A 21-year-old woman was referred due to secondary amenorrhea. Her past medical history was significant for persistent ductus arteriosus (PDA), she underwent surgery when she was 11 months old, and she was diagnosed with type 2 diabetes mellitus (DM), which was incidentally detected at the age of 18 years. At that time, the physical examination findings were as follows: height of 155 cm, body weight of 80 kg, body mass index (BMI) of 33.3 kg/m2, and BP of 108/76 mmHg. After being diagnosed with type 2 DM, the patient took metformin for a few months, and she tried to lose weight through exercise and diet control. Recently, although she had not taken metformin for several months, her blood glucose was within normal ranges. At this visit, a physical examination showed a height of 155.3 cm and a weight of 53.7 kg, with a BMI of 22.3 kg/m2. Her BP was 130/80 mmHg, with a regular heart rate of 80 beats/min, and her body temperature was 36.5 °C. The development of her breasts and her pubic hair were Tanner stage 2 and stage 3, respectively. The female internal genitalia were infantile. However, there was no webbed neck or skeletal deformities.
Laboratory tests revealed a fasting glucose level of 88 mg/dL, HbA1C 4.8%, C-peptide 6.34 ng /mL(reference range, 0.4–4 ng/mL), and anti-glutamate decarboxylase (GAD) antibody < 0.5 U/mL(reference range, 0–1.0 U/mL). Hormonal tests showed a thyroid-stimulating hormone (TSH) level of 2.45 μIU/mL (reference range, 0.3–5.0 μIU/mL), a T3 level of 169.8 ng/dL (reference range, 80–200 ng/dL), a free T4 level of 1.15 ng/dL (reference range, 0.75–2.0 ng/dL), a prolactin level of 8.18 ng/mL (reference range, 1.9–19.7 ng/mL), a luteinizing hormone (LH) level of 20.2 mIU/mL, a follicular stimulating hormone (FSH) level of 100 mIU/mL, a testosterone level of 0.01 ng/mL (reference range, 0–0.77 ng/mL), an oestradiol level of 1.06 μg/dL(reference range, 30–333 μg/dL). A small uterus was detected, and both ovaries could not be identified on pelvis ultrasonography and computed tomography (CT) (Fig. ). However, there was no renal abnormality (Fig. ). A chromosome study finally showed a karyotype of 46,X,i (X)(q10) Turner syndrome. Transthoracic echography (TTE) revealed no residual PDA shunt flow and bicuspid valve. Bone mineral density (BMD) using dual-energy X-ray absorptiometry showed an age-matched Z score of − 0.7 at the lumbar spine. She was regularly followed up for type 2 DM and took ethinyl oestradiol/drospirenone for regular menstruation.
Three years after the diagnosis of Turner syndrome, the patient complained of mild headache, intermittent palpitation, and dizziness without neurological deficit. Her measured BP was 166/100 mmHg at the doctor’s office and 145/90 mmHg at home. Her BP at the time of the Turner syndrome diagnosis (3 years ago) was within normal ranges. There was no radio-femoral delay which meant delay between the radial pulse and femoral pulse suggesting coarctation of aorta. Recent TTE showed no residual PDA shunt flow and cardiac valve abnormality. There was no family history of hypertension. A thyroid function test and chemistry were within normal ranges. We consider other important secondary causes of hypertension like a pheochromocytoma. Thus, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine (Table ). We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass, measuring 42 Hounsfield units pre-contrast, heterogenous contrast enhancement with a contrast wash-out ratio of 65% (Fig. and ). According to her clinical manifestations, biochemical results and atypical CT phenotype, I-131 meta-iodo-benzylguanidine (MIBG) scintigraphy was performed to detect of extra-adrenal pheochromocytoma. The results showed MIBG uptake on the right adrenal gland (Fig. ). She had no family history of pheochromocytoma. After pre-operatively administering phenoxybenzamine, laparoscopic adrenalectomy was performed. Final pathology revealed that the pheochromocytoma extended to the adrenal cortex but was well-circumscribed. The cut surface of the tumour was tan and darkened with focal haemorrhage. The tumour showed characteristic “Zellballen” architecture. The tumour cells were larger than normal chromaffin cells, and their cytoplasm was granular. Immunostaining for S-100 protein demonstrates the sustentacular framework surrounding the tumour cells and positive for chromogranin (Fig. ). Postoperative blood pressure was recorded as 120/70 mmHg without any anti-hypertensive drugs. Postoperative hormonal tests revealed decreased catecholamine levels (Table ). The postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months.


An 8-year 5-month old boy came with his parents to the Paediatric Dental Clinic of the Dental Faculty at the National University of Malaysia (UKM) with a primary complaint of maligned teeth. Parents noticed that some of their son's upper teeth were behind his lower teeth. The patient has no previous history of dental treatment, and his medical history was noncontributory.
Intraoral examination revealed the patient in mixed dentition stage with the first permanent molars in a Class I relationship. Three of his permanent maxillary teeth, right lateral incisor (tooth 12), left central incisor (tooth 21), and left lateral incisor (tooth 22), were in a crossbite relationship (). Slight enamel attrition was noted on the labial surface of tooth 22 close to the incisal edge due to traumatic occlusion. Space analysis using the Moyer's mixed dentition analysis showed the availability of adequate space within the arch for realignment of teeth.
After discussing the treatment modalities with parents, we selected a short-span wire-fixed orthodontic treatment with four preadjusted edgewise brackets with a 0.022″ slot. The brackets were bonded on the labial aspects of the four maxillary permanent incisors. A short-span nickel-titanium (Ni-Ti) 0.014″ round archwire is cut equally on both sides of the centreline and placed into the bracket slots (). The wire was stabilised in its position using elastic ties. The patient's bite was raised using 2 mm thickness of glass ionomer cement (GIC) placed on the occlusal aspects of both the mandibular first permanent molars (tooth 36 and tooth 46).
Two weeks later, there was some evidence of anterior movement of the maxillary teeth that were in crossbite. Within a month after the initiation of treatment, the anterior crossbite was corrected successfully. The 0.014″ round Ni-Ti archwire was changed to the 0.016″ round Ni-Ti archwire and retained for further two weeks before debonding of the brackets. At 3-month review, the incisor teeth were still in positive overjet ().


A 7-year 2-month old boy was seen in the Paediatric Clinic at the Faculty of Dentistry, National University of Malaysia (UKM), for routine dental assessment. He had previous dental treatment under general anaesthesia two years ago, and his medical history was noncontributory.
Intraoral examination showed all primary teeth of the patient missing due to the previous extraction. Both the permanent maxillary and mandibular first molars on either side have erupted into occlusion. Anteriorly, the permanent maxillary right central incisor (tooth 11) was in a crossbite with the permanent mandibular right central incisor (tooth 41). In occlusion, tooth 11 was trapped between tooth 41 and the permanent mandibular right lateral incisor (tooth 42) (). Tooth 41 has Class II tooth mobility and gingival recession on its labial aspect.
After discussion with the parents on the treatment options, we decided on using a short-span wire-fixed appliance with two preadjusted edgewise brackets. The patient's bite was raised with 2 mm thickness of GIC placed on the occlusal aspects of the permanent mandibular first molars. GIC placement allowed opening of the anterior bite and released the lock of trapped tooth 11. Two preadjusted edgewise brackets with a 0.022″ slot were bonded to the labial surface of tooth 11 and the permanent maxillary left central incisor (tooth 21). A short Ni-Ti 0.014″ round archwire was placed into the brackets and held in place with elastic ties ().
Two weeks later, the crossbite was corrected. The brackets were debonded, and the GIC on teeth 36 and 46 was removed using an ultrasonic scaler. The occlusion was stable, and the gingival height of tooth 41 showed significant improvement at 6-month review ().


An 8-year 2-month old boy presented to the Paediatric Dental Clinic of the Dental Faculty at the National University of Malaysia (UKM) with a chief complaint of trapped upper teeth. He had restorative dental treatment to some of his teeth a year ago, and his medical history was noncontributory.
The intraoral assessment showed that the patient was in his mixed dentition stage and the first permanent molars were in a Class I relationship on either side. The permanent maxillary lateral incisors (teeth 12 and 22) were trapped palatally in an anterior crossbite behind the maxillary deciduous canines (teeth 53 and 63) and the permanent maxillary central incisors (teeth 11 and 21), respectively (). He has a Class-I incisor relationship with an overjet and an overbite of 3 mm each. Some evidence of wear facets was noted on the occlusal surfaces of the primary and permanent molars although the patient denied any parafunctional activity. A panoramic radiograph taken a year ago showed the presence of tooth germs of the permanent maxillary canines in a favourable position with no overlapping of the crowns over the roots of teeth 12 and 22 (). However, tooth 53 and tooth 63 were relatively big, and limited space was available for teeth 12 and 22 to move anteriorly. Upon consultation with an orthodontist and taking into consideration the patient's molar and incisor relationship, we decided to extract the primary canines to allow distalization of teeth 12 and 22.
A month later, after observing slight distalization of teeth 12 and 22, a lower removable bite-raising acrylic appliance was made to open up the anterior bite. Then, four preadjusted edgewise brackets were bonded to the labial surfaces of the maxillary incisors, and a short Ni-Ti 0.014″ round archwire was placed into the brackets and held in place with elastic ties (). A month later, anterior movement of teeth 12 and 22 was noted. The existing Ni-Ti wire was changed to the Ni-Ti 0.016″ round archwire, and the patient was reviewed monthly. After three months, we were able to correct the anterior crossbite of teeth 12 and 22. At 6-month review, the corrected teeth were still in positive overjet (). The patient is currently under review for the monitoring of the permanent canines eruption.


A 77-year-old man was admitted to our Internal Medicine Department for fever, diarrhea, and a 1-month history of persistent polyarthralgia and prolonged morning stiffness at both ankles and knees. Almost 40 days before, the patient had been hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), which was treated with a fluoroquinolone. Subsequently, he developed a Clostridium Difficile induced colitis, treated with oral metronidazole. The patient was a former port worker and had been a heavy smoker for 40 years. Past medical history included ischemic heart disease and arterial hypertension, for which he was taking anti-platelet and anti-hypertensive therapy.
On physical examination, he was febrile (37.9 °C) and had a heart rate of 95 beats/min and a blood pressure of 135/70 mmHg. His oxygen saturation was 96% on room air. His body mass index was 27 Kg/m2 and he reported a 5 Kg weight loss over the last 3 months. His ankles appeared clearly swollen, with reduced range of motion. There was a tense effusion in the left knee and a moderate joint tenderness in all limbs. Fingers and toes presented with a low grade digital clubbing, whose first appearance could not be precisely dated. Laboratory exams showed C-reactive protein (CRP) of 116.1 mg/L (normal values < 5 mg/L), erythrocyte sedimentation rate (ESR) of 90 mm/hr. (normal values < 35 mm/hr), white blood cells (WBC) of 11.860/mm3 (normal values between 4.000 and 11.000/mm3) and a rheumatoid factor of 56 U/mL (normal values < 20 U/ml). Blood and urine cultures were negative. The left knee synovial fluid aspiration showed an aseptic synovitis (8.226 WBC/hpf, with 90% neutrophils, while crystal detection, gram stain and cultures were negative). Moreover, Clostridium Difficile toxin in stool samples was still detectable.
Based on this presentation, a reactive arthritis due to a Clostridium Difficile induced colitis was suspected and oral vancomycin, oral prednisone, and painkillers were prescribed. Five days later, since fever, diarrhea, and polyarthralgia had apparently resolved, the patient was discharged, and a post-discharge visit was scheduled at the Rheumatology Office 1 month later.
When the patient came to the Rheumatology Office, he reported a relapse of polyarthralgia and joint tenderness while he was gradually reducing oral prednisone. He was slightly febrile (37.5 °C) but had denied relapse of diarrhea. On physical examination, his ankles were still swollen, while the left knee effusion had resolved. The fingers of both hands were also diffusely swollen and digital clubbing had worsened, with an increase of distal phalangeal/interphalangeal depth ratio (greater than 1.05). Lung auscultation revealed fine crackles at the base of the right lung. In laboratory exams, CRP was 101.1 mg/L, ESR was 99 mm/h and WBC was 14.380/mm3. Chest radiograph was unchanged as compared to that performed when the patient had the COPD exacerbation, revealing a possible patchy infiltrate at the base of the right lung, while radiograph of the ankles was inconclusive (Fig. ). At that stage, given the presence of a lung infiltrate and systemic inflammatory features (fever and elevated inflammatory markers), a relapse of right base pneumonia was suspected; thus, an empiric antibiotic therapy with a broad-spectrum penicillin and pain killers were prescribed. In addition, bone scintigraphy and chest computed tomography (CT) were promptly performed. The first revealed increased linear periosteal 99mTc-hydroxymethylene diphosphonate (HMDP) uptake, which is a typical sign of HOA (Fig. ). The second revealed a lung infiltrate with a partly ground-glass aspect (Fig. ).
Owing to the high association between HOA and lung malignancies [], the patient underwent a bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies of the right lung infiltrate. Unfortunately, biopsies could not be performed because of the complexity in localizing the infiltrate under fluoroscopy. On the other hand, we were unable to schedule a CT-guided percutaneous biopsy or a diagnostic surgery because the patient’s general conditions dramatically worsened. He developed high fever (39.4 °C) and severe respiratory failure, which we ascribed to a severe bilateral pneumonia. During the hospitalization in a semi-intensive care unit, bronchoscopy was tried again and, finally, a transbronchial small biopsy could be performed. In the BAL, there were no malignant cells or infectious pathogens; likewise, blood and sputum cultures turned out negative. When the result of the transbronchial biopsy pathology examination (Fig. ) became available, showing a lepidic pattern adenocarcinoma, no specific therapy was prescribed due to the extreme gravity of the patient’s general conditions. Despite the use of noninvasive ventilation and extended spectrum antibiotic therapy, the patient died 4 days after the biopsy results and roughly 5 months after the initial clinical presentation. Autopsy confirmed the diagnosis of lepidic predominant adenocarcinoma of the right lung, associated with massive bilateral destructive pneumonia and severe emphysema with centrolobular pattern (Fig. ).


The patient was a 27-year-old Caucasian woman with a history of previous orthodontic treatment. A severe car accident led to the loss of five anterior teeth and alveolar bone. The patient had been unsuccessfully treated orthodontically; an alveolar bone graft had been previously placed.
Clinical examination revealed no evident skeletal disharmony; she had an Angle’s Class II subdivision with crowded mandibular incisors. There was slight asymmetry of her lower lip due to a scar caused by the accident. All permanent maxillary incisors, the left canine, and the mandibular right first molar were absent. Initial panoramic radiograph confirmed the absence of teeth and the extent of alveolar bone loss (Fig 1). The patient had been orthodontically treated, and an alveolar bone graft from the patient’s iliac crest had already been placed. One year after this treatment, she was not satisfied with the treatment outcomes and sought a second treatment option ().
The treatment objectives were to: 1) open enough space for mandibular right first molar rehabilitation; 2) align and upright the mandibular incisors; 3) obtain a canine Class I relationship on the right side; 3) establish functional occlusion; and 4) improve the balance of the subnasal region while smiling and, consequently, improve the patient’s self-esteem. Uprighting of the mandibular incisors was necessary to establish the correct positioning of the maxillary implants in the anterior area.
The patient had three treatment alternatives for loss of the maxillary incisors and bone: 1) alveolar bone grafting, orthodontic treatment and implant rehabilitation; 2) orthodontic treatment and placement of a prosthetic bridge; 3) orthodontic treatment and placement of removable partial dentures. It is important to consider the biological and functional factors, aesthetics, and costs when determining the best treatment option.
The steps, benefits and risks of the procedure were explained to the patient, and written informed consent was obtained prior to treatment. After consent was obtained, a multidisciplinary approach involving the previous alveolar bone grafting, orthodontic treatment, and placement of five dental implants was selected for the maxilla, and placement of one dental implant was planned for the mandible. The main risks in this case involved the success of bone grafting and osseointegration of the dental implants. The major treatment challenge was achievement of satisfactory gingival aesthetics because of the extent of the edentulous area. The minimal gingival exposure during smiling was an advantage.
A 0.022-in standard non-torqued, non-angulated bonded Edgewise appliance was used. Alignment and leveling of the maxillary teeth were performed, as well as placement of a removable appliance in the anterior region, to maintain the space and improve aesthetics. Posteriorly, artificial teeth were bonded to the brackets and fixed on a 0.019 x 0.025-in rectangular archwire to function as temporary prostheses. In the mandibular arch, the crowded incisors were aligned and leveled. An open coil spring was used to open the space for the dental implant by moving the right first molar to the distal aspect and moving the canines to the mesial aspect, to obtain a Class I canine relationship (). Improvement in mandibular incisor positioning was necessary to establish the correct position of the maxillary implants in the anterior area. Finally, the prosthesis was created with a more convex shape in the cervical region of the maxillary incisors, to support the subnasal region, and aesthetic and functional rehabilitation was completed ().
Once the correct occlusion was established, five dental implants were placed in the anterior area, and one was placed in the right first molar area. The prostheses were placed to complete the aesthetic and functional rehabilitation (). The long-term maintenance of these results after 2 years of follow-up (), with a pleasing smile and adequate overbite and overjet, and adequate positioning of the implants are shown in .


We report the case of a 62-year-old Sri Lankan Sinhalese man who presented to our Teaching Hospital, Peradeniya with a history of generalized malaise and anorexia of 1 week’s duration.
He had had poorly controlled type 2 diabetes for 12 years treated with orally administered hypoglycemic agents, which was complicated by diabetic nephropathy with a baseline serum creatinine of 220 micromol/L which was done 3 months back with urine analysis showing ++ protein. He was on thyroxine 100 mcg for hypothyroidism. He was a hypertensive for 10 years on losartan potassium. He was dyslipidemic and was on orally administered atorvastatin 40 mg daily. Serum lipids done 1 month back revealed high serum cholesterol with elevated triglycerides (TG) of 350 mg/dL. Gemfibrozil 600 mg twice daily was added on top of the statin by his general practitioner. Soon after starting gemfibrozil, our patient developed myalgia and he himself stopped taking gemfibrozil after 5 days. He then noticed gradual resolution of symptoms.
He developed generalized malaise and anorexia 3 weeks after the initial event. He noticed a reduction in urine output with dark urine for 2 days prior to admission. He noticed a reduction in exercise capacity with shortness of breath at rest.
On examination his temperature was 36.7 °C (98 °F). He was oriented in time, place, and person. He had mild pallor and bilateral ankle swelling. His pulse rate was 96 beats/minute with a blood pressure of 140/80 mmHg; his precordium examination was normal. He was dyspneic at rest with a respiratory rate of 24 cycles per minute and he had bilateral fine crackles up to mid zone. An abdominal examination was unremarkable. He had mild tenderness of his thigh muscles. He had 4/5 of normal strength against resistance in proximal muscles and his distal muscles had strength close to normal. Deep tendon reflexes were present but diminished.
Laboratory investigations revealed a serum creatinine of 1232 micromol/L with a blood urea of 27.7 mmol/L. His serum potassium was 8 mmol/L with electrocardiographic evidence of hyperkalemia. His serum alanine transaminase (ALT) was 413 U/L and aspartate transaminase (AST) was 229 U/L. Hemoglobin was 9.4 g/dL with a mean corpuscular volume (MCV) of 85 fL. His white cell count was 6.6 × 106/microL and platelet count of 87 × 103/microL. Corrected serum calcium value was 1.63 mmol/L for an albumin value of 31 g/L. His serum phosphate was 4.7 mg/dL (2.5–4.5 mg/dL). His lactate dehydrogenase level was 240 U/L (88–230 U/L) and uric acid was 12.4 mg/dL (2.4–7.4 mg/dL). His C-reactive protein was 68.5 mg/L. Arterial blood gas revealed severe metabolic acidosis with a pH of 7.12: bicarbonate 8.8 mmol/L, partial pressure of carbon dioxide (PCO2) 27 mmHg, and base excess of − 20.5 mmol/L. An ultrasound scan of his kidney-ureter-bladder revealed normal size kidneys with slightly altered corticomedullary demarcation and no obstruction to outflow tract. His creatine kinase (CK) level was 49,146 U/L and urine myoglobin was positive. A diagnosis of rhabdomyolysis leading to acute-onset chronic renal failure was made. His random blood sugar was 145 mg/dL and urine ketone bodies were negative. He was clinically euthyroid while on thyroxine 100 mcg/day and his thyroid-stimulating hormone (TSH) was 6.5 u/L (normal range 0.4–4 u/L). Other causes of rhabdomyolysis, such as hyperthermia, prolonged seizures, trauma, physical muscle damage or stress, dehydration, burns, or alcohol abuse were not evident in our patient. He did not have fever preceding the event. His clinical course and laboratory data suggest that the combination of atorvastatin and gemfibrozil is the most probable cause of rhabdomyolysis.
He was catheterized. He was given calcium gluconate and insulin dextrose to manage the hyperkalemia. Acidosis was corrected with an 8.4% sodium bicarbonate infusion. He was started on intravenously administered furosemide. Considering his high serum creatinine, severe metabolic acidosis, and hyperkalemia, he was offered urgent hemodialysis via a vascular catheter. His daily renal functions and CK were monitored. He was offered four consecutive hemodialysis sessions every other day. Gradual improvement in his urine output was noted. His CK levels normalized over the days. He was discharged on day 8 of admission with a serum creatinine of 280 micromol/L and normal CK level. On a follow-up visit 1 week later, his serum creatinine was 256 micromol/L with normal CK level.


A 37-year-old woman presented with several years of progressively worsening continuous dizziness, headache, and fatigue. The dizziness consisted of sensations of spinning, tilting, disequilibrium, and head fullness. She did not report tinnitus or hearing loss. She was employed as a military flight refueler and exposed to JP-8 vapors and exhaust while working full-time on and around a KC-135E tanker aircraft, a plane used for performing in-flight refueling missions. She worked in a large enclosed hangar that housed all but the tail section of the tanker aircraft. During inspection and maintenance of the aircraft, up to 9,750 gallons of fuel would be loaded. Jet fuel vapors were always present in the hangar due to venting, small leaks, and fuel residue. Fuel vapor concentrations were even greater when engine maintenance necessitated removal of fuel filters and fuel components, draining of fuel into buckets, and opening of fuel lines. She worked in engine maintenance with over 4 years of inhalational and dermal exposure to JP-4 and JP-8.
Her examination showed moderately impaired equilibrium to walk only three steps in tandem before taking a sidestep. Romberg testing revealed more sway during eye closure but no falling. Her medical and neurological examinations were normal. There was no spontaneous, gaze, or positional nystagmus. Qualitative head impulse test was not performed at that time.
A brain SPECT study at an outside facility revealed mild-right frontal hypoperfusion that persisted on a repeated study the following year. Neurocognitive examination showed overall memory function in the 97th percentile. An MRI brain without gadolinium and an EEG were normal. An initial hydrocarbon assay revealed the presence of 3-methylpentane and n-hexane in the blood at concentrations of 27 and 15.7 ng/ml (parts per billion), respectively (none should be measurable in normal individuals). Ten months later, 3-methylpentane and n-hexane remained present although at significantly lower concentrations. Eighteen months after presentation, 3-methylpentane and n-hexane persisted in the blood and had only diminished an additional 20%. Rotational chair, more so than caloric vestibular testing, demonstrated bilateral vestibular dysfunction (Figures and ) with reduced gain values on step velocity along with a reduced time constant. Gain was also reduced on all sinusoidal rotations with increase phase lead at 0.01, 0.02, and 0.04 Hz rotations. The patient reported that her headaches, dizziness, fatigue, and mild unsteadiness improved somewhat following a transfer to the finance department where no JP-8 exposure existed. There was a long interval of 15 years since her initial visit when she was lost to follow up. Now, 16 years after her initial presentation, she reports that the dizziness is mild but headaches and severe fatigue persist. She has continued to work but plans to retire earlier than originally anticipated due to the ongoing symptoms. Recently, cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP, respectively) and video head impulst testing for each canal were performed and all results were normal.


A 45-year-old female contracting officer for the National Guard reported several years of imbalance, headache, fatigue, eye and skin irritation, coughing, sinus congestion, recurrent urinary tract infections, chest tightness, irritability, depression, shortness of breath, palpitations, and numbness. She described her dizziness as an intermittent floating and a rightward tilting sensation with imbalance lasting minutes to hours without any particular pattern. She had a history of asthma and allergies including reaction to aspirin causing urticaria and airway obstruction. In 1998, she developed syncope and dizziness though no specific cause was found. She started working in the building in 1994 and worked there full-time for 5 years.
Her examination was normal except that she fell on Romberg testing and could only walk a few steps in tandem. Brain MRI, EEG, audiogram, and pulmonary function tests were normal. Quantitative rotational chair and caloric vestibular tests revealed bilateral peripheral vestibular dysfunction (Table ; Figure ). Her caloric responses improved following removal from the under-ventilated environment (Table ).


A 54-year-old female National Guard contract specialist presented with 2 years of intermittent dizziness, blurred vision, and occasional palpitations. Dizziness was experienced at least 3 days a week. She reported intermittent problems with erratic heart beats, cough, sneezing, headaches, fatigue, recurrent sinus infections, upper respiratory tract, and bladder infections. She worked in the purchasing warehouse full-time for 3 years. When away from the workplace her symptoms were improved. After moving with her colleagues into a new building, the frequency of dizziness was lessened.
Her medical, neurological, and oto-neurological examinations were normal. Electronystagmography revealed somewhat reduced caloric vestibular responses for age and a 33% reduced vestibular response on the left. Rotational testing showed reduced gain with sinusoidal rotational stimuli at frequencies from 0.02 to 0.16 Hz (Figure ). Her caloric responses improved following removal from the “sick-building” environment (Table ). Computerized dynamic posturography showed falls on conditions 4, 5 and 6 indicating some general impairment of equilibrium and a predominant vestibular deficit pattern. Audiometric tests were normal except for mild-sensorineural hearing loss in the right ear from 250 to 8,000 Hz and borderline normal left-sided hearing from 250 to 2,000 Hz sloping to a moderate loss between 3,000 and 8,000 Hz.


A 77-year-old female presented with one day of sharp, severe right upper quadrant pain and nausea and vomiting. The pain did not radiate. Two years previously, she had undergone wide local excision of a superficial spreading melanoma of the upper back with a thickness of > 2.0 mm (Stage IIa, T3a N0 M0). Sentinel lymph node biopsy was negative for tumor. Her physicians deemed her to be in complete remission.
On physical exam, she was afebrile and anicteric. Vital signs were within normal limits without postural change. Abdominal exam was notable for marked right upper quadrant tenderness with guarding, but without signs of peritoneal irritation, mass, or organomegaly. White blood cell count was elevated to 13.1 × 103/μL, hemoglobin was within normal limits, and creatinine was 2.6 mg/dL. Serum liver chemistries, amylase, and lipase were all normal.
She received imaging studies in the emergency department. Plain abdominal flat plate revealed air outlining the gallbladder (). Helical CT images through the abdomen after oral and intravenous contrast showed extensive intramural gas with a thickened gallbladder wall surrounded by marked inflammatory changes. Imaging was consistent with a perforated, emphysematous gallbladder ().
The patient was admitted and started on intravenous ampicillin-sulfabactam. Urgent open cholecystectomy was performed after an unsuccessful attempt at laparoscopic cholecystectomy. The surgical specimen revealed perforated emphysematous cholecystitis and biliary sludge. A 1 cm brownish polypoid lesion projected into the lumen, arising from the mucosa of the fundus, but not obstructing the cystic duct. The lesion was positive for malignant melanoma by immune-histochemistry. No microorganism was isolated. Subsequent chest and abdominal CT scans revealed unsuspected, irregular lesions in the left lung consistent with metastatic melanoma, a probable metastatic lesion in the liver, and enlarged lymph nodes in the upper abdomen. After discussion, the patient decided to delay treatment until she became symptomatic. She died within months.


In November 2015, we observed a woman 82-year-old, with an episode of caustic soda ingestion at the age of twenty-three for suicidal purpose. At that time, she presented to the emergency department with chest pain, vomit and hematemesis. The patient was hemodynamically stabilized and underwent a gastric lavage. Esophagogastroduodenoscopy showed several esophageal burns, ulcerations and liquefactive necrosis. In the following days, the patient experienced dysphagia, odynophagia, heartburn, hematemesis and weight loss. After three months, the symptoms gradually decreased but a cicatricial fibrotic stenosis of the lower third of the esophagus aroused. The patient started self-dilatation with semi-rigid dilators without reaching any relevant symptomatology relief. At one year from the ingestion, she autonomously bought a Maloney dilator of 5 mm of calibre, and started periodically self-dilatations, after an adequate training, consisting of undergoing physician-performed endoscopic dilation and participating in three self-dilation practice sessions supervised by a physician, according to the technique described by Dzeletovic []. The periodical self-dilations and semi-liquid nutrition led to a great improvement of her nutritional status (Figs. , and ). The patient had been in good wellness for about 40 years, when she presented to the Emergency department of Surgical Endoscopy for an esophageal obstruction. A food remnant was endoscopically removed, and for the first time the patient underwent an esophageal dilatation with a Savary bougie. For the following 20 years, the woman has practised occasional Savary bougie endoscopic dilatation (maximum calibre 7 mm) alternated with self-bougienage, achieving a good control of symptoms. Moreover, only over the counter, drugs as dimethicone and sodium alginate have been seldom administered. Only during the last year, the patient has experienced dysphagia, heartburn and nocturnal reflux, so an upper gastrointestinal barium examination has been carried out. A stenosis of the middle and lower third of the oesophagus with a delayed emptying was identified (Fig. ). An endoscopic 7 mm Savary bougie dilatation was performed with a significantly relief of symptoms. Currently, the patient undergoes monthly standard Savary bougie dilatation with an excellent control of the symptoms.


A 75-year-old female with history of Type II diabetes presented to the emergency department (ED) with “double vision and right eye redness” for several weeks with isolated right eyelid swelling for one week. She had recently seen her ophthalmologist who noted the swelling and ordered magnetic resonance imaging (MRI), which showed inflammation extending from the right paranasal sinuses into the orbit. She was sent to the ED with concern for an infectious process such as mucormycosis. She had never had nasal, septal, or sinus surgery; however, she did have a remote history of trigeminal neuralgia treated with neurectomy 30 years prior. In the five years prior to this presentation, she had experienced facial paresthesias and pruritus managed by compulsive manipulation of her face, nose and sinuses with cotton tip applicators and fingers.
On physical exam, the patient was nontoxic with normal vital signs: temperature 98.1° F, heart rate 94 beats per minute, respiratory rate 18 breaths/min, blood pressure 121/72 mm/Hg. Visual acuity in each eye was 20/20 without visual aids. She was noted to have right eye proptosis, periorbital edema and erythema, in addition to right medial gaze palsy. She had erosive necrosis with complete destruction of the right ala nasi and grossly patent right nasal aperture. While the right inferior turbinate appeared normal, the right middle turbinate was scarred with extensive right septal scarring and scabbing ().
The patient’s laboratory testing revealed a white blood cell count 8.7 103/cmm and serum glucose 216 mg/dl. Axial computed tomography (CT) () showed dehiscence of the inferomedial right orbital wall with soft tissue density and stranding extending into the medial retro-orbital fat posterior to the orbital apex resulting in proptosis of the right eye. The right optic nerve sheath appeared thickened. The right nare was partially absent giving the appearance of a chronic wound or previous sinus surgery. Underlying encephalomalacia of the right temporal lobe from previous right neurectomy was also noted.
The patient was admitted with the diagnosis of orbital cellulitis and treated with parenteral vancomycin and piperacillin-tazobactam. Otolaryngology, ophthalmology, and psychiatry were consulted. Fiber optic endoscopy demonstrated extensive paranasal sinus destruction, with friable mucosa. The tissue destruction seen on CT and subsequent MRI was initially concerning for other serious infections, such as mucormycosis or malignancy; however, frozen pathology showed no evidence of an invasive fungal infection or malignant transformation. Other possible etiologies such as the autoimmune disorders Wegener’s granulomatosis or granulomatous polyangitis were considered.
The required rheumatologic work up to evaluate for these potential causes would include the following: antinuclear antibody; C-reactive protein; erythrocyte sedimentation rate; and anti-neutrophil cytoplasmic antibodies. These lab tests were abandoned when the sinus culture was positive for Staphylococcus aureus, and the patient rapidly improved with the appropriate intravenous antibiotics. Psychiatric consultation determined that the patient had a component of an unrecognized OCD. The combination of ongoing facial paresthesia in the V2 division of the trigeminal nerve resulting from the previous trigeminal neuralgia surgery and the newly diagnosed OCD provided the diagnosis of TTS leading to the orbital cellulitis.
The patient was ultimately discharged on a course of oral amoxicillin-clavulanic acid and daily fluoxetine to address her previously undiagnosed obsessive-compulsive behavior. In a four-month clinic follow-up, the right ala nasi still appeared necrotic with the right nasal aperture still being widely patent. There was no overt evidence of active infection. The patient did not complain of any visual compromise and no visual acuity was obtained. The patient reported medication non-compliance and continued repetitive manual manipulation of her nose. She refused any further treatment.


An 18-year-old male presented to the ED with left testicular pain and swelling following blunt scrotal trauma sustained during a wrestling match. The pain was immediate, but did not necessitate removal from play. Post-injury, the pain progressed, prompting presentation to our ED. The patient denied dysuria, hematuria, or any other symptoms. Past medical and surgical histories were unremarkable. Vital signs were normal. On physical examination, the left testis was tender to palpation, grossly swollen, and tense compared to the right. The remaining physical examination, including abdominal exam, was unremarkable.
Scrotal POCUS was carried out by the EP using a Sonosite Edge system using an L13–6 linear transducer operating at 10 MHz. Sagittal and transverse images of the affected testis along with comparison views of the unaffected side were obtained. Analysis with color and spectral Doppler was performed. The left testis was enlarged with a grossly heterogeneous texture as seen in and the . Discontinuity of the tunica albuginea and irregularity of the testicular margins were noted as seen in and the . Additionally, a hypoechoic complex fluid collection consistent with hematocele was present in the left hemiscrotum, and blood flow was not uniformly identified throughout the left testis. The left epididymis was unremarkable. The right testis appeared normal with homogenous parenchyma, intact tunica albuginea, smooth, preserved borders, and uniform distribution of blood flow throughout by color Doppler analysis (seen in , panel A, ). No fluid collection was observed within the right hemiscrotum and the right epididymis was unremarkable. A rapid diagnosis of left testicular rupture was made in the ED, and urology was consulted.
The patient was taken to the operating room for scrotal exploration. The left testis was found to be fractured, without viability of the lower segment. All nonviable tissue was removed, and bleeding was controlled. The upper pole was preserved, the tunica albuginea and vaginalis were re-approximated, and the scrotum was closed. The patient was admitted overnight for observation and discharged the following morning. At six-week follow-up, the patient had returned to normal activity.


A 27-year-old 58-kilogram Caucasian female presented to the emergency department (ED) with acute onset cough, increased secretions, and dyspnea. She had a history of asthma, pulmonary embolism and double seronegative myasthenia gravis (MG) status post thymectomy and was gravida one para zero at 31-weeks gestation. Her MG had been refractory to standard medical therapies during pregnancy, necessitating scheduled plasmapheresis every three weeks. Additional management included systemic corticosteroids and Lovenox injections, though previous hypercoagulable testing had been negative. Her pregnancy had been uncomplicated except for mild MG symptoms of ptosis and difficulty with mastication.
Further review of systems revealed nasal congestion for three days with sore throat but no fever. She denied chest pain or edema but did complain of resting dyspnea and generalized weakness, similar to past myasthenic flares. That evening, she had increasing difficulty clearing her secretions despite her cough, and albuterol treatment by emergency medical services did not improve her symptoms.
On exam, she was in respiratory distress with accessory muscle usage. Vital signs were heart rate 120 beats/minute, blood pressure 120/84 millimeters of mercury (mm Hg), respiratory rate 26 breaths/minute, oxygen saturation 100% on 35% fraction of inspired oxygen by facemask, and temperature 36.7 degrees Celsius. She had stridor on exam, but otherwise heart and lungs were normal. Her abdomen was gravid but nontender. The remainder of her physical exam was unremarkable. Chest radiograph was normal. Her initial maximum inspiratory pressure (MIP) was -15 centimeters of water (cm H2O) and forced vital capacity (FVC) was 2.0 liters, with an arterial blood gas (ABG) showing pH 7.54, partial pressure of carbon dioxide (PaCO2) 21.5 mm Hg, bicarbonate 18 milliequivalents/liter (mEq/L), partial pressure of oxygen (PaO2) 177 mm Hg.
Given her poor respiratory status and worsening fatigue, the patient was trialed on bilevel positive airway pressure (BiPap) but had minimal improvement, so she was intubated without complications. A computed tomography pulmonary angiogram demonstrated a small, clinically insignificant subsegmental pulmonary embolism. Testing for rhino/enterovirus was positive, bilateral lower extremity Dopplers were normal, and the patient was admitted to the intensive care unit for myasthenic crisis and respiratory failure.
She was started on pyridostigmine and dexamethasone for MG and fetal lung maturity. Intravenous immunoglobulin (IVIg) was previously ineffective, so she underwent plasmapheresis every other day for five treatments. She was successfully extubated and transferred to the antepartum service, but her course was further complicated by hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) with rising blood pressure, necessitating cesarean section. Magnesium was avoided for fear of worsening her MG. A vigorous female infant was delivered without evidence of neonatal MG or arthrogryposis and was discharged after one month of management for prematurity. The mother also recovered completely.


A 69-year-old man with a past medical history of untreated hypertension, chronic back pain, and heavy smoking was brought in by ambulance to a community emergency department (ED) for severe bilateral leg pain and paraplegia. He had been unable to ambulate and remained lying on the floor for the prior three days. The patient also admitted to chronic low back pain that had worsened over the preceding week and not improved with his usual pain medications of naproxen and aspirin. He had no other complaints and denied any fevers or chills.
The patient’s initial vital signs were as follows: temperature 36.6 degrees Celsius, blood pressure 157/84 mmHg, heart rate 95 beats/min, respiratory rate 38 breaths/min, oxygen saturation 94% on room air. On physical examination, the patient appeared cachectic and chronically ill. His cardiac exam revealed a regular heart rate and rhythm without murmur. He had no palpable femoral, popliteal, or dorsalis pedis pulses bilaterally. A Doppler ultrasound performed at bedside further demonstrated a lack of pulses bilaterally from the femoral to the dorsalis pedis arteries. Abdominal examination showed a scaphoid, soft, non-tender abdomen without a pulsatile mass. There was no midline spinal tenderness or step-offs on musculoskeletal examination. Neurological evaluation demonstrated complete sensory loss from T10 and ending on the S1dermatome bilaterally. He had 5/5 motor strength in both upper extremities and 0/5 strength in hip flexion and extension as well as ankle dorsiflexion and plantar flexion bilaterally. The dermatological examination of the lower extremities revealed pale, cold, and mottled-appearing skin from the hips to the ankles bilaterally.
Initial laboratory data for the patient revealed white blood cells (WBC) 26.9 x109/L with neutrophil count 88.8%, hemoglobin 14.3 g/L, hematocrit 44.4%, and platelets 288 x 109/L complete metabolic panel showed the following: sodium (Na) 127 mmol/L, potassium (K) 7.3 mmol/L, chloride (Cl) 99 mmol/L, carbon dioxide (CO2) 18 mmol/L, blood urea nitrogen (BUN) 82 mg/dL, creatinine (Cr) 4.4 mg/dL, glucose 123 mg/dL, alanine transaminase 288 units/L, aspartate transaminase 1,372 units/L, albumin 3.4g/dL, alkaline phosphatase 86 units/L, direct bilirubin 1.0 mg/dL, indirect bilirubin 0.2 mg/dL, and total bilirubin 1.2 mg/dL. Prothrombin time, international normalized ratio, and partial thromboplastin time were 11.0, 1.0, and 26.9 seconds, respectively. Lactic acid was 3.36 mmol/L and creatinine kinase was 111,693 units/L. Troponin was also elevated at 3.850 ng/mL, and the electrocardiogram showed diffuse and deep T-wave inversions in the inferior, anterior, and lateral leads.
Point-of-care ultrasound of the abdominal aorta revealed a linear hyperechoic shadow in the aorta. Chest radiograph displayed a mildly tortuous ectatic aorta and evidence of chronic obstructive pulmonary disease (COPD). CT of the chest demonstrates a Stanford Type B aortic dissection (). The dissection starts from the subclavian and extends well into the infrarenal region of the abdominal aorta with significant mural thrombosis. On three-dimensional reconstructed images of the CTA abdominal aorta and bilateral lower extremities with runoff, significant stenosis is visible in both renal arteries, especially in the left (). The right lower extremity demonstrates near-complete occlusion of the right common iliac artery and both internal and external iliac arteries. The popliteal artery and arteries below the right knee are occluded. No blood flow to the right lower extremity is noted. The left lower extremity also demonstrates severe narrowing with moderate thrombosis in the iliac arteries with complete occlusion of the left external iliac artery. The left popliteal artery is likewise occluded, and no blood flow to the left lower extremity is visible. In addition to the above findings, intramuscular gas is seen in the thighs bilaterally, raising suspicion for myonecrosis ().
In the ED, the patient was aggressively resuscitated with an initial two-liter bolus of normal saline. A central venous catheter was inserted in the left internal jugular vein and the patient was started on an intravenous (IV) esmolol drip. He also received IV heparin, calcium chloride, sodium bicarbonate, insulin, glucose, and morphine during his ED stay. Shortly thereafter, the patient was taken for emergent dialysis in the intensive care unit (ICU) to further correct his electrolyte abnormalities, renal failure, and rhabdomyolysis prior to operative treatment. The laboratory abnormalities were partially corrected to a WBC of 17.5 with neutrophil count of 79.7%, K of 6.6, BUN of 87 and Cr at 3.6. The patient subsequently underwent open bilateral iliofemoral aortic popliteal thrombectomy, stent placement in the abdominal aorta and bilateral iliac arteries and bilateral femoral endarterectomy and patch angioplasty. While in the operating room, the patient became hypotensive and bradycardic and eventually suffered cardiopulmonary arrest. Despite a brief return of spontaneous circulation after resuscitative efforts, the patient died shortly thereafter in the ICU.


An 88-year-old Caucasian male presented to our ED by ambulance after being found unresponsive on the floor of his home by family. On arrival he was pale and mottled, with a Glasgow Coma Scale of 3. He was normothermic, tachycardic in sinus rhythm, hypertensive, and severely hypoxic. Traumatic injuries on exam were significant for large anterior chest wall contusion, right leg laceration, and inwardly rotated legs of equal length with symmetric hips. Peripheral pulses were 1+ palpable. The patient was intubated in upright positioning due to oxygen desaturations while lying flat. An orogastric tube drained coffee-ground fluid and a urethral catheter initial efflux was clear yellow and then transitioned to gross hematuria. The patient’s initial labs were significant for influenza A, acute kidney injury, ischemic hepatitis, rhabdomyolysis, lactic acidemia, non ST-segment elevation myocardial infarction, and a negative comprehensive drug screen. His family arrived later and provided additional history. He had been a healthy, independent octogenarian who played tennis weekly, had no medical problems, and took no prescription medications. In the week prior to the incident, the patient exhibited flu-like symptoms but sounded well on the phone one day prior to presentation. When they found him unresponsive, he was not found near stairs.
Computed tomography revealed bilateral posterior hip dislocations with both femoral heads superior and posterior to the acetabulum ( and ). There were no pelvic fractures. Bilateral closed hip reduction was performed at the bedside using the Allis reduction maneuver. With the hip stabilized by an assistant, traction was applied to the femur with the knee in flexion, as the hip was slowly flexed to 90 degrees. An obvious “clunk” occurred as the femoral head slid back into the acetabulum. The hip was then slowly extended maintaining traction and the leg positioned in abduction and external rotation while post-reduction films were obtained. There was concern for right hip instability because the patient required multiple right hip reductions, including axial traction as described above, and modified Allis maneuver without knee flexion. The left hip was reduced easily with axial traction. Both legs were placed in knee immobilizers and positioned in hip abduction and flexion. Reduction was confirmed with AP pelvis radiograph (). Dorsalis pedis and posterior tibial pulses were palpable before and after the reduction. The patient was transferred to the intensive care unit (ICU).
The patient was awake and following commands while intubated on ICU day 1, and was extubated on ICU day 10. His only neurologic deficit was mild difficulty with concentration. On follow-up, patient recalled that he was standing on a level surface and reaching for a glass of water when he lost balance and fell with his legs “doing the splits.” He denied head trauma or loss of consciousness with his fall. He was unable to call for help despite dragging himself across the floor, and he lay on the ground for approximately 30 hours. He had never sustained prior hip injury or dislocation. On ICU day 9, orthopedic surgery performed an exam under anesthesia and found no joint instability. Later, he developed decreased sensation in the right leg attributed to sciatic neuropraxia. His hospital course was complicated by multisystem organ failure requiring initiation of dialysis, possible aspiration pneumonia, atrial fibrillation with rapid ventricular rate, metabolic encephalopathy, and hematochezia with acute blood loss anemia. He was eventually transferred to the inpatient hospice unit and expired on hospital day 23.


A 33-year-old female with a history of mild intermittent asthma was sent from a mental and behavioral healthcare facility for evaluation of acute dyspnea. Her dyspnea began three hours prior to arrival and was associated with chest tightness, which she described as similar to previous asthma exacerbations. In addition, her medical history included hypertension, generalized anxiety disorder, bipolar disorder, and polysubstance abuse. She denied hemoptysis, lower extremity swelling, history of prior deep vein thrombosis or PE, estrogen use, current or prior malignancy, recent surgery or trauma.
Triage vital signs were temperature 36.5°C, blood pressure 106/58 mmHg, heart rate 120 beats per minute, respiratory rate 32 breaths per minute, and oxygen saturation 92% on room air. She appeared anxious and unable to sit still on the gurney. Her lungs were clear to auscultation with symmetric air movement bilaterally without wheezing. Her exam was otherwise normal. Her electrocardiogram (ECG) demonstrated sinus tachycardia with right bundle branch block (RBBB) (). Portable chest radiography demonstrated no cardiomegaly, pulmonary edema, pleural effusion, or pneumonia.
On initial impression, the diagnosis of pulmonary embolism was considered. The patient was risk stratified with a Wells Criteria for Pulmonary Embolism score of one and a half, for tachycardia, and a Pulmonary Embolism Rule-out Criteria (PERC) score of two, for tachycardia and hypoxemia., With a low-risk Wells score and a positive PERC score, a D-dimer was obtained in addition to cardiac biomarkers and lactic acid. She was treated initially with intravenous (IV) fluids and aspirin 324mg, but she continued to be restless, refusing oxygen and unable to sit comfortably.
Laboratory results were significant for elevated D-dimer of 2524 ng/mL (normal <230 ng/mL), B-type natriuretic peptide (BNP) 7295 pg/mL, troponin I 0.117 ng/mL, and lactic acid 5.4 mmol/L. POCCUS demonstrated signs of RV strain with a dilated RV on the parasternal long axis (PLAX) () and septal flattening with RV dilation on the parasternal short axis (PSAX) view (). Computed tomography pulmonary angiography (CTPA) confirmed extensive thrombus within the distal right main pulmonary artery extending into the segmental and subsegmental branches, as well as the segmental and subsegmental branches supplying the left upper and lower lobes.
Treatment with therapeutic heparin was initiated. Despite this, the patient remained dyspneic, uncomfortable and anxious with no improvement in vital signs. The risks and benefits of thrombolytic therapy, compared to observation, were discussed in depth with the patient. She elected for thrombolytic therapy and was treated with alteplase 100 mg infused over two hours. Repeat POCCUS performed one hour after thrombolytic administration demonstrated significant improvement of RV strain (), and repeat ECG at 24 hours showed resolution of the RBBB (). Complications included only minor bleeding from her nose, mouth, and peripheral IV sites. She was admitted to the medical intensive care unit and discharged to the psychiatric facility on hospital day three on oral anticoagulation.


A previously healthy 10-month-old female presented to our emergency department (ED) with a two-day history of multiple episodes of non-bilious vomiting and abdominal distension. One week prior to presentation, the parents had noticed an irreducible umbilical mass. There was no history of diarrhea or fever. On examination she was alert, her heart rate was 108 beats per minute, blood pressure was 84/50 millimeters of mercury (mmHg), capillary refill was less than two seconds, and there were no signs of dehydration. Her abdomen was distended but soft and bowel sounds were present. An irreducible tense umbilical mass of 3×3 centimeters (cm) was noted. The skin was normal around the umbilicus, but appeared shiny over the mass. Her cardiovascular, respiratory and central nervous system examination was unremarkable.
An initial diagnosis of incarcerated umbilical hernia was considered. The pediatric emergency medicine (PEM) fellow performed a POCUS using linear transducer (14-5MHz), which showed a well-circumscribed hypoechoic structure suggestive of a fluid-filled sac. The sac did not communicate with the intra-abdominal cavity, and there was no evidence of bowel loops or peritoneum in the sac (). A diagnosis of urachal cyst was considered. In view of the multiple episodes of non-bilious vomiting, a trial of oral rehydration therapy was done in the ED for two hours, which the baby tolerated well. On reassessment, the abdomen was soft and there were no signs of dehydration. The baby was discharged home with a diagnosis of acute gastroenteritis with no dehydration and an incidental finding of probable urachal cyst. A comprehensive ultrasound done by the radiologist the next day confirmed the presence of urachal cyst with no evidence of vesico-urachal diverticulum, and the baby was followed up in the outpatient urology clinic.
A two-year-old male presented to the ED with redness and a prominent protrusion in the umbilical area for two days. There was no fever, vomiting, abdominal pain or discharge from the umbilicus. He had a recent hospitalization for urinary tract infection requiring intravenous antibiotics. On examination he was alert, his heart rate was 96 beats per minute, blood pressure was 104/72 millimeters of mercury (mmHg) and capillary refill was less than three seconds. The abdomen was soft and non-tender, with no guarding or rebound tenderness. An umbilical mass of 2×2 cm was noted, and the overlying skin was erythematous and tender. The skin around the mass was not erythematous or indurated. The genitourinary examination showed normal, bilaterally descended testes and no inguinal hernia.
The PEM fellow performed a POCUS using linear transducer (14-5MHz), which revealed a protruding hypoechoic structure suggestive of a fluid-filled sac that did not communicate with the intra-abdominal cavity. There were no bowel loops within the sac and there was no cobblestoning of the overlying skin (). A probable diagnosis of infected urachal cyst was considered. Urology was consulted and agreed with the diagnosis of infected urachal cyst/remnant. The patient was started on oral cefprozil for 10 days and advised to follow up in the urology clinic. A comprehensive ultrasound done by the radiologist the next day revealed the urachal cyst with a vesico-urachal diverticulum.


A 63-year old-female presented to the ED with three days of headache, diplopia, and gait instability. The symptoms began while the patient was watching television and progressively worsened over three days. The headache was described as a pressure, located on the left temple without associated neck stiffness or photophobia. The diplopia was binocular and horizontal. She described her gait instability as “walking like I am drunk.” She reported decreased oral intake over the previous day due to “not feeling well.” Recent medical history included community-acquired pneumonia, currently on day 5 of 10 of moxifloxacin. She had no recent travel or changes in her daily activities. The patient had no history of stroke, bariatric surgery or recent vomiting. The patient and family denied a history of alcohol use.
On exam, blood pressure 139/80, heart rate 67, respiratory rate 16, room air oxygen saturation 98% and temperature 97.3 degrees Fahrenheit. She was well nourished, well developed and in no acute distress. Her head was atraumatic with moist mucous membranes. The patient was awake, alert, and oriented to person, place and time. Her eyes were anicteric and the left eye displayed ptosis. Her left pupil was sluggish compared to the right, but both were reactive. Uncorrected visual acuity was 20/60 OD and 20/60 OS. Left eye demonstrated complete paralysis of extraocular movements; right eye demonstrated 10–15 degrees of movement in all directions, and nystagmus in right eye on lateral gaze. The remaining cranial nerves were intact. She had intact strength and sensation to light touch throughout the upper and lower extremities. Cerebellar testing was remarkable for past pointing on the left with finger to nose, and her gait was characterized by small, unsteady steps with ambulation in the ED. The remainder of her exam was unremarkable.
Ancillary testing in the ED was remarkable for a white blood cell count of 14,400/uL, hemoglobin of 15.0 g/uL, hematocrit of 43.4%, and platelet count of 527,000/uL Chemistry panel, liver function studies and erythrocyte sedimentation rate were all within normal limits.
An emergent, non-contrast head computed tomography (CT) was performed, which did not show an acute intracranial hemorrhage, mass effect or midline shift. A brain and neck magnetic resonance imaging and angiography (MRI/MRA) were obtained, which did not demonstrate a cortical lesion, aneurysm or other vascular defect to explain her symptoms. Her case was discussed further with neurology and she was started on high-dose thiamine for concerns of WE and admitted to the internal medicine service for further evaluation. No thiamine level was obtained during her initial admission.
Her symptoms did improve after parenteral high-dose thiamine. She was discharged on hospital day three with continued oral thiamine supplementation. At her one-month neurology follow-up appointment she still had a mild ophthalmoplegia but was otherwise back to her baseline functional status.


A 24-year-old female with a BMI of 22 had dry needling to her left posterior shoulder for MSK pain; 30 minutes later she developed severe pain around the site and shortness of breath. She presented to the ED five hours later with a respiration rate of 22 breaths per minute (BPM) and SpO2 of 98% on room air. Her pain score was 7/10 on a numeric rating scale (NRS). Reduced air entry over the left anterior chest was noted by auscultation. A chest radiograph (CXR) revealed a 22% left apical pneumothorax (calculated by interpleural distance). The patient was observed overnight and discharged after a repeat CXR the following morning showed no change of the pneumothorax size. A repeat CXR 10 days later showed full resolution.


A 21-year-old female with a BMI of 18 developed severe, right-sided chest pain and shortness of breath shortly after receiving acupuncture for “knots” in her neck. She presented to the ED the following day with 7/10 NRS right-sided pleuritic chest pain. Her vital signs were a heart rate of 102, a respiration rate of 22 BPM and SpO2 of 100% on room air. Decreased breath sounds were noted over the right upper zone. A CXR demonstrated a 26.3% right-sided pneumothorax. The patient was discharged home and re-presented the following day for a repeat CXR, which demonstrated no change in pneumothorax size. On day four after her initial presentation, the patient re-presented with sudden onset of worsening shortness of breath and pain. A CXR was taken and showed that the pneumothorax was resolving. She was given stronger analgesia, which improved her symptoms. A further repeat CXR at nine days showed full resolution of the pneumothorax.


A 21-year-old female with a BMI of 21 presented with 6/10 (NRS) sharp left-sided chest pain, dizziness, nausea and pre-syncope one-and-a-half hours after dry needling for left-sided MSK shoulder pain. Her vital signs were a heart rate of 66, a respiration rate of 24 BPM and SpO2 of 100% on room air. Decreased breath sounds were noted over the left lung field. A CXR demonstrated a 16.2% left apical pneumothorax. A repeat CXR four hours later showed a 20.6% pneumothorax. Since the patient remained clinically stable, she was managed conservatively with a follow-up appointment three days later. Here, CXR showed that the pneumothorax was resolving. At a further appointment 21 days after the initial presentation, CXR demonstrated full resolution.


A 15-month-old male infant presented for failure to thrive, irritability, and constipation since the age of 6 months. He was the product of full-term pregnancy with no antenatal or perinatal complications. Physical exam revealed a small, undernourished baby with a peculiar facies. His weight was 6.3 kg; length 74 cm; and head circumference 42 cm, all significantly below the third centile for age. The rest of the physical exam was unremarkable. Laboratory tests revealed hypercalcemia at 17.5 mg/dl (normal: 8.4–10.6 mg/dl), normal serum phosphorus at 4.2 mg/dl (normal: 2.4–4.9 mg/dl), and high urinary calcium/creatinine ratio (UCa/UCr) at 1.1 (normal value up to 0.5) () with normal serum 25-hydroxyvitamin D (25 OH-vit D) at 32.3 ng/ml (normal: 20–60 ng/ml). Renal ultrasound showed grade III bilateral medullary nephrocalcinosis and echocardiography detected mild supravalvular aortic stenosis. The diagnosis of Williams’s syndrome was then confirmed by FISH probe analysis which revealed a deletion at 7q11.23 encompassing the elastin gene. Hypercalcemia was treated by the traditional approach with intravenous hydration and furosemide infusion (1 mg/kg). Serum calcium decreased to 12 mg/dl and the patient was discharged on calcium-restricted diet. Ten days later, however, serum calcium rose to 16.1 mg/dl. The same intravenous treatment regimen was used and serum calcium decreased to 11.6 mg/dl for 48 h, only to rise to 17 mg/dl following discontinuation of furosemide. Serum intact parathyroid hormone (PTH) was suppressed at 1.5 pg/ml (normal: 10–65 pg/ml). He received, then, an infusion of 1 mg/kg pamidronate over 6 h with no side effects observed. Two days post-infusion, serum calcium dropped to 11.8 mg/dl and UCa/UCr to 0.6. Patient was discharged home on calcium unrestricted diet. One month later, he received a second intravenous infusion of 1 mg/kg pamidronate for recurrent hypercalcemia up to 14.1 mg/dl, which decreased serum calcium again to 9.9 mg/dl. Subsequently, the patient was kept on a calcium unrestricted diet and maintained normal serum calcium level of 9.5 mg/dl, UCa/UCr of 0.12 as well as 25 OH-vit D of 30 ng/ml, at 5 years of follow-up. At 6 years of age, his growth parameters had improved considerably. He is currently at the fifth percentile for height and between fifth and tenth percentile for weight. Renal ultrasound showed stable grade III bilateral medullary nephrocalcinosis.


Case 1 is a 24-year-old trans woman, working as a plumber, and single. She was referred for a psychiatric screening as the first step for the referral pathway to the Gender Identity Clinic after she disclosed to her GP that she was using hormones purchased online. The patient has no previous history of mental or physical illness, she described herself as TGNC since age 14 and started the transition, without medical supervision two years before the assessment. The patient joined on line forums where she received the information regarding the hormonal protocols and the websites selling hormones. She started the treatment on her own and subsequently asked the GP to be referred for gender reassignment/gender affirmation. At the time of the assessment, the patient did not present any comorbid psychiatric or physical conditions.


Case 2 is a 22-year-old trans woman with a previous history of depression at the age of 14 that was successfully treated with a Serotonin Reuptake Inhibitor (SSRI). The patient stated that she felt like a person “trapped in the wrong body” ever since she could remember. She complained of being bullied at school for this reason, and she thinks that the bullying and the non-acceptance from her friends caused the depressive episodes in her teens. She started the protocol online and asked the GP to continue prescribing, and the GP asked for a psychiatric opinion before proceeding. She had been using oestrogens, finasteride, and spironolactone intermittently in the last two years. The patient also has type I diabetes, treated with insulin. According to the GPs notes, the compliance with the insulin treatment and the control of his diabetes is not optimal. The mental state examination was unremarkable; the patient presented, however, traits of emotionally unstable personality disorder.


Case 3 is a 19-year-old trans woman, a college student, and single. She was referred by the GP for a psychiatric assessment following numerous suicidal attempts and self-harm episodes. She had a provisional psychiatric diagnosis of Emotionally Unstable Personality Disorder—Borderline type. During the psychiatric assessment, she disclosed using oestrogens and finasteride purchased online in order to proceed with the transition. She also reported that since she started using these hormones the emotional instability became more severe and was partly responsible for the deterioration of her clinical presentation.


Case 4 is a 26-year-old trans woman, living with a partner and working as an administrator. She was referred by her GP for psychiatric assessment as part of the procedure for a referral to the Gender Identity Clinic. The patient had no previous history of mental illness, no medical comorbidity. During the interview she disclosed using oestrogen cream and finasteride tablets purchased online although she did not disclose it before (even with the GP). The mental state examination was unremarkable.


Case 5 is a 36-year-old TGNC woman, single and unemployed. She was referred by the GP for a psychiatric assessment due to low mood and polysubstance misuse (cocaine, cannabis, amphetamine and gamma-Hidroxybutyric acid (GHB). During the interview, the patient stated that she has been taking oestrogen, spironolactone and finasteride for 15 years. A year ago, she was referred to the gender reassignment clinic where she was diagnosed with moderate depression and generalised anxiety disorder, but she was asked to see a general adult psychiatrist for the treatment. The patient complained that the main contributing factors to her depression were the stigmatisation and the lack of acceptance, in which she felt that she was victimised mainly by members of her family and her community. She also was frustrated with the length of the waiting list.


Case 6 is a 25-year-old TGNC man, unemployed, living with his partner. The patient was referred for a psychiatric assessment after he disclosed to the GP about using androgens without medical advice and supervision. The patient complained of The Gender Identity Research and Education Society feeling “uneasy with his body” since the age of 12. He started to purchase androgens online, 2 years before the psychiatric assessment, following a protocol available online. The patient also has stage 4 renal failure, and he was under the care of the renal team.


Case 7 is a 27-years-old TGNC man and a university student. He was admitted to an inpatient psychiatric unit after a suicidal attempt. The patient was presenting with moderate depression, on admission, he reported of using androgens purchased online while on the waiting list for an assessment by the Gender Reassignment Clinic. The patient was using the hormones without any medical advice or supervision. The low mood and the suicidal attempt were linked to his stressful situation at the university (where he struggled to cope with academic pressure) rather than to the hormonal treatment, that he also stated that he found the hormones to be beneficial. He was also frustrated by the long waiting list before he was able to start his gender affirmation process.


Patient24, an 11-month-old girl, was the first and only child of a non-consanguineous Chinese couple. Decreased fetal movement was noted during pregnancy. She was born by cesarean section at full-term, with a birth weight of 3800 g, length of 49 cm, and head circumference of 34 cm. She visited our hospital at 4-month-old due to growth delay and examinations including head MRI, thyroid function assay, limb electromyography, urine gas chromatography-mass spectrometry, blood amino hydroxy acids and carnitine spectra detection, and karyotype analysis found no abnormity. This time, she hospitalized because of fever with vomiting for 1 day and febrile seizures for 4 hours. The child manifested as loss of consciousness, opening eyes, and rhythmic movement of the arms and legs for a few minutes (Fig. ). The symptoms could be relieved, however, attacked about every half an hour. She lapsed into mild coma, with the GCS of 9 (eye 2+ verbal 4+ motor 4). Skin mottling was found around all her skin and contracture of fingers was noted (Fig. ). Fasting blood glucose test was 1.5 mmol/L (reference value: 3.9–6.2 mmoL/L), indicating hypoglycemia. Immediately after admission, glucose, and midazolam were applied and the seizure stopped quickly. Unfortunately, coarse crackles were noted around the lung and the proband showed dyspnea symptoms and obvious facial cyanosis. She passed away due to cardiovascular failure 5 days after admission.
The girl was firstly suspected as metabolic disease or mitochondrial disease, but no disease related to mitochondrial gene mutation was found. As a result, some suspicious nuclear genes were screened out (Table ), however, these genes did not match family segregation analyses or their harmfulness was uncertainty. Additionally, no exons indel was found by checking the NGS data. We recently encountered a patient with genetic disorder caused by imprinting gene, therefore, we focused on the variants of imprinted genes. Finally, we locked into a genetic variant in MAGEL2. Trio-WES showed a novel heterozygous c.1628delC(p.Pro543Leufs*159) variant in the patient and her father while the mother showed the “reference allele” at this site. This variant has not been recorded in SNP database (dpSNP, 1000 Genomes, ExAC, ESP, HGMD, Clinvar) or in-house control database. Standard interpretation according to ACMG guideline showed that the variants were PVS1+PM2+PP4, met the standard of “pathogenic”. Heterozygous mutation in MAGEL2 was found both in P24 and her father, notably, the girl developed symptoms whereas her father was normal. As MAGEL2 is reported to be maternally silenced, it is possible to assume that the mutation of the patient was inherited from her grandmother. In order to validate our hypothesis, Sanger sequencing was applied to the pedigree. As illustrated in Fig. , however, the identified site in the grandmother presented reference allele. In addition, her grandfather, aunts, and cousins all were normal in this site.


Patient31 was a one month and 14 days old boy when he hospitalized in our hospital. He was the second child born to healthy non-consanguineous Chinese parents after 37 + 4 weeks of gestation. His birth weight was 2820 g, length was 48 cm, and head circumference was 31 cm. Dyspnea appeared without obvious cause, and no fever, cough, expectoration, vomiting, diarrhea, or convulsion was noted. He suffered from poor reaction, sucking rejection, and joint contracture (Fig. ). Dysmorphic facial features including low set ears and micromandible were found. The scrotum was small, scrotal fold reduced, and the testicle had not fallen. Limb and toe joint contractions were revealed, with extension lag. Limbs muscle tone decreased and the physiological reflex disappeared. Dyspnea was alleviated by tracheal intubation and mechanical ventilation, however, hypotonia still existed. After 1 week of admission, the patient had a stable breathing, and then discharged with a nasal feeding tube. Follow up at two weeks after discharge showed that he was died one week after discharge (two months old).
A de novo c.1996insC(p.Gln666Profs*47) variant in MAGEL2, which was reported as the mutational hotspot in patients with Schaaf-Yang syndrome was identified by WES. The variant in the family trio was confirmed by Sanger sequencing (Fig. ). As MAGEL2 is an imprinted gene, it is necessary to confirmed that the variant was located on the paternal allele. Unfortunately, the patient passed way and we had no sample to perform further tests. However, combining the clinical manifestation and molecular results, the patient was diagnosed as Schaaf-Yang syndrome.


The patient’s father provided written consent to the use the patient’s medical information for research and publication.
A 1-year-old girl (weight 10 kg) had suffered from a cough with sputum production for more than 2 days. She had a medical history of having swallowed a TFB 2 days earlier. The physical examination was normal, except for a wheezing sound in the right lung. A chest computed tomography scan revealed an 8 × 4 × 21 mm3 mass in the trachea near the carina, which given the patient’s history, was suggestive of the diagnosis of a TFB aspiration. After careful preoperative preparation, we scheduled the patient to undergo an emergency rigid tracheobronchoscopy to remove the TFB under general anesthesia. In order to keep the patient in spontaneous breathing, the combination of intravenous and inhalant anesthesia with propofol, fentanyl, and sevoflurane was planned to be administered. In the operating room, standard monitoring was installed, including SpO2, noninvasive blood pressure, and an electrocardiogram. Before administration of anesthesia, the child was premedicated with atropine (0.1 mg) and dexamethasone (2 mg)intravenously. Then anesthesia induction was performed with 8% sevoflurane carried by 6 L/min oxygen flow. After the patient became unconscious, anesthesia was maintained with 3–5% sevoflurane and 1 L/min oxygen flow for more than 5 min. Before rigid tracheobronchoscopy introduced into the trachea, the child received propofol (20 mg) and fentanyl (10 μg) intravenously to deepen the anesthesia. After 1–2 min, when her lower jaw was flabby, the surgeon introduced a LTA applicator into the trachea under the guidance of rigid tracheobronchoscopy, and then sprayed topical 1% lidocaine on the surfaces of the vocal cords and trachea. After the surgeon applied the topical anesthetic to the trachea, the girl suddenly suffered from bucking, which made it difficult to withdraw the LTA applicator. The surgeon quickly examined the opening of the main trachea using rigid tracheobronchoscopy, and found the TFB had migrated to the subglottic region against the LTA applicator. In this situation, manual ventilation became impossible and within half a minute, the patient’s SpO2 decreased to 91% and her heart rate dropped from 150 to 100 bpm. We administered an intravenous injection of atropine (0.3 mg) and succinylcholine (10 mg). Meanwhile, the surgeon tried to free the TFB by pushing it back into the trachea, after which the LTA kit was easily withdrawn. We then mask-ventilated the lungs successfully. The patient’s SpO2 quickly increased to 97% and her heart rate rose to 140 bpm. After deepening the anesthesia with propofol (20 mg) intravenously, the surgeon successfully grabbed and removed the TFB under jet ventilation (Fig. ). Afterwards, the girl’s condition improved quickly and she recovered uneventfully. She was discharged from the hospital 2 days later without complications.


The patient in this case was a 16-year-old female with orthopedic problems who had undergone several spine surgeries for kyphoscoliosis, and had received gentamycin after the procedures. After 6 months, the patient experienced continuous dizziness, unsteadiness and oscillopsia after using aminoglycoside (gentamicin). She also had abnormalities in movement due to inner ear and orthopedic problems, especially upon standing and walking. The vertigo was continuous and worsened upon motion, particularly in relation to vertical head movement and walking. Patients with this condition also tend to suffer severe imbalance, oscillopsia, gait abnormality and frequent falling. The patient had been treated by several ear, nose and throat (ENT) specialists and a neurologist with betaserc and cinnarizine since first experiencing vertigo in the 4 months prior to our visit. The patient left school because of her vertigo and imbalance.
Initially, the patient underwent a case history and several auditory tests, and showed normal hearing in pure tone and speech audiometry, good speech discrimination, type A tympanogram and present acoustic reflexes. The result of previous electrocochleography also was normal. The patient did not demonstrate ear fullness, low pitch tinnitus or episodic vertigo. For vestibular assessment, we performed several physical and functional vestibular tests to determine the extent of the abnormality, including electronystagmography (ENG) (Hortmann, Otometrics, Denmark), a Halmagyi head impulse test (HIT), cervical vestibular evoked myogenic potential (cVEMP) (EP25, Intra acoustic, Denmark), ocular vestibular evoked myogenic potential (oVEMP; EP25, Intra acoustic, Denmark), a bedside dynamic visual acuity test (DVT), Romberg test and Persian dizziness handicap inventory (DHI). DHI showed high validity, reliability and internal consistency (). ENG and HIT are used for assessing semicircular canals; cVEMP and oVEMP evaluate otolith organs; DVT shows visual acuity during movement and is related to vestibular abnormality. The Romberg test is used for balance evaluation, and DHI shows the impact of vertigo and imbalance on the patient.
The result of ENG showed normal ocular motor function, no spontaneous or positional nystagmus and BVD in a caloric test (less than 3° nystagmus for cold and warm stimulus in both ears). The bedside HIT was abnormal, and overt catch-up saccade was observed. The cVEMP and oVEMP results were abnormal on both sides. The patient could stand in the open-eye situation of the Romberg test, but lost balance after closing her eyes. The DVT was positive and the patient missed nine lines in the Snellen chart between visual acuity in the static situation and DVT. The DHI score was 84, representing profound disability and decreased quality of life. These results represent abnormal function in the horizontal semicircular canals, saccular and utricular system on both sides, loss of vestibular ocular reflex and a much-decreased quality of life.
The vestibular rehabilitation requires nine sessions (over 8 months), but the patient and rehabilitation team were well connected. The rehabilitation plan mainly focused on gaze stability and adaptation exercises including horizontal X1 exercise with near object, vertical X1 exercise with near object, horizontal X1 exercise with far object, vertical X1 exercise with far object, horizontal X1 exercise with near object and large target, vertical X1 exercise with near object and large target, diagonal gaze stability exercise, horizontal X2 exercise with near object, vertical X2 exercise with near object, horizontal head movement while waking with fixed vision, vertical head movement while waking with fixed vision and bouncing up and down a trampoline with fixed vision. We assessed the patient’s progress (quality of life, balance and oscillopsia) using DHI, the Romberg test and DVT through rehabilitation, as shown in ().
These results showed no change in the first three sessions (roughly a 2-month period) in quality of life, vertigo, imbalance or oscillopsia. However, after this period, the patient showed gradual progress in all areas. The DHI score must change by at least 19 to be considered significant progress (); therefore, change in this parameter from Session 1 to 4 is considered significant progress and clinically important. In last session, the DHI scores were close to normal and the Romberg test and DVT results were normal. These findings show complete compensation of the vestibular ocular reflex, normal balance function and a good quality of life.


A 56-year-old woman was referred to the emergency department due to a severe headache in the frontal area for 2 days before admission. The patient had nausea and vomiting in the morning but had no history of seizures or decreased consciousness. The examination of neurological symptoms was completely normal and showed no symptoms of meningeal irritation. The patient's vital signs were recorded as follows: blood pressure (BP)=130/85 mmHg, heart rate (HR)= 86/min, and temperature (T)=37.3 °C. In her past history, the patient had undergonetympano- mastoidectomy surgery and resection of the cholesteatoma 1 week earlier, and a canalwall down mastoidectomy (CWD) was performed due to right ear cholesteatoma. According to the information obtained from the previous surgeon, microtrauma was inflicted in the dural plate during surgery, but since no significant cerebrospinal fluid (CSF) leak occurred during the procedure, reconstruction was not necessary. After admission, examination and initial evaluation, the Mount Fuji sign was found on the brain CT scan of the patient, but no evidence of brain abscess or intracranial hemorrhage. The patient was immediately admitted to the intensive care unit (ICU).
Initial treatments such as CBR, 30-degree head elevation, anti-fever therapy, analgesics and oxygen therapy, along with anti-compulsive drug (phenytoin), were prescribed. The patient did not undergo surgery due to a lack of neurological symptoms and a decreased level of consciousness or seizures. However, in the ICU, the patient was maintained under regular and continuous monitoring of vital and neurological signs and level of consciousness. The day after admission, the patient’s headache had completely resolved. The patient was admitted to the ICU for 5 days and was monitored for volume ofpneumocephalus every day with a CT scan. At the end of 5 days, the patient's pneumocephalus was resolved completely, and she was transferred to the ward. The patient was discharged after complete recovery.


A 30-year-old male patient diagnosed with SS sickle cell disease presented with
sickle cell crisis and decompensated heart failure. Echocardiogram showed left
ventricular dilatation (left ventricle end-diastolic diameter of 7.1 cm and
end-systolic diameter of 5.1 cm), an ejection fraction of 53%, and a pulmonary
arterial pressure of 70 mmHg, as well as a bicuspid aortic valve with severe
insufficiency (). At admission, the
patient had hemoglobin (Hb) of 3 g/dL, hematocrit of 9%, and Hb electrophoresis with
89.3% of hemoglobin S (HbS). Angiotomography showed a 4.8 cm dilatation in the
tubular portion of the ascending aorta (). As a result of the multiple triggering factors for pulmonary
hypertension, a right cardiac catheterization was performed, which demonstrated mean
pulmonary artery pressure of 56 mmHg, mean capillary pressure of 30 mmHg, and
pulmonary vascular resistance of 8.9 Wood units, characterizing a pulmonary
hypertension by pre and post-capillary components.
Due to the challenges imposed by the case, a wide discussion was made by the
institution's heart team. Considering the cardiovascular component's contribution in
the symptomatology and that this prevented any reasonable quality of life, a
surgical procedure was indicated.
In preoperative management, an exchange transfusion was planned aiming at hematocrit
values > 25%, Hb > 10 g/dL, and HbS < 30%. However, simple blood
transfusions were performed daily, which led to a hematocrit of 30.3%, Hb of 10 g/dL
and 27.1% of HbS.
The patient underwent an aortic valve replacement and ascending aortic aneurysmectomy
in October of 2016 at Hospital de Clínicas de Porto Alegre, a tertiary-level
hospital. Anesthetic induction was performed with 12 mg of midazolam, 500 mcg of
fentanyl, and 30 mg of rocuronium. Anesthesia was maintained with 0.7% isoflurane,
midazolam, fentanyl, and rocuronium. Cardiac arrest was achieved by administering 20
ml/kg of Custodiol(r) hypothermic cardioplegia to the coronary ostia, according to
the manufacturer's instructions, additional topical hypothermia was not used. During
extracorporeal circulation, in order to avoid the occurrence of sickle cell crisis,
the patient was maintained in normothermia (nasopharyngeal temperature above 34ºC)
and hypoxia and acidosis were avoided, maintaining arterial oxygen saturation
between 97.7% and 99.9%, and serum pH between 7.31 and 7.82. Resection of the native
and ascending aorta was performed with subsequent implantation of a bovine
pericardial prosthesis nº 25 and a supracoronary Dacron tube nº 26. Cardiopulmonary
bypass and ischemic time were 95 and 85 minutes, respectively. There were no
surgical or anesthetic complications. Cell saver was used throughout the procedure.
Coagulation disorders were corrected based on activated clotting and
thromboelastometry tests (ROTEM(r)).
In the immediate postoperative period, the patient presented hypovolemic shock and
required an exploratory mediastinotomy, which didn't indicate the presence of active
bleeding sites.
He presented a satisfactory postoperative evolution and he was discharged on the
18th postoperative day, presenting complete symptoms resolution. In
an outpatient follow-up, the patient showed significant symptomatic improvement and
absence of major surgical complications.


Case 1: A five-year-old Moroccan girl was diagnosed clinically as having AS at 12 months. Her apparently healthy parents were third cousins. She was born by normal vaginal delivery after a full-term pregnancy with a normal birth weight of 3800 g. From the age of 5 months she had a history of asthenia, anorexia and vomiting. From 12 months, she had generalized hyperpigmentation of the skin and failure to thrive. She had not been able to produce tears since infancy. Physical examination at this time showed height 67 cm (− 2.84 SD), weight 8.300 g (− 1.27 SD), blood pressure 84/43 mmHg. No abnormality was found in the heart, lungs, abdomen, nervous system and external genitalia. Baseline investigations revealed normal full blood count, serum creatinine and electrolytes. Basal serum cortisol at 8 AM was unrecordable at < 0.3 nmol/L while plasma adrenocorticotropic hormone (ACTH) was markedly elevated at 228.8 pmol/L. The results of a bilateral Schirmer test confirmed the diagnosis of alacrima. Hydrocortisone therapy replacement was started at 10 mg/m2/day with artificial tears and topical vitamin A. At this time, esophagography showed no abnormality. At follow up, aged 2 years, the patient presented with high blood pressure - 120/70 mmHg. Plasma aldosterone was 170 pmol/l (reference range 22–477) and plasma renin activity was 359.7mUI/l with a normal aldosterone to renin ratio. Echocardiography was normal. Autonomic dysfunction and hence the 4 A syndrome was therefore diagnosed. After 10 months of the treatment with captopril, the blood pressure normalized at 90/50 mmHg and antihypertensive treatment was stopped. At this time, the patient presented with perioral cyanosis and cold extremities and was found to have hyponatraemia (plasma sodium 126 mmol/L) with high urine sodium (35 mmol/24 h). Mineralocorticoid deficiency was diagnosed and treated with fludrocortisone 50 μg per day. Partial loss of primary teeth was noted from 2 years of age at which time esophagography showed a dilated esophagus with distal narrowing. Manometry was not performed in view of the patient’s age. Following the diagnosis of achalasia, the patient underwent surgery with esophago-cardiomyotomy and fundoplication. She became symptom free for about 19 months, but the dysphagia recurred and was treated with balloon dilatation of the esophagus. A year later the symptoms recurred and balloon dilatation was again performed but without relief of symptoms on this occasion. High resolution manometry showed normal lower esophageal sphincter (LES) resting pressure (29 mmHg) with incomplete relaxation, prolonged integrated relaxation pressure (IRP) (27 mmHg) and aperistalsis. By the age of 3 years and six months, her weight had become static at 10 kg (− 2.5 SD) and a gastrostomy tube was inserted. Currently the patient is aged five years, weight 15 kg (− 1.5 SD) and height 97 cm (− 2 SD).


A 44-year-old female patient with a history of nodular goiter presented with progressive dyspnea and noisy breathing for several months. In ENT outpatient department, subglottic stenosis was discovered through endoscopy. A computed tomography (CT) scan demonstrated a 4.0 × 3.0 × 1.7 cm hypodense mass with ill-defined margins in the left thyroid gland (Fig. ). The thyroid tumor was accompanied by three enlarged neck lymph nodes in the left level II and level III regions. Neither a nasopharyngeal lesion nor a lung mass was indicated through serial CT scans. The patient underwent FNAC for evaluation of the left neck lymph node and thyroid tumor. FNAC of the lymph node indicated cohesive epithelial fragments with syncytial appearance and lymphocytic infiltrates, resembling metastatic nasopharyngeal carcinoma (Fig. and ). The FNAC sample of the left thyroid disclosed loosely cohesive clusters of follicular epithelial cells, as well as an abundant dense extracellular matrix (Fig. ). Only a few atypical epithelioid cells were recognized through the thyroid FNAC (Fig. ). The unusual presentation and cytomorphological features posed a diagnostic difficulty.
Under the impression that a malignant thyroid tumor was present, the patient received debulking surgery, including a total thyroidectomy and bilateral neck lymph node dissection. The histologic slides of the left thyroid tumor revealed undifferentiated carcinoma with lymphoepithelioma-like features, (Fig. and ) and a hyaline matrix was observed focally. The left and right thyroids were extensively sampled for characteristic components of well-differentiated carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3) and p40 but negative for TTF-1, Pax-8, and CD5. In situ hybridization for EBV-encoded RNA (EBER-ISH) was diffusely positive in the tumor cells (Fig. ). Seventeen and five lymph nodes were dissected from left and right soft neck tissue, respectively. The left metastatic node indicated metastatic carcinoma with lymphoepithelioma-like features, whereas metastatic papillary carcinoma was recognized in all of right neck lymph nodes (Fig. ).
The tumor could not be completely removed because of laryngeal invasion. Therefore, the surgeon performed a total thyroidectomy with preservation of the hypopharynx and larynx. Postoperative radiotherapy was provided for the gross residual local disease. After completion of adjuvant radiotherapy, a follow-up CT scan indicated a prominent regressive change in the tumor. At the time of study, the patient had been living with the disease for 1 year and 10 months.


A 53-year-old woman was admitted to the infectious diseases department presenting with a 24 h history of high fever, chills, vomiting, headache, confusion and altered general condition. The patient had a cholecystectomy several years ago and in the last month was evaluated for a possible diabetes mellitus. The patient had no history of travelling in foreign countries in the past five years. At admission the clinical examination revealed a partially conscious, delirious patient with nuchal rigidity, oliguria and haematuria. The skin was pale, with several bilateral ecchymoses on the legs and arms and papular exanthema on the calf (). The ophthalmic examination showed retinal haemorrhage and uveitis in the right eye.
Laboratory test showed leukocytosis (19 700 cells mm−3) with neutrophilia (18 700 cells mm−3) severe thrombocytopenia (7000 cells mm−3), high d-dimers (15 505 ng ml−1), inflammation (fibrinogen 8.1 g l−1, serum procalcitonin 60.3 ng ml−1), creatinine (406.7 µmol l−1), urea (244.5 mg dl−1), hyponatraemia (131 mmol Na l−1), hypokalaemia (3.3 mmol K l−1), cytolysis: aspartate aminotransferase 1.1× upper limit of normal (ULN), alanine aminotransferase 1.5× ULN, increased gamma-glutamyl transferase level (3× ULN), hypoalbuminaemia (2.5 g dl−1) and hyperglycaemia 14.2 (mmol l−1).
Because of the haemorrhagic risk, the lumbar puncture was delayed, but we microbiologically sampled the skin lesions on her calves and we took three sets of blood cultures. Treatment with vancomycin and ceftriaxone was started. We used insulin in order to normalize hyperglycemia and collyrium with dexamethasone, antibiotics and an anticholinergic for eye involvement.
A head magnetic resonance imaging (MRI) examination was performed, showing diffuse oedema and a minor lenticular lesion, possible an infarction. The echocardiography did not retrieve endocardial lesions. Abdominal echography revealed a liver mass and MRI was performed that showed an abscess with dimensions of 9.0×6.0 cm in the VIIth liver segment. Considering the probable involvement of a Gram-negative rod, the antibiotic treatment was changed to meropenem (2 g every 8 h).
On the second day of hospitalization the cultures performed from the skin lesions yielded Gram-negative lactose-fermenting rods, subsequently identified as Klebsiella pneumoniae through MALDI–TOF MS. The isolated strain had a positive string test, indicating a possible hypermucoviscosity phenotype. The antimicrobial susceptibility test yielded an isolate susceptible to cephalosporins, aminoglycosides and fluoroquinolones and we changed the antibiotic therapy to ceftriaxone (2 g every 12 h). On the third day of hospitalisation the blood cultures were also positive for Klebsiella pneumoniae with similar antimicrobial susceptibility.
On day 7, platelets count were 84 000 mm−3 and a lumbar puncture was performed, sampling a xanthochromic cerebrospinal fluid (CSF), with pleiocytosis, 15 leukocytes mm−3, elevated lactic acid (5.4 mmol l−1) and elevated proteins (2.54 g l−1). After 15 days of ceftriaxone (4 g per day) the patient underwent percutaneous drainage of the hepatic abscess. Combined therapy, both antibiotic and surgery, leaded to important improvement of the patient. The antibiotherapy was switched to oral amoxicillin–clavulanate (1 g three times a day) and the patient was discharged with close follow up until total remission of the hepatic abscess was confirmed through abdominal echography. Three months later she had good glycaemic control with oral medication and almost normal visual acuity.