vein thrombus () were noted on CT. The patient was started on low-molecular-weight heparin while undergoing further evaluation for his nephrotic-range proteinuria.
Antinuclear antibody, HIV, hepatitis B/C, and phospholipase-A2 receptor antibody titers were negative. Serum and urine protein electrophoresis showed decreased and increased total protein, respectively, but were otherwise unremarkable. Serum κ and λ light chains were within normal limits, and no urine Bence-Jones proteins, dysmorphic cells, or casts were detected. A kidney biopsy was deferred due to concern for risk of bleeding in the setting of renal vein thrombosis and anticoagulation. Therefore, it was concluded that the patient’s nephrotic syndrome and venous thromboemboli, a known complication of nephrotic syndrome, were due to CLL given his otherwise unremarkable nephrotic syndrome workup. He was started on 6 cycles of reduced-dose fludarabine, cyclophosphamide, and rituximab (FCR-Lite) chemotherapy and continued on low-molecular-weight heparin. At 6-month follow-up, the patient achieved complete remission of his CLL with normalization of all cell lines, serum creatinine, hypoalbuminemia, and nephrotic range proteinuria (). No lymphadenopathy was noted, and repeat CT scans showed no evidence of recurrent venous thromboemboli.


A 57-year-old gravida 6, para 3, Asian Taiwanese woman presented to our hospital for scheduled surgery due to endometrial cancer. At admission, her body temperature was 36.8 °C, pulse rate 78 beats/minute, respiratory rate 20/minute, and blood pressure 136/98 mmHg. Her family and environmental history were unremarkable. She did not receive surgery before nor take any medication for systemic disease, such as diabetes mellitus or hypertension. She was a housekeeper. She did not smoke tobacco or consume alcohol. On physical examination, she had normal breathing sound, without wheezing or crackle, and a regular heartbeat without murmur. Her abdomen was soft with normoactive bowel sound on auscultation. Her extremities were freely moveable without edema. She exhibited severe morbid obesity (body weight, 128.4 kg; height, 155.7 cm; BMI, 52.9 kg/m2). Her daily activities were independent most of the time, except for some episodes of exertional dyspnea. Computed tomography (CT) revealed a ventral hernia with a large fascial defect (Fig. ). There were no clinical symptoms, such as abdominal pain or tenderness. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and ventral herniorrhaphy with Goretex mesh (GORE DUALMESH®).
Her early postoperative course was smooth. She consumed water on postoperative day (POD) 3, a clear-liquid diet on POD5, and a semi-liquid diet on POD7. She began bedside ambulation, and half of her stitches were removed on POD10. However, progressive dyspnea was noted after bedside ambulation. Intra-abdominal free air with elevation of right-side hemidiaphragm was noted by chest X-ray (Fig. ) on POD14. There was no abdominal tenderness or rebounding pain, but there was moderate abdominal distension. She was kept under close observation and began nil by mouth (NPO) for possible visceral perforation.
Two days later (POD16), severe dyspnea and extensive abdominal distention were noted. Her respiratory rate was elevated to 26/minute with accessory muscle use. Arterial blood gas analysis (under simple O2 mask, 10 L/minute) showed: pH, 7.42; partial pressure of carbon dioxide in arterial blood (PaCO2), 44.8 (mmHg); partial pressure of oxygen in arterial blood (PaO2), 86.2 (mmHg); bicarbonate (HCO3-), 28.5 (mmol/L); blood oxygen saturation (SpO2), 96.7%; and blood pressure, 102/75 mmHg. Laboratory tests revealed leukocytosis with a white blood cell (WBC) count of 12,900/uL, hemoglobin (Hb) 12.6 g/dL, and platelet count 310,000/uL. Her C-reactive protein (CRP) was elevated at 165.7 mg/dL. Serum creatinine was 0.99 mg/dL, while serum sodium was 131 mmol/L, and potassium was 3.9 mmol/l. A physical examination showed severe abdominal distension without rebound pain. A pelvic examination demonstrated good healing of the vaginal cuff without leakage. CT showed a large amount of intra-peritoneal free air with little ascites (Fig. ). Because clinical visceral perforation was less likely, under the impression of pneumoperitoneum, in this emergent situation, an 8-Fr. pigtail catheter was inserted under CT guidance for decompression. A massive amount of gas was drained. Subsequently, her dyspnea and abdominal distention dramatically subsided. She re-started oral intake on POD20, and the abdominal pigtail catheter was removed on POD24 after no more free air was revealed by chest X-ray. No further abdominal distention was noted, and she was discharged on POD28. The clinical course of the endometrial cancer and repaired hernia were well at the 1-year follow-up.


A 43-year-old female presented at a dermatology clinic at an outside institution with a small nodule on the right side of her neck, which had been present for over a year. A biopsy was taken for histopathologic examination, which showed a nodular mass with fascicles of spindle cells () with clear cytoplasm and wreath-like giant cells (), involving the entire dermis, with focal extension into the superficial subcutaneous tissue.
Immunohistochemistry was performed on the tissue sections according to the standard method for formalin-fixed paraffin-embedded tissue (FFPET) by the Laboratory Corporation of America Inc. (New Jersey), using the following antibodies; S100, Human Melanoma Black 45 (HMB-45), vimentin, Melan A, factor XIIIa, and CD68. Control stainings were satisfactory. The neoplastic cells were positive for S-100 (), HMB-45 (), and vimentin. The tumour cells were negative for Melan A, factor XIIIa, and CD68. The results led to a diagnosis of malignant melanoma of the dermis (Clarke Level V). Because of the unusual histologic presentation, which included the presence of clear cells, multinucleated giant cells, and with no epidermal in situ component, the differential diagnosis included clear cell sarcoma and Spitz nevus. The lesion was re-excised, and sections of the re-excision were negative for any residual tumour. The case was sent out for an expert consultation to two facilities, which agreed with the initial diagnosis of malignant melanoma but could not exclude intradermal clear cell sarcoma. Fluorescence in situ hybridization (FISH) was ordered on the specimen, and the case was sent to our institution for another opinion. Upon examination, there was a nodular proliferation of malignant spindle cells with clear cytoplasm and wreath-like giant cells, occasional mitotic figures, and no obvious melanin. The tumour measured 0.5 cm and involved the dermis and the subcutaneous tissue, with no epidermal involvement. FISH was performed using the standard method for FFPET with the Abbott Molecular LSI EWSR1 Dual Color Break Apart Probe (Illinois, United States). According to protocol 200, interphase cells were examined, and 59.5% of these were positive for the split signals, indicating a positive rearrangement of the EWSR1 gene at chromosome 22q12 (). Based on the FISH results and the lack of an in situ involvement, the diagnosis of a dermal clear cell sarcoma was made, rather than nodular malignant melanoma. Physical and imaging studies showed no evidence of metastasis. The patient was initially scheduled for prophylactic IL-2 treatment for melanoma. However, once the diagnosis was changed to primary clear cell sarcoma, no further treatment was initiated. The patient is currently disease free, with no evidence of metastatic disease 6 months after initial biopsy. An Institutional Review Board waiver of consent was obtained for the case report.


A 58-year-old female with a history of hypertension and open cholecystectomy sustained a ground-level fall while jumping from one stump to another. After initially visiting her local urgent care, she was transferred to the emergency department on a minor trauma protocol. She endorsed flank pain and hematuria, but no dizziness or pain in other locations and the remainder of her review of systems was negative. She arrived hemodynamically stable, with initial vitals demonstrating a blood pressure of 148/92 mmHg, heart rate of 79 beats/min, respiratory rate of 12 breaths/min, oxygen saturation of 98% on room air, and temperature of 37.1°C (98.7°F). She was alert, oriented, and answered all questions appropriately. Her first and secondary trauma surveys revealed a right flank abrasion as well as tenderness to palpation in the right upper quadrant and at the right costovertebral angle. The remainder of her physical exam was unremarkable.
In tandem with the secondary survey, a FAST was conducted using a 5-1 MHz phased array probe (Sonosite, Bothell, WA) to evaluate for possible intraperitoneal or pericardial bleeding. The assessment was negative in the subxyphoid, left upper quadrant, and pelvic views, but positive for fluid in the right upper quadrant (Figure ). The fluid was identified in what was initially interpreted as the hepatorenal recess, commonly referred to as Morison’s pouch, with some hyperechoic blood clotting. Upon closer examination, the bright ribboning of Gerota’s fascia surrounding the kidney was visible on both sides of the fluid collection, suggesting an alternate scenario of subcapsular fluid originating from injury to the kidney itself.
A CT scan was obtained, demonstrating Grade IV laceration of the inferior pole of the right kidney extending to the renal hilum (Figure ). There was no evidence of active hemorrhage, no extraluminal urine to suggest damage to the collecting system, and no involvement of the renal vasculature. A large retroperitoneal, subcapsular perirenal hematoma was observed extending from the superior pole of the right kidney to just beyond the bifurcation of the left common iliac arteries, entirely contained within Gerota’s fascia. A urinalysis exhibited full field red blood cells. The laboratory findings included a white blood count of 18.8, initial hematocrit of 35.9%, and a normal creatinine at 0.81. Subsequent hematocrit measurements were 33.1% and 30.7%.
Both the general surgery and urology services provided consultation on this patient, recommending conservative management in light of the isolated injury and hemodynamic stability. The patient was admitted, placed on bedrest, and continued on intravenous fluids. She was followed with serial examinations and six-hour complete blood counts. Over the course of her stay, her hematocrit stabilized at 30.6%. Her gross hematuria resolved by the following morning, after which she could ambulate without difficulty, and she was discharged home with a plan to follow up in the urology clinic. Follow-up ultrasound imaging showed interval reduction in the hematoma surrounding the right kidney, down to approximately 12.84 x 9.2 x 5.4 cm. A final follow-up CT demonstrated organization and loculation of a 5.0 x 5.4 x 5.8 cm heterogeneous right perinephric collection with a peripheral rim of hyperdensity, on the whole consistent with a hematoma decreasing in size over time.


A 23-year-old Caucasian woman suffered from blunt abdominal trauma due to a fall from a bicycle onto the bicycle handlebar. She was a university student and had an unremarkable medical history. Social history was significant for occasional tobacco smoking and alcohol consumption. She was treated in a Dutch hospital for 6 days prior to transfer to our clinic. Magnetic resonance imaging (MRI) revealed complete rupture of the pancreatic body (Fig. ): grade 3 pancreatic trauma (see Table ) []. Unsuccessful stenting of the ruptured main pancreatic duct (MPD) was performed via endoscopic retrograde cholangiopancreatography (ERCP). Computed tomography (CT)-guided drainages were placed percutaneously in epigastric fluid collections. She became septic and was then transferred to our clinic with the following medication: intravenously administered metamizole 500 mg (every 6 hours), subcutaneous octreotide 100 μg (1 dose in the morning, 1 dose at midday, and 1 dose in the evening), intravenously administered pantoprazole 40 mg (1 dose in the morning, 0 dose at midday, and 0 dose in the evening), and intravenously administered ceftriaxone 2 g (1 dose in the morning, 0 dose at midday, and 0 dose in the evening). On admission, she was hemodynamically unstable (blood pressure 85/65 mmHg, heart rate 120/minute, oxygen saturation 95%, and body temperature 37.5 °C) with a significantly increased C-reactive protein level of 212 mg/l (< 5) and procalcitonin level of 10.7 ng/ml (< 0.005). The following laboratory values were determined as well: White blood cell count 8830/μl (4600–9500), hemoglobin 9.8 g/dl (12–16), thrombocytes 225,000/μl (150,000–400,000), international normalized ratio (INR) 1.13 (0.8–1.1), partial thromboplastin time 30 seconds (26–40), amylase 169 U/l (13–53), lipase 183 U/l (13–60), lactate dehydrogenase 219 U/l (135–214), aspartate amino transferase 21 U/l (10–35), alanine amino transferase 14 U/l (10–35), cholinesterase 2404 U/l (4260–11,250), gamma glutamyl transferase 42 U/l (6–42), alkaline phosphatase 56 U/l (35–104), bilirubin 0.4 mg/dl (< 1.2), and creatinine 0.41 mg/dl (0.5–0.9). Blood cultures were positive for Pseudomonas aeruginosa. General abdominal tenderness was palpable indicating peritonitis. Her cardiorespiratory state was remarkable for tachycardia and hypotension. A neurological examination was unremarkable apart from a somnolent state. A transverse explorative laparotomy was performed immediately. On intraoperative examination, a severe peritonitis and necrotizing pancreatitis were identified as complications of a complete rupture of the pancreatic body (Fig. ). Furthermore, the percutaneous drainage had perforated her transverse colon. A distal pancreatectomy, splenectomy, removal of the drainage, suturing of the colon perforation, and a protective ileostomy were performed. Subsequently, she underwent two further surgeries with abdominal cavity lavages. Posttraumatic complications in this case comprised severe peritonitis, necrotizing pancreatitis, critical illness polyneuropathy, and pancreatic fistula. She spent 48 days in our surgical intensive care unit and was discharged on postoperative day 68.
A follow-up investigation 6 months after the primary surgery showed a regular postoperative state without signs of pancreatitis, fluid collections, or abscesses. Reconstruction of the ileostomy was uneventful.


A 15-year-old Caucasian boy was transferred to our clinic exactly 1 day after case 1. He was a middle school student and had an unremarkable medical history. His social history was unremarkable for tobacco smoking, alcohol, or drugs. Four days before, he fell from a bicycle and hit his abdomen on the bicycle handlebar just like the first patient. Initial ultrasound and laboratory tests were uneventful. However, his amylase and lipase levels were not tested. CT was performed due to progressive abdominal pain which again showed a complete rupture of the pancreatic body; once again grade 3 pancreatic trauma []. Laboratory values were significant for C-reactive protein 66 mg/l (< 5), amylase 160 U/l (13–53), and lipase 150 U/l (13–60). The following laboratory values were determined as well: White blood cell count 9650/μl (4600–9500), hemoglobin 12.4 g/dl (14–18), thrombocytes 176,000/μl (150,000–400,000), INR 1.16 (0.8–1.1), partial thromboplastin time 37 seconds (26–40), lactate dehydrogenase 223 U/l (< 271), aspartate amino transferase 16 U/l (< 46), alanine amino transferase 15 U/l (< 45), cholinesterase 5131 U/l (5320–12,920), gamma glutamyl transferase 17 U/l (< 29), alkaline phosphatase 116 U/l (< 381), bilirubin 0.9 mg/dl (< 1.2), and creatinine 0.56 (0.8–1.4). He was then transferred to our hospital with the following medication: acetaminophen 500 mg (1 dose in the morning, 1 dose at midday, and 1 dose in the evening) and pantoprazole 40 mg (1 dose in the morning, 0 dose at midday, and 0 dose in the evening). The following vital parameters were taken on admission: blood pressure 100/80 mmHg, heart rate 98/minute, oxygen saturation 100%, and body temperature 37.9 °C. A physical examination revealed a general tenderness of his abdomen indicating peritonitis. Neurological and cardiorespiratory examinations were unremarkable. An explorative laparotomy with subsequent distal pancreatectomy and splenectomy was performed. Lower grade signs of peritonitis were present intraoperatively compared to case 1 (Fig. ). Postoperatively, he developed a pancreatic fistula. He was discharged on postoperative day 29.
A follow-up investigation 6 months after the primary surgery revealed a regular postoperative state without signs for infections, fluid collections, or abscesses.
Both patients were vaccinated against Streptococcus pneumoniae, Haemophilus influenza, and Neisseria meningitidis 6 weeks after discharge to prevent overwhelming postsplenectomy infection syndrome.


The patient is a 72-year-old female with a history of diabetes mellitus, hypertension, and bicuspid aortic valve status post aortic valve and root replacement using a 23 mm Freestyle (Medtronic, Minneapolis, MN) aortic valve and root bioprosthesis implanted by root inclusion method 12 years prior to admission. She was transferred from an outside hospital with acute-onset chest pain and shortness of breath. She denied fever and chills. Physical examination was notable for blood pressure 100/30 mmHg and hypoxia. Grade 3/6 systolic and diastolic murmurs were heard at the right 2nd intercostal space. Subsequently, she developed pulmonary edema and shock necessitating mechanical ventilation and vasopressor support. A transthoracic echocardiogram suggested flail aortic valve leaflet (), and transaortic Doppler signal was suggestive of wide-open aortic regurgitation ().
Due to rapid deterioration of the patient, the heart team was immediately organized. Two cardiac surgeons deemed her unsuitable for redo surgical aortic valve replacement (Society of Thoracic Surgeons predicted operative mortality >50%). Therefore, valve-in-valve TAVI was considered. After review of the operative report and manufacturer product information, the inner diameter of the Freestyle valve was confirmed to be 20 mm. A 23 mm S3 valve (Edwards Lifesciences, Irvine, CA) was selected. Images from a remote contrast-enhanced CT scan suggested absence of peripheral arterial calcification and adequate caliber of iliofemoral arteries for large-bore sheath insertion.
Transesophageal echocardiography (TEE) was used to guide the procedure. The etiology of valve deterioration was confirmed to be leaflet flail; no vegetations were identified. Arterial and venous access was obtained followed by placement of a transvenous pacemaker. Aortography was performed (), followed by insertion of a 14 F × 36 cm E sheath (Edwards Lifesciences, Irvine, CA). The 23 mm S3 valve was implanted during rapid pacing, using nominal inflation volume (). Of note, wide pulse pressure was observed even during pacing at 200 beats per minute. Pre-TAVI central aortic pressure was 114/30 mmHg, and left ventricular pressure was 120/30 mmHg (). Post-TAVI central aortic pressure was 90/40 mmHg with a left ventricular pressure of 90/13 mmHg (). The final TEE images and aortogram showed trivial aortic regurgitation (Figures –). Blood cultures, which had been obtained at presentation, were negative. The patient was discharged home in stable condition after 7 days. At a 30-day postprocedure follow-up visit, she was asymptomatic and had returned to working as a teacher. An echocardiogram at that time revealed normal left ventricular size and function, no aortic insufficiency, mean transaortic gradient 12 mmHg, and calculated aortic valve area 1.0 cm2 (, ).


A 65-year-old lady was admitted in the surgical emergency with complaints of acute onset of right-sided groin pain followed by diffuse abdominal pain and distension over a period of one week. She also had a history of obstipation for the past one week. The onset of obstipation was associated with bilious vomiting for the past five days. She had no other significant medical history in the past. On physical examination, she was poorly built and nourished and had signs of dehydration. Her lower abdomen was tense and distended with diffuse tenderness. There were no peritoneal signs but bowel sounds were exaggerated. The digital rectal and vaginal examinations were normal. A local examination revealed a fullness in the right groin region around the pubic tubercle with tenderness along the medial thigh (Howship-Romberg sign). The pain was exacerbated by the adduction of the hip or medial rotation of the thigh.
Abdominal radiography showed evidence of dilated small bowel loops with multiple air-fluid levels, suggesting intestinal obstructions. An ultrasonography of the abdomen and pelvis showed dilated small bowel loops with decreased peristalsis, but the cause of obstruction could not be identified. Contrast-enhanced computed tomography (CECT) of the abdomen revealed the ileal loop entering through the right obturator foramen and was found between the pectineus and obturator externus (Figure , Figure ). A diagnosis of right-sided obstructed obturator hernia was made. The patient was optimized and taken up for emergency laparotomy. Intra-operatively, a 5-cm loop of ileum was found entering the right obturator canal, which was 10 cm proximal to the ileocecal junction (Figure ). This loop of bowel was brought into the abdominal cavity. There were pregangrenous changes and a constriction ring in that bowel segment, which was resected, followed by anastomosis. The hernial sac was left in situ and the neck was closed by a nonabsorbable purse-string suture. Her postoperative period was uneventful and she was discharged on postoperative day 10.


A 25-year-old black African woman, gravida 1 para 1, presented on 15 May 2015 with a 5-day history of cramp-like lower abdominal pain radiating to her lower back. This was associated with a foul-smelling hydrorrhea, difficult micturition, and partial urinary retention that occurred 2 days ago. She had a past history of menorrhagia. She had four intramural uterine fibroids measuring 62, 64, 70, and 94 mm diagnosed with standard ultrasound scan in April 2013 during work-up for menorrhagia. She got pregnant in July 2014. A standard ultrasound scan done on 31 August 2014 at 10 weeks’ gestation identified four intramural uterine fibroids, including a left lateral intramural uterine fibroid of 150 mm (biggest) and a posterior intramural uterine fibroid of 70 mm (smallest; Fig. ). Her pregnancy was well followed up, without any complications. During pregnancy, her uterus had always an irregular shape and a high symphysis-fundal height (20 cm at the 14th week of gestation, 30 cm at the 24th week, 34 cm at the 28th week, and 40 cm at the 38th week). At the 38th week of gestation, two fibroids of 7 cm and 8 cm were palpated on the uterine corpus (the first anteriorly at the right side of the uterine corpus and the second anteriorly on the uterine fundus). At the left lateral side of her uterus, there was also a low situated large fibroid that could not be well palpated and measured. The presentation was cephalic with an unmovable fetal head. The fetal heart tones were normal. She delivered a baby girl, who weighed 3000 g, vaginally on 10 April 2015 at 41 weeks 6 days in the same health facility. A placenta examination revealed retention of parts of fetal membranes. They were removed manually during uterine exploration. During this procedure, no pedunculated submucosal fibroid was found. There were neither maternal nor neonatal complications.
On physical examination at admission, her temperature was 38.5 °C. There was hypogastric tenderness. She had a myomatous uterus with a symphysis-fundal height of 16 cm. There was a foul-smelling vaginal discharge. On speculum and digital vaginal examinations, a mass of approximately 10 cm in diameter was present in her vagina, rendering examination of the cervix difficult.
The diagnosis of an infected prolapsed pedunculated uterine fibroid associated with urinary retention was made. An indwelling urinary catheter was set up, as well as an intravenous drip. Antibiotic therapy was started intravenously with ceftriaxone (1 g twice daily) and metronidazole (500 mg thrice daily). Two days later, under general anesthesia, the almost necrotic fibroid was held with two big toothed forceps and easily twisted off per vaginal route, without any significant bleeding, which relieved her symptoms. On speculum and vaginal examinations, her cervix was normal and 4 cm dilated with the base of the fibroid’s pedicle located in the posterior uterine wall at 3 cm from the external cervical os. The fibroid was sent for pathology, which later confirmed uterine leiomyoma. Five days after fibroid removal, she developed a urethrovaginal fistula due to prolonged urethral obstruction.


We describe the case of a 46-year-old female patient with rheumatic valvulopathy and
a history of mitral and tricuspid valve repair 6 years prior who was hospitalized
for heart failure associated with mitral and aortic insufficiency. The
echocardiogram on admission revealed considerable dilated left ventricular
cardiomyopathy (diastolic diameter: 65mm; systolic diameter: 42mm) with 68% ejection
fraction and 49mmHg pulmonary artery systolic pressure. The examination revealed
marked mitral insufficiency and moderate stenosis in addition to moderate aortic
insufficiency and mild tricuspid insufficiency.
The patient underwent mitral and aortic valve replacement with mechanical prostheses.
During surgery, she sustained iatrogenic laceration of the left lung followed by
severe and refractory acute respiratory insufficiency associated with massive
hemoptysis. Selective intubation was attempted but failed. The laceration was
surgically corrected, but arteriography was not performed.
The patient developed refractory hypoxemia (partial pressure of oxygen
[PaO2] of 54mmHg, oxygen saturation [SatO2] of 84% and
fraction of inspired oxygen [FiO2] of 100%) and hypercapnia (partial
pressure of carbon dioxide [PaCO2] of 109mmHg and pH 6.9). The
intraoperative echocardiogram revealed preserved biventricular function, but the
pulmonary artery systolic pressure was 62mmHg. Venovenous ECMO (VV-ECMO) was
initiated during surgery. However, due to the associated severe hemodynamic
instability (noradrenaline 1mcg/kg/minute, vasopressin 0.04u/minute and dobutamine
10mcg/kg/minute) and problems with the VV-ECMO flow, we opted for immediate change
to venoarterial ECMO (VA-ECMO) (MAQUET® Rotaflow RF 32 Console,
Quadrox PLS System). A 17Fr cannula was inserted in the left femoral artery, and a
21Fr cannula was inserted in the right femoral vein. The latter was positioned in
the right atrium and guided by echocardiography. Both cannulas were inserted during
surgery and by dissection. An anterograde reperfusion cannula (6Fr) was inserted in
the left superficial femoral artery by dissection. Invasive blood pressure was
placed in the right radial artery. We programmed the VA-ECMO at 4,200rpm, 4L/minute
flow, and 4L/minute sweep with 80% FiO2. The initial mechanical
ventilation programming was performed in the pressure-controlled mode with positive
end-expiratory (PEEP) of 10cmH2O, FiO2 of 25%, respiratory
rate of 12irpm, controlled pressure of 15cmH2O, and plateau pressure of
25cmH2O, maintaining the tidal volume at 5mL/kg. Lactate was
4.8mmol/L at admission to the intensive care unit and 2.1mmol/L after 24 hours of
ECMO.
After surgery, the patient developed a large number of clots in the bronchial tree,
which were difficult to remove due to the tree's dryness. Sequential bronchoscopies
were performed on the first and second postoperative days in an attempt to remove
the clots, but all were unsuccessful ().
Forty-eight hours after VA-ECMO was installed and when hemoptysis was controlled
safely, anticoagulation was started with intravenous unfractionated heparin (500
units per hour) to maintain an activated coagulation time of 150 - 180 seconds.
The patient presented progressive hemodynamic improvement with suspension of the
vasoactive drugs on the second postoperative day. However, she persisted with a
severe pulmonary condition and was dependent on ECMO without tolerating the
FiO2 reduction in this device. On the third postoperative day,
endobronchial streptokinase (30,000u/30mL) was infused with 10 mL infused every 15
minutes (total of three 10mL infusions) with subsequent removal of large clots. The
process was repeated for three consecutive days, after which a significant
improvement in the pulmonary picture was observed both from the radiological and
gasometric points of view (). It was
possible to progressively reduce the ECMO FiO2 with maintenance of
adequate PaO2 and SatO2 (PaO2/FiO2 ratio
greater than 300 with ECMO FiO2 of 21% and FiO2 of 40% with
mechanical ventilation). After four days of support, withdrawal of the ECMO was
planned. The patient was sedated (Richmond Agitation and Sedation Scale [RASS]: 5)
with midazolam and fentanyl without vasoactive drugs with a mean arterial pressure
of 66mmHg, heart rate of 77bpm, arterial lactate of 1.1mmoL/L, central venous oxygen
saturation (SVcO2) of 76% and bicarbonate of 24mEq/L, revealed by
arterial gasometry, with a PaO2/FiO2 ratio of 305. The patient
presented mechanical ventilation FiO2 of 40% and ECMO FiO2 of 21%. The
patient maintained a good urine output with 1.0mg/dL creatinine and 70mg/dL
urea.
An echocardiogram was performed at the bedside, and the ECMO support was reduced to
1,500rpm, corresponding to a flow of 1.3L/minute. In this condition, the examination
revealed an estimated ejection fraction of 45%, aortic valve velocity-time integral
of 14cm and systolic velocity (S-wave) of the mitral annulus of 9cm/s via tissue
Doppler. Based on the clinical and echocardiographic data, the ECMO support was
removed after 91 hours.
On the sixth postoperative day, antibiotic therapy was initiated due to focal sepsis
in the lung. Vancomycin and meropenem were administered for 10 days with good
clinical response. The requested cultures (blood cultures, uroculture and tracheal
aspirate culture) did not identify microorganism growth.
Due to the progressive respiratory improvement, extubation was performed after 7 days
of mechanical ventilation and 3 days after ECMO withdrawal. The patient developed
left lower limb paresis with detection of peripheral nerve damage related to the
ECMO arterial cannulation site.
The patient presented good clinical evolution with complete recovery of the
respiratory condition (). She was
discharged on the 30th postoperative day with left lower limb paresis
(grade 3 muscle strength by the Medical Research Council). The patient was followed
up on an outpatient basis and resumed her usual activities with independence. She
remained asymptomatic from a respiratory and cardiovascular point of view,
maintaining outpatient use of 35 mg/week warfarin, 5mg/day enalapril and 12.5mg/day
carvedilol. The control echocardiogram at 6 months after discharge revealed an
ejection fraction of 52.82% with mechanical prosthesis in a normal mitral position,
discrete mitral valve insufficiency, a maximum diastolic gradient of 14mmHg and a
mean diastolic gradient of 5.5mmHg. The mechanical prosthesis in aortic position
functioned normally. The maximum systolic gradient was 21mmHg, and the mean was 11
mmHg. Discrete left ventricular systolic dysfunction was noted with a slight
increase in the left atrium and a moderate increase in the left ventricular diameter
(diastolic diameter: 58mm; systolic diameter: 42mm). Discrete tricuspid
insufficiency was also observed, and the pulmonary artery systolic pressure was
estimated at 43mmHg.
The patient was discharged from the valvulopathy outpatient clinic of the
Instituto de Cardiologia do Distrito Federal, Brasília 6
months after hospital discharge to continue follow-up in her hometown in the state
of Bahia ().


A 56-year-old Hispanic male with no comorbid conditions presented to our emergency department with a 2-day history of fever, generalized weakness, abdominal pain, nausea, and vomiting. He had no hemoptysis, hematemesis, arthralgia, or headache. He denied recent contact with sick humans, exposure to pets or birds, or travel. He smoked 5 cigarettes per day for over 20 years but denied using alcohol or recreational drugs.
On physical examination, the patient was in respiratory distress, with a respiratory rate of 24 breaths per minute and pulse oxygen saturation of 90% on 2 liters per minute oxygen via a nasal cannula. His temperature was 101.5°F, heart rate was 68 beats per minute, and blood pressure was 80/50 mm·Hg. On lung examination, bilateral rales were noted. His heart sounds were normal. His abdomen was soft upon palpation, with slight tenderness in the right upper quadrant; no organomegaly was noted. Neurologic examination was unremarkable. The patient was intubated immediately because of his respiratory distress, and an intravenous infusion of norepinephrine was begun for the presumptive diagnosis of septic shock.
Relevant laboratory results on the day of admission were as follows: leukocytosis (white blood cell count: 20 × 103 cells/µL), lactic acidosis (serum lactate: 17.5 mmol/L), pH of 7.15, bicarbonate of 15 mEq/L, blood urea nitrogen of 37 mg/dL, serum creatinine of 4.5 mg/dL, and increased serum aspartate transaminase (1532 unit/L), alanine aminotransferase (683 unit/L), and alkaline phosphatase (149 unit/L). Chest X-ray showed bilateral diffuse alveolar infiltrates ().
The patient underwent fiberoptic bronchoscopy with bronchoalveolar lavage; diffuse alveolar hemorrhage was excluded, and cultures from the lavage samples were negative. Bedside ultrasound of the abdomen revealed acalculous acute cholecystitis, and a percutaneous cholecystostomy tube was placed. Blood cultures from admission grew P. multocida, and gram-negative Pasteurella rods were seen on gram stain during examination via light microscopy. Cultures from the gallbladder fluid were negative. Transthoracic echocardiography showed a left ventricular ejection fraction of 74% and no vegetations.
The patient was diagnosed with multiorgan failure, septic shock with severe lactic acidosis, acute respiratory distress syndrome (ARDS), and renal failure requiring hemodialysis. Broad-spectrum intravenous antibiotics were begun. His condition rapidly deteriorated, and his clinical course was further complicated by disseminated intravascular coagulation, gastrointestinal bleeding, and refractory shock requiring multiple vasopressor medications. He subsequently died of a cardiopulmonary arrest. Despite all measures, the serum lactic acid at the time of his death was 12 mmol/L.


A 34-year-old male presented to our service four years after surgery in another hospital for a posterior fossa tumor reported as a medulloblastoma. The posterior fossa tumor was excised, and gross total resection was achieved at that time. Pathology reported the tumor to be consistent with medulloblastoma. Spinal magnetic resonance imaging (MRI) and a lumbar puncture did not demonstrate neuroaxis dissemination. The patient received standard craniospinal irradiation (CSI) consisting of 36 Gy, a boosted primary posterior fossa site dose of 54 Gy, in prone position, and chemotherapy. When he presented at our hospital with a two-week history of headache, somnolence, nausea, and vomiting; his family reported hypersexuality and abulia during the last four months. The MRI demonstrated two tumors located at each middle cranial fossa in the temporal poles (Figure ).
He was admitted with a presumptive diagnosis of medulloblastoma seedings. The posterior fossa and spine were without evidence of tumor. Both tumors were surgically treated at different times (Figure ). Macroscopically, both tumors comprised soft purplish tissue easily cleavable from the surrounding brain parenchyma and moderate vascularization. The histopathological diagnosis was classic medulloblastoma for both tumors (Figure -).


A 38-year-old male with a history of hydrocephalus secondary to a tumor located in the posterior fossa had been treated six years before in another hospital. At that time, the patient underwent ventriculo-peritoneal shunt and tumor resection. The histopathological report was medulloblastoma. The patient received standard craniospinal irradiation (CSI) consisting of 36 Gy, a boosted primary posterior fossa site dose of 54 Gy, in prone position, and chemotherapy. Four years after the surgery, he presented with progressive memory impairment and abulia. Finally, he presented with somnolence, which was the reason why he was brought to our emergency department. The patient underwent an MRI where two well-circumscribed lesions, in both middle floors and no tumoral activity in the posterior fossa were demonstrated (Figure ). Both tumors were resected in separate surgeries achieving gross tumor total resection on either side (Figure ). The histopathology also demonstrated a classic medulloblastoma in both right and left tumors (Figure -, respectively).


A 73-year-old woman presented with severe pain in the left upper extremity following a ground-level fall at her home. Physical examination revealed shoulder deformity and restricted range of motion, crepitus from the fracture fragments and extensive ecchymosis to the elbow on her left shoulder. No neurovascular impairment was found. Plain radiographs and computed tomography (CT) scans showed a Neer Group VI proximal humeral fracture (Fig. ) []. Her medical history was significant for lacunar infarction, hypertension, type 2 diabetes and schizophrenia, which were all controlled with oral medications. She was diagnosed with schizophrenia by the Shanghai Mental Health Center. Medical records showed that the patient had irregular fever along with symptoms of schizophrenia such as impulsive tendencies of self-mutilation and aggressive behaviors over decades. Additionally, the patient had a history of eating raw clams (Tegillarca granosa) and years of working barefoot in paddy fields without wearing protective clothing.
In this case, the patient stayed in hospital for 134 days. On the basis of the maximum body temperature and laboratory examinations, hospitalization was divided into three stages, namely, fever of unknown origin (FUO) stage (days 1–36), antiamebic treatment (AT) stage (days 37–85), and treatment failure (TF) stage (days 86–134) (Additional files and ).
After surgery contraindications were ruled out, the patient underwent a hemiarthroplasty surgery performed by an experienced orthopedic surgeon on day 9 (Fig. ). The operation was successfully performed without any intraoperative complications. Six hours after the surgery, she developed continuous fever (body temperature 40.3 °C) (Fig. ). Measures for lowering body temperature were taken immediately. Physical examination showed her vitals were normal. The patient had negative Kernig’s sign and neck stiffness. Motor, sensory and cranial nerve examinations were within normal limits. Laboratory and radiographic examinations revealed no obvious evidence of infection, except for elevated procalcitonin levels (0.38 ng/ml, normal levels 0–0.1 ng/ml). Blood (1,3)-β-D-glucan assays were taken 5 times during this stage, and the results were negative. Blood culture was performed several times and revealed no bacterial or fungal growth. Meropenem, cefoperazone/sulbactam, cefathiamidine, vancomycin, azithromycin, fluconazole, ceftazidime, phosphonomycin and linezolid were used as mono- or combination antibiotic therapy successively. The operated upper limb healed uneventfully. However, cooling treatment and empirical broad-spectrum antibiotic therapy showed no apparent effect.
To investigate the etiology of continuous fever, blood, urine and cerebrospinal fluid (CSF) samples were sent for parasite detection. Surprisingly, large numbers of FLA-like pathogens were discovered microscopically (Fig. ; Fig. ). The patient was initially diagnosed as having FLA infection and treated with antiamebic therapy.
On day 37, after the diagnosis of FLA infection was made, the patient was immediately started on a combination therapy with metronidazole, fluconazole, compounded sulfamethoxazole and sulfadiazine (COSMZ), and meropenem [–]. Meropenem was used in case that the patient was infected with other pathogens in addition to FLA. On day 52, Duo-Cotecxin (Beijing Holley-Cotec Pharmaceuticals Co., Ltd., China) was added to the antiamebic therapy. Additionally, the medical team attempted to obtain miltefosine, which did not arrive in time. From day 61–85, remission of clinical manifestations of the patient was observed. During this period, her mental status remained stable, no schizophrenia related symptoms appeared, and the body temperature was lower than 38.0 °C most of the time (Fig. ). Laboratory results were normal. A decrease in FLA-like pathogen from 5.25 to 1.95 counts under high power field at magnification (× 100) field in blood samples was also observed by microscopy (Fig. ).
Although a remission of clinical manifestations of the patient was observed for approximately 25 days (days 61 to 85), the patient’s condition deteriorated from day 86. Her body temperature was higher than 38.0 °C most of the time (Fig. ), and the FLA-like pathogen count in the blood samples as determined by microscopy increased again to 3.85 (Fig. ). Although frequently received blood transfusions (10 times comprised of 1 international unit of red cell suspension liquid and 100 ml of blood plasma, or 2 international unit of red cell suspension liquid and 200 ml of blood plasma each time), the patient became severely anemic. Her hospital course was complicated by refractory hypernatremia and hyperchloremia (sodium–153 mmol/L, chloride–114 mmol/L), leading to multiple blisters on the left leg (Fig. ). FLA-like pathogens were also detected in the blister fluid samples. She finally died of multiple organ failure and intractable fever on the 134th day of hospitalization.
Prior to observing in the microscope, blood, CSF and blood samples were processed with the physiological saline method of direct smears.
In the blood samples, many cells looked like “straw hats” (Fig. ). The cells were discoid in shape; the cytoplasmic humps were surrounded with flattened hyaline margins, some of which were fan-shaped. The surfaces of the cells were warty. The dimensions of these cells ranged from 10.2–25.4 × 11.8–26.5 μm with average dimensions of 17.8 × 19.3 μm. Smaller cells were easily observed. Owing to the granular mass on the surface, the nucleus could be not clearly seen. Locomotion was not visible in most microscopic fields. But sometimes cells displayed short blunt or fila-pseudopodia and slow deformation (Additional file ).
In CSF samples, we found different cells that appeared irregular and had vacuoles (Fig. ) and finger pseudopodia (Fig. ). Some had circular shells that looked transparent, but no structures could be observed (Fig. ). Occasionally, black spheres were observed (Fig. ).
In urine samples, single cells displayed different morphological forms; some were spherical (Fig. ), whereas others had huge vacuoles (Fig. ) and/or possessed fan-shaped pseudopodia (Fig. ). Some “cells” clustered together.
After the antiamebic treatment, when the body temperature of the patient came down, the discoid-like unicellular body could not be detected in blood samples (Fig. ). Most forms were oval; the cell bodies were approximately 13.0–16.1 μm long and 8.8–11.7 μm wide with average dimensions of 15.0 × 10.1 μm. Locomotive cells displayed short filopodia or conical non-branching pseudopodia arising from apical and/or lateral parts of the cell (Fig. ). Furthermore, some small cells showing small, refractive outlines with single long (over 10 μm) filopodia (Fig. ) and large irregularly shaped cells (more than 10 μm) with short (3–5 μm) filopodia (Fig. ) could be seen occasionally.
The morphological characteristics of the pathogen resemble species of FLA, Vannella sp. [], and another type of scale-bearing amoeba: Cochliopodium sp. [], and with no similarity with known pathogenic amoeba such as Acanthamoeba sp., Balamuthia mandrillaris, Entamoeba histolytica, Naegleria fowleri, Sappinia diploidea, etc. [].
To confirm the morphological findings and further discover the cause of the infection, uncultured blood serum samples were sent for molecular identification. The blood serum samples were taken on day 44 and preserved in liquid nitrogen. Total genomic DNA was extracted from the samples and polymerase chain reaction (PCR) was performed using prokaryotic universal primers and eukaryotic universal primers (Additional file ). Primer sequences were 16 s-27F 5′-AGAGTTTGATCATGGCTCAG-3′, 16 s-1390R 5′-ACGGGCGGTGTCTACAA-3′, 18S-F 5′-ACCTGGTTGATCCTGCCAGT-3′, 18S-R 5′-CTTGTTACGACTTTTACTTCC-3′, 18S-1080F 5′-GGGRAACTTACCAGGTCC-3′ and 18S-1578R 5′-GTGATRWGRTTTACTTRT-3′. The obtained sequencing data (1300 bp) using prokaryotic primers were compared with all published sequences in GenBank using BLASTn at National Center for Biotechnology Information (/) and submitted to the GenBank database (Accession No. MG581460). Results showed that the sequence had a maximum of 80% identities with multiple Acinetobacter baumannii strains (Additional file ). Comparison of the obtained sequence with Acinetobacter baumannii strain KAB05, complete genome (Accession No. CP017650.1) was shown in Additional file . Another sequencing data (1800 bp) were obtained using eukaryotic universal primers pair 18S-F/18S-R and had a maximum of 99% identities with Human Genomic sequences. No sequencing data were obtained using universal primers pair 18S-1080F/18S-1578R.


A non-medicated 51-year-old man with a 30-year history of depression presented to a local hospital complaining of fatigue and loss of appetite. The initial vital signs were: Glasgow Coma Scale 15 (E4V5M6); blood pressure, 139/81 mmHg; heart rate, 114 b.p.m.; respiratory rate, 31 breaths/min; body temperature, 37.2°C; and SpO2, 98%. Physical examination revealed that his abdomen was hard and tender on the left flank, showing signs of peritoneal irritation. The blood test revealed leukocytosis, iron deficiency anemia, thrombocytosis, hypoalbuminemia, hyponatremia, and high C-reactive protein, but did not show liver or kidney dysfunction (Table ). Plain chest and abdominal X-rays showed numerous round-shaped radiopaque foreign bodies suggestive of coins (Fig. A). The patient was diagnosed with coin pica complicated with gastrointestinal tract perforation and he was transferred to the hospital for surgical treatment. On the same day, an emergency laparotomy was performed. Following celiotomy, a hole approximately 5 mm in size was observed on the anterior wall and greater curvature side of the stomach, from which coins were identified. The stomach was remarkably distended with a large number of coins. No coins spilled out from the stomach to the abdominal cavity. The hole seemed to be eroded by the pressure of heavy solid materials. In order to remove the coins, an incision of approximately 5 cm was made on the greater curvature of the stomach separately from the hole that was first observed. After coins in the stomach were removed by hand, the incision was closed primarily. The hole and surrounding tissue seemed structurally weak, presumably due to erosive changes, and, therefore, was closed by a single stitch with the same suture material and an omental patch was applied to the site for reinforcement.
Subsequently, a small number of residual coins in the esophagus were removed by endoscopy (Fig. B). The total number of coins removed was 1,894 and their weight was 8,076 g. All of the ingested coins were Japanese yen consisting of 140 1-yen coins, 99 5-yen coins, 1,642 10-yen coins, 8 50-yen coins, and 5 100-yen coins (Fig. C). The postoperative course was uncomplicated. The patient underwent a psychiatric evaluation and was diagnosed with schizophrenia. He was transferred to a psychiatric facility for treatment on post-operative day 16. The laboratory results of serum concentration of copper and zinc were 56 μg/dL (reference value, 80–135) and 21 μg/dL (reference value, 80–130), respectively.


A 77-year-old male with a history of IHES, COPD, CKD stage III, and active Mycobacterium avium complex (MAC) infection on treatment with rifampin, azithromycin, and levofloxacin was sent to the ER from oncology clinic for evaluation of progressive weakness, lethargy, and hyperkalemia.
The patient had outpatient workup for unexplained hypereosinophilia. He underwent lymph node biopsy which showed no evidence of lymphoma (). Peripheral blood flow cytometry showed myeloid and lymphoid cells with unremarkable immunophenotypic expression. Bone marrow biopsy showed eosinophilia that varied from approximately 25% in the aspirate smears to 60% in the core biopsy (). The infiltrate of eosinophils consisted of eosinophilic myelocytes and mature eosinophils. There were no increase in blasts and no morphologic evidence of lymphoma. The patient had negative fluorescence in situ hybridization (FISH) results using a panel for hypereosinophilia containing probes for 4q12 (SCFD2, LNX, and PDGFRA) rearrangement, 5q32 (PDGFRB) rearrangement, 8p11.2 (FGFR1) rearrangement, and 9q34 and 22q11.2 (BCR/ABL1) rearrangement on a bone marrow specimen. He had normal cytogenetic studies and male-type karyotype. A final diagnosis of idiopathic hypereosinophilic syndrome was made. His disease was resistant to steroids and brief course of chemotherapy with methotrexate.
On his current admission, he was lethargic and cachectic. Vital signs were normal. Skin examination showed widespread erythroderma, scaling, and excoriations. Initial laboratory workup revealed potassium 6.9 mmol/L, creatinine 1.3 mg/dL, alkaline phosphatase 671 unit/L, and WBC 18,000 cells/mcL with 58% eosinophils. Hyperkalemia resolved on the third day of admission. Subsequently, a decision was made to start imatinib at a lower than recommended dose due to the high risk of developing tumor lysis syndrome. Shortly after initiation of imatinib, the patient developed acute restlessness, agitation, shortness of breath, and acute urinary retention. His condition rapidly deteriorated and progressed to acute respiratory failure requiring intubation and mechanical ventilation. He also developed distributive shock with hypothermia and nonanion gap metabolic acidosis. Absolute eosinophil count dropped dramatically from 9,500 cells/mcL to 0 cells/mcL within less than 24 hours following administration of imatinib (). Given the dramatic decline in clinical condition, imatinib was immediately discontinued, and the patient was treated empirically with methylprednisolone and broad-spectrum antibiotics. The patient had normal echocardiogram and brain CT scan. On the next day, chest X-ray showed patchy airspace infiltrates in the left lower lobe suggestive of pneumonia (). Blood cultures showed no microbial growth, and respiratory culture eventually grew multidrug-resistant organisms (MDROs) Klebsiella pneumoniae and moderate Pseudomonas aeruginosa. A CT abdomen and pelvis showed prominent bowel loops with wall thickening, suggestive of bowel ischemia (). The patient condition dramatically declined and died following acute cardiac arrest on the sixth day of admission.


A 25-year-old male presented at our clinics for a right shoulder pain related to a dorsal scapular mass first observed 4 months earlier. The main symptom was a shoulder discomfort when lying on his back, sometimes compromising the sleep. The patient also complained of some weakness when using his right arm under the shoulder level. The medical history consisted in a unique kidney and past treatments for a nodular sclerosis-subtype Hodgkin lymphoma (chemotherapy and radiotherapy, last treatment twelve years ago and no recurrence).
The physical examination revealed a nonmobile 3 cm T × 3 cm AP × 2 cm CC hard mass on the posterior superomedial angle of the right scapula, sensitive to palpation (). Muscle trophicity was symmetrical. The right shoulder presented a full range of motion in all directions without scapulothoracic dyskinesis. Weakness and pain were observed when raising the right shoulder or during active abduction (at all levels).
A right shoulder radiological series including AP, lateral, and Neer views was described normal and conducted additional investigations. A thoracic computed tomography was performed and described a 2.6 cm T × 2.6 cm AP × 2.2 cm CC solid bone mass at the posterior aspect of the superomedial angle of the scapula. The diagnosis of an osteochondroma without signs of malignancy was stated (). No adenopathy or recurrence of the past Hodgkin lymphoma was observed. Retrospectively, the mass was apparent on the shoulder Neer view. A magnetic resonance imaging (MRI) including the right shoulder and scapula confirmed the benign character of the osteochondroma. The accessory nerve (XI) was compressed between the osteochondroma and the deep layer of the trapezius; no muscle atrophy was described ().
The osteochondroma was surgically removed under general anesthesia. The patient was prone, and a 10 cm incision was centered on the mass. The trapezius muscle was split at its superior part at the level of the scapula spine. The accessory nerve was visualized and protected in the deep layer of the trapezius muscle. The osteochondroma was exposed and resected from the supraspinatous fossa with an osteotome. The mass was perfectly smooth and measured 3 cm T × 3 cm AP × 2 cm CC (). The integrity of the accessory nerve was checked before closure. The histopathologic analysis confirmed the diagnosis of a benign osteochondroma ().
The shoulder was immobilized in a sling 10 days for wound care. Free mobilization was then granted. No physiotherapy was needed.
The patient was followed annually up to 3 years. He regained full shoulder range of motion and complete symmetric trapezius and rotator cuff strength. The patient has no clinical and radiological recurrence of the osteochondroma.


The patient was a 12-year old female suffering since early infancy from atopic dermatitis and asthma. Both skin and respiratory symptoms were perennial, with worsening in spring and autumn. Allergy testing, performed at the age of 18 months, resulted positive to Dermatophagoides pteronyssinus and farinae. In addition, tomato, hen’s egg and cow milk were positive to skin prick tests. Following environmental measures to reduce house dust mite exposure and the elimination of tomato, egg and milk from the diet, there was an improvement of the patient’s asthma condition but not in atopic dermatitis. At 3 and 6 years of age, there was a worsening of dermatitis with modest response to topical corticosteroids, while asthma was no longer present. A further worsening of atopic dermatitis occurred at 9 years of age, which was treated with oral bethametasone and topical pimecrolimus. In September 2014, the patient was referred to our Unit; we found peripheral eosinophilia of 14.4% and, suspecting parasitic infections, we evaluated specific IgE for A. lumbricoides, which had a value of 32.50 kU/L. Anthelmintic therapy was prescribed using mebendazole (one 100 mg 1 tablet b.i.d. for 3 days), repeated after 20 and 50 days. Table shows patient data. One month after the first two cycles of therapy, the patient showed progressive improvement of symptoms (Fig. ), and eosinophilia was 12%. Six months after the end of therapy, the skin was free from dermatitis and a further decrease was observed for eosinophilia (11.20%) and Ascaris-specific IgE (23.90 kU/L).


A 59-year-old Caucasian male with a history of hepatitis C cirrhosis and history of hepatitis B exposure presented 8 months after orthotopic liver transplant (LT) with fever, fatigue, myalgia, night sweats, nonproductive cough, and shortness of breath. He received tacrolimus (TCR) 3 mg twice daily and prednisone 7.5 mg daily for immunosuppression. He was afebrile at the time of admission and vitals were stable. His physical exam was normal. White blood cell count was 2.9, hemoglobin 7.1, hematocrit 23, platelets 94,000, AST 44, ALT 64, total bilirubin 1.5, albumin 2.7, protein 6.4, and INR 1.5. The basic metabolic panel was normal. Infectious workup including blood culture, urine culture, CMV, HIV, hepatitis A/B/C serologies, and urine histoplasma antigen was negative. CT scan of the chest showed borderline enlarged axillary lymph nodes. CT scan of the abdomen/pelvis showed moderate retroperitoneal adenopathy and ill-defined soft tissue density within the region of the porta hepatis. Bone marrow biopsy was performed for pancytopenia and showed hypercellular bone marrow (80%) with erythroid hyperplasia and dyserythropoiesis. Flow cytometry showed polyclonal B-cells and plasma cells; no evidence of lymphoma was found. Epstein-Barr virus (EBV) DNA in bone marrow was positive. Periaortic lymph node biopsy showed human herpes virus 8 (HHV8) associated Castleman's disease and marked vascular proliferation (). Immunostain for HHV8 was negative in the bone marrow. Quantitative HHV8 DNA was 611,000 DNA copies/mL. EBV antibody was positive; level was less than 2.70. The patient was started on valganciclovir 900 mg daily, prednisone dose was decreased to 5 mg daily and later discontinued, and rituximab was started. Tenofovir 300 mg daily was started for hepatitis B exposure with negative hepatitis B DNA and positive core antibody. He completed 8 doses of rituximab. Clinical improvement was noticed. TCR dose was reduced to 1 mg twice daily. His tacrolimus levels before dose reduction were between 6.6 and 8.3 ng/ml and after dose reduction they were between 4.6 and 6.5 ng/ml. He required filgrastim for neutropenia. Follow-up CT scan showed decrease in size of lymphadenopathy. HHV8 DNA level was <1000 DNA copies/mL after 4 months and undetectable at 6 months of treatment. Valganciclovir was discontinued after HHV8 viral load remained negative for 3 months. He did have recurrence of hepatitis C and was successfully treated with a combination of Sofosbuvir and Simeprevir. His HHV8 DNA level has remained undetectable.