A 46-year-old Korean man, a general office worker, was referred to our institution for the evaluation of congenital heart disease with severe pulmonary arterial hypertension (PAH). He was a social drinker and current tobacco smoker. He had a history of type 2 diabetes controlled with orally administered hypoglycemic agents (metformin, linagliptin, and glimepiride). A cardiac defect was suspected when he was young, but he was asymptomatic and his somatic growth was normal. Detailed assessment of his cardiac lesion was conducted when he was 30-years old. Even after the detection of cardiac defects, he missed routine follow-ups because he was asymptomatic. One month prior to admission, he suddenly developed intermittent chest pain at rest that continued for several minutes. At the primary hospital, he was diagnosed as having a congenital heart disease of VSD, tricuspid regurgitation, and severe PAH; he was transferred to our hospital for further evaluation and management. His general condition was quite good and there was no evidence of neurological or cardiovascular disorder except a pansystolic murmur. His vital signs were as follows: blood pressure of 129/79 mmHg, heart rate of 78 beats/minute, respiratory rate of 18 breaths/minute, and body temperature of 36.6 °C. Electrocardiography demonstrated a sinus rhythm with an incomplete right bundle branch block and bi-atrial abnormality, and a chest X-ray showed mild cardiomegaly. The results of laboratory tests were within normal limits: white blood cells of 6600/μL, hemoglobin of 16.1 g/dL, platelets of 212 k/μL, blood urea nitrogen of 12 mg/dL, serum creatinine of 0.93 mg/dL, aspartate aminotransferase of 28 IU/L, and alanine aminotransferase of 26 IU/L.
On TTE, the pulmonary valve was at the center position of the parasternal short axis view (Fig. a), and was opening well and arising from the right-sided ventricle. The aortic valve was on the left anterior side of the pulmonary valve, suggesting ventriculo-arterial discordance (Fig. a). CCT and three-dimensional modeling demonstrated the aorta and pulmonary trunk to be in similar positions to those shown by TTE (Fig. b, c), and demonstrated the parallel arrangement of the great arteries (Fig. b, d). TTE and CCT showed atrioventricular discordance in addition to ventriculo-arterial discordance (Fig. a-c). The left-sided morphologically RV was a systemic ventricle with prominently coarse trabeculation and an apically displaced atrioventricular valve as a tricuspid valve. The other smooth-wall right-sided pulmonic ventricle was morphologically a LV. Three-dimensional modeling of the chamber revealed similar information (Fig. c). The ejection fraction of the left-sided systemic ventricle (RV) was 58%.
A large VSD was also detected by TTE and CCT (Fig. a, b). While the left-sided atrioventricular (tricuspid) valve of the systemic ventricle was free of regurgitation, a moderate amount of regurgitant flow, with a peak velocity of 5.0 m/second, was noticed at the right-sided atrioventricular (mitral) valve (Fig. c, d), which we assumed was the reason why our patient was diagnosed as having tricuspid regurgitation and severe PAH at the primary hospital. However, we also detected pulmonic stenosis, with a maximal velocity of 4.2 m/second (Fig. a, b), even with the normal morphology and opening of the pulmonic valve (Fig. a).
Pressure measurement of each chamber by cardiac catheterization demonstrated almost equalization of both the ventricles; the systolic/diastolic/mean pressure of the LV and RV were 114/12/78 mmHg and 120/13/80 mmHg, respectively. Importantly, while the pressure of the aorta was 117/76/94 mmHg, the pulmonary arterial pressure was 36/17/24 mmHg, suggesting the protection of pulmonary vasculature by the presence of severe pulmonic stenosis. Oxygen saturation at the superior and inferior vena cava was 72.3% and 69.2%, respectively, but there was unexpectedly high oxygen saturation (93.9%) at the LV (pulmonic ventricle) near the VSD. Oxygen saturation at the pulmonary artery returned to 88.0% and the saturation at the aorta was 96.9%.
We thought it necessary to assess the detailed morphological features to explain the anatomic substrates of the pulmonary stenosis and the discrepancy in the oxygen saturation data at the right-sided LV. Detailed morphological analysis of the CCT and three-dimensional modeling and printing data were applied to understand the mitral/tricuspid valves and the VSD (Figs. e, f and e, f; supplementary video is available in Additional file ). The pulmonary trunk was shifted to the left and overrode the ventricular septum to become a double outlet RV relation of the arterial trunks. However, the outflows to the aorta and pulmonary trunk were separated by a prominent outlet septum (Fig. e; supplementary video is available in Additional file ). Because of the prominent outlet septum, the actual interventricular communication was smaller at the lower end of the outlet septum than at the real VSD (Fig. e, f; supplementary video is available in Additional file ). In addition, there was a straddling of the mitral valve, with a chordal attachment of the mitral valve to the outlet septum of the RV near the pulmonary valve (Fig. c). The straddling mitral valve and the outlet septum together formed a severe subvalvular pulmonic stenosis (Fig. c, e, f; supplementary video is available in Additional file ). In addition, the subvalvular structure of the tricuspid valve was connected to the interventricular septum (Fig. d). We interpreted these anomalies to reflect the mitral valve straddling over the posteriorly positioned VSD and hypertrophied outlet septum, which together could explain the functional and anatomical sub-pulmonary stenosis and a small amount of shunt flow through the large VSD. Based on these results, we decided to continue medical management, as well-balanced systemic/pulmonary circulations would be maintained with this particular combination of cardiac lesions.
Fifteen days after discharge, our patient visited our emergency room for chest pain, similar to the pain that occurred a month prior. Electrocardiography demonstrated atrial fibrillation with a rapid ventricular response. After direct current cardioversion, his rhythm was converted to sinus rhythm and his chest pain was relieved. He was subsequently started on aspirin and amiodarone and has been asymptomatic for 3 years.


A 67-year-old woman presented with bilateral NPDR and treated hypertension. BCVA was 20/40–2 OU at the first visit in April 2014. Fundus photos showed multiple MAs, mild dot and blot retinal hemorrhages with some exudates in the right eye (OD) (Fig. a). She was instructed to take 3 capsules of Eyefolate™ daily with food. In October 2015, the BCVA was 20/50 in OD, and 20/30 in the left eye (OS). Reduced MAs and retinal hemorrhages were observed (Fig. b). At that visit, mild diabetic cystoid macular edema (CME) was found in the OCT image (Fig. d). In September 2018, the subject received bilateral intraocular lens (IOL) implantation surgery after which the BCVA improved to 20/30 in OD and 20/25 in OS. The right eye showed fewer hemorrhages and MA (Fig. c) and less CME on OCT examination (Fig. e).


An 82-year-old woman presented with diet-controlled type 2 diabetes and medication controlled hypertension. In June 2014, the BCVA in OD was hand movement (HM) due to an old macular scar and the BCVA in OS was 20/20. Intra-retinal hemorrhages and 2 small MAs were found in the fundus photo OS (Fig. a). She began 3 capsules of Eyefolate™ daily with breakfast. In October 2014, her BCVA remained HM in OD and 20/25 OS, but the hemorrhages resolved and only 1 faint MA was seen in the fundus photography in OS (Fig. b).


An 84-year-old woman presented with a seven-year history of type 2 diabetes and medically controlled hypertension. She had a history of amblyopia OD and a resolved branch retinal vein occlusion (BRVO) in the left eye. In October 2013, the BCVA was 20/150 OD and 20/25 OS. A large MA in the superior temporal region with exudates is seen in the fundus photo OS. She was instructed to take 3 capsules of Eyefolate™ daily. In August 2014, the BCVA was 20/200 OD and BCVA OS was improved to 20/20. Decreased exudation was found in OS fundus photo (Fig. a). In December 2014, the BCVA was 20/200 OD and 20/25 OS. The large exudates had almost completely resolved OS (Fig. b). In January 2016, the BCVA was 20/400 OD and 20/25 OS. The MA was resolved in the OS fundus photo (Fig. c) in 2016.


The fourth case was a 59-year-old man with an 11-year history of type 2 diabetes who had required insulin for the past 8 years. On his first visit in October 2014, the BCVA was 20/20 OU. Multiple small intra-retinal hemorrhages and MAs with exudates superotemporally were found OS as seen in the fundus image (Fig. a). He began 3 capsules of Eyefolate™ daily. In October 2015, the number of retinal hemorrhages and MAs declined OS (Fig. b), then he switched from Eyefolate™ to Ocufolin™. In April 2016, the number of hemorrhages and MAs continued to decline, and the exudates resolved OS (Fig. c).


A 76-year-old nondiabetic man was examined with a 10 year history of medication controlled hypertension and dry age-related macular degeneration (AMD) (drusen) OU. In June 2014, multiple small MAs with exudates and one cotton wool spot was found OD as seen in the fundus photo (Fig. a) inferotemporal to small drusen. The retinopathy was likely initiated by a small BRVO, with hypertension as a continuing co-factor, the BCVA was 20/20 OU. He began to take 3 capsules of Eyefolate™ daily. In December 2014, resolution of the cotton wool spot, exudates, and MAs was found OD (Fig. b). In May 2018, smaller MAs and exudates reappeared in the original locations after he had self-discontinued the Eyefolate™ (Fig. c).


The sixth case was a 56-year-old man with a 15-year history of NPDR OU. He had a remote history of pan-retinal photocoagulation and Avastin injections for the severe proliferative disease. In June 2015, his BCVA OD was 20/30, his BCVA OS was HM. He had bilateral intra-retinal hemorrhages and MAs with old retinal scarring and silver wiring of the vessels. He began taking 3 capsules of Eyefolate™. In July 2015, his BCVA remained at 20/30 OD but improved to 20/400 OS. He switched from Eyefolate™ to Ocufolin™. In May 2016, his BCVA of this patient remained at 20/25 + 1 OD and improved to 20/200 OS. Figures d-f OD shows resolution of intra-retinal hemorrhages and MAs between 12/2015 and 5/2018. Figures a-c OS show resolution of intra-retinal hemorrhages and exudates. MAs improved then remained stable over more than 3 years of follow up from 12/2015 through February 2019.


The seventh case was a 64-year-old man with a 10 year history of medication controlled hypertension and newly diagnosed type 2 diabetes. In August 2018, a diabetic intra-retinal hemorrhage was found OS (Fig. a) and he then began to take Eyefolate™. By December 2018, the intra-retinal hemorrhage was resolved (Fig. b).


The eighth case was a 68-year-old man with NPDR OS. Initially, he was diagnosed with mild NPDR OS (October 2017). The BCVA was 20/20 OU. A MA was apparent in the superonasal quadrant OS in 2017 (Fig. ). He participated in a clinical trial of Ocufolin™ at the Bascom Palmer Eye Institute, University of Miami and was instructed to take Ocufolin™ on December 19, 2017. During the April 2018 office visit, the BCVA remained 20/20 OU and the macular edema had resolved (Fig. ). A dilated fundus examination indicated no visible retinopathy. In January 2019, a dilated fundus documented absence of macular edema and no evidence of background diabetic retinopathy (Fig. ). Detailed inspection of the fundus photos shows two small MAs in the superior nasal periphery of the OS eyes in the fundus photo taken in October 2017 and resolved in the photo taken in January 2019. The retinal blood flow was increased at the six-month study visit (June 11, 2018, Fig. ).


In our first case, a 67-year-old female patient presented with aseptic loosening findings on both knees. The patient was operated on the right knee five years ago and on the left knee four years ago. The operation lasted about 160 minutes. One unit of erythrocyte suspension (ES) replacement was given in response to bleeding of the patient, who did not develop any complications during the operation. Patient-controlled analgesia (PCA) application was performed via an epidural catheter for postoperative pain. An intra-articular transamine application was performed. In the first 24 hours, the patient needed one unit of ES replacement (Figure ).


In our second case, a 65-year-old female patient was admitted to our service due to bilateral aseptic loosening. The patient was operated by simultaneous bilateral total knee arthroplasty six years ago. Regional anesthesia could not be performed due to implants placed in the spondylolisthesis operation 10 years ago. Surgical procedures, which lasted 150 minutes, were repeated as in the first case for the patient undergoing general anesthesia. The patient needed two units of ES replacement. Due to her comorbid diseases and general anesthesia, the patient was taken into the intensive care unit postoperatively and was returned to the ward and mobilized on postoperative Day 2 (Figure ).


Our third case was a 59-year-old female patient who was operated on the right knee six and on the left knee four years ago. The patient had a history of needing intensive care unit support due to pneumonia after primary knee arthroplasty surgeries. It was taken into consideration that each operation poses a separate risk for the patient and bilateral implementation was decided. One unit of ES replacement was given intraoperatively. The operation lasted for 200 minutes, without deterioration in the general condition of the patient who did not need postoperative intensive care (Figure ).


Our fourth case, a 68-year-old female patient was operated by simultaneous bilateral primer total knee arthroplasty 12 years ago. The patient had a two-stage revision knee arthroplasty due to septic relaxation in her right knee six years ago. The patient was admitted to our service due to bilateral aseptic loosening. The operation lasted about 130 minutes. One unit of erythrocyte suspension (ES) replacement was given in response to bleeding in the patient, who did not develop any complications during the operation. PCA application was performed via an epidural catheter for postoperative pain. An intra-articular transamine application was performed. In the first 24 hours, the patient needed two units of ES replacement (Figure ).


A 40-year-old woman was referred to our hospital because of a cystic tumor in the tail of the pancreas found by medical examination. She had no symptoms. Laboratory tests were all within normal limits: carcinoembryonic antigen (CEA) 0.4 ng/mL, carbohydrate antigen (CA)19-9 11 U/mL, duke pancreatic monoclonal antigen type 2 (DUPAN-II) < 25 U/mL, and s-pancreas antigen-1 (Span-1) 6 U/mL. Computed tomography (CT) revealed a 0.7-cm diffuse and non-enhanced cystic tumor in the tail of the pancreas but no septum or nodules in the cyst (Fig. a). Endoscopic ultrasonography (EUS) showed suspicious structure of the septum but no nodules in the cyst (Fig. b). Magnetic resonance imaging (MRI) showed that the tumor had a low-intensity signal on T1-weighted imaging (WI) and high-intensity signal on and T2-WI, which revealed water-like content (Fig. c). All images showed that the connection between the cyst and main pancreatic duct was indistinct. The tumor was diagnosed as a simple cyst at that time. However, 2 years later, the tumor had increased by 2.6 cm to become 3.3 cm in diameter. The tumor was then diagnosed as SCN and considered at that time to be a simple cyst with MCN as the differential diagnosis. Thus, laparoscopic distal pancreatectomy was performed. The operation time was 283 min and the intraoperative blood loss was 137 mL. Severe adhesion near the splenic hilum was considered to have been caused by pancreatitis. Thus, it was decided that the spleen could not be preserved safely, and splenectomy was also performed. The content of the cyst was serous and did not include mucin or yellow fluid (Fig. d). The resected specimen showed that the tumor was a unilocular cyst and had a thin septum (Fig. d). The epithelial cells were lined with a single layer of cuboidal pancreato-biliary cells and did not show signs of malignancy. HE staining showed that the cellular ovarian-like stroma was present beneath the epithelium. No malignant or invasive lesions were found. Immuno-pathologically, the tumor showed nuclear expression of ER and PgR but not inhibin in the stroma cells (Fig. e). The epithelial cells showed no expression of MUC1, 2, 5AC, and 6, which showed that the tumor had ovarian-like stroma but not mucin secretion (Fig. e). The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with pancreato-biliary phenotype and ovarian-like stroma. The patient’s postoperative course was uneventful, and she remains well 12 months postoperatively with no evidence of tumor recurrence.


A cystic tumor was found by medical examination in the pancreas of a woman in her sixties who presented without any symptoms. Laboratory tests were all within normal limits: CEA 1.3 ng/mL, CA19-9 9 U/mL, and DUPAN-II < 25 U/mL. CT showed a 1.5-cm cystic tumor in the tail and body of the pancreas and a septum in the cyst, and the tumor was suspected to be MCN. Observation was selected as the treatment of choice after obtaining informed consent. However, 9 years later, the tumor had grown to 2.4 cm in diameter and there was a clear septum in the cyst. This tumor was not enhanced in all phases (Fig. a). MRI showed low intensity on T1-WI and high intensity on T2-WI, and magnetic resonance cholangiopancreatography (MRCP) did not reveal a connection between the main pancreatic duct and the cystic tumor (Fig. b). EUS showed a thickened cell wall in the cyst (Fig. c). This tumor was diagnosed preoperatively as MCN. Thus, laparoscopic distal pancreatectomy with splenectomy was performed. The operation time was 260 min and intraoperative blood loss was 175 mL. The cyst contained serous fluid (Fig. d). Microscopic examination showed no ovarian-like stroma and the epithelial cells were lined by a single layer of cuboidal pancreato-biliary cells (Fig. d, arrow). Although the stromal cells expressed ER and PgR, no malignant or invasive lesions were found. The epithelial cells showed no expression of MUC1, 2, 5AC, and 6 (Fig. d). The final pathological diagnosis was non-mucinous cystadenoma of the pancreas with pancreato-biliary phenotype and ovarian-like stroma. The patient remains well 15 months postoperatively with no evidence of tumor recurrence.


A 7-month-old castrated male Italian Greyhound, weighing 5.5 kg was presented with vomiting and acute onset of severe dyspnea. According to the owner, the dog had been otherwise healthy without any relevant history. The dog had vomited several hours before attending the veterinary clinic, and subsequently, developed severe dyspnea after vomiting. On initial examination by the referring veterinarian, the dog was tachypneic (50 breaths/min). A large amount of air accumulation was observed in the left pleural space by radiographic evaluations done by the referring veterinarian. Left-sided thoracocentesis was performed with evacuation of 1.5 L of air from the thoracic cavity. After thoracocentesis, the dog was referred to the Veterinary Medical Teaching Hospital as an emergency case.
On physical examination, the dog was alert and responsive with normal mucous membrane color and normal capillary refill time. The dog had a rectal temperature of 38.2 °C, pulse rate of 160 beats/min and a respiratory rate of 60 breaths/min showing labored breathing. The auscultation revealed indistinct heart and lung sounds on the left side of the thorax, but normal auscultation on the right side. Plain thoracic radiographs revealed the accumulation of a large volume of air in the left pleural cavity inducing displacement of diaphragm and mediastinum, and a hyperlucent left cranial lung lobe (Fig. ). After emergency treatment including oxygen supplementation and thoracocentesis, computed tomography (CT) scanning was performed under general anesthesia and mechanical ventilation for further investigation. The CT images revealed the left-sided tension pneumothorax and emphysematous left cranial lung lobe with several bullae (Fig. ). On CT scanning images, the left cranial lung lobe appeared as a single lobe with a single lobar bronchus that was not divided into cranial and caudal parts (Fig. a). Based on these findings, CLE and a ruptured pulmonary bulla were the most likely cause of the tension pneumothorax. After CT examination, a left-sided thoracostomy tube was placed, and continuous suction with a three-bottle system providing 10 to 15 cm negative pressure was applied for 3 days because of the rapid accumulation of air. Since the amount of air in the thoracic cavity did not decrease despite continuous suction, a surgical treatment was decided upon to remove the affected left cranial lung lobe.
The dog was premedicated with cefazolin (20 mg/kg intravenously [IV]), butorphanol (0.2 mg/kg IV), famotidine (0.5 mg/kg IV), and midazolam (3 mg/kg IV). After induction with propofol (4 mg/kg IV), the patient was intubated with an endotracheal tube and maintained with isoflurane (2%) in oxygen. Left fifth intercostal thoracotomy was performed in a routine fashion. The left cranial lung lobe appeared to be emphysematous with several small bullae and a large bulla, which was confirmed as the source of air leakage (Fig. a). A complete lobectomy of the left cranial lung lobe was performed using a thoracoabdominal stapler (DSTseries™ TA 30 mm Stapler, Covidien). The remaining left caudal lung lobe appeared to be collapsed, but its re-inflation was confirmed after positive end pressure ventilation (Fig. b). On inspection of the removed left cranial lung lobe, there was no division into cranial and caudal parts, but a tissue mass that was flat and less than 1 cm in size was attached to the hilum of the left lung lobe and located cranial to the left cranial lung lobe (Fig. c, d). Before closing the thoracotomy site, the thoracic cavity was filled with warm saline to detect any air leakage. A thoracostomy tube was placed and the intercostal thoracotomy was closed with 2-0 polydioxanone sutures around the ribs near the incision. Positive end pressure ventilation was maintained during the slow evacuation of the air from the thoracic cavity via the thoracostomy tube.
The dog recovered smoothly from anesthesia without any complications. Postoperatively, the dog exhibited a normal condition without dyspnea, and air retention was not identified in the thoracic cavity on postoperative radiographs. The radiographs revealed adequate expansion of the collapsed left caudal lung lobe. For postoperative analgesia, a continuous rate infusion of fentanyl (0.004 mg/kg/h) and lidocaine (1.2 mg/kg/h) was administered for 24 h postoperatively, followed by oral carprofen (2.2 mg/kg) and tramadol (4 mg/kg) twice daily for 7 days. The dog was discharged on the fifth postoperative day after removal of the thoracostomy tube. During 16 months of follow-up, the dog stayed well without any respiratory or radiographic abnormalities.
The excised left cranial lung lobe and tissue mass attached to it were histologically examined. The mass was identified as completely atelectatic lung tissue that was suspected to be the cranial part of the left cranial lung lobe (CrLtCr) based on its anatomical location. In the section, most alveoli had collapsed and bronchioles appeared to be somewhat dysplastic with normal columnar type epithelial cell lining. There were also areas of disorganized cartilage plate morphology and excessively smaller airways that may represent tertiary bronchi without adjacent cartilage plates (Fig. a). There was indications of hypertrophy of the medium-sized pulmonary arteries with vascular proliferation (Fig. b). The excised left cranial lung lobe, thought to be the caudal part of the left cranial lung lobe (CauLtCr), based on the anatomical location and shape, was characterized by the presence of emphysematous lung tissue, with marked ectasia of the alveolar lumens and terminal bronchioles and occasional formation of blebs and bulla (Fig. c). The classification of blebs and bullae was made by those location in the lung, that the bleb was found between the lung parenchyma and visceral pleura and the bulla was within the emphysematous parenchyma. Despite blebs is usually considered to be smaller than bullae, the diameters of the bleb and the bulla measured approximately 7 mm and 4 mm, respectively (Fig. d). This specimen also revealed that the cartilaginous plates lining the smaller or medium-sized bronchi appeared to be dysplastic and occasionally underdeveloped. According to the gross and histopathological findings, the excised pulmonary tissues were confirmed to have PH of CrLtCr and CLE of CauLtCr.


In June 2016, a 28-year old male sought health care at People’s Hospital in Anhua County, Hunan Province for testicular swelling and pain. An ultrasound scan was performed and determined to be inconclusive; no treatment was provided. The patient subsequently developed a fever and received outpatient care at a local private clinic. In October 2016, the patient experienced recurrent swelling of the right testicle and again sought hospital care. He was treated for 7 days with Ciprofloxacin and Rifampicin. The patient improved and was discharged without a diagnosis.
In November 2016, a 26-year female, the wife of the 28-year old male patient and X months pregnant, developed a fever without obvious cause. She was diagnosed with acute nephritis at a local hospital, and, based on her complete blood count (CBC), was treated with Penicillin and Ampicillin for 3 days. In December 2016, the female patient sought care for a recurring fever and right thigh and hip pain. She was again diagnosed with acute nephritis and treated with Penicillin and Ampicillin for 15 days. In February 2017, the patient reported additionally unexplained right thigh and buttock pain and improved following analgesic therapy at home for 3 days.
On 5 April, 2017, the patient delivered a male neonate at 34 weeks of gestation through natural labor at People’s Hospital in Anhua County. At birth the neonate weighed 2500 g, with a length of 50 cm, but was in poor health (Apgar = 4) with a temperature of 37.6 °C along with an enlarged liver and spleen. The neonate was initially treated with a six-day course of Penicillin and Ampicillin. The clinical events of this family cluster of brucellosis are shown in Fig. .


A 79-year-old male presented to a district emergency department having been sent in by his GP for review of a left leg ulcer. His history included type 2 diabetes mellitus. In spite of living independently at home, he was noted to have dementia with significant cognitive impairment.
The patient was a vague historian and was unable to give sufficient details regarding the genesis or duration of the wound. He stated the ulcer might have been present for two weeks and had occurred subsequent to a fall. No further information regarding the cause of the ulcer could be elicited. His GP had treated the ulcer unsuccessfully with a one-week course of antibiotics prior to presentation. On examination, the patient was noted to be malnourished and cachectic with significant lower limb oedema. Mini Mental State Examination on review was 12/30. Circumferential ulceration of the left lower leg was noted (). The wound was approximately 2 cm wide and extended through the fascia throughout the wound. There was a large burden of tenacious slough, obscuring the base of the wound. The presence of larval infestation was identified. The wound was dressed, antibiotics were commenced, and the patient was transferred to a tertiary referral hospital for review and management by the vascular surgery and geriatric medicine teams.
The patient was reviewed in the emergency department of the tertiary hospital where the wound was inspected before transfer to the ward. A plain radiograph of the area of concern noted a soft tissue defect with no bony abnormality. On review of the wound by the admitting team, the peculiar morphology of the ulcer was noted. The uniform circumferential nature of the wound resembled that of a ligature type injury. Additional questioning however revealed no further clues to elucidate the causative mechanism. The patient denied any process that could adequately explain the circular nature of the lesion. A management plan of elevation, compression, antibiotics, and a dressing regime with the aim of eventual grafting was commenced.
The wound was debrided on the ward, removing the bulk of the tenacious slough covering the wound bed and revealing a clean wound with the base visible. This cleaning demonstrated a thin, tan coloured structure running transversely through the wound. On closer inspection, this was found to be an elastic band, that was constricting the leg down to the level of the fascia and was clearly the aetiological factor precipitating the wound. This had not been previously visible due to the thick layer of slough enveloping the wound. The band was transected and removed (Figures and ). Further discussion with the patient gave no further insight into how, when, or why the band was placed.


We describe a 15-year old boy who is the second child of healthy and non-consanguineous parents. At the time of pregnancy, his mother was 29 years old and his father was 36 years old. He has two healthy brothers and his family and gestational history are unremarkable. Perinatal attention was performed at 41 weeks of gestation after spontaneous vaginal delivery (birth weight, 3.200 kg; length, 51 cm; occipital-frontal circumference and APGAR, unknown). The parents did not remark upon any complication at birth. He was referred to our institute at 24 months of age due to the presence of developmental delay. Physical examination revealed that his weight was 10.200 kg (Z-3.09) and his height was 80 cm (Z-1.16). His head circumference was 46 cm (Z-2.28), and he exhibited bifrontal narrowing, arched eyebrows, down-slanting palpebral fissures (Fig. a), bilateral retroauricular pits, global muscular hypotonia and normal external male genitalia. Our clinical approach for assessing global neurodevelopmental delay included brain computed tomography and a basic metabolic screening in dried blood sample, both of which were normal at 2 years of age. At 6 years of age, renal ultrasound and column X-ray were requested because of the presence of retroauricular pits, but the findings were within normal limits. Currently, the patient is 15 years old and has a weight of 31.4 kg (Z-4.17), a height of 1.49 m (Z-2.4) and a head circumference of 51.3 cm (Z-2.9). He has a large and smooth philtrum, thick and everted lips, a wide chin, large ears (Fig. b), a high and arched palate (Fig. c), hypertrichosis of the elbows and back (Fig. d and e) and camptodactyly (Fig. f). His pubic development corresponds to Tanner stage II, with delayed genital somatometry (penile length 7 cm, penile volume index 27.75 [Z − 1.86], right testicle 6.91 [Z-3.33], left testicle 6.09 [Z-3.71]). He also exhibits hypotrophy of the extremities, claw toes and decreased distal strength. A bone age assay showed a 2-year delay and hormonal profiling revealed that the values of FSH (0.73 [Ref. 1.0–11 mUI/mL]) and testosterone (85.2 [Ref. 100–1000 ng/dL]) were below the reference ranges, while his LH level (0.85 [Ref. 0.4–7 mUI/mL]) was within the normal range. He has a normal echocardiogram. He achieves self-care, knows numbers from 1 to 20, writes his name and makes sentences of two to three words. In clinical terms, he has a moderate intellectual disability. He is currently homeschooled.


A 49-year-old Jamaican female with insignificant past medical history presented to the Emergency Department of an urban hospital with a chief complaint of progressively worsening shortness of breath of approximately 4 weeks evolution. Physical exam was remarkable for marked jugular venous distension, bilateral basal wet crackles, a distended and globally tender abdomen with positive fluid shift and positive hepatojugular reflex, as well as bilateral +2 lower leg edema. The patient's labs are shown in and were remarkable for anemia, elevated troponin, markedly elevated pro-BNP, transaminases, mildly elevated TSH, and CRP. ECG tracing showed atrial flutter with a ventricular rate of 126 bpm (). Chest X-ray showed a markedly enlarged cardiac silhouette with a water-bottle appearance suspicious for pericardial effusion (), for which an echocardiogram was done on hospital day 1, and confirmed the presence of a significantly dilated right ventricle, severe tricuspid, and moderate mitral regurgitation with no valvular structural abnormalities described. In addition, a moderately compromised left ventricular ejection fraction (LVEF) (30–40%) and a large pericardial effusion () were shown. CT of the chest with pulmonary artery protocol was not supportive of pulmonary embolism as the underlying etiology. While the syndromic diagnosis of dilated cardiomyopathy with right sided heart failure was made, the etiology remained unknown.
The patient was started on beta-blocker and diuretic therapy, and with close monitoring began to improve from her heart failure. While aggressive medical management continued, an etiologic search for the underlying pathology began. Toxicology and infectious disease markers were negative. A viral panel was sent out, and later returned as unremarkable. A search for underlying malignancy also was negative. Left heart catheterization showed normal coronaries but was remarkable for severe mitral and tricuspid regurgitation. Right heart catheterization was performed due to the patient's persistently labile hemodynamics intermittently requiring pressor support suggestive of cardiogenic shock due to right heart failure and to establish an initial baseline of pulmonary artery pressure in newly diagnosed heart failure without clear etiology. This revealed severe mitral and tricuspid regurgitation with moderate pulmonary regurgitation and only mildly increased pulmonary artery pressure, thereby supporting the mechanism of decompensated heart failure as secondary to dilated cardiomyopathy.
It was only when ANA titers came back strongly positive with low C3 and C4 complement levels that the etiology was suspected to be most likely autoimmune. The patient was immediately started on prednisone (40 mg daily), and further workup showed elevated levels of both anti-double-stranded DNA and anti-Smith antibodies along with decreased levels of C3 and C4, confirming a diagnosis of SLE and lupus myopericarditis. On further examination of the patient, no other clinical findings of Lupus could be identified besides microcytic-hypochromic anemia.
On subsequent follow-up, the patient showed continuous improvement with steroid therapy and was ultimately scheduled for valve replacement surgery. As heart function monitoring and prednisone therapy continued, surgical intervention was ultimately averted. The patient progressed with complete functional recovery. A year later, EKG showed a normal sinus rhythm; ECHO analysis showed a LVEF of 55%; and the patient remained clinically stable on maintenance hydroxychloroquine and prednisone therapy, avoiding surgical intervention.


A 52-year-old woman with a history of chronic deep vein thrombosis (DVT) on warfarin, presented to the emergency department (ED) for expedited incision and drainage (I&D) of a mons pubis abscess. She complained of progressively worsening mons pubis pain, redness, and swelling for the prior week. The patient had been seen by her primary care physician at the onset of symptoms and diagnosed with a mons pubis abscess. She was prescribed oral antibiotics (sulfamethoxazole/trimethoprim) and scheduled for an I&D later that day with a general surgeon. However, due to intractable pain after sexual intercourse the previous night, she presented to the ED to have it drained sooner. She denied any systemic symptoms including fevers, chills, nausea, vomiting, dysuria, hematuria, vaginal bleeding, or unusual vaginal discharge. In addition, the patient reported intermittent lower abdominal pain for years, which had not recently changed. On further questioning she admitted to not being compliant with warfarin on multiple episodes in the past, but was compliant at the time of presentation.
Physical exam revealed a middle-aged obese female in no acute distress. Vital signs on presentation were significant for a temperature of 36.1 degrees Celsius, pulse rate of 66 beats per minute, and a blood pressure of 166/82 millimeters of mercury. Evaluation of the genitalia revealed a warm, indurated, fluctuant, 5 centimeter (cm) × 5cm × 4 cm left mons pubis area of swelling with moderate tenderness to palpation, and overlying induration. Point-of-care ultrasound (POCUS) revealed multiple fluid-filled tubular structures tracking into the abdomen and left femoral vein with intermittent areas of color flow.
Given the unusual ultrasound appearance, a computed tomography (CT) of the abdomen and pelvis with intravenous contrast was ordered along with laboratory studies. White blood cell count and international normalized ratio were 8.8×10(3)/microliters and 2.9 respectively. CT revealed multiple prominent collateral venous vessels over the mons pubis and lower abdominal wall consistent with PCS ( and ). I&D was not performed and vascular surgery was consulted. Vascular surgery noted a superficial venous thrombosis within the collection of the mons pubis vessels resulting in a clinical picture similar to a mons pubis abscess.
The patient was provided outpatient follow-up with vascular surgery for monitoring and potential thrombectomy. She was also counseled on medication compliance. At follow-up, the pain and swelling had resolved with hot compresses and continuation of anticoagulation therapy.


The patient, a 12-year-old boy, the only child of healthy unrelated parents, was referred to the department of developmental behavior of Shanghai Children’s Medical Center due to delayed development and growth. He was born with a cesarean section at term with a birth weight of 2.2 kg but without been told had intrauterine growth retardation during pregnancy period. The boy was purple after birth and improved after stimulation, but had feeding difficulties, so the boy was subsequent admission to the neonatal intensive care unit for weight management. Feeding difficulties and developmental delay were observed in infancy. He only sat at 10 months, walked at 18 months and spoke his first sentences at 2 years old. Growth delay persisted (current weight is 31.5 kg [P3–10], height 146.8 cm [P10–25], body mass index 14.62 kg/m2 [P3–5], and occipitofrontal circumference 52 cm [− 0.14SD] according to Chinese domestic data. Mild clinodactyly of both hands and abnormal facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia were noticed (Fig. & Table ). There was no history of seizures. Brain magnetic resonance image (MRI), EEG, X-ray of chest and spine, echocardiography and abdominal ultrasound were normal. Molecular karyotyping was normal.
Ethical approval for this study was obtained from the ethics committee of Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine. Written informed consent permit to pusblish was obtained from the proband’s parents.
Whole exome capture was performed with Agilent SureSelect V6 enrichment capture kit (Agilent Technologies, Inc., Woburn, MA, U.S.) according to the manufacturer’s instructions. The captured library was then sequenced on an Illumina HiSeq 2500 System (Illumina, Inc., San Diego, CA, U.S.). Raw sequencing data was process as previously described []. All detected variants were analyzed on the TGex (Translational Genomics Expert) platform featuring with the VarElect scoring system []. An insertion variant c.4029_4030insAA leading to frameshift mutation (p.Glu1344Lysfs*49) on NSD2 was detected and thought to have high probability as a candidate mutation.
The primers for amplification of the NSD2 gene (NM_ 133,330.2) were designed using UCSC Exon Primer online software () and synthesized. The primer sequences for the truncating variant to be confirmed were forward5’-agtttgtctgcccgtcctgt-3′ and reverse 5′-TGAGGATGGCTCAGTGGTG-3′.
The target fragments were amplified from the patients as well as his parents using polymerase chain reaction (Takara Biotechnology, Co., Ltd., Dalian, China). The PCR products were sequenced using an ABI3730XL sequencer (Applied Biosystems; Thermo Fisher Scientific, Inc., Waltham, MA, U.S.) with the forward and reverse primers. The sequence data were analyzed using Mutation Surveyor® software Version 4.0.4 (SoftGenetics, LLC). The truncating variant has been confirmed as de novo variants in the proband.


Patient 1 was a right-handed woman of 72 years old with a known history of anxiety. She experienced tremors of the tongue and both arms. She complained of fatigue, memory impairment, and important tremors, which were more important in her right side. When distracted, her physical exam appeared to be normal. Her symptoms persisted for a total of 180 months, and she has experienced no remission.
As shown in , the first scan revealed moderate bilateral hypoperfusion in the frontal, temporal, and parietal lobes. This hypoperfusion was more pronounced on the left side of the brain. On repeated scan, findings were similar but with a much more severe global hypoperfusion of the brain.


Patient 2 was a right-handed man of 47 years old with a known history of depression. He experienced a sensorimotor deficit on the left side of his body. He complained of fatigue, memory impairment, diffuse pain paraesthesia, and muscle spasms. His neurological exam appeared normal. His symptoms persisted for a total of 24 months, and he has experienced no remission.
As shown in , the first scan revealed moderate bilateral hypoperfusion of the frontal, temporal, and parietal lobes. These changes were more pronounced in the frontal lobes. On repeated scans, the brain shows severe generalized hypoperfusion.


Patient 3 was a right-handed man of 45 years old. He experienced a motor deficit in his left arm. He also complained of memory impairment, abulia, sexual dysfunction, and difficulty walking. When distracted, his physical exam was normal. His symptoms persisted for a total of 12 months, and he has experienced a near-total remission.
As shown in , the scan revealed mild hypoperfusion in the left medial and inferior temporal lobes as well as decreased parietal perfusion slightly more pronounced on the left side.


An 89-year-old male smoker patient presented at the emergency department of our hospital with left, deep purplish cervical swelling with draining sinuses. The patient reported that three months ago, painless erythematous nodular swellings appeared in the left lateral neck area. No respiratory symptoms, fever, or weight loss were reported except for occasional dry cough and mucous expectoration since he had been a lifelong smoker of 70 pack-years. The patient was a taxi and bus driver. His past medical history included surgery for benign prostate hypertrophy 15 years ago, as well as an unscheduled visit to the emergency department of our hospital, 6 months ago, due to an acute hypertensive episode associated with pulmonary edema, being treated by intravenous diuretics. Since then, he had been on valsartan-hydrochlorothiazide therapy (16 mg + 12.5 mg), once daily. On examination, the patient, a tall and thin man, (BMI = 19.6 Kg/m2), with normal skin color, had a normal physical appearance except for his left lateral neck lesion including draining tract sinuses with purulent material () and scarce low-pitched expiratory wheezes. The cardiovascular examination showed a mild systolic murmur in the right second intercostal space compatible with moderate aortic valve regurgitation. On admission, the blood pressure (BP) and heart rate (HR) were 145/70 mmHg and 86 beats per minute, respectively, while blood and biochemistry tests were as follows: Hct = 37.3%; Hb = 13.8 g/dL; MCV = 81.7 fL; MCH = 29.6 pg; PLT = 214 × 103/μL; WBC = 6.3 × 103/μL (leukocyte type: NEU% = 70%, LYM% = 20%, MON% = 7%, and EOS = 3%); INR = 1.22; serum glucose = 101 mg/dL; urea = 39 mg/dL; creatinine = 1.02 mg/dL; Na+ = 139 mmol/L; K+ = 4.2 mmol/L; and erythrocyte sedimentation rate (ESR) = 52 mm/1st hour. The Mantoux test showed 10 mm induration, and his chest X-ray had no significant findings. The computed tomography (CT scan) showed minimal fibrous bands in the upper zone area of the right upper lobe, while a small calcified nodule (3 mm diameter) was also found in the periphery of the apical-posterior segment of the left upper lobe (). Fiberoptic bronchoscopy revealed a diffusely red and hyperemic bronchial mucosa, particularly intense in the segments of the right upper lobe, with the presence of some small anthracotic areas (). Bronchoalveolar lavage fluid (BAL) obtained from the apical-posterior segment of the left upper lobe showed increased (>70%) lymphocytes, 15% neutrophils, few (<8%) macrophages, and scarcity of bronchial epithelial cells with no evidence of malignancy. Direct smear for acid-fast bacilli was also negative. The surgical biopsy and the microscopic examination of the cervical lymph node showed epithelial granuloma with central coagulative (caseous) necrosis and the presence of M. tuberculosis complex, respectively. In addition, the microscopic examination of the purulent content of draining sinuses in the patient's neck also revealed the presence of M. tuberculosis complex. Final diagnosis for TL was established by histopathologic examination (Figures and ).
The patient was started on a four- (4-) drug antituberculous regimen. One month after the initiation of the antituberculous regimen, and after an initial remission regarding the magnitude of the patient's neck growth, he experienced an enlargement of his lymph nodes with reappearance of draining sinuses. It was then decided to add oral steroids (20 mg prednisolone daily). Four weeks after steroid administration, there was a spectacular, almost complete remission, of his neck growth. The antituberculous treatment was continued for 6 months, and the patient was free of disease after its completion.


A four-year-old girl presented to the emergency department (ED) complaining of sudden onset severe left thigh pain after sustaining a fall from the standing height while playing a game of tag. The patient’s parents denied pain with ambulation prior to this episode, previous nocturnal pain, a family or patient history of cancer, fever, chills, weight loss, or any other symptoms. On physical exam, the patient was in moderate distress and screamed at any attempt to move her leg. She was unable to bear weight on the affected leg and the thigh was exquisitely tender to palpation with diffuse swelling.
X-rays demonstrated an expansile lytic lesion of the left distal femur with a pathologic fracture and a positive fallen leaf sign (Figure ). Magnetic resonance (MR) imaging showed a lesion measuring 3.5 x 3.0 cm in the greatest axial cross-section and 5.2 cm in the craniocaudal extent. The lesion was centered within the metaphysis and appeared expansile with surrounding cortical thinning, without invasion of the physis. There were multiple blood-filled cystic spaces with fluid levels. There were no underlying soft tissue elements noted, suggesting this was a primary ABC (Figures -).
Left femoral bone cyst curettage and bone grafting were performed. First, the femur was exposed through a 3 cm lateral incision of the distal thigh and a periosteal window in the bone was created. Electrocautery was used to achieve hemostasis and lesion curettage was performed. Tissue samples were analyzed as a frozen section and, once determined to be a benign lesion, the lesion was thoroughly curetted. Chemical adjuvant was withheld secondary to the close proximity of the lesion to the growth plate. A titanium nail was used to establish communication between the various cystic components of the lesion and the bony medullary canal. A bone void filler consisting of calcium sulfate and calcium phosphate was placed under X-ray guidance. After confirming appropriate fracture reduction, the patient was closed and placed in a Spica cast. The formal pathological report demonstrated a cystic lesion with bland fibroblasts and myofibroblasts admixed with seams of osteoid and scattered multinucleated giant cells without significant cellular atypia suggestive of ABC (Figure ).
At the six-week follow-up appointment, X-rays demonstrated interval consolidation of the bone graft with callus formation at the fracture site (Figure ). There was no sign of lesion recurrence and the patient was able to return to full preoperative weight-bearing activities.


A fifty-three-year-old African American female with a past medical history of HIV, hypertension, and asthma presented to the emergency room of our Institution with diffuse abdominal and bilateral lower extremity pain of one day-duration. The abdominal pain was described as crampy, knot-like, 9/10, and fluctuating in intensity with no radiation. The pain began the night before after eating a macaroni and cheese. Shortly after dinner, she had an episode of non-bloody, non-bilious vomiting. The next morning, the patient woke up with severe abdominal pain which prompted the arrival to the emergency department (ED). In the ED, the patient had a second episode of emesis. There was no associated fever, diarrhea, cough, weight loss, recent travel, sick contacts, changes in bowel movements, increased urinary frequency or history of diabetes, drug use or ingestion of toxic substances.
Patient has a history of multiple hospitalizations, ten within the last six years, for similar non-specific presenting complaints (consisting of abdominal pain and leg cramps) with anion gap metabolic acidosis of uncertain etiology that corrected within a few days of IV fluid administration and often sodium bicarbonate infusion. Only one admission was attributed to alcohol-induced acidosis and all of the other admissions were considered not be related to alcohol consumption.
Patient’s past medical history was significant for HIV, maintained on emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) for the past three years and emtricitabine/rilpivirine/tenofovir disoproxil fumarate (Complera) for the last six years. She took amlodipine 10 mg daily for blood pressure control. Patient also reported having taken supplements containing potassium chloride, thiamine, and magnesium oxide, that were prescribed during previous hospital discharges for electrolyte deficiency.
Patient had no surgical history or known allergies. However, she reported a ten-year history of alcohol abuse (one vodka shot per day) that had ended three years ago. Patient denied current alcohol consumption, except for a glass of wine 2–3 times per year. She denied smoking and recreational drugs use. She was unemployed, living with her parents and used to take daily walks that lasted less than one hour. Her diet consists mainly of oatmeal, grilled cheese sandwiches, pasta, and chicken. She denies consuming any exotic products or supplements which would have contributed to her current state.
In the ED, her vital signs were within normal limits. Physical exam was unremarkable with a soft non-distended, non-tender abdomen and lower extremities with full range of motion and strength.
Laboratory studies were significant for severe metabolic acidosis (pH of 7.11) with an anion gap of 33 [142 – (103+6)] and bicarbonate of 6 mmol/L. Urinalysis was positive for ketones and urine toxicology screen was negative. Other results included blood urea nitrogen (BUN)/Creatinine of 21mg/dL/1.20mg/dL (baseline), total protein 10.4 g/dL, albumin 5.34 g/dL, alkaline phosphatase 137 Bodansky Units/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 105 u/L/43 u/L, calcium 9.9 mg/dL, magnesium 1.8mg/dL, phosphorus 7.0 mg/dL, total bilirubin 2.0 mg/dL, and lactic acid 2.0 mg/dL. Patient had a normal white blood cell count, hemoglobin, platelet count, and coagulation profile.
Normal saline (NS) was initiated and within fifteen hours, the bicarbonate was 12 mmol/L and the calculated anion gap was 17. She was admitted for further stabilization and work-up. On hospital day 2, additional tests were returned including beta-hydroxybutyrate 1.75 mmol/L, serum osmolality was 302 mOsm/kg and urine osmolarity was 710 mOsm/kg. Urine lytes were as follows: Sodium 203 mmol/L, potassium 24.6 mmol/L, and chloride 273 mmol/L. A right upper quadrant ultrasound demonstrated diffuse fatty infiltration of the liver.
The patient’s laboratory results from previous hospitalizations are summarized in . Each hospitalization followed a very similar course. The patient would present to the emergency department with crampy abdominal or lower extremity pain, laboratory values revealing severe anion gap metabolic acidosis as high as 33 and pH as low as 7.05. Patient’s discomfort and laboratory abnormalities corrected every time within 24 hours with only IV fluids with addition of bicarbonate on some occasions. Patient was usually released the following day with a normal anion gap. Urinalysis consistently revealed large ketones and work-up was negative for salicylates, acetaminophen, ethylene glycol, and ethanol. Interestingly, every admission was associated with multiple episodes of non-bloody, non-bilious (NBNB) vomiting. Patient reported 2–3 episodes of NBNB vomiting the prior three admissions but reported an average of 10–12 episodes of NBNB vomiting with the earlier admissions.
The index admission followed a similar trajectory as the patient recovered within 24 hours on IV normal saline as the anion gap decreased from 33 to 15 overnight. The bicarbonate improved from 6mmol/L to 12 mmol/L and the patient reported resolution of her symptoms by the next morning. To isolate possible causes, her home medications were held, and patient was only given IV normal saline. The patient was thoroughly interviewed before discharge to assess for any unusual dietary habits or psychiatric disease. Patient was emotionally stable and endorsed a normal, regular diet with exercise. She was discharged with the same home medications wand given close outpatient follow-up.


A 67-year-old female patient was admitted to the clinic with a complaint of painful swelling of the right submandibular region. She had a 1-year history of a hard, painless mass present in the submandibular region, which worsened in the 10 days prior to admission, with swelling of the submandibular region and fever. On palpation, the right submandibular salivary gland was hard and painful. Palpation and massage of the submandibular duct was painful, and there was no saliva evacuated from the duct.
Ultrasound examination revealed enlargement of the right submandibular gland measuring 54.4 × 29.9 mm, with unclear borders. The echotexture revealed diffuse changes with low echogenicity, local anechoic areas, and hardened zones with severe peripheral vascularization. The gland was surrounded by a small amount of free fluid, and there was mild enlargement of the lymph nodes, measuring 13.0 × 13.3 mm (Figure A and B). Hepatomegaly and diffuse fatty liver were also found in this patient. She noted a 4-year history of autoimmune hemolytic anemia and had been taking prednisolone prescribed by a hematologist for 3 years and ammonium glycyrrhizinate for the last year.
After a 7-day course of antibiotic therapy, the patient noted reduction in pain and swelling. However, a new manifestation of inflammation was observed, and the patient was hospitalized with fever, pain, and swelling. The swelling of the submandibular space was firm, without clear boundaries. The color of the skin had not changed. Her hemoglobin (HGB) level was 109 × 109 g/L, her red blood cell (RBC) count was −3.56 × 1012/L, her lymphocyte (LYMPH) percentage was 23.3%, and her erythrocyte sedimentation rate (ESR) was 50 mm/h. Submandibular gland extirpation by urgent indications was planned for this patient.
Surgery was performed under general anesthesia. After incision of the skin and subcutaneous tissue, a hard mass with a rough surface without clear borders that was fused with the surrounding tissues (muscles, fascia, and blood vessels) was revealed (Figure ). The adjacent muscles exhibited a hyaline-like hardness and structure. There was no pus in the submandibular space. Clinically, the lesion appeared to be a malignant neoplasm. The classical horizontal incision for submandibular gland extirpation was modified by performing a vertical incision for better visualization of the affected area. Extirpation via resection of the submandibular gland conglomerate and enlarged lymph nodes was performed (Figure ). Macroscopically, the gland measured 6.0 × 5.2 × 5.0 cm3. After formalin fixation, on the cut surface, the gland had a “pineapple-like appearance with yellow and white layers” (Figure ).
Microscopically, histological examination revealed extensive periductal and perivascular fibrosis and sclerosis, foci of hyalinosis, infiltration by mononuclear cells (mostly lymphocytes and plasma cells), acinar atrophy, and obliterative phlebitis (Figure A-C). Thus, the histological diagnosis was CSS.


A 76-year-old woman experienced nocturnal dyspnea and obviously fewer pulses than usual for over a year. Her primary physician detected frequent PVCs, which prompted her referral to our outpatient department. Neither cardiac computed tomography nor echocardiography showed structural heart disease. A Holter monitor recorded PVCs for 35.1% in 24 hours. The 12-lead electrocardiography (ECG) showed tall R waves in I and aVL, in addition to a near-QS pattern in V1, relatively narrow QRS waves in V1-2, and a precordial transition zone between V3 and V4 (Figure ). All these findings strongly suggested that the PVCs originated from the right ventricular septum close to the His bundle., , , , ,
After informed consent was obtained, a cardiac electrophysiological study was performed with the patient fasting and not taking antiarrhythmic drugs. A 4-Fr hexapolar electrode catheter (Supreme™, St. Jude Medical, Inc) was positioned in the His bundle region. A 7-Fr straight eicosapolar electrode catheter (CristaCath®, Biosense Webster, Inc) was carried into the right ventricle via an 8.5-Fr bidirectionally deflectable sheath (Agilis™ NxT, St. Jude Medical, Inc), and a three-dimensional (3D) electroanatomical map was created using EnSite™ NavX™ System (St. Jude Medical, Inc). The His potential location was marked on the 3D map. A total of 193 points of potentials were acquired. The mean amplitude of five consecutive His potentials recorded with the His catheter was 0.10 mV. The activation map revealed that the earliest ventricular activation of PVCs was located 5 mm inferior to the His bundle (Figure A1), where a 6-mm-tip-cryoablation catheter (Freezer™ Xtra, Medtronic CryoCath LP) was subsequently positioned (Figure A2). The PVC potentials recorded by the distal electrode of the ablation catheter preceded the rise of the QRS on surface ECG by 14 msec (Figure ). A good pace map was thereby obtained (Figure A). Two sequential cycles of cryoenergy were delivered at −80°C for 4 minutes while monitoring the PR interval with a few seconds of interruption for thawing. The first ablation attempt only minimally decreased the number of PVCs. Another four applications of cryoenergy were placed at an adjacent region, but the only effect was to rotate the QRS transitional zone counterclockwise (Figure B). Therefore, the newly acquired five points of potential were superimposed on the existing activation map. The earliest activation site shifted to a higher position on the revised activation map (Figure B1). The distance between this activation site and the first targeted site was <5 mm. Therein, the pace mapping did not match the clinical PVCs well (Figure B). However, the potential recorded at the cryocatheter tip preceded the rise of the QRS complex by 27 msec, which was much earlier than that obtained at prior attempt sites (Figure ). Compared with the previously targeted points, the bipolar electrogram recorded by the cryocatheter showed a significantly longer duration (49 msec) and a higher frequency potential (Figure ). Prior to delivering cryoenergy, we made sure that the His potential was not recorded with the distal electrode of the cryocatheter. However, pacing at the site with maximum output (9.9 V) made the QRS width slightly narrow in the first beat, suggesting that the first pacing pulse was captured at the His bundle (Figure ). The sixth attempt eliminated the PVCs within 10 seconds after the start of the application (Figure B2). Nevertheless, the PVCs appeared again soon after the discontinuation of cryoenergy. The potential recorded at the site adjacent to the sixth site further preceded the QRS complex by 29 msec (Figure B2, Figure ). The PVCs were completely abolished within 21 seconds after cryoenergy application. The last two attempts were also performed with the freeze-thaw-freeze method (delivered at −80°C for 4 minutes, interrupted only for a few seconds for thawing), similar to previous sequential attempts. The total procedure and fluoroscopy times were acceptable (86 minutes and 17 minutes, respectively). Neither junctional rhythm nor ventricular ectopy was induced while delivering cryoenergy. At the completion of all procedures, neither atrial-His bundle (AH) nor HV intervals showed any change compared to baseline values.
A 24-hours Holter monitor placed on the patient, and 2 days after, the catheter procedure only recorded 15 isolated PVCs. The patient has been symptom-free since the procedure. The 12-lead ECG showed no PVCs 12 months after cryoablation.


A 61-year-old male was transferred to our center from a peripheral hospital as a case of OP poisoning for further management. He was a chronic alcohol consumer (> 160-180 mg/day) for the past 30 years and had accidentally consumed an unquantifiable amount of insecticide along with a binge of alcohol. He became drowsy and disoriented and was hence admitted to hospital. Initial clinical evaluation revealed the patient to be drowsy, hypotensive, and had tachycardia. On examination, he had miosis and tachycardia. In view of the clinical presentation, he was started on management for OP with gastric lavage, intravenous (IV) fluids, vasopressors, broad-spectrum antibiotics, atropine, pralidoxime (PAM), and blood component support. However, he responded poorly to atropine and PAM and continued to deteriorate.
During the hospital stay, the patient developed hemolysis and acute kidney injury (AKI), which was managed with hemodialysis. He also developed severe hemolytic anemia requiring transfusions, which has been described in the literature with xylene (solvent for amitraz) poisoning []. He also required mechanical ventilatory support due to poor sensorium. Meanwhile, a review of the insecticide revealed it to be amitraz. Also supporting against the diagnosis of OP poisoning were the normal serum choline-esterase levels - 8432 IU/L (normal range: 2710 to 11510 IU/L).
Electrocardiogram (ECG) showed normal sinus rhythm, and imaging studies showed cardiomegaly on chest radiograph and normal-sized kidneys with increased cortical echogenicity, perirenal collection and fatty liver on abdominal ultrasonography.
His baseline and subsequent laboratory investigations are listed in Table .
The patient was managed with central venous pressure (CVP) guided fluids, hematinics, antibiotics, and supportive measures. He made an uneventful recovery in one week. Most cases recover entirely with aggressive supportive treatment.


A 62-year-old female, known case of primary hypertension, was brought in at a tertiary care center with a history of alleged consumption of a pesticide, details of which were not available. She came in at the tertiary center followed by immediate loss of consciousness. Her relatives had also noticed profuse diaphoresis, frothing at the mouth and high colored urine. No history of generalized tonic-clonic movements, loose stools, hematemesis, melena, hematuria, or oliguria was present. Initial evaluation revealed the patient to be hemodynamically stable with a respiratory rate of 26/min, oxygen saturation (SpO2) 86% on room air. Excessive oral secretions were noticed, and pupils were bilaterally constricted. Chest examination revealed bilateral diffuse crackles. She received saline gastric lavage, IV fluids, oxygen supplementation. She was atropinised in view of miosis and intermittent bradycardia with excessive oral and respiratory secretions. During the course of hospital stay, she developed labored breathing and desaturation for which she was intubated and placed on a mechanical ventilator. The management for OP poisoning was stopped after reviewing the composition of the insecticide, which revealed it to be amitraz.
She was then transferred to our center for further management. On examination at our center patient was afebrile with a heart rate of 90/min and blood pressure of 138/90 mm Hg. Grade II bedsores were present. Glasgow coma score (GCS) was nine. Right pupil showed normal reaction whereas the left remained constricted. Horizontal and vertical gaze palsy along with skew deviation in the left eye was present. There was spastic quadriparesis with bilaterally extensor plantar response, deep tendon reflexes (DTRs) were bilaterally exaggerated. Chest examination revealed bilateral normal air entry. Rest of the examination was within normal. Investigations done at our center revealed the figures (Table ).
A peripheral blood smear done showed neutrophilic leukocytosis, and an MRI brain revealed Osmotic Demyelination Syndrome.
She was managed at our center with IV fluids, Ryles tube feed, IV antibiotics, and supportive measures. She was given supportive care; but because of the central nervous system (CNS) depression and respiratory failure, she was placed on ventilatory support. During hospitalization, she developed hypokalemia (2.7 mEq/L), which was corrected with IV and oral supplements. In view of expected prolonged mechanical ventilation, she was tracheostomised. On day 11 of admission, she developed sudden onset bradycardia and hypotension. Cardiopulmonary resuscitation (CPR) as per advanced cardiac life support (ACLS) protocol was initiated; however, despite all measures, she succumbed to her illness. Severe bradycardia responding promptly to atropine boluses have been described in previous case reports but the event, in this case, could have multifactorial etiology like dyselectrolytemia, respiratory failure, sick sinus or underlying coronary and hypertensive heart disease.


A 59-year-old woman had a palpable mass in the right midabdomen during routine physical examination by her primary care physician. Other than abdominal pain, she had no signs or symptoms of urogenital disorders, such as hematuria or irritative voiding symptoms. She had no prior history of renal disease or trauma. Family history included a brother who underwent nephrectomy for RCC at age 62.
An abdominopelvic computed tomography (CT) scan revealed a large, solid, right renal mass (14x13x12 cm) and several hypoenhancing liver lesions suspicious for metastases. CT also identified a focal, slightly lucent lesion with sclerotic rim in the T10 vertebral body which was felt to represent a small hemangioma of bone or metastatic lesion, but a subsequent bone scan was negative. CT thorax revealed no metastases. There was significant enhancement of the solid components of the tumor and finger-like extensions of absent enhancement throughout the renal mass consistent with areas of necrosis or acute inflammation (). The mass arose from the mid and upper pole of the right kidney and extended superiorly displacing the right lobe of the liver and inferior vena cava (IVC) anteriorly, making the liver palpable (). The liver, in fact, extended down to her right iliac crest and below her umbilicus on both sides of her abdomen (). There was no evidence of tumor thrombus in the right renal vein or IVC. A diagnosis of likely malignancy with potential liver metastases was made and she was scheduled with interventional radiology for biopsy for pathologic confirmation.
CT scan revealed multiple indeterminate lesions on her liver, the largest of which was 12x10 mm. She was referred for percutaneous biopsy of the kidney and liver lesions for tissue pathology and staging. As well-defined liver lesions were identified, the interventional radiologist performed liver mass biopsy only based on the perceived additional risk of biopsy of the hypervascular renal tumor. Pathology revealed liver parenchyma with fatty deposits, negative for malignancy. Given the negative liver biopsies and normal bone scan, an open radical nephrectomy with right retroperitoneal lymph node dissection was performed for suspected localized RCC using a subcostal incision. With a fixed retractor for the bowel and manual retraction of the liver, exposure of the renal hilum was quite good. No blood transfusion was necessary (estimated blood loss = 100 ml) and the patient was discharged home on postoperative day four without complication. According to final pathologic analysis, including a panel of immunochemical stains which excluded RCC and metanephric adenoma, the diagnosis was renal oncocytoma (). Preoperative glomerular filtration rate (GFR) was 101 ml/min/1.73m2 and new baseline GFR was 58 ml/min/1.73m2. The liver and bone lesions identified prior to surgery have been stable and no local or distant metastases have been seen now nearly four years postoperatively.


A 26-year-old Chinese male was referred for infertility consultation in our center after 1 year of regular unprotected coitus and no pregnancy. His height was 170 cm and weight was 70 kg. He presented cryptorchidism and the left and right testicular volume is about 8 mL separately. The development/growth of penis was normal. Moreover, no other abnormal physical examinations were observed. A series of routine examinations were conducted. Semen analysis and levels of sex hormones are listed in Table . The male was finally diagnosed as azoospermia according to the semen routine examination.[ The proband’ father was 49 years old when he was recalled to undergo the azoospermia factor (AZF) microdeletion examination. Our study protocol was approved by the Ethics Committee of the First Hospital of Jilin University, and the informed written consents were obtained from the patients for publication of this case report and accompanying images.


A 6-year-old male patient reported to the outpatient department of Department of Pedodontics and Preventive Dentistry, Faculty of Dental Sciences, SGT University, Bhudera, Gurugram, with a chief complaint of missing upper and lower front teeth since the past two years. The patient also experienced sudden sharp shooting pain on mastication in the left lower back tooth since the past one month. The patient also gave history of repeated injuries due to fall. Three years back, the patient had been diagnosed with rickets, specifically VDDR II. He had also been hospitalized twice before due to his inability to walk. His family reported that the patient had never been immunized. This was his first dental visit.
On extraoral examination, a bruise was observed on the right cheek which had occurred due to a fall two days back. Characteristic signs of rickets were observed such as—alopecia, frontal bossing, and bowing of legs ().
On intraoral examination, clinically missing 51, 52, 61, 65, 71, 72, 81, 82 were observed. Decay was present in 55, and 75 was grossly decayed. All the permanent first molars were found to be hypoplastic ().
His orthopantomogram (OPG) findings revealed absence of permanent tooth buds of all four second premolars. Resorbed roots were observed in 75. Large pulp chambers were observed with thin overlying enamel and dentin ().
On the first visit, the patient along with his family was counselled about the proper diet, oral hygiene measures, and preventive measures. Restorations of the carious teeth and extraction of the left mandibular primary molar under local anesthesia were conducted in the subsequent visits. Stainless steel crowns were then given on the hypoplastic permanent molars. The patient is currently on follow up and we await the mesial shift of the left mandibular permanent first molars ().


A 65-year-old man presented with a four-week history of chronic cough and progressive dyspnoea. The computed tomography (CT) scan of his thorax revealed left lower lobe collapse with consolidation, presence of mediastinal lymphadenopathy (ML) and the absence of distant metastasis (Fig. ). EBUS was performed under conscious sedation. Systematic assessment of the ML with linear EBUS showed enlarged nodes at stations 4R, 4L, 5, 6 and 7. Three aspiration passes were performed on station 4R of the ML. Following this, despite being given appropriate intravenous sedation (titrated to a maximum cumulative dose of 5 mg midazolam and 50 μg fentanyl), the patient had an intractable cough and reduced tolerance towards the procedure. This was overcome when EBUS was replaced with endoscopic ultrasound-echobronchoscope (EUS-B). Another three passes were performed on station 7 of the ML. Total procedure time was 42 min. A cytology examination was performed and revealed an abundant amount of abnormal cells on both of the samples obtained from stations 4R and 7. The patient was diagnosed with non-resectable stage IIIB small cell lung carcinoma.


A 38-year-old man presented with a two-month history of chronic cough. On arrival, he was intubated for severe acute respiratory failure with an arterial blood gas result of pH: 7.033, PaO2: 141 mmHg, partial pressure of carbon dioxide: 123 mmHg, and HCO3−: 21.3 mmol/L). A CT scan of the thorax was carried out to assess the suspicion of a widened mediastinum on the chest radiograph and confirmed the presence of a large, right-sided heterogeneous pulmonary lesion with numerous ML. All lesions had multiple large, ill-defined, scattered necrotic areas. We carried out a thorough review of the CT images to determine suitable non-necrotic areas for aspiration (Fig. ).
Bronchoscopy inspection revealed a narrowed central airway from the mid-trachea extending down to proximal segments of the bilateral main bronchus. EBUS-TBNA with three real-time passes was performed at stations 4R and 7. This was followed by three FNA passes via EUS-B on a non-necrotic area adjacent to the proximal paraoesophageal area at the level of the sternal angle with the scope positioned at the 1 o'clock position. Total procedure time was 45 min. Final cytology results from EUS-B guided aspirations confirmed the diagnosis of metastatic adenocarcinoma of the lungs.


A 70-year-old male was admitted for exacerbation of chronic obstructive pulmonary disease. A CT scan of his thorax was arranged to confirm the suspicion of a large bullae at the right lung. Results of the CT scan of the thorax revealed a heterogeneous lung mass at the posterior mediastinum that measured 3.4 cm × 3.1 cm (Fig. ). The lesion demonstrated a standardized uptake value (SUV)max of 10.6 on 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) scan with evidence of distant bone metastasis. Under conscious sedation, systematic assessment of the mediastinum using linear EBUS was insignificant. The heterogeneous mass was found to be paraoesophageal and adjacent to the descending aorta (Fig. A). A total of five real-time passes (aspiration) were performed (Fig. B) with a procedure time of 35 min. Final cytology examination and immunohistochemical testing on aspiration samples was consistent with lung adenocarcinoma. Patient was diagnosed with stage IV disease.


A 58 years old male patient, with poorly controlled diabetes mellitus type 2 presented to the outpatient clinic for 4 days history of redness, blackish discoloration of the penis, painful swelling of penile shaft associated with high grade fever of 40 °C and purulent discharge from the penis. The patient denied any recent sexually transmitted disease, genitourinary trauma, urethral instrumentation. He is non-smoker and non-alcoholic. He had no sexual intercourse during the last few months. His past medical history was unremarkable except for poorly controlled diabetes (last HBA1C of 13% (normal: 4%–5.5%).
On admission, his temperature was 40 °C and the vital signs were stable. Physical examination revealed penile edema, severe tenderness of the penile shaft with no skin breaks, normal glans, blackish discoloration of the penis (). The testicular, digital rectal examinations were normal. No dysuria or frequency or hematuria. He also reported chills and nausea.
Laboratory examination revealed WBC of 22000/mm3 with left shift, CRP of 240 mg/L, random blood sugar 400 mg/dl. Urine analysis showed 1–2 WBC per high power field. Blood urea & serum creatinine were within the normal limits. Purulent material discharge from penis was sent for culture. HIV test and STD panel were negative. Blood, urine, and pus cultures were obtained.
The patient was started on broad-spectrum antibiotics (Ertapenem &Vancomycin) and fluid resuscitation was initiated. Urgent surgical intervention under general anesthesia was done. Before the operation, an 18-Fr Foley catheter was inserted. After degloving of the penis, it was noticed that there was a necrosis of the tissue below the skin on the ventral and dorsal aspect of the penis involving penile dartos layer up to the corpora spongiosa. Adequate debridement with excision of all necrotic tissue was done (). Necrotic tissue was debrided to bleeding edges. Tissue was send for culture and histopathological examination.
Postoperatively, the patient remains stable with no fever or chills. Laboratory studies improved, leukocyte count and CRP decreased. The culture of the pus materials revealed S. aureus and E. coli, the patient was completed a further 3 weeks of antibiotic according to the sensitivity test (Ertapenem 1 g once daily). Blood and urine culture revealed no growth. Regular dressing was done three times daily. After 10 days, the wound bed was granulated and healthy. An unexpanded, meshed, split-thickness skin graft was placed on the ventral and dorsal aspect of the penis (). The patient was discharged on the 18th postoperative day. He was seen in the outpatient clinic 3 weeks after discharge and he was markedly improved with no infection or flap necrosis was noted. A satisfied aesthetical appearance was obtained (). The patient provided a written consent for the publication of this clinical case.


A 40-year-old man with 4-year history of dyslipidemia and T2DM had a symptom of general fatigue. He enjoyed SUMOU, which is a traditional Japanese sport, in his high school days, and thereby he ate over 10,000 kcal/day of diet every day when he was young. For that reason, he sometimes ate 3000–5000 kcal of diet at once even at that time. His past history was acute pancreatitis at the age of 36, and after the onset of pancreatitis, he stopped drinking alcohol and smoking.
At the age of 36, metabolic markers were as follows: total cholesterol, 644 mg/dL; Low Density Lipoprotein (LDL)-cholesterol, 127 mg/dL; High Density Lipoprotein (HDL)-cholesterol, 23 mg/dL; triglyceride, 3207 mg/dL; plasma glucose, 244 mg/dL; hemoglobin A1c (HbA1c), 10.3%. His height, body weight and BMI were 180.0 cm, 121.5 kg and 37.5 kg/m2, respectively. Acute pancreatitis markers were as follows: lipase, 987 U/L; trypsin, 6662 ng/mL; pancreatic phospholipase A2, 1150 ng; pancreatic amylase, 290 IU/L. He had no family history of them. Although during hospitalization period we treated him with intensive insulin therapy for T2DM, after the improvement of acute pancreatitis, he was taking 400 mg/day of bezafibrate and 1800 mg/day of ethyl icosapentate for the treatment of dyslipidemia and 30 mg/day of mitiglinide, 0.6 mg/day of voglibose, 1500 mg/day of metformin and insulin therapy (4 units of glargine) for T2DM at discharge. His triglyceride levels were 64–734 mg/dL for 2 years after discharge of acute pancreatitis, but he stopped the medication for dyslipidemia on his own judgement. We started 10 mg/day of ezetimibe for the treatment of dyslipidemia because his triglyceride level was as high as 1921 mg/dL, and after then his triglyceride level was decreased to 416 mg/dL. His HbA1c levels were 7.0–9.1% for 2 years after discharge in outpatient clinic in spite of stopping insulin. At that time, he was treated with mitiglinide, 0.6 mg/day of voglibose, 1500 mg/day of metformin and 0.9 mg/day of liraglutide, but he stopped the medication for T2DM on his own judgement. We started the same medication and added 2.5 mg/day of luseogliflozin for the treatment of T2DM because his HbA1c levels were as high as 12.9%. However, after 6 months, he stopped receiving the treatment for about 1.5 years on his own judgement. In outpatient clinic, his body weight was 111.6–120.0 kg.
At the age of 40, after his interruption of therapy, he felt general fatigue and visited the emergency room of our office once more. His height, body weight and BMI were 180.0 cm, 114.4 kg and 35.3 kg/m2, respectively. His vital signs were normal. Laboratory data were as follows: plasma glucose, 260 mg/dL; plasma insulin, 27.6 μU/mL; HbA1c, 12.9%; glycoalbumin 33.5%; total cholesterol, 1055 mg/dL; LDL-cholesterol, 240 mg/dL; HDL-cholesterol, 17 mg/dL; triglyceride, 11,175 mg/dL. Urine glucose (3+) and urine ketone body (2+) were detected in urinalysis. Furthermore, his blood sample showed white and opaque (Fig. a). He did not agree to the hospitalization and frequent insulin injection. In addition, his dyslipidemia and T2DM had been improved with previous oral medication. Therefore, we started 160 mg/day of fenofibrate and insulin therapy (8 units of degludec) on an outpatient basis. At that time, his life style was markedly disturbed; for example, he drunk over 1.5 L of PET bottle of juice, ate a lot of snacks and fruits and fast food in eating out. He sometimes continued to eat 3000–5000 kcal of diet at once even at that time. We treated him with therapeutic lifestyle changes and diet therapy of 2200 kcal/day (about 30 kcal/ideal body weight kg). After 4 days, we examined laboratory data in the fasting state. Laboratory data were as follows (Table ): total cholesterol, 705 mg/dL; LDL-cholesterol, 117 mg/dL; HDL-cholesterol, 20 mg/dL; triglyceride, 5555 mg/dL; Remnant like particle (RLP)-cholesterol, 264.8 mg/dL; Apolipoprotein A-I, 121 mg/dl; Apolipoprotein B, 145 mg/dl; Apolipoprotein E, 33.4 mg/dl. In addition, lipoprotein fractions showed Very Low Density Lipoprotein (VLDL) and MIDBAND fractions were elevated (VLDL, 44%; MIDBAND, 33%). Another fasting laboratory data were as follows: plasma glucose, 279 mg/dL, total ketone bodies, 1275.1 μmol/L; β-hydroxybutyrate, 750.8 μmol/L; acetoacetate 524.3 μmol/L. TSH, FT3 and FT4 levels were 1.562 μIU/mL, 2.83 pg/mL and 1.29 ng/dL. In spite of such very severe hypertriglyceridemia, he did not have acute pancreatitis (lipase, 30 U/L; trypsin, 262 ng/mL; pancreatic phospholipase A2, 167 ng/dL; pancreatic amylase, 15 IU/L). He frequently visited our office every 1–2 weeks, and we increased insulin therapy little by little (from 8 to 14 units of degludec) in outpatient clinic. One month later, his serum triglyceride level was reduced.
Two months later, however, his life style became markedly disturbed once more and quitted his therapy again. At that time, surprisingly, his serum triglyceride was markedly increased up to 16,900 mg/dL (Table ). He ate high calorie diet including large amounts of rice, which is known as a main source of carbohydrate in Japan. It was estimated that he ate over 1000 kcal of rice. In addition, he ate large amounts of oily food such as fried chicken and fried potato. He failed to precisely explain how many amounts of fat he ate, but it was estimated that he ate 3000–5000 kcal of diet in total at once. Moreover, he drunk over 2.0 L of PET bottle of juice and ate a lot of snacks at the same time. He stopped injecting insulin and his glycemic control was very poor (plasma glucose, 310 mg/dL; HbA1c, 13.1%). We re-tried the education, diet therapy and medication. One month later, serum triglyceride level was dramatically decreased which was accompanied again by the amelioration of glycemic control and marked reduction of ketone body (Table ). Furthermore, his blood sample showed clear fluid (Fig. b). At that time, his medication was 160 mg/day of fenofibrate for the treatment of dyslipidemia and insulin therapy (18 units of glargine) for T2DM. We examined lipid parameters once more 1.5 months after treatment restart. Laboratory data were as follows (Table ): total cholesterol, 224 mg/dL; LDL-cholesterol, 151 mg/dL; HDL-cholesterol, 31 mg/dL; triglyceride, 328 mg/dL; RLP-cholesterol, 15.8 mg/dL; Apolipoprotein A-I, 84 mg/dl; Apolipoprotein A-II, 15.1 mg/dl; Apolipoprotein B, 140 mg/dl; Apolipoprotein C-II, 91 mg/dl; Apolipoprotein C-III, 11.8 mg/dl; Apolipoprotein E, 7.0 mg/dl. Lipoprotein fractions showed VLDL and MIDBAND fractions were decreased under stable dyslipidemia (VLDL, 16%; MIDBAND, 24%). After then, his body weight was reduced to under 110 kg.


A 30-year-old man presented to the cornea service at the Athens Vision Eye Institute for evaluation of a new rapidly enlarging lesion in his right eye over the last 6 months. His past medical history was significant for Escherichia coli prostatitis 1 year prior to presentation. He had significant sun exposure since childhood, and he worked as a skipper in a sailboat for the last 12 years. His best-corrected vision was 20/20 in both eyes. Upon examination of the right eye, a fleshy pink conjunctival lesion was noted in the medial canthal area (Fig. a). In addition, a pterygium-type lesion encroaching on the cornea was noted. Examination of the left eye revealed a smaller fleshy pink conjunctival lesion in the medial canthus (Fig. a). High resolution anterior segment optical coherence tomography (OCT) (Optovue Avanti, Fremont, CA, USA) of the bilateral medial canthal lesions revealed homogeneous hyporeflective lesions with thin overlying epithelium (Figs b, b). Upon further questioning the patient and his family, they reported the presence of the bilateral medial canthal lesions since the patient was a teenager, but the patient had never sought ophthalmic care. The pterygium had been present for 1.5 years and the corresponding OCT revealed mild hyper-reflectivity of the otherwise thin epithelium with underlying subepithelial hyper-reflective “stringy” tissue.
Small incisional biopsies (2 mm in diameter) of the medial canthal lesions were undertaken and samples were submitted both in formalin and as fresh tissue for flow cytometry. The slightly atypically appearing pterygium was also biopsied. The patient was started on oral doxycycline 100 mg two times a day. Histopathology of the medial canthal lesions revealed lymphoid follicles of variable size that were composed of a polymorphic population of lymphocytes, dendritic cells and tingible body macrophages. Immunohistochemical staining was positive for CD20, CD3, Bcl-6, CD10 and Ki-67, and negative for Bcl-2 and Cyclin D1 (Fig. ). Flow cytometry showed a polyclonal population of lymphocytes in both medial canthal lesions. Finally, histopathology of the other lesion in the patient’s right eye revealed elastotic degeneration consistent with pterygium. Oral doxycycline was continued for a total of 2 months. The medial canthal lesions continued to shrink as evidenced both on clinical exam (Figs. c, c) and high resolution anterior segment OCT (Figs. d, d). A month later, the patient requested surgical excision of the pterygium for cosmetic reasons and the residual medial canthal lesion in the right eye was also removed. He is free of recurrence of the BRLH for the past 1.5 years. The residual medial canthal lesion in the left eye has not increased in size since stopping the oral doxycycline.


The patient is a 46-year-old female with a psychiatric history of Bipolar Disorder I and depression presenting after a suicide attempt via OP ingestion at Scheer Memorial Adventist Hospital in Banepa, Nepal. She ingested 120 mL of chlorpyrifos in 2.5 hours. No one was home at the time. She was found by neighbors who called her estranged daughter to take her to the hospital. The patient reports that her attempt was a result of her daughter marrying a man in a lower caste system, which by Nepalese Hindu culture mandates that the patient disown her.
The patient presented to the emergency department (ED) with bradycardia, miosis, lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, and diarrhea. ED vitals were HR of 104 beats per minute (bpm), BP of 140/90 mmHg, oxygen saturation of 98%, temperature of 97°F, RR of 20 breaths per minute. She was immediately given a loading dose of 1.8 mg atropine IV and 2 g pralidoxime IV. Subsequently, charcoal packing and nasogastric lavage were performed within an hour of presentation. She required an additional 2 mg of atropine for resolution of respiratory distress. ED labs were significant for hyponatremia (131 mmol/L) and low serum cholinesterase of (895.5 mU/mL). She was then transferred to the ICU where she stayed for 14 days. She was given 1 g of pralidoxime every 8 hours for 4 days. Her atropine dose was increased 20% per day to maintain HR over 80 bpm until she reached a max dose of 10.2 mg atropine per day (three times the normal dose). The patient's signs and symptoms of cholinergic excess resolved; however, she developed atropine-induced psychosis. Per nursing reports, patient was agitated, delusional, giving inappropriate responses, and alert and oriented to self and day. She was weaned off atropine by 20% each day and by day 8 her psychosis resolved. Her ICU course was also complicated by aspiration pneumonia with fevers (Temperature max of 102.4°F) which resolved with clindamycin. Once she was stable, she was downgraded to a medicine unit where she remained for 4 days and was discharged on hospital day 19.


A 30-year-old gravida 2 para 0101 (0 full term, 1 preterm, 0 abortions, and 1 live child) woman at 32 weeks, 3 days gestation presented to our hospital with a two-day history of nausea and vomiting. Her prior medical history included type 1 diabetes mellitus on continuous glucose monitoring and insulin pump. She has had a history of prior episodes of diabetic ketoacidosis requiring hospitalization; however, as her home glucose readings were only marginally elevated at 100–200 mg/dL, she did not think to present to the hospital sooner than she did. Upon initial examination in the emergency department, she appeared uncomfortable with Kussmaul breathing. Fetal heart monitoring showed absent variability and recurrent late decelerations. Her initial admission laboratory results showed a blood glucose of 183 mg/dL, acidosis with an anion gap of 23, pH 7.11, β-hydroxybutyric acid (β-HA) 9.6 mmol/L (normal 0.02–0.27 mmol/L), and lactate 0.65 mmol/L (normal 0.3–1.5 mmol/L). The patient was admitted to the high risk obstetrics service for further management of her acidosis and resulting fetal distress. As the patient was initially euglycemic, insulin infusion was initiated at 2 units/h as per the institution's DKA protocol. After four liters of bolus intravenous fluids, a maintenance fluid rate of 5% dextrose/0.45% NaCl solution at 250 mL/h was initiated.
Approximately four hours after admission, the patient's euglycemia continued to persist with serum glucose readings averaging 165 mg/dL (). Given this euglycemia, the obstetrics team continued to cautiously titrate the patient's insulin drip. Over the next hour, her acidosis progressively worsened with a blood pH nadir of 6.97. Fetal heart tracings continually deteriorated. Unfortunately, the patient was not a surgical candidate for emergent fetal delivery due to her severe acidosis. Bicarbonate containing maintenance fluids were not utilized; however, a total of seven ampules of bicarbonate were administered to the patient throughout her hospitalization to attempt to stabilize the fetus, though bicarbonate containing drips were never initiated. The obstetrics team at this time consulted the medical intensive care unit (MICU) for assistance with further management. At this time, the MICU team consulted endocrinology for assistance with management. The patient's fluids were changed to a 10% dextrose containing fluids at 250 mL/h with the goal of intensifying the insulin infusion to correct the ketoacidosis. Despite this, however, the patient's respiratory status declined to the point of requiring intubation and mechanical ventilation. Approximately eight hours after admission, the fetal heart rate became difficult to detect, and intrauterine fetal demise was declared.
Despite fetal demise, the patient's insulin requirements were still larger than expected at 7 units/h. Endocrinology believed that this was secondary to the placental hormones still in the patient's circulation causing significant peripheral insulin resistance. It was determined that until delivery occurred, the patient would continue to have significant insulin resistance. As soon as one hour after delivery, the patient's insulin sensitivity rapidly improved, and glucose sequestration by the placental circulation disappeared. Acidosis began to rapidly improve. Her glucose now ranged between 200 mg/dL and 400 mg/dL. Her insulin drip was rapidly weaned to 3 units/h, pH continued to rise to 7.33, and the anion gap closed to 7 (). The patient was extubated on hospital day 2, and was discharged home three days later without any further events.


A 45-year-old gentleman presented to our emergency department with a five-day history of perianal discharge, a three-day history of high-grade fever and a one-day history of acute shortness of breath. The patient revealed that he had felt something protruding around his perianal region and had previously consulted a traditional healer who had prescribed an ointment - the contents of which were not identified. The ointment had provided him no relief.
He had a respiratory rate of 42 breaths/minute, a pulse of 132 beats/minute, blood pressure of 111/50 mmHg and a temperature of 39.5 degrees Celsius. Chest auscultation revealed bilateral equal air entry. The abdomen was firm, distended and non-tender with audible gut sounds. He was drowsy with a Glasgow coma scale (GCS) score of 12/15. Local examination revealed foul smelling, small necrotic patch on his perianal region with purulent discharge (Figure ). The patch was tender and swollen and there was associated erythema extending to the entire perineal region. Suspecting a case of necrotizing fasciitis, the patient was rushed to the operating room for debridement.
During local debridement, necrotic foul-smelling pus was found throughout the ischiorectal fossae bilaterally and was communicating between the retropubic spaces (Figure ). It was also involving the retroperitoneal spaces on both sides. A midline laparotomy was also performed with thorough irrigation, along with bilateral flank incisions and drainage of pus. A diverting colostomy was attempted, however, there was continuous drainage of pus from the abdominal cavity. A relook debridement procedure was performed 24 hours later to remove any further necrotic tissue, irrigate the involved areas and remove any remaining pus. The rectus sheath was closed and a transverse loop colostomy was formed. A final debridement of the perineal wound was carried out nine days later with a washout of the abdominal cavities and spaces with peroxide.
The patient was transferred to the surgical intensive care unit (SICU) where he remained intubated for the next three days. The patient was administered meropenem, vancomycin, and clindamycin during the procedure and afterward in the SICU as well to address ongoing sepsis. For pain control morphine was administered for the first two days then switched to tramadol.
After the first two days in the SICU, renal function started deteriorating and a diagnosis of acute kidney injury secondary to sepsis was made. He was started on hemodialysis and vasopressor support. The patient remained in the SICU for 15 days and after successful reduction of creatinine to near baseline values, the patient was discharged after a total hospital stay of 25 days.