A 55-year-old male patient with a history of neck pain and numbness of extremities for 6 years presented with hypoesthesia below the inguinal plane. The right upper extremity numbness was heavier than the left. The abovementioned symptoms were aggravated for 1 year resulting in a walking disorder. The patient required crutches when walking, and the maximum distance that he could walk was 50 m. Physical examination showed grade III strength of each muscle in both upper extremities, grade II grip strength, and grade IV strength of each muscle in both lower extremities. Bilateral Hoffman tests were positive, whereas the tendon reflex of both lower extremities was hyperactive. Magnetic resonance imaging (MRI) of the cervical vertebra showed that abnormal odontoid in the occipitocervical junction area and severe surrounding hydrops. The atlantoaxial instability resulted in mild AAD, as detected via computed tomography (CT), and the spinal cord was compressed by the posterior atlas arch (Fig. ).
After failure of conservative treatment, we decided to perform surgical treatment on the patient to address the walking disorder. Preoperatively, we performed cervical CT angiography (CTA) to evaluate the relationship between the important blood vessels and bone in the cervical area. At the same time, 3D CT of the cervical region was performed to make a 3D print model of the patient's occipitocervical area (Fig. ). We simulated the depth and angle of cervical screw insertion according to the 3D print model, and finally determined the most suitable cervical screw for the patient. After adequate preoperative preparation, we performed posterior-only occipitocervical fusion combined with intraoperative 3D navigation system.
After induction of general anesthesia, the patient was placed in a prone position. The vertebrae were exposed through an approximately 25-cm longitudinal midline skin incision from the occipital tuberosity to the spinous process of C6. The skin, subcutaneous tissue, ligaments, and deep fascia were exposed layer by layer. The occipital to the C5 spinous processes were fully exposed. The 3D navigation patient tracker was placed at the C5 level, and C-arm scan of the cervical vertebra with preoperative CT imaging after matching was performed. After matching to obtain high quality images, the navigation device was along the left side of the C2 articular process to determine the nail's insertion point, angle, and depth. Pedicle screws were placed at the C2 level on the left, and pedicle screws were placed at the right side of C2 vertebra in the same manner; then, the lateral mass screws were placed at the sides of C3 and C4. The pre-bent connecting rod was inserted into the screw tail groove and the top wire was locked. Three cranial screw casings were inserted into the left connecting rod. The position and angle of the casings were adjusted. Three cranial screws were inserted into the screw holes, and the right cranial base was manipulated in the same manner. The 3 cranial screw casings and screws were then inserted. The positional depth of the pedicle screw was determined to good by c-arm fluoroscopy. The posterior arch edge was removed by grinding and drilling on the right side of the posterior arch of the atlas, and part of the bone was removed by laminar forceps. With the hook nerve dissection, the dural sac was separated from the posterior arch of the atlas, and the posterior arch of the atlas was removed, thereby fully exposing the spinal cord pulses. The spinal cord surface is covered with thickened fibrous scar bands, which are carefully removed (Fig. ). The spinal cord was covered with a gelatin sponge. The trimmed autogenous cancellous bone and allogeneic artificial bone were implanted on the polished bone surface. After the implantation was confirmed, the neck muscles were restored, and a negative pressure drainage box was retained and fixed. The pedicle screw system was in the right position without displacement, which was confirmed on the intraoperative and postoperative X-ray films (Fig. ).
Owing to the operation in the upper cervical vertebra and the medulla oblongata region, the patient's respiratory and circulatory systems were very likely to be damaged. After the operation we managed to keep the patient in the state of endotracheal intubation for 24 hours and then slowly come out of the anesthesia, and the patient's vital signs were closely monitored. The patient's vital signs were stable when he woke up, and he was conscious and had good limb movements. His grip strength increased from grade II before surgery to grade IV after surgery. Dexamethasone 5 mg/bid was administered twice a day for 5 days. Neurotrophic and anti-infective therapies were given at the same time. The wound healed at the first stage, and the stitches were removed at 14 days postoperatively. After removal of the stitches, 3D-CT was performed, which showed that the position of the pedicle screw was not significantly changed from that of the X-ray obtained 2 weeks prior (Fig. ). Postoperative MRI was not included in this paper due to the severity of the artifacts. At 3 weeks postoperatively, the patient's walking was ability improved and he was able to walk approximately 100 m by himself when he was allowed to get up and move around with the use of a neck brace. At 6 months postoperatively, the patient reported that the numbness of the limbs was reduced, and he was able to walk >500 m by himself. Physical examination showed grip strength of grade IV, and the rest of the limb muscle strength was grade IV. The tendon reflexes of both lower limbs were normally elicited without hyperactivity. In the past 6 months, there were no other discomforts and related complications, indicating that the operation was successful.


A 72-year-old female patient was admitted to our hospital due to recurrent dysphagia for more than 5 years and aggravated dysphagia for 1 year. Two years prior to admission, the patient started to experience dysphagia but had no symptoms of hematemesis, melena, diarrhea, abdominal pain, headache, dizziness, progressive dysphagia, or history of special diseases. A physical examination showed no abnormal heart–lung auscultation, a flat belly, a soft abdominal wall, no palpation or rebound tenderness, and no involvement of the liver, spleen, or under the ribs. A routine blood examination showed that the white blood cell count (WBC) was 5.39 (∗10^9/L), heartbeat (HB) was 112 (g/L), and platelet count (PLT) was 243 (∗10^9/L), and the fecal occult blood test was weakly positive. A significant diverticulum with food residue was found on gastroscopy at the entrance of the esophagus (Fig. ). The patient was diagnosed with ZD.
Because of her age and the invasiveness of surgical excision, she opted for treatment with STESD. After completing a relevant examination and excluding surgical contraindications, the patient signed an informed consent document and underwent STESD under general anesthesia. A diverticulum was found at the esophageal entry. Adrenaline saline was injected submucosally at 3 cm above the diverticular septum. A longitudinal mucosal incision was made using a hook knife. A submucosal tunnel was established to the diverticular septum. The mucosal layer at both sides of the septum was isolated and fully exposed. Then, the muscle layer was dissected from the middle of the septum down to the bottom of the diverticulum using a Dual knife. The wound was treated with coagulation forceps, and the tunnel entry was closed with titanium clips (Fig. ). Any mucosal injury or perforation should also be clipped. The operation was completed in <1 h. Minor bleeding occurred after septotomy and stopped after endoscopic placement of endoclips. The patient fasted without food or water intake, and intravenous antibiotics and nutrition rehydration were given for 2 days postsurgery. Semi-fluid diet was resumed on postoperative day 3, and the patient was discharged after the symptoms alleviated on postoperative day 4. A 3-month follow-up gastroscopy showed the disappearance of the diverticulum and the recovery of the esophageal anatomical structure. No symptom relapse was found at the 6-month follow-up assessment.


A 62-year-old female patient underwent a gastroscopic examination due to “recurrent dysphagia for 10 years and aggravated dysphagia accompanied by bad breath for 1 year.” A diverticulum with a diameter of 2.5 cm and depth of 3.0 cm was found below the posterior wall of the esophageal entry, 15 cm from the incisors. A 1.5-cm-long ridge-like tissue was found between the diverticulum and the esophageal lumen. Food residue and fluid were found inside the diverticulum. The patient was diagnosed with ZD. The patient was mostly healthy and did not have abdominal pain, diarrhea, heartburn, reflux, headache, or dizziness. A physical examination showed no abnormal heart–lung auscultation, a flat belly, soft abdominal wall, no palpation or rebound tenderness, and no involvement of the liver, spleen, or under the ribs. After completing the relevant examination and signing an informed consent document, the patient underwent STESD under general anesthesia. Adrenaline saline was injected submucosally 3 cm above the right side of the diverticular septum. A 2.0-cm longitudinal mucosal incision was made with a hook knife, and a tunnel was established. The mucosal layer was separated using a Dual knife to the muscle layer of the diverticular septum. Then, the muscle layer was dissected from the middle of the septum down to the bottom of the diverticulum. The wound was treated with coagulation forceps, and the mucosal incision was closed with titanium clips. The procedure time was 45 min, and minor bleeding occurred during the operation. The patient fasted without food or water intake, and intravenous antibiotics and nutrition rehydration were given for 3 days after surgery. The patient was discharged after the symptoms alleviated on postoperative day 4. The 3-month follow-up endoscopy showed the disappearance of the diverticulum. No symptom relapse was found at the 6-month follow-up assessment.


A 56-year-old woman presented with dysphagia in 2007. The results of an endoscopic examination performed at the previous hospital were unremarkable. Her complaints became more severe in November 2009, and she was referred to our hospital for treatment.
Endoscopic examination at our institution revealed a circumferential erosion of the esophageal mucosa 28-40 cm from the incisors, and it was impossible to advance the endoscope due to stenosis at 37-40 cm (Fig. a). Type A vessels were detected by magnified narrow band imaging (NBI) (Fig. b), and the lesion did not stain with iodine (Fig. c). Esophagography revealed smooth stenosis of the lower esophagus (Fig. ). A CT scan showed mild thickening of the lower thoracic esophageal wall but no evidence of lymph node swelling in the thoracic or abdominal cavity. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) did not show FDG uptake, and the levels of the tumor markers SCC, CEA, and anti-p53 antibody were within their normal ranges. Although the lesion was suspected of being a malignant tumor of the esophagus, pathological examination of biopsy specimens from four different sites resulted in a diagnosis of esophagitis. We then performed esophageal high-resolution manometry and an esophageal pH study, but because these studies did not reveal abnormal esophagogastric reflux or esophageal motor dysfunction, we followed up the lesion by upper gastrointestinal endoscopy every 3 months.
Polypoid lesions and fungal infection were observed on the erosive lesion during the follow-up examination after 1 year (Fig. a, b), but no evidence of malignancy was detected during the pathological examination of the biopsy specimens (Fig. c, d), and the CT scan showed no particular changes during the period. Antifungal agents were administered for 1 month for fungal infection of the lesions, but the lesions did not change.
Polypoid lesions have further increased in size (Fig. a, b), and the biopsy specimen was diagnosed as highly suspicious of well-differentiated squamous cell carcinoma. Esophagography revealed irregular stenosis (Fig. c), and a CT scan showed circumferential wall thickening in the lower esophagus (Fig. a) with increased FDG uptake (SUV max, 9.5) on PET/CT (Fig. b). Because the patient’s condition rapidly deteriorated due to worsening of the dysphagia and weight loss, we performed a thoracoscopic esophagectomy with lymph node dissection and reconstruction with a gastric tube via the posterior mediastinal route. The postoperative course was uneventful, and the patient was discharged on postoperative day 28. The patient did not receive any adjuvant chemotherapy, and there have been no recurrences as of 8 years after surgery.
Macroscopic examination of the resected specimen revealed a white protruding lesion with an irregular surface in the lower esophagus (Fig. ). Microscopic examination showed epithelial downgrowth and invasive findings of the tumor, and the diagnosis was xwell-differentiated squamous cell carcinoma. Focal hyperkeratosis with a church spire configuration was also seen (Fig. ). These macroscopic and microscopic features were consistent with the growth pattern of VC. The pathological stage was T3N0M0, pStageIIA (UICC7th). No venous or lymphatic invasion was detected. All surgical margins were negative for malignancy.


A 2-year-old girl referred for the cytogenetic exploration with a family history of lissencephaly (Fig. .II-2), is the second child of a healthy consanguineous Tunisian couple. The patient’s weight at birth was 3500 g (+ 0,6SD). She measured 52 cm (+ 1,05SD) and had a head circumference of 35 cm (+ 0,4SD). At 2 years of age, her height and head circumference were 88 cm (+ 0,9SD) and 45 cm (− 2,5SD), respectively. At physical examination, she had psychomotor development delay and an abnormal behavior including aggressiveness, anger and agitation. Furthermore, she had craniofacial dysmorphic features (Fig. a, A’) including a long face, a high forehead, down-slanting palpebral fissures, epicanthus, a wide nose, a long philtrum, a thin upper lip, large and high implanted ears and a pointed chin with micrognathia. In addition, she showed arachnodactyly. Her cerebral magnetic resonance imaging (MRI) was performed at two years and five months of age, and corpus callosum hypoplasia was detected.


An 84-year-old male patient fell while walking and suffered left intertrochanteric fracture (Fig. ). He refused the surgery recommendation, chose to remain bedridden. Physical therapy for prophylaxis of thromboembolism at home was prescribed. Ten days later, his left calf swelled, and venous thrombosis was identified by ultrasound in popliteal vein and posterior tibial veins. The patient was admitted to our department 13 days after the injury to evaluate and improve medical fitness and prepare for internal fixation. The patient had a medical history of cerebral infarction more than 10 years ago, and long-term use of aspirin. The platelet count was 349 × 10^9/L, and the haemoglobin count was 112 g/L on the first day of admission (Table ). Aspirin was stopped and LMWH (FRAGMIN, Pfizer) 5000 IU was given twice daily as therapeutic anticoagulation therapy. Moreover, the inferior vena cava filter was placed. Unfortunately, serious blood shortage happened which led to the postponement of the internal fixation. The patient had abdominal distention and melena on the 16th day after admission (Table ). He developed hematochezia 3 h later without peritoneal irritation. Redness and swelling were found at the LMWH injection site. The platelet count was 3 × 10^9/L, and the haemoglobin count was 98 g/L. The sum of the 4 T’s scores was 6. Autoantibodies, anti-ds DNA antibody, and other tests for differential diagnosis were normal. Therefore, we made the clinical diagnosis of HIT, digestive hemorrhage, VTE, and intertrochanteric fracture. We stopped LMWH therapy and underwent gamma globulin infusion (0.4 g/kg, iv), methylprednisolone infusion (60 mg, iv, QD), platelet transfusion and total parenteral nutrition (TPN). After that, the platelet count increased steadily, and the digestive haemorrhage gradually stopped. On the 24th day after admission (Table ) (the 5th day of the use of gamma globulin) the platelet count recovered to 60 × 10^9/L, and the haemoglobin count recovered to 96 g/L. On the 35th day after admission (Table ), the patient developed abdominal distending pain. Physical examination indicated the weakening of bowel sounds without abdominal tenderness. The platelet count was 87 × 10^9/L. The haemoglobin count was 108 g/L. The WBC count was 12.8 × 109/L, and the potassium concentration was 5.59 mmol/L. Abdominal X-ray showed colonic dilatation. The abdominal CT scan showed colonic dilatation with no sign of thromboses and mechanical obstruction, such as thickening of the colonic wall or thrombosis of mesenteric vessels (Fig. ). Therefore, we performed a multidisciplinary consultation and made a diagnosis of ACPO and performed conservative treatments, such as TPN and gastrointestinal decompression therapy. On the 39th day after admission (Table ), the patient developed high fever and unconsciousness without acute abdominal pain and tenderness. The platelet count was 14 × 10^9/L. The haemoglobin count was 95 g/L, and the WBC count was 4.8 × 109/L. The serum lactate was 4.0 mmol/l, the blood pressure was 90/63 mmHg, and heart rate was 98 beats per minute, which suggested of septic shock. We diagnosed the patient with gut-origin septic shock and micro-angiopathic hemolysis. The conservative treatments, such as gastrointestinal decompression, TPN, anti-infection and somatostatin were ineffective, and the patient died 4 days later.


A 30-year-old male has sustained an open distal femoral fracture (AO/OTA classification 33-C3, Gustilo-Anderson classification IIIA) from a motorcycle accident. He was initially treated with debridement, followed by open reduction and internal fixation with lateral locking plate two days after the injury. He was referred to our institution for the treatment of metaphyseal nonunion six months after the injury (). Computed tomography (CT) also revealed malunited articular fragment with step-off (). His femorotibial angle was 167°. At presentation, he could not bear weight on his injured leg, and the range of motion was -20° of knee extension and 90° of knee flexion. He underwent simultaneous corrective osteotomy for articular malunion and induced membrane technique for metaphyseal nonunion 14 months after the initial surgery.
A preoperative 3D-printed model was made to gain the clearer picture of both articular malunion and metaphyseal nonunion (). Malunited articular lesions were separated into three components. Longitudinal skin incision over the midline of the patella was placed. Subsequently, the medial parapatellar approach with the split in the quadriceps was used to acquire better exposure of the articular surface. Screws and the plate were removed with the additional incision over the iliotibial tract. Malunited articular fragments were separated into anterolateral, posterolateral, and medial fragments. Osteotomy of the malunited articular fragments was performed using an oscillating saw and chisel (). The anterolateral fragment was moved distally and temporally fixed to the medial condyle fragment (). External rotation of the posterolateral fragment was corrected, and the fragment was temporally fixed to the medial condyle fragment (). The anterolateral and posterolateral fragments were fixed with two partially threaded 6.5 mm cannulated screws (). Subsequently, anterolateral and medial condyle fragments were fixed with one partially threaded 6.5 mm cannulated screw (). For the metaphyseal nonunion, necrotic bone fragments were removed, and the edge of each fragment was refreshed until the good hemorrhage from the bone marrow was confirmed, leaving a maximum of 9 cm defect. 4.5 mm LCP® Distal Femur Plate 9 Holes (DePuy Synthes®, USA) was placed over the lateral side of the femur. 3.5 mm LCP® Proximal Tibia (DePuy Synthes®, USA) was added in an inverted manner as a medial plate to provide more stability (Figures and ). Metaphyseal bone defect was filled with bone cement (Cemex fast Tecres® S.p.A, Italy) with vancomycin (). The wound was irrigated, and each layer was closed. Postoperative radiograph and CT scan showed the correction of valgus knee deformity and articular step-off (Figures and ). Six weeks after the osteotomy, bone grafting was performed. The bone cement in the metaphyseal part was removed, and the defect was filled with cancerous bone graft from the iliac crest. Both the articular osteotomy site and the metaphyseal nonunion demonstrated radiographic union at two months. For the remaining leg discrepancy, the patient underwent the additional distraction osteogenesis at the proximal femur with external fixator six months after the osteotomy.
Six years after the osteotomy, the patient regained full weight bearing without pain (). The range of motion has improved to 0° of knee extension and 120° of knee flexion, and the femorotibial angle is 172°. There is a mild bony spur formation over the tibia side of the knee, but there is no sign of necrosis of the epicondyle. The patient was informed that data from his case would be submitted for publication, and he provided consent.


A 64-year-old man with ESRD from diabetic nephropathy on hemodialysis for one year presented for transplant evaluation. He had a remote history of polysubstance addiction including heroin injection with methadone detoxification and then complete nonuse of illicit drugs for decades; he did not want opioid agonist therapy and was active in Narcotics Anonymous for years. He had a 30 pack-year smoking history, but had quit tobacco at the same time as illicit drugs.
He had a history of well-controlled HIV diagnosed in 1987, with an undetectable viral load and CD4-infected cell count >500 cells/mm3 for many years. He had been on numerous prior antiretroviral regimens to treat his HIV and harbored multiclass resistance to agents in the nonnucleoside reverse transcriptase inhibitor (NRTI: M184V and T215N/S/Y) and protease inhibitor (PI: L33I, M46I, I54V, I62V, and V82A/I/T) classes. He ultimately achieved long-term virologic suppression with etravirine, darunavir, ritonavir, and raltegravir (the TRIO [, ] regimen). In advance of transplant, his resistance history was reviewed and an HIV-1 proviral DNA genotype archive was sent, which did not demonstrate any resistance to the integrase inhibitor or the NNRTI class. He was switched to rilpivirine and dolutegravir [] to reduce the risk of drug-drug interactions (DDI) (ritonavir significantly increases calcineurin inhibitor (CNI) levels) and to avoid complex dose adjustment with fluctuating renal function post-transplant.
The patient was also infected with HBV. Tenofovir disoproxil fumarate had been discontinued several years before due to concern for contribution to his progressive renal disease, and he was maintained on lifelong entecavir treatment. He also had chronic hepatitis C virus (HCV), genotype 2b, and declined interferon therapy for years. By the time DAAs became available, there was no DAA for genotype 2 that could be given with his degree of advanced renal disease. When he developed advanced fibrosis (F3), it was recommended that consideration of renal transplant be accelerated given advancing liver disease. He had a history of coronary artery disease (CAD) and inferior myocardial infarction eight years before, with a stent placed to the right coronary artery (RCA). He was taking aspirin 325 mg daily and atorvastatin 40 mg daily. As part of his pretransplant evaluation, a nuclear myocardial perfusion test revealed a large-sized inferior and inferolateral fixed defect with preserved ejection fraction. The patient had very good functional status and did not report any symptoms, so further preoperative cardiac workup was not pursued.
Three months after listing, he underwent deceased donor kidney transplant from an HCV-positive donor (by antibody and nucleic acid-testing (NAT)-genotype 1a) with basiliximab induction. Maintenance immunosuppression included mycophenolate sodium, tacrolimus, and prednisone. He was also started on valganciclovir and atovaquone prophylaxis due to sulfonamide allergy. On postoperative day (POD) 1, he developed substernal anginal chest pain. An electrocardiogram (EKG) showed ST depressions in the anterolateral leads and transient ST elevation in lead III (). His serum troponin peaked at 31 ng/ml (normal <0.06 ng/ml). He was treated with aspirin, clopidogrel, and nitroglycerin drip, without anticoagulation, for fear of hemorrhage due to extensive retroperitoneal blunt dissection during transplant. He underwent cardiac catherization on POD3, which revealed 3-vessel disease, with near-complete occlusion of the RCA stent (). On POD 10, he had successful placement of two drug-eluting stents in the RCA (). The patient experienced delayed graft function, requiring hemodialysis but was eventually discharged off dialysis on POD 15. Of note, on POD 9 his HCV genotype was 2b, but subsequent genotype before initiation of treatment (POD 81) was only 1a (donor-derived). On POD 100, the patient was admitted for febrile neutropenia, requiring colony-stimulating growth factor support and discontinuation of both valganciclovir and mycophenolate.
On POD 141, he was started on therapy for HCV, with pangenotypic glecaprevir/pibrentasvir (GLE/PIB) for 12 weeks, targeting both donor and recipient genotypes. Concomitant use of GLE/PIB and atorvastatin is contraindicated; thus, he was switched to pravastatin during treatment. Additionally, therapeutic drug monitoring of tacrolimus levels was increased to twice weekly for the first month and weekly for the next 2 months, before resuming laboratory workup per transplant protocol (twice every month until 6 months after transplant, then monthly). He required transient reduction of his tacrolimus dose from 2 mg to 1 mg twice daily (bid) because of supratherapeutic trough levels (highest: 18 mg/dL, post-transplant goal: 7 mg/dL), one week after starting GLE/PIB. After 3 weeks, the tacrolimus dose was again increased to 2 mg bid (). He achieved sustained virologic response (SVR) 12 weeks after treatment completion (SVR 12). He developed high-level BK viremia 1.5 year after transplant, which resolved by decreasing the tacrolimus trough goal to 4 mg/dL. Two years after transplant, he is doing well, and has excellent graft function and undetectable HIV, HCV, and HBV viral loads. He remains on entecavir prophylaxis.


A 92-year-old male presented to the emergency department with a 4-day history of flu-like symptoms and shortness of breath that had progressed to respiratory failure. On admission, he was intubated and on vasopressors due to circulatory shock. Endotracheal intubation had been performed at an outside facility; mechanical ventilation was reportedly difficult. At examination, no breath sounds were audible on the left side, and the jugular veins were distended. Point-of-care ultrasound showed no lung sliding on the left. Tube thoracostomy was performed and a pigtail catheter placed, with positive air drainage. Chest radiograph showed a well-positioned catheter and good lung expansion ().
On day two, the patient was extubated and transferred to the Intermediate Care Unit. Three days later he had abrupt onset of dyspnea, extensive subcutaneous emphysema, and drainage of serosanguinous fluid through the chest tube instead of air. Chest computerized tomography showed the pigtail within the lung parenchyma and a residual pneumothorax ().
The decision was to remove the pigtail and place a traditional chest tube. The patient had an uneventful course, with complete resolution of pneumothorax. The chest tube was removed after six days, and the patient was discharged without further complications.


A 1-year-old spayed female domestic shorthair cat weighing 4.3 kg presented for
evaluation of an acute (<24 h) non-weight bearing right pelvic limb lameness
sustained after falling approximately 4 m in height. The cat was reluctant to
ambulate and would not bear weight on the right pelvic limb. There was substantial
swelling and pain on manipulation of the right metatarsus and phalanges.
Radiographs of the right pes revealed dorsoproximal metatarsophalangeal joint
luxations of the third, fourth and fifth digits, with moderate associated soft
tissue swelling extending proximally to the tarsocrural joint (). There was lateral rotation of the
second digit relative to the head of the second metatarsal bone. Closed manual
reduction of the metatarsophalangeal luxations was attempted under sedation but was
unsuccessful.
Open reduction and stabilization were performed under general anesthesia the
following day. The cat was positioned in dorsal recumbency with the right pelvic
limb extended caudally. A 2 cm dorsal incision was made, extending proximally from
the metatarsophalangeal joint of the third digit. The digital extensor tendon was
separated from the underlying bones and joint capsule using blunt dissection.
Hohmann retractors were placed medial and lateral to the distal aspect of the third
metatarsal bone to expose the metatarsophalangeal joint space. A Backhaus towel
clamp was placed on the distal phalanx to traction the digit as a Freer elevator was
used to successfully lever the proximal phalanx into reduction. The articulation was
re-luxated and a pilot hole was made centrally in the articular surface of the head
of the third metatarsal bone using a 1 mm Kirschner wire. The pilot hole completely
penetrated the subchondral bone and appropriate positioning of the Kirschner wire in
the medullary canal of the distal metatarsal bone was confirmed by fluoroscopy. The
wire was removed and normograded from the proximal articular surface of the proximal
phalanx, penetrating the dorsal cortex of the body of the phalanx. The wire was
driven out of the skin overlying the proximal phalanx, until only 5 mm of wire was
protruding proximal to the articular surface of the phalanx. The protruding segment
of wire was inserted into the pilot hole and advanced into the medullary canal of
the metatarsal bone. A second 2 cm dorsal incision was then made over the fourth
metatarsophalangeal joint. Once the luxation was exposed, a Backhaus towel clamp was
placed on the fourth distal phalanx and manual reduction was attempted but could not
be obtained. The medial collateral ligament was transected in order to allow for
reduction of the joint. A 1 mm Kirschner wire was then placed in a similar fashion
as previously described, except that the proximal tip of the wire was trimmed before
the wire was seated in the fourth metatarsal bone. Accurate positioning of the
Kirschner wires was confirmed via fluoroscopy (). The second and fifth
metatarsophalangeal joints were then tractioned into reduction and were palpably
stable. The surgical approaches were closed routinely in two layers.
A 1 mm Kirschner wire was percutaneously placed transversely through the base of
metatarsal bones II–V. Radiographs were obtained and the transverse Kirschner wire
was noted to impinge on the tarsometatarsal joints (). This wire was not removed and a
second Kirschner wire was placed transversely through the proximal third of the
metatarsal bones II–V. Two pairs of heavy needle drivers were used to bend the
protruding portion of the Kirschner wires to converge over the dorsal aspect of the
pes. The transarticular wires were bent as close as possible to the proximal
phalanx, while the transverse pins were bent 5–10 mm from the skin surface laterally
or medially. A sphere of polymethylmethacrylate (Technovit 6 Treatment Kit;
Jorgensen Laboratories) was applied, enveloping the ends of the Kirschner wires, and
was allowed to polymerize. The skin surface was protected during application of the
acrylic to prevent hyperthermic injury. A centimeter of clearance was maintained
between the skin surface and the polymethylmethacrylate to allow for postoperative
swelling ().
The cat was willing to ambulate and bear weight on the right pelvic limb the morning
following surgery, although there was marked swelling of the distal right pes,
particularly digits III and IV. The cat was hospitalized for 48 h postoperatively,
during which time the majority of swelling abated. The cat was discharged and the
owner given instructions to administer meloxicam (0.1 mg/kg PO q24h) and
buprenorphine (0.01 mg/kg sublingually q8–12h) for 3–5 days. Strict cage confinement
was recommended and the owners were instructed to clean the wire–skin interfaces
daily with dilute chlorhexidine solution followed by application of triple
antibiotic ointment.
The cat was ambulating well when evaluated 1 week after surgery, but had a persistent
weight bearing right pelvic limb lameness. The swelling had resolved, but there was
visible internal rotation of the fourth digit. By 3 weeks, the cat was consistently
bearing substantial weight on the right pelvic limb. The two wires stabilizing the
luxations had minor wire tract inflammation. Radiographs revealed a moderate increase of the right third and fourth
metatarsophalangeal joint spaces, and a mild amount of smooth periosteal
proliferation along the plantar aspect of the proximal- to mid-diaphysis of the
fifth metatarsal bone adjacent to the distal transverse Kirschner wire. Internal
rotation of the third and fourth distal metatarsal bones and digits was also noted.
All implants were removed and subsequent radiographs obtained, which showed markedly
improved rotational alignment of the digits. The pes was placed in a plantar
metasplint that extended to the proximal aspect of the calcaneus fashioned from
thermoplastic material (Vet-lite Thermoplastic Casting Materials; Veterinary
Specialty Products) for an additional week. At splint removal, the wire tract
inflammation had resolved and the cat had a mild weight bearing lameness.
The cat was re-evaluated 6 months after surgery, at which time no lameness was
observed. The third and fourth metatarsophalangeal joints were immobile on
palpation, while the tibiotarsal and interphalangeal joints had maintained a normal
range of motion. Pain was not elicited on manipulation of the pes or tarsus.
Radiographs revealed moderate lateral displacement of the fourth digit and
associated sesamoid bones relative to the fourth metatarsal bone (). There was mild
metatarsophalangeal osteoarthrosis of the third and fourth digits. In addition,
there was mild distal intertarsal and moderate tarsometatarsal osteoarthrosis.


A 69-years-old man with chronic hepatitis B was admitted to our hospital for right subcostal pain and loss of appetite of four days duration. Laboratory data showed increased white blood cell of 12.7 × 103/ μl, serum C-reactive protein of 20.88 mg/dl, total bilirubin of 1.8 mg/dl, aspartate aminotransferase of 56 IU/l, alanine aminotransferase of 72 U/l, alkaline phosphatase of 206 IU/l, and gamma glutamyl transferase of 93 IU/l. Abdominal computer tomography (CT) revealed wall thickening of the gallbladder with air density (A) and an 80-mm tumor with early enhancement in the segment 8 of the liver (B and C). With a diagnosis of emphysematous cholecystitis, percutaneous transhepatic gallbladder drainage (PTGBD) was performed. Clostridium perfringens was identified from the culture of bile. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) revealed a liver tumor, which demonstrated hyper-vascularity in the arterial phase (D) and washout in the hepatocyte phase (E. Serum tumor markers were as followed; Carcinoembryonic antigen 1.8 ng/mL, alpha-fetoprotein 41 ng/mL, Protein Induced by Vitamin K Absence or antagonists-II (PIVKA-II) 1,120 mAU/ml. Therefore, we diagnose the liver tumor as hepatocellular carcinoma (HCC). The patients underwent extended anterior segmentectomy of the liver and cholecystectomy on 24 days after PTGBD. The gallbladder was necrotic and partially perforated, and peritoneal cavity was contaminated with yellow-white bile. A drain was placed in the right subphrenic space. The patient was given Flomoxef Sodium (FMOX) as perioperative antibiotic, which was sensitive for Clostridium perfringens. Pathological examination of the liver tumor revealed moderately differentiated HCC (A–C) with interface hepatitis, and gallbladder wall showed necrosis. Escherichia coli was cultured from the intraoperative bile.
After the operation, the drain was removed on postoperative day (POD) 5 (). However, the patient developed fever on POD 15 and CT demonstrated the emphysematous subphrenic abscess (A), for which CT guided percutaneous abscess drainage was performed (B) and Ciprofloxacin and Clindamycin were started intravenously. Clostridium perfringens was cultured from the drainage fluid which was sensitive to Ciprofloxacin. Thereafter, the patient made a satisfactory recovery, and the drain was removed on POD 75 after confirming that the drainage fluid become negative. After confirming disappearance of subphrenic abscess on CT, the patient was discharged on POD 95 (C) and remains well with no evidence of tumor or abscess recurrence as of 8 years after resection.


A 56-year-old male patient with typical clinical and electroneurographic findings of carpal-tunnel-syndrome caused by an intraneural PN of the right median nerve presented to our neurosurgical department. The patient complaint about a progressive hypaesthesia and paresis of the hand and underwent 4 surgeries over a period of 30 years without long term benefit because of suspected carpal-tunnel-syndrome. HRNS and magnetic resonance imaging (MRI) of the right-hand depicted an intraneural PN of the median nerve (Fig. ). Follow-up examination 27 months after surgery showed an improvement in motor function undergoing physiotherapy, but no change of the sensory deficits. HRNS revealed stable intraneural PN.


A 16-year-old left-handed male patient presented with an intraneural PN of the left ulnar nerve. Symptoms lasted over 2 years, showing a progressive atrophy of the intrinsic muscles of the left hand without any sensory deficit. Electrophysiological testing revealed an impairment of the left ulnar nerve, HRNS and MRI of the left arm showed intraneural PN of the ulnar nerve with a length of about 15 cm reaching from the middle of the upper arm to the middle of the forearm (Fig. ). Despite the atrophy of the intrinsic muscles of the hand, follow-up examination 24 months after surgery showed a stable state of the PN on HRNS, without any sensory deficit. The functionality of the hand improved under consequent physiotherapy.


A 17-year-old female patient complained about progressive impairment of foot elevation over a period of 3 years, showing a paresis of 2/5. The patient was treated by the neurologist due to the suspicious of an idiopathic peroneal paresis. Electrophysiological testing showed impairment of the left peroneal nerve. HRNS and MRI of the left leg revealed an intraneural PN of peroneal nerve (Fig. ). Postoperative, the paresis of the foot elevation increased to 1/5. Follow-up examination 30 months after surgery showed an improvement of the foot elevation, now 3/5.


A 31-year-old female with no family history of infertility, POI, or autoimmune disease visited our hospital for a long-desired early pregnancy. The patient denied a history of chemotherapy or radiation therapy. The patient had menarche at the age of 13, with regular menstruation until the age of 17; then, disordered menstruation emerged, and amenorrhea occurred at the age of 20. POI was diagnosed by several hospitals; chromosomal analysis demonstrated a normal female karyotype (46, XX); treatment with estradiol valerate and progesterone led to menstruation, while amenorrhea continued after withdrawal of HRT. The patient married at the age of 23 and had tried to conceive by HRT until the age of 25 (at which point she had given up after failing to conceive); her last menstruation was July 2014; amenorrhea continued to date. At the age of 29, because of her yearning for fertility, the patient visited a general hospital in Shanghai. Clinical tests showed luteinizing hormone (LH), 23.9 IU/L; follicle-stimulating hormone (FSH), 69.1 IU/L; estrogen, 43.3 pg/mL; and testosterone, 1.1 nmol/L. Infertility and POI were again confirmed. No sinus follicles were found in either ovary under ultrasonography. The patient lived a normal couple's life after marriage. On March 4, 2019, the patient visited our department due to nausea, vomiting, a small amount of vaginal bleeding, and a positive urinary pregnancy test. Examinations showed a normal physique for women of childbearing age, normally developed breasts, a normal distribution of pubic hair, vaginal patency, normal cervical development, and a uterus size consistent with 6+ weeks of pregnancy.
Ultrasonography showed an intrauterine early pregnancy with an insufficiently filled gestational sac sized 23 × 20 × 11 mm; the yolk sac, punctate embryo tissue and heart tube pulsation could be seen. HCG, estrogen, and progesterone were 32987.7~119151.4 mIU/ml, 671.0~>1,000 pg/mL, and 6.6~27.9 ng/ml, respectively. Anti-Müllerian hormone (AMH) was 0.08 ng/ml. Considering the threat of spontaneous abortion, POI and insufficient luteal function, luteum support therapy was adopted. The treatment regimen included intramuscular injection of progesterone (40 mg, QD, 15 days), dydrogesterone (10 mg BID orally for 45 days), and estradiol valerate (4 mg BID orally for 15 days). On March 8, 2019, the vaginal bleeding stopped. On March 22, 2019, ultrasonography showed a normally developed gestational sac sized 45 × 42 × 32 mm and a 17 mm crown-rump length; the yolk sac, punctate embryo tissue, and heart tube pulsation could be seen. The patient was in normal progress of a full-term pregnancy. On October 29, a 3,400 g healthy girl baby was delivered; the patient had a spontaneous delivery with natural labor.


A 33-year-old man underwent a CT scan after a mild traumatic brain injury. The study revealed an incidental brain mass, which was initially considered to be a meningioma. The patient was referred to the National Institute of Neurology and Neurosurgery for surgical treatment. His family history was unremarkable for oncologic diseases. His past medical history as recalled by the patient included the resection of an abdominal para-aortic PGL at 11 years of age and a Pheo at 19 years of age. At that time, the patient was living abroad, where he was evaluated and treated, but his medical records were not available after request at the time of his referral to our center. During his childhood, he was initially evaluated because he had clinical symptoms of intermittent claudication, chest pain associated with exertion, severe hypertension, tachycardia, and excessive sweating. After a PGL was diagnosed, he was subject to a complete tumor resection and remained asymptomatic for 8 years, when the routine follow-up examination showed a marked elevation of catecholamines. A new imaging study was made, which revealed a right adrenal gland pheochromocytoma, which was also surgically removed, becoming once again asymptomatic for several years, after which he lost follow-up in that facility. During that time, he moved to Mexico, where he continued having an apparently normal life without any further medical evaluation for the next 14 years, up until the event of the head trauma.
During our initial evaluation, the patient was found to have right moderate hearing loss, right proptosis, optic nerve atrophy with right temporal hemianopsia, and face hyperesthesia in the area corresponding to the V2 and V3 branches of the trigeminal nerve. Blood pressure was reported to be intermittently high, between 130/90 and 140/100 mmHg. No weight changes, fatigue, nausea, hair loss, or other hormone deficiency-related symptoms were referred by the patient after purposely inquiring. The MRI was initially reported to be compatible with a meningioma vs. a hemangiopericytoma; however, the medical history called for additional diagnostic workup (). Laboratory results showed normal metanephrines 208 μg (normal range 86–320 μg/24 H) and elevated normetanephrines 10,828 μg (normal range 120–400 μg/24 H; 27 times the upper limit of normal); the rest of the hormonal tests were normal. The diagnosis of a functioning PGL was then established, but the low incidence of functioning HNPG as well as the apparently aggressive behavior lead us to request a positron-emission tomography-computed tomography (PET-CT) with 68Ga-DOTATATE, which showed an increased expression of somatostatin receptors in the lesion (). The single-photon emission computed tomography with metaiodobenzylguanidine (SPECT-CT 131-MIBG) was also positive in the skull base lesion, related to an abnormal synthesis of catecholamines ().
The patient was started on medical preoperative management with selective alpha-blockade (Prazosin) in a 3 mg three times a day dose and nifedipine 30 mg daily for two weeks, with the systolic blood pressure being lowered to 130/80 mmHg, when he was started on beta-blockers (Atenolol) 50 mg twice a day for an additional six weeks. In order to reduce excessive bleeding risk during open surgery, the decision was made to perform an endovascular preoperative embolization of the right maxillary artery using polyvinyl alcohol microspheres. Despite adequate preoperative medical treatment, the patient suffered from alternating episodes of bradycardia and supraventricular tachycardia, as well as hypertensive crisis during the procedure, when only 40% of the tumor been successfully embolized. The endovascular procedure was stopped, and an emergency MRI was performed. The image showed signs of increased intracranial pressure without any areas of hemorrhage or ischemia; however, since the patient had an altered mental status and bilateral pupillary dilation, a decompressive hemicraniectomy was emergently performed. After a successful intervention, he was transferred to the intensive care unit (ICU) for recovery.
After 20 days from the initial procedure, the patient was scheduled for a second embolization procedure and tumor resection surgery. After the second embolization, 95% of the tumor was successfully embolized without any complications, and 48 hours, later the patient underwent surgery achieving a subtotal tumor resection (). He had an excellent postoperative recovery period with normalization of previously elevated catecholamines and improvement of his visual field, and was discharged home without further complications. He has now been followed-up for an additional 2 years. His blood pressure is normal without any medication, his urinary and serum catecholamines are normal, and the tumor remnant has not increased in follow-up MRI scans ().
The genetic testing showed a heterozygous SDHB gene mutation, reference sequence; NM_003000.2: c.136C>T, NP_002991.2: p.Arg46 (clinvar: RCV000505277.1), which has been reported to be a pathogenic variant.


An 86-year-old male, with prior coronary artery bypass grafting and severe peripheral arterial disease (PAD), presented with New York Heart Association class III exertional dyspnea. Echocardiography revealed severe calcific AS with normal left ventricular systolic function. Cardiac computed tomography (CT) showed adequate left (14 mm) and right (21 mm) coronary heights. Previous coronary angiography had demonstrated non-occlusive triple-vessel coronary artery disease with a functional left internal mammary artery graft to the left anterior descending artery and a dominant native left circumflex artery. A Symetis Acurate ‘Large’ (Boston Scientific,
Boston, MA, USA) TAVI prosthesis was deployed transapically in the hybrid operating theatre. Immediately thereafter, the patient became hypotensive and developed posterolateral ST-segment elevation. Emergent coronary angiography showed a critical, calcific filling defect at the junction of the distal end of the short left mainstem and proximal-mid circumflex arteries (, Panel A). Through the radial access, a 6-French Cordis XB 3.5 guide catheter (Cardinal Health, Vaughan, ON, Canada) was used to cannulate the left main coronary artery. Heparin was administered to maintain ACT > 250 seconds and clopidogrel 600mg was administered. The lesion resisted extensive attempts at balloon delivery. A 0.009” RotaWire Floppy guidewire was inserted to facilitate the 1.5 mm Rotablator Rotational Atherectomy System (Boston Scientific Corporation, Boston, MA, USA) burr passage at 180,000 rpm. Three passes were undertaken into the mid-circumflex artery (, Panel B). A 2.5 x 20 mm non-compliant balloon was subsequently inserted unimpeded in the left main coronary artery (post-RA and balloon dilatation-figure 1, panel C) extending into the proximal circumflex segment over a Pilot 50 guidewire (Abbott Vascular, Abbott Park, IL, USA). A 3.25 x 38 mm Xience Xpedition (Abbott Vascular, Abbott Park, IL, USA) drug-eluting stent was successfully deployed extending from the ostium of the left main coronary artery into the proximal-mid circumflex lesions and post-dilated with a 3.5 x 20 mm non-compliant balloon at high pressures with a good angiographic result (, Panel D) and resolution of electrocardiographic changes along with marked hemodynamic improvement. The patient subsequently recovered uneventfully in the intensive care unit and was extubated the following day and transferred to the ward uneventfully. Peak creatine kinase and high-sensitivity troponin T levels were 961 U/l and 1921 ng/l respectively.


A 32-year-old female reported to the Department of Operative Dentistry and Endodontics, Banaras Hindu University, Varanasi, India, with a chief complaint of pain in the upper left back tooth, which she reported was increasing while biting and taking cold or hot beverages. The patient's medical history was noncontributory. On clinical examination, there was deep proximal caries with the maxillary left second molar; thus, intraoral periapical radiograph (IOPA) of tooth 27 was advised. The tooth was nonmobile, and periodontal probing was also within the physiological limit. Radiographic examination revealed the carious exposure of tooth 27, and thus, root canal treatment of the teeth was advised. Radiographic examination also revealed some variation in root canal anatomy with tooth 27, and having a single root and single canal () was suspected.
The tooth was anesthetized with 1.8 mL (30 mg) 2% lignocaine containing 1 : 200,000 epinephrines (Xylocaine; AstraZeneca Pharma Ind Ltd., Bangalore, India.) followed by rubber dam isolation. Access opening with the aid of magnifying loupes (zumax 3.5X) of tooth 27 revealed a large single orifice and one single wide root buccolingually extending toward the root apex. Working length (WL) was determined with an apex locator (CanalPro Apex Locator, Coltene) and was confirmed with k-file (). WL IOPA also confirmed the single-rooted maxillary second molar with a single canal. Root canal shaping was done with k-files using the conventional method of canal preparation and was irrigated with sodium hypochlorite (Sigma Aldrich, Germany). EDTA was used to remove the inorganic component of the root canal system, and a smear layer formed with filing the dentin. Saline was used as intermittent irrigation. Due to the wide nature of the canal, more attention was paid on chemical disinfection.
After canal preparation was done, IOPA was taken to confirm the fit of the master gutta percha cone. A lateral condensation technique of obturation with Apexit Plus as a sealer was used.
Post obturation, IOPA was taken to examine filling of the root canal system (). Follow-up IOPA two weeks after () was taken, and final restoration with amalgam was done, and the patient was referred to the Department of Prosthodontics for further treatment.


A 75-year-old hypertensive man presented with an elevated PSA of 9 ng/dL and a normal prostate on digital rectal examination. Following a multi-parametric MRI (mp-MRI) of the prostate, a transrectal ultrasound-guided biopsy confirmed a Gleason 6 prostate cancer disease in both lobes, consistent with a cT1c disease. Metastatic work-up was negative. Patient elected to undergo an open radical retropubic prostatectomy. No intraoperative complications were encountered.
Post-operatively, the drainage from the Foley catheter was not as expected, and intravenous fluid was initially increased. The patient was clinically doing well, until we gradually noticed increase in urine leak around the indwelling catheter, which we initially thought secondary to bladder spasms. Later, a soaked wound dressing, having a urine-like odor, was noted. Repeated blood tests revealed leukocytosis of 23,000/μL, with 86% left shift, and an elevated serum creatinine of 2.14 mg/dL, from a 1.14 mg/dL baseline. Urine leak was suspected. Creatinine level taken from the wound drainage was 48.16 mg/dL, which confirmed the diagnosis of a urine leak. Although a malfunctioned indwelling catheter was suspected, irrigation through the catheter confirmed its patency. Broad-spectrum antibiotics were started.
A scout KUB image showed the catheter tip at a more cephalad position than the usual position at the bladder neck (). A plain CT scan was done confirming the tip of the indwelling catheter within a diverticular pouch of the bladder (A&B). Retrograde cystography revealed the filling of two anterior diverticular pouches, giving the shape of a “Mickey-Mouse” like bladder (). Leakage at the urethro-vesical anastomosis site was noted, with subsequent seepage of contrast to the subcutaneous tissue and thus from the abdominal wall wound ().
The explanation is that the urine, coming from both ureteral orifices, was not captured by the Foley catheter, which was stuck in a bladder tic, forcing the urine to leak through the urethra-vesicle anastomosis, and from there to the abdominal wound. The balloon was deflated, and the Foley catheter was repositioned within the bladder, under fluoroscopy, and the balloon was again inflated. (). The leak from the surgical wound, and through the urethra, completely stopped.
Follow-up blood tests showed a gradual decline in leucocyte count to 9800/μL and creatinine level to 1.24 mg/dL. The patient was discharged home, four days later. The final pathology was upgraded to Gleason 7(3 + 4) prostate cancer, with negative surgical margins, consistent with pT2cNxMx disease. No lymph nodes dissection was performed.
The indwelling catheter was kept for 2 weeks, and removed after resolution of leak on retrograde cystography. Six months later, the patient was voiding adequately, with no urinary incontinence, and complete wound healing.


A 12-year-old boy with autism spectrum disorder presented at a surveillance consult
with bilateral breast growth, which was noticed on the last few months. He did not
mention other symptoms, such as headache, vomiting, and polyuria polydipsia. Growth
was unremarkable, with height on the 75th centile and weight on the
75-90th centile. His mother denied he had been exposed to
medications, herbal medicine drugs, or estrogen-containing creams.
The family history showed that his parents were non-consanguineous. He had a
first-degree cousin from his father’s family with gynecomastia since adolescence and
other first-degree cousin from his father’s family with a recent diagnosis of
myotonic dystrophy type 1. His father had cataracts diagnosed at 49 years-old and a
history of puberty delay. The cousin’s diagnosis led to family genetic study, and
his father and older brother were waiting for their results. His mother was healthy
().
On physical examination, he had an eunuchoid phenotype and bilateral gynecomastia
(). Testicular volume was 2 mL
bilaterally, with no palpable nodules, penis length was 5 cm (-2 standard deviation
according to age), and there were sparse long, slightly pigmented curled pubic hairs
at the base of his penis (external genitalia at Tanner stage 1 and pubic hair at
Tanner stage 2). There was no tachycardia or tremor and nonpalpable thyroid. Body
mass index was 18.8 kg/m2 (50th to 75th centile).
There were no other relevant findings. Neurologic examination was regular, without
demonstrable myotonia.
Analytical evaluation showed total testosterone=0.13 ng/mL (reference value=0.24±0.01
for male and Tanner stage 1), estradiol=49 pg/mL (reference value=4.6±5.8),
estradiol/testosterone ratio=400 (reference value <10), LH=0.19 UI/L, and FSH
1.02=UI/L, prolactin=8.6 ng/mL (reference value=2.6-13.1), b-hCG=0.3 mUI/mL
(reference value=0-3), TSH=2.33 uUI/mL (reference value=2.0±1.8), and free
thyroxine=13 pmol/L (reference value=16.6±3.6). Complete blood count, kidney
function, liver profile, and muscle enzyme levels were normal.
The presence of autism spectrum disorder in association with gynecomastia caused the
consideration of genetic diseases. Karyotype was 46, XY normal and molecular genetic
testing of FMR1 gene excluded X-Fragile syndrome. Molecular genetic testing of DMPK
gene confirmed the diagnosis of myotonic dystrophy type 1. His father and brother
were also diagnosed with the same condition.
Pubertal development was observed, and gynecomastia remained stable during the
follow-up. On the last consult, at 14 years-old, he presented bilateral gynecomastia
classified as Tanner stage 3, testicular volume of 8 mL on the left, and 6 mL on the
right and pubic hair at Tanner stage 4. Analytical evaluation showed: total
testosterone of 1.82 ng/mL (reference value=0.68±0.02 for male and Tanner stage 2),
estradiol of 15 pg/mL (reference value=7.3±3.7), LH=3.7 UI/L, and FSH=6.9 UI/L.
Electromyography was regular.


We report the case of a 43 years old female patient with gross hematuria and renal colic who was evaluated by a community urologist. An abdominal non-contrast CT showed small kidney stones without obstruction and a left 14mm renal mass. She underwent abdominal magnetic resonance imaging (MRI), which revealed two right hyper-intense masses (9×7mm and 6×5mm) and one left mass (16×9mm), which was associated with one unspecific left pulmonary node ( and ). These findings were evaluated at the uro-oncology clinic in March 2013. Initially, surgery was not recommended considering the young age of the patient and the small size of the tumors (less than 3cm). Furthermore, since this was a case of bilateral renal cell carcinoma (RCC), preserving renal function was important for future treatments. An active surveillance protocol with strict follow-up instructions was established according to the recommendations set by the National Cancer Institute. In September 2013, the MRI revealed that the left mass had grown to a volume of 21x15mm, but other tumors did not grow according to the imaging results.
A genetic test was performed in June 2013. This test specifically genotyped single nucleotide polymorphisms (SNPs) that were relevant to: (a) pharmaceutical drug response (b) genetic diseases and (c) complex diseases. In the latter group, colorectal, lung and breast cancer were included. Results from this genotyping test are presented in .
In January 2014, we asked for a genetic sequence specific for renal cancer. We carried out a very extensive genomic sequencing study to identify polymorphisms associated with renal cancer and Birt-Hogg-Dubé (BHD) syndrome. This study sequenced a panel of five genes: the VHL gene, which has been associated with von Hippel-Lindau disease (, ), the MET gene, which is associated with papillary carcinoma of kidney cells (, ), genes SDHB and SDHD, which are associated with hereditary paraganglioma-pheochromocytoma (, ), and the FLCN gene, which is associated with BHD syndrome (, ). Predictive studies in silico of variants with unknown significance were performed using Alamut software V.2.11 (Interactive Biosoftware, http://www.interactive-biosoftware.com). Results from this sequencing are shown in .
As shown in , a total of twelve variants were found in the patient. These variants were already reported in the literature. Out of these twelve, four are localized to the coding region of the analyzed genes. However, they are silent mutations since they do not change the sequence of the encoded protein. The remaining eight mutations were intron-located variants. Six of the eight were deep intronic variants, which are generally considered innocuous. The other two (rs8065832 y rs2018781) are located near splicing sites, which makes them clinically relevant but still unknown. These variants were analyzed using an in silico splicing analysis tool to predict whether they cause splicing defects ().
Five different splice site prediction algorithms were used: (a) Splice Site Finder - SSF (http://www.interactive-biosoftware.com), (b) Gene Splicer -GS (http://www.tigr.org/tdb/GeneSplicer/gene_spl.html), (c) Splice site prediction by Neural Network - NNS (http://www.fruitfly.org/seq_tools/splice.html), (d) MaxEntScan–MES (http://genes.mit.edu/burgelab/maxent/Xmaxentscan_scoreseq.html), and (e) Human Splicing Finder - HSF (http://www.umd.be/HSF3/). SSF, MES, GS, and NNS were run simultaneously using the Alamut V.2.11. Default thresholds were used for all the analyses. The results of these in silico analyzes are shown in .
The in silico analyses () predicted that the variant rs2018781 most likely has probably no impact on splicing. However, for the variant rs8065832, two of the algorithms predicted a higher score than the natural splicing site score (> 10%). According to the criteria by Thery et al., this result indicates that this variant may generate a novel splice site (). In addition, variant rs8065832, was referenced in the Clinvar database (https://preview.ncbi.nlm.nih.gov/clinvar/) and Leiden Open Variation Database-LOVD (http://www.lovd.nl/3.0/home); In Clinvar, six reports were found for this variant, all of which categorize it as a benign mutation. However, LOVD yielded nine reports, which all categorized it as having an unknown effect.
The follow-up abdominal MRI scans performed in April 2014 and November 2014 showed no significant changes compared to the previous scans. When the February 2015 MRI scan showed a tumor greater than 3cm, she underwent three right partial nephrectomies. In February 2015, the pathology report revealed that this tumor was multiple (#3) clear cell carcinoma, Fuhrman grade 2, one of them with positive margins (). In August 2015, she underwent two partial nephrectomies on the left kidney, which pathology reported as being two papillary-type renal carcinomas with negative margins (). The patient was classified as having right clear cell carcinoma (T1aN0M0) and left papillary-type renal carcinoma (T1aN0M0). In June 2017, the new MRI revealed a hypervascular solid lesion of 10mm in the posterior middle-third portion of the left kidney, which suggests the formation of a new tumor under actual surveillance.


A 60-year-old male with a history of non-small-cell lung cancer treated with chemotherapy and chest radiation over four years presented in an outpatient clinic setting with three weeks of gait ataxia and significant upper thoracic back pain. Neurological examination demonstrated subtle weakness against resistance in the lower extremities, but ataxia when ambulating. He had diminished sensation to light touch over the C8 dermatome of the left arm. He demonstrated non-sustained myoclonus in the ankles bilaterally. Sample images from a magnetic resonance image (MRI) of the cervical and thoracic spine are provided in Figure .
The images are notable for spinal cord compression from an epidural tumor arising from the chest wall. The patient was admitted to the hospital, and a computer-aided tomography (CT) scan of the cervical and thoracic spine demonstrated significant osseous involvement of the tumor and destruction on the left side of T1, T2, and T3 (Figure ). Ribs, one through four, on the left, also show significant destruction from the malignancy. Given the patient’s deteriorating but functional neurological examination, surgery was offered to try and preserve his ability to ambulate for as long as possible; however, it was felt that a combined anterior and posterior decompression procedure might be greater than the patient could tolerate. The kyphotic angle of the cervical spine in relation to the thoracic spine was concerning. The patient’s pedicles measured less than 4mm in the cervical vertebra, making him a less than ideal candidate for pedicle screws at these levels. Given his malignancy and kyphotic deformity, we felt he was at high risk for failure at the top of whatever fusion construct we would create given the difficulty of pedicle screws with a small pedicle diameter.
The patient was taken to the operative suite and placed in a prone position in a Mayfield pinion head holder. The neck was slightly flexed but left essentially neutral. A midline incision was carried out from the spinous process of C4 to T6. The laminas of C5, C6, C7, T1, T2, T3, T4, and T5 were exposed. The tumor was encountered on the left side from C7 to T3. The facet joints and lateral masses were exposed laterally at C5, C6, and C7. Lateral mass screws were placed utilizing the Magerl technique at C5, C6, and C7 bilaterally. At this time O-arm navigation was brought in and utilized to place 4.5mm pedicle screws into the right T1 pedicle, right T3 pedicle, and bilateral T4 and T5 pedicles. Once the screws were placed, a decompression of the spinal cord was undertaken by removing the T1, T2, T3, and bottom portion of C7 laminae. The ligament between C4-5 and C5-6 was removed to make room for sub-laminar Atlas cables, which were passed bilaterally. A tapering rod 3.5mm to 5.5mm in diameter was bent and placed to connect the screws at each level. Then a trans-connector was placed atop the C5 lateral mass screws. The sub-laminar cables were then wrapped around the connector as an extra guard against pull out of the lateral mass screws, which would be under greater load in comparison to their thoracic counterparts, especially in the context of the patient’s kyphotic deformity. The cables were then tightened down to 35 pounds of torque. A picture of the final construct can be seen in Figure .
Two 10 french round drains were left in the epidural space for the first two postoperative days to reduce the risk of an epidural hematoma. Intra-operative neurophysiological monitoring of upper extremity electromyograms (EMGs), upper and lower extremity somatosensory evoked potentials and motor evoked potentials were utilized throughout the case and demonstrated no changes. Samples were taken of the tumor, compared against previous biopsies and were consistent with a lung carcinoma that was positive for CK7, CK5/6 immunohistochemical stains and negative for TTF-1 and CK20 immunohistochemical stains.
Postoperatively the patient was placed in a cervical collar with a thoracic extension. He demonstrated continued ataxia with subtle weakness in his lower extremities against resistance. He continued to have numbness in his 4th and 5th digits of the left hand without a change in his pre-operative sensory loss pattern. After just under a week in the hospital, he was deemed a candidate for inpatient rehabilitation and was discharged to such a facility for one month’s duration.
After discharge from rehab, the patient had two falls within two weeks. One of which was not in his brace and occurred when his wheeled walker became caught on a piece of furniture causing him to fall onto his right shoulder. This led him back to the emergency room where on neurological examination, he demonstrated bilateral weakness against resistance in hip flexion, knee extension, and ankle plantar and dorsiflexion. He continued to demonstrate non-sustained clonus in both ankles. Progression of the tumor had furthered cord compression at the T1, T2, and T3 levels. CT of the cervical and thoracic spine did not demonstrate any fracture or failure of the hardware. His CT scan is presented in Figure . The patient, with his rapidly deteriorating neurological examination, decided to pursue hospice rather than further medical, surgical, or radiation therapy options.


A 53-year-old man presented to our hospital with cough and a mediastinal tumor, and based on pleural biopsy, he was diagnosed with a malignant pleural mesothelioma, clinical stage III (T2 N1 M0). He received two courses of chemotherapy with cisplatin and pemetrexed, after which we performed right-sided extrapleural pneumonectomy with pericardial resection, and pericardial and diaphragmatic reconstruction with expanded polytetrafluoroethylene (ePTFE) sheets using interrupted non-absorbable monofilament sutures.
He was transferred to the postoperative care unit and no significant symptoms and hemodynamic impairment were observed at that time. He complained of feeling unwell 18 h postoperatively and developed hypotension (89/57 mmHg with noradrenaline 0.015 μg/kg/min). Routine chest radiography revealed unexpected cardiac herniation into the right-sided thoracic cavity (). The patient was immediately transferred to the operating room and underwent emergency thoracotomy. Cardiac herniation had occurred secondary to tearing of sutures on the posterior aspect of the ePTFE sheet. We placed the heart back within the pericardium and repaired the tears by fixing another ePTFE sheet to close the defect between the posterior pericardium and the previously placed ePTFE sheet using horizontal mattress and continuous sutures (). The postoperative course was uneventful, and he was discharged 43 days after second operation. He died of tumor progression 2 years after the second operation. However, Cardiac herniation did not recur postoperatively.


The patient was a 68-year-old man with a past medical history of hypertension and coronary heart disease. The American Society of Anesthesiologists risk score was II and his body mass index was 28.1 kg/m2. The endoscopy examination found a 2-cm lesion in the gastric antrum and 3-cm lesion in the middle rectum. Pathological biopsy showed that both lesions were adenocarcinoma. No distant metastasis was found on computed tomography scan. No abnormal result was found in his laboratory examination. Preoperative staging of gastric cancer was cT2N0M0 (America Joint Committee on Cancer [AJCC] stage I) and rectal cancer was cT2N0M0 (AJCC stage I). A multidisciplinary treatment team assessed the patient’s general condition and agreed with preforming NOSES for simultaneous resection of the rectal and gastric cancer.


Before commencing the study, written consent was obtained from the patient for publication of clinical findings, preoperative, and postoperative photos.
A 66-year-old woman was admitted with back and abdominal pain, inability to sit straight, abdominal discomfort, and numbness in the lower extremities after prolonged sitting. Her first complaints, face and upper extremity weakness, started when she was 18 years old. She was diagnosed with FSHD clinically at the age of 21 when her lower extremity weakness started. Her lumbar lordosis increased gradually. She became wheelchair dependent at the age of 44. She suffered right femoral neck fracture after a fall injury at 47, which limited her mobility and daily activities further. Her hip fracture was not operated. She has had abdominal complaints and lower extremity numbness for the last 5 years. She was not diagnosed with any specific gastrointestinal (GI) disorders.
She was operated due to left breast cancer at the age of 45, used tamoxifen for 5 years after the surgery. Difficulties with breathing started at the age of 60 and she has started using bilevel positive airway pressure device (BIPAP) since the age of 63. In her family, her maternal grandmother, mother, sister, and single daughter were diagnosed with FSHD as well. She was working as a columnist for a national newspaper for the last 8 years. Her daily practice was particularly affected due to discomfort with prolonged sitting.
The patient was unable to walk or stand. She was able to sit without support with hypokyphosis and extreme hyperlordosis (Fig. ). Her spinal deformities were noted as flexible with remaining mild hyperlordosis in supine position. Facial muscle atrophy was consistent with FSHD. Her muscle strength using Medical Research Council (MRC) Scale were measured as: neck extension 3/5, neck flexion 4/5, deltoid bilateral 0/5, elbow flexion bilateral 3/5, elbow extension bilateral 0/5, wrist extension bilateral 0/5, wrist flexion bilateral 3/5, hip and knee flexors and extensors bilateral 0/5, ankle dorsiflexion 0/5, ankle plantarflexion 3/5. Beevor's sign was positive. No scapular winging was observed. Four centimeters of lower extremity shortening was measured on her right side.
FSHD evaluation scale[ was calculated as: I – facial weakness 2 points, II – scapular girdle involvement 3 points, III – upper limbs involvement 2 points, IV – legs involvement 2 points, V – pelvic girdle involvement 5 points, VI – abdominal muscle involvement 1 point, with the total point of 15.
Quality of life before and after surgery was documented using Individualized Neuromuscular Quality of Life Questionnaire (INQoL) Version 2.0.[ Preoperative INQoL scores in the symptoms domain were calculated as: I – weakness 100%, II – pain 94.74 points, III – fatigue 94.74 points, IV – muscle locking 0 points, V – droopy eyelids 47.37 points, VI – double vision 0 points, VII – swallowing difficulties 63.16 points. Life domain scores were calculated as: I – activities 76.85 points, II – independence 97.22 points, III – social relationships 44.44 points, IV – emotions 19.44 points, V – body image 88.88 points. Her expected treatment score was 83.33 and her quality of life score was 55.55 (Table ).
Lateral sitting, supine antero-posterior (AP) and lateral X-rays, computerized tomography (CT), and magnetic resonance imaging (MRI) of the whole spine were obtained. Lateral spinal X-rays in sitting position revealed hypokyphosis and extreme hyperlordosis which was flexible as shown in Figure A and B. Paraspinal muscle atrophy was observed in MRI (Fig. C). No myelopathy or radiculopathy was noted on any level. Electromyography (EMG) showed non-specific myopathic changes in both upper and lower extremities and no findings associated with radiculopathy. EMG during sitting was not performed.
The patient was prepped and draped in prone position under general anesthesia. T2–S1 posterior midline incision was used. Severe paraspinal muscle atrophy was noted (Fig. C). Facet joints of all levels between T3 and L5 were bilaterally exposed and joints were removed. Polyaxial pedicle screws (Medtronic, Minneapolis) were introduced to levels from T2 to S1 (17 bilateral levels). Cement was used in T4–5–6, L3–4–5 and iliac screws due to low bone quality. Three rods were used for fixation (Fig. ). Autograft from spinous processes and 120 cm3 spongious allograft were used to facilitate fusion. Three units of packed red blood cells and 2 units of fresh frozen plasma were administered during the operation.
The patient was extubated 3 hours after surgery in the intensive care unit. Two units of packed red blood cells and 1 unit of fresh frozen plasma were administered postoperatively on the day of the surgery. Noninvasive respiratory support was utilized following extubation on the day of surgery. Sitting with support was permitted on the day after surgery and without support 1 week after surgery. No problem was observed with wound healing. A soft neck collar was used to support neck extension. The patient was discharged on the 16th day postoperatively. Follow-ups were performed at 3 and 6 months and 1, 2, and 3 years postoperatively. Spinal fusion was confirmed on all levels with CT in the 3rd year. She returned to her professional daily routine 1 month after surgery and preoperative complaints regarding sitting balance, gastrointestinal discomfort, and radicular symptoms recovered completely (Fig. ).
Postoperative INQoL questionnaire was administered on 3rd year. Postoperative INQoL scores in the symptoms domain were calculated as: I – weakness 94.74 points, II – pain 0 points, III – fatigue 52.63 points, IV – muscle locking 0 points, V – droopy eyelids 0 points, VI – double vision 0 points, VII – swallowing difficulties 0 points. Life domain scores were calculated as: I – activities 57.41 points, II – independence 100 points, III – social relationships 0 points, IV – emotions 0 points, V – body image 61.11 points. Her perceived treatment score was 100 and her quality of life score was 40.


An asymptomatic 45-year-old woman was referred to our institution with an exercise testing suggestive for myocardial ischemia (ST segment depression), according to AHA guidelines.[ She was not under pharmacological treatment. Echocardiography and biochemical parameters were within the normal limits. Afterwards, a CTCA was planned to rule out CAD. The examination was carried out by a 128-slice computed tomography (Revolution GSI, GE Healthcare) with 0.35 second rotation time, prospective ECG triggering and 40 mm total collimation width. The angiographic scan was preceded by a baseline acquisition for calcium score evaluation. Therefore, 100 mL of high concentration contrast medium (Iomeprol 400 mg I/mL, Iomeron 400, Bracco, Milan, Italy) were injected at 5 mL/s and bolus tracking technique was used to synchronize the start of the acquisition with contrast bolus arrival. Images were reconstructed using the GE advantage workstation 4.6 (GE Healthcare) and Cinematic Rendering Prototype (version 1.0.1, Syngo.VIA Frontier Platform, Siemens Healthineers).
The phase with least residual motion was utilized for further evaluation. Maximum intensity projection (MIP), multiplanar reformations (MPR), 3D volume rendering (VR) and cinematic rendering (CR) were generated (Figs. and ).
The examination showed the absence of any artery arising from the right sinus of Valsalva. The left anterior descending artery (LAD) and the left circumflex artery (LCX) presented regular origin and course with no evidence of CAD (Calcium score = 0). LCX provided a wide obtuse marginal branch, a filiform posterior interventricular artery and a noticeable posterolateral artery running in the inferior atrioventricular groove reaching the crux cordis up to the right atrioventricular sulcus. The LAD provided an acute margin branch and the conus artery while the sinoatrial nodal artery originated from proximal LCX. In light of imaging findings, the surgical intervention was not kept under consideration. Therefore, the patient was kept under pharmacological control by anti-platelets and monitored over time without any surgical intervention. Moreover, she was advised to avoid heavy exercise and to observe a proper nutrition and a healthy lifestyle to prevent the onset of coronary atherosclerosis.


A 19-year-old man developed blurry vision with new headaches in November 2014. He had bilateral papilledema. A MRI brain showed a large right-sided lesion involving the parieto-temporal lobes, hyperintense on T1 and T2-weighted sequences, with significant surrounding vasogenic edema on T2-weighted fluid-attenuated inversion recovery (FLAIR), contrast enhancement post-gadolinium, and a right-to-left midline shift (Fig. a, b). The overall appearance of this lesion looked a bit unusual for a classical GBM. He had a subtotal resection on January 30th, 2015, and was diagnosed by a local pathologist with a “GBM”. He completed 6 weeks of radiation therapy (RT) and temozolomide (TMZ). Four months later, a follow-up MRI showed an increase in the size of the enhancing tumor and, despite the possibility of pseudoprogression, a second surgical resection was performed on June 2nd, 2015 and showed “GBM”. Maintenance TMZ was started and follow-up imaging showed stable disease (Fig. ).
The patient was referred to the Neuro-Oncology clinic at MCC in June 2015. Histology review showed that he had a malignant PXA grade III–IV, rather than a GBM. It had multinucleated giant cells, prominent nucleoli, and eosinophilic granular bodies on 600 × HPF, and a high mitotic index with dysplastic neurons on 200 × HPF (Fig. ). Histological samples were GFAP positive, with necrosis, ATRX retained, had a proliferation rate of 2% by Ki-67, and was positive for BRAF V600E on IHC (Fig. ). Foundation one testing confirmed the BRAF V600E mutation, IDH1 wild-type, and no EGFRviii. Other testing showed that the tumor was negative for 1p/19q co-deletion and was O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated.
After an initial 17 months of stable disease, on his MRI, there was a small increase in the size of his tumor (Fig. ). Accordingly, combination therapy with BRAF kinase and MEK inhibitors, Dabrafenib 150 mg PO BID and Trametinib 2 mg PO OD, was started on November 2016. As soon as 2 months after starting treatment, there was radiographic evidence of disease regression, though it did not meet the criteria for a Partial Response because of its small size. The patient was continued on this treatment regimen for 10 months and further serial imaging showed stable disease.
After 8 months of treatment, in July 2017, treatment was held to give the patient a “drug holiday,” but, 2 months later, his MRI showed disease progression. Dabrafenib and Trametinib were re-started, and he remained stable until January 2018 when he had disease progression with BRAF MEKi. Since resistance to BRAF inhibition can be overcome by autophagy inhibition [–], we added the autophagy inhibitor chloroquine (500 mg PO daily) to his BRAF MEKi therapy. Each tablet of chloroquine contains 500 mg of chloroquine phosphate USP and the equivalent to 300 mg chloroquine base, which is the standard, maximal safe dose that is FDA-approved for adults [].
Based on the Response Assessment in Neuro-Oncology (RANO) criteria, the lesion size was measured, the sum of the perpendicular diameters (SPD) calculated and plotted (Fig. ). The tumor decreased by more than 25% after BRAF MEKi was started (Fig. a) but unfortunately increased after a drug holiday (Fig. c), and continued to grow despite re-starting therapy with BRAF MEKi (Fig. d), at which point the autophagy inhibitor chloroquine was added halting the rate of tumor progression and even causing a slight decrease in the lesion size (Fig. e).
There are no reported potential interactions between chloroquine and Dabrafenib and/or Trametinib. Chloroquine’s adverse effects can be multisystemic affecting the eyes (e.g., retinopathy, visual disturbances), hearing, liver, gastrointestinal system (e.g., nausea, vomiting, diarrhea, abdominal cramps), muscles (e.g., myopathy), skin (e.g., erythema multiforme, Stevens–Johnson syndrome), cardiac (e.g., prolonged QT interval), hematologic system (e.g., pancytopenia), and nervous system (e.g., seizures, extrapyramidal signs) []. Given these side effects, we had taken precautionary measures with close monitoring every 1–2 months since started triple therapy, checking complete blood cells counts, complete metabolic panels, electrocardiogram, and echocardiograms. Overall, our patient tolerated the triple therapy well for 17 months until recently, when he complained of mild nausea, diarrhea, and a skin rash. The decision was made to hold chloroquine, while continuing Dabrafenib and Trametinib, with plans to re-assess him in 2 months.
In summary, radiographically, he has had Stable Disease with BRAF MEKi for 14 months, and later with the addition of chloroquine for a total of > 2.5 years of treatment (triple therapy for 17 months), without major side effects from the treatment, until recently for which he is receiving a drug holiday from chloroquine.


A 9 years old girl was admitted to a general pediatrics department and she showed symptoms of cough, vomit, abdominal pain, and twitching. The patient rapidly developed severe hypoxemia (SpO2: 45–70%), dyspnea, and heart failure on the next day. She was then transferred to the ICU (Intensive care unit), initial echocardiography at ICU showed enlargement of the left atrium and left ventricle, the magnitudes of ventricular wall motion was lower with an estimated 36% ejection fraction. A series of rescue treatment were implemented such as Continuous renal replacement therapy, large doses of dexamethasone impact therapy, and antibiotics. Most surprisingly is that the initial Chest CT (Computerized tomography) scan revealed extensive calcification of both ventricular walls and chordate on the 14th day (Fig. a.), which was confirmed by Cardiac Revolution CT scan subsequently (Fig. b). As her condition was improving, the follow-up echocardiography on the 16th day demonstrated that the ejection fraction of the left ventricular had recovered to 50%. A series of diagnosis was established including multiple organ failure (heart, lung, liver, and kidney), septic cardiomyopathy, systemic inflammatory response syndrome, pulmonary hemorrhage, viral encephalitis, myocardial calcification, bacterial pneumonia, electrolyte disorder (hyperkalemia, hyponatremia, hypocalcemia), metabolic acidosis, and disseminated intravascular coagulation.
Compared to treatments in other case of myocardial calcification, there were negligible difference in standard treatments that were carried out in this case study. However, it is summarized that the favorable outcome in the patient was mainly attributed to the series of rescue treatments that were carried out when the MODS (Multiple organ dysfunction syndrome) appeared, the advantages and disadvantages for all the treatments that were implemented to protect the organs were took in account. During the intensive care unit admission, every vital signs were recorded every 1 h and the dose of antibiotics were calculated according to the weight of the child. The dose of antibiotics were used with half a dose of norepinephrine which was only used only one time. The dose of norepinephrine was given by the lowest amount which is 12 mg because when the patient is in hypotension shock, the norepinephrine can help avoid catecholamine-ranted ischemia. When considering that the current occurrence of MODS may be related to the storm of inflammatory factors, methylprednisolone pulse therapy (500 mg QD) was used. The dose was reduced and maintained after 3 days, and stopped when the vital signs were normal and stable.
Furthermore, there was a follow-up on the patient for 18 months and the Magnetic Resonance Imaging images showed no changes in the myocardial calcification, showing that the patients didn’t have further extensive myocardial calcification. The cardiac function and the wall motion of the patient had also completely recovered in the 18 months follow-up. The follow-up echocardiography showed that the patient’s condition and cardiac function were completely normal.


A 19-year-old African-American female presented to the emergency department for evaluation of subacute onset of left-sided hemianesthesia that started in the left hand and gradually progressed proximally to the entire left upper and lower extremities, and then the right side of the body over a course of two weeks. The patient reported associated weakness and bifrontal throbbing headache. She also reported decreased bowel and bladder sensation, but no episodes of bowel or bladder incontinence.
On physical examination, the patient had 4/5 strength in the left upper extremity and 5/5 strength in the right upper extremity. She had decreased sensation to light touch on the left side of her body, and a mild decrease in rectal tone.
MRI of brain and spine showed sharply delineated ovoid mass within the spinal cord at the level of C3 that measured approximately 1.7 cm (SI) x 6.4 mm (AP). This lesion had high intensity on T2 and was isointense to the spinal cord on T1, with partial central enhancement. No syringomyelia or surrounding cord edema was identified, but the cord was expanded at the level of the mass (Figure ).
Based on the radiological findings, low-grade astrocytoma, ependymoma, and inflammatory or demyelinating lesion were in the differential diagnosis.
The patient was then started on steroids and cerebrospinal fluid (CSF) was obtained. CSF analysis was positive for oligoclonal bands. This raised the suspicion for a demyelinating lesion, and the patient was treated with combination of high-dose steroid and five plasma exchange sessions.
After completing the treatment inpatient, the patient started to have significant improvement in her left side weakness and numbness. She was cleared by physical and occupational therapy to be discharged home. At two-month follow-up, the patient continued to do well, and the repeat MRI showed mild reduction in the size of the lesion and no contrast enhancement, indicating an inactive inflammatory lesion (Figure ).


A 63-year-old Malaysian man of Chinese ethnicity underwent cardiac bypass surgery in 2013 for triple-vessel disease, which was complicated postoperatively by cardiac arrest resulting in hypoxic coma. He was hospitalized for three months, of which one-and-a-half months was in the intensive care unit. During his recovery, the patient experienced jerks involving the whole body and difficulty walking. There was also significant cognitive impairment. Epileptic seizures occurred during his hospitalization but not after discharge. He was treated with twice-daily clonazepam 0.5 mg, levetiracetam 500 mg, and sodium valproate 200 mg.
He was referred to our center in November 2017 from the rehabilitation physician with a diagnosis of "ataxia" causing gait difficulty as his main problem. On examination, there was an obvious "bouncy gait," requiring close supervision and, frequently, assistance to walk just several feet within the consulting room; gait was very hesitant and wide-based with an obvious tendency to falls. There was positive action myoclonus in the arms when performing the finger-to-nose test, more obvious on the left (mild-to-moderate amplitude) but no significant myoclonus at rest nor with the arms outstretched (and no asterixis). There was no significant stimulus-sensitivity to touch. Eye movements were normal, with mild-to-moderately slurred speech. There were no other features of cerebellar ataxia, Parkinsonism, or dystonia. The Montreal Cognitive Assessment (MoCA) score was 17/30. Brain MRI was normal. Lance-Adams syndrome (LAS) was diagnosed. Acetazolamide 250 mg bid was added, without significant improvement. We have in our patient medical records three video recordings taken, with the patient's written permission, over approximately two years, showing the relative stability of the patient's condition. These are available upon request from the corresponding author.
Due to ongoing gait difficulty and based on emerging reports of perampanel use in myoclonic disorders [], we added perampanel in August 2019. Improvement occurred within the first week on 2 mg/d, with further improvement on 4 mg/d. A home video sent to us by the patient's family showed that his gait was obviously improved. He was able to walk independently, without a walking aid, at home and in a shopping center, with no "bouncy gait" evident. There were no adverse effects, and the benefit has been sustained at least until the time of writing of this report (October 2019).


Our patient was a 74-year-old Chinese man who had undergone left radical nephrectomy 10 years earlier. Postoperative pathological examination revealed clear cell carcinoma. One year later, he returned for laparoscopic cystectomy due to cholelithiasis, and we found a mass in the subcutaneous tissue protruding by about the size of a thumb into the abdomen. We did not resect the protruding mass, and we decided to see our patient on an annual follow-up basis. Nine years later, he came back to see us because he noticed the protruding mass in the subcutaneous tissue had grown larger within the last year. His physical examination revealed two masses, and enhanced computed tomography (CT) showed a 5 × 6-cm mass in the left side of the anterior abdominal wall and a 5 × 6-cm mass in the back of the right waist (Fig. ). Enhanced CT also revealed a hypervascular lesion in the pancreas (Fig. ). The patient’s tumor marker carcinoembryonic agent concentration was 6.0 ng/ml. Malignant tumors were suspected, and resection of the tumors was performed.
In surgery with the patient under general anesthesia, we first placed the patient in prone position to resect the tumor in the back of the right waist. Then, he was placed in supine position to resect the tumor in the left side of the anterior abdominal wall. Both tumors in the front and back were around 5 × 6 cm in size, and clear cell carcinoma was suspected. Later, we performed distal pancreatectomy with spleen preservation because enhanced CT showed a hypervascular lesion of approximately 3 × 3 cm in the pancreas. The size of the resected tumor in the left side of the anterior abdominal wall was 4 × 2.8 cm; the one in the right waist was 4 × 2.5 cm, and the ones from the pancreas were 1.8 × 1.3 cm and 1.9 × 1.5 cm. All resected tumors were of the clear cell type. Histopathological examination revealed they were paired box gene 8-positive (PAX8+), cluster of differentiation 10-positive (CD10+), RCC-positive, creatine kinase-positive (CK+), vimentin-positive, hepatocyte-negative, and thyroid transcription factor 1-negative (TTF-1−) (Fig. ).
After surgery, our patient was seen in regular follow-up. One year later, our patient came back for a routine checkup, and CT showed recurrence in the pancreatic head. On the basis of our patient’s condition, our group offered him a palliative treatment plan, which is tyrosine kinase inhibitor (TKI) therapy. He refused any further treatment. The timeline of our patient’s case is listed in Table .


An 82-year-old man was brought to the hospital after sustaining a mechanical fall at home and was found to have a non-operable left greater trochanter fracture. On abdominal imaging, he was incidentally found to have a 9.2 cm dominant mass at the dome of the liver straddling the left and right hepatic lobes with a 6 mm right lower lobe pulmonary nodule, which was suspicious for metastatic intrahepatic cholangiocarcinoma. A subsequent liver biopsy confirmed moderately differentiated adenocarcinoma. Based on his age and performance status, the patient began treatment with single agent gemcitabine 1000 mg/m2 on days one and eight every three weeks in conjunction with pegfilgrastim.
On the fourth day of his first cycle with gemcitabine, the patient developed a blanchable maculopapular rash on his upper chest, which eventually resolved with loratadine and diphenhydramine. However, the patient became increasingly fatigued after day eight of gemcitabine. Due to these side effects, gemcitabine was dose reduced to 500 mg/m2 every other week. Although his fatigue improved on the days he did not receive chemotherapy, the patient complained of new onset of shortness of breath and a dry cough that persisted into his second treatment cycle. During an office visit, a pulse oximetry measurement registered the patient as breathing 92% on ambient air. A chest X-ray showed bilateral pleural effusions (). Even after initiating furosemide to facilitate diuresis and a short course of corticosteroids, the patient continued to have dyspnea on exertion. The patient, who had no significant history of cardiac or pulmonary disease, underwent a transthoracic echocardiogram, which revealed an estimated pulmonary artery systolic pressure of 35 mmHg assuming a right atrial pressure of 15 mmHg; this finding was consistent with pulmonary hypertension likely secondary to gemcitabine (). Computed tomography (CT) angiogram of the chest was performed to rule out pulmonary thromboembolism (PE), and it was negative. The patient was promptly treated with diuretics and gemcitabine was discontinued given the high suspicion of drug related toxicity causing pulmonary hypertension.
The patient could not tolerate any further treatment with gemcitabine at which point his regimen was changed to fluorouracil and leucovorin. Despite this, he endured worsening symptoms and ultimately opted for hospice care.