A 40-year-old obese African American female was brought in an unconscious state to the emergency department (ED) of Allegheny General Hospital, USA, in August 2017. Patient was received at her home in a cardiac arrest state by the emergency medical services (EMS) which prompted them to do CPR (cardiopulmonary resuscitation) on her.
With 35 minutes of CPR, spontaneous circulation was restored and then she was transferred to the hospital. On presentation, she was hypotensive, intubated, nonresponsive to noxious stimuli and had minimally reactive pupils. On further inquiry, it was found out that the patient had been ingesting Epsom salt for quite some time, apparently, to lose weight (and might have had over-ambitiously taken a large dose that day). Patient did not have any history of drug abuse or any findings suggestive of physical trauma. Differential diagnosis of acute coronary syndrome) (ACS), stroke and toxic ingestion of magnesium sulfate was contemplated. Initial blood work up revealed hypermagnesemia (9.7 mg/dL), lactic acidosis (AG metabolic acidosis), mild elevation of liver enzymes and negative urinary drug screen. 12 Lead ECG ruled out possibility of ACS, and a normal sinus rhythm with a prolonged QT (non-diagnostic for ischemia) was noted. The patient was then transferred to the ED of our hospital.
Her glasgow coma scale (GCS)at the time of presentation was 3 and ECG revealed normal sinus rhythm with first degree atrioventricular (AV) block (PR interval=220 milliseconds), QRS interval of 120 milliseconds and nonspecific intraventricular block. Brain CT scan was unremarkable for any acute intracranial process and it effectively ruled out the possibility of stroke. Despite high blood magnesium level, nephrology and poison control team initially recommended only supportive therapy without any need for dialysis as serum creatinine (0.9 mg/dL) was normal. Her urinary output was consistently normal (between 1350-1600 milliliters per day) throughout. Later, the decision was taken to dialyze the patient despite normal renal functions (creatinine=1.1 mg/dL, BUN= 17 mg/dL) because of the severity of the signs and symptoms and continuous increase of serum magnesium level in the presence of ongoing supportive therapy. The patient was then transferred to the medical intensive care unit (MICU) and it turned out that dialysis effectively lowered the serum Mg level. However, she still remained encephalopathic. Neurological assessment demonstrated bilaterally reactive pupils and extensor posturing on painful stimuli. Brain magnetic resonance imaging (MRI)findings were consistent with hypoxic-ischemic injury, possibly because of prolonged cardiac arrest, and electroencephalography (EEG) recording was also suggestive of severe cortical injury with a minimal response to pain. Meaningful recovery of the brain functions was deemed unlikely based on the clinical status of the patient, the findings of MRI and that of EEG. The family was informed about the poor prognosis of the patient and the decision was made to provide comfort measures only. Unfortunately, patient expired on the 6th post-admission day.


The patient was a 12-year-old female for whom a diagnosis of R(20) was made in a context of refractory epilepsy with learning disorders.
The diagnosis was confirmed by karyotype at the Department of Clinical Genetics of Rouen University Hospital, Rouen, France, when she was 9 years old. Breakpoints (p13 and q13.3) were confirmed by FISH analysis. Overall, 20% of analyzed cells were found to be R(20). No deletion was found in the subtelomeric regions of chromosome 20 for both short and long arms.
No complications were reported during her mother's pregnancy and delivery. She was eutrophic at birth (weight = 3400 g; height = 50.5 cm; cranial perimeter = 35 cm). APGAR score was 10/10. Regarding psychomotor development, no delays were found during her first years of life.
Learning disorders began in primary school, with reading difficulties. In this context, she was evaluated with standard metric test and prescribed speech rehabilitation. This initial evaluation found attention and memory disabilities with a speech delay. First epileptic seizures appeared at 6 years old.
At the age of 10 years, our patient had a complete neuropsychological evaluation. The Test of Everyday Attention for Children found a deficit in executive function with distractibility, fatigability, and psychological slowness. The Wechsler Intelligence Scale for Children (WISC—IV) was homogeneous without intellectual disability (Verbal Comprehension Index = 79; Perceptual Reasoning Index = 90; Working Memory Index = 88; Processing Speed Index = 96; Full Scale IQ = 83).
Cardiological assessment found a prolapse of the mitral valve without any clinical impact.
At twelve years old, the patient presented a nonconvulsive status epilepticus with altered consciousness and no recovery period for about 1 month. Concomitantly, parents reported an acute change in her behavior. Her antiepileptic treatment was adapted with phenobarbital 60 mg/d, oxcarbazepine 900 mg/d, sodium valproate 1 g/d, hydroxyzine 25 mg/d, and amitriptyline 12 mg/d. EEG showed alternative records switching between normal trace periods and mainly bifrontal slow bursts with spikes and waves and slow rhythmic bursts. This phenotype was associated with major behavioral symptoms including aggressiveness, self-injury, and sleep disorder. Cerebral MRI found an asymptomatic pineal cyst but no other abnormalities were reported.
Therefore, the patient was hospitalized in our child and adolescent psychiatric unit. Clinical examination found severe psychomotor symptoms including negativism, ambitendency, motor and verbal perseverations, aggressiveness, irritability, and impulsivity. Disinhibition was observed with very foul language, sexual behaviors toward even young peers, and disobedience of rules. Frequent visual hallucinations were reported by the patient and retrospectively confirmed by parents. These hallucinations occurred especially in conditions of low luminosity and were attributed to status epilepticus.
During the first weeks of hospitalization, we observed rapid fluctuations in mood and behavior with oscillations between “depressive-like” (irritability, aggressiveness, sadness and lethargy) and “manic-like” symptoms (disinhibition, psychomotor agitation, hyperactivity). The intensity of symptoms was evaluated weekly by a senior physician (VF) using the Aberrant Behavior Checklist (ABC).
Regarding psychiatric features fulfilling the diagnosis criteria for bipolar disorder not otherwise specified (BP-NOS) (considering the short duration of both depressive and manic symptoms and rapid fluctuations in mood features), and the risk of modifying the epileptic threshold with other therapeutic options as antipsychotics, we decided to challenge this patient with lithium. We introduced lithium 400 mg extended-release (ER) 2 weeks after her admission. The therapeutic dose (0.8-1.2 mEq/L) was obtained with lithium 1 g/d ER after 6 weeks.
We observed a drastic clinical improvement especially for impulsivity, irritability, and aggressiveness. ABC subscores were reduced by 30 points for hyperactivity, 25 points for irritability, and 16 points for lethargy between week 1 and week 14 (Figure ), in line with the classical time frame for action of lithium.
Moreover, the average number of seizures per week decreased significantly. Initially, about two to three seizures were observed each day. After 6 weeks, some days were free of seizures, and finally, there was no seizure at all during the last week (Figure ). However, some oppositional features remained.
Four months after the patient's discharge, monthly follow-up showed sustained improvement on both epileptic seizure (less than one seizure per week) and mood disorder.
No adverse event concerning lithium was reported, either during hospitalization, or during follow-up since the end of hospitalization.
This case brings into questions the pathophysiology of neuropsychiatric symptoms in R(20). We found rationale to justify the interest of lithium in R(20) behavioral and epileptic mechanisms.


A 76-year-old Caucasian female with a past medical history of chronic obstructive pulmonary disease (COPD), hypertension, and osteoarthritis had developed a COPD exacerbation requiring steroids and antibiotics. Her primary care physician ordered a chest X-ray (CXR) due to persistent cough and abnormal breath sounds on physical exam. The CXR revealed a moderate-sized infiltrate in the inferior portion of lingular segment which likely represented a pneumonic infiltrate. She was treated with a 10-day course of antibiotics. Repeat chest X-ray revealed minimal clearing of parenchymal infiltrate from the lingular segment. A subsequent computed tomography (CT) scan of the chest showed evidence of residual infiltrative changes involving the right middle lobe as well as the lingular division of the left upper lobe. There was also evidence of diffuse low-attenuation density involving the mediastinum highly suggestive of diffuse adenopathy which was concerning for lymphoma.
At initial consultation by oncology, her vital signs were stable, and she denied B symptoms including fevers, night sweats, and weight loss. She denied any hemoptysis or worsening shortness of breath. Physical exam was unremarkable with no palpable cervical, axillary, or inguinal adenopathy or hepatosplenomegaly, and respiratory exam was clear to auscultation bilaterally. CBC with differential showed a white blood cell count of 4.4 × 10 mm3 with an absolute lymphocyte count of 0.66 × 10 mm3, hemoglobin of 13.7 gm/dL, and platelet count of 178 × 10 mm3. She had an unremarkable complete metabolic panel (CMP) and mildly elevated lactate dehydrogenase (LDH) at 235. Due to concern for lymphoma and findings on CT of the chest, a PET/CT was ordered which showed an infiltrative mass in the mediastinum with diffuse uptake (maximum standardized uptake value (SUV) 5.94 ().
There were small lymph nodes in the left axilla showing low level uptake with maximum SUV 1.73 and 1.52, respectively. Finally, there was a hypermetabolic mass within the left iliac bone with a maximum SUV 11.71 ().
She underwent an endobronchial ultrasound and transbronchial biopsy of station 7 lymph node which revealed lymphoid tissue composed of small, mitotically inactive cells with round to slightly irregular nuclear contours and scant cytoplasm ().
Flow cytometric analysis demonstrated an abnormal CD5+ B cell population. Immunohistochemical stains showed that the cells were positive for CD20 () and CD5 () and negative for Cyclin D1 ().
Scattered CD3 positive T cells were also present. The morphology and phenotype supported the diagnosis of small lymphocytic leukemia (SLL). Since SLL does not typically present with bone lesions and there was concern for another primary cancer, a CT-guided biopsy was performed of the PET avid left iliac bone. Pathology from that biopsy showed both bone and marrow with involvement of CLL/SLL ().
Flow cytometry from the left iliac bone biopsy revealed monoclonal kappa light chain restricted B-cell population phenotypically consistent with CLL/SLL ().
No specific abnormalities were detected by CLL fluorescence in situ hybridization (FISH) including centromere 12, 13q14 (DLEU1), ATM/11q, TP53/17p13, and CCNDQ/IGH–t(11; 14).
Currently, she does not have cytopenias, B symptoms, or bulky disease; however, there was concern that the mediastinal adenopathy may be contributing to her pulmonary symptoms and that the left hip lesion was causing discomfort. Consequently, systemic therapy was offered as was radiation to the hip; however, the patient declined and opted for observation and close surveillance. She will return for further evaluation of symptoms and laboratory data in 2 months.


A 28-year-old man was brought to our emergency department with severe right hip pain with deformity following a high-velocity motor vehicle accident due to the collision of his car with a truck. He was conscious with Glasgow Coma Scale 15 with stable vital parameters. After an initial assessment of the patient, according to the Advanced Trauma Life Support protocol, a secondary survey revealed his right hip in an abducted and externally rotated position with shortening of the right lower limb. On further examination, the femoral head was palpable in the ipsilateral inguinal region. There was no external bleeding wound and no associated distal neurovascular deficit.
The routine imaging investigations and examination ruled out any head, cervical, thoracic or abdominal injury. Plain radiograph of the pelvis with both hips revealed a pubic-type anterior dislocation of the right hip with ipsilateral greater trochanter fracture. A computed tomography (CT) scan of right hip was also ordered to look for any associated acetabular fracture, intra-articular fragment, occult femur neck or intertrochanteric fracture; it ruled out any associated injury and confirmed anterior hip dislocation with ipsilateral greater trochanter fracture (Figure ).
We performed a closed reduction of the dislocation under sedation within two hours of the accident in the emergency department. The patient was positioned supine and the reduction involved the collective effort of four persons; the pelvis was stabilized by one resident, another person pushed the femoral head into the acetabulum by direct palm pressure while the other two gave continuous axial traction in the extended position followed by flexion and internal rotation. A snap sound suggesting relocation of the femoral head followed this reduction maneuver. The post-reduction plain radiograph of the pelvis showed a congruent reduction of the hip joint along with a displaced fracture of the greater trochanter. Subsequently, open reduction and internal fixation were planned for the fracture in the elective theatre the next day. Under C-arm guidance in the left lateral position, the fracture was reduced and two 6.5 mm partially threaded cannulated cancellous screws were inserted through a mini-incision under spinal anaesthesia (Figure ).
The postoperative period was unremarkable and the patient was kept non-weight bearing on the affected limb for two weeks followed by partial-weight bearing over the next two weeks. The patient was allowed full-weight bearing after one month. At the last follow-up of one year, the patient was asymptomatic with a full range of active and passive right hip joint motion. There was no evidence of hip osteoarthritis or osteonecrosis of the femoral head.


A 71-year-old female presented to an ear, nose and throat specialist in November 2014 complaining of obstructive dysphagia for 4 months, without pain. She did not report haemoptysis or other clinical signs or symptoms.
During the clinical examination, the physician found a bulky mass localized to the left tonsillar bed, without the presence of mucosal ulceration. There was no clinical evidence of any pathological cervical lymph nodes. A maxillofacial CT scan and MRI were then scheduled.


A 72-year-old male with a long-standing history of polyostotic fibrous dysplasia presented with chest and back pain and was evaluated with a 99mTc-methylene diphosphonate (MDP) bone scan, which revealed intense uptake in several right facial bones, including the frontal, zygomatic and nasal bones, maxilla and the mandible. There was also intense uptake involving the right ribcage (). The patient was referred for 18F-fludeoxyglucose (FDG) positron emission tomography (PET)/CT imaging to evaluate for possible malignant transformation. Maximum intensity projection images showed intense heterogeneous 18F-FDG uptake in the bones of the right face and right hemithorax (). The 18F-FDG uptake in the facial bones was variable, with the maximum standardized uptake value (SUVmax) ranging from 2.1 to a maximum of 5.4 in the right maxillary bone. The right hemithorax lesions appeared to arise from the right eighth and ninth ribs, with involvement of the T7 vertebra, which was collapsed. The SUVmax in the right hemithorax lesions ranged from 4.0 to 7.5 (). Mildly FDG-avid lesions were also noted in T4 (SUV 3.1), left lateral tenth rib (SUV 2.2) and left sacral wing (SUV 2.4). The heterogeneous nature of 18F-FDG uptake and the wide range of SUVmax values raised concern of malignant transformation (or sarcomatous degeneration), and follow-up with a CT scan was recommended. Subsequent 8 years of follow-up with CT scans () did not reveal the development of any aggressive bone lesions, and the patient remains clinically stable with no evidence of malignant transformation.


Patient 1 was a 4-year-old male. The onset of the disease was 20 months before the transplantation. He presented with symmetrical proximal muscle weakness, dyspnea, dysphagia and dysphonia. On physical examination, his muscle strength was as following: right lower extremity proximal 1–2/5, distal 3/5; left lower extremity proximal 3/5, distal 4/5; upper extremities proximal 3/5, distal 4/5. He had positive Gottron’s sign and heliotrope rash. His laboratory results showed: CK 1200 U/L (0–195 U/L); negative antinuclear antibody (ANA). Electromyogram (EMG) showed myogenic damage. Muscle MRI showed diffuse muscle involvement of proximal legs. HRCT showed mild pulmonary interstitial disease. A left quadriceps biopsy showed extensive muscle atrophy, focal necrosis, small vessel wall degeneration and thickening, fibrous thrombosis, and fatty tissue hyperplasia. Initially we gave him intravenous immunoglobulin (IVIG) (2.0 g/kg per month for 3 months), cyclophosphamide (CTX) (1 g/m2 body surface area monthly intravenously for 6 months), and high-dose methylprednisolone (MP) (20 mg/kg per day for 3 days) followed with prednisone 2 mg/kg daily. After 6 months of treatment, his rash, expiratory dyspnea, dysphagia and dysphonia improved, but muscle weakness remained. Therefore, we recommended AHSCT and he received the transplantation in June 2005.


Patient 2 was a 7-year-old girl. The onset of the disease was 31 months before AHSCT. Her symptoms included fever, muscle weakness, dysphonia, dyspnea and dysphagia. On physical examination, her muscle power was as following: right lower extremities proximal 2/5, distal 4/5; upper extremities proximal 3/5, distal 3/5. Gottron’s sign is positive. Her laboratory results showed serum CK 500 U/L (0–195 U/L) and negative ANA. EMG showed myogenic damage. Muscle MRI showed diffuse muscle enhancement of proximal legs and limbs. HRCT showed severe pulmonary parenchyma and interstitial disease. A right quadriceps biopsy showed denatured, broken and dissolved muscle, along with focal chronic inflammatory cells and positive Masson staining. We intubated her and placed her on a ventilator, and simultaneously gave her IVIG (2.0 g/kg per month•3 months), CTX (1 g/m2 body surface area intravenously monthly for 6 months), high-dose MP (20 mg/kg daily for 5 days) and followed by prednisone 2 mg/kg daily. Two weeks later, her dyspnea improved, and tracheal intubation was removed. One month later, her dysphagia and dysphonia improved. But the improvement of muscle weakness and rash was not obvious. So we gave her methotrexate (MTX) 15 mg/ m2 body surface area and cyclosporine A (CsA). Nine months after the initial treatment, her muscle weakness and rash were not improved. Therefore, we recommended AHCST and she received the transplant in January 2008.


Patient 3 was a two and half years old female. The onset of JDM was 6 months before the transplant. She presented with muscle weakness and dysphagia. On physical examination, her muscle strength was as following: lower extremities proximal 2/5, distal 3/5; upper extremities proximal 2/5, distal 3/5. Gottron’s sign was positive. Her laboratory tests showed high serum CK 2569 U/L (normal: 0–195 U/L) and negative antinuclear antibody. EMG showed myogenic damage. Muscle MRI showed diffuse muscle involvement of proximal legs. HRCT showed spot shadow in left lung, and focal interlobular septal thickening. Parents refused muscle biopsy. Initially, we gave her IVIG (2.0 g/kg per month•3 months), CTX (1 g/m2 body surface area intravenously monthly for 5 months), high-dose MP (20 mg/kg daily • 5 days), followed by prednisone 2 mg/kg daily. After 5 months of treatment, her rash and dysphagia improved, but muscle weakness remained the same. Therefore, we recommended AHCST, and the girl received the transplant in July 2015.
Three to eight days after the AHSCT, the leukocyte and lymphocyte levels of all 3 patients decreased to the lowest level (0.01 × 109/L). The platelets decreased to 5–10 × 109/L. Haemoglobin (HGB) decreased to 30–60 g/L. 10 to 14 days after AHSCT, the neutrophils increased to more than 1.0 × 109/L. 14 to 16 days after the AHSCT, the platelets came back to 20 × 109/L. Those results indicated that AHSCT for all three patients were succeeded.
The immunological function was obviously inhibited after the auto-PBHSCT (Fig. ). The number of CD4 and CD8 cells remained low within 3 months after the transplantation. 6 months later, the number of CD4+ and CD8+ cells returned to normal.
In the first 6 months after AHSCT, muscle weakness and rash improved slowly for all three patients. However, after 6 months, the improvement was much faster. About 12 months later, all of their monitoring indexes, including immunological function, CK, AST, height, weight and academic record in their class ranking, returned to normal without taking any medication. They remained stable without relapse till this article was written.


A 6-month-old female infant (6000 g; 3rd percentile) with an unremarkable medical history was transferred to our pediatric ward because of postprandial vomiting for 5 days. On clinical examination, she was subfebrile (38°C) and had a distended but soft abdomen. No mass was palpable. Abdominal ultrasound suggested the possibility of intussusception. As an enema to reduce intussusception was no therapeutic option at our center, the abdomen was surgically explored. On laparotomy, blood-stained but clear ascites was found as well as intestinal adhesions. Moreover, we saw diffuse granulations, mesenteric lymphadenopathy, and ischemia of the terminal ileum (
and
). Peritoneal cultures were harvested, appendectomy was performed, and the intestinal lymph nodes were biopsied. Postoperatively, tuberculin intradermal reaction (IDRt) was positive at 9 mm and cultures grew tuberculous contagium. The Anti-TB treatment administered was: rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) for 2 months, then RH the following 4 months. This regimen was applied before receiving the biopsy results which showed tuberculoid follicular lesions (
and
). The patient was declared cured after this treatment. She had no abdominal symptoms after 2 years of follow-up.


An 8-month-old (7000 g; 3rd percentile) boy from Mauritania with no particular pathological history was transferred from a health center near the Senegal–Mauritanian border for the management of peritonitis. The clinical picture had evolved for 15 days, with the appearance of abdominal bloating associated with vomiting and cessation of bowel movements. On clinical examination, he had a temperature of 38°C, and was tachycardic at 148 beats per minute. He showed nutritional edema and flank dullness. His abdomen was distended and had peritonitis on palpation. Therefore, the boy was taken to the operating room. Surgical exploration revealed clear ascites associated with small intestinal granulations and adhesions. We performed adhesiolysis, biopsies, and drainage of the peritoneal cavity. Postoperatively, GeneXpert tests were performed on the peritoneal fluid and the IDRt was negative. Anatomopathological examination of the operative specimens revealed the presence of caseous necrosis compatible with peritoneal TB. The medical treatment and the evolution were identical to Case 1.


A 34-day-old female infant, weighing 2.3 kg, was admitted to our institute with severe respiratory distress. Physical examination demonstrated severe tachypnea (respiratory rate = 35-40/min), sweating during breastfeeding, peripheral cyanosis, and indrawing of the chest cavity with inspiration. Chest X-ray revealed only cardiomegaly (). Transthoracic echocardiography showed massive pericardial effusion with a space-occupying mass lesion, 5 × 4 cm in size, in the pericardial cavity on the right side. Based on the infant’s clinical condition and the echocardiographic findings, she was scheduled for emergency tumor removal.
The preoperative heart rate was between 130 and 140 bpm. The peripheral capillary oxygen saturation (SpO2) before induction was 88% and after the administration of 100% oxygen with a mask, SpO2 rose to 94%. Considering the infant’s age, severe respiratory distress, and cardiovascular instability, we performed awake-sedate intubation after the administration of 5 μg of fentanyl and topicalization of the tongue, larynx, and vocal cords with 15 mg of 1.0% lidocaine and a 3.0-mm Portex tracheal tube. Subsequently, the general anesthesia was maintained with a mixture of oxygen/air, isoflurane, 1-mg increments of atracurium, and 5 μg of fentanyl intermittently. Thereafter, an arterial line and a central venous line were established. Other monitoring modalities such as the bispectral index (BIS), capnograph, and pulse oximetry were utilized as well. Extracorporeal circulation was on standby. Via a median sternotomy with the preservation of the thymus gland, the pericardium was opened and a large quantity of cloudy yellow fluid was aspirated. A multicystic lesion, around 50 × 45 × 30 mm in size, was revealed. It covered most of the right ventricle and pressed on the right atrium ( and ). Furthermore, the mass was polycystic and attached to the right anterior wall of the ascending aorta. The whole tumor was successfully removed. The patient was extubated in the intensive care unit on the first postoperative day and was discharged from the hospital on the fifth postoperative day.
Histologically, it was a mature teratoma with the representation of all 3 germinal layers: endoderm 50%, mesoderm 25%, and ectoderm 25%.


A 55-year-old Thai man presented with dyspnea for 1 day. The patient had a history of odynophagia and dysphagia for a week. He had a history of poor oral hygiene. On physical examination, he had low-grade fever (38°C), dyspnea, and marked swelling of the base of tongue (BOT) with partial occlusion of the oropharyngeal airway. Complete blood count (CBC) showed his white blood cell (WBC) count was 9300/mm3 with predominant neutrophil. Orobuccal computed tomography (CT) scan revealed the large abscess at the BOT. Tracheostomy and surgical drainage were performed. Streptococcus viridians was identified from pus culture. Amoxicillin-clavulanic acid 1.2 g 8 hourly plus ceftriaxone 2 g once daily were administrated for 2 weeks with an excellent outcome. The patient could be decannulated after the sixth day of treatment with airway patency.


A 52-year-old Thai man presented with a painful tongue and odynophagia for 7 days. The patient had a history of well-controlled diabetes mellitus (DM). He denied either trauma or infection at orobuccolingual regions. Also, the patient had poor oral hygiene. Physical examination showed the patient was afebrile (36.6°C). The antero-lateral aspect of the tongue was swollen and fluctuation. The airway was patent. CBC showed WBC was 4500/mm3 with neutrophilic predominance. Surgical drainage was performed under local anaesthesia. The pus culture did not show any organisms. Empirical antibiotics with amoxicillin-clavulanic acid 1.2 g 8 hourly and ceftriaxone 2 g once daily were administrated for 10 days, and the outcome was good.


A 52-year-old Thai woman reported having odynophagia and dysphagia for 1 week. She took amoxicillin for 5 days without signs of improvement. Her symptoms worsened, as did limitation of her tongue movement. She denied local trauma of orobuccolingual regions. Examination showed that her floor of mouth (FOM) and BOT were swollen without airway obstruction. She was afebrile (36.6°C), but her WBC was 14500/mm3. Contrast-enhanced CT scan demonstrated an abscess at the sublingual space and BOT. The pus was drained with the patient under general anaesthesia. The organism was identified as Acinetobacter lwoffii. Clindamycin 600 mg 8 hourly and ceftriaxone 2 g once daily were prescribed for 2 weeks, with good clinical response.


A 46-year-old Thai woman with poorly controlled DM presented to the emergency department with dyspnea for 1 day. She had odynophagia and dysphagia for 4 days. She denied a history of trauma at orobuccolingual regions. On physical examination, her body temperature was 37.5°C. Limitation of tongue movement and swelling of the tongue and FOM were observed. The oropharyngeal airway was partially obstructed. Contrast-enhanced CT scan showed the abscess confined to the ventral aspect of the tongue with sublingual space cellulitis (). CBC showed WBC was 12,100/mm3 with neutrophilic predominance. The patient underwent tracheostomy and surgical drainage under general anaesthesia. The tracheostomy tube was safety removed 5 days after the operation. Beta-haemolytic non-group A, B, D Streptococcus Spp. was identified; then, clindamycin 600 mg 8 hourly and ceftriaxone 2 g once daily were administrated intravenously, and all symptoms were completely resolved 2 weeks after initiation of treatment.


A 58-year-old Thai male was admitted due to pain in the BOT with referred pain to the ear for 1 week. He had poor oral hygiene. He took amoxicillin for 5 days without clinical improvement. On physical examination, he was afebrile (37.3°C). Pain was detected at the left side of BOT just behind the circumvallate papillae with marked fluctuation. The other orobuccal regions were normal without evidence of airway obstruction. CBC showed WBC was 5500/mm3. Contrast-enhanced CT scan demonstrated an abscess at the left posterior tongue (). In addition, an incidental thyroglossal duct cyst was identified without sign of infection (). The patient underwent surgical drainage under general anaesthesia. Streptococcus viridans was identified. Amoxicillin-clavulanic acid 1.2 g 8 hourly and ceftriaxone 2 g once daily were prescribed for 2 weeks, with an excellent outcome.


A 59-year-old Thai woman reported having mass within her tongue for 10 days. She had mild degree of pain and took amoxicillin-clavulanic acid for 7 days. Her tongue's mass was still the same size while the pain was resolved. Her oral hygiene was good with no active dental and periodontal conditions. Physical examination showed the patient was afebrile (37°C). The firm mass within the antero-midline of the tongue of about 1.5∗1.5 cms in size was palpated without any sign of inflammation. CBC showed WBC was 5800/mm3 with neutrophilic predominance. The patient was informed about the treatment option and she decided to remove the mass under general anaesthesia. Intraoperative finding showed well circumscribed loculated abscess and the pus was drainage. Pathologic report for surrounding tissue was acute and chronic inflammation with abscess formation. The pus culture did not show any organisms. Empirical antibiotic with amoxicillin-clavulanic acid 1.2 g 8 hourly was administrated for 1 week, and the outcome was good.
All patients' demographic data are described in , and the details of investigation, treatment and clinical outcome are shown in .


We here report a case of an 85-year-old male who was apparently well 15 days back, when he started developing swelling of bilateral feet. The patient also complained of decreased urine output with poor urinary stream. The patient has a history of breathlessness, more so on exertion. The patient is an ex-smoker and has a history of loss of appetite and loss of weight since 1-2 months. Also, there is a history of anemia in the past with a recorded haemoglobin (Hb) level of 78 g/l. The patient's clinical examination showed multiple, nontender firm lymph nodes in the right upper jugular, middle jugular, right and left submandibular, and multiple right-sided axillary lymph nodes. His complete blood count parameters were as follows: Hb, 58 g/l; platelet count, 63 × 109/l; and total leukocyte count (TLC), 230 × 109/l. Differential counts on peripheral blood smear (PBS) were as follows: blasts, 30%; promonocytes, 5%; monocytes, 5%; neutrophils, 3%; and lymphocytes, 57%. Lymphocytes appeared mature with many smudge cells. Clinical and laboratory features of the patient were consistent with tumor lysis syndrome (TLS). Laboratory parameters supporting TLS were as follows: uric acid, 11.5 mg/dl; calcium, 7.7 mg/dl; phosphorus, 4.8 mg/dl; potassium, 4.2 meq/L;and serum creatinine, 2.42 mg/dl.
Bone marrow examination showed markedly hypercellular smears with reduced megakaryocytes and erythropoiesis. Bone marrow differential counts are summarized in . Bone marrow biopsy was markedly hypercellular with sheets of immature cells with abundant cytoplasm (monocytic look) replacing normal hematopoietic elements. In addition, there were interstitial increase and intertrabecular small to large collections of mature lymphocytes. Representative pictures of peripheral blood and bone marrow findings are compiled in .
PBS and bone marrow aspirate lymphocytosis made us to suspect a dual disorder, and we put a combined flowcytometry panel for acute leukemia and chronic lymphoproliferative disorder. Gating was done on CD45 versus the side scatter plot. The gating plot revealed two different populations, CD45 positive with moderate side scatter (Population 1-monoblasts) and CD45 positive with low side scatter (Population 2-lymphocytes). Population 1 showed monocytic markers with negative MPO, B-lineage, and T-lineage markers. Population 2 was positive for CD19 and showed dual positivity for CD5 and CD23. Overall immunophenotyping features were consistent with acute leukemia with monocytic differentiation and chronic lymphocytic leukemia. Immunophenotyping features are compiled in and .
The patient was explained about treatment options and prognosis, and he refused to undergo any further investigations and therapy.


A 69-year-old male was referred to Cardiovascular Center Oberallgäu-Kempten with ST segment elevation myocardial infarction (STEMI). Typical symptoms of chest pain started at 10.00 p.m. The hemodynamically stable patient was admitted to the hospital at 1.30 a.m. the next day. Medical history revealed adenocarcinoma of the medial rectum (pT1, pN0 (0/14), L0, V0, R0, GII, cM0 (UICC I)) with anterior rectum resection in 2014 and complete remission. Furthermore, the patient suffered from chronic kidney disease, stage 3.
ECG showed anterior wall myocardial infarction (). The patient was immediately transferred to the cardiac catheterization laboratory and received successful emergency angioplasty/drug-eluting- (DE) stenting of the subtotally occluded left anterior descending artery (). Transthoracic echocardiography showed left ventricular hypertrophy, moderately reduced systolic left ventricular function (LVEF 40%) with anterior, septal, anteroseptal, inferior-apical, and apical hypo- and akinesia. The hemodynamically stable patient was monitored at the chest pain unit. CRP apheresis [] using the CRP adsorber (PentraSorb® CRP) within C-reactive Protein Apheresis in Acute Myocardial Infarction (CAMI-1) trial [] was performed 34 h and 58 h after the onset of symptoms. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Plasma CRP levels declined from 28.77 mg/l to 12.58 mg/l during the first apheresis session and from 24.17 mg/l to 11.55 mg/l during the second session, respectively (Figures and ). also shows cardiac enzyme progress over 72 h. Elevated creatinine kinase (CK), CK-MB, and troponin levels at admission documented acute STEMI. CRP levels, however, were normal at admission and, as a result of myocardial necrosis, increased with time []. CRP apheresis efficiently counteracted acute phase CRP elevation and reduced peak CRP plasma levels.
The patient tolerated apheresis with no clinically relevant symptoms. No side effects were observed, especially signs of infection. The patient was, on his own request, discharged in a good general condition, on day 5 after the onset of symptoms.


A 70-year-old man was referred to the S. Anna University Hospital in Ferrara (Italy) for a left upper quadrant abdominal mass incidentally discovered on a contrast-enhanced CT of the chest performed to investigate a 15-mm right pulmonary nodule.
The patient was asymptomatic, his past medical history was positive for essential hypertension, and physical examination was unremarkable.
CT scan showed a homogeneous 83-mm left adrenal lesion with an average density of 45 HU; rare peripheral dot-like calcifications were also observed (Fig. ). The right adrenal gland was normal. Due to high-density values of the left adrenal lesion excluding classic low-density adrenal adenoma, an abdominal magnetic resonance imaging (MRI) examination was subsequently performed. MRI with chemical shift imaging showed absence of signal intensity decrease in out-of-phase compared with in-phase images, restriction of intralesional molecular water diffusion in Diffusion Weighted Imaging (Fig. ) with high-intensity intralesional areas both in T1 and in T2 and T2 fat-saturated weighted images suggesting areas of intralesional subacute hemorrhage (Fig. ). After intravenous contrast medium administration of gadoteric acid (DOTAREM©, GUERBET S.p.A., Genova, Italy) at 0.1 mmol/kg, a thin capsular rim of early enhancement with slow heterogeneous centripetal enhancement was observed (Fig. , ).
Biochemical tests ruled out any endocrine dysfunction (plasma renin 20,5 μU/ml, plasma aldosterone 7,6 ng/dl, urinary adrenaline 4.59 μg /24 h; urinary noradrenaline 43.35 pg/24 h, urinary metanephrine 120.75 μg/24 h, urine normetanephrine 250.25 μg/24 h). A subsequent iodine 123 metaiodobenzylguanidine whole body scintiscan single-photon emission computed tomography-CT (I123-MIBG-SPECT-CT) ruled out the presence of a pheocromocitoma.
Due to the non-specific radiological findings and the size of the lesion, a surgical resection was then elected to establish the final diagnosis. The patient underwent a left adrenalectomy trough a left subcostal incision. Intraoperatively, the mass appeared encapsulated and hypervascularised. No evidence of hepatic as well as other peritoneal lesions was present. The operation was straightforward and the postoperative course was uneventful, with the patient discharged home on postoperative day six.
The pathological examination revealed a large lesion of 90 mm × 65 mm × 70 mm with spongy appearance due to large vascular spaces. Histologically, the lesion showed a conglomerate of widely open vascular lumina lined by endothelial cells and separated by thick nearly acellular fibrous septa (Fig. ). The final diagnosis of cavernous hemangioma was then made.
A portion of the tissues was obtained at time of surgery and a primary culture was obtained, as described previously []. Cells were then incubated without or with 5 μM mitotane (an adrenolitic drug), 50 nM doxorubicin (a cytotoxic drug) or with 1–10 μM sunitinib (a VEGF inhibitor) and cell viability was assessed after 48 h, as previously described []. As shown in Figure , doxorubicin (− 18%; p < 0.05 vs. control), but not mitotane, was capable of reducing primary culture cell viability. Similarly, sunitinib significantly reduced cell viability both at 1 and at 10 μM (− 16% and − 27%, respectively; p < 0.01 vs. control).
At 53-month follow-up the patient is doing well and has no evidence of recurrence. However, he underwent a laparoscopic prosthetic repair of incisional, umbilical and left inguinal hernias 20 months following the adrenalectomy.


A 67-year-old male with a history of chronic kidney disease (CKD) stage 2 with a baseline creatinine of 1.25 mg/dl, hypertension, diabetes, and coronary artery disease, presented to us with difficulty urinating for four hours. The patient took a total of 400 mg sildenafil between 2 pm and 6 pm on the day of admission. He had sex at around 7:30 pm. After that, he was having difficulty urinating, with clamminess and intermittent palpitations. He arrived in the emergency department at 11:55 pm. He developed hematuria after Foley catheter placement for urinary retention. Home medication included lisinopril 40 mg daily for hypertension and clopidogrel post stent placement.
At admission, his temperature was 97.5 °F, and his blood pressure was 91/62 mmHg. An examination was remarkable for an absent left testicle due to orchiectomy in childhood. Serum creatinine and blood urea nitrogen (BUN) were 1.94 mg/dl and 16 mg/dl, respectively. Urinalysis revealed albumin 3+. Urine culture was negative. Parathyroid hormone (PTH) was elevated at 304 pg/ml. The calculated fractional excretion of sodium (FeNa) was 1.4%. Ultrasound showed increased echogenicity of bilateral kidneys.
The patient was put on continuous bladder irrigation for hematuria. He received two liters of normal saline bolus in the emergency department upon presentation and was continued on intravenous normal saline at a rate of 100 ml/hr. On the second day of admission, he developed lower extremities edema. Urine output was not calculable because of continuous bladder irrigation. His creatinine was increased from 1.94 mg/dl to 3.60 mg/dl for which intravenous fluid was suspended and one dose of 40 mg intravenous furosemide was administered; however, serum creatinine continued to rise to 4.60 mg/dl and his 24-hour estimated urine output was less than 400 ml, for which nephrology service was consulted and the patient was put on normal saline intravenous infusion at a rate of 50 ml/hr, clopidogrel was discontinued due to persistent hematuria, and bladder irrigation continued. On Day 4, his serum creatinine rose to 5.07 mg/dl, intravenous (IV) fluid was then suspended and intravenous furosemide was increased to 80 mg twice daily. On Day 5, the number dropped to 4.44 mg/dl, and they continued to improve as 3.70 mg/dl on Day 6 and 3.39 mg/dl on Day 7. Peak serum creatinine was recorded at 5.07 mg/dl on Day 4 (Figure ) while blood urea nitrogen (BUN) peaked on Day 6 at 71 mg/dl (Figure ). On Day 8, he was in a polyuric state with a urine output of four liters. A biopsy was not performed since it would not change the management and his kidney function was improved during a short period of time. The patient was discharged with a creatinine at 2.18 mg/dl on Day 11 and he never required dialysis. Based on the clinical scenery, a diagnosis of acute kidney injury due to acute tubular necrosis (ATN) was made. Hypoperfusion of kidneys induced by sildenafil overdose was concluded as the cause of his acute tubular necrosis, even though his blood pressure measured at the emergency department and during hospitalization was within normal limits.


The patient is a 39-year-old Caucasian male with long-standing ESRD who presented for evaluation and exchange of a malfunctioning internal jugular hemodialysis catheter. Notably there was chronic hemodialysis access malfunction due to known SVC stricture with four previous SVC venoplasties performed. The normal anatomic orientation of the cardiac vessels is depicted in Figure for reference.
In this patient, an anomalous small cardiac vein draining directly into the SVC was incidentally discovered during evaluation and exchange of the malfunctioning tunneled hemodialysis catheter. Using manual dissection, the dialysis catheter was withdrawn, and a central venogram was performed to evaluate the proximal venous structures for possible stenosis or occlusion (Figure ).
High grade SVC stenosis was noted near the cavoatrial junction with filling of multiple collateral veins in the vicinity of the heart. Additional venograms were performed to further characterize this unusual anatomy (Figure ).
These subsequent venograms demonstrated two vascular structures which followed the contour of the right heart border (small cardiac vein) and base of the heart (coronary sinus). Additionally, refluxed contrast was seen within the azygos vein, excluding this as a possible explanation for the abnormal vascular filling. The immediate and most pressing concern was a possible arteriovenous fistula involving the right coronary artery and the SVC. Cardiology was consulted and the patient was taken to the cardiology department for coronary arteriogram. Directed angiographic evaluation of the coronary arteries demonstrated no evidence of fistulous communication of the SVC with the coronary arterial system (Figure ).
Delayed views did show contrast enhancement of the previously identified abnormal vessel, confirming an anomalous venous drainage of the right heart. On repeat venogram, the small cardiac vein had direct communication with the superior vena cava and there was early filling of the coronary sinus (Figure ).
Contrast enhancement of the coronary sinus did not occur when the catheter was slightly retracted and additional venogram was performed, likely indicating collateralization from the small cardiac vein. Notably, the small cardiac vein was significantly dilated measuring 3–5 mm, indicating a chronic process with dilation occurring due to worsening stenosis of the superior vena cava.


A 51-year-old woman with no prior underlying disease, presented with four days of fever, myalgia, and vomiting. Previously, she had a history of polydipsia, polyuria, nocturia, and weight loss for one month. She denied tobacco, alcohol, or illicit drug use. There was no family history of diabetes mellitus. On examination, her blood pressure was 115/78 mm Hg, the temperature was 36.6oC, and pulse rate was 96 beats per min. Volume status was mildly dehydrated. Venous plasma glucose was recorded at 467 mg/dL. Wide anion gap metabolic acidosis and high levels of serum beta-hydroxybutyrate were present. A diagnosis of DKA was made based on the above findings. Clinical features and laboratory investigations are summarized in Table . An electrocardiogram showed sinus tachycardia and a chest X-ray showed no abnormalities. She was initially treated with isotonic saline of 1 liter (L) in one hour. Subsequently, intravenous isotonic saline was continuously administered at the rate of 500 mL/hr, along with the repletion of potassium. A bolus of insulin, followed by continuous insulin infusion, was administered.
In addition, the etiology of her acute fever was revealed as dengue infection (laboratory results in Table ). A systemic review found that she currently had vaginal bleeding. DHF was evidenced by hemoconcentration, thrombocytopenia, and hemorrhagic manifestation. After six hours of treatment, she complained of chest discomfort and developed puffy eyelids and mild pitting edema in both legs. Lung examination revealed fine crepitation in both lungs. A chest x-ray revealed bilateral hilar congestion (Figure ). These abnormalities occurred after the administration of 3 L of isotonic saline. After the detection of leakage syndrome, the rate of intravenous fluid was decreased from 140 to 60 mL/hr. Urine output was closely monitored every hour. The fluid management was aimed at a negative balance. The patient’s clinical status gradually improved and repeated chest x-ray demonstrated no sign of fluid leakage (Figure ). Eight hours after being admitted, there was finally a resolution of the DKA in the patient without additional complications. The patient was discharged the fifth day of admission with a premixed insulin injection. At her eight-month follow-up, she was able to discontinue insulin therapy and received a triple combination of oral hypoglycemic agents as long-term therapy.


A 33-year-old Taiwanese man presented to the emergency department with bilateral limb weakness (more severe in the lower limbs than in the upper limbs). The patient's vital status on arrival was as follows: blood pressure, 160/86 mmHg; heartbeat, 96 bpm; and, body temperature, 36.3 °C, with clear consciousness. He denied experiencing recent trauma, back pain, chest pain, abdominal pain, headache or dizziness, or a fever episode. Physical examination showed no specific findings. Neurological examination showed weakness in the muscles of the bilateral upper limbs (muscle power score 4) and of the bilateral lower limbs (muscle power score 3). Muscle weakness was more severe in the proximal site than in the distal site. Blood examination included complete blood count, tests for renal and liver function, measurement of electrolyte levels (including potassium, sodium, and calcium levels), and tests for thyroid function. Blood examination showed normal complete blood count, normal renal and liver function, and normal potassium (3.5 mmol/L, normal range 3.5–5.1 mmol/L), sodium, and calcium levels; however, the examination showed impaired thyroid function (thyroid stimulating hormone: 0.04 uIU/mL, normal range 0.34–5.60 uIU/mL; free T4: 1.96 ng/dL, normal range 0.61–1.12 ng/dL). A 12-lead electrocardiogram showed normal sinus rhythm. Brain computed tomography without contrast showed no obvious intra-cranial lesion. Intravenous potassium infusion (20 mEq/L) with normal saline was prescribed for the patient. After the treatment, he felt a decrease in limb weakness. The clinical diagnosis favored TPP. This diagnosis was based on the clinical condition (bilateral muscle weakness that was more severe in the proximal site than in the distal site), age and race (33 years, Asian), family history (no history of periodic paralysis), blood examination results (hyperthyroid status but no obvious signs or symptoms of hyperthyroidism such as tremors, palpitation, or body weight loss), and imaging findings (brain computed tomography showed no obvious lesion); all these conditions matched the characteristics of TPP. The patient was discharged from our emergency department with a scheduled follow-up in the endocrine outpatient department (follow-up period of approximately 2 months). Methimazole (5 mg 3 times per day orally) was prescribed for controlling hyperthyroidism. He did not have any paralytic attack after discharge from our emergency department. Follow-up blood examination showed the following results: thyroglobulin antibody, <20 IU/mL and microsomal antibody, 36.9 IU/mL. Thyroid ultrasonography performed in the outpatient department showed no obvious mass or goiter.


A 53-year-old man was admitted for mobility of tooth. The dentist suggested the presence of a mass located at the tooth root by physical examination. Computed tomography revealed a well-demarcated radicular cyst of 4 cm in diameter at the tooth base. Carcinomatous infiltration of squamous cell carcinoma was observed in the excisional biopsy of the lesion. In microscopic evaluation, tumoral infiltration revealed features of moderately differentiated squamous cell carcinoma. Malignant cells infiltrated the underlying connective tissue stroma in solid groups and sheets. Numerous neutrophils were present within the cytoplasm of the malignant cells as well as in the surrounding stroma. The internalized neutrophils were intact (). Desmosomal connections were observed between the tumor cells in some areas. The tumor cells showed moderate cellular pleomorphism. The diffuse immunoreactivities of P63 and CK5/6 were determined in the malignant cells by immunohistochemical staining. Additionally, perineural invasion was found, whereas vascular invasion was not observed. Because surgical margin was positive for tumor cells, partial maxillectomy and bilateral neck dissection was performed. Bone infiltration was present. Furthermore, diffuse neutrophilic emperipolesis was observed in cancer cells by microscopic evaluation. Some of the neutrophils in the tumor cells revealed degenerative changes by high-power field (×1000) microscopic evaluation (Figures –), while some neutrophils included apoptotic bodies. Nearly one year later, local relapse developed and additional therapeutic manipulations including surgery, radiotherapy, and chemotherapy (cisplatin) were done. Tumor recurrence occurred in the periparotid and right neck lymph nodes after six months (). Chemotherapy (cisplatin) and radiotherapy were performed for the recurrence. Two more relapses developed in the right neck, left submandibular lymph nodes and in the superficial and deep soft tissues of the neck three months apart. Tumor showed continuity along the surgical margin in the excised biopsy sample and a pericapsular invasion at the submandibular lymph node. Chemotherapy was continued. The endmost tumor recurrence was in the palatine tonsil and posterior parotideal region. Following unresponsive chemotherapy, pembrolizumab treatment was started eight months prior to this study (). A complete response occurred following the sixth dose of pembrolizumab. Secondary adrenal insufficiency and pulmonary reactivation tuberculosis developed as the side effects of treatment. Tuberculosis was identified by PCR and compatible chest CT findings. Pembrolizumab was interrupted and antituberculous treatment was started. Pembrolizumab was commenced when the tumor progressed to a 15 cm mass (). Following the fourth dose of pembrolizumab, the tumor regressed to 4 cm () and the patient is currently alive for four years.


A 74-year-old Japanese woman was referred to our hospital with a history of several days of jaundice. She had no past medical history and no family history. On examination, her skin was jaundiced, and her abdomen was flat and soft. Her laboratory data revealed obstructive jaundice and cholangitis, and tumor marker levels were elevated with carcinoembryonic antigen at 3.6 and carbohydrate antigen 19-9 at 4573.9. Computed tomography (CT) revealed an enhancing mass in the biliary duct hilum and dilation of the intrahepatic bile ducts, and there was no evidence of lymph node metastasis or distant metastasis. Endoscopic retrograde cholangiopancreatography revealed a luminal filling defect in the biliary hilum (Fig. ). We diagnosed the tumor as a Bismuth type 1 cholangiocarcinoma, and performed endoscopic retrograde biliary drainage. Biopsies of the tumor revealed adenocarcinoma. The estimated volume of the postoperative liver remnant was less than 35%. Therefore, percutaneous transhepatic portal vein embolization (PTPE) of the right branch of her portal vein was performed (Fig. ). Twenty-one days later, the volume of the left lobe of her liver increased, and we performed right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and lymph node dissection. Node dissection included resection of hilar and pericholedochal nodes in the hepatoduodenal ligament, common hepatic artery nodes, and those at the celiac trunk, and posterior and anterior pancreaticoduodenal nodes.
Histological examination of the tumor showed moderately differentiated tubular adenocarcinoma without regional lymph node metastasis, a pathological stage II tumor according to the Union for International Cancer Control classification of malignant tumors, 7th edition (Fig. ). Postoperative blood laboratory tests showed that liver enzymes were slightly elevated, but that total bilirubin was within normal limits. Resumption of diet started on postoperative day (POD) 3. Although the fluid in the abdominal drain had been serous until POD 4, the appearance of the fluid became milky on POD 5, and the amount of the drainage increased up to 1 L/day. CT showed a large amount of ascites with a small right pleural effusion. We placed our patient on total parenteral nutrition (TPN), and the ascites gradually decreased and became serous again. The abdominal drain was removed on POD 27, and an oral diet was restarted. She experienced sudden dyspnea on POD 42, and CT showed a massive right pleural effusion and a small amount of ascites (Fig. ). We performed a thoracentesis and placed a chest tube. One liter of chylous effusion was drained, and the triglyceride concentration of the pleural fluid was 1026 mg/dL. With a diagnosis of chylothorax, she was started again on TPN and given subcutaneous octreotide injections. Although the chest drained approximately 2 L/day for several days, both the output and the pleural effusion decreased on chest X-ray. On POD 46, the pleural effusion nearly completely resolved and the chest tube was removed. From then on the octreotide was stopped. Her oral diet was resumed on POD 57, and subsequent CT revealed recurrence of the massive right pleural effusion and a small amount of ascites, leading us once again to make our patient take nil by mouth (Fig. ).
Given that conservative management was ineffective in definitively treating the chyle leak, we performed lymphangiography through the inguinal lymph nodes with Lipiodol (ethiodized oil) on POD 62 to identify the location of the chyle leak and to develop a therapeutic strategy. Lymphangiography and post-procedure CT revealed that there was extravasation of the Lipiodol (ethiodized oil) near the right mediodorsal pleural space along the diaphragm, with an accumulation of Lipiodol (ethiodized oil) located near the staple line of the stump of the right hepatic vein; the exact location of the leak was not identified (Fig. ). CT also showed that there was neither obstruction nor dilation of the thoracic duct (Fig. ). An abdominal source of the chyle leak was not demonstrated. A chest tube was placed after the lymphangiography. The tube drained less than 500 mL/day for a week, and the pleural effusion resolved 10 days after the lymphangiography. She was discharged on POD 72. Two and a half years after the original surgery, she is doing well without evidence of recurrence of either chylothorax or cancer.


A 38-year-old female patient presented with abdominal pain and right upper quadrant mass for 10 days. She had a history of pregnancy and caesarean section in the lower abdominal region 10 years before, but there was no history of trauma and upper abdominal surgery. Clinical examination showed a huge mass about 15 × 10 cm over right upper abdomen. There was moderate tenderness in the area of the mass, and the abdominal skin was intact and smooth except the lower abdominal surgical scar. Abdominal wall ultrasonography showed mixed echo-mass under the muscle layer of right upper abdominal wall. Contrast-enhanced computed tomography (CECT) of abdomen was performed. The images revealed the dilated small intestine between the swelling ventral muscles in the right upper abdominal wall which suggested a ventral hernia in the right upper abdominal wall (Fig. ). There was no history of right upper abdominal surgery or trauma, therefore the surgeons considered it was a spontaneous hernia. The patient had much more severe abdominal pain and began to present hematochezia during her hospitalization. Two hours later, she underwent emergency surgery. The intraoperative finding was an atypical ventral hernia, and the ileum loop was incarcerated with necrosis. The hernia sac was located between the semilunar line and the edge of the rectus abdominis muscles in the right upper abdominal wall (Fig. ), which confirmed it was a Spigelian hernia. The defect size was 2.0 × 1.5 cm. The necrotic ileum segment was resected and end-to-end anastomosis was performed. Considering the small defect and the necrotic ileum, a simple herniorrhaphy was made by suturing the internal oblique and transverse muscles to the rectus sheath. The postoperative course was uneventful, the patient recovered well and was discharged after 1 week of hospitalization. The patient had a favorable outcome for 1 year without recurrence.


A 71-year-old man, known with polycythemia vera and aortastenosis, sustained a wound laterally on his right mid lower leg when he fell and struck a hospital bed, which failed to heal over a 2-year period. The patient was referred 2 years post trauma to a wound centre as the wound had failed to heal after 6 months of treatment by his General Practitioner.
At the wound centre the patient received treatment for a non-healing ulcer by means of various ointments, honey and dressings, with a view to referral for skin transplantation if the wound did not heal satisfactorily. It is noted that the patient was not diabetic and did not have any cardiovascular risk factors but was undergoing follow-up for aortastenosis and polycythemia vera. There was initially improvement in the wound over an approximately six-month period, but due to the return of hypergranulation tissue, increasing size of the wound and a request from the patient, a punch biopsy of the wound was taken which confirmed basal cell carcinoma. The patient was referred to The Department of Plastic Surgery and Breast Surgery, Roskilde Hospital for excision of the carcinoma. The ulcer, approximately 4 cm in diameter (), was surgically excised with a 5 mm margin, without the use of frozen sections, and covered with a split thickness skin transplant. The histology showed an ulcerated basal cell carcinoma of nodular type, with growth deep into the dermis, but not involving the subcutaneous tissue. Histology also showed that the BCC was radically removed. Post-operative control included follow up in the Plastic Surgery clinic for approximately one month. After the skin transplant healed the patient was discharged from follow up in our clinic to yearly control at his Dermatologist. There has been no local recurrence of the BCC. The patient was subsequently diagnosed, with diabetes mellitus type two (DMT2) and started treatment with dietary changes and exercise.


A 55-year-old female veteran presented with complaints of intermittent twitching of her left face. The twitching has been ongoing for the last two years and had been progressively worsening over a period of time. The twitching involved the eyelid and the angle of the mouth on the left side. She was initially treated with antispasmodic medications, which failed to provide relief. She also failed trials of botulinum toxin injections locally to treat the spasms.
Her past medical history was significant for hypertension and hyperlipidemia. She was on three antihypertensives for blood pressure control, which included amlodipine, metoprolol, and chlorthalidone. Her only other medication was a low-dose aspirin daily. She also smoked cigarettes, approximately one pack per day for more than 20 years. She is a veteran and served in the airforce in the post-Vietnam era.
On arrival to the emergency department, the patient was afebrile, with heart rate (HR) 80 beats/minute, blood pressure (BP) 146/84 mmHg, and she was saturating 95% on room air. Her physical examination was unremarkable apart from the occasional twitching noticed on the left side of her face. The laboratory evaluation was also unremarkable. Magnetic resonance imaging (MRI) of the brain with and without intravenous contrast showed an ectatic left vertebral artery compressing cranial nerve seven as it exited from the brainstem. (Figure ) The patient was referred to neurosurgery. She underwent a left-sided craniotomy and microvascular decompression of the dolichoectatic vertebrobasilar junction using Teflon paddies. The patient did well postoperatively, with an almost immediate resolution of the hemifacial spasms.
However, on Day 3 post-procedure, she started complaining of severe headaches. The headaches were associated with nausea, vomiting, left-sided earache, and low-grade subjective fevers. She was afebrile and hypertensive with a blood pressure of 170/100 mmHg. On physical examination, she appeared to be in distress and sutures were present in the left posterior auricular area. The rest of the examination was within normal limits. Her laboratory evaluation was remarkable for leukocytosis of 22x103/uL with 82.5% neutrophils. In this clinical setting, a postoperative infection was suspected and the patient was started on broad-spectrum antibiotic coverage with intravenous (IV) vancomycin and cefepime. A computed tomography (CT) scan of the head showed no acute intracranial pathology. A lumbar puncture was done and a cerebrospinal fluid (CSF) analysis was significant for an elevated white count of 3077 with 69% neutrophils, CSF glucose was low (12mg/dL), and protein was elevated (200mg/dL). The culture from the CSF grew MRSA and the patient was diagnosed with MRSA meningitis as a post-operative complication. On post-op Day 7, sutures from the surgical site were removed and about 100 ml of purulent fluid was drained. The culture from the wound was also MRSA positive. The wound was debrided again and the patient was continued on IV vancomycin for a total of six weeks. She responded appropriately to the antibiotic and did well with a resolution of her symptoms.


A 45- year old unmarried heterosexual, otherwise healthy and non-smoking female with no previous history of cancer, diabetes or lichen sclerosus was referred to the Department of Breast and Plastic Surgery for reexcision of a histopathologically verified 20 mm x 10 mm perianal verrucous carcinoma. The resection base margin was not free, so the patient was referred to Dep. of Plastic Surgery for further surgical intervention and follow-up. Histopathologically, there was some discussion whether the tumor excised prior to admission should be described as a verrucous carcinoma or a Buschke Loewenstein tumour. However, since no Human Papilloma Virus (HPV) could be found in the tissue by immunohistochemical staining, the final conclusion was verrucous carcinoma of the anogenital area ().
The tumour had been present and growing for 3 months. As local treatment by Podophyllotoxin failed to treat the lesion, the patient was referred to a general surgeon in a private clinic, who had excised the tumor. Resection borders were not reported.
No bleeding, itching, painful sensations or previous history of lichen sclerosus were reported. The patient had no risk factors for HIV or symptoms from the gastrointestinal tract. The only medicine prescribed was peroral Imigrane for intermittent migraine. No lymphadenopathy was found.
The clinical presentation was a scar (a) of 20 × 18 mm located in close proximity to the anus remained from the primary excision (). A stalked, soft mobile tumor of 5 × 4 mm (b) was also observed in the perianal region at 4 o’clock (). Histopathologic evaluation of a 4 mm punch biopsy from lesion b determined that is was a benign fibroepithelial tumor. The patient was referred to the department of surgical gastroenterology, Herlev, Denmark, for endoscopy and further surgical intervention on the suspicion of involvement of the anal canal. PET-CT scan determined no signs of dissemination. A transrectal ultrasound examination revealed a tumour observed at 4 o’clock. This tumour involved the internal muscular sphincter of the anus and it was excised in toto. Histologic diagnosis was lichenoid inflammation.
Follow-up was set for 6 months in which the patient did not display any signs of relapse ().


A 79-year-old woman with an increasingly distended abdomen, fatigue and dyspnoea was referred to a secondary clinic in the Netherlands. During primary workup with CT-scan, an enlarged ovary and extensive ascites with omental cake were demonstrated. In addition, the serum marker CA-125 was elevated (808 kU/L). Based on histopathological results of an omental biopsy and prior aspiration of ascitic fluid the diagnosis of stage IIIC epithelial ovarian cancer was established. Unfortunately, the biopsy was complicated by a septic peritonitis with fever up to 39.8°C for which she was admitted to the intensive care unit and was treated accordingly. Differential diagnosis involved intra-abdominal contamination or bowel puncture/injury during the biopsy procedure. Although the patient recovered, her physical condition afterwards did not allow a surgical debulking procedure or neoadjuvant chemotherapy. She was discharged from the hospital with palliative comfort care.
Six months later, she was referred to our hospital for a second opinion as she was in a good physical and mental condition. During physical examination she did not show signs of lymphadenopathy, ascites or an abdominal mass. The serum marker CA-125 was normal (10 E/mL). An additional CT-scan demonstrated no pulmonary or pleural abnormalities and no signs of lymphadenopathy. Both the left ovary (42 × 24 mm) and the right ovary (23 × 11 mm) were slightly enlarged. There were no signs of free fluid, ascites, omental cake, peritonitis carcinomatosis, or other abnormalities.
An uncomplicated laparoscopic bilateral salpingo-oophorectomy was performed including peritoneal biopsies and a partial omentectomy along with free fluid collection from the pouch of Douglas. Intraoperative findings showed an enlarged left ovary, without further residual tumor deposits intra-abdominally. In concordance with the prior omental biopsy, a high-grade serous carcinoma was noted within the left ovary. There were no tumor deposits detected in the right ovary, the omentum or in any of the other biopsies. After counseling, the patient opted for expectant management and did not receive adjuvant systemic chemotherapy. To date, 42 months after diagnosis, she shows no signs of recurrent or progressive disease with a serum CA-125 at 11.0 E/mL.
We conclude that this patient represents a very rare case, and the only case described in literature, of spontaneous regression of a histologically confirmed stage IIIC ovarian carcinoma after a septic peritonitis. Since we were interested in the immunological mechanisms at play in our patient, we set out to study this further.


A 12-year-old female with SW-CAH presented to the pediatric endocrinology clinic for routine follow-up. She was diagnosed with SW-CAH in the newborn period after presenting with ambiguous genitalia and was treated with supraphysiologic hydrocortisone divided three times daily throughout her life (prepubertal dosing range 10-15 mg/m2/day, pubertal dosing range 15-25 mg/m2/day), as well as fludrocortisone (0.1 mg daily). She was monitored every 3-4 months with clinical examinations, growth parameters, and serum measurements of 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone (Esoterix Laboratory, Calabasas Hills, CA), which together guided her medication dosing. She had no evidence of glucocorticoid excess and her growth velocity was normal, without evidence of acceleration or suppression. She and her parents reported continued excellent compliance with her medication regimen.
At age 12 3/12 years, she reported 3 recent emergency department visits for persistent vomiting without diarrhea, abdominal pain, inability to tolerate oral steroids, and tachycardia. One of the episodes was accompanied by fever >39°C. There was no hypotension during any of these episodes, but heart rates were elevated ranging from 124 to 154 beats per minute. Sodium and potassium were normal: Na 137-140 meq/L (reference range, 133-143 meq/L) and K 3.6-4.1 meq/L (reference range 3.4-4.7 meq/L). Each episode was treated with normal saline boluses and intravenous stress dose steroids, and treatment led to immediate improvement in symptoms. She was discharged from the emergency department with recommendations for stress dose steroids by mouth. Over the prior 9 months, she had also unintentionally lost 2.6 kg and had an accelerated annualized growth velocity of 10.6 centimeters per year. BMI was 15.4 kg/m2 (Z-score -1.38). She denied any heat intolerance, jitteriness, palpitations, sweating, diarrhea, or vision complaints. While in clinic, her resting pulse was elevated at 136 beats per minute and blood pressure was normal. She was noted to have new symmetric thyromegaly without nodules. She had no lid lag or stare. She was in mid-puberty, with tanner 3 breasts. There was no family history of autoimmune disease or thyroid disease. Labs () showed a suppressed TSH, and an elevated free T4 and Total T3. Thyroid antibodies were consistent with Graves' disease, with a thyroid stimulating immunoglobulin (TSI) of 652% (reference range <140%). She had no prior thyroid studies for comparison. Adrenal androgens were markedly elevated with 17-OHP 11,600 ng/dl (reference range 11-155 ng/dl, target <1000 ng/dl in SW-CAH). At a clinic visit 15 weeks prior to this evaluation, her 17-OHP on the same dose of hydrocortisone (25 mg/m2/day) was improved at 639 ng/dl. She was initiated on methimazole 0.5 mg/kg/day. Her hydrocortisone dose was not changed and remained at 25 mg/m2/day. Four weeks later, repeat labs demonstrated normal free T4 with mildly suppressed TSH and normal total T3. 17-OHP was stable at 717 ng/dl (). She had no further vomiting episodes after initiation of methimazole, and her tachycardia resolved.
Three months after treatment began for Graves' disease, her TSH and free T4 were in the reference range, and methimazole was decreased to 0.3 mg/kg/day. Repeat 17-OHP was low at 33 ng/dl, indicating suppression on the unchanged hydrocortisone dose of 25 mg/m2/day. Her hydrocortisone dose was decreased to 21 mg/m2/day.


An 11-year-old, intact male German Shepherd dog (GSD) was referred to the emergency service of the Department of Clinical Sciences of Companion Animals of the Faculty of Veterinary Medicine of Utrecht University with a 2-day history of acute onset dyspnea and generalized weakness. Vaccination and deworming were performed regularly. The dog had visited Southern Europe 6 months before presentation. No drugs were administered prior to the development of the clinical signs and no environmental circumstances that could cause dyspnea (e.g. tobacco, organic solvent exposure, dust) were reported.
Physical examination showed a responsive but lethargic dog with generalized weakness, severe dyspnea, cyanotic mucous membranes, prolonged capillary refill time, weak peripheral pulses, tachycardia (heart rate 180 beats/min) and a grade one out of six systolic murmur with the point of maximal intensity over the right cardiac apex. Harsh lung sounds were heard on lung auscultation. Complete blood count (CBC) showed a mild mature leukocytosis (white blood cells: 18.9 × 109/L; reference interval 4.5–14.6 × 109/L) and a haematocrit of 56% (reference interval 42–61%). Biochemistry did not show any abnormalities. Arterial blood gas analysis showed a severe hypoxemia (PaO2: 48.5 mm Hg; reference interval 85–103 mm Hg) and mild hypocapnia (PaCO2: 27.0 mm Hg; reference interval: 32–43 mm Hg). The suspected cause for the hypocapnia was hyperventilation. D-dimer and antithrombin concentrations were within the reference intervals. Dirofilaria immitis antigen snap test (SNAP® Heartworm RT Test, IDEXX Laboratories) and faecal examination (flotation and Baermann larval isolation technique) were both negative.
Thoracic radiographs showed a dilation of the pulmonary artery trunk and right-sided cardiomegaly (Fig. ). Echocardiography was severely complicated due to the severe anxiety and panting of the dog and was therefore limited. It showed severe right ventricular dilation, mild uniform dilation of the main pulmonary artery, systolic flattening of the interventricular septum and moderate tricuspid regurgitation (Fig. a). Application of the modified Bernoulli equation to the velocity of the tricuspid regurgitation jet showed an estimated systolic pulmonary artery pressure of 77 mm Hg, graded as severe PH (reference < 25 mm, severe > 75 mm Hg) []. The left ventricular dimensions were markedly reduced, consistent with left-sided volume depletion. A saline contrast echocardiography was performed, which was negative, thereby excluding intra- and extra-cardiac right-to-left shunting. To address the severe hypoxemia and PH the dog was placed in an oxygen cage with an inspired concentration of oxygen between 40 and 50%. Furthermore, 1.5 mg/kg/8 h oral sildenafil (Viagra®, Pfizer, New York, USA) and 0.25 mg/kg/12 h oral pimobendan (Vetmedin®, Boehringer Ingelheim, Germany) were administered. This therapy did not significantly affect the clinical condition of the dog. However, the arterial hypoxemia mildly improved after the first day of therapy (PaO2 increased from 48.5 to 53 mm Hg, reference interval 85–103 mm Hg). The echocardiogram was repeated on the third day of therapy and the echocardiographic changes and the severity of the PH were markedly reduced. The right ventricular dilation had dramatically decreased, the interventricular septum was no longer flattened, and the pressure gradient of the tricuspid regurgitation was reduced from 77 mm Hg to 41 mm Hg (reference < 25 mm Hg) (Fig. b). Therefore, therapy with pimobendan and sildenafil was continued during the hospitalized period (7 days).
As further diagnostic steps a (pre-and post-contrast) computed tomography (CT) scan with an apnoea, followed by a surgical lung biopsy in the same anaesthetic session were performed 4 days after the initial presentation. A single slice helical CT scanner (Philips Secura, Philips NV, Eindhoven, the Netherlands) was used. Technical settings included 3 mm helical slices, 120 kV, 200 mA, 292 mm field of view, 512 × 512 matrix and a high spatial frequency algorithm. On CT images, the lung parenchyma showed subtle centrilobular ground glass nodules and an enlarged pulmonary artery. Septal lines, pleural effusion and lymphadenopathy were absent (Fig. a, b). CT findings were compatible with PH without a conclusive diagnosis. Following the CT scan, a lung biopsy from the left cranial lung lobe (3 × 2 cm) was taken for histopathological examination with a mini-thoracotomy. Directly after this procedure a therapy with dexamethasone (0.25 mg/kg q24 h I.V., Rapidexon ®, Eurovet Animal Health, Bladel, the Netherlands) was initiated as a last resort while histopathological results were pending (3 days).
Histopathology of the surgical lung biopsy showed a moderate chronic interstitial histiocytic pneumonia of unknown aetiology and atelectasis by haematoxylin and eosin, periodic acid–Schiff, and Van Gieson’s stainings. Vascular changes were initially not clearly identified. Because of the poor response to the initiated treatment and the suspected poor prognosis based on the histopathologic results, the dog was euthanized. Autopsy was performed with the owner’s informed consent.
Gross pathology of the lungs showed moderately collapsed firm lungs with a diffuse mottled appearance with multiple dark red foci of 1 × 1 × 3 mm, and small numbers of white foci of 1 × 1 × 1 mm, often surrounded by a dark red zone (demarcation) randomly distributed throughout all lung lobes (Fig. ). Routine histopathology of the lungs showed multifocal vascular remodelling. In order to differentiate between small arteries and veins, essential to diagnose PVOD, an additional stain visualising elastic fibers and collagen (Weigert’s Resorcin Fuchsin) was added to identify elastic laminae. In this dog, like in people with PVOD, all three compartments (arteries, veins and capillaries) of the pulmonary microcirculation were affected, although the changes in the pulmonary venous system were the most pronounced. Venular lesions included severe concentric intimal proliferation, partial to complete obliteration of the lumina (Figs. , ) and post-thrombotic recanalization (Fig. c). Capillary lesions were organized in foci, most obvious adjacent to remodelled venules and were characterized by proliferation of plumb endothelial cells (similar to PCH) (Figs. , b, d). Segmental congestion of alveolar capillaries was also regularly associated with the foci of PCH (Fig. ). Arterial lesions resembled those of PAH with concentric intimal thickening by increased extracellular matrix and medial hypertrophy, but complex plexiform lesions were absent (Fig. ). These findings were consistent with the findings described by Williams et al. [] and therefore the human equivalent of PVOD.
The genomic DNA of the case was isolated from EDTA-blood using a semi-automated Chemagen extraction robot (PerkinElmer Chemagen Technologie GmbH) and was stored at − 20 °C. Approximately 6 years later, the genomic DNA of the case and an unrelated healthy GSD were analysed by whole genome sequencing. Integrity of DNA was checked on a Bioanalyzer (Agilent, Santa Clara, USA) and quantified using Qubit dsDNA HS (Thermo Fisher Scientific, Waltham, USA). DNA libraries were prepared using TruSeq Nano library prep kit (TruSeq Nano library prep kit, Illumina, San Diego CA, USA) using 200 ng gDNA input. Whole genome sequencing information at 30× coverage was obtained using a HiSeqX Ten instrument (HiSeqX Ten instrument, Illumina, San Diego CA, USA) and 2 × 150 base pair paired-end reads.
Data was processed with our in-house developed pipeline v1.2.1 () including somatic mutation analysis (Strelka, VarScan, FreeBayes, and MuTect) and a genome analysis toolkit (GATK v. 3.2.2) [] according to best practices guidelines []. Sequence reads were mapped against the Canine Reference Genome (CanFam 3.1) using Burrows-Wheeler alignment with maximal exact matches (BWA-MEM) v0.7.5a [] followed by marked duplicates, merging of lanes, and realignment of indels. Base recalibration was not performed. In human medicine, mutations in BMPR2, ACVRL1, ENG, KCNK3, CAV-1, and SMAD9 have been suggested to be causative for an autosomal dominant form of PAH []. These genes were included in analyses to prevent missing candidate mutations due to phaenotypical misclassification. Comparing the case and control, analysis of these genes revealed 196 unique intronic variants. Comparing the sequence of EIF2AK4 in the case and the healthy GSD revealed 124 unique variants, of which 9 were located in the 3`-UTR, 112 were intronic and 3 were exonic variants. The case was homozygous mutant for c.2961T>C and c.1266G>A, a heterozygous variation was found at c.2092G>A. Variant validation was performed by Sanger sequencing on amplified polymerase chain reaction products from genomic DNA using Platinum Taq Polymerase (Invitrogen). After exonuclease I treatment DNA sequence reactions were performed using BigDye v3.1 on, sequenced on an ABI3130XL and analyzed in Lasergene (version 12.0 DNASTAR). Four of the five additional GSD's, unknown for any form of respiratory stress and aged ≥ 10 years revealed the identical genotype as the case and therefore excluded these as causal variants for PVOD.


A 13-year-old boy with no past medical history presented with six months of progressive left knee pain. He denied any trauma or constitutional symptoms. On physical exam, the patient had a moderate left knee effusion with some warmth and no erythema. There was tenderness to palpation along the medial joint line and a marked decreased passive range of motion, 40-90 degrees. His neurovascular exam was intact with no signs of lymphedema, adenopathy, or instability.
Computed tomography (CT) revealed a mixed radiolucent and sclerotic permeative lesion within the left posterior medial epiphysis with medial cortical destruction (). There was an associated suprapatellar effusion without evidence of infiltration through the physis.
Magnetic resonance imagining (MRI) demonstrated a nonspecific infiltrative process involving the left distal medial femoral epiphysis, extending proximally along the posterior femoral cortical surface, appearing dark on T1 and bright on STIR and T2 weighted images (). The radiographic differential diagnosis included chondroblastoma, osteomyelitis and eosinophilic granuloma.
Metastatic workup including CT chest, abdomen, and pelvis, three phase bone scintigraphy, and fludeoxyglucose-positron emission tomography scans (FDG-PET) were all otherwise unremarkable (Figures and ).
Fluoroscopic guided core biopsy was performed (). Histologic analysis revealed a round cell tumor (). Immunohistochemistry was positive for CD20 and CD79a, confirming diffuse large B-cell lymphoma (). Further analysis revealed positivity for BCL-6 and CD10, and negativity for MUM1, confirming a germinal center phenotype (GC type).


A 31-year-old Mestizo-Mexican woman presented to our emergency department (ED) with DKA. She did not have a family history of diabetes or previous autoimmune diseases. She mentioned multiple hospitalizations due chronic idiopathic pancreatitis between 12 and 16 years of age. At that time, laboratory tests ruled out the presence of gallstones, tumors, autoimmune diseases, or metabolic diseases. Her pancreatic exocrine and endocrine functions were completely normal after each episode. Fifteen years after the last episode of pancreatitis, she presented with alopecia, malar rash, and oral ulcers. She was initially diagnosed as having discoid lupus with the skin biopsy results. However, a week later, she developed severe neuropsychiatric manifestations of SLE, including focal motor seizures, with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of 18 points. Rheumatologists prescribed methylprednisolone (three doses of 1 g daily by intravenous injection) with improvement of neurological symptoms. Her treatment at hospital discharge was: chloroquine (225 mg/day), levetiracetam (1.5 g twice a day), phenytoin (100 mg twice a day), lorazepam (1 mg/day), and a monthly bolus of CY. In addition, she was treated with weekly down-titrating doses of prednisone (initial dose of 1 mg/kg).
Seven days after administration of the sixth dose of CY (cumulative dose of 6.25 g), she presented with asthenia, adynamia, polydipsia, nausea and vomiting, food intolerance, impaired visual acuity, and abdominal pain. The physical examination at our ED revealed tachycardia (125 beats per minute), tachypnea (27 breaths per minute), drowsiness, and dehydration. She presented with a normal body mass index and no stigmata associated with insulin resistance. Laboratory tests reported: serum glucose of 1240 mg/dl, sodium of 127 mEq/L, potassium of 5.56 mEq/L, chlorine of 86 mEq/L, arterial pH of 7.07, bicarbonate of 3.00 mmol/L, and ketonuria (80 mg/dl) with effective serum osmolarity of 322.8 mOsm/kg and total osmolarity of 334.1 mOsm/kg, with an anion gap of 43.56, urea 63 mg/dl, and creatinine of 1.58 mg/dl. Liver tests, amylase, and lipase were normal. After the diagnosis of a mixed hyperglycemic state with predominance of severe DKA, she was started on an aggressive intravenously administered fluid schedule with saline solution 0.9% and intravenous continuous insulin infusion (CII). During the first day she required a total of 165 units of insulin per day (2.75 U/kg per day). Table shows the clinical and biochemical evolution from first evaluation to resolution of DKA.
During the first hours, traditional precipitant factors for DKA, such as infections or cardiac ischemia were ruled out. With an aliquot from the first serum sample in the ED, we measured anti-insulin, anti-GAD65, and anti-IA2 antibodies that were reported as negative; C-peptide was determined to be 0.5 ng/ml and the glycated hemoglobin (HbA1c) was 12.0%. The diagnostic consideration was of T1DM, so once DKA remission was achieved, she was prescribed an intensive insulin scheme at a dose of 1.09 IU/kg per day with 70% of basal insulin glargine daily and 30% of lispro boluses divided in three doses.
With the multi-drug immunosuppressive treatment her symptoms improved and 3 months after discharge the CY was switched to azathioprine and then to chloroquine. Three weeks after the switch from CY to other immunosuppressive therapies, she presented with symptomatic hypoglycemia and insulin doses were tapered down. Five months after the switch, insulin was completely withdrawn. At last follow up, 1 year after the hyperglycemic crisis, she had no symptoms related to hyperglycemia and her blood glucose remains under 100 mg/dl. She continues to have a well-balanced, low-carbohydrate diet and her last HbA1c was 5.2% and C-peptide was 1.8 ng/ml without any antidiabetic drugs.


Patient CS, a single 60-year-old male presenting with a history of generalized anxiety with panic, major depressive disorder, and excessive guilt, was referred from a county hospital to a tertiary psychiatric facility for clarification of diagnosis and a more comprehensive assessment. His sister, and the family physician that had been following the patient for the past 4 years, helped provide collateral history. His family noted that he was born with a large head. He had a history of meningitis at the age of 9 or 10 after which it is thought that he developed a non-communicating hydrocephalus. His past psychiatric diagnoses included major depressive disorder, generalized anxiety disorder with panic, personality disorder, and “borderline intelligence.” He had several admissions to a psychiatric ward over the past 3 years for low mood and had been trialed on numerous psychotropic medications (citalopram, lithium carbonate, risperidone, olanzapine, quetiapine, paliperidone, clomipramine, clonazepam, lorazepam) with little effect or benefit. At the time of admission, he did not smoke, drink alcohol, or take illicit drugs. His past medical history was significant for hypothyroidism corrected with the use of thyroxine, bowel resections secondary to possible malignant changes, fatty liver with lobar resection secondary to liver cancer and nephrolithiasis.
He was born and raised in Europe until the age of 5, when he immigrated to Canada, and is bilingual. His family reported that he had always had a large head, micropenis, central obesity and short stature. He had a history of being bullied for “looking like a girl” and being different. At school his peers were physically aggressive, hitting him on his head. Born the youngest of seven siblings, he was raised by his parents and lived under their care into adulthood, until both parents passed away—his father had Diabetes Miletus and his mother had a brain tumor. Thereafter, he was taken care of by his sister. He had an older brother who also passed away secondary to a brain malignancy. One brother has dyslipidemia, and two sisters and one brother are healthy. He had no employment history and as a child had always struggled in school, completing a vocational stream of education until grade 10. Socially, he was active in a band for a few years (plays guitar well) and sang in a church choir. However, he never lived independently, and had no romantic relationships.
Initial assessment revealed that he was a poor historian unable to give an accurate timeline of events. He often expressed fears that he was going to die. He suffered from delusions of guilt that he had caused the deaths of family members. His conversation was repetitive, he repeatedly asked the same questions and restated his fear of dying despite several reassurances. He had no history of self-harm or suicide attempts. On physical examination, he had a wide stance waddling gait, slow movements, limited arm swing and masked facies. He was noted to have enlarged head circumference (62.5 cm) and limited insight into his illness and the need for treatment. His clinical presentation prompted examination with magnetic resonance imagining (MRI) of the brain and formal neuropsychological testing.
A sagittal T1, axial T2, axial T2 FLAIR and diffusion-weighted images were acquired throughout the brain. Findings indicated a long-standing overt ventriculomegaly, likely due to aqueductal stenosis, with bilateral gross dilation of the lateral and third ventricles, with a small aqueduct and fourth ventricle, with significant thinning of the corpus callosum and overlying cerebral cortex. Vascular flow-voids at the base of the brain were normal and there were no mass lesions, significant sulcal effacement, downward tonsillar herniation or restricted diffusion observed.
Manual segmentation of gray and white matter and cerebrospinal fluid (CSF; Figure ) of high-resolution T1 weighted MRI images was completed with Freeviewer in FSL (Jenkinson et al., ). Automatic segmentation of a comparison group of sex and age matched healthy controls (HCs; one aged 60, three aged 55 years, Table ) was completed with the FreeSurfer () recon tool. The participant’s volumes were converted to Z scores for comparison. Compared to similarly aged control participants, the patient had extremely large ventricular volume (821,452 mm3, Z = 161), reduced white (333,606 mm3, Z = −2.655) and gray (432,184 mm3, Z = −3.07) matter volume, and within normal range total intracranial volume (1,587,242 mm3, Z = 0.57) see Table and Figure .
The patient’s neurological exam was unremarkable.
The Wechsler Adult Intelligence Scale (WAIS-III; Wechsler, ) revealed a borderline IQ of 79, with a verbal IQ of 88, non-verbal performance IQ of 74, poor working memory IQ of 71, verbal comprehension IQ of 93, and visual-spatial IQ of 80. The patient had difficulty completing tasks requiring working memory, which was in the 3rd percentile, and processing speed was extremely slow (in the 1st percentile). Hopkins Auditory Verbal Learning Test (Brandt, ) indicated severe memory impairment, with initial memory for only a few items, no significant recall between administrations, and inability to recall any information after a brief delay. Rey-Osterrieth Complex Figure Task (Osterrieth, ; Rey et al., ) performance indicated impaired visual spatial and working memory abilities with more attention to small details, missing elements and less attention to the overall image. The Stroop test (Stroop, ) indicated impaired executive function, scoring below the 1st percentile, with a severe inability to suppress automatic responses.