A 56-year-old woman was complaining about decrease in vision on her left eye.
Prior ocular history involved corneal leucoma on her right eye due to a previous herpes infection (Fig. ). She was currently on the waiting list for a corneal transplantation.
At the ophthalmologic emergency unit, she was diagnosed with a retinal detachment due to an intraocular mass in her left eye (Fig. ). She was sent immediately to the retinal division where ultrasound, ocular biomicroscopy, and wide-field photography were performed (Fig. ). Best-corrected visual acuity (BCVA) was 20/80 on her right eye and 20/200 on her left eye. Intraocular pressure was 14 mm Hg in her right eye and 17 mm Hg in her left eye. The right cornea was opaque due to leucoma (Fig. ). Ocular examination of the left eye revealed an elevated pigmentary choroidal tumor, covering the temporal half of the fundus and accompanied by an exudative retinal detachment involving the macula (Fig. ). B-scan ultrasound confirmed the presence of a choroidal melanoma, showing medium internal reflectivity on A-mode and large size (longitudinal diameter >10 mm; anterior-posterior diameter >16 mm). General oncology screening ruled out systemic dissemination. Macular optical coherence tomography (OCT; Cirrus HD-OCT, Zeiss, Germany) showed a smooth dome-shaped choroidal elevation compatible with choroidal melanoma and associated retinal detachment. Due to the large tumor size, the patient decided to undergo enucleation, after being informed about different treatment options (brachytherapy and enucleation). The patient showed her willingness to use the cornea of the left eye as a transplant for her right eye. After discussion with the ethical committee, its approval, and signing informed consent, the patient underwent enucleation of her left eye (Fig. ). The enucleated sample was examined by a pathologist and found to be free of melanoma cells in the corneolimbal tissue. Afterwards, trepanation of the donor cornea button was performed, and the cornea was transplanted to the right eye (Fig. ).
The patient has been followed for over 60 days without any sign of corneal transplant rejection, and her left eye was according to the enucleation protocol. BCVA in her right eye improved to 20/40 (Fig. ).


A 51-year-old premenopausal woman gravida 3, para 3, was diagnosed with left MCTO 7 years ago. The size of the MCTO was 59 mm at the time of diagnosis. She underwent regular ovarian examination for 2 years after the diagnosis but had not visited the hospital for 5 years. She had a history of appendectomy at 7 years of age and received medication for hyperthyroidism since she was 37 years old. She experienced left lower abdominal pain for 2 days and visited the hospital due to increasing pain. Physical examination showed a flat abdomen with tenderness around the left lower abdomen. A solid tumor was palpable by bimanual examination on the left side. Transvaginal ultrasonography revealed a 91-mm cystic and solid ovarian mass on the left ovary (). She was diagnosed with ovarian tumor torsion and had to undergo emergency surgery. Height, weight, and body mass index (BMI) were 165 cm, 96 kg, and 35.3 kg/m
2, respectively. Body temperature was within the normal range, pulse rate was 84 beats/min, and blood pressure was 121/55 mmHg. Peripheral blood examination showed that the white blood cell count was 8,820/μL, red blood cell count was 4.65 × 10 6/μL, hemoglobin was 12.1 g/dL, and hematocrit was 37.5%. Biochemical data revealed that the C-reactive protein level was as high as 13.9 mg/dL. Levels of tumor makers, namely serum α-fetoprotein, carbohydrate antigen 19-9 (CA19-9), CA125, and squamous cell carcinoma (SCC) antigen were 4.0 ng/mL (reference, <10.0 ng/mL), < 2.0 U/mL (reference, < 37.0 U/mL), 84.1 U/mL (reference, < 35.0 U/mL), and 1.4 ng/mL (reference, < 1.5 ng/mL), respectively. Laparotomy was immediately performed. Operative findings showed 360° torsion of the left ovarian tumor without ascites in the pelvic cavity. There were no sign of congestion and rupture on the surface of the twisted ovary. The uterus and right ovary appeared normal. Left salpingo-oophorectomy was performed. The duration of operation was 54 min, and the volume of blood loss was 30 mL. The diameter of the extirpated ovarian tumor was 11 cm, and the tumor contained fat and hair. Histopathological findings showed both components of mature cystic teratoma and SCC with marked nuclear and cellular atypia in the solid part (). The pathological diagnosis was malignant transformation with SCC of MCTO. We recommended staging laparotomy to determine the treatment strategy. The patient refused to undergo the procedure; subsequently, a strict follow-up for stage IA ovarian cancer was conducted. The patient was discharged from the hospital 10 days post operation. On postoperative day 112, the serum CA125 level was as high as 101.4 U/mL. Positron-emission tomography and computed tomography (CT) showed some nodal lesions with remarkable uptake of 18F-fluorodeoxy glucose (). She was referred to a university hospital due to cancer recurrence. Her BMI was as high as 37.8 kg/m
2, and biochemical examination showed that she had hyperlipidemia and diabetes mellitus. The serum CA125, SCC antigen, CA19-9, and carcinoembryonic antigen (CEA) levels were 216 U/mL (reference, < 35.0 U/mL), 2.0 ng/mL (reference, < 1.5 ng/mL), < 2.0 U/mL (reference, < 37.0 U/mL), and 3.5 ng/mL (reference, < 5.0 ng/mL), respectively. The patient underwent radical surgery with total abdominal hysterectomy, right salpingo-oophorectomy, partial omentectomy, and pelvic and para-aortic lymph node dissection. Operative findings revealed that there was no ascites or dissemination in the abdominal cavity; no metastatic lesion was found in the uterus and right adnexa. The enlarged pelvic and para-aortic lymph nodes were removed. Thereafter, complete surgical treatment was achieved. The duration of operation was 360 min, and the volume of blood loss was 370 mL. Histopathological examination showed positive lymph nodes with SCC. The numbers of positive/total resected lymph nodes in the left obturator, left external iliac, and para-aortic nodes were 1/5, 2/7, and 1/1, respectively. Immunostaining was performed to assess whether the tumor cells were of epithelial or germ cell origin (); the results confirmed recurrence of the malignant transformation of MCTO with SCC (). The postoperative course was uneventful, and the patient was discharged 10 days post-op. She received 6 courses of conventional paclitaxel and carboplatin as adjuvant chemotherapy. She has had no recurrence for 2 years after treatment. The treatment course is shown in .


A 70-year-old man presented with a 3-month history of mild dysphagia and progressive dyspnea. The dyspnea occurred after physical activity and sometimes lasted for 10 days thereafter. Because the patient had a history of emphysema, he first sought medical treatment in the respiratory department. The respiratory physician found no obvious abnormalities in his lungs, and the patient was then recommended to visit the ear, nose, and throat department. Our physical examination revealed no stridor. Transnasal flexible endoscopy () showed a large, round, smooth mass on the posterior wall of the subglottic region. Approximately 75% to 80% of the subglottic area was obstructed. The lesion was about 1.5 × 1.0 cm in size, translucent in appearance, and covered by normal nonhemorrhagic mucosa. Both vocal cords were mobile and symmetrical. The aryepiglottic folds and pyriform sinuses showed no abnormalities. We recommended that the patient be immediately admitted to the hospital for computed tomography (CT), magnetic resonance imaging (MRI), pulmonary function testing, and other examinations. A neck CT scan showed an approximately 1.4- × 1.2- × 1.4-cm low-density area in the posterior wall of the subglottic region. The average attenuation was −84 Hounsfield units (). MRI showed a nodular abnormal signal of about 1.1 × 1.7 cm in size, protruding into the tracheal cavity from the posterior wall of the subglottic area with clear boundaries. T1- and T2-weighted imaging showed high signal intensity, and fat suppression imaging showed low signal intensity. An enhanced scan showed no significant enhancement (). Both CT and MRI suggested that the mass was a lipoma.
The patient underwent tracheotomy and endoscopic excision of the lipoma under general anesthesia. The mass accounted for 80% of the subglottic area and was completely resected with low-temperature plasma assisted by endoscopy (). Bleeding was minimal during the operation, and no postoperative complications occurred.
Pathological examination revealed a 1.5-cm fleshy yellow lesion covered by pseudostratified ciliated columnar epithelium. Many mature fat cells were present in the lesion. Immunohistochemical staining showed a specific immune response of tumor cells to S-100 (). We finally diagnosed the lesion as a subglottic lipoma.
The patient recovered well after the operation. During the 3-month follow-up, transnasal flexible endoscopy showed no recurrence, and the subglottic airway remained unobstructed ().
Ethics approval and patient consent were obtained for publication of this report.


A 38-year-old Caribbean-Black (Afro-Trinidadian) female with a medical history of endometriosis, intermittently adherent with the oral contraceptive pill, initially presented to the adult emergency department with acute dyspnea during the preceding 2 days. Her vital signs reflected systolic blood pressures of 142 mm Hg, heart rate of 112 beats per minute, and respiratory rate of 20 breaths per minute with an oxygen saturation of 92% on room air. Her physical examination revealed a mildly elevated jugular venous pulse (10 cm of water), right chest stony dullness, no peripheral edema, and active menses.
A 12-lead electrocardiogram revealed sinus tachycardia with an incomplete right bundle branch block, right ventricular hypertrophy, and subtle secondary ST-T segment changes (see ). A portable chest radiograph revealed a large-sized, right pleural effusion with mild perihilar congestion (see ). Pertinent diagnostic laboratory investigations included a D-dimer 208 ng/dL (normal ≤500 ng/mL), pro–brain natriuretic peptide (pro-BNP) 323 pg/mL (normal ≤300 pg/mL), cardiac troponin I (cTnI) 0.08 ng/mL (normal = 0.0-0.15 ng/mL). The patient’s arterial blood gas was consistent with mild hypoxia on 24% fractional inspiration of oxygen (FiO2) with an alveolar-arterial gradient (A-a gradient) of 14 mm Hg.
The patient was subsequently admitted for an inpatient hospitalization, and computed tomography (CT)-guided therapeutic thoracentesis was performed with a resultant hemorrhagic exudative effusion. Despite this intervention, the pleural effusion recurred within 48 hours, and cardiothoracic surgery was consulted for a video-assisted thoracoscopic surgery (VATS) pleural biopsy, which later affirmed the presence of endometrial tissue on clinicopathological examination. The tentative diagnosis at this juncture was recurrent catamenial pleural effusions. On further interview, the patient acknowledged that she often experienced dyspneic episodes during menstruation.
During the ensuing hospitalization, she continued to experience persistent shortness of breath with an episode of paroxysmal atrial fibrillation (PAF). A 2-dimensional transthoracic echocardiogram (TTE) revealed preserved left ventricular function with moderate right heart enlargement, septal flattening, and mild pHTN with estimated right ventricular systolic pressures of approximately 45 mm Hg. A 2-dimensional and 3-dimensional transesophageal echocardiogram (2D/3D-TEE) also revealed an intact interatrial septum with agitated saline “bubble” study. The PVs were incompletely visualized and hence the rationale for further advanced imaging (see ). A cardiac CT angiogram (CCTA) affirmed the presence of the suspected PAPVC of the left inferior PV to the left brachiocephalic (innominate) vein with angiographically normal coronary arteries (see ). The patient also underwent cardiac magnetic resonance imaging (CMRI), which demonstrated the same aberrant connection with the remaining pulmonary venous vasculature appearing dilated in addition to the RA, right ventricle, and main pulmonary artery (see and , respectively). Left heart catheterization established angiographically normal coronary arteries with right heart catheterization revealing a significant hemodynamic left-to-right shunt with Qp:Qs ratio of 3:1, mild pHTN, and elevated pulmonary vascular resistance (see for a summary of the pertinent cardiovascular investigations).
Cardiothoracic surgery was reconsulted regarding the surgical repair of the PAPVC. In the interim, the patient was instituted on an optimal cardiovascular regimen that included apixaban for her PAF, angiotensin receptor blocker with a neprilysin inhibitor (ARNI), β-blocker (BB), mineralocorticoid receptor antagonist (MRA) for her heart failure and nitrates, tadalafil, and calcium channel blockade (CCB) for her pHTN. The rest of her hospital course was uneventful, and she was discharged home with scheduled corrective surgery in 2 months (due to our limited resource setting pending consultation from an international specialist CHD cardiothoracic surgeon).


An 82-year-old male in whom progression of anemia was observed on a periodic medical check-up was referred to our hospital. Based on close examination, the patient was diagnosed with ascending colon cancer and bilateral inguinal hernias. Since the right inguinal hernia included the urinary bladder and contained stones, the patient was referred to our department.
The patient had a past history of right inguinal hernia surgery, had noticed difficulty in urination and was being treated with oral tamsulosin and dutasteride. An operative scar and chicken egg-sized bulge were noted in the right inguinal region, and a ping-pong ball-sized bulge was noted in the left inguinal region. Blood and biochemistry tests showed mild anemia, but no other particular finding was noted. Urine examination showed microscopic hematuria and pyuria. The prostate volume was 40 mL, showing enlargement on abdominal ultrasonography, and the maximum urinary flow was 11.6 mL/s on uroflowmetry, indicating a two-stage urination pattern. The residual urine volume was 32 mL. On contrast-enhanced abdominal computed tomography, progressive ascending colon cancer and bilateral inguinal hernias were noted. The urinary bladder had prolapsed from the right inguinal region and it contained several stones (Fig. ).
Based on the above findings, the patient underwent right colectomy and radical surgery for the bilateral inguinal hernias. The inguinal hernia was internal on both sides and was repaired using the McVay method, followed by lithotrity of the urinary bladder. Three stones with a diameter of 5–10 mm were found in the urinary bladder and were transurethrally removed. On stone analysis, the stones were found to be uric acid calculi.


A 72-year-old Asian male was consulted to our hospital with sudden scrotal swelling but no additional symptoms. His past history included low risk CLL in revised Rai stage 0 without any treatment 16 years ago. On physical examination, his left scrotum was slightly swollen, whereas his right scrotum had marked swelling and a detectable hard mass. Blood examination showed high levels of white blood cell (27 840 μL: normal range 3300–8600) and LDH (341 U/L: normal range 124–222); however, other abnormalities including for the testicular tumor markers, serum alpha fetoprotein and human chorionic gonadotropin, were not evident. Enhanced CT showed a round, bilateral testicular tumors (right side 72 × 58 mm and left side 22 × 18 mm) with homogeneous iso-enhancement relative to normal testis, and 8-mm–sized para-aortic masses. These masses were slightly and gradually enhanced in dynamic contrast-enhanced CT without any suspicious lesions of visceral metastases noted except the surrounding lesions of the para-aorta (Fig. a,b). MRI revealed a low intensity on T2-weighted images compared to those of normal testis and a low intensity on an apparent diffusion coefficients map (Fig. c,d). The clinical diagnosis was bilateral testicular tumors including malignant lymphoma, and after informed consent, an immediate bilateral orchiectomy was performed. The tumor was solitary, and rounded shape, with the cut surface of that showing a yellowish color (Fig. a). Pathological finding revealed that the tumor consisted of blastemal cells, each with an atypical small round shape, and scant cytoplasm. These cells morphologically composed of confluent sheets of large neoplastic B lymphocytes resembling either centroblasts or immunoblasts (Figs b,c,a). The tumor lesion of large neoplastic B lymphocytes was immunoreactive for CD20 (Fig. b), and negative for CD5 (Fig. c), CD3 (Fig. d), and CD23 (Fig. e). Atypical small round cells around large neoplastic B lymphocytes were immunoreactive for CD20, CD5, CD23, and Bcl2 (Fig. f), and negative for CD3. These histopathological findings were consistent with a DLBCL variant, a transformation of CLL, with the final diagnosis being RS. PET–CT revealed the presence of positive lesions in the nasal septum, a tiny subcutaneous tumor in front of the left chest, and bilateral adrenal glands that could not be detected on CT (Fig. e–h). Therefore, the patient immediately underwent an induction combination of rituximab with cyclophosphamide, doxorubicin, vincristine, prednisone immunochemotherapy, and the intrathecal administration of chemotherapeutic agents, including methotrexate, cytarabine, and prednisone. After four cycles of the regimen, the patient showed a complete response in an imaging study. Totally, eight cycles of chemotherapy was performed, and the patient was monitored on an outpatient basis. He was successfully in remission for 14 months after the end of immunochemotherapy.


A 39-year-old woman presented to the former hospital due to abnormal findings in her right kidney during an ultrasound on a physical examination. At the time, she was 18 weeks pregnant. The ultrasound findings comprised a heterogeneous, well-demarcated mass at the middle pole of the right kidney with an approximate diameter of 28 mm (Fig. a). Magnetic resonance imaging revealed a multifocal cystic renal mass at the middle pole (Fig. b). The initial treatment plan was observation, followed by resection after birth. However, the tumor increased in size by 4 mm over a period of 4 weeks (Fig. c). Thus, the patient was recommended to undergo resection, and was referred to our hospital.
Fine-needle biopsy was performed to rule out benign tumors, such as mixed epithelial and stromal tumors. The pathological diagnosis was RCC. As the tumor showed definite growth, we chose to perform resection after discussion with the patient, as well as our anesthesiology and obstetrical services. At 26 weeks’ gestation, right open PN was performed. We chose a retroperitoneal approach in the left lateral position with fetal monitoring because we thought it to be important to perform the procedure safely in a conventional procedure. If symptoms of premature labor were observed in association with the operation, administration of a uterine contraction inhibitor was considered. The surgery was successfully completed without any problems for the patient or fetus. Compared to typical PNs, the vessels around the kidney were well-developed; thus, more careful manipulations were needed. The patient recovered well and was discharged on postoperative day 5. Pathological examinations showed clear cell RCC, G2 >G3, Fuhrman grade 2 (Fig. b) with progesterone receptor expression and without estrogen receptor expression (Fig. c). The patient delivered her baby naturally without further complications at 40 weeks’ gestation.


A 30-year-old male presented with diffuse abdominal pain and constipation of 2-day duration. The patient reported no history of blunt trauma or previous surgeries. On clinical examination, the patient was conscious, agitated and disoriented with vital signs including pulse 170 bpm, blood pressure 80/53 mmHg, and saturation 99%. A chest examination was unremarkable. The patient’s abdomen was distended and tense with signs of peritonitis. Laboratory investigations revealed a white blood count of 23x109 and Lactate 5.6mmol/L. A chest x-ray showed no signs of pneumonia or pneumothorax. An erect abdominal x-ray revealed a dilated bowel (see ). The patient was resuscitated with aggressive intravenous fluid therapy and broad-spectrum antibiotics. The patient was admitted to the surgical intensive care unit to stabilize his condition. We shifted the patient to the operative theater after achieving relative stabilization (pulse 120 bpm and blood pressure 105/60 mmHg). An exploratory laparotomy was performed and revealed the distal ileum knotted around the base of the sigmoid loop base (see and ). The closed sigmoid loop and the knotted distal ileum were gangrenous. Ileum segment resection and sigmoid resection were performed, which left 10 cm of terminal ileum. End functional ileostomy and non-functional colostomy (mucus drainage of the colon) were positioned through the skin. Anastomosis was not performed due to the hemodynamic instability of the patient’s condition. The abdomen was laid open due to extensive bowel edema and to prevent abdominal compartment syndrome. The patient had a subsequent second-look operation on post-operative day two, which revealed subsiding general bowel edema with unremarkable abdominal cavity. The midline laparotomy wound was partially closed. The patient was shifted to the surgical intensive care unit with nasogastric tube and urinary bladder catheter. Feeding via nasogastric tube was initiated on the second day post-operatively. Full closure of the laparotomy wound was achieved on post-operative day six. The post-operative period was uneventful. Normal oral diet was initiated on the six post-operative days and shifted to surgical ward. A re-continuation surgery of the bowel was performed two months later. The patient was discharged on the 7th post-operative day of the A re-continuation surgery.


Patient is a 43-year-old female with past medical history of hypothyroidism and obesity. She sought surgical consultation since her body mass index (BMI) was high (36) and she had failed numerous attempts to lose weight over the past 10 years. Preoperative exams including an upper endoscopy were normal. LGS was planned. During the procedure, we used one 15 mm port, one 12 mm port and three 5 mm ports. A 30 telescope was used during the procedure to achieve visualization of the angle of his, a grasper was used as a liver retractor and a 36 French bougie was inserted to decompress the stomach. The incisura was located and a small window in the lesser sac was created 4 cm away from the incisura, the omentum was mobilized cranially, the bougie was advanced to the first part of the duodenum and staplers were used to create the sleeve. () After this, the staple line was reinforced using a 3-0 synthetic absorbable monofilament suture (PDS 3-0, Ethicon, Johnson & Johnson). The specimen was retrieved from the 15 mm port, and the procedure was completed without complications. During the procedure, no lymph nodes or masses were seen. The patient underwent full recovery and was discharged without any apparent complications. Five days later, pathology reported that on the specimen, a small 4-mm polyp was detected in the staple line in the upper part of the fundus, a finding that was not detected on the previous endoscopy. After further evaluation, a grade II well-differentiated multifocal neuroendocrine tumor with vascular and perineural invasion was detected. Ki 67 index was 17% and 3/10 hpf mitosis were discovered (, ).
The prognosis changed immediately, the patient was immediately notified of this finding and a new contrast-enhanced computed tomography revealed no masses or lymph nodes, therefore a D2 radical gastrectomy reconstructed with an esophagojejunal roux-en-y was performed, a drain was placed near esophagojejunal anastomosis and the remainder of the procedure was achieved without any complications. Pathology reported the same neuroendocrine tumor without lymph nodes involvement. After recovery, oncologist consultation was needed and five cycles of adjuvant chemoradiotherapy were achieved. One year after initial surgery and after psychiatric aid, the patient is doing well.


A 62-year-old male presented to the hospital with a 1-week history of headache and an episode of transitory paresthesia in the left upper limb followed by a 2-min lapse in awareness and a claw-like left hand position highly suggestive of an atypical absence seizure. He had no history of fever, malignancy, diabetes mellitus, or corticosteroid use. Laboratory results revealed a normal white blood cell count and a moderately elevated C-reactive protein (63.6 mg/L–normal levels are below 10 mg/L–). The patient was alert and presented neither neurological deficits nor signs of meningeal irritation. An urgent brain computed tomography (CT) scan demonstrated an expansive process in the right parietal lobe []. For better characterization a magnetic resonance imaging (MRI) was also performed, revealing a cystic cortico-subcortical lesion []. Gadolinium injection demonstrated an irregular rim enhancement of the lesion that spread to the subarachnoid space. Restricted diffusion-weighted imaging (DWI) and diminished apparent diffusion coefficient (ADC) along with high lipids and low N-acetylaspartate levels in MR spectroscopy led to the diagnosis of a brain abscess. Therefore, the patient was immediately placed on triple empiric intravenous antibiotic therapy (vancomycin, ceftriaxone, and metronidazole). The workup to identify the infection source included a thoracoabdominal CT scan, transthoracic cardiac ultrasound, and fundoscopy. All of these were unremarkable, but direct visualization of the oral cavity showed very poor oral health.
On day 3, the patient underwent craniotomy with neurophysiological monitoring given the proximity of the lesion to the motor cortex. After opening the dura mater, a swollen brain was found []. A catheter was first used to drain purulent fluid and reduce brain swelling. Then, the adjacent cortex was opened to wash the cavity with saline, antibiotics (vancomycin, and gentamicin), and hydrogen peroxide. Several tissue samples from the cavity were also taken for pathological study, which revealed acute inflammatory changes but no malignant cells. The blood cultures were negative. Likewise, Gram staining of the abscess fluid exhibited no organisms, and routine aerobic/anaerobic cultures revealed no bacterial growth. Therefore, abscess samples were sent to another hospital for the amplification of bacterial 16S ribosomal RNA (rRNA) with polymerase chain reaction. When Pm was demonstrated as the causative agent of the infection, vancomycin was discontinued.
The patient was also assessed by maxillofacial surgeons who detected severe periodontitis with infected mandibular cysts. This condition was considered the primary source of brain infection, and 1 week after craniotomy the patient underwent extraction of the lower teeth and curettage of mandibular cysts. Unfortunately, the material of the extracted teeth was not sent for microbiological studies. The patient was discharged in excellent conditions after 3 weeks of intravenous antibiotics, followed by 1 week of oral metronidazole and moxifloxacine. Oral antibiotics were maintained for 5 additional weeks. Follow-up MRIs demonstrated favorable progress without any radiological suspicion of recurrence [].


An intubated 53-year-old man was transferred to a tertiary burn centre with 24% total body surface area (TBSA) burns to the head, back, arms, legs and inhalation injury secondary to a caravan explosion. Medical history included chronic alcoholism, active smoker and a previous open appendicectomy. Despite fluid resuscitation as per Parkland’s formula, inotropic support was still required. Computer tomographic (CT) trauma series demonstrated stable old and new cervical, thoracic and sacral fractures. He was admitted to the intensive care unit for continued resuscitation.
By day five of admission all burns, including full thickness burns on his back and arms, were debrided and grafted with no further coverage required. On day nine, he developed paralytic ileus, which required colonoscopic decompression. Colonoscopy showed faecal impaction and large, coalescent ulcers in the sigmoid colon suggestive of stercoral colitis.
Subsequently, he remained stable in his systemic inflammatory state tachycardic to 115, blood pressure of 114/59 with minimal noradrenaline requirement, and febrile to 39°C. He had continued small liquid stools and developed larger nasogastric aspirates. Abdomen was tense, distended and tender on the right lower quadrant. He was not peritonitic and bowel sounds were not appreciable. Repeat imaging demonstrated a thickened caecal wall, pericaecal fat stranding and a transition point in the ascending colon secondary suspected stercolith ().
Due to failure of medical management and a mechanical obstruction, the patient received an emergency laparotomy. The greater omentum off the hepatic flexure was found to be adhered to the right iliac fossa at the previous open appendicectomy site causing flexion narrowing of the ascending colon. This was released with diathermy ablation. Multiple segments of viable small bowel appeared oedematous with venous congestion. No bowel resection was performed however 1.3 L of fluid was suctioned from the peritoneal cavity and 1.2 L aspirated from the nasogastric tube. Given the distended loops of bowel, tight abdominal wall, and plan for relook, temporary abdominal closure was achieved with ABTHERA ADVANCE™ Open Abdomen Dressing ().
Relook 24 h later, demonstrated viable bowel and abdomen closure was achieved. Total parental nutrition was subsequently weaned over the week. Extubation and discharge to the ward occurred 2 weeks after presentation. His recovery was complicated by a hospital-acquired pneumonia and large pleural effusion, which was managed with antibiotics and a chest drain. He was discharged to rehabilitation 7 weeks from presentation.


A 42-year-old male with a history of chronic alcoholism and alcoholic liver cirrhosis
presented to the emergency department with epigastric pain. He reported no smoking
or illicit drug use. On presentation, he was afebrile with a blood pressure of
130/80 mmHg, heart rate of 122 beats per minute, respiratory rate of 18 breaths per
minute, and oxygen saturation of 98% on room air. His physical examination was
remarkable for scleral icterus, abdominal ascites, and epigastric tenderness.
Initial laboratory evaluation was remarkable for lactic acidosis of 9.8 mmol/L,
hypomagnesemia of 1.4, elevated B-hydroxybutyric acid of 53.9 mg/dL, low bicarbonate
level of 8 mmol/L, and venous pH of 7.27, as shown in . Chest X-ray was unremarkable, and
computed tomography scan of the abdomen showed findings of chronic pancreatitis. He
was admitted to the intensive care unit for management of suspected starvation
ketoacidosis and lactic acidosis, which was thought to be secondary to
alcoholism/underlying liver cirrhosis. He was administered aggressive volume
resuscitation and electrolyte replacement, as shown in . His markedly elevated lactate on
admission of 9.8 mmol/L decreased to 5.1 mmol/L, yet a few hours later it increased
to 9 mmol/L. During this same time period, his phosphate level dropped from 2.5
mg/dL to 1.1 mg/dL. At that point, phosphate replacement was initiated without
further intravenous fluid and with the correction of phosphate levels, the lactate
normalized, as shown in . He was discharged home in stable condition on multivitamins, magnesium
oxide, thiamine, and folic acid. Five months later, he presented to the emergency
department with encephalopathy secondary to hypoglycemia with a glucose level of 26
mg/dL that was thought to be largely related to poor oral intake and vomiting before
presentation, which was corrected by dextrose 50%. His vital signs were stable, and
his initial laboratory work was remarkable for lactic acidosis of 21.1 mmol/L,
elevated β-hydroxybutyric acid of 33.6 mg/dL, low bicarbonate level of <5 mmol/L,
and venous pH of 6.96, as shown in . He was started on aggressive
volume resuscitation and electrolyte replacement, as shown in . Notably, his lactate again
initially improved from 21.1 mmol/L on admission to 14.5 mmol/L. However, his
phosphate level over that same time period dropped from 6.5 mg/dL on admission to
1.1 mg/dL. Phosphate replacement was initiated without additional intravenous fluid
resuscitation. With the correction of phosphate levels, his lactate normalized, as
shown in .


A 9-year-old female was admitted to a closed psychiatric ward for evaluation and treatment of acute behavioral problems. She was born to healthy non-consanguineous parents with a planned pregnancy, and had no perinatal problems. Her neonatal period was unremarkable, including no history of seizure events. She reached regular developmental milestones, except for a delay of several months with respect to language and motor development, which she quickly compensated for. She did not experience separation or stranger anxiety. There was no family history of psychiatric, neurological, metabolic, or genetic disorders.
After a few stressful events related to her academic work, her symptoms began in the form of somatic complaints, such as abdominal pain, headache, and eye discomfort. The patient refused to go to school and experienced mild sleep disturbances such as fragmented sleep and early awakening. A week after the first symptoms began, she abruptly developed severe symptoms manifesting as psychotic behavior and cognitive disturbance. The patient suddenly ceased all verbal ex-pression, and occasionally made strange sounds as if she were swimming in water. At night, she did not sleep and cried while displaying signs of irritability and agitation, such as pulling her own hair. The parents attempted to communicate with her about these behaviors; however, she was unable to explain herself logically or provide adequate responses to their questions. A neurological abnormality of mild bilateral stiffness in her upper extremities was also noted.
Brain computed tomography was performed in the emergency room (ER) to rule out any neurological condition such as a vascular disease or tumor. There were no abnormalities in her laboratory examinations; therefore, the patient was referred to a psychiatric department with provisional diagnosis of psychotic disorder not otherwise specified. Her severe condition required intensive treatment and assessment; however, her parents refused to hospitalize her. Thus, she was discharged from the ER with a prescription of risperidone (1 mg daily), paroxetine (10 mg daily), and benztropine (0.5 mg daily). Continuous medication failed to improve her symptoms, and her psychotic symptoms worsened. She reported both auditory and visual hallucinations. Five days later, she visited the ER again and was hospitalized in the child and adolescent psychiatric inpatient unit for thorough assessment and treatment.
Atypical antipsychotics were initiated to reduce her irritability and psychotic behavior, with a provisional diagnosis of early-onset schizophrenia. Risperidone 0.5 mg was administered daily and titrated up to 0.5–2 mg b.i.d., but the patient experienced acute dystonic reaction. As such, olanzapine was administered as a substitute. Olanzapine 1.25 mg was administered and titrated up to a tolerable dose, which was 2.5–12.5 mg b.i.d. The treatment slightly improved her irritability and sleep disturbance, but her bizarre behavior continued, and communicating with her remained difficult. There were no clear neurological abnormalities, although she was disoriented in time, place, and person.
Steady antipsychotic treatment did not appear to have an effect; therefore, a neurology consultation was arranged to identify possible neurological causes. A faculty member of the neurology department suggested performing a series of neurologic examinations to rule out organic causes. Ten days after her initial admission, the patient underwent brain magnetic resonance imaging (MRI); however, no abnormalities in the parenchyma or CSF spaces were detected. Medical staff planned to administer electroencephalographic (EEG) recording followed by a spinal tap; however, both tests were postponed because the patient was unable to cooperate for the required procedures to be performed. Autoimmune encephalitis was suggested as a possible diagnosis, as she was too young and the disease progressed too rapidly to be considered early-onset schizophrenia, and she did not respond well to standard antipsychotic treatment. On the 34th day of admission, she underwent an autoimmune antibodies titer, which revealed antibodies to NMDA receptors present in her serum (1:80 titer).
She was treated with methylprednisolone (25 mg b.i.d. for seven days), intravenous immunoglobulin (10 g daily for five days), and rituximab (400 mg per cycle). Pelvic MRI performed on the 60th day of admission revealed no signs of ovarian teratoma. Meanwhile, 2.5 mg of olanzapine and 0.5 mg of lorazepam were concurrently administered to manage her residual behavioral symptoms and anxiety, which eventually decreased and ceased by the time of discharge.
Her mental status and behavioral symptoms began to improve as treatment for the encephalitis was initiated. She was discharged on the 107th day of admission following a third cycle of intravenous rituximab treatment. An antibody titer test performed 1 week before discharge reported a weak positive result. At every follow-up, her impulsivity and negativity were found to be gradually improving, and she began to regain her academic abilities. The fifth (and final) cycle of rituximab treatment was administered 63 days after discharge. A follow-up serum autoimmune antibodies titer test was conducted 5 months after the first test. It was negative for anti-NMDA receptor antibody, highlighting the efficacy of her treatment.
shows the results of neurocognitive testing performed 4 months after discharge. She communicated easily with the tester and her answers to questions were mostly appropriate during the test. However, the report also noted that she had difficulty performing tests that required verbal ex-pression. Her full-scale Intelligence Quotient was shown to be 76, which is categorized as borderline intellectually functioning. This result was considered to reflect substantial progress, as she had been unable to perform the basic tests or answer simple questions during the acute stages of her disease. The results of the childhood autism rating scale and Asperger syndrome diagnostic scale were normal, and the social maturity index was age-appropriate. Her cognitive function was not considered to have fully recovered compared to her baseline status.
An Advanced Test of Attention was administered to assess symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) []. The patient showed one of four total T-scores exceeding 65 (over 1.5 standard deviations from the mean), placing the performance of the patient within a range typical of ADHD in both visual and auditory attention tests (). She was especially impaired in the section on “commission errors,” indicating impulsivity and disinhibition.
Approximately 1 year after discharge, the patient is clinically well, and her mother has reported that she has nearly returned to a functional level similar to that before the onset of her disease.


A 65-year-old woman presented in the emergency department complaining about acute diffuse abdominal pain that had begun 10 h earlier. She did not mention any pre-existing gastrointestinal disorders and was not on regular medication. Her medical history included non-metastasized ovarian cancer, treated with double oophorectomy and salpingectomy through Pfannenstiel incision, 1 month previously. She was given the first dose of bevacizumab as postoperative adjuvant therapy 10 days before the initiation of her present symptoms.
The patient was afebrile but hemodynamically unstable, with 115 bpm and a systolic pressure of 80 mmHg on presentation. Clinical examination revealed abdominal distension, diminished bowel sounds and severe tenderness with peritoneal signs in all of the abdominal quadrants. Her laboratory blood examination showed elevated number of neutrophils (7.77 K/μl), elevated C-reactive protein value (82.46 mg/dl) and decreased Na+ (119 mEq/l). After initial resuscitation, a computed tomography (CT) scan was performed. It showed free abdominal air and fluid in the peritoneal cavity, indicating an intestinal perforation (–).
Subsequently, an emergent exploratory laparotomy was decided upon. The exploration of the peritoneal cavity revealed a large amount of dirty fluid, total absence of the anterior and lateral walls of the first part of the duodenum and total bowel discontinuation after the pylorus (). No other disorder or sign of metastasis was present. The pylorus was sutured, a transmesocolic gastroileac anastomosis was performed and a Pezzer tube was placed in the duodenal remnant. Three drains, in Douglas, and in the right and left space were also placed. Empirical triple antibiotic treatment was administered. Postoperatively, the patient remained in the intensive care unit for 24 h. Her hospital stay was further complicated with wound dehiscence and spontaneous low-output enterocutaneous fistula, which were treated conservatively. The patient was discharged in good health on the 28th postoperative day, and the Pezzer tube was safely removed 1 week later.


A healthy 47-year-old male with past medical history significant only for hypertension and nephrolithiasis presented to Englewood Health Medical Center in October 2019 with right flank pain radiating to the pubis, hematuria, hard stool with straining and fifteen pound weight loss over 6 months. On physical examination, multiple café au lait spots, small neurofibromas on his trunk and arms and axillary and inguinal freckling were observed. On CT scan, he was found to have a 10.1-cm soft tissue mass in the right hemipelvis and a nephroureteral stent with a 3-mm stone in the proximal right ureter (). Further history revealed the patient had a known pelvic mass discovered on CT approximately 10 years prior (), which was again observed on CT in June 2019 during a hospitalization for nephrolithiasis at Hackensack University Medical Center (); he had been lost to follow-up.
During this hospitalization, colonoscopy with biopsy of the mass and partial polypectomy of a large benign-appearing polyp in the ascending colon was performed. Pathology revealed spindle cells and a tubular adenoma with intramucosal adenocarcinoma, respectively. He was discharged home with scheduled follow-up for preoperative planning for robotic resection of the pelvic mass via abdominoperineal approach. However, days later, he returned to the emergency department with worsening right flank pain. He was taken to the operating room for mass resection. Rectal examination revealed a palpable large pelvic mass displacing but not invading the rectum. Initial laparoscopy revealed no abnormality in the small or large intestine, omentum, liver or spleen. Robotic approach was utilized to enter the mesorectal space posterior to the rectum, taking care to preserve the ureters and hypogastric nerves (). Robotic dissection continued to open the anterior peritoneal reflection, where a large tumor was noted abutting the right side of the rectum, pelvic bone and obturator canal. The mass was carefully separated from these structures using sharp dissection and electrocautery (). The urology team then continued dissection, freeing the mass from the prostate, bladder and right seminal vesicle. The tumor was removed through a Pfannenstiel incision covered by a GelPort. The incisions were closed. The patient was extubated in the OR, having tolerated the procedure well. His postoperative course was only remarkable for a brief period of urinary retention, which resolved spontaneously. He was discharged home on postoperative day 3 with scheduled follow-up appointments with urology and colorectal surgery.
The pathology revealed a 282-g nodular tumor measuring 10.7 × 8.5 × 7 cm that was grossly tan, fibrotic and firm with focal yellow discoloration and soft flesh areas (). Microscopic analysis revealed high-grade spindle cell sarcoma arranged in intersecting fascicles with extensive areas of necrosis (). The lesional cells had fibrillary eosinophilic cytoplasm and evoid nuclei with nuclear pleomorphism (). Areas of rhabdomyoblastic and chondroid differentiation were also noted ( and ). Immunostaining was positive for desmin, focally for CD 34 and Bcl2, while Cam 5.2, CD117, S-100, SMA and HME45 immunostains show patchy staining for myogenin. Expression of H3K27me3 was completely lost in the tumor cells. MyoD1, SOX10, MDM2 and CDK4 were negative. It was identified as a high-grade MPNST with heterologous rhabdomyosarcomatous differentiation, i.e. MTT. All margins were negative.


A 35-years-old male patient, originally from Russia, attended the Dermatology Service of the General Hospital in Mexico due to two ulcerative skin lesions with a semi-dry appearance, active borders, one of which was in the lower left pre-atrial region and the other in the dorsal region of the left forearm (). The patient referred having travelled to different Middle Eastern countries (Israel, Turkey), and to the Balkan region (Armenia, Georgia) and Russia, between May and June 2019. In August of the same year, he detected red and indurated papules, leading him to seek medical attention in San Cristobal de las Casas, located in the Mexican State of Chiapas, in late August. Cryotherapy with liquid nitrogen was applied to the lesions, leading to their temporary reduction in size. After a renewed flare-up of the lesion edges, the patient was attended at the Tropical Medicine Center (UNAM/Hospital General de Mexico), where he was clinically diagnosed as having localized cutaneous leishmaniasis (LCL). For the confirmation, Giemsa-stained smears of the lesion and ELISA tests for L. braziliensis, L. infantum/chagasi, L. major and L. mexicana were carried out. Additionally, an aspirate of the lesion was performed and the recovered material was grown in NNN medium (Novy-MacNeal-Nicolle) and in 199 Hank’s culture medium (Cat. 12350039, Gibco, Burlington, Ontario, Canada), supplemented with 10% decomplemented fetal bovine serum- FBS (Cat. 16000044, Gibco, Burlington, Ontario, Canada). The quickly growing promastigotes were used for species identification. To this end, promastigote DNA was extracted with DNeasy Blood & Tissue kit (QIAGEN Inc., Hilden, Germany) following the manufacturer’s guidelines. For the PCR analysis, a 589 bp segment of the alanine aminotransferase gene (ALAT), a 350 bp of the heat shock protein 70 (hsp70) and 300 bp of the internal transcribed spacer 1 (ITS1) were amplified using 25 µL QIAGEN Master mix (QIAGEN Inc., Hilden, Germany), 1 µL (10 µM) of each primer (ALAT: Fwd 5´-GTGTGCATCAACCCMGGGAA-3´and Rvs 5´-CGTTCAGCTCCTCGTTCCGC-3´; Hsp70: Fwd 5´-GGACGAGATCGAGCGCATGGT-3´ and Rvs 5´-TCCTCCGACGCCTCCTGGTTG-3´; ITS1: Fwd 5´-CTGGATCATTTTCCGATG-3´ and Rvs 5´-TGATACCACTTATCGCAC-3´ ), 2-3 µL of extracted DNA and bi-distilled sterile water in a final volume of 50 µL. Additionally, L. mexicana DNA and bi-distilled sterile water were used as positive and negative controls, respectively. We followed the amplification conditions previously reported. The PCR products were run on a 1% agarose gel stained with Smartglow (Cat. E4500-PS, Accuris Instruments, Edison, NJ, USA). The PCR products were purified using the Agencourt AMPure XP kit (Cat. A63882, Beckman Coulter, Brea, CA, USA). Amplicons were sequenced using the BigDye Terminator v3.1 Cycle Sequencing Kit (Cat. 4337455, Thermo Fisher, Waltham, MA, USA). The sample was purified by the BigDye XTerminator (Cat. 4376486, Thermo Fisher, Waltham, MA, USA) prior to loading on the ABI 3730xL DNA analyzer (Thermo Fisher, Waltham, MA, US). Sequencing was carried out at the Sequencing Unit of the National Institute of Genomic Medicine. Chromatograms were visualized and a consensus sequence was generated using the Chromas software (version 5, Technelysium, South Brisbane, QLD, Australia). The consensus sequence was compared to reference sequences deposited in GenBank using the BLASTn tool (National Center for Biotechnology Information, Bethesda, MD, USA). Sequences of validated Leishmania species were downloaded and a global alignment was conducted using the Clustal W algorithm (Informer Technologies, Inc., Dallas, US) with the software Bioedit (Informer Technologies, Inc., Dallas, US). Finally, a Maximum Likelihood phylogenetic reconstruction was carried out using the Tamura-three parameters model with invariant sites (I) with 10,000 Bootstrap replicates in Mega 6.0. Gaps were excluded from the analysis. Sequences were deposited in GenBank under the accession numbers MT157311, MT157312, and MT140349.
The Giemsa-stained smears of the lesion showed abundant amastigotes within macrophages. The ELISA analyzed the patient’s serum revealing some degree of cross reactivity between four Leishmania species: L. braziliensis, L. infantum/chagasi, L. major and L. mexicana, yet higher antibody levels were recorded for L. major and L. mexicana antigens (). The isolated parasites were used for the PCR evaluation and a successful amplification of the three genes was achieved (). Using the BLAST analysis, these consensus sequences were 99% (538/544 bp), 100% (323/323 bp), and 100% (277/277 bp) identical to the corresponding sequences of the ALAT (MH455379), hsp70 (LN907846), and ITS1 (FN677341), genes respectively, of L. tropica from Israel and Russia. For the phylogenetic analyses, we only included fragments of 540, and 320 bp of the ALAT, and hsp70 genes, respectively. The Maximum Likelihood analysis confirmed that the parasite recovered from the patient corresponded to L. tropica (). The patient was treated with intralesional applications of 1 mL of glucantime per lesion at 5-day intervals with outpatient monitoring for 4 weeks. The case resolved favorably, the lesions healed adequately and the patient was discharged ().


A previously healthy 24-year-old woman had been admitted to a local hospital 10 days before on suspicion of meningitis due to fever, headache, nausea, and malaise. She subsequently became drowsy, incontinent, and unresponsive to external stimuli for the last 4 days. She was referred to our emergency center on January 25, 2017 with complaints of abnormal movement and decreased mental status.
The patient's initial vital signs were stable. Her mental status was stupor and she was not able to obey to command. Involuntary movements of both arms and legs were present. However, brainstem reflexes were normal and there was no evidence of motor weakness or sensory deficit. Pathologic reflexes were absent. Routine laboratory examinations were normal except mild leukocytosis (white blood cell [WBC], 12,790/µL). Cerebrospinal fluid (CSF) examination disclosed mild pleocytosis (WBC, 260/µL; lymphocyte, 91%) and CSF protein (25.7 mg/dL) and glucose (72 mg/dL) were within normal range. All viral and bacterial markers were negative. Brain magnetic resonance imaging (MRI) revealed no significant abnormalities. Electroencephalography (EEG) showed frequent runs of rhythmic theta activities with slow background activity. Under the diagnosis of infectious meningoencephalitis, she was empirically treated with antibiotics, antivirals, and anticonvulsants. However, her neurologic deficits such as mental change and motor weakness continued to worsen and she underwent mechanical ventilation and tracheostomy. She started to show involuntary movements on her face, mouth, and tongue (oro-linguo-facial dyskinesia) in 2 weeks after the admission. We started immunotherapy on suspicion of autoimmune encephalitis based on characteristic features such as persistent altered mental status and oro-linguo-facial dyskinesia. Intravenous steroid pulse therapy (methylprednisolone 1 g daily for 5 days) was not effective. However, her mental status started to improve after 5 cycles of plasma exchanges. She showed dramatic improvement in mental status and quadriplegia accordingly with plasmapheresis that she could breathe without a mechanical ventilator, obey to command, and move her limbs voluntarily. Positive results of anti-NMDAR antibodies in her CSF and serum prompted us to explore for underlying tumor.
Computed tomography of the thorax, abdomen, and pelvis was performed and revealed a 1 cm sized mass suggestive of MCT arising from the right ovary. Serum tumor markers were within normal limits: CA 125 was 5.0 U/mL and CA 19-9 was 4.6 U/mL. We promptly performed laparoscopic right ovarian cystectomy on March 29, 2017. Intraoperative frozen section analysis and the final pathological diagnosis was MCT (). Her mental status continued to improve and returned to normal. On postoperative day 8, her tracheostomy tube was removed. She was transferred to the rehabilitation department for mild quadriparesis and ataxia. She was discharged 2 weeks post-operatively with mild memory deficit.
The requirement for patient consent was waived by the Institutional Review Board of Dongguk University Ilsan Hospital (DUIH 2020-03-004).


A 38-year-old right-handed man with mild intellectual disability was admitted to our department with the primarily complaint being acute confusion. He had a history of two GTCS at 22 years of age. EEG and magnetic resonance imaging showed no evidence of epilepsy, but the patient was diagnosed with epilepsy based on the clinical course of his condition; valproate (VPA; 600 mg/day) was started (because carbamazepine induced skin eruptions). No obvious convulsive seizures were witnessed thereafter.
At 23 years of age, the patient presented with episodic mental alterations lasting from 30 min to 1 h and characterized by disoriented behavior followed by partial amnesia. These episodes were interpreted as focal impaired awareness seizures (FIAS) with subsequent postictal confusion. Thus, phenytoin (PHT; 250 mg/day) was added to the VPA.
At 24 years of age, the patient experienced acute confusion even without GTCS or FIAS. He exhibited agitation, visual hallucinations, and assaultive behavior toward his family members, for which he required psychiatric hospitalization. The onset of this behavior was abrupt and the confusional state lasted several days, following a fluctuating course until it gradually resolved. The patient had partial memory of his abnormal behavior and explained that family conflicts had triggered these episodes. The attending psychiatrist interpreted these transient confusional states as reflecting “acute interictal psychosis” or “brief reactive psychosis” and started the patient on risperidone (2 mg/day) to prevent the recurrence of the psychotic episodes. After discharge from the psychiatric ward, the patient had ideas of reference and subtle auditory hallucinations.
At 28 years of age, VPA was discontinued because the patient developed liver dysfunction, and PHT monotherapy was prescribed.
He started to experience recurrent episodes of acute confusion at 30 years of age. The clinical symptoms and courses of these episodes were similar to those he had experienced at 24 years of age. Antipsychotics (risperidone 10 mg, propericiazine 150 mg, haloperidol 18 mg, levomepromazine 100 mg, olanzapine 10 mg) failed to resolve the acute confusion occurring at a yearly basis, and the patient required psychiatric admission every time.
None of the bedside EEG results were diagnostic, even though they were performed as soon as the patient had recovered from his agitation. Some EEGs showed excessive theta activity that may be explained by his antipsychotic medications; however, there was no evidence of epileptiform discharges. Additionally, he underwent several routine outpatient EEG examinations, but interictal EEGs during wakefulness and sleep did not reveal any diagnostic epileptiform abnormalities. HV activation provoked high-amplitude slow waves that were maximal bifrontally at diffuse regions, without clear clinical symptoms. EEG recovery times were sometimes slow, exceeding 60 s, but these findings were nonspecific.
On his most recent day of admission at 38 years of age, the patient was brought to the emergency room after an episode of acute confusion without an obvious trigger. Clinical examination showed no signs except for partial amnesia regarding his violent behavior toward his mother. His mother had witnessed him falling after hyperventilating, and the transient confusional state had begun after he arose. Based on this account and past EEG findings showing EEG slowing after HV activation, an urgent EEG was conducted to evaluate the patient's conscious state. During the first half of the recording, numerous alpha waves appeared in the occipital region, with frontal dominant theta/delta activities. However, voluntary HV triggered diffuse, high-amplitude slow waves that lasted 1 min post-HV and gave way to frontally predominant rhythmic delta activity (RDA) 1 min later (Fig. ). Over time, some sharp waves were superimposed on RDA and RDA spread from the frontal region to the general region (Fig. , Fig. ). The RDA with superimposed sharp waves lasted over 5 min, during which time the patient became restless and removed the electrodes without following instructions. The clinical interview performed by the EEG technician revealed that the patient was disoriented.
Given the patient's medical history, EEG findings (continuous RDA with “evolution” in frequency, morphology, and location [Fig. , Fig. , Fig. ]) and clinical symptoms, we diagnosed the patient as having NCSE with impairment of consciousness and concluded that this condition had caused both his “acute confusion” and “prolonged FIAS-like episodes at the age of 23.” Thus, PHT was discontinued and replaced with VPA (1,200 mg/day) as indicated in cases of AS, one of the subcategories of NCSE. The patient was prescribed monotherapy with VPA [], but sporadic AS recurred. Therefore, levetiracetam (1,000 mg/day) was added. This drug combination has kept him seizure-free for 3 years. The cytogenetic study carried out on phytohemagglutinin-stimulated blood lymphocytes stained with trypsin-Giemsa banding technique showed no anomaly of chromosomes, such as ring chromosome 20.


We present the case of a 68-year-old woman who presented with weakness and syncope after large volume hematemesis. She was not on any prior antiplatelet or anticoagulant therapy. Physical examination revealed tachycardia to 127 bpm (beats per minute), hypotension to 76/45 mm Hg, and conjunctival pallor. Her hemoglobin and hematocrit on admission were 8.5 g/dL and 25.6%, respectively. She was managed with IV (intravenous) fluids, packed red blood cell transfusion, and Pantoprazole and Octreotide infusions. An upper endoscopy (esophagogastroduodenoscopy) within 24 hours revealed erythematous, friable, spontaneously oozing mucosa with neovascularization in gastric fundus, which was treated with bipolarcautery as depicted in . Biopsy was not obtained due to recent bleeding. She was discharged on oral Pantoprazole.
Two days later, she was readmitted due to severe recurrent hematemesis with similar findings on repeat esophagogastroduodenoscopy with the addition of an adherent clot over the area of previously oozing and friable mucosa, as depicted in . Bleeding was controlled with argon plasma coagulation and biopsies were obtained from the gastric fundus. Due to the recurrent bleeding, an angiogram was performed. Active bleeding could not be seen. Prophylactically, the left gastric artery was embolized. The biopsies revealed low-grade B cell MALT lymphoma with negative H pylori. She was treated with 20 fractions of radiotherapy with the intention to cure. She did not experience further episodes of bleeding and has remained in remission since.


An 84-year-old male with past history of hypertension, aneurysmal coronary artery disease (CAD), abdominal aortic aneurysm (AAA) treated previously with endovascular repair 2 years ago presented for surveillance of his AAA repair. Computed tomography angiogram (CTA) revealed persistent endoleak from the repaired AAA. It also demonstrated interval growth of previously known right coronary artery (RCA) aneurysm from 4 cm to 7 × 8 cm in diameter (). Patient denied any symptoms including angina but was admitted to the hospital for further work-up. Vital signs at the time of admission revealed a blood pressure of 159/78 mmHg, heart rate of 65 beats/min, oxygen saturation (SpO2) of 95% on room air. Physical examination was otherwise unremarkable. At home, he was on low dose daily aspirin and high intensity rosuvastatin for known CAD and CAA. His electrocardiogram (EKG) showed inferior lead Q waves suggesting previous inferior infarction and occasional premature ventricular complexes (). Cardiac troponin was unremarkable. Transthoracic echocardiogram showed borderline left ventricle ejection fraction of 50% with inferolateral wall hypokenesis. It also revealed a large CAA containing partially thrombosed material and compressing the right ventricle inflow at the level of tricuspid valve, consistent with patient’s previous history of RCA aneurysm (). A review of patient’s myocardial perfusion scan performed 2 years back for pre-operative evaluation showed mixture of scar and ischaemia in the left circumflex coronary artery (LCx) territory. Coronary angiography (CA) was performed which showed diffuse aneurysmal and obstructive coronary artery disease with a giant partially thrombosed mid-vessel RCA aneurysm, 7 × 8 cm in its greatest dimensions with distal chronic total occlusion (). Retrograde collaterals from left circumflex (LCx) were seen filling the RCA. Diffuse small-sized multiple aneurysms of left anterior descending artery with multiple areas of complex 75% narrowing and mid-vessel LCx ectasia/small aneurysm with complex 50–70% stenosis were also seen on CA. Vascular surgery recommended no further intervention for the AAA as they deemed the endoleak to be stable after carefully reviewing the images. However, considering the massive size and rapid growth of the RCA aneurysm with impending risk of rupture and sudden death, percutaneous management with coil embolization was considered as the size of the aneurysm precluded stenting as an option and patient’s age, frailty, and comorbidities made surgery prohibitive. Patient underwent successful coiling of the aneurysm and proximal RCA using seven coils with good recovery. At discharge, patient’s aspirin and statin were resumed.


A 68-year-old Chinese man, an ex-smoker with a 40 pack-year history (quit three years ago), initially presented with low-grade fever, intermittent cough, yellow sticky sputum, and bilateral neck masses in August 2018. Chest computed tomography (CT) scan showed an irregular mass in the middle lobe of the right lung, swollen bilateral hilar and mediastinal lymph nodes, and right inferior pulmonary embolism. Histologic examination of an initial bronchoscopic biopsy showed poorly differentiated lung adenocarcinoma (Fig ). Immunohistochemistry studies revealed that PD-L1 (clone SP142) was highly expressed in the tumor cells (tumor proportion score [TPS] was about 70%, Fig ) and approximately 40% of the tumor-infiltrating cells had PD-1 expression (clone NAT105, Fig ). Next-generation sequencing revealed that this patient had a high tumor mutational burden (TMB, 20.7 mut/Mb, Nanjin Geneseeq Technology Inc.) with no alteration in EGFR, EML4-ALK, ROS-1, c-MET, and BARF. The fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed an irregular mass in the right middle lobe, right adrenal gland metastatic nodule, splenic metastatic nodule, and lymph node metastasis of the bilateral neck, supraclavicular region, right axilla, mediastinum, hilar, and retroperitoneum (Fig ). Contrast-enhanced magnetic resonance imaging (MRI) of the brain showed no abnormalities. Therefore, this patient was staged as cT3N3M1c (IVB).
The patient received the first cycle of pembrolizumab 200 mg intravenously without contraindications on 9 November 2018 (Fig ), based on KEYNOTE-024 and continuous treatment with enoxaparin (6000 IU per time, subcutaneous injection, every 12 hours) for pulmonary embolism. Alanine aminotransferase (ALT) levels increased from 59 units per liter (U/L) before treatment to 132 U/L (reference range: 15–40 U/L) on day 7, with aspartate aminotransferase (AST) levels of 53 U/L (reference range: 15–40 U/L) and alkaline phosphatase (ALP) levels of 296 U/L (reference range: 45–125 U/L). Although the patient received immediate outpatient therapy with diammonium glycyrrhizinate and polyene phosphatidylcholine, the ALT, AST, and ALP levels peaked at 233 U/L, 89 U/L, and 296 U/L, respectively, 13 days after pembrolizumab infusions (Fig , Table ), reflecting a grade 3 (severe) elevation in ALT levels as per Common Toxicity Criteria for Adverse Events, Version 4.0 (CTCAEv4.0). His synthetic liver function remained intact, with normal bilirubin, albumin, and blood coagulation function. There were no clinical or biochemical signs of acute liver failure, such as jaundice, coagulopathy, hepatomegaly, or hepatorenal syndrome.
There was no history of chronic liver disease, alcohol consumption, intravenous drug use, the use of other medications or herbal supplements. A comprehensive screening was performed to evaluate the potential causes of hepatitis. Serologies for hepatitis A, B, C, and E were negative. Autoimmune tests for antismooth muscle antibody (Ab), antimitochondrial Ab, antiparietal cell Ab, antiliver and kidney microsomal Ab, anticardiac Ab, and antimitochondrial Ab M2 subtypes were also negative. Antinuclear antibody was mildly elevated at 1:160 (cytoplasmic type), but it was not considered clinically significant in this setting. Ultrasound showed that the liver was normal in shape and size, with no evidence of hepatic lesions or fibrosis. Finally, the patient was admitted for grade 3 ICI-induced hepatitis, according to CTCAEv4.0.
Treatment for hepatitis was initiated with methylprednisolone at 0.5 mg/kg (intravenous 40 mg per day, Fig ). ALT levels decreased to 145 U/L with AST levels of 49 U/L and ALP levels of 144 U/L after six days of intravenous methylprednisolone. Intravenous methylprednisolone was discontinued and changed to an oral form at 20 mg and 12 mg/day for six days, followed by 8 mg/day. However, ALT levels returned to 201 U/L. Considering that long-term high-dose corticosteroids would compromise the efficacy of immunotherapy, bicyclol, a Chinese hepatoprotective agent, was added at 50 mg three times per day without adjusting the dose of methylprednisolone. Elevated ALT levels rapidly resolved to 52 U/L 7 days later, and bicyclol was discontinued on day 40 (Fig ). The patient reported significant improvement in physical activity. Physical examination showed that supraclavicular lymph node metastasis had dramatically shrunk in size and disappeared one month after the first cycle of pembrolizumab. Therefore, the patient received retreatment with pembrolizumab on day 38. During this period, ALT levels were well-controlled with 8 mg methylprednisolone and were only increased to 159 U/L on day 54 (Fig ). CT scan showed a significant decrease in the size of known tumors in the right lung mass, the right adrenal gland metastatic nodule, and the mediastinal lymph nodes on day 67. The splenic metastatic nodule had completely disappeared (Fig ). ALT levels increased again to 249 U/L on day 103, followed by a gradual decrease to normal levels after the addition of bicyclol. The patient did not experience recurrence of hepatitis, even after the withdrawal of methylprednisolone and bicyclol on day 195 (Fig ). After nine cycles of pembrolizumab, the treatment response was assessed by durable partial remission (50% reduction), based on radiographic assessment and resolution of pulmonary embolism (Fig ).
Blood count tests showed a high pretreatment neutrophil-to-lymphocyte ratio (NLR) (Fig , Table ), indicating a poor outcome. However, 14 days after the initiation of pembrolizumab treatment, an increased lymphocyte count and a decreased neutrophil count resulted in a dramatic decrease in NLR detected in the peripheral blood (Fig , Table ), which was associated with a better outcome. The levels of proinflammatory cytokines IL-6 and TNF-α were upregulated with the onset of hepatitis and returned to normal when hepatitis was controlled (Fig ). The absolute number of lymphocytes and neutrophils, NLR, and the percentage of CD8+ and CD4+ T cells was not significantly affected by hepatitis or methylprednisolone administration (Fig ). However, the production of granzyme B and IFN-γ in CD8+ T cells was diminished by one-third after the administration of high doses of methylprednisolone and restored when the dosage of methylprednisolone was reduced to 8 mg/day, while granzyme B+ and IFN-γ+ CD4+ T cells were not alerted (Fig ). The levels of IFN-γ and IL-2 in the plasma were elevated after retreatment with pembrolizumab (Fig ). These results indicated that the antitumor activity of T cells was impaired with high, but not low-dose methylprednisolone. In accordance with previous reports,, we also found a reduction in senescent T cells (Fig ) and MDSCs (Fig ), and two biomarkers associated with better outcomes, in the peripheral blood during treatment. These results indicated that long-term low doses of methylprednisolone combined with bicyclol to control pembrolizumab-induced hepatitis did not affect ICI efficacy.


A 69-year-old female was diagnosed with A-com aneurysm [] with left A1 dominance. The patient was operated with left pterional craniotomy with a transsylvian approach. Intraoperatively, aneurysm was found as shown in . After application of the first clip [], ICG was done suggestive of complete occlusion of the aneurismal sac [] and no residual. After doing intraoperative endoscopy, we found a residual aneurysm below the first clip [], hence, the second clip application was needed for residual aneurysm [].


A 79-year-old female presented with A-com aneurysm with right A1 dominance []. The patient was operated with right pterional craniotomy with transsylvian approach, and aneurysm was visualized as shown in . Preclipping endoscopy was done [] which showed small perforator adherent to dome of the aneurysm, but the aneurysm neck was free. Aneurysm was clipped under the microscope [], but no perforator compromise was noticed, however, after doing postclipping endoscopy [], we found that perforator is kinked and part of its wall is caught in the clip, hence, the readjustment of the clip was done [] and perforator was separated.


Patient A is a 61-year-old female with a longstanding history of scoliosis treated with Harrington rod instrumentation in 1969 with subsequent removal in 1990. She had been fused down to L5 and now presented with severe distal degeneration at L5–S1, with fixed coronal and sagittal imbalance in the setting of a flatback syndrome (, , and ). The patient complained of persistent pain mostly in her back and some in her bilateral legs extending down into her feet. She also noted numbness to her bilateral calves and feet. At this point, the patient could only tolerate standing or walking for 10 minutes at a time. On exam, the patient was pitched forward. She had a mild weakness with ankle and toe dorsiflexion on the left. Imaging showed a prior fusion from T5–S1 (), with 49° of residual thoracic curve, 54° lumbar curve, 44° of thoracic kyphosis and only 5° on lumbar lordosis. She had a positive sagittal alignment of 17.4 cm, and her C7 plumb line was 7.5 cm to the right. Given the patient’s persistent pain and severe coronal and sagittal imbalance, she was taken to the operating room (OR) for a planned revision posterior instrumentation and fusion from T3 to sacrum and ilium, L5 pedicle subtraction osteotomy (PSO), and interbody fusions at L4–5 and L5–S1 (, ).
The patient was brought to the OR and placed prone in standard fashion. We applied Gardner-Wells tongs with 6.8 kg of traction. Her previous incision was used, and the prior fusion mass was exposed, showing a solid fusion from T7–L5, with movement at L5–S1 as suspected, and at T3–7 as well. Facetectomies were performed from T3–7, and decompressions at L4 to S1. We then placed bilateral dual S2AI screws as described above, as well as our iliac screw for the kickstand rod. Reduction screws were placed at L5 and S1, and an interbody cage was placed. We placed the remaining pedicle screws from T3–7 and L1–4, and an intraoperative computed tomography scan was used to confirm the acceptable placement of all screws (). A temporary rod was then placed on the left side 2 levels above and 1 level below L5 as well as a hook rod construct at L3 down to S2. The L5 PSO was performed. Excellent lordosis was obtained by compressing across the central hook rod construct. A permanent 5.5- to 6.0-mm hybrid rod was then placed on the right side from T3 to the S2AI screws contoured to maximize sagittal correction; of note, this rod had a domino connector placed before setting cap placement to attach to the kickstand rod. The left rod was then contoured and placed from T3 to S2 as well. After intraoperative X-ray, the right hemipelvis was noted to be high. So a 5.5-mm cobalt chrome rod was placed between the domino connector on the right and our kickstand iliac screw. The domino connector was tightened, and we sequentially distracted across this kickstand rod using a rod gripper to push the right hemipelvis down, thus obtaining even more coronal correction. After all set caps were tightened, a 4th rod was contoured and placed from the central hook rod construct to a domino connector at the T8 level, and a final 5th rod was placed on the left side from a domino above L1 down to the S1-iliac junction. Lastly, an interbody cage was placed at the L4–5 level. A total of 5 rods crossed the lumbosacral junction, two 6.0-mm and three 5.5-mm cobalt chrome rods. The patient is now 2 years postoperative, and excellent alignment has been well maintained without complication (, ).


A 66-year-old male presented to the local hospital with a 2-month history of edema of the right lower extremity in May 2019. B-ultrasound revealed that the right inguinal swollen lymph node was about 2.3 cm*1.0 cm in size. A computed tomography (CT) scan revealed multiple bone destruction of the bone, and ECT showed focal increased bone metabolic activity. PET-CT showed multiple osteolytic bone destruction with increased metabolism, pathological fracture of the right third rib (). The right inguinal lymphadenectomy biopsy showed carcinoma of unknown primary site with metastatic poorly differentiated adenocarcinoma. Immunohistochemistry demonstrated strong positivity for Glypican-3 and GATA, negativity for CK7, Napsin, TTF-1, CK20, CDX2, PSA.
After 1 month, the patient was hospitalized for cancer of unknown primary in our hospital. After a detailed medical history inquiry, the patient reported that there has been a rupture in the scrotum for approximately 4 years. Eczema-like change in the skin of the scrotum at the base of the penis was observed, with a size of 2.0x1.5 cm (). Then, the scrotal skin lesion biopsy was performed and pathological examination showed primary EMPD with Paget’s cells in the spinous layer (). Capture-based ultra-deep targeted sequencing was performed with a panel consisting of all exons and critical introns of 520 cancer-related genes. The next-generation sequencing assay showed that this patient had triple uncommon HER2 mutation, namely HER2 R678Q in exon 17, S310Y in exon 8 and S310F in exon 8 (). Laboratory examination showed severe anemia (47g/L), thrombocytopenia (27*109/L), elevated CEA (17.8ng/mL), with ECOG PS 3 scores and pain NRS 6 scores.
Due to poor conditions, the patient could not tolerate any traditional chemotherapy or radiotherapy. Then, the patient participated in a registered clinical trial (NCT03239015) in Shanghai Changzheng Hospital and received HER2 inhibitor pyrotinib (400 mg po qd). After pyrotinib treatment, the general pain and discomfort symptoms were significantly relieved, platelets and hemoglobin were increased (). The Mefecon use dose for bone pain was also decreased to 1/3 of the original analgesic dose. After 2 months, CT scans revealed a significant decrease in tumor size of right inguinal lymph. According to the response evaluation criteria in solid tumor (version 1.1), the patient was considered to have a partial response to pyrotinib (). The last CT scan showed that the right inguinal lymph node was stable (). The follow-up is ongoing. Written informed consent has been provided by the patient to have the case details and any accompanying images published. Institutional approval was not required to publish the case details.


A 49-year-old right-handed Caucasian man with a recent diagnosis of HIV presented with a 4-month history of progressive left-sided arm and leg weakness. Patient was diagnosed with HIV 2 months prior to this visit (CD4+ count: 270 cells/mm3) but he refused to start ART. At that time, he was also diagnosed with latent syphilis (rapid plasma regain [RPR] 1:32), and he received a 14-day course of IV penicillin. Neurological examination revealed mild cognitive impairment, left-sided spastic hemiparesis sparing the face with intact strength on the right side, impaired left-sided primary somatosense to temperature, pinprick, and vibration at the distal joint of the great toe. Appendicular ataxia (left more prominent than right) was also observed. Brain MRI revealed a punctate pattern with innumerable T2-FLAIR (fluid attenuated inversion recovery) hyperintensities in the cortex, brainstem, cerebellum, subcortical, and periventricular areas ( and ). These areas also demonstrated hyperintensity on diffusion weighted imaging (DWI) and few of them revealing T2-shine through on the apparent diffusion coefficient (ADC) sequence. Around the periventricular region, there were areas of punctate enhancement ( and ). The right hemisphere demonstrated a higher lesion burden than the left. A hypointense rim involving the subcortical U-fibers on susceptibility-weighted imaging (SWI) was also observed (). Cervical and thoracic spine MRI were unremarkable. Serum demonstrated a CD4+ count of 197 cells/mm3 with a HIV viral load of 23 290 copies/mL and RPR titer of 1:256. The results from a comprehensive diagnostic evaluation were inconclusive. Lumbar puncture revealed 9 nuclear cells/mm3 (95% lymphocytic), 9 red blood cells/mm3, protein of 86 mg/dL, and glucose of 54 mg/dL (serum 100 mg/dL). Infectious investigation of the CSF was significant for positive Epstein-Barr virus (EBV) PCR (483 copies/mL) and indeterminate for JC virus (JCV) PCR. Cytology revealed no abnormal cells and flow cytometry did not show evidence of non-Hodgkin’s lymphoma. He was started on ART. He received a 14-day course of IV penicillin, given the elevated RPR titer, although it is possible that was still elevated due to inappropriate response to the original course of penicillin, it was most likely thought to be elevated due to recent syphilis treatment completion given the negative VDRL in CSF. He was also started on acyclovir but due to the lack of response and negative infectious work up, it was discontinued. The presence of EBV was thought to be a concomitant opportunistic colonization as prior studies have described in severely immunosuppressed HIV patients. Brain biopsy was not performed due to the non-targetable lesions. Single-photon emission computed tomography/computed tomography (SPECT/CT) brain was negative for Thallium avid-lymphoma. Repeat brain MRI (1½ months later) performed in the setting of further neurological decline demonstrated interval progression of the T2-FLAIR hyperintensities involving the subcortical U-fibers and extending to the corona radiata, with evolution into a large confluent white matter lesion in the right frontoparietal lobe ( and ). There was also increased patchy enhancement along these FLAIR hyperintensities ( and ). Ultimately, his neurological deterioration stabilized, and he transitioned to acute in-patient rehabilitation. In a recent 3-month follow-up visit, he still demonstrated left-sided arm and leg spastic hemiparesis although he was able to ambulate with a cane.
The appearance and characteristic progression of the lesions in successive imaging in the setting of severe immunosuppression, with extensive negative infectious workup, was indicative of PML. Cytomegalovirus encephalitis, toxoplasmosis, and fungal infections such as cryptococcosis, candida, and aspergillosis were ruled out with a negative serological tests. Other diagnosis in the differential were considered such as HIV encephalopathy and primary CNS lymphoma. However, despite an indeterminate JCV PCR, this presentation was radiologically and clinically consistent with PML.


A 59-year-old male was admitted to the medical intensive care unit (ICU) for acute respiratory failure. He complained of 4 weeks of progressive dyspnea, skin changes on his hands consistent with Gottron’s papules, and 30-lb weight loss. His medical history was significant only for hypertension, which was managed with amlodipine. He had no prior history of autoimmune disease. He was admitted to a local hospital twice in the preceding month for dyspnea and treated for presumed bacterial pneumonia. He received azithromycin, vancomycin, and ceftriaxone during those hospitalizations for approximately 10 days. His symptoms improved minimally during those hospital stays and so he was admitted to our hospital 1 day after his most recent discharge. Computed tomography scan of the chest showed extensive reticular opacities largely sparing the periphery, scattered areas of ground-glass changes, and traction bronchiectasis. High-flow nasal cannula and noninvasive positive-pressure ventilation were required for respiratory support. Empiric vancomycin and cefepime were started for presumed pneumonia until it could be ruled out. He underwent bronchoscopy after admission, which did not reveal any infectious causes for his respiratory disease so the antibiotics were discontinued.
The patient reported that about a month before admission, he had noticed skin changes on his hands. On examination, he had small papules on the metacarpophalangeal and proximal interphalangeal joints of the fingers, consistent with Gottron’s papules (). He did not have muscle weakness on physical examination. The Rheumatology service evaluated the patient and felt that his clinical findings were highly suspicious for undiagnosed amyopathic DM, favoring a diagnosis of anti-MDA5-associated DM.
The patient had noticed new skin lesions that began to develop just 2 to 3 days before presenting to our hospital. On initial evaluation, the lesions were violaceous, flat, and scattered on his trunk and extremities without a clear pattern. After admission, these skin lesions began to increase in number and size. Over the following 3 days, the skin lesions evolved to separation, suggestive of epidermal necrosis (). He also developed erosions on the oral mucosa and on his scrotum. During this same time frame, he developed significant laboratory abnormalities. Laboratory results were available from a week prior to arrival at our hospital. Those laboratory results showed a platelet count of 250 000/mm3 and mildly elevated liver enzymes to 166 IU/L for aspartate aminotransferase (AST) and to 172 IU/L for alanine aminotransferase (ALT). On arrival to our hospital, the platelet count had decreased to 16 000/mm3, then decreased to 8000/mm3 after receiving 2 units of platelets in preparation for bronchoscopy. The liver function tests increased exponentially after admission, in synchrony with worsening of the skin lesions. The AST peaked at 2081 IU/L and ALT at 1427 IU/L. The total bilirubin was initially normal but increased to 6.2 mg/dL by day 4 at its peak.
Dermatology evaluated the patient and performed skin biopsies. While waiting to confirm the cause of the skin lesions, rheumatology advised initiating immunosuppression for suspected DM. Hematology evaluated him for his thrombocytopenia and favored an immune-mediated mechanism. For this, they advised providing IV dexamethasone at 40 mg, and this was continued for 4 doses. He was started on IV immunoglobulin at the same time and received 400 mg/kg daily for 3 days. His laboratory abnormalities improved by the following day and were nearly normal by a week later. His respiratory failure also improved after starting immunosuppressive therapy.
Days later, the skin biopsies returned and revealed epidermal apoptosis and areas of full-thickness epidermal necrosis, findings that were consistent with SJS. Intravenous antibiotics, either vancomycin or cefepime, were favored to be the cause. He was taken off IV antibiotics after 2 days in the hospital. His laboratory testing revealed a positive result for the anti-MDA5 autoantibody. Rheumatology began treatment with cyclophosphamide infusions and oral tacrolimus therapy, with a plan to continue this therapy in the outpatient setting for his anti-MDA5 DM. After approximately 2 weeks, we re-evaluated his skin lesions and they had all healed with hyperpigmentation at previous areas of skin loss.


A 79-year-old woman presented to the Emergency Department with slurred speech and arm weakness in the context of deteriorating mobility, cognition and oral intake for 3 months.
She was not taking regular medications and her only medical history consisted of radioactive iodine treatment for hyperthyroidism in 1990 and subsequent iatrogenic hypothyroidism. The patient had chosen to stop taking levothyroxine in 2010.
On arrival she had a temperature of 33.3°C, a heart rate of 45 bpm and a blood pressure of 170/99 mmHg. Her oxygen saturations were 90% on room air. Her GCS was 9/15. She had dry flaky skin, coarse hair, frontal balding, globally depressed reflexes, a hoarse voice and peripheral oedema. There was no palpable goitre. A CT scan of the head demonstrated focal right cerebellar calcification of questionable clinical significance, but otherwise no acute pathology to explain her stupor.
Blood tests demonstrated Na+ 127 mmol/l (133–146), CRP 19 mg/l (<10), creatine kinase (CK) 586 IU/l (25–200), TSH 51 mU/l (0.35–5.0), T4 2.6 pmol/l (9–24), T3 <0.8 pmol/l (3.5–6.5) and cortisol 1,001 nmol/l (140–690).
Re-warming was initiated alongside the administration of broad-spectrum intravenous antibiotics for possible aspiration pneumonia. The patient was later commenced on combination treatment of T4 25 μg via the nasogastric (NG) route and 10 μg IV T3 replacement three times a day (due to concerns about poor absorption). This was initially combined with regular hydrocortisone as adrenal insufficiency often coexists.
Although no organ support was required, the patient was taken to the critical care unit for close monitoring as treatment risks arrhythmia and myocardial infarction.
Unfortunately, the patient passed away after a 28-day admission, which was complicated by recurrent hospital-acquired pneumonias, non-ST-elevation myocardial infarction (NSTEMI), a subsequent per rectum bleed, and raised CK secondary to thyroid myositis.


A 44-year-old woman was admitted in the emergency department after 3 days of headache followed by hyperactive delirium. Brain tomography showed a hypodense lesion on the superior left cerebellum compatible with pneumocephalus ().
A lumbar puncture was performed for extensive microbiological investigation and broad-spectrum antibiotics were initiated with vancomycin, ceftriaxone and ampicillin. Cerebrospinal fluid analysis showed 42/mm3 leucocytes with polymorphonuclear leukocytes and clear glucose consumption (1 mg/dl). The blood cultures as well as the cerebrospinal fluid culture disclosed the presence of Streptococcus pneumoniae (against which the patient had been vaccinated 3 years previously with the pneumococcal saccharide conjugate vaccine). Antimicrobial therapy was adjusted accordingly. Follow-up brain imaging (48 h later) showed resolution of the pneumocephalus (). Despite receiving full intensive care treatment, the patient deteriorated and died on the third day after admission.


A 47-year-old left-handed man developed word-finding difficulties. He reported ‘writing letters backwards’ upon switching from print to cursive. He received failing grades throughout school until a formal diagnosis of developmental dyslexia was eventually made. With appropriate tutoring, his grades improved to passing levels and he graduated from high school, after which he took on several jobs in retail and sales. His new onset of word-finding deficits was initially attributed to mild depression and anxiety. As symptoms progressed he was referred for clinical evaluation, at age 51. On presentation, he displayed prominent challenges understanding long strings of auditory/verbal information but denied difficulties with episodic memory, object recognition or knowledge, visuospatial or executive functioning. Spontaneous speech was hesitant, with phonological paraphasias and long pauses disrupting fluency. Cranial nerve, motor, sensory and gait exam were all unremarkable. Neuropsychological testing confirmed severe phonological short-term memory deficits with only minor deficits in episodic memory and executive functioning (). Family history was negative for neurodegenerative disease, left-handedness or learning disability. Brain MRI revealed left-sided temporo-parietal atrophy (). He met diagnostic criteria for lvPPA (). PiB-PET imaging showed elevated cortical tracer uptake, consistent with the presence of moderate to frequent neuritic plaques (). Genetic testing revealed E3/E3 APOE genotypes and H1/H2 MAPT haplotypes. Over a 4-year period, his language deteriorated to neologisms and yes/no substitution, he developed episodic memory loss, dyscalculia, apraxia and progressive right-sided hemineglect. He developed jaw and hemibody myoclonus. He passed away at age 58.


A 54-year-old, right-handed woman with a childhood history of dyslexia, developed word-finding difficulties while teaching class. Three years later, she presented for evaluation. Her speech was slow without deficits in articulation or grammar. Intermittent myoclonus was observed in all four limbs. The remainder of the neurological exam was normal. Cognitive testing revealed isolated deficits in phonological short-term memory with spared object knowledge, fluency, long-term memory, visuospatial abilities and executive functioning (). Her father was diagnosed with amnestic Alzheimer’s disease at age 72. Her brother had dyslexia. Her brain MRI showed left predominant temporo-parietal atrophy (). She was diagnosed with lvPPA (). PiB-PET imaging was positive for cortical uptake (). Genetic testing revealed E3/E4 APOE genotypes and H1/H2 MAPT haplotypes. Language symptoms remained relatively isolated for years, eventually developing repetitive questioning, temporospatial disorientation, visuospatial deficits and agitation. She died at age 66.


A 12-year-old male presented with headache, emesis for 10 days. Head magnetic resonance imaging (MRI) examination showed a mass effect from right occipital lobe to falx cerebrum with large area cerebral edema and partial cystis degeneration (. He had no trauma history and physical examination didn’t find any enlarged lymph nodes. The patient received open craniotomy and biopsy of some gray white tissues of right occipital lobe. The mass was poorly circumscribed, gray white like fish with cystis degeneration and partially suppurative discharge.
The surgically resected specimen was fixed in 10% neutral buffered formalin and embedded in paraffin. Hematoxylin-eosin staining and immunohistochemical analysis were performed on 4-µM-thick paraffin-embedded sections. Microscopic examination revealed no evidence of normal cerebral histomorphology. The neoplastic component was lymphoid cells showing a diffuse monotonous growth pattern. Focal or sheets of necrosis and starry-sky mimicking presented (). The neoplastic lymphoid cells were not large cells obviously. Nuclei of most tumor cells were subtle irregular-shaped and contain multiple basophilic nucleoli. The cytoplasm were abundant pale or basophilic. Many mitoses could be easily found ().
Immunohistochemical staining showed that neoplastic cells stained strongly for CD30 on the cell membrane and in the Golgi region () and ALK1 (). The cells lacked expression CD2, CD3, CD5 and CD7, but Granzyme B and TIA-1 expression was seen. In addition, the tumor cells were positive for CD56, MUM-1, EMA, and negative for glial fibrillary acidic protein (GFAP), PLAP, CD34, CD45, CD20, CD79a, TdT, CD99, BCL-2, BCL-6 and CD10. Few tumor cells were positive for CD4. Ki-67 index was up to 95%. In situ hybridization for Epstein–Barr virus-encoded small RNAs (EBER) was negative. Monoclonal T-cell receptor (TCRγ) gene rearrangement was detected. Gene translocation involving ALK was identified by fluorescence in situ hybridization (FISH) using ALK break apart probe (). In conclusion, the final diagnosis as ALK + ALCL was made. Unfortunately, the patient died without any further treatment in one month.


A 34-year old Caucasian woman treated for ankylosing spondylitis (AS) with certolizumab for 6 months was admitted to our department with symptoms of palmoplantar pustulosis of 2 months duration accompanied by painful abscesses on the arc of the feet, painless abcesses on the breast and pubic mount and hair loss and severe desquamation in the frontoparietal area.
The patient was diagnosed with AS in 2006 with positive HLB27 antigen and a family history of AS. Due to its progressive course complicated by recurrent uveitis, the patient was being treated with certolizumab 200 mg injected subcutaneously (s.c.) every 2 weeks, with good clinical response. No side effects had been reported until the onset of skin lesions. During month 6 of treatment with certolizumab, pustules on an erythematous base with desquamation developed symmetrically on the patient’s palms and feet. Enhanced sweating of the palms and soles was noted. A layer of thick yellowish scale on the scalp appeared simultaneously. Initially the patient was suspected of acquiring a Coxsackievirus infection. No improvement was noted with either topical treatment with hydrocortisone, natamycin and neomycin cream and salicylic oil or following treatment with more potent steroids, including clobetasol propionate. The lesions kept exacerbating despite discontinuation of the anti-TNFα treatment. Extensive scaling of the scalp with hair loss, painful abscesses on the lower surface of the right breast and pubic area, abscesses on a violaceous base that excreted pus and blood and several tiny pustules on the back and left calf were noted. There was no personal or family history of psoriasis or other skin diseases. The patient has been an active smoker for 15 years and denied abuse of other substances.
One week prior to admission the patient had received an empiric treatment with oral clarithromycin 500 mg twice daily due to an upper respiratory tract infection. Following treatment initiation, the respiratory symptoms subsided but the skin lesions persisted, causing a significant decline in the patient’s quality of life due to severe pain and disability. Smaller pustules on a violaceous basis appeared a few days prior to the admission, on the left calf.
On admission the patient presented symptoms of pustular psoriasis of the palms and soles accompanied by abscesses on a violaceous basis with a clinical resemblance to pyoderma gangrenosum (Fig. ). Two smaller abscesses were found on the right breast, in the pubic area and on the left calf. Plaque with silver scale developed on the occipital area of the scalp, with an alopecia, that was positive for the pull test.
Swabs for bacteriological and mycological cultures were performed, and both were negative. The only deviations in the laboratory test results were slightly elevated inflammatory markers, including C-reactive protein (10.9 mg/l) and erythrocyte sedimentation rate (50 mm/h), minor leucocytosis (10.62 × 103/ul) and neutrophilia (6.88 × x103/ul). Chest X-ray showed no obvious pathology.
Treatment was initiated with a once-daily dose of hydrocortisone 200 mg administered intravenously. Additional therapy was implemented with an oral antibiotic treatment comprising doxycycline 200 mg daily combined with nonsteroidal non-inflammatory drugs (ketoprofen) and a topical treatment with a boric acid solution and betamethasone with gentamycin cream. However, there was only a mild improvement in the condition and only a mild reduction in pain intensity. Secukinumab (anti-interleukin [IL] 17A) was then added as a new biologic treatment of both the AS and the reaction to certolizumab, at a dose regimen of 150 mg at weeks 0, 1, 2, 3 and 4, followed by a dose of 150 mg every 4 weeks. After two doses of secukinumab, a new lesion developed on the patient’s right thigh which subsequently developed into an abscess from which there was a constant purulent discharge that appeared on the lateral surface of the right thigh (Fig. ); there was increased desquamation on the scalp and feet; and there was an enlargement of the plantar and breast lesions, with a purulent discharge (Fig. ). The pain was severe (numeric rating scale 10/10), and the patient required opioid analgesics. A pathergy phenomenon was observed at the site of venipuncture (Fig. c). Onychomadesis and onycholysis of the fingernails became visible (Fig. ). A surgical skin biopsy was taken from the patient’s left calf for histopathologic examination. It showed an erosion filled with neutrophils, epidermis with irregular acantholysis and abundant underlying neutrophilic infiltration in the dermis, with a tendency to perivascular accumulation and leukocytoclasis. This clinical picture was interpreted by the pathologist to be indicative of pustular psoriasis (Fig. ).
Having taken into consideration the clinical and histological picture, a diagnosis of overlapping palmoplantar pustular psoriasis, scalp psoriasis and pyoderma gangrenosum as a paradoxical skin reaction to the anti-TNFα drug was made.
A decision was taken to add once-weekly methotrexate (MTX) 20 mg s.c to the treatment with secukinumab. Follow-up after 2 months of combined therapy with secukinumab and MTX showed a regrowth of hair and less undermined lesions with less inflammatory borders, as well as ulcerations that were healing, with cribriform scars on the previously pustular lesions (Fig. ).