A 30-year-old man complained of a gradually enlarged mass in the right lower abdomen. The results of an abdominal ultrasound taken at the local hospital 3 months prior showed a heterogeneously mixed echo mass located in the right lower abdomen, and the size of the mass was approximately 8.6 cm × 7.3 cm. He had no family history of malignancy but had a history of bilateral undescended testis since birth. The local medical officer suspected a testicular tumor according to the history of cryptorchidism. At the same time, his rapid HIV-1 antibody test showed positive results, and the baseline CD4 count was 70 cells/ml (normal: 404–1612 cells/ml) upon further testing, which suggested severe immunosuppression. The patient initially received combination antiretroviral therapy (cART) but refused treatment for the abdominal mass. As the mass rapidly grew for 3 months, he came to our hospital for treatment of abdominal neoplasm. Upon examination, an immobile and nontender mass was visibly noticeable and palpable in the right lower abdomen. The bilateral testis was not visualized and could not be palpated. The patient had significantly elevated levels of alpha-fetoprotein (AFP), slightly elevated levels of beta-human chorionic gonadotropin (β-HCG), moderately decreased levels of hemoglobin and a low CD4 count (Table ). Further evaluation revealed a low viral load, which was less than 40 copy/ml. Computed tomography (CT) images showed a large, lobulated, ill-defined heterogeneous retroperitoneal mass measuring 17 cm × 16 cm × 24 cm without fat or calcifications and with marked inhomogeneous enhancement due to the presence of necrotic-colliquative areas (Fig. a). The lesion displaced the bilateral lower ureters, resulting in bilateral hydronephrosis. The lesion also compressed the surrounding small intestine, with possible infiltrating signs. Around the mass, ascites was detected, but no enlarged lymph nodes were found. Cystic-solid masses (5 cm × 5 cm) were detected in the bilateral inguinal regions, and their density and enhanced characteristics were similar to those of the retroperitoneal neoplasm (Fig. a, b). A diagnosis of testicular tumors with bilateral inguinal region metastases was suspected. The patient underwent routine clinical staging and prognosis evaluations according to the results of radiological and laboratory examinations. Clinical staging and risk group categorization were classified as stage IIIC and poor prognosis using the American Joint Committee on Cancer staging system (AJCC) [] and the International Germ Cell Cancer Collaboration Group (IGCCCG) prognostic scoring scheme (IGCCCG, 1997), respectively [].
An ultrasound-guided biopsy was performed on the 5th day after admission, and histology revealed a malignant yolk sac tumor of the testis. Then, the patient underwent exploratory laparotomy, retroperitoneal neoplasm resection, partial ileum resection, ileal anastomosis, and double J ureteral stent implantation under general anesthesia on the 11th day after admission. Histopathological examination revealed the lesion as a malignant mixed GCT of the undescended testis composed predominantly of yolk sac tumors with foci of embryonal cell carcinoma and seminoma (Fig. a, b). The repeated hematological and tumor markers 2 days after the operation are listed in Table . Hemoglobin level was still low; then, 4 Units of suspended red blood cells were transfused to correct anemia with no obvious transfusion reaction. The level of AFP was still high, and the follow-up CT scan showed a gradually enlarged right inguinal mass (Fig. c, d) 1 week and 2 weeks after the surgery, respectively. On the 17th day after the operation, the patient underwent right inguinal mass resection under local anesthesia. Pathological examination revealed mixed GCT metastasis (Fig. c), accompanied by hemorrhage and necrosis. Subsequently, the patient received salvage chemotherapy with a regimen of cisplatin, etoposide, and ifosfamide. Hematology was closely monitored during the treatment. After the first cycle of chemotherapy, the full blood counts remained within the normal range. CD4 count did not decrease during the course of treatment and remained at 118 cells/ml. Then, the patient was discharged and waited for the next cycle chemotherapy. Unfortunately, on the 4th day after discharge, he showed several symptoms of cancer cachexia including fever, progressive weight loss, pain, and severe weakness. Moreover, a low platelet count, which is a side effect of chemotherapy, was found (20 × 109/L, normal 125–350 × 109/L). Therefore, IL-11 was administered subcutaneously at a dosage of 50 μg/kg/day for thrombocytopenia. Two days later, the platelet count was still low (23 × 109/L); on the next day, the patient died because of severe immunosuppression, a low platelet count and cancer cachexia.


A 75-years-old man was admitted due to respiratory failure (day 0). The patient had history of colonic and prostatic cancer 11 and 7 years earlier, respectively, both successfully treated without recurrence. He also had a history of hypertension, alcoholism, smoking and chronic obstructive pulmonary disease. During his transfer to the hospital in ambulance, he was given intravenous infusion of furosemide. Upon arrival his physical exam was significant for fever, cough, tachypnoea and tachycardia He was admitted to the intensive care unit (ICU), requiring mechanical ventilation. Laboratory was remarkable for a white blood cell count of 10.5/mm3, C-reactive protein, lactate dehydrogenase and lactic acid were increased. An initial lung CT angiography showed bilateral ground glass pulmonary infiltrate without evidence of pulmonary embolism. With presumptive diagnosis of community acquired pneumonia, bronchoalveolar lavage (BAL) and BCs were done (Bactec aerobic medium; BD Diagnostic Instrument Systems; Bactec 9240). Fungal and bacterial stains and cultures from BAL were negative, and Galactomannan (PlateliaTM Aspergillus Ag) OD index was 0,45. Patient was started on piperacillin-tazobactam, vancomycin and hydrocortisone, and become afebrile at 24 hs.
On day 4, BCs were negative, thus vancomycin was discontinued. On day 6, after a short period of stabilization, he became hypotensive requiring inotropic assistance. Three BCs (1 from peripheral vein and 2 from CVC) were taken. A transthoracic echocardiogram didn't show valvular lesions.
On day 8 abdominal laparoscopy was done due to ascites. Ascitic fluid culture was negative. During the procedure a liver biopsy was done, later showing cirrhosis.
On day 9 the pair of BCs taken at day 6 showed a positive growth index. Direct microscopy showed hyaline, ovoid to elliptical yeasts (). A new set of BCs were drawn in order to confirm that finding. On day 13, yeasts were found on all BCs samples from days 6 and 9. The patient denied outdoor activity or recent traveling. No skin lesions were found on physical exam, and the portal of entry remained unclear. After 3 days, subcultures on Sabouraud agar showed slow-growing colonies, initially with smooth glossy mucous appearance, that over time became velvety olivaceous black ( A, B). Microscopy revealed pigmented septate branched hyphae with annelidic conidiogenesis, and ellipsoidal conidia of different sizes with a thin wall, forming aggregates (). The isolate was identified as Exophiala spp. MALDI-TOF (Bruker Daltonics) identified the colonies as E. dermatitidis with a 1.689 score. Patient was diagnosed of CLASBI due to non-Candida fungus according to CDC definition. Anidulafungin was started and CVC was removed. The strain was submitted to the national mycology reference center (“Departamento de Micología, Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbrán”), for further for molecular identification. Sequence data of the rDNA ITS regions of the D1-D2 of the large (28S) ribosomal subunit of the isolate resulted in 98.6% similarity to E. dermatitidis. Antifungal susceptibility testing was performed according the methodology recommended by the CLSI, document M38-A2 (2008), revealing a MIC (μg/mL) for amphotericin B, anidulafungin, and caspofungin of 0.125, 0,008 and 0,008 respectively.
Neither renal ultrasound nor ophthalmologic examination, reveal evidence of disseminated fungal infection. Standard histological stains for fungi were requested on liver histological sample with negative results. Histological diagnosis of cirrhosis was done.
BCs done on day 16 were negative. On day 18 the patient died due to haemoptysis and supraventricular tachycardia.
Due to described outbreaks of Exophiala spp. caused by medication contamination, audit and surveillance of the practices of preparation and administration of intravenous medication was made. No irregularities were found. ICU drug preparation surfaces were cultured in search for fungi, which were negative for Exophiala spp. Surveillance for secondary cases in ICU patients was conducted by incubated all BCs in a prolonged manner (14 days) during a period of 3 months from the index case. No other patient presented E. dermatitidis fungemia.


A 66-year-old man, who complained of upper abdominal pain, was found to have EGJ tumor by endoscopy (Fig. ). He was diagnosed as having Siewert type II adenocarcinoma (E=G, cT1b, cN0, cM0, cStage I) []. We planned to perform lower esophagectomy and proximal gastrectomy with double tract reconstruction.
In the computed tomography (CT) scan before surgery, a 10-mm aneurysm in the middle third of the splenic artery was found (Fig. ). Due to the anatomical location of the aneurysm, endovascular treatment was not considered due to recanalization and coil migration. The size of the aneurysm was not a high risk of rupture [], but we concerned about the possibility of SAA rupture due to postoperative pancreatic fistula (PF) associated with suprapancreatic lymph node dissection such as station 11p and 11d. We thought that spleen blood flow could be preserved even after SAA resection by preoperative CT scan and unnecessary invasive procedures could be avoided by simultaneous surgery. However, during simultaneous proximal gastrectomy and SAA resections, it was not clear whether there was sufficient blood supply to the spleen. Thus, we performed the surgery with a minimally invasive abdominal and left thoracic approach (MALTA) while continuously examining for the presence of blood supply to the spleen using fluorescence imaging.
The patient was placed under general anesthesia and was positioned in reverse Trendelenburg with the left side of the upper body lifted and the legs spread. Laparo- and thoracoscopic proximal gastrectomy and lower esophagectomy with D1+ lymph node dissection and double tract reconstruction were performed. First, we resected the SAA. Next, laparoscopic proximal gastrectomy was performed using five ports. Four ports were inserted into the thoracic cavity through the 9th, 10th (× 2), and 11th intercostal spaces, with the patient in the same body position. Lower thoracoscopic esophagectomy and lymph node dissection of the lower mediastinum was performed under artificial pneumothorax. The lower esophagus was resected under the thoracoscopic view to ensure an adequate margin. SAA located at the distal side of the branch of the great pancreatic artery (Fig. ), so we clamped the splenic artery to preserve the great pancreatic artery temporally. Then, we injected 5 mg of indocyanine green (ICG) intravenously to the patient. Blood supply to the spleen was confirmed using fluorescence imaging (Fig. ). Therefore, we resected the SAA without splenectomy (preserving the great pancreatic artery and the spleen). Intrathoracic esophagojejunostomy was performed with a transoral anvil (OrVil™) and a circular stapler (EEA25™) using the laparo- and thoracoscopic techniques. In addition, an oblique jejunogastrostomy for double tract reconstruction was performed. The operative time was 362 min, and there was no blood loss.
Histopathological diagnosis of the tumor was adenocarcinoma with enteroblastic differentiation (pTIb, pN1, pStage IIB according to the UICC Classification, 8th edition,) and with clear margins. Oral intake was resumed on postoperative day 5. Postoperative CT scan revealed the preservation of the great pancreatic artery and omental branches of the left gastroepiploic artery (Fig. ). There was no splenic abscess due to ischemia or other complications. The patient’s length of hospital stay was about a month.


A 13-year-old male presented to the Pediatric Emergency Room at a tertiary care academic medical center due to progressive quadriparesis that reportedly began after a prolonged episode of coughing 3 days earlier. His neurological symptoms manifested as bilateral hand numbness with persistent back and neck pain, but rapidly progressed to quadriparesis and widespread tactile and proprioceptive sensory loss over 2 days. The day prior to his presentation, he was unable to walk without support. He was subsequently admitted to the Pediatric Intensive Care Unit (PICU) due to concern for potential rapid respiratory compromise.
Other than a cough, the patient reported no recent acute illness and denied travel, trauma, exposures, and vaccinations (all childhood vaccinations were up to date). Additionally, there was no history of developmental or cognitive impairment (was performing well in eighth grade), no drug or alcohol use, and no history of smoking or e-cigarette use. He had a history of mild persistent asthma, and his only medication was his albuterol inhaler that he had been using about twice daily for a week prior to admission. There were no reported allergies.
At the time of admission, he was hemodynamically stable with normal vital signs. He was afebrile and in no acute distress. Heart and lung exams were normal. Neurological exam revealed diffuse hypotonia, diminished deep tendon reflexes in all extremities, persistent quadriparesis with most marked weakness in the radial, median, and ulnar nerve distributions (C5-T1 levels), and decreased sensation at the C4-L2 levels. Additionally, the patient had diffuse, severe hyperesthesia in response to sharp stimuli. There was no evidence of acutely altered mental status, visual or other cranial nerve deficit, nystagmus, or overt ataxia. Babinski and Hoffman's signs were negative and there was no ankle clonus. There was no spinal or paraspinal tenderness to palpation.
On hospital day (HD) 1, still unable to support himself while standing, the patient developed urinary retention requiring multiple straight catheterizations, representing a symptomatic nadir 2–3 days after initial symptom onset. He otherwise remained hemodynamically and neurologically stable during his stay in the PICU. He showed steady recovery after the following workup and treatment on HD 3–10 and was discharged to the Pediatric Acute Rehabilitation Unit on HD 22 in good condition.
Given the acute nature of the patient's neurological symptoms, on HD 1 brain and spine imaging were performed. Brain CT and MRI were unremarkable—there were no lesions, structural abnormalities, or edematous changes of the parenchyma or cranial nerves, and there was no contrast enhancement or leptomeningeal disease. Total spine MRI, however, showed a longitudinally extensive, non-enhancing, T2-hyperintense central cord lesion strictly involving the gray matter from C2-T2 with mild edema, intervertebral disc intensity changes in the cervical levels () and robust diffusion restriction (). These findings were initially thought to be suggestive of spinal cord infarct, although no abnormal flow void, cord compression, mass lesion, discrete disc herniation or desiccation, or other spinal or foraminal stenosis was noted. Follow-up MRA of the thoracic aorta was inconclusive, and concern for spinal ischemia necessitated high-resolution intravascular imaging. On HD 3, interventional angiogram showed brisk, robust filling and collateralization of the vascular supply of the spinal cord, and canal after left vertebral artery injection (). The anterior spinal artery was patent and of normal caliber. There was no evidence for aortic dissection or other vascular abnormality. Furthermore, serial fibrinogen, coagulation, and liver function tests showed no evidence of coagulopathy.
Out of secondary concern for an autoimmune or infectious etiology, the patient was started on Intravenous Immunoglobulin (IVIG) (400 mg/kg daily), high-dose steroids (methylprednisolone 1 g daily), vancomycin, ceftriaxone, and acyclovir for empiric meningoencephalitis coverage, and aspirin (81 mg daily) for secondary prevention of possible cord ischemia. Initial laboratory workup, however, was not indicative of an infectious or an acute inflammatory etiology with a normal white blood cell count (7.1*103/μL), negative blood cultures and respiratory viral panel, and normal sedimentation rate and C-reactive protein levels (1 mm/h and <0.1mg/L, respectively). Urine studies, including toxicology, were likewise unremarkable. Cerebrospinal fluid (CSF) obtained by lumbar puncture also proved unrevealing (WBC 0, RBC 9, glucose 65, protein 27.3). CSF infectious studies for enterovirus, HSV 1/2, syphilis, Lyme disease, ehrlichiosis, Cryptococcus, Epstein-Barr virus, and cytomegalovirus were negative, and serum titers for additional pathogens including mycoplasma and West Nile virus did not support acute infection. Additional workup for common autoimmune myelopathies including neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) was non-diagnostic (serum was negative for aquaporin-4 antibodies (AQP-4) (titer <1:10), myelin oligodendrocyte glycoprotein antibodies (MOG) (titer <1:10), and CSF was negative for oligoclonal bands). Serum tests for myositis (aldolase, creatine kinase) were negative.
After two doses of high-dose steroids (total 5 day course) and IVIG on HD 3–5, the patient's lower extremity strength began to improve, urinary retention resolved, and deep tendon reflexes returned to baseline. Given the negative infectious workup, antibiotics and acyclovir were discontinued on HD 3. However, the patient demonstrated a persistent weakness of the bilateral upper extremities that prompted a 5 day plasmapheresis course (HD 5–10) as salvage therapy for medically-refractory myelitis. Over the next few days, the patient achieved significant gains in strength, sensation, and balance.
The patient was transferred to a pediatric acute rehabilitation unit on HD 22. His exam remained notable for diminished hand, wrist, biceps, and triceps strength bilaterally, but he was able to walk with minimal assistance and his muscle strength normalized. Sensation was intact in the extremities but remained slightly diminished in the T4-T10 dermatomes. Paresthesias were no longer present. At his 3 month follow-up with the pediatric neurologist, his only residual finding was bilateral hand weakness, although greatly improved. He was back at school on a full-day, regular schedule. Diagnosis remained “unspecified inflammatory spinal cord syndrome.”


The patient was a 3-year 7-month-old female referred by her speech-language pathologist, presenting with oromyofascial dysfunction characterized by speech sound production errors, difficulty swallowing, open mouth breathing, and noisy breathing during sleep. With respect to sleep, there were reports of difficulties going to sleep, waking up two to three times per night to drink water, getting up to go to the bathroom, open mouth breathing while asleep (), snoring during sleep, and sweating more than usual during sleep. She experienced wheezing that was associated with asthma, which was treated with an Albuterol sulfate inhaler. There were reports of difficulty with effective chewing. In addition, the patient would eat around 50% of her meals, before refusing the rest. She experienced chronic cough and recurrent upper respiratory tract infections.
Physical examination () of the patient showed her to be well developed, well nourished, and to appear the stated age. The patient was alert, oriented, able to communicate, and respond appropriately to questions. During the nasal examination, the nose had no external deformity. The nasal septum was straight, and the inferior turbinates were grade 2 bilaterally. There were class 3 dental occlusion and a class 3 facial-skeletal relationship characteristic of anterior-posterior maxillary deficiency. Oropharyngeal examination showed grade 3 modified Mallampati tongue position and grade 2 tonsils. The patient was found to have a restrictive class 2 upper labial frenulum with tethering of the upper lip () and restrictive grade 4 lingual frenulum [] ().
Based on the patient history and the physical examination, the assessment revealed that the patient had functional and structural mouth breathing due to open mouth posture and low tongue posture in the setting of restrictive labial and lingual frenulum. The risks and benefits of lingual and labial frenuloplasty to facilitate lip closure and proper tongue resting posture were discussed with the parents and included, but were not limited to pain, inflammation, bleeding, scarring, need for revision surgery, and failure for significant improvement. An informed consent document was signed by the parents.
The maxillary labial frenuloplasty was performed under general anesthesia. Local anesthesia was achieved by applying 1 cc of 0.25% Marcaine with 1 : 200000 epinephrine to the maxillary labial frenulum via a 27-gauge needle. Pressure was applied lateral to the frenulum to locate the point of maximum tension. The maxillary labial frenulum was incised at the base of attachment with the use of sharp scissors. A V-to-Y lip closure was performed with a 4-0 chromic suture applied in a simple interrupted fashion ().
The lingual frenuloplasty procedure was then performed. A 2-0 silk suture was applied to the tip of the tongue as a retraction stitch. Local anesthesia was achieved by applying 1 cc of 0.25% Marcaine with 1 : 200000 epinephrine to the lingual frenulum via a 27-gauge needle. The tongue was retracted in the anteroposterior direction extending to the roof of the mouth and maxillary central incisors. Tension was applied to the floor of the mouth to protect the floor of mouth salivary glands, as well as Wharton's duct. A hemostat was used to clamp the restrictive lingual frenulum 5 mm above the attachments of the sublingual gland duct. The fibrous band was gently excised with the use of iris scissors. The underlying myofascial fibers of the genioglossus muscle were dissected further, with blunt cotton tips and sharp iris scissors being used to release the muscle from the overlying mucosa. The dissection was continued until there was adequate improvement to the tongue range of motion such that the tongue could extend up towards the maxillary central incisors in maximal mouth opening position. Simple interrupted sutures were used to close the diamond-shaped defect into a vertical line, as a means to lengthen the ventral tongue, with 4-0 chromic suture applied in a simple interrupted fashion. In total, the tongue was released from a grade 4 restricted range of motion to a grade 1 range of motion (). All wounds were hemostatic at the completion of the procedure. The patient was gently awoken from anesthesia and taken to recovery in stable condition.
The patient returned to the clinic four days after the procedure. The wound sites were healing appropriately, and there were no postoperative complications observed. The patient's mother reported that within the first day of returning home, the patient's issues with chewing had improved significantly, and she was more interested in eating different foods. In addition, her appetite appeared to have increased, and the patient would complete her entire meal before asking for more food (as compared to having only eaten around 50% before treatment). By the fourth day after surgery, the patient exhibited closed-mouth nasal breathing while asleep (). There were no longer any observed events of snoring and/or noisy breathing. The mother reported that the patient had remained compliant with myofunctional and speech therapy.
The patient returned for a 2-month postoperative visit. During the examination at this visit, no scar tissue was observed, and the wound sites had closed. Grade 1 tongue range of motion was observed ().
The patient's family wrote in a letter to the clinic approximately six months after the procedure, mentioning that the patient was doing very well with no complications. In addition, the patient had been reported to have completely stopped mouth breathing and snoring while asleep. However, the patient was reported to still have occasional episodes of cold and cough, as well as one episode of asthma exacerbation. Finally, the patient was reported by her family to have made progress with myofunctional and speech therapy, but the goals of eliminating the tongue thrust, achieving proper resting posture, and improving speech sound production errors were not met due to early discontinuation of treatment.


A 72-year-old man visited our hospital with a 1-day history of severe lower abdominal pain, vomiting, and the inability to pass gas or stools. Two months prior to presentation, the patient underwent a robotic-assisted laparoscopic prostatectomy with ePLND for prostate cancer. The patient had no history of previous illness except for prostate cancer and was not taking any regular medications. On physical examination, he showed a pulse of 97 beats/min and blood pressure of 122/64 mmHg. His abdomen was distended and tympanitic with rebound tenderness and muscular defense. Bowel sounds were absent. His groin examination was normal with no signs of herniation through the femoral or inguinal canals. Laboratory data showed only a marked elevation of the white blood cell count (15.0 × 103 μL) and no elevation of his C-reactive protein level (0.01 mg/dL). Abdominal non-enhanced computed tomography (CT) showed a small bowel obstruction (SBO) with marked ascites. Also, a coronal non-contrast CT image revealed thickened loops of small bowel with surrounding mesenteric edema in the left lower quadrant (Fig. ). Based on these physical and radiological findings, the patient was preoperatively diagnosed as having strangulated SBO. Enhanced CT was not performed because we decided to perform urgent surgery for the patient as soon as possible. The patient thus underwent urgent laparotomy that initially showed bloody ascites in the peritoneal cavity. The ileum, which was approximately 60 cm proximal to the ileocecal junction, formed a closed loop beneath the tortuous and elongated left external iliac artery after ePLND (Fig. ), and it was also strangulated by this artery. The incarcerated ileum was gently released by a pressing maneuver from the orifice. The released ileum, 120 cm in length, appeared non-viable, showing a color change to black. We therefore resected the strangulated ileum for a length of 120 cm and performed a functional end-to-end anastomosis. The orifice beneath the left external iliac artery was about 4 cm in diameter (Fig. ). In addition, there was no hernia sac around the artery. We found it risky to try to close the orifice because of the risk of injuring the iliac artery and decided to leave it unrepaired. The postoperative course was uneventful, and the patient was discharged from our hospital 10 days after surgery. Presently, the patient is doing well 5 months after surgery without recurrent disease.


A 21-year-old male inmate presented to our facility with generalized weakness, abdominal pain, nausea, and right eye pain with associated inflammation and blindness. The patient reported that, 3 days prior to arrival, he was involved in an altercation where he was struck in the face and had feces smeared over the right side of his face. Past medical history was significant for type 1 diabetes mellitus and methamphetamine abuse.
On admission, the patient was in acute distress due to lack of vision in his right eye. The patient's clinical examination was consistent with orbital apex syndrome with injury and inflammation in the cavernous sinus. The right eye had a fixed, non-reactive pupil and exhibited ophthalmoplegia, scleral injection, periorbital edema, and erythema. Remaining physical and neurological examination were normal.
On admission, his glucose was 437 mg/dL, Hb A1c was 14.5%, ß-hydroxybutryate/acetoacetate ratio was 9.00, HCO3: 5 meQ/L, WBC 21.7, Urinalysis: 4+ ketones, 4+ glucose, and urine drug screen (UDS) was negative.
The patient was admitted to the intensive care unit (ICU) under our institution's diabetic ketoacidosis (DKA) protocol where he remained for 48 h. Ophthalmology was consulted for his right orbital cellulitis and ophthalmoplegia and Oral and Maxillofacial Surgery (OMFS) was consulted for reducing his nasal fracture. Soft tissue cultures were taken of the region. No interventions were recommended at the time by either service except for intravenous antibiotics. There was no suspicion for fungal infection on their respective evaluations. After resolution of DKA, he was transferred to the general floor. During this time, he experienced no changes in neurological exam or in his ocular exam.
Less than 24 h after transfer, the patient developed sudden-onset left facial droop, gaze preference to the right and left-sided hemiplegia. Immediate CT of the head revealed no obvious acute abnormalities (); however, CTA head demonstrated occlusion of the cavernous segment of the RICA. The patient was immediately evaluated by the on-call vascular neurologist where he was diagnosed with an acute ischemic stroke with LVO of RICA and right MCA syndrome. Subsequently, the patient was administered IV-tPA per our institution's stroke protocol. The patient did not improve in his symptoms after completion of IV-tPA. Neurointerventional surgery was consulted for possible mechanical thrombectomy and the patient was immediately taken for a cerebral angiogram, confirming complete occlusion of the RICA. Utilizing standard thrombectomy techniques, a TICI III (Thrombolysis in Cerebral Infarction) revascularization was achieved () using a retrievable stent system. Direct evaluation of the embolus did not seem consistent with a standard thrombus as it had a fibrous appearance with minimal blood product. Given this finding, the specimen was sent for pathology and culture.
The patient recovered in the ICU after the procedure. Post-procedural MRI demonstrated diffusion restriction over the right basal ganglia, middle and inferior frontal lobes, and anterior temporal lobe (). Final pathology and culture were positive for fungal hyphae consistent with RCM (). Additional blood cultures were positive for multi-drug resistant Klebsiella pneumoniae. Once the diagnosis was confirmed, the patient was started on micafungin, amphotericin B, and meropenem. He then underwent urgent ethmoidectomy and maxillary antrostomy with OMFS followed by right orbital exenteration with ophthalmology. He completed an 8-week course of IV micafungin, amphotericin B, and meropenem per infectious disease recommendations. The patient was transitioned to oral posaconazole for an additional 3 months. The patient recovered to a Modified Rankin Scale of 2 at 90 days with the aid of acute rehabilitation.


An 84-year-old woman underwent total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy 18 years ago because of right ovarian fibrothecoma. After surgery, she was followed up regularly. During follow-up, she presented no androgenic or estrogenic manifestations. She was found to have a pelvic tumor that was suspected to be recurrence of fibrothecoma. Her pelvic tumor was located in the mesentery of the distal ileum. She underwent ileocecal resection to remove the mesenteric tumor. She received no additional therapy. She had an uneventful postoperative course and no recurrence for 1 year after surgery.
We re-evaluated the right ovarian tumor collected 18 years ago. The right ovarian tumor was a yellowish white solid tumor the size of an adult head. Fourteen tissue sections were prepared from the right ovarian tumor. Microscopically, theca cell-like cells and collagen-producing fibroblasts were observed in all tissue specimens (Fig. a–c). No SLCT component was observed in any of the tissue specimens. We diagnosed the patient with fibrothecoma as a result of re-evaluation.
Macroscopically, the mesenteric tumor was nodular and well circumscribed, measuring 75 × 65 × 50 mm (Fig. a, b). The cut surface was yellow (Fig. c). The tumor did not invade into the ileal wall. Microscopically, duct-like structures, which consisted of Sertoli cell-like tall columnar cells, were observed in the diffuse growth of scant cytoplasmic ovoid cells (Fig. a, b). Additionally, nests of Leydig cell-like cuboidal cells with eosinophilic cytoplasm were observed (Fig. c). The mitotic rate of the tumor was 2 per 10 high-power fields (Fig. d). No heterologous elements were observed.
An automatic staining machine (DAKO Envision+ system; DakoCytomation, Glostrup, Denmark) was used for the immunohistochemical procedure. The antibodies used in this study are shown in Table . Positive immunohistochemical expression of steroidogenic factor-1 (SF-1; Fig. a), inhibin-α (Fig. b), cluster of differentiation 56 (CD 56; Fig. c), Wilms tumor 1 (WT-1; Fig. d), AE1/AE3, and vimentin was found in Sertoli cell-like tall columnar cells. Inhibin-α and vimentin were expressed in Leydig cell-like cuboidal cells. Positive expression of SF-1, inhibin-α, CD56, and vimentin was found in ovoid cells.
Finally, we examined hotspot mutations in exons 24 and 25 encoding the DICER1 ribonuclease IIIb domain using a direct sequencing method. Before DNA extraction, neoplastic cells accounted for at least 50% of the tissue cell population. DNA was extracted from formalin-fixed, paraffin-embedded tissues. No DICER1 hotspot mutation was detected in this tumor tissue.
We therefore diagnosed the patient with primary mesenteric moderately differentiated SLCT without DICER1 hotspot mutation.


A 52-year-old woman visited a hospital with complaints of right axillary swelling. Computed tomography (CT) imaging identified a space-occupying lesion in the S2 region of the right lung. On histological analysis, the tumor showed high-grade cytological atypia with poor intercellular cohesion (Fig. a). Immunohistochemical analysis revealed that the tumor was positive for pan-cytokeratin, vimentin, and thyroid transcription factor 1, but negative for CD45 and CD30, indicating pleomorphic adenocarcinoma of the lung. Programmed cell death ligand 1 was positive in more than 95% of tumor cells (Anti-PD-L1, Clone 22C3; DAKO, Glostrup, Denmark; data not shown). The tumor was evaluated as cT4N2M0 in accordance with TNM classification of Malignant Tumors 8th edition (Union for International Cancer Control, Geneva, Switzerland). The patient underwent four courses of chemotherapy (nab-paclitaxel plus carboplatin). She had fever, polyarthralgia, and muscle soreness. In addition, leukocytosis and thrombocytosis were detected on laboratory testing (data not shown). Based on these clinical features, she was diagnosed as having paraneoplastic syndrome and not an adverse effect of chemotherapy because of paucity of association between symptoms and medication. The patient showed a partial response to chemotherapy based on the Response Evaluation Criteria in Solid Tumors guidelines at which time the tumor was 70 × 55 × 48 mm in size (Fig. b; left panel). Then, she was treated with four courses of 120 mg (3 mg/kg) of nivolumab every 2 weeks. Although the patient still had the same symptoms that was diagnosed as paraneoplastic syndrome before, there was no newly developed prodrome or mild noticeable irAEs until the last administration of nivolumab. In addition, laboratory tests performed in each hospital visit did not show any remarkable abnormality.
However, 14 days after the last nivolumab administration, she was admitted to our hospital with complaints of asthenia. The patient felt sick only one day before the admission. She had a fever of 38.6 °C. There was livedo reticularis on the extremities with systemic purpura. Laboratory results on admission are shown in Table . The patient had no relevant past medical history or family history including autoimmune disease. In addition, autoantibodies, including antinuclear antibodies, proteinase 3, myeloperoxidase-antineutrophil cytoplasmic, and anticardiolipin antibodies, as well as multiple aminoacyl-tRNA synthetases or anti-CL-β2GP1 antibodies, were not detected. Culture and microscopy of the blood smear did not detect bacterial infection. Conversely, significantly increased serum levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF indicated a state of cytokine storm. Thrombocytopenia and increased serum soluble IL-2 receptor, ferritin, and triglyceride levels would imply possible HLH. Impaired liver function with increased lactate dehydrogenase and creatine phosphokinase together with exacerbated muscle soreness suggested rhabdomyolysis. The activity of A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) was decreased but not less than 10%, which is a criterion for TTP. There was no evidence of infection on blood culture.
Immediately after admission to the intensive care unit, pulse steroid therapy with methylprednisolone 1000 mg/day for 3 days and systemic prednisolone administration (50 mg/day) were instituted. Thrombomodulin and mycophenolate mofetil was administered thereafter. Any of them could not provide a dramatic amelioration of her general condition, although the laboratory test showed improvement after administration of thrombomodulin and mycophenolate. Trend of platelet count, blood concentration of lactate dehydrogenase and creatine phosphokinase, which were useful as indicator of the clinical state, are depicted in Fig. c and d. By 3 days after hospitalization, general hypokinesis of the left ventricular wall resulted in reduced ejection fraction (20%) and aggravation of respiratory distress. Although we did not perform myocardial biopsy, this was probably caused by CRS induced myocarditis, as evidenced by increased levels of the cardiac marker creatine kinase-muscle/brain in the circulation. Continuous hemodiafiltration was also initiated because of renal failure.
By 7 days after hospitalization, the lower extremities were turning black due to circulatory failure (Fig. e). Gangrene then spread with infection involving the entire lower extremities, suggesting PF. Amputation of the left and right lower limbs was performed at three and four months after admission, respectively. We could not find active microangiopathy or inflammation in the resected limbs presumably because of the modification by immune suppressants and complete necrosis.
CT evaluation of the pulmonary lesion at 4 months after the last administration of nivolumab demonstrated significant regression; the tumor had become a scar-like lesion (Fig. b; right panel) and there was no further progression thereafter. The patient was finally discharged from the hospital at 6 months after admission.


A 67-year-old man presented himself in our emergency department after having several episodes of hematemesis and melena associated with chest pain over the previous 24 hours. The patient had a known history of gastric ulcer developed 20 years before without any other comorbidities except for class II obesity (BMI 36.68 kg/m2). Electrocardiogram (ECG) and serum troponin levels excluded an ischemic cardiac event, but the results for complete blood cell counts and hemocoagulation revealed a hemoglobin value of 9.6 g/dL. Two days before, the patient had undergone an esophagogastroduodenoscopy (OGD; Figure ) for a recurrent digestive discomfort after eating, and he was found to have a 30-mm submucosal lesion in the posterior wall of the greater curvature at the gastric fundus that was biopsied. The following OGD performed in urgency identified the origin of bleeding at the biopsy site; a temporary hemostasis was attempted using epinephrine injection therapy. In addition, an abdominopelvic computed tomography (CT) with enhanced scans was performed to check for any further bleeding, with negative result (Figure ). Nevertheless, 12 hours following endoscopy the patient had another melena accompanied by an episode of loss of consciousness; the hemoglobin level was 6.9 g/dL. Based on the recurrence of the gastric bleeding, the patient was prepared for surgery.
Diagnostic laparoscopy was performed to further evaluate the cause of the acute abdomen revealing only distension of the stomach, with no evidence of exophytic lesion, and ruled out signs of distant disease. An intraoperative endoscopy with a standard endoscope (Olympus GIF-Q-165®) was used to aspirate and lavage the stomach as well as confirming the localization of the bleeding lesion in the greater curvature at the gastric fundus. Subsequently, a laparoscopic sleeve gastrectomy (LSG) was carried out. Five trocars have been placed in the upper abdominal quadrants: one 12-mm trocar above the umbilicus in the midline, three 12-mm trocars in right subcostal, subxiphoid, and left subcostal, and one 5-mm trocar in the left anterior axillary line. The gastric resection was performed using a linear stapler (Echelon Flex™ 60 Endopath®) applied alongside a 38-Fr bougie. The next step has been a methylene blue dye test in order to check the sealing of the staple line that was additionally reinforced by nebulization with cyanoacrylate sealant (Glubran 2®) used also to create an adhesion with the greater omentum as a chemical omentoplasty. The surgical gastrectomy specimen (Figure ) was retrieved through the slightly enlarged left subcostal access. A drain was placed at the end of the procedure. The patient was administered 3 units of packed red cells to stabilize his hemoglobin up to 9.7 g/dL. Operative time has been 92 minutes.
The patient's postoperative course was uneventful, except for a left subcostal wound infection which was opened and drained at the bedside and for a E coli urinary tract infection which was successfully treated with antibiotics. The diagnosis of gastric GIST was confirmed on the surgical specimen that showed a polypoid mass with hemorrhagic foci 40 × 35 mm in size; surgical resection margins were negative (R0). The mitotic rate was <1/50 HP; CD34, CD 117/C-kit, and smooth muscle actin were positive; the Ki67-MIB1 immunostaining indicated a low proliferative rate (count rate 4%). The tumor was staged as GIST of gastric origin in the very low-risk category so that a systemic adjuvant chemotherapy was not needed Oral nutrition commenced on postoperative day 6, after a Gastrografin® swallow that confirmed a regular gastric transit and the absence of leaks. The patient was discharged on the 8th postoperative day. At one-month postoperative follow-up, no discomfort on eating or other symptoms were referred; he had lost 15 kg from the day of the operation (BMI 29.41 kg/m2).


A 83-year-old female patient was referred to the intensive care unit (ICU) in emergency state for the acute onset of a respiratory failure accompanied by high-frequency atrial fibrillation (AF). She had a body mass index (BMI) of 29.52 kg/m2 and a past medical history of hypertension, hyperthyroidism, and atrial fibrillation (AF) under treatment with direct oral anticoagulants (DOACs). The patient also had a history of previous surgery represented by a laparotomic left hemicolectomy for a benignant colonic stenosis. She was initially managed with intubation and received mechanical ventilation, and once hemodynamic stability was achieved, her conditions worsened due to unexpected upper gastrointestinal bleeding (UGIB). She was given a blood transfusion of 4 units of red blood cells, but her hemoglobin value continued to stay under 9.0 g/dL. The following OGD showed an ulcerated submucosal lesion of 3 cm at the greater curvature of the gastric fundus (Figure ). Abdominopelvic computed tomography (CT) with enhanced scans revealed the presence of a solid mass with a soft contour enhanced by the intravenous contrast at the gastric fundus 4.5 × 4.5 cm in size (Figure ).
In the management of this acute situation in order to avoid any further delay of surgical intervention, the patient was prepared for an emergency laparoscopy. Four trocars have been placed in the upper abdominal quadrants: one 12-mm trocar above the umbilicus in the midline, two 12-mm trocars in right and left subcostal, and one 5-mm trocar in the right anterior axillary line. The exploration of the abdomen cavity showed the adhesions attributable to the previous lower abdominal surgery as well as the cirrhotic changes of the parenchymal status of the liver. Once the stomach has been exposed, a nodule appeared on its surface near the greater curvature at the fundus. Subsequently, a laparoscopic sleeve gastrectomy (LSG) was carried out. The gastric resection was performed using a linear stapler (Echelon Flex™ 60 Endopath®) applied alongside a 38-Fr bougie. The gastric specimen (Figure ) was extracted through the epigastric access. One Jackson-Pratt drainage tube was positioned on the resected gastric surface. Upper gastrointestinal contrast (Gastrografin®) was performed on the fifth postoperative day. Afterward, the patient was put on a liquid diet and discharged from the intensive care unit on the seventh postoperative day. The histopathology report of the gastric specimen showed a polypoid submucosal mass of 3 cm with smooth margins and a normal overlying mucosa with a central ulceration; there was no margin involvement (R0). Immunohistochemistry indicated positivity for CD34, CD 117/C-kit, and smooth muscle actin; the mitotic count was <5/50 HP, and ki67-MIB1 revealed a low proliferative rate. These findings were compatible with a gastric GIST in the low-risk category.
The postoperative period was uneventful for complications except for the incidental finding of a lump in the patient's right breast The lesion was biopsied, and she was found to have an invasive ductal carcinoma for whom she was referred to the hospital's breast unit after discharge. The patient was discharged on the 15th postoperative day. She was subsequently seen at one month after surgery once resumed a normal diet with no reported symptoms.


A 40-year-old multiparous African American woman at 21 weeks' 4-day gestation, with known chronic hypertension, was transferred to our medical center for management of hypertensive emergency. Prior to transfer, the patient had marked blood pressure elevation (peak 192/129 mmHg) and laboratory evaluation notable for hemoglobin 11.0 g/dl, platelet count 66 k/μl, alanine transaminase (ALT) 20 U/L, aspartate transaminase (AST) 40 U/L, and creatinine 0.7 mg/dl ( for laboratory trends and reference range). Urine dipstick detected 4+ protein, 4+ blood, and +nitrites, and urine drug screen was positive for methamphetamines and marijuana. Intravenous ceftriaxone was given empirically for urinary tract infection.
On arrival to our medical center, blood pressure peaked at 205/114 mmHg and laboratory findings were like those noted above. In addition, lactate dehydrogenase (LDH) level was 985 U/L, with haptoglobin <8 mg/dl and 3 schistocytes per high power field on peripheral smear. Urine protein/creatinine ratio was 2.61 mg/mg (normal <0.3 mg/mg). Estimated fetal weight by ultrasound was 451g, which was appropriate for her gestational age. We suspect that methamphetamine use precipitated her hypertensive crisis, but the clinical picture and laboratory findings were concerning for severe preeclampsia and HELLP syndrome. Due to her previable gestational age and the life-threatening nature of her condition, termination of pregnancy was recommended, and she agreed. Magnesium sulfate was initiated for seizure prophylaxis, and she was managed in the intensive care unit on an intravenous nicardipine drip. Within 12 hours of her first misoprostol dose for labor induction, she had a precipitous vaginal delivery of a nonviable female neonate. Pathology examination of the placenta revealed decidual arteriopathy and accelerated villous maturation, which are findings reflective of severe hypertension and placental hypoxia.
Following delivery, severe hypertension (≥160/110 mmHg) persisted throughout the postpartum period despite triple agent antihypertensive therapy. On postpartum day 5, she continued to have severe range blood pressures, but declined inpatient stay and was discharged home on an oral regimen of chlorthalidone (50mg daily), amlodipine (10mg daily), and telmisartan (80mg daily). During her postpartum course in the hospital, patient had a work-up for secondary causes of hypertension. She had maternal echo showing mild left ventricular hypertrophy, but normal left ventricular ejection fraction (69%) and no evidence of aortic coarctation. She had normal renal artery Dopplers, ruling out renal artery stenosis. Serum aldosterone/renin ratio was normal, ruling out primary aldosteronism. She did not complete a 24-hour urine collection to measure total metanephrines and therefore pheochromocytoma was not formally ruled out. We suspect that methamphetamine use precipitated her hypertensive emergency, but blood pressures remained severe despite 7 days of inpatient observation and drug cessation.
TMA also persisted despite termination of pregnancy and drug cessation. On postpartum day 1 laboratory values were as follows: hemoglobin 8.4 g/dl, platelet count 90 k/μl, LDH 706 U/L, haptoglobin <8 mg/dl, 2-3 schistocytes per high power field on smear, and reticulocyte count 4.6% (normal 0.5-2.0%). Her reticulocyte production index was noted to be suboptimal at 2.1% (normal >3.0%), after adjustment for low hematocrit (30.5%) []. Considering that the patient's liver enzymes remained normal after delivery despite ongoing hemolysis and thrombocytopenia, the diagnosis of HELLP syndrome was questioned. Alternative TMA etiologies were considered, including aHUS, TTP, and vitamin B12 deficiency. Serum creatinine peaked at 0.9 mg/dl and aHUS genetic panel was negative for disease-associated complement gene variants (Machaon Diagnostics), making a diagnosis of aHUS less likely. ADAMTS13 activity was 75% (normal >67%), making a diagnosis of TTP less likely. Meanwhile, vitamin B12 level was undetectable <146 ρg/ml (normal 213-816 ρg/ml) and intrinsic factor blocking antibodies were positive, consistent with pernicious anemia. Mean corpuscular volume was paradoxically low at 75.3 FL (normal 80-100 FL), and other causes of anemia were ruled out with normal iron panel, hemoglobin electrophoresis, and folate level.
Following diagnosis of pernicious anemia, the patient was started on subcutaneous B12 injections at a dose of 1000 mcg daily. She received 5 injections of vitamin B12 during her postpartum hospital stay. While blood pressures remained severely elevated on the day of discharge (postpartum day 5), laboratory parameters showed signs of improvement: Hemoglobin 9.5 g/dl, platelet count 175 k/μl, and LDH 404 U/L ( for laboratory trends). The patient was discharged home with a plan for continued B12 supplementation and close outpatient follow up. At 2 weeks postpartum the patient had normal blood pressure (127/82) and was clinically well, but she declined additional laboratory testing.


A 47-year-old female with triple negative right-sided breast cancer on carboplatin and paclitaxel chemotherapy, underwent a molar tooth extraction for toothache with concern for abscess. The procedure was uneventful until about two weeks after when she started to develop toothache, with sudden left-sided frontotemporal headaches radiating down her face, ear and neck, left ear fullness associated with hearing loss, and left orbital pain with blurry vision. She returned to her dentist and was given 10 days of amoxicillin for suspected sinus infection. Her symptoms worsened and she presented to emergency department (ED). In the ED she was afebrile and hemodynamically stable. Her physical exam was remarkable for left conjunctival injection with tenderness along the left side of the orbit and pain with lateral/upward/downward gaze ocular movements. Her right eye was normal in appearance. She had reduced hearing in her left ear when compared to her right, mild mastoid tenderness on the left with no edema or fluctuance with serous amber colored effusion in the left middle ear with no evidence of otitis media. The tympanic membranes bilaterally appeared intact with no effusion in the right middle ear. Her neurological exam was unremarkable with no focal neurological deficits. The rest of her physical exam was unremarkable. Initial labwork was significant for an elevated white count of 11.4 cells/mm3 (4-10.5), and computed tomography (CT) of the head did not show any abnormalities. Given her aural fullness and hearing loss, magnetic resonance imaging (MRI) of the brain and internal auditory canal was performed, which showed thrombosis of the left transverse and sigmoid sinus (Figure ). A magnetic resonance venogram (MRV) was performed as per neurology recommendations, which re-demonstrated occlusion of the left transverse sinus, sigmoid sinus, and internal jugular vein (Figure ). A CT scan of the internal auditory canal performed at the time showed fluid in the middle ear and multiple left mastoid sinus air cells, consistent with acute otomastoiditis (Figure ). As the imaging helped to clarify the diagnosis, unfractionated heparin drip and broad spectrum antibiotics with vancomycin and cefepime were immediately initiated and later changed to meropenem and cefepime for the acute mastoiditis to cover Gram positive and Gram negative organisms. She was evaluated by an ear, nose and throat (ENT) specialist and no surgical intervention was indicated. Her symptoms dramatically improved and she was transitioned to subcutaneous enoxaparin, continued on intravenous (IV) antibiotics mentioned above and seen in follow-up with complete resolution of symptoms.


The patient was a 75-year-old woman who presented with severe bilateral leg edema and epigastralgia. There was no past history of chronic hepatitis or blood transfusion. Admission laboratory tests revealed an elevated serum aspartate aminotransferase level (48 U/L), mildly decreased serum albumin (3.6 g/dL), mildly decreased serum (74%), mildly elevated D-dimer (12.9 μg/mL), and mildly elevated fibrin degradation product (12.6 μg/mL). The tumor marker AFP was slightly elevated to 585 ng/mL. The Child-Pugh classification was A, and the indocyanine green retention rate at 15 min was 12%. CT scans showed a huge tumor, 21 cm in diameter, in the right liver and TT, 37 mm in diameter, in the right atrium (Figs. and a). The TT was pedunculated, swung like a pendulum with the heartbeat, and reached the tricuspid valve on a transesophageal ultrasound video (Fig. b). The symptomatic patient had a risk of sudden death due to TT in the right atrium. Therefore, we explained the high surgical mortality rate to the patient and her family, and they decided to proceed with surgery.
At first, a partial sternotomy was made, and cardiopulmonary bypass (CPB) via the aorta, superior vena cava, and right femoral vein and electrical ventricular fibrillation were performed after intravenous injection of 25,000 units of heparin sodium. Although the TT in the right atrium was very soft and fragile, thrombectomy from the right atrium and inferior vena cava (IVC) was successful (Fig. a–d). After the removal of TT, the IVC was clamped with a tourniquet above the diaphragm and the right atrium was sutured with 5–0 Prolene. After DC defibrillation was carried out, CPB was stopped, the tourniquet on the IVC was released, and 100 mg protamine was administered for the neutralization of heparin. The open heart surgery time was 23 min, and the CPB time was 42 min. Next, a reverse T incision was made, and right hepatectomy by anterior approach and IVC tumor thrombectomy were performed. After ligation of the anterior and posterior Glissonean pedicles, the liver parenchyma was transected under the Pringle maneuver and IVC clamping below the liver. After the IVC and right hepatic vein were confirmed by anterior approach, the IVC was opened and a residual TT in the IVC was removed under total hepatic vascular exclusion (THVE) (Fig. a–d). Finally, the huge tumor was removed with the diaphragm without pulmonary embolism. The total operation time was 9 h, and the total blood loss was 8200 mL. The tumor was of the massive type macroscopically (Fig. ), and cancer cells showed moderately to poorly differentiated HCC with invasion to the portal vein, hepatic vein, and diaphragm. The patient’s postoperative course was uneventful, and she was discharged 14 days after surgery. She is still alive 14 months after surgery with recurrence in the lung.


A 28-year-old Togolese woman of Ewe ethnic origin working part-time in a prison setting with no previous history of disease was admitted in August 2017 for left hemibody sensory problems with ataxia. These problems were observed while the patient was hospitalized for a few days in the hepato-gastroenterology (HGE) department. She had been referred to the HGE department for vomiting, abdominal pain and persistent hiccups lasting for about a month, which were thought to be due to gastritis with multiple ulcers based on a digestive endoscopy. Prior to admission to the HGE department, she initially received anti-ulcer and antiemetic drugs, but the outcome was marked by persistent vomiting and the appearance of episodes of prolonged loss of consciousness. Before the appearance of digestive problems, the patient presented with headaches and auditory and visual hallucinations due work-related stress. The examination also confirmed the existence of evening fever, weight loss without cough and secondary amenorrhea unrelated to pregnancy.
On day 1 of neurological problems, an examination confirmed the persistence of digestive symptoms, apyrexia, the existence of a headache, left hemibody ataxia with nystagmus when looking to the left, pronounced left osteotendinous reflexes, and left hemibody hypoesthesia up to the base of the neck. Encephalic magnetic resonance imaging (MRI) showed a hypersignal lesion in the bulbar more lateralized on the left in the fluid-attenuated inversion recovery (FLAIR) sequence not enhanced after a gadolinium injection (Fig. ). The infectious assessment showed a normal pulmonary X-ray, a negative human immunodeficiency virus (HIV) serology, negative plasmodium tests but the presence of Mycobacterium tuberculosis deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) (using GeneXpert) with normal cytochemistry and a sedimentation rate (SR) of 120 mm in the 1st hour. The pregnancy test was negative. On day 3 of the neurological problems, digestive problems subsided, and even though the results of the examinations were not yet compiled, the patient presented three episodes of cardiopulmonary arrest with a fever of 39 °C without an infectious contact point. She successfully benefitted from orotracheal intubation with broad-spectrum antibiotic treatment and intravenous corticosteroids in the intensive care unit. In the presence of the digestive symptomatology with a bulbar lesion, we alluded to an APS within the framework of an NMOSD, and a sample for the anti-AQP4 antibody tests was sent to Paris, France. Upon leaving the intensive care unit after 72 h, anti-tuberculosis treatment was established. The outcome was favorable with apyrexia, a modification in the nystagmus and an improvement in the ataxia. Subsequently, the result of the anti-AQP4 antibody test was positive (indirect immunofluorescence on transfected cells, anti-AQP4 Euroimmun reagent, CERBA file No. 17 T0483884 of 01/09/2017). In September, 2 months from the onset of digestive problems, with Lhermitte’s sign and hand and foot contracture access without vesico-sphincter problems were established. At the neurological examination, the osteotendinous reflexes were pronounced. Cervical medullary MRI showed an additional intramedullary hypersignal lesion in the T2 sequence at the C2 level without contrast enhancement after a gadolinium injection (Fig. ). In addition to the symptomatic treatment of spasticity, a second course of intravenous corticosteroids was administered, and anti-tuberculosis treatment was continued. The outcome was favorable, and the patient resumed her usual activities as of February 2018, which was 8 months after the first onset. After 8 months of anti-tuberculosis treatment, the patient was started immunosuppressive therapy (azathioprine 50 mg twice daily) to limit the risk of recurrence of NMOSD.


Case 1 was an 8-year and 2-month-old boy. The patient was born at 40 weeks gestation by cesarean section, with a birth weight of 3,200 g (−0.3 SD) and a body length of 50 cm (−0.2 SD). His parents were healthy and nonconsanguineous. His developmental milestones were delayed, with head control at 10 months, sitting at 12 months, standing at 24 months, walking at 38 months, putting two words together at 24 months. The patient exhibited hypotonia, amblyopia, astigmatism, teeth hypoplasia, and dysmorphic features including hypertelorism, a broad forehead, long philtrum, upslanting palpebral fissures, hypoplastic columella and ala nasi thin upper lip, high-arched palate, epicanthic fold, and micrognathia. He had brachydactyly and a simian crease on his right hand (Figure ). Electroencephalogram was abnormal, showing sharp waves and sharp slow complex waves on bilateral forehead and central region. The boy presented to our Endocrinology clinic at the age of 6 years and 2 months with a height of 102 cm (−3.6 SD) and a weight of 16.8 kg (−2.2 SD) (Z-scores were calculated based on the China's 2009 urban 0 to 18-year-old male height and weight growth reference standards; Li, Ji, Zong, & Zhang, ). Urine and plasma amino acid testing revealed hyperlactatemia. Other laboratory test results including thyroid function, serum insulin-like growth factor I level, Insulin-like growth factor-binding protein 3 level, serum glucose, routine urine analysis, routine blood test, renal function test, liver function test, and levels of electrolytes were all within normal ranges. Growth hormone provocative tests revealed that the peak growth hormone levels responding to two provocative tests (clonidine 5 µg/kg, orally, and arginine 0.5 g/kg, intravenously) were 5.60 ng/ml (Table ). Peak growth hormone levels between 5 and 10 ng/ml on provocative testing are defined as partial growth hormone deficiency according to current guidelines (Grimberg et al., ).
Brain magnetic resonance imaging (MRI) scan showed widened sulci and lateral ventricles and reduced volume of white matter. No signs of hypoplastic corpus callosum, delayed myelination, or simplified gyral pattern (Figure ). Bone age was delayed and was compatible with that of a 3-year-old boy.
Due to the partial growth hormone deficiency and short stature, growth hormone replacement therapy at a dose of 0.12–0.15 IU kg−1 day−1 was initiated. After 2 years of treatment, at the age of 8 years and 2 months, his height was 121.0 cm (−1.9 SD) and weight 19.8 kg (−2.4 SD). The growth hormone therapy markedly improved the linear growth of the patient with a growth velocity of 9.5 cm/year during the 2 years. Growth hormone doses and growth chart in case 1 are shown in Figure . The serum levels of IGF1 increased to 304 ng/ml during the treatment.


Case 2 was a 4-year-old boy. He was the only child of a consanguineous parents. Pregnancy and delivery were uneventful. He was born with a birth weight of 2,900 g (−1 SD) and a birth length of 50 cm (−0.2 SD). He held head at 7 months, sat at 13 months, stood at 18 months, walked at 24 months, put two words together at 20 months, spoke in full sentences at 3 years. He exhibited hypotonia. His dysmorphic features include a broad forehead, hypertelorism, upslanting palpebral fissures, hypoplastic columella and ala nasi, flat nasal bridge, long philtrum, upturned earlobes, high-arched palate, micrognathia. He had brachydactyly and simian crease in both palms (Figure ). The boy was presented to our Endocrinology clinic at the age of 3 years and 6 months. At that time, his height was 90 cm (−2.9 SD), and weight 15.5 kg (−0.1 SD). Laboratory test results including the thyroid function, serum glucose, routine urine analysis, routine blood test, renal function test, liver function test, and the levels of electrolytes were within normal ranges. Growth hormone provocative test also revealed a partial growth hormone deficiency (7.11 ng/ml). The serum insulin-like growth factor I level was low (48.7 ng/ml) and insulin-like growth factor-binding protein 3 was low (2.41ug/mL) (Table ). Brain magnetic resonance imaging (MRI) showed an enlarged cerebellomedullary cistern and arachnoidal cyst. (Figure ). Bone age was delayed and was compatible with that of a 1.5 years old boy.
The patient also underwent growth hormone replacement therapy at a dose of 0.13–0.15 IU kg−1 day−1. After being treated for 9 months, at the age of 4 years and 3 months, his height was 99.3 cm (−1.7 SD) and weight 16.6 kg (−0.4 SD). The growth velocity during 9 months is 12.4 cm/year. Growth hormone doses and growth chart in case 2 are shown in Figure . The serum levels of IGF1 increased to 209 ng/ml during the treatment.


We present the case of a 75-year-old man with a history of hyperlipidemia, giant cell arteritis on steroids, and recent urinary tract infection on antibiotics, who presented acutely with a complex aortic arch aneurysm. Ten days prior, he experienced chest pain and voice hoarseness, which persisted. CT angiogram revealed two saccular aortic aneurysms arising from penetrating atherosclerotic ulcers (PAUs). Between the origins of the left common carotid and left subclavian arteries (LSCA), there was a 3.7 × 4.4 × 5.2 cm aneurysm directed towards the left, inferiorly and posteriorly (). A second 4.3 cm saccular aneurysm arose from left lateral wall of the descending thoracic aorta. The presence of peri-aneurysmal fluid, left hemothorax, and hemopericardium as well as his clinical presentation, confirmed relatively acute contained rupture (). The patient was hemodynamically stable, with weak but symmetrical peripheral pulses and a normal neurologic exam except for a hoarse voice. We counselled him about the natural history and possible therapies including medical management, possible enrollment in the Terumo Aortic Relay Plus Dual Branched-graft clinical trial (NCT03214601) or open therapy. Over the following 6 hours, the patient became hypotensive with a drop in his hemoglobin concentration, so with the patient’s consent, we proceeded emergently to the hybrid operating room.
Right axillary cannulation was performed for systemic and later antegrade cerebral perfusion (ACP), by suturing a 10 mm Dacron graft to the right axillary artery. A right femoral arterial sheath was placed through which a soft guidewire was traversed to the descending thoracic aorta under transesophageal echocardiographic (TEE) guidance. Following sternotomy, the patient was placed on cardiopulmonary bypass (CPB) and cooling was started to 28 °C. The aorta was cross-clamped and dissected. On inspection, the ascending aorta had heavy intramural hematoma requiring debridement to the sinotubular junction, which was reconstructed with felt. The aortic valve was structurally normal and was resuspended at the level of the commissures. Upon reaching 28 °C, hypothermic circulatory arrest (HCA) was initiated with ACP through the right axillary artery. Extensive destruction of the distal aortic arch including the os of the LSCA, necessitated debridement to zone 3. The cut end of the proximal DTA was inflamed, atherosclerotic, and friable. Next, a TEVAR (34 × 100 mm Terumo Aortic Relay Plus) was deployed antegrade over the guidewire placed initially through the right femoral artery (). The stent-graft size was based on measurements on the CT scan (oversizing by approximately 10%). Use of the TEVAR as a frozen elephant trunk (FET), allowed reconstruction of this totally destroyed arch tissue, and provided a stable platform on which to construct the proximal arch graft, as well as a landing zone for future TEVAR within the FET. Importantly, when deployed antegrade, the Terumo Aortic graft allows a Dacron end to sew to. The proximal end of the TEVAR stent-graft was allowed to protrude 1.5 cm out of the arch. The cut end of the DTA was approximated to the stent-graft using a running horizontal 4-0 polypropylene suture. The distal anastomosis was constructed between the stent-graft and a 30 × 10 × 8 × 8 mm trifurcated Dacron arch graft (). CPB was resumed and the arch vessels were anastomosed starting with the LSCA, with sequential replacement of the clamp proximal to each completed anastomosis. During this time, the body was perfused with CPB and the brain with ACP for a total of 55 minutes. Finally, the graft to STJ anastomosis was completed (). Cross clamp was removed after 189 minutes. There was significant bleeding at the stent-Dacron graft anastomosis due to the stiff nature of the stent-graft which did not conform well to the Dacron graft to allow for hemostasis. Therefore, a second proximal retrograde TEVAR (Terumo Aortic 36 X 150 mm) was deployed via right femoral artery under fluoroscopic guidance. The proximal landing zone was at the level of the proximal arch just distal to the take-off of the side branches. The patient was weaned from CPB with ease after a total of 258 minutes, hemostasis was achieved and ultrasound examination revealed bilateral carotid flow. The patient’s postoperative recovery was complicated by poor calorie intake requiring the placement of a feeding gastrostomy and a perforated stress gastric ulcer that required emergent exploratory laparotomy and repair. He also required tracheostomy for airway protection due to weakness and vocal cord paralysis. He was subsequently discharged to a rehabilitation facility on post-operative day 14. In follow-up, the patient was clinically well and resumed light activities. Interval CT angiogram re-demonstrated the second saccular aneurysm which had now grown to 2.9 x 3.8 cm, as well as two PAUs (). The patient was offered endovascular repair which we performed 13 weeks after the index procedure. He underwent TEVAR extension with 36 X 200 mm Terumo Aortic Relay Plus endograft with use of a spinal drain. Completion angiogram revealed no endoleak and the final CT shows exclusion of the second aneurysm and PAUs (). The patient was discharged in excellent condition on lifelong suppressive antibiotics for Salmonella UTI in the setting of extensive graft material. No definitive evidence of salmonella aortitis was found.


A 62-year-old female with no significant past medical history presented to our facility with complaints of palpitations and associated dizziness for three months. Prior work-up of her palpitations with Holter monitoring showed no irregularities. On arrival, she was in no acute distress and her palpitations had subsided. Vitals that were obtained were largely unremarkable except for a blood pressure of 142/77. Her EKG showed no acute irregularity and laboratory testing was within normal limits. On physical, a regular rate was observed, no murmurs, gallops or rubs were auscultated. She did not exhibit jugular venous distention or peripheral edema and other organ systems did not yield and irregularities.
The patient was admitted for further evaluation and a transthoracic echo was performed, revealing a 4.4 x 3.0-cm mass in the left atrium attached at the interatrial septum and aortomitral intervalvular fibrosa. Additional imaging studies including cardiac magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) were obtained for further confirmation of the mass and its location (Figures , ). Surgical resection was planned, and pre-operative cardiac catheterization was performed which revealed mild prolapse of the mass causing intermittent obstruction of the mitral valve.
The patient underwent full-thickness resection of the mass, resulting in an iatrogenic atrial septal defect which was closed with a Dacron patch. Her postoperative course was complicated by the development of intermittent complete heart block with junctional bradycardia and subsequent atrial fibrillation. She was evaluated by electrophysiology and a permanent pacemaker was implanted without complication. Discharge follow-up several weeks later noted the resolution of her prior symptoms, and repeat imaging showed no evidence of mass recurrence or mitral valve prolapse.


A 74-year-old male retired accountant with a background of asthma, atrial fibrillation, and gout presented to our emergency department with syncope following an insidious 6-month history of systemic symptoms. He had had intermittent fevers, 15-kg weight loss, general malaise, regular diaphoresis that occurred day and night, nausea, vomiting, diarrhea, and a nonproductive cough with sporadic morning hemoptysis. His exercise tolerance had reduced from unlimited walking capacity to breathlessness after roughly 2 km. His medications included rivaroxaban, verapamil, digoxin, and fosinopril. He had received a short course of prednisolone 25 mg daily for a flare of gout 3 weeks prior. He had a 50-pack-year ex-smoking history, having given up smoking 30 years prior. He lived independently with his wife. He had undergone outpatient chest computed tomography (CT) 2 months earlier that showed consolidation in the left lower lobe and a peripheral opacity in the right lung base measuring 14 mm by 12 mm. He had received several courses of oral antibiotics, including amoxicillin for 10 days and doxycycline for 2 weeks for presumed pneumonia. Because of his ongoing cough, he had a repeat CT scan 1 month later that showed resolution of the consolidation but no change in the peripheral opacity. His general practitioner had then referred him to a respiratory specialist, who felt that his illness was in keeping with a pneumonia that was now resolving. He advised withholding fosinopril, cessation of antibiotics, repeat CT scan in 3 months, and follow-up in 3 weeks. Prior to this appointment, he had had the syncopal episode that led to this presentation.
On arrival to the emergency department, he felt washed out, with vital signs that were notable for low-grade fever of 38.3 °C, sinus tachycardia to 130 beats per minute, and fluid-responsive hypotension (82/45 mmHg), and his physical examination was largely unremarkable. Investigations revealed a white blood cell (WBC) count of 10.6 × 109/L (neutrophil count 9.1 × 109/L, lymphocyte count 0.9 × 109/L), C-reactive protein (CRP) 119 mg/L (normal range 0–5 mg/L), Streptococcus mitis on blood cultures (penicillin minimum inhibitory concentration [MIC] 0.030 mg/L [susceptible = MIC < 0.5 mg/L]), and transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) demonstrating a mobile 30 × 25-mm vegetation on the PV that extended into the right ventricular outflow tract (Figs. and ). Complete destruction of the anterior cusp with severe pulmonary regurgitation was seen. Initial management included intravenous benzylpenicillin and gentamicin for a total of 4 and 2 weeks, respectively. A surgical opinion was obtained, but a trial of medical management was advised. The patient felt better, and his inflammatory markers normalized.
Two months after antibiotic cessation, the patient still felt well, with a normal WBC count and CRP of 5.3 mg/L (normal range 0–5 mg/L). Cardiac and chest imaging was performed to check resolution of lesions. TTE showed a reduction in the PV vegetation to 29 × 9 mm. A follow-up chest CT scan, however, showed new nodular lesions thought to be due to embolization (Fig. a), suggesting persistent endocarditis. Repeat blood culture results remained negative.
After 3 months, he again began to feel lethargic with breathlessness on exertion. His examination was unremarkable, but his WBC count was 16.1 × 109/L and CRP was 182 mg/L. Results of five sets of blood cultures were negative, and the vegetation size had improved on TTE to 23 × 10 mm. He was then started on a 2-week course of amoxicillin and clavulanic acid. Again he began to feel well, with improvement in his CRP and WBC count, so he was discharged to home.
Repeat outpatient CT of the chest 1 month later showed new lesions, including a cavitating lesion (Fig. b). In light of the recurrent lung lesions, he underwent surgical PV replacement. His PV had been destroyed with a perforated anterior leaflet that was completely encompassed by a large vegetation. The other leaflets were untouched. After valve and vegetation excision, a 27-mm Carpentier-Edwards PERIMOUNT tissue valve (Edwards Lifesciences, Irvine, CA, USA) was inserted. Histology confirmed IE with expansile inflammatory masses composed of fibrin and neutrophils. Small clusters of degenerate bacterial cocci were noted, but a valve culture revealed no growth. The patient made a good recovery on intravenous benzylpenicillin and oral clindamycin. TTE showed a normal-functioning bioprosthetic PV. Over the following weeks, the patient’s radiographic and inflammatory markers normalized.


An 83-year-old Hispanic male with an extensive past medical history including chronic hepatitis C, coccidioidomycosis, ocular myasthenia gravis, and interstitial lung disease presented to the Emergency Department (ED) with a complaint of chronic cough, shortness of breath, upper extremities weakness with diplopia, and dysphagia. The patient reported a daily cough with sputum production since Thanksgiving 2017 and became more severe in the past 3 days. He denied any weakness in his lower extremities and reported that he was able to garden up until 3 months ago when he started having upper extremities weakness. In the ED, the patient's SPO2 was 94%, initial chest X-ray showed no acute pathology, and CT of the chest showed no signs of thymoma or any other lung pathologies. He was admitted to telemetry with a BiPAP for further evaluation. The patient's Video Swallow Study showed severe oropharyngeal dysphagia. We were consulted as the patient had severe dysphagia and a history of ocular myasthenia gravis. However, the patient developed acute respiratory failure and was intubated before an assessment and evaluation can be performed.
Upon review of the patient's medical record, it showed that he was diagnosed with myasthenia gravis in 2017 when he was found to have AChR binding antibodies of 40.70 nmol/L, AChR blocking antibodies of 56%, and AChR modulating antibodies of 54%. He was prescribed pyridostigmine 60mg 1 tablet three times daily as treatment; however, his adherent to treatment regime was questionable; and he has had recurring follow-ups with his primary care physician for ocular myasthenia gravis. The patient's lab result in the ED showed AChR binding antibodies of 276 nmol/L, AChR blocking antibodies of 75%, and AChR modulating antibodies of 91%, all of which displayed a major increase in antibodies compared to his results at time of diagnosis. Due to the patient's history of ocular myasthenia gravis, his current state of severe dysphagia, and acute respiratory failure, we ordered a serum anti-GBS antibody work-up for our patient when he showed signs of improvement from diplopia but his respiratory status remained the same. The results revealed that the patient had GM1 antibodies of 81 units and GD1b antibodies of 52 units, which are serology markers seen in GBS. The patient was started on IVIG and methylprednisolone while continuing with pyridostigmine. Several days later, the patient exhibited significant improvement in respiratory status and clinical signs of improved swallow function, and his diplopia has been resolved.


A 9-years-old spayed female mixed-breed dog was referred for the evaluation of moderate neurological signs. It tended to seek narrow places, experienced body tremors, and had lost its vision 6 months before the referral, although its eyesight had been weakening since 2 years. The owner was provided detailed information on the diagnostic and surgical procedures required, and consent was also obtained. A bilateral menace response was absent on neurological examination, with no other abnormalities. Normal findings were obtained on performing echocardiography and abdominal ultrasound. The left and right adrenal glands measured 56 and 57 mm in length, respectively. Minimal increase in alanine aminotransferase (312 IU/L; reference, 5–60), gamma glutamyltransferase (64 U/L; reference, >9 U/L), and lipase (521 U/L; reference, 24–108) levels, and a moderate increase in the alkaline phosphatase (973 U/L; reference, <280) level was observed on complete blood count, a chemistry panel, and urinalysis. The thyroxine (T4) level was slightly decreased (13.6 nmol/l; reference, 17–54). MRI and computed tomography were recommended for further assessments.
Following intravenous cannulation, the dog was anesthetized using propofol injection (5 mg/kg body weight [bwkg]; Narcofol®, CP-Pharma GmbH, Burgdorf, Germany). After intubation, anesthesia was maintained with a mixture of isoflurane and oxygen gas (Forene®, AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany; 1.5% volume/volume; oxygen flow, 2 1/min). MRI was performed using a 1.5-T device (Siemens Magnetom Avanto, Siemens, Erlangen, Germany) to acquire the following sequences: T2W images in the transverse (echo time [TE]/repetition time [TR], 112/4,220 ms; slice thickness [SL], 3 mm), sagittal (TE/TR, 112/3,500 ms; SL, 3 mm), and dorsal (TE/TR, 112/3,500 ms; SL, 3 mm) planes; thin-slice native images (TE/TR, 9.1/550 ms; SL, 2.5 mm); fat-suppressed images (TE/TR, 9.1/749 ms; SL, 0.9 mm); post-contrast images (0.2 mL/bwkg; Dotarem 0.05 mmol/l injection, Guerbet, Villepinte, France); T1W three-dimensional images (magnetization prepared rapid gradient-echo) in the sagittal, transverse, and dorsal planes; and time-of-flight angiography (TE/TR, 7/25 ms; SL, 0.7 mm). The field of view was 170 × 170 mm.
During the same session, native, and post-contrast computed tomography images of the brain were obtained using an inner ear (SL, 1.0 mm; kernel, H60s; SL, 0.75 mm; kernel, H70h) and carotid angio (SL, 2.0 mm; kernel, B30f; SL, 0.6 mm; kernel, B26f) protocol, followed by maximum intensity projection reconstructions in the dorsal plane.
An intra- and suprasellar mass was observed on MRI (). The intrasellar portion appeared iso- and hyperintense on T2W images, and hyper- and hypointense on T1W images, with marked contrast enhancement along the dura mater. A multicompartmental cyst-like component was attached to the mass; this component showed T1 hypointensity and T2 hyperintensity, and compressed the thalamus and pons in the caudal direction. The optic chiasma was also compressed in the cranioventral direction. The cystic structure showed late enhancement, particularly in the fluid-filled areas. The size of the cyst was 16 × 18 × 14 mm. The radiological diagnosis was an intra- and suprasellar lesion connected to a multicompartmental fluid field. Differential diagnoses included suprasellar arachnoid cyst, epidermoid cyst, craniopharyngioma of the pituitary gland, and myxomatous tumors.
Preoperative three-dimensional planning was performed using MeshMixer (AutoDesk, Inc., San Rafael, CA, USA) and Amira for LifeSciences 6.0 software (Thermo Scientific, Waltham, MA, USA) for identification of the landmarks for the surgical approach, and measurement of the exact volume and extension of the lesion. During surgery, the dog was placed in sternal recumbency, and its mouth was held open with a special equipment. Videoendoscopy was used for better visualization (Karl-Storz 2.7 mm 30° optic kit, 6703BA, Tuttlingen, Germany). Fentanyl (5 μg/bwkg; Richter Gedeon, Budapest, Hungary), dormicum (0.05 mg/bwkg; Egis Pharmaceuticals PLC, Budapest, Hungary), and ketamine (CP Ketamin 10% AUV; Medicus Partner, Hungary) were used as premedication before anesthesia induction using propofol (5.5 mg/bwkg; propofol 1% MCT/LCT; Fresenius Kabi AB, Bad Homburg, Germany). Anesthesia was maintained with a mixture of isoflurane and oxygen gas (Isoflutek 1,000 mg/g, 1.5% volume/volume; Laboratorios Karizoo SA, Barcelona, Spain). The buccal hair was removed, and the mouth area was disinfected using chlorhexidine (Curasept Chlorhex 30 mL, 0.5% spray, Curaden Swiss, Marleston, Australia). Subsequently, the soft palate was incised in the midline using an electrocautery device, and a hole was drilled into the basisphenoid bone according to the preoperatively determined landmarks. Under continuous endoscopic guidance, the hole was enlarged until the medial edges of both cavernous sinuses were visible around the pituitary gland. The cyst was drained and the entire pituitary gland was removed along with a part of the cyst wall. The opened third chamber was visible after complete gland removal. The bone defect was closed using a special bone reconstruction and anticoagulant sponge (Cerasorbe Foam; Curasan AG, Kleinostheim, Bayern, Bavaria, Germany), and the soft palate wound was closed with monofilament absorbable sutures (Surgicryl, SMI AG, Hünningen, Belgium).
During and 24 h after surgery, strict monitoring and tests were conducted at 1-h intervals. Examinations included measurement of the body temperature, blood pressure, acid-base status, electrolyte status, urine specific gravity and volume, heart and respiratory rates, blood lactate and glucose levels, and tear production. No abnormalities were noted.
Substitution therapy was initiated immediately after surgery. This included intramuscular hydrocortisone injections (Solu-Cortef 1 mg/bwkg TID; Pfizer, New York City, NY, USA) and desmopressin eye drops (Nocutil 0.1 mg/mL spray, one drop TID; Gebro Pharma GmbH, Fieberbrunn, Austria). A buprenorphine injection (Bupredine Multidose 0.3 mg/mL, 0.03 mg/bwkg; Produlab Pharma B.V., Raamsdonksveer, Netherlands) was administered every 6 h, while an amoxicillin-clavulanic acid injection (Augmentin 1000/200 mg, 20 mg/bwkg; GlaxoSmithKline Pharmaceuticals, Ltd., Brentford, UK) was intravenously administered BID for 3 days. The surgery and the first post-operative day were uneventful.
One day after surgery, MRI was performed using the same 1.5-T scanner (Siemens) to acquire the following sequences: T2W fast spin echo images in the transverse (TE/TR, 83.3/3,920 ms; SL, 3 mm) and sagittal (TE/TR, 96.5/4,500 ms; SL, 3 mm) planes; T2W fluid-attenuated inversion recovery images in the dorsal plane (TE/TR, 127.4/8,002 ms; SL, 3 mm); T2W gradient recalled echo images in the horizontal plane (TE/TR, 20/620); T1-weighted spin echo images in the sagittal plane (TE/TR, 15/240 ms; SL, 2 mm); post-contrast images (0.2 mL/bwkg; Dotarem 0.05 mmol/l injection, Guerbet, Villepinte, France); and three-dimensional T1W images (magnetization prepared rapid gradient-echo) in the sagittal, transverse, and dorsal planes. The sella turcica and cyst were both empty, although the cyst walls showed contrast enhancement on post-contrast images ().
Cytological analysis of the surgical specimen indicated a high probability of a neuroendocrine or ependymal origin of the mass.
The presence of normal adenohypophyseal tissue was observed on histopathological analysis of hematoxylin- and eosin-stained slides; intact acidophilic, basophilic, and chromophobe cell populations; acute hypophyseal hyperemia; and dilatation of the intrahypophyseal vessels filled with erythrocytes. Immunohistochemical examination of the intact adenohypophyseal cells showed diffuse, intense, homogeneous cytoplasmic synaptophysin-positivity; multifocal, intense, homogeneous cytoplasmic pancytokeratin-positivity; and Ki-67-negativity. The intact endothelial cells in the intrahypophyseal vessels showed diffuse, intense, homogeneous, and membranous CD31-positivity.
No abnormalities were observed on neurological examination performed on the first post-operative day, and 2 days after hospitalization, the dog regained vision in both eyes.
Normal tear production was observed on Schirmer's test. The dog was discharged 3 days after surgery. Oral administration of prednisolone (Prednisolon-Richter 5 mg, 1 mg/kg BID; POS Richter Gedeon), desmopressin eye drops (one drop TID; Gebro Pharma GmbH), oral amoxicillin-clavulanic acid (Synulox 250 mg BID; Zoetis, Parsippany-Troy Hills, NJ, USA), and oral levothyroxine sodium (L-thyroxin Henning 100 μg, 15 μg/bwkg BID, Sanofi Aventis, Paris, France) were continued at home.
Blood and urine tests were repeated at 1, 5, 10, 20, and 25 days after surgery. Moderate increase in alanine aminotransferase (mean, 315 IU/L), gamma glutamyltransferase (mean, 71.7 IU/L), lipase (mean, 1,871 IU/L), and alkaline phosphatase (man, 1,173 U/L) levels was observed in complete blood count, a chemistry panel, and urinalysis. The T4 level slightly decreased (8.7 nmol/l) in the initial post-operative period, although it normalized by day 25 (20.2 nmol/l).
However, the dog presented with the same preoperative signs and symptoms 73 days after surgery, exhibiting obtundation and depression, and a tendency of seeking tight spaces again. No other problems were observed on neurological examination, and normal findings were obtained on thoracic radiography and abdominal ultrasound. Regrowth of the cyst to its original size was apparent on MRI, and was compressing the surrounding structures (). Because of the poor prognosis and worsening clinical signs, the owner requested euthanasia.
Macroscopically, the location of the cyst was accurately identified on the formalin-fixed brain ex situ (). The wall of the intracerebral cyst consisted of a thin external layer of astrocytic glial tissue, as observed on histopathological analysis of hematoxylin- and eosin-stained slides prepared from the brain sample obtained during necropsy, and internal single and multifocally double layers of ciliated, cuboidal-to-flattened, ependyma-like cells. Positivity of the cyst wall for glial fibrillary acidic protein, S100 protein, and vimentin, and negativity for synaptophysin and epithelial membrane antigen was observed on immunohistochemical examination. Thus, the final diagnosis was ependymal cyst.


An 18-year-old white male was diagnosed with a 1.3 cm testicular tumor in July 2012. Pathology revealed a mixed, non-seminomatous germ cell tumor with elements of teratoma, embryonal carcinoma, and yolk sac; the dominant component of the tumor was embryonal. He was treated with orchiectomy in August 2012 and then underwent surveillance. In October 2012, he was found to have lymphatic enlargement on CT scan. In November 2012, chemotherapy was initiated with bleomycin, etoposide, and cisplatin. Follow-up CT scan showed an enlarged cystic inter-aorto-caval mass suspicious for teratoma. In January 2013, retroperitoneal lymph node dissection found 3/10 positive nodes, which were resected. Pathology showed pure teratoma. HCG levels on 2 occasions thereafter (ie, on January 17, 2013, and January 23, 2013) were undetectable. Later, the HCG levels became positive and gradually rose from 2.9 to 4.3 mIU/mL between July 24, 2013, and April 14, 2014 (). On April 24, 2014, a mass was felt on palpation of the left testicle, which was confirmed on ultrasound imaging. Accordingly, a left orchiectomy was performed on April 24, 2014. The pathology was reported as mixed germ cell tumor containing embryonal carcinoma, yolk sac tumor, mature teratoma, and immature teratoma with the dominant tumor type embryonal carcinoma (50%). Preoperatively his LH was 1.2 mIU/mL, his FSH 3.8 mIU/mL, and testosterone 435 ng/dL. He was then started on intramuscular testosterone injections followed by testosterone gel. Postoperatively his HCG was found to be elevated at 4.2 mIIU/mL and testosterone levels exceeded 1000 ng/dL. Serial HCG, LH, FSH, and testosterone levels are shown in . Furthermore, gonadotropin assays were performed by Esoterix laboratory (subsidiary of Labcorps) and found to be persistently elevated. No residual tumor was found on extensive imaging including serial CT scans of the abdomen and pelvis and also chest X-rays. The key question was whether the patient had a residual tumor lurking somewhere or whether the HCG was somehow falsely elevated.


A 78-year-old woman with an unremarkable past medical history presented to the clinic with symptoms of progressively worsening myelopathy including gait dysfunction and impairment of upper extremity fine motor skills. Noncontrast MRI of the cervical spine demonstrated multilevel degenerative disease and a dorsal intradural extramedullary lesion extending from C3-C6.
The patient underwent an elective posterior C3-7 decompression, C3-T1 instrumented fusion, and resection of intradural tumor. Final pathology was psammomatous meningioma. The patient tolerated the procedure well and postoperatively was transferred to the neurological ICU for close monitoring.
The patient was initially discharged from the hospital to an inpatient rehabilitation facility on POD 6. At the time of discharge, she was awake, oriented, and followed commands in all extremities with some mild weakness in the right deltoid and biceps, graded 4/5; the remaining muscle groups were 5/5. On POD 10, the patient developed progressive lethargy and was readmitted to the hospital for further evaluation. Upon readmission, she opened her eyes to verbal command, had incomprehensible speech, and would move all extremities spontaneously with strength 3/5 but did not follow commands. She was afebrile with WBC = 6.9 and no metabolic abnormalities. Given her recent intradural surgery, a lumbar puncture was performed. CSF cytology demonstrated 397 WBC, 20 RBC, 291 protein, and 40 glucose. CSF PCR was positive for HSV 1. Interestingly, intracranial imaging did not demonstrate the typical findings associated with herpes encephalitis (). She was initially placed on broad spectrum antibiotics in addition to antiviral therapy. She was also connected to continuous EEG monitoring, found to be in status epilepticus, and required escalating therapy to the point of intubation with midazolam infusion. Seizure control was ultimately achieved, and she was maintained on levetiracetam 1500 mg q12H for 30 days and lacosamide 200 mg q12H for 7 days. The remainder of her infectious work-up was unremarkable, allowing her to be narrowed to only a 21-day course of IV acyclovir 500 mg q12H. Due to acute respiratory failure from encephalopathy, she underwent tracheostomy and PEG placement (POD 29); she underwent repeat MRI approximately 2 weeks after HSV diagnosis which still lacked typical findings of HSV (). However, she continued to improve clinically; at the time of discharge, she would open her eyes spontaneously and followed simple commands in all extremities. Approximately 3 months out from being diagnosed with HSV encephalitis, she was oriented twice and followed commands in all 4 extremities with 5/5 strength in the bilateral upper and 3/5 in the bilateral lower extremities.
At a three-month follow-up, the patient presented no new symptoms. The PEG was still in place and EEG revealed excessive theta waves during wakefulness and bilateral midtemporal delta slowing (left more prevalent than right). Though the patient had dysarthria and poor attention/processing, she followed commands in all 4 extremities consistent with her last evaluation. Vimpat 200 BID and 1500 mg of Keppra were prescribed for ongoing clonus spasticity. All other medications were continued as prescribed. In the following month, the patient had a normal LOC, very slight dysarthria, and improved situational awareness. No recent seizures had occurred. Lacosamide was reduced to 150 mg every 12 hours and Vimpat was reduced to 150 BID. Upon final examination, she followed commands in all 4 extremities with 5/5 strength in the bilateral upper and 4-/5 in the bilateral lower extremities.


A 48-year-old-male with a history of inferior ST-elevation myocardial infarction (STEMI) status post percutaneous coronary intervention (PCI) with drug-eluting stent (DES) to the distal right coronary artery (RCA) eight months prior, presented with recurrent angina, described as pressure-like, substernal, radiating to both arms, and similar to his previous STEMI presentation. His angina occurred at rest and was alleviated with sublingual nitroglycerin. The patient was compliant with guideline-directed medical therapy with dual antiplatelet therapy (DAPT), statin, and beta-blocker (BB). His family history did not have any history of premature coronary artery disease or of sudden cardiac death. He never smoked and rarely consumed alcohol. His vitals on presentation to the emergency room were: blood pressure (BP) 146/82 mmHg; heart rate (HR) 88/min; respiratory rate (RR) 16/min; afebrile; and oxygen saturation of 98% on room air. His physical exam, including cardiac and pulmonary exams, were unremarkable. His electrocardiogram (EKG) demonstrated signs of prior inferior infarct with no acute signs of ischemia or ST-changes (Figure ). Serum troponin was initially 0.37 ng/L (normal <0.05 ng/L) and subsequently peaked at 1.93 ng/L. The patient was diagnosed with non-STEMI. A heparin infusion was started per acute coronary syndrome (ACS) protocol. Given the diagnosis of non-STEMI, left heart catheterization was performed, revealing severe focal stenosis just proximal to the previously placed stent. A decision to proceed with PCI was made. Immediately after guidewire passage into the RCA, acute spasm developed, resulting in diffuse, severe stenosis, extending over previously normal segments to the proximal RCA. This completely resolved with intracoronary nicardipine and nitroglycerin, including the initial focal stenosis (Figure ). The patient was diagnosed with vasospastic angina (VSA). He was continued on DAPT, BB, and statin with the addition of the non-dihydropyridine calcium channel blocker (CCB), verapamil. Despite this, the patient continued to experience intermittent angina and verapamil was increased to the maximum dose. An oral long-acting nitrate was additionally added but quickly discontinued due to intolerable headaches. Various second CCBs were added, including a dihydropyridine CCB, but intermittent angina continued. At this point, the patient was diagnosed with refractory VSA. Clonidine (alpha-2-agonist) was also tried, with no benefit. Eventually, a nitroglycerin patch was added with reduced headaches and a modest decrease in the frequency of angina episodes.