We report the case of a 25-year-old African-American male with OCA2, who was admitted in response to a phone call his mother made to emergency services after making threats to kill himself. The patient was admitted with symptoms of auditory hallucinations, paranoid delusions of people stalking him and stealing his thoughts, self-neglect, depression, and suicidal thoughts, which, according to his mother had increased when he became medication noncompliant. He had been hospitalized and discharged one month prior at a different facility, when he had shot himself in the forehead with a BB gun in response to command auditory hallucinations. His mother called 911 when she discovered two BBs lodged in his forehead. He had been released after a two-week stay, but continued to experience command auditory hallucinations to kill himself. His mother again called 911 when he expressed his urges to attempt suicide again. Physical examination revealed the presence of one BB in his forehead, as well as nystagmus and hypopigmentation over his entire body. Social history revealed no smoking or alcohol usage, but a urine test was positive for cannabis. An inquiry into family history was made, and it was noted that the patient has a paternal female cousin with albinism (with no current signs of schizophrenia) and maternal grandmother with schizophrenia. As for his immediate family, there were no other cases of either schizophrenia or albinism among his biological parents or three siblings. According to his mother, he had previously lived a rather normal life (although more on the withdrawn side) and schizophrenic symptoms had only developed a few years prior, when he was around 22 years old.
The patient was started on risperidone, which was uptitrated to 6 mg daily, and escitalopram at 10 mg daily for ongoing depressed mood. This medication combination lessened the intensity of auditory hallucinations significantly, but he remained very depressed and isolative on the inpatient psychiatric ward, and continued to express thoughts of hopelessness. Lithium augmentation was started, and lithium was uptitrated to 900 mg daily. With the addition of lithium, the patient’s neurovegetative symptoms of depression and his sense of hopelessness lessened. He ceased to have thoughts of suicide, and began to interact with treatment staff, as well as psychotherapeutic rehabilitation activities offered on the ward. He also allowed treatment team to consult with ENT (ear, nose, and throat) services to have the BB removed from his forehead. He agreed to engage with intensive wrap-around mental health services, along with ongoing psychosocial rehabilitative treatment offered as part of outpatient mental health treatment. He returned home with his mother after his positive, cognitive, and negative symptoms of schizophrenia lessened to a degree that he no longer expressed any hopelessness or wishes to die.


The patient is a 10-year-old boy from a non-consanguineous and healthy couple. Two younger siblings, a girl aged 5½ years and a boy aged 3, are healthy. During the pregnancy of the proband, intrauterine growth retardation was detected. He was born at 37 weeks by caesarean section with Apgar scores 9/10 at 1 and 5 min, respectively. At birth, weight was 2.04 kg (2nd percentile, − 2.04 SD), height 43 cm (<3rd percentile, − 2.91 SD), and cranial circumference 30 cm (<3rd percentile, − 3.77 SD). The infant presented dysmorphic features such a triangular facies, low-set ears, and short neck, in addition to cryptorchidism. Abdominal and cranial ultrasound studies were performed with no evidence of malformations. Serology for common neonatal infections (toxoplasma, rubella, cytomegalovirus, and herpes simplex) as well as brain computerized tomography (CT) and funduscopy were normal.
At the 5th month of life, a prominent metopic suture was observed. The helical CT confirmed craniosynostosis of the metopic suture and ossification of the anterior fontanelle. At this follow-up visit developmental delay and limb hypertonia were detected. The subject began to crawl at 4 years of age and made his first unassisted steps at age 5. At 9 years of age absence seizures were clinically suspected and he was treated with valproate, showing good response. At 11 years the treatment was discontinued as the patient did not present seizures anymore and EEG was normal. Brain MRI (magnetic resonance imaging) was always normal. He was also treated with botulinum toxin because of hypersalivation due to dysphagia. The boy was also followed-up for severe myopia and constipation. He had a non-symptomatic large atrial septal defect, ASD (ostium secundum type).
At 10 years of age the dysmorphic traits continued, suggestive of Opitz C syndrome. The patient presented bulging eyes with true proptosis, mild epicanthus, hypoplastic nose, small mouth with normal philtrum and palate, and normal auricles (see detailed description in Table and Fig. : a, g and l). From the neurological point of view he presented with spastic tetraparesis, with ulnar deviation of the hands, wide-base gait (increased distance between the tibial malleolus when walking) not in the range of a cerebellar ataxia but denoting clumsiness and a subtle gait disturbance, and flexion of hips and knees. The patient lacks expressive language, but has improved his ability to understand and to establish communication. He does not respond to simple commands and has poor attention span. He is unable to chew and is fed mashed food. He walks with increased lift base and can take some steps alone. Usually, he needs walker support to get around and has no sphincter control. The patient is currently on physiotherapy and speech therapy, and pharmacological treatment with risperidone and methylphenidate due to behavioural disturbances and ADHD (attention deficit-hyperactivity disorder) traits, respectively.


The patient is an 11-year-old boy, the first child of healthy non-consanguineous parents. He was born at 38 + 5 weeks via caesarean section due to breech presentation after an uneventful pregnancy. At birth, weight was 2.97 kg (30th percentile, − 0.45 SD), length was 49 cm (25th percentile, − 0.28 SD), and cranial circumference was 33 cm (10th percentile, − 0.61 SD). On neonatal examination, sacral and suprasternal dimples were observed on ultrasound with normal subjacent tissues and reducible bilateral inguinal hernia.
The neonatal period was significant for poor feeding, mild hypertonia of limbs, and delayed gross motor development. He achieved head control at 3 months, sitting at 15 months, and crawling and kneeling later than 24 months; currently he walks only with a walker. His speech was also delayed as he started babbling at 22 months. His fine motor skills have improved with therapy; he is able to grab objects and play with both hands. Recurrent pneumonias were diagnosed with several hospital admissions, and dysphagia to liquids was observed, requiring thickeners. At age 2 years, an echocardiogram showed a 12-mm small ASD, ostium secundum type that was occluded with vascular plug system. Testing for inborn errors of metabolism (with plasma amino acids, acylcarnitine profile, total and free carnitines, and urine organic acids) was negative.
At age 6 years, he presented 2 episodes of loss of consciousness but electroencephalogram (EEG) did not confirm electric seizures. He was treated with valproic acid, currently on withdrawal. Brain MRI showed areas of polymicrogyria on the posterior right insula, delayed myelination, and slight descent of the cerebellar tonsils through the foramen magnum (Arnold-Chiari malformation).
On physical examination at age 11 years (Table and Fig. : b, c and h), the patient was found to have a short stature (height 113 cm, <3rd percentile, − 4.75 SD), microcephaly (cranial circumference of 49.5 cm, <3rd percentile, − 3.74 SD), and dysmorphic facial features such as flat facies, hypertelorism, mildly blue sclera and proptosis, full lower lip and protruding tongue that led to an open mouth expression, and low-set dysplastic ears. Ocular abnormalities included endotropia, astigmatism, and myopia. Additionally, the patient had one right supernumerary nipple, a single palmar crease on the right hand, poor palmar sulcation, and mild fifth finger clinodactyly in both hands. Neurologically, he showed intellectual disability, poor eye contact, generalized hypertonia, the need for a stroller to walk, and absence of comprehensible language, but with babbling. He presents midline manual stereotypies and suffers sleep disturbances with frequent awakenings.


The patient is a 9-year-old female, the only child of healthy non-consanguineous parents. Intrauterine growth retardation and mild left pyelectasis were detected during pregnancy. Birth weight was 2.30 kg (1st percentile, − 2.25 SD) and cranial circumference was 30.5 cm (<3rd percentile, − 3 SD). Screening for congenital disorders of metabolism was negative. Feeding difficulties and oral candidiasis were observed during the perinatal period. The subject achieved head control at 2 months, sat up at 10–12 months, began to crawl at 23 months, and presented unstable gait at age 3. At age 2, she was diagnosed with beta-thalassaemia minor (of paternal inheritance). Mild valvular pulmonary stenosis was also observed, although this problem had disappeared by 6 years of age. EEG was normal at the age of 3 years. Brain MRI, performed at few months of age, showed unspecific delayed myelination, although repeated imaging was considered normal when the patient was 3 years old.
At 6 years of age, when she was recruited by the SpainUDP (Spanish Undiagnosed Rare Diseases Program, ), she had global developmental delay, intellectual disability, language impairment, stereotypies, astigmatism, amblyopia, and recurrent conjunctivitis. Her physical exam showed craniofacial dysmorphisms including microcephaly, midface retraction, mild hypoplasia of the ear lobe, prominent antitragus, sparse medial eyebrows, proptosis, strabismus, broad and bifid nasal tip, short philtrum, prognathism, and big mouth (Table and Fig. : d and i). She also had wide intermammillary distance, bulging abdomen, protruding umbilicus placed on a small depression of the abdomen, mild genu valgo, pes planus, and fibular deviation of halluces.


The patient is an 8-year-old boy, the only child of non-consanguineous parents. No problems were detected during pregnancy and the neonatal period. He was born at term with a birth weight of 3.7 kg (76th percentile, + 0.70 SD) and a cranial circumference of 35 cm (34th percentile, − 0.42 SD). He achieved head control at 3 months, sat up at 8.5 months, and began to walk independently at 16 months. Microcephaly was detected at 2 months of age and he was diagnosed with atypical absences with eyelid myoclonias at the age of 16 months. He was treated with valproate from 21 months to 5 years with acceptable control of seizures. When the proband was 5 years old, it was withdrawn due to its association with adverse reactions (nauseas, vomiting, and weight loss). A few months later, valproate treatment was administered again since the number and intensity of epileptic crises had increased. In this recurrence of epilepsy, ethosuximide was needed together with valproate to achieve seizure control. Several EEGs carried out starting at age 3 years have disclosed spike-wave anomalies. When he was admitted to SpainUDP, at 6 years of age, the subject showed intellectual disability with altered fine motor coordination, unstable gait with frequent falls, language impairment, and autistic behaviour. He has always had sleep disturbances and hyporexia. Hypotonia with reduced muscle bulk has also been observed. Physical examination (Table and Fig. : e and j) showed microcephaly, long face, mid facial asymmetry, frontal central bossing, swollen skin on the upper eyelids, epicanthus, deep set eyes, mildly everted lower eyelid in its external part, and deep horizontal groove under the lower lip. Additional features include a slender appearance, scarce body adiposity, long and narrow thorax, mild genu varo (bilateral), pes planus, short halluces, sandal gap between the first and second toes, and flexed fifth toes.
Metabolic testing (including urine organic acids and glucose in cerebrospinal fluid) was normal. Brain MRI was normal.


The patient is a 6.5-year-old girl, first child of healthy non-consanguineous parents and with a healthy younger sister. The subject was born at term with an uneventful delivery and with a birth weight of 3.14 kg (42nd percentile, − 0.2 SD), a cranial circumference of 33 cm (10th percentile, − 0.61 SD), and Apgar 9/10 at 1 and 5 min. New-born screening for inborn errors of metabolism was normal. She had feeding problems from the neonatal period. During her hospital admission for dysphagia at 2 months of age, an atrial septal defect (ASD) was detected, which was surgically repaired at 16 months. She had delayed motor skills, with head control at 6 months, sitting up at 13 months, crawling at 16 months, and autonomous although unstable gait developing at age 2.
The subject has received physical, speech, and behavioral therapies and has attended a special school since 6 years of age. She is not able to talk, shows difficulties in adapting to new environments, shows significant behavioral problems with particular impact on the social domain, and has poor eye contact. Physical examination (Table and Fig. : f, k, m and n) showed dysmorphic features characterized by midface hypoplasia, almond-shaped eyes, and slightly upslanted palpebral fissures, and absent Cupid’s bow. Ears have underdeveloped antihelix, and are slightly low set, with increased posterior angulation. The hands show a complex palmar dermatoglyphic pattern with abnormal square radial border morphology. Tone, strength, and deep tendon reflexes are normal.
Remarkably, cranial MRI at age 6 revealed prominent cerebellar interfolia space compared with a previous MRI at 2 years of age; this is compatible with progressive cerebellar atrophy. No other significant alterations were detected on MRI. The subjected was recruited by the Undiagnosed Rare Disease Program of Catalonia ().


A 23-year-old previously healthy male presented to the ED with complaints of a headache that was gradual in onset and had been present for the prior 24 hours. He noted some lightheadedness and dizziness while standing, which prompted him to present to the ED for evaluation. He was febrile to 100.5 degrees Fahrenheit (F) and tachycardic to 110 beats per minute (bpm). The remainder of his physical exam was grossly unremarkable with no meningeal signs or focal neurologic deficits. He was provided antipyretics and intravenous (IV) fluids with complete resolution of his symptoms and discharged home with a diagnosis of viral syndrome.
Two days later, he returned to the ED with complaints of continued headache and fever. He recalled a “dry, tickling throat,” which was brief and self-limited in the prior two days. He was tachycardic, but afebrile on exam. With the exception of his tachycardia, his physical exam was again unremarkable without an identifiable infectious source. Laboratory evaluation demonstrated a bandemia of 8% (reference range 0–5) as well as mild transaminitis with alanine aminotransferase (ALT) 177 units per liter (U/L) (reference range 17–63) and aspartate aminotransferase (AST) 171 U/L (reference range 12–39). His rapid heterophile antibody test was positive. He was discharged home with precautions to avoid contact sports and to have repeated liver function tests performed by his primary care provider.
Three days after his second ED visit, he returned with jaundice, dark urine, and with continued fever and fatigue. He denied sore throat, cough, chest pain, abdominal pain, vomiting, diarrhea, hematuria, dysuria, or rash. He was again febrile with a temperature of 100.9° F and a pulse rate of 109 bpm. There was noticeable scleral icterus and diffuse jaundice. He was also noted to have multiple, palpable, posterior cervical lymph nodes.
Laboratory evaluation was notable for a leukocytosis of 14.8 ×10^3 cells per microliter (mcL) (reference 4.0–10.5) with lymphocytic predominance of 24% and thrombocytopenia of 99×10^3 cells/mcL (reference range 150–450). Comprehensive metabolic panel was notable for mild hyponatremia of 133 millimoles (mmol) per L (reference range 136–145 mmol/L), total bilirubin of 7.93 milligrams per deciliter (mg/dL) (reference 0.15–1.00), direct bilirubin of 6.9 mg/dL (reference range <0.2–0.3), alkaline phosphatase of 198 U/L (reference range 40–129), ALT of 753 U/L (reference range 17–63), and AST 692 U/L (reference range 12–39). Coagulation studies were within normal limits. Acetaminophen level was negative at <1.5 micrograms per milliliter (reference range 10–30). Hepatitis serologies were notable for a reactive hepatitis B virus core antibody, non-reactive hepatitis B core antibody IgM, positive hepatitis B surface antibody, and negative hepatitis B surface antigen consistent with immunity due to natural infection. Hepatitis C antibody was non-reactive. Human immunodeficiency virus testing was negative. Blood cultures were also negative. EBV heterophile antibodies were positive.
A formal right upper quadrant ultrasound demonstrated a mildly enlarged liver with normal contour. The gallbladder was visualized and noted to be contracted. The gallbladder wall was noted to be mildly thickened with a measurement of 0.34 centimeters. There was no evidence of cholelithiasis.
The patient was admitted to the hospital for supportive care and further laboratory evaluation. He was provided IV fluids, and liver function tests were trended every six hours. Liver enzymes gradually decreased and his jaundice resolved. His thrombocytopenia was thought to be related to acute hepatitis. Coagulation studies remained within normal limits. He was discharged from the hospital with a diagnosis of cholestatic hepatitis secondary to EBV. He followed up with internal medicine and had serial liver function tests over the subsequent weeks.


An 85-year-old female with a medical history of meningioma, seizures, and hypertension, presented to the ED after a ground-level fall. On physical examination, the patient was uncomfortable and tender to her right flank. Chest radiography (CXR) and computed tomography (CT) demonstrated six posterior rib fractures (T4 to T9). The patient had pain with an intensity rating of 10/10, and reported minimal improvement despite administration of intravenous (IV) morphine sulfate at 8 milligrams (mg). The SAPB was performed using 30 mL of 0.25% bupivacaine deposited superficial to the SAM, with complete relief of pain 10 minutes after the block. The patient did not require any further pain medication in the ED, and received only acetaminophen during her inpatient stay. She was discharged without any use of opioids.


A 72-year-old male with medical history of diabetes and hypertension, and daily use of ticagrelor presented to the ED after a fall from standing that day. On physical examination, he was not in any respiratory distress and had tenderness to the left lateral chest wall. CXR showed displaced overriding, left-sided posterolateral fractures of ribs 8 to 11 that was confirmed on CT. SAPB was performed using 30 mL of 0.25% bupivacaine deposited superficial to the SAM. No other analgesics besides the SAPB were given. The patient reported complete pain relief after the procedure, required no further pain medication in the ED, and was admitted to the trauma service.


A 78-year-old female with a history of diabetes and hypertension presented to the ED with six days of “pimples” to her right chest with pain intensity rating of 10/10. On physical examination she had a classic zoster rash localized to lateral chest within the distribution of T5 to T8 dermatomes. The patient had a SAPB performed with 20 mL of 0.5% bupivacaine mixed with 60 mg of solumedrol deposited superficial to the SAM. The patient did not require any other pain medicine during her ED stay and reported significant pain relief. She was discharged on gabapentin 100 mg three times per day upon discharge, and did not have any return visits to the ED.


An 89-year-old female with history of atrial fibrillation on aspirin, hypertension, congestive heart failure (CHF), and chronic obstructive pulmonary disease presented to the ED, after being found on the floor by family, complaining of left-sided chest wall pain. On physical examination, the patient was tachypneic with a respiratory rate of 25 breaths per minute, and had left lateral chest wall tenderness. She was placed on bi-level positive airway pressure (BIPAP). Her CXR demonstrated left-sided rib fractures of indeterminate age with prominence of interstitial lung markings bilaterally. Her CT was remarkable for left-sided rib fractures 2 to 11 with a segmental fracture of rib seven and trace left-pleural effusion. Her venous blood gas showed a pH of 7.29 (7.320–7.430) and PCO2 of 71 millimeters of mercury (mm Hg) (38–50 mm Hg).
She and the family did not want intubation. Despite administration of 650 mg of oral acetaminophen, 10 mg of IV ketorolac, and 25 micrograms of IV fentanyl, the patient continued to complain of severe pain. There was concern that more opioids would worsen her sedation, hypercarbia and respiratory acidosis. Thus, the SAPB was performed with 30 mL of 0.25% bupivacaine with epinephrine deposited deep to the SAM. After the procedure, the patient reported numbness to her left chest wall and complete relief of her pain. She was discharged two days later with a prescription for acetaminophen and lidocaine patch.


A 94-year-old female with history of CHF and atrial fibrillation not on anticoagulation presented to the ED in respiratory distress. On arrival, her respiratory rate was 32 breaths per minute and oxygen saturation was 94% on non-rebreather. Her physical examination was significant for a chronically ill-appearing female in respiratory distress with decreased bibasilar breath sounds and poor air movement. Her B-type natriuretic peptide was 1180 picograms (pg) per mL (<100 pg/mL) and CXR showed new bilateral moderate-sized pleural effusions. She was placed on BIPAP without improvement. The patient and family did not want intubation, so the decision was made to insert a pigtail catheter for drainage of the pleural effusion. Pre-procedurally, a SAPB was performed using 30 mL of 0.25% bupivacaine deposited deep to the SAM. The patient tolerated the procedure well and did not require any pain medication besides the SAPB in the ED.


A 60-year-old female with no past medical history presented to the ED with severe, left-sided chest pain two days after a mechanical fall down a flight of stairs. She went to an urgent care center and had a CXR showing five displaced rib fractures and was sent to the ED. On arrival to the ED, the patient was tachypneic with a respiratory rate of 25 breaths per minute. On physical examination, she was uncomfortable appearing with tenderness to palpation over the left lateral ribs. In the ED she was given 4 mg of IV morphine but still could not tolerate lying flat for a chest CT due to worsening pain. A SAPB was performed with 20 mL of 0.25% bupivacaine deposited superficial to the SAM. The patient had significant relief of pain and was able to lie flat almost immediately after the block, which allowed her to tolerate lying supine for a CT that showed anterior rib fractures T5 to T9 and posterior rib fractures T8 to T10. The patient was admitted to the trauma service.


A 63-year-old man presented to the ophthalmologist with complaints of painful red eye on his right. His vision was satisfactory, and there were no complaints on the opposite eye. He denied any trauma or ocular surgery in the past. There were no systemic complaints such as joint pains, dryness of mouth, fever, cough, or any evidence of renal involvement. He was averagely built with normal systemic examination. Ophthalmological examination revealed bilateral normal visual acuity and normal intraocular pressure. The sclera of the right eye was inflamed with multiple nodules on the temporal sclera. The left eye was normal. He was diagnosed as having anterior nodular scleritis () and was treated with topical steroids. Initial laboratory investigations were normal, and an apparent systemic cause for the scleritis could not be found. His chest radiograph, Mantoux test, sputum for AFB, and ultrasound scan of the abdomen were negative. The initial autoimmune markers (ANA, ANCA, and RF) were also negative.
During the next two months, he experienced frequent relapses of scleritis with gradual worsening with a poor response to the topical steroids so that the ophthalmologist decided to proceed with systemic steroids considering the progressive nature of the disease which appeared sight threatening. He received 3 pulses of intravenous methyl-prednisolone, but he did not have a durable response. Thereafter, the patient developed high-grade continuous fever for three weeks despite broad spectrum systemic antibiotics (intravenous ceftriaxone and doxycycline), and the blood, urine, and sputum cultures revealed negative results.
Thereafter, he was referred to medical ward for further evaluation of prolonged pyrexia. His investigations were full blood count showed lymphopenia with a high monocyte count (WBC: 5.9 × 103/μL, neutrophils: 4.47 × 103/μL (76%), lymphocytes: 0.83 × 103/μL (14%), and monocytes: 0.49 × 103/μL (8.2%)). There was a mild normochromic normocytic anaemia with a hemoglobin count of 8.8 g/dL, and the platelet count was normal (204 × 103/μL). His inflammatory markers were elevated (CRP 121 ⟶ 100 ⟶ 128), and the ESR was 79 ⟶ 100 ⟶ 134 mm/1st hour). Repeat chest radiograph and ultrasound scan of the abdomen were normal.
Re-examination disclosed the new occurrence of bilateral cervical and inguinal lymphadenopathy so that we proceeded for a cervical lymph node biopsy. The computed tomography of chest and abdomen revealed mediastinal, para-aortic, and inguinal lymphadenopathy with tree-in-bud pattern in the right lung apex suggesting the possibility of tuberculosis (). By this time, the sclera was also biopsied, and staining with Ziehl–Neelsen demonstrated AFB scattered in scleral tissue (). Histology of the sclera () and the cervical lymph node (Figures and ) revealed granulomatous caseating inflammation, and sputum for GeneXpert became positive confirming the diagnosis of tuberculosis. His HIV screening test was positive, and subsequently coexisting HIV infection was confirmed with Western Blot (CD4 count of 71 cells/mm3). Once the diagnosis of TB scleritis was made, he was started on the standard four-drug regimen for TB and continued for one month before the commencement of antiretroviral treatment (HAART). Treatment was continued uninterruptedly with close observation and follow-up. After two months of combined treatment, he showed evidence of healing scleritis () with no further relapses.


A previously healthy 39-year-old woman from the southern part of Saudi Arabia, who had no medical conditions of note other than hypertension, for which she was being treated with amlodipine, presented to our hospital with progressive, severe, left-abdominal pain and a history of weight loss over the previous two months without history of fever. She had had a laparoscopic removal of an ovarian cyst two years prior to her presentation. She had no history of trauma or of any unusual habits. She had sought care from several other hospitals before being referred to our hospital for further management as a case of retroperitoneal fibrosis. The physical examination showed no abnormalities and no palpable masses.
We initially worked-up the patient as a case of retroperitoneal fibrosis. The initial laboratory results revealed white blood cells (WBC) 5.47 × 109 cells/L, eosinophils 15.7%, absolute eosinophils 0.86 × 109 cells/L, erythrocyte sedimentation rate (ESR) 101 mm/h, and C-reactive protein (CRP) 8.63 mg/L. Additionally, immunological testing revealed that her antinuclear antibody (ANA) was negative, and her immunoglobulin G (IgG) subclasses were elevated as follows: IgG1 12.5, IgG2 9.49, IgG3 1.76, and IgG4 6.7 g/L.
A computerized tomography (CT) scan of her abdomen () revealed a large, retroperitoneal, hypodense, ill-defined mass surrounding the aorta and encasing the celiac artery, superior mesenteric artery, and left renal artery, causing severe narrowing of these vessels. It was also invading and occluding her left renal vein.
We performed CT-guided biopsy of the mass. The histopathological evaluation revealed broad and branching fungal hyphae with presence of eosinophilic sheets, an appearance characteristic of basidiobolomycosis (). We initiated antifungal treatment (oral itraconazole 200 mg twice daily) without any surgical intervention. A follow-up CT scan, performed 5 months later showed an excellent response to treatment, with a >60% reduction in the size of the retroperitoneal mass. In addition, laboratory investigation showed the following improvements: eosinophils 7.3% (compared to 15.7%), absolute eosinophils 0.68 × 109 cells/L (compared to 0.86 × 109 cells/L), ESR 42 mm/h (compared to 101 mm/h), and CRP 0.45 mg/L (compared to 8.63 mg/L). Currently, she is still on treatment and undergoing follow-up.


A 15-year-old boy was admitted to the Dermatology Department of the Second Hospital of Jilin University due to recurrent thrush for more than 10 years. The patient was of full-term normal delivery, with non-consanguineous marriage of his parents. Family history revealed no members with relevant infectious diseases, genetic abnormalities or immunodeficiencies. During the long course, the patient had been taking oral azole antifungal drugs intermittently for many years and the specific dose was unknown.
There was obvious white membrane on his oral mucous membranes and tongue, which was cracked with pain. There were erythema and papules on his face (Fig. a). The right sided toenails were hyperkeratotic with brown discoloration for many years (Fig. b).
Direct microscopic examination of mucous samples, which were obtained from patient’s oral cavity by sterile swabs, revealed the presence of yeast cells along with pseudohyphae, resembling Candida spp. infection (Fig. c). Typical white creamy yeast colonies were grown on Sabouraud Dextrose Agar (SDA, Fig. d). C. albicans was identified as the causative agent by sequencing of internal transcribed spacer region (ITS). Anti-fungal drugs susceptibility test showed that the minimun inhibitory concentration (MIC) of anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, fluconazole, and amphotericin B were 0.125 μg/m L, 0.06 μg/m L, 0.25 μg/m L, 0.125 μg/m L, > 8 μg/m L, > 8 μg/m L, > 16 μg/m L, > 256 μg/m, and 1 μg/m L. respectively. Lymphocytes analysis showed CD4+/CD8+ 1.02 (normal range 1.06–2.66), CD3-CD19+ 22.0% (normal range 5.0–18.0), CD3-CD(16 + 56) + 4.7% (normal range 7.0–26.0), other laboratory examinations, including complete blood count, serum immunoglobulin levels, and serum complement levels were normal. Glycemia, thyroid, parathyroid and adrenal hormones were within physiological limits.
On the basis of all the above findings, we made a diagnosis of CMC with resistant to azoles. However, after informing the patient and his family of the currently feasible treatments and considering the economic status of the patient’s family, the patient was still treated with itraconazole 200 mg (bid, PO). Fortunately, partial improvement was observed after 1 week. The patient is still under treatment now.
After signing the informed consent, peripheral blood was extracted by QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany). All exons of STAT1 were amplified by PCR. Sequencing was performed by Sangon Biotech (Shanghai, China). A heterozygous mutation (c.1162A > G, p.K388E) was identified in exon 14 of the patient (Fig. a and b). Such mutation was not identified in the samples from his parents (Fig. c and d).
C. albicans strain, termed as CA-R, was isolated from the oral cavity of the patient. The type strain SC5314 served as control. All strains were routinely cultured on yeast extract peptone dextrose medium (YPD) at 37 °C under constant stirring of 220 rpm/min for 12–24 h. C. albicans genomic DNA was extracted as described previously []. The extracted DNA was used as template for amplification of the full-length ERG3 and ERG11 genes, using the specific primers listed in Table . Compared with SC5314 strain, 8 nucleotide substitutions were identified in ERG11 gene of CA-R and 6 nucleotide substitutions were identified in ERG3, respectively. Among these substitutions, 13 were synonymous mutations and 1 was missense mutations of ERG11 resulting in amino acid changes (p.E266D, Table ). Amino acid exchange (E266D) was identified in fluconazole resistant isolates, however, such sequence differences may simply reflect the allelic variation.
RNA was isolated using RNeasy Mini Kit (QIAGEN, Hilden, Germany) according to the manufacturer’s instructions. The cDNA was synthesized with 1 μg RNA using the PrimeScriptTM RT Reagent Kit with gDNA Eraser (TaKaRa). RT-PCR was performed for independent amplification of internal reference gene (18S rRNA) and ERG11, CDR1, CDR2 genes to be quantified from the same cDNA template using a 7300 Real-Time PCR System (Applied Biosystems, Shanghai, China), with SYBR Premix Ex Taq (Tli RNaseH Plus. TaKaRa) using the primers listed in Table . PCR cycling conditions were 95 °C for 5 min, followed by 40 cycles of 95 °C for 5 s and appropriate annealing temperature for 30 s. SPSS 19.0 software was used for the analysis. The data were expressed as mean ± standard deviation (SD). The CT value of 18S rRNA was subtracted from the detected genes to obtain a ΔCT value. The ΔCT value of type material was subtracted from the ΔCT value of CA-R to obtain ΔΔCT. The relative quantification was performed using the 2-ΔΔCT method []. Expression of ERG11, CDR1 and CDR2 mRNA was detected in SC5314 and CA-R. The expression of CDR1 mRNA in CA-R was about 4.28-fold than that of the SC5314, while the expression of CDR2 mRNA in CA-R was about 5.25-fold than that of SC5314. The expression of ERG11 mRNA in CA-R was about 0.79-fold than that of the SC5314 (Table ).


On 15 July 2018, a five-year-old girl from Pedernales province in DOM arrived at the emergency room of Elias Fiallo hospital with a history of a fever (up to 38.5 °C) for five days, breathlessness, sore throat, irritability, anorexia, anxiety/panic attacks, and tachycardia. Antibiotics, antipyretics, and analgesics were prescribed with an initial diagnosis of febrile illness and moderate dehydration. A blood screening test showed neutrophilic leukocytosis (15.8 × 103/mm3, 92.2% neutrophils) and hyperglycemia (296 mg/dL). No additional testing was recommended. On 16 July 2018, the patient showed no improvement in response to treatment of symptoms, and her health worsened, presenting with alteration of behavior, hyperactivity, anxiety/panic attacks, and hallucinations. At this time, her parent requested she be transferred to a tertiary care hospital in Santo Domingo. The patient was referred to a pediatric psychology department with alteration of consciousness and rheumatic fever diagnosis. The father took the patient to Santo Domingo by public transportation. While in route she began vomiting and died while in the process of being admitted to the Hospital Taiwan in Azua province. Febrile illness and unknown history of animal exposure was the initial clinical diagnosis after the patient was deceased. Brain tissue was collected after authorization by the district attorney and preserved in formalin for pathology examination. A diagnosis of rabies was suspected based on the patient’s clinical symptoms. The DOM National Laboratory of Public Health “Dr. Defillo” submitted formalin-fixed brain cortex tissue to the rabies laboratory at the Centers for Disease Control and Prevention (CDC) in the United States. The sections of the brain required to rule out rabies (brain stem and cerebellum) were not submitted. RABV antigen was detected in the formalin-fixed tissue on August 3 by IHC. Specific RABV nucleic acid was also detected from different sections of the formalin-fixed brain tissue by the LN34 real-time RT-PCR assay.


A 23-year-old female presented to the emergency department (ED) with two days of acutely worsening bilateral blurry vision in the setting of a constant low-grade bitemporal and occipital headache different from her usual headache. She reported nausea and vomiting for the past month and seeing "bright spots" for two weeks. She also reported decreased appetite, night sweats, dyspnea on exertion, palpitations, and anxiety over the past month and a half. Review of system was negative for fever, chills, neck pain, head trauma, diplopia, or sudden onset of headache. Her past medical history included tension headache and anxiety. Her surgical history included appendectomy, tonsillectomy, and wisdom tooth extraction. Medications included citalopram, aspirin-acetaminophen-caffeine, ibuprofen, and levonorgestrel-ethinyl estradiol.
On arrival to the ED, the patient’s vital signs were blood pressure 161/86 mm Hg, pulse rate 114 beats/min, respiratory rate 20 breaths/min, temperature 36.8oC (98.3oF), and SaO2 95% on room air. On exam, the patient was anxious but alert and oriented with an otherwise unremarkable neurological exam. Her head and neck exam were notable for a supple neck without adenopathy and moist mucous membranes. Her cardiovascular exam was notable for tachycardia and a systolic 2/6 murmur. The patient’s ocular examination was notable for visual acuity of 20/90 in the right eye and 20/50 in the left eye, with intraocular pressures 13 and 12 mmHg, respectively. Pupils were equal and reactive without an afferent pupillary defect, and extraocular movement, confrontational visual fields, and anterior slit-lamp examination were normal. Her fundus examination, performed by an ophthalmologist, demonstrated bilateral diffuse intraretinal hemorrhages in all quadrants, white-centered retinal hemorrhage and dilated and tortuous retinal vessels without disc edema, concerning for bilateral CRVO. The reminder of her exam was unremarkable.
Laboratory testing disclosed numerous chemical and serologic abnormalities with concerning findings for hyperviscosity syndrome secondary to leukocytosis (see Table for details). Infectious workup for human immunodeficiency virus, hepatitis B, and hepatitis C was negative. Urine pregnancy test was negative. Chest radiograph (Figure ) demonstrated a widening of the mediastinal silhouette with a non-contrast computed tomography (CT) of the chest demonstrating a lobulated anterior mediastinal soft tissue mass concerning for lymphoma and splenomegaly (Figure ). Her brain CT was negative for intracranial hemorrhage or mass effect.
The patient was diagnosed with bilateral CRVO and leukemic retinopathy with serologic and radiographic testing consistent with ALL with blast crisis, characterized by an increased number of blast cells (immature blood cells). She was admitted to the oncology service where her hospitalization stay was complicated by tumor lysis syndrome, peripherally inserted central catheter line related deep vein thrombosis, hyperglycemia secondary to aggressive steroid therapy, and transient hypotension of unclear etiology with a negative infectious workup. Her bone marrow biopsy showed T-cell acute lymphoblastic leukemia (T-ALL) with >90% marrow involved with three signals for the ABL1 gene. She was initially managed with intravenous fluids, hydroxyurea, and dexamethasone, and started treatment for T-ALL with induction chemotherapy. She was discharged after 18 days of hospitalization with prophylactic acyclovir, sulfamethoxazole/trimethoprim, and prednisone as part of her chemotherapy regimen and outpatient retina clinic follow -up.


A 65-year-old male with a past medical history of hypertension, diabetes, renal cell carcinoma, status-post nephrectomy, and chronic kidney disease stage IV presents to the emergency department with sudden chest pain and shortness of breath. He denies any fever, chills, or prior episodes. Social history was significant for a 20 pack-year smoking history and intravenous drug abuse. Vitals were blood pressure 160/95 mm Hg, pulse 90 beats per minute, respiratory rate 18 breaths per minute, and temperature 37.8°C. Physical examination was significant for a nonobese male in acute distress and chest wall tenderness on palpation. A 12-lead electrocardiogram obtained revealed no ischemic findings. Laboratory findings revealed a creatinine of 4.3 mg/dL, baseline (3.0-4.5 mg/dL). Other laboratory findings including troponin and brain natriuretic peptide were normal. Planar V/Q scan obtained 8 hours later revealed a large filling defect in the inferior lingula and small defects in the posterior inferior left lower lobe and posterior inferior right upper lobe characteristic for PE ( and ).
Follow-up transthoracic echocardiogram revealed no evidence of ventricular strain. The patient was started on heparin drip and admitted for further management.
He remained stable throughout the admission and was successfully bridged to warfarin. He was later discharged home in stable condition, and international normalized ratio at that time was 2.3.
Two weeks later, he presented to the emergency department with similar complaints. Vitals were unremarkable, and physical examination was unchanged from prior. Significant laboratory finding was the international normalized ratio of 1.12. The patient reports nonadherence to warfarin. Due to concern for recurrent PE, 2 hours into admission, we obtained repeat V/Q scan, this time with single-photon emission computed tomography (SPECT) owing to improved sensitivity and specificity as well as its enhanced ability to differentiate resolving from acute perfusion defects. It revealed no filling defects ( and ).
Lower extremity Doppler ultrasound revealed no clot, and D-dimers were normal. Urine drug screen obtained was positive for cocaine. He later admitted to inhaled cocaine use a few hours prior to presentation. With the help of the radiologist, we compared both V/Q scans, and it was deemed that the filling defect initially identified was due to vasospasm of the pulmonary vessels, likely secondary to cocaine.
Warfarin was discontinued, cocaine cessation was advised, and his chest pain was managed as musculoskeletal pain. He was discharged home in stable condition.


A three-year-old male was admitted to the Pediatric Intensive Care Unit (PICU)
because of dizziness, vomiting, dysarthria and seizures. Meningoencephalitis was
suspected, and thus a cerebrospinal fluid exam was performed, which showed increased
cellularity with 70% neutrophils cells, 30% lymphomononuclear cells, glucose 60
mg/dL, proteinorrhage 55 mg/dL and a positive Pandy’s test. The bacterioscopy, latex
reaction, culture tests and Herpes virus serology were all negative. He was treated
with the diagnostic of an unspecified viral meningoencephalitis with acyclovir at a
dose of 30 mg/kg/day for 14 days, due to clinical improvement after starting the
medication. After the infection was stabilized, the neuro-pediatric team requested a
magnetic resonance imaging (MRI) of the child’s cranium because he was already in
the infirmary ward. The MRI was performed under Propofol-induced anesthetic effect
and maintained with sevoflurane through a laryngeal mask. No opioids, muscle
relaxants or benzodiazepines were administered. The child tolerated the procedure
well, and was transported back to the infirmary ward after recovering from the
anesthesia. Approximately three hours after the procedure, the patient presented
tachycardia, tachypnea, generalized muscle stiffness (especially in the masseter),
and hyperthermia, in that order.
Initially, seizures were considered to be the cause due to his underlying
pathological condition (meningoencephalitis). However, after receiving paranasal
catheter oxygen therapy and two doses of diazepam at 0.1 mg/kg/dose, his symptoms
persisted. The child was again referred to the PICU. Both the pediatric anesthesia
and neurology teams, made a diagnosis of MH, which was considered late, received 48
points in the MH Risk Rating Scale (
and ), and was classified as “very likely”.
Following intravenous administration of dantrolene at a dose of 2.5 mg/kg, the child
responded effectively and the symptoms disappeared almost immediately. His
hyperthermia subsided (), as well as
muscle contractions and other symptoms. Approximately 15 minutes after the
dantrolene was administered, his symptoms already under control, and laboratory
tests were performed (). Among the
laboratory findings, the changes related to MH found in the patient were hypoxemia
(partial arterial oxygen pressure - PaO2 63 mmHg), hyperlactatemia (26.9
mg/dL) and an elevation of muscle enzymes (creatine kinase - CK 1592 U/L).
Even though the patient evolved well, two days later his symptoms returned, probably
because he did not maintain the doses. Dantrolene had to be administered again and
maintained at a dose of 0.5 mg/kg every 12 hours. After starting doses that were
maintained, the patient’s clinical condition was stabilized again. Dantrolene was
administered continuously for 48 hours without further seizures.
After the diagnosis became clear and effective treatment was given, the patient’s
family members were advised about the need for follow-up at the Center for Study,
Diagnosis, and Investigation of Malignant Hyperthermia of the Universidade de São
Paulo (CEDHIMA/Unifesp), which also provides guidance via a telephone hotline to
assist healthcare professionals in diagnosing and treating MH.


A 46-year-old male patient presented with weakness, lethargy, night sweats, unwanted weight loss (− 12 kg), and sudden onset of cough at a local physician. The physical examination was inconspicuous. Blood test showed increased inflammatory values (C-reactive protein (CRP) 6.2 mg/dl, normal < 0.5 mg/dl) and leukocytosis (leukocytes 21,900/μl), body temperature was initially not measured. After empirical antibiotic therapy had no effect, a CT scan was performed. Here, a lesion with an axial diameter of 4 cm was found in segment VII of the liver (Fig. ). Extended laboratory tests 2 weeks later showed anemia (hemoglobin 11.3 g/dl), increased lactate dehydrogenase (278 U/l, normal ≤ 250), progredient CRP (18.27 mg/dl), and progressive leukocytosis (56.090/μl). The peripheral blood smear yielded 88.3% neutrophils, 4.3% lymphocytes, 4% monocytes, and < 1% eosinophils and basophils, respectively. Immature granulocytes were increased to 4.3% (norm ≤ 0.6%). Serum level of alfa-fetoprotein (AFP) was normal.
In the subsequent liver MRI examination, the lesion displayed an inhomogeneous T2-hyper and T1-hypointense signal (Fig. ). In light of the clinical presentation, the lesion was initially regarded as a liver abscess and recommendation for histological assurance was given. The following sonographically controlled liver biopsy could not distinguish between undifferentiated sarcoma and poorly differentiated sarcoma, so the exact diagnosis remained unclear.
To exclude further tumor manifestations, a whole-body [18F]-FDG PET-CT examination was performed 18 days after computed tomography. In this short-term interval, the lesion showed a slightly progressive diameter (5.3 × 6 cm vs. 4 cm) and a very high glucose metabolism activity (SUVpeak 33, SUVmax 41, SUVmean 23). PET-CT additionally showed significantly increased glucose metabolism in the entire bone marrow, which could be interpreted as unusually high bone marrow activation or as diffuse malignant bone marrow infiltration. There was no evidence of further suspicious lesions (Fig. ). The following bone marrow puncture revealed a clearly hypercellular bone marrow with a pronounced increase in granulopoiesis and megakaryopoiesis and relatively reduced erythropoiesis. Although this finding was compatible with a myeloproliferative disease, it was considered pronounced paraneoplasia, which also explained the patient’s symptoms. Laparotomy with resection of liver segment VII followed. Immediately after surgery, the paraneoplastic symptoms of fever, cough, night sweats, high inflammatory values (CRP up to 20.9 mg/dl), and extreme leukocytosis (up to 100.370/μl) completely declined within hours (Fig. ).
Accordingly, in follow-up [18F]-FDG-PET-MRI, a complete normalization of bone marrow metabolism was observed (Fig. ). Combination chemotherapy with actinomycin D, ifosfamide, and vincristine followed for 26 weeks. There was no proof of recurrence in the post-therapy CT and MRI examinations.


Our patient was a 56-year-old postmenopausal African American woman with no past medical history who was previously treated at an outside oncology clinic for breast masses until 2010, when we first saw her. Her family history was negative for breast or ovarian carcinoma. She had a negative smoking history and endorsed drinking one drink per week. Per reports obtained, she first presented in 2006 with left breast lesions located in the upper inner breast that were documented as complicated cystic masses within the 9 o’clock and 9:30 positions on the basis of ultrasound (US). Subsequent US core biopsy in both areas revealed intraductal papilloma (IDP), and the patient was referred for a surgical consultation. No additional documentation of clinical visits was available until 1 year later. That documentation was in the form of a core biopsy pathologic report documenting the patient’s history of IDP at 9:00 and 9:30 positions as well as intraductal papillomatosis of the breast. A core biopsy taken at that time was from the left breast (location not mentioned) as well as the left axilla. The patient’s left breast showed fibrosis of mammary stroma including intralobular stromal sclerosis as well as microcalcifications in the lobular lumens. An axillary core biopsy confirmed IDP of the breast with stromal hyalinization as well as lymph node tissue adjacent to the papilloma. One month later, she underwent lumpectomy, with pathology reporting a 7-mm intracystic papilloma within a lymph node that was completely excised, as well as an epidermal inclusion cyst. The pathologist noted that the tumor was located near the periphery of a lymph node, probably arising in ectopic breast tissue in the capsular region. Approximately 11 months later, she developed another left breast mass. This was excised after a US-guided core biopsy once again revealed a benign IDP. The patient was then lost to follow-up at the outside clinic. She presented to our clinic 2 years later for an evaluation of a new left breast lesion. A bilateral diagnostic mammogram revealed two masses in the left breast, which were not well visualized, owing to heterogeneously dense breast tissue. Diagnostic US revealed a solid superficial mass measuring 0.81 × 0.76 × 0.81 cm corresponding to palpable findings also seen at the 6 o’clock position (Fig. a). Additionally, the patient had a large, complex cystic mass measuring 7 cm at the 1 to 3 o’clock position abutting the pectoralis muscle (Fig. a). A core biopsy of the 6 o’clock lesion was recommended. A US-guided, vacuum-assisted core biopsy of the 6 o’clock mass revealed an intracystic papillary neoplasm. Per the report, the patient denied nipple discharge, dimpling, thickening, redness of the skin, swelling, or tenderness at the time. A few weeks later, she underwent left breast lumpectomy with pathology revealing a complex cystic mass with fibrocystic changes at 1 to 3 o’clock and intraductal papilloma at 6 o’clock. The patient missed her 6-month follow-up mammogram. She returned 8 months later for a bilateral diagnostic mammogram, which showed a new 2.5-cm mass in the deep central aspect of her left breast at the 12 o’clock position. US showed a cystic mass measuring 3 cm and containing an intracystic solid component measuring 1 × 1 × 2 cm. No axillary or supraclavicular adenopathy was noted on the basis of imaging or physical examination. Her surgical team decided on left breast excisional biopsy with preoperative mammogram guidewire localization. Pathology revealed a benign papilloma measuring 1 cm, focally extending into skeletal muscle in the area adjacent to the previous biopsy site, but with negative margins and no signs of atypia. On the patient’s 6-month follow-up surveillance diagnostic mammogram, another new 3-cm density was noted at the 12 o’clock position. This was most consistent with a benign cyst and was aspirated. She was again lost to follow-up for more than 2 years until July 2015, when she presented with a 2-month history of a slowly enlarging left breast mass in the same region as her previous papillomas. A bilateral diagnostic mammogram with US showed a large mass at the 12 o’clock position measuring 7 × 2.5 cm. Her physical examination revealed that there were two areas of concern: first, a mass measuring 7.5 × 6.3 cm in the 1 o’clock position, and second, an area of nodularity measuring 4.6 × 3.1 cm in the 11 o’clock position. One month later, computed tomography (CT) of the chest and magnetic resonance imaging of the breast revealed a predominantly cystic mass with a solid component extending into the chest wall and approaching the pleural space (Fig. ). These tests also revealed a suspicious internal mammary lymph node (Fig. a). A positron emission tomographic (PET)-CT scan showed a hypermetabolic nodule located in the pretracheal space (Fig. b) with a corresponding standardized uptake value (SUV) of 6.1 and multiple associated hypermetabolic internal mammary lymph nodes with the highest SUV of 6.0 and nodular hypermetabolic activity along the inferomedial aspect of the cystic mass (SUV, 2.7).
Her case was discussed at the multidisciplinary breast tumor board, and the recommendation was to proceed with a biopsy of the left internal mammary lymph nodes. Core biopsy revealed a papillary neoplasm with benign morphology with immunostains positive for estrogen receptor (ER) at 99%, positive for progesterone receptor (PR) at 85%, HER2/neu 1+, and a Ki67 proliferation index of 6%. An independent external pathologist agreed with the finding of histologically benign papilloma. The patient sustained a biopsy-related internal mammary artery injury and as a result developed a hemothorax requiring video-assisted thoracoscopic surgery.
Upon recovery from the hemothorax, the patient was referred to the medical oncology department of our hospital. Given the malignant behavior of her tumor, a recommendation of aggressive local control was made. She was started on endocrine therapy with palbociclib and letrozole as a neoadjuvant strategy. Repeat PET-CT following 4 months of combination antiestrogen therapy demonstrated near-complete resolution of metastatic internal mammary lymph nodes (white arrows in Fig. a) and reduced size and avidity of the paratracheal nodes (arrows in Fig. b). A physical examination did not show any significant changes in the size of the left breast mass. She went on to complete 6 months of neoadjuvant therapy. The primary lesion demonstrated minimal clinical response after 6 months of combination endocrine therapy, and then she underwent a left simple mastectomy and sentinel lymph node biopsy. Once again, the pathology revealed a 7.1-cm papillary neoplasm described as microscopically bland and mitotically inactive, with a retained ME layer. Several similar-appearing satellite papillomatous lesions were also seen within the skeletal muscle and deep adipose tissue. Margins and all five sentinel lymph nodes were negative (Figs. and ).
Given the extent of her local involvement and history of recurrent disease, she underwent adjuvant chest wall radiation for 6 weeks, followed by adjuvant endocrine therapy with letrozole. Six months after mastectomy, a repeat PET-CT scan showed no evidence of disease. She continues to undergo surveillance CT of the chest and mammography of her right breast. One year after her mastectomy, she underwent left breast reconstruction (Fig. d). She remained without evidence of disease 2.5 years after mastectomy and continued on endocrine therapy during that time.


A 54-year-old Chinese man of Han nationality, a retiree, went to a local hospital because of hematuria. He had an abdominal computed tomography (CT) scan showing right renal mass and bilateral adrenal nodules. He was referred to our hospital for further examination and treatment. He denied any medical history, except for a 4-year history of hypertension. He took 5 mg amlodipine besylate every day. He was married and living with his family; he had smoked tobacco for 30 years and denied alcohol consumption. Members of his family had no history of endocrine diseases or malignant tumors.
At the time of admission, his temperature was 37 °C, the pulse was 80 per minute, and his blood pressure was 161/75 mmHg. His height was 168 cm and weight 64 kg. There was no physical sign of Cushing’s syndrome, such as central obesity, skin atrophy, buffalo hump, red striae of skin, or moon face. The results of his cardiovascular, respiratory, abdominal, and neurological examinations were all unremarkable. A laboratory examination (Table ) showed an electrolyte disturbance, in particular, a very low serum potassium level. His 24-hour urinary free cortisol was elevated. The function of his thyroid gland, parathyroid hormone, metanephrine, and normetanephrine were in normal range.
The endocrine findings (Table ) showed high plasma aldosterone level and low plasma renin concentration. He then underwent a captopril challenge test which did not show suppressed level of plasma aldosterone concentration. A diagnosis of PA was of no doubt. On the other hand, the circadian rhythm of cortisol disappeared, and his serum cortisol level was not suppressed by an overnight dexamethasone suppression test (ODST) and low-dose dexamethasone suppression test (LDDST). He was diagnosed as having SCS.
An abdominal CT scan revealed a mass in the parenchyma of his right kidney (Figs. and ) and there was a rounded, low-density mass in his right adrenal gland and a rounded, low-density mass in his left adrenal gland (Figs. , , , and ); the larger adrenal mass was approximately 2.6 cm × 2.3 cm on the left adrenal gland. These findings indicated the possibility of a renal tumor and bilateral adrenocortical adenomas.
Sequential adrenal venous sampling (AVS) without adrenocorticotropic hormone (ACTH) stimulation was performed next. The result of AVS (Table ) reminded us that the right adrenal gland was responsible for aldosterone hypersecretion, and, quite possibly, the left was responsible for hypercortisolism.
Right nephrectomy and right partial adrenalectomy were performed first. The golden-yellow nodule in the right adrenal was approximately 2.5 cm × 2 cm × 0.8 cm macroscopically. The pathological diagnosis of the right adrenal nodule was adrenocortical adenoma. The right kidney tumor was proven to be a fibroma. Three days after operation, our patient’s serum potassium was 4.5 mmol/L without any supplementary treatment. The hypertensive drug was changed to 2 mg terazosin every day.
A laparoscopic left partial adrenalectomy was conducted 1 month later. When admitted to hospital, his blood pressure was 127/83 mmHg controlled by 2 mg terazosin every day, and his level of potassium was 4.9 mmol/L without any supplementary treatment. We examined his cortisol at 8 a.m. before operation, which was 344.81 nmol/L. The operation was successful and the level of cortisol at 8 a.m. had reduced to 192.01 nmol/L 2 days after operation. The nodule in the left adrenal was golden-yellow; it was approximately 3 cm × 2.5 cm × 2 cm. The pathological diagnosis of the left adrenal gland nodule was proven to be adrenocortical adenoma. After the second operation, doctors advised 30 mg hydrocortisone should be taken once a day with a weekly reduction of 10 mg until withdrawal, and 2 mg terazosin should be taken once a day.
During postoperative follow-up, terazosin was gradually stopped, and blood pressure and serum potassium remained normal. Approximately 2 months later, his ACTH concentration was 98.73 pg/ml which was above the reference value. This meant our patient had adrenocortical insufficiency, and he continued to take hydrocortisone. Months later, hydrocortisone was stopped, the concentration of cortisol and ACTH were 233.46 nmol/L and 49.43 pg/ml, respectively. The plasma aldosterone concentration was 104 pg/ml and plasma renin concentration was 3.1 uIU/ml. Normalization of aldosterone-to-renin ratio (ARR), cortisol, and ACTH were reached and our patient did not complain of any discomfort.
Immunohistochemistry (Fig. ) of the two adrenal nodules revealed that the right one had positive immunostaining for CYP11B2, which is essential to synthesize aldosterone, and the left one had positive immunostaining for CYP11B1, which is essential to synthesize cortisol. These results confirmed the right nodule was responsible for the secretion of aldosterone and the left nodule was responsible for the secretion of cortisol. Somatic KCNJ5 mutation (Leu168Arg) was found in the right adrenal tumor (Fig. ), and there was no KCNJ5 mutation in the left adrenal tumor.


A 34-year-old male smoker presented at the emergency department with a rapid onset of high fevers, chills, and myalgia. His past medical history is significant for stab wounds to the chest and abdomen that required an emergent exploratory laparotomy, a diaphragmatic repair, and a splenectomy 15 years ago. Unfortunately, he did not receive post-splenectomy prophylactic vaccinations for Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae. His initial mean blood pressure measurements were normal with mean arterial pressure of 70-90 mm Hg with no vasopressors required. His clinical exam was notable for cold, pale palms, and feet. However, serologic workup was remarkable for leukocytosis (47,720/mm3), lactic acidosis (12.5 mmol/L), new-onset severe thrombocytopenia (15 K/cu mm), and d-dimer levels > 30.00 mg/L fibrinogen equivalent unit. The patient presented clinically in septic shock with disseminated intravascular coagulation and a petechial rash covering his face, hands, and feet. His metabolic panel indicated decreased protein S activity (47%) and protein C activity in the low end of normal range (74%). After obtaining blood cultures, aggressive fluid resuscitation, vancomycin, and piperacillin/tazobactam were initiated.
The patient was admitted to the Medical Intensive Care Unit (MICU), and subsequent workup suggested Streptococcus pneumoniae bacteremia. Over the next 48 hours (hospital day 2), the patient developed extensive necrosis of the bilateral upper and lower extremities concerning for PF. Furthermore, he developed an acute kidney injury, required vasopressor support (norepinephrine drip, as high as 0.1 mcg/kg/min), and was ultimately intubated for respiratory distress. The treating physicians determined that the patient was likely in a cytokine storm secondary to the Streptococcus pneumoniae bacteremia. In the setting of PF with extensive necrotic wounds, the patient was transferred to the Burn Intensive Care Unit (BICU) for further management (hospital day 12). His vitals on BICU admission were notable for temperature 37.3oC, blood pressure 136/78 mmHg (on norepinephrine drip, 0.1 mcg/kg/min), heart rate 122 bpm, respiratory rate 17 bpm, and oxygen saturation 97% while on mechanical ventilation. His laboratory data were significant for white count 28,720/mm3, hemoglobin 6.5 g/dL, hematocrit 20.4%, blood urea nitrogen 49 mg/dL, creatinine 9.10 mg/dL, and elevated prothrombin time 40.1 seconds.
The patient continued to demonstrate progressive severe necrosis in the affected extremities. He was taken to the operating room for debridement of bilateral upper extremities (hospital day 14 and 17). The bilateral lower extremity wounds were initially managed with local wound care, but severe wet gangrene complicated the situation. Given the significant and persistent hemodynamic instability, operative attempts at limb salvage were considered an unviable option. The decision was made to perform a right transradial forearm amputation (hospital day 23), as well as bilateral transtibial amputations (hospital day 30). He tolerated these procedures and was discharged (hospital day 55) to an inpatient rehabilitation facility on intermittent hemodialysis.
While at inpatient rehabilitation, the patient diligently adhered to clinic follow-ups with physical medicine and rehabilitation, burn surgery, and occupational therapy. He was successfully transitioned off of hemodialysis and was fitted for bilateral lower extremity prosthetics at approximately four months following his bilateral below knee amputations (hospital day 142). He had difficulty wearing the prosthetics secondary to pain and eventually discontinued use altogether. At home, during the weeks following being discharged, he continued to ambulate by bearing weight on his knees while wearing kneepads. At his follow-up evaluation appointments, he continued to report significant tenderness and pain along the bilateral below knee amputation stumps. His physical examination was concerning for significant distal bone formation in his bilateral amputation stump sites without evidence of skin breakdown. Radiographic studies were obtained and demonstrated significant bony mineralization extending from the distal most aspect of his bilateral tibiae (Figures , ). He was electively scheduled for an amputation revision of his bilateral lower extremities with a primary focus on excising calcified tissue, indicative of HO. Intraoperatively, extensive bony formation was found bilaterally within his soleus muscle flaps, concerning for HO. Postoperatively, the patient was refitted for lower extremity prosthetics.
Initially, he was able to ambulate with only mild discomfort along the stump sites and transient complaints of phantom pain. One year later, the patient now uses the prosthetics regularly. He partakes in all daily activities including, but not limited to, yard work, playing with his dog, and walking on uneven surfaces as well as up/down stairs. He also developed wounds on his left stump which were debrided and treated topically in the clinic (Figure ).


A 56-year-old female, who had been followed for diabetes since 2004, was admitted to the emergency service as pedestrian who was hit by a car traveling about 60 miles per hour. On physical examination, she was conscious and hemodynamically stable with a blood pressure of 135/85. Her right lower limb was short and deformed in abduction and external rotation, and there was open wound in the distal 1/3 anterior of the tibia measuring 7 cm with moderate soft tissue injury, corresponding to grade II of the Gustilo classification. The neurovascular examination was uneventful. Radiographs indicated right hip dislocation, displaced posterior acetabular wall fracture (), femoral shaft fracture at distal third, and concomitant fracture in the distal third of the tibia (Figures and ). Chest radiograph revealed a small pneumothorax. A pelvis computed tomography confirmed the posterior fracture dislocation and showed the presence of intra-articular fragments (). Urgently, the patient was taken to the operation room following resuscitation. Under general anesthesia, an intercostal tube was inserted for the pneumothorax. Closed reduction of the hip dislocation was performed. Then, the open fracture of the tibia was stabilized with an external fixator after debridement of all devitalized tissues ().
Two days later, the patient was taken back to the theatre. Under general anesthesia, she was positioned in the left lateral decubitus. First, the diaphyseal femoral fracture was fixed with an antegrade intramedullary nail with 2 distal locking bolts following open reduction (). Then, the acetabular fixation was performed through a Kocher-Langenbeck approach. The posterior wall fracture was stabilized using 2 screws due to the presence of large fragment and good bone quality. Finally, the intraoperative exploration found the existence of a detached fragment of the femoral head, which was fixed by direct screw ().
Postoperatively, there was no acute complication such as infection, venous thrombosis. The chest drain was removed on the fifth day. The tibial wound was well cicatrized, and the wound cultures were sterile. After two weeks, the patient was discharged to go home. Initially, she was mobilized non-weight-bearing on crutches for ten weeks. Then, partial weight-bearing was allowed. The rehabilitation protocol included muscular exercises especially quadriceps and early mobilization of the hip and knee for prompt recovery of the joint range of motion. After seven months, the follow-up radiographs showed bony consolidation of all fractures except the tibia which was completely consolidated in 10 months (Figures –). We opted to remove the external fixator. We authorized the full weight-bearing, and we asked the patient to use a walking stick. At 1 year after trauma, the patient returned to normal activities. The hip and knee functions were recovered with limited flexion of the knee at 110 degrees.


A 92-year-old African American female with past medical history significant for toxic megacolon for which she underwent a colectomy with an end ileostomy five years prior was admitted to the hospital for failure to thrive for several months. She had no history of dementia or liver disease, and extensive evaluation revealed no etiology for her condition besides poor intake. A decision to supplement her nutrition enterally was made. She underwent a PEG tube placement after a successful trial of nasogastric feeding.
During her PEG tube placement, her upper endoscopy demonstrated no gastric pathology. A pull method with transillumination was used to insert the PEG tube into position. No immediate complications were noted, and the patient was discharged home.
Two weeks later, she presented with fatigue and abdominal discomfort. On examination, her vital signs were stable, her mucous membranes dry, and her ileostomy and PEG sites were normal. Her initial labs demonstrated a normal white cell count, a hemoglobin of 10.6 g/dl (10.7 g/dl pre-procedure), aspartate aminotransferase of 74 U/L (58 U/L pre-procedure), alanine aminotransferase of 74 U/L (28 U/L before procedure), alkaline phosphatase of 108 U/L (30 U/L before procedure), blood urea nitrogen of 128 mg/dl, and creatinine of 2.45 mg/dl (baseline of 1.2 mg/dl). Intravenous hydration was initiated, and a computed tomography (CT) of the abdomen with oral contrast was obtained which incidentally showed that the PEG tube coursed through the left hepatic lobe with no extravasation of enteric contrast or adjacent hematoma (). Given the patient's hemodynamic stability, absence of leak or hematoma, and the need to maintain enteral access given dehydration, a decision to keep the PEG tube in place was done with plans for removal if further complications arose. The PEG tube flushed with no difficulty and was used for enteral nutrition during the patient's inpatient stay.


This article reports the case of a 23-year-old male patient diagnosed with HIV, who started two years ago with a clinical picture of hemicranial headache and left palpebral ptosis. He underwent a nuclear magnetic resonance imaging (MRI), which showed a solid lesion that occupied the cavernous sinus on the left side. He was taken to an excisional biopsy that reported fusocellular mesenchymal neoplasm with smooth muscle differentiation. With this result, he underwent a partial resection, according to the surgical description, and he was not given any adjuvant treatment, leaving the patient under follow-up. A year later, a follow-up contrasted cerebral MRI showed a receiving lesion of the contrast medium with an intimate relationship to the cavernous sinus with extra axial extension towards the mesial temporal lobe, with 50% growth compared to a previous study. With these results, the patient was referred to our institution where a review of the pathology plaques and a cerebral MRI with spectroscopy was requested. The pathology reports fusocellular mesenchymal neoplasia with smooth muscle differentiation by immunohistochemistry, compatible with low-grade leiomyosarcoma.
Immunohistochemistry reported Vimentin (+), SMA (+), H-Caldesmon (+) focal, KI67:15%, CKAE1AE3 (-), CD34 (-), STAT-6 (-), Chromogranin (-), Synaptophysin (-), EMA (-), S100 (-), PGFA (-), Progestogen (-), Desmin (-), PGP9.5 (-), CD99 (-), CD31 (-), HHV8 (-), ACL (-). In addition to this, a fluorescence in situ hybridization (FISH) test was performed, which was Epstein-Barr virus-encoded small ribonucleic acid (EBER) positive confirming coinfection by Epstein-Barr virus (EBV). In extra axial location with epicenter in the cavernous sinus and with extension to the medial temporal fossa on the left side, the MRI (Figure ) identified a solid mass of well-defined and irregular contours, with low signal intensity to T2-enhanced sequences, without significant restriction in the diffusion sequences, with intense enhancement after intravenous contrast administration and with central focal areas of necrosis and/or malacia due to the history of partial resection, and surrounding the entire cavernous portion of the internal carotid artery without secondary occlusion. This lesion has diameters greater than 32 x 35 x 46 mm. In the spectroscopy sequences (Figure ), decreased levels of neuronal metabolic components choline (Cho), creatine (Cr) and N-acetylaspartate (NAA) were identified with a significant increase in the values of lactate and lipid levels attributable to anaerobic activity.
The patient was assessed by the board of neurosurgery, who considered that the lesion is unresectable due to its location and the risk of motor sequelae after treatment. Clinical oncology considered that given the low tumor grade, the patient should be initially treated with radiotherapy. The patient was presented to the radiotherapy board, which defined treatment with intensity-modulated radiation therapy (IMRT) technique external radiotherapy (Figure ), total dose of 54 Gy, in fractionation of 1.8 Gy. The patient completed treatment referring headache improvement without evident secondary toxicity. Six months after the treatment, the patient continued asymptomatic with stable disease.


This 38-year-old woman with background of Marfan’s syndrome was admitted to hospital following an episode of syncope. Echocardiography (ECHO) showed severe dilation of the ascending aorta with mild mitral and aortic regurgitation (AR) and normal left ventricular systolic function. Computed tomography confirmed dilation at 57 mm. Valve sparing aortic root replacement (David procedure) was carried out 2 months later after which she made an unremarkable recovery, being discharged home 5 days post -operatively. She was not on any regular medications prior to admission and refused any medications on discharge from hospital.
She was readmitted 10 days post -operatively directly from home to interventional cardiology via our regional optimal reperfusion service with an inferior ST-elevation myocardial infarction (STEMI) and cardiogenic shock [electrocardiogram (ECG) shown in Figure ]. Prior to this, she had experienced a short history of exertional chest pain. Angiography showed the right coronary artery (RCA) was occluded proximally with thrombus and appearance of mechanical disruption of the aorto-ostial anastomosis (Figure ). Reperfusion was achieved after wiring and export of a large thrombus, followed by ventricular fibrillation (VF) cardiac arrest after which an intra-aortic balloon pump was inserted and the patient intubated. After discussion with the multidisciplinary team (MDT) in the catheterization lab, the decision was to proceed with intravascular ultrasound (IVUS)-guided percutaneous intervention. IVUS confirmed extrinsic mechanical compression at the right coronary neo-ostium with no atherosclerosis present. This was successfully treated with one drug-eluting stent (DES) (Figure ). Emergency ECHO in the catheterization lab showed severe right and left ventricular systolic dysfunction (LVSD). She was extubated the next day. Echocardiography on the 8th day of admission showed a dilated left ventricle with moderate segmental function and notably dilated failing right ventricle. Her recovery was complicated by ventilator acquired pneumonia and atrial fibrillation (AF) and she was discharged home after 3-week hospital admission.
At 18 months of follow-up, her symptoms and ventricular function had significantly improved [New York Heart Association I–II and mild systolic impairment without right ventricular (RV) impairment].


This 53-year-old gentleman with known bicuspid aortic valve and dilated aortic root developed decompensated heart failure related to severe AR in the setting of severely dilated aortic root (70 mm). His left ventricular (LV) function was moderately impaired which improved with medical therapy prior to operation. Computed tomography coronary angiography (CTCA) showed trivial plaque without obstructive coronary artery disease. Three weeks later after optimizing his medical treatment, he underwent aortic valve repair with valve-sparing aortic root replacement (David procedure). Post-procedure ECHO showed no AR with good LV function. Aspirin was started in the post -operative period with plan to continue for 3 months. After developing AF, he commenced on treatment dose low- molecular-weight heparin, amiodarone, and beta-blocker. His other medications included an angiotensin-converting enzyme inhibitor, statin, and omeprazole.
His inpatient recovery was complicated by recurrent chest pain on mobilizing. Levels of high-sensitivity troponin remained elevated at levels higher than expected in the post-operative period ( high-sensitivity troponin T peak 489 ng/mL) raising clinical concern regarding ongoing ischaemia. ECG showed AF with an uncontrolled ventricular rate and new right bundle branch block (Figure ). Therefore, a CTCA was performed which was suggestive of distortion of the proximal RCA (Figure ). Urgent invasive angiography showed proximal RCA stenosis which was treated with one DES with good angiographic results. Echocardiography at Day 5 showed basal to mid-infero-lateral akinesia with overall moderate LVSD. The right ventricle size was normal with mildly impaired systolic function. Recovery was complicated by lower respiratory tract infection and ongoing AF but he was discharged home 12 days later. At clinic review 2 months post-operatively, he was well with no symptoms of angina or syncope and with mild shortness of breath only on moderate exertion. At follow-up, there was moderate segmental LVSD (consistent with the target vessel infarction), whilst RV function was normal.


A 60-year-old man was diagnosed with psoriasis 20 years ago for a widespread rash on the trunk. He was diagnosed with diabetes in his twenties and hypertension in his thirties but was untreated. He developed a necrotizing soft tissue infection of the thigh 12 years ago, and diabetes treatment was started. He was treated with cyclosporine 10 years ago at another hospital; this was discontinued due to renal dysfunction. Renal function gradually declined, and hemodialysis was introduced 2 months ago. During his visit to our department, psoriatic plaques were seen on his scalp, face, trunk, and limbs (Figures and ). He had a Psoriasis Area and Severity Index (PASI) score of 39.6. In clinical examination, blood urea nitrogen was 48 mg/dL, serum creatinine was 11.57 mg/dL, and C-reactive protein was normal. Serum 1, 3-beta-D-glucan was negative. The T-SPOT.TB test was negative. He had no history of interstitial pneumonia and no specific findings on chest computed tomography (CT). He had received hemodialysis for diabetic nephropathy. He previously suffered from necrotizing soft tissue infection and had a high risk of developing infection. Although his skin lesion was severe, his adherence to the treatment was poor. Rapid onset of efficacy was considered to be important for treatment adherence. Treatment with brodalumab was initiated in terms of the efficacy and safety. After 4 weeks, the generalized rash was mainly pigmented; 100% improvement in the PASI score was achieved at 12 weeks (Figures and ). He began to have a chronic cough four months after the start of the biologic treatment. He ceased his dermatology visit and had not been given brodalumab for a month. Coughing continued, and CT showed diffuse ground-glass opacities and pleural effusions in both lungs (). Transbronchial lung biopsy showed no findings suggestive of interstitial pneumonia. Grocott staining was negative in bronchoalveolar lavage fluid (BALF), as were acid-fast bacilli and fungal cultures. Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were not identified by polymerase chain reaction in BALF. The T-SPOT.TB test was also negative. It was considered to be a symptom of overflow due to excessive fluid volume because of insufficient dietary management. Brodalumab was continued, and respiratory symptoms improved with proper weight setting and adequate dietary control. Chest CT showed improved pleural effusion and opacity (). No recurrence of rash has been seen twelve months after the initiation of brodalumab. There were no serious adverse events.


A 15-year-old male, presented with fever, nausea, and three weeks of worsening right upper quadrant pain, preceded by three months of vague upper abdominal pain. Review of systems was otherwise normal. The patient had no travel history. Computed tomography (CT) imaging of the abdomen and pelvis showed an 18-cm heterogeneous hepatic mass as well as several pulmonary nodules (Figure , ).
Given the patient’s history and the morphology of the lesion, an infectious process was initially suspected. A set of blood cultures was obtained, and serological tests including Entamoeba histolyticaantibody, serum (RIDASCREEN Entamoeba histolytica IgG, R-Biopharm AG, Darmstadt, Germany); Echinococcus antibody, IgG, serum (RIDASCREEN Echinococcus IgG, R-Biopharm AG, Darmstadt, Germany); and fungal antibodies by immunodiffusion were sent to Mayo Medical Laboratories. Initial complete blood count and blood chemistry results revealed elevated leukocytes (16,200/mm3), thrombocytes (536,000/mm3), bilirubin (2.1 mg/dL), lactate dehydrogenase (531 IU/L), gamma glyamyltransferase (119 U/L), and alkaline phosphatase (268 U/L), with normal liver transaminases and alpha-fetoprotein (AFP). Due to suspicion of a pyogenic or amoebic liver abscess, the patient was started on ceftriaxone and metronidazole.
A CT-guided needle biopsy of the liver mass taken the next day was positive for malignant cells by hematoxylin and eosin staining; however, surrounding fluid was negative for infectious agent by culture. A second set of blood cultures continued to show no growth, and antibiotics were discontinued. Subsequent laparoscopic liver biopsy (Figure ) led to the diagnosis of undifferentiated embryonal sarcoma, but was negative for any infectious agent. The pathology report indicated markedly pleomorphic cells with brisk mitotic activity with no differentiation and areas of hemorrhage and necrosis. Immunohistochemical staining was positive for alpha-I-antitrypsin, vimentin, and desmin; weakly positive for OSCAR focal pancytokeratin; and negative for actin and hepatocyte specific antigen; together, this was most consistent with embryonal sarcoma. The presence of lung nodules suggested stage IV metastatic disease; however, these were not biopsied.
The ELISA serological results for infectious diseases, completed after the malignancy was confirmed by biopsy, were positive for antibodies against Echinococcosis and Entamoeba histolytica, and the fungal antibody panel was positive for Histoplasma. Subsequent specific testing for Histoplasma antibody via complement fixation and immunodiffusion was negative. These confounding positive antibody results were thought to be a false positive due to a cross-reaction with the patient’s hepatic mass; as all cultures taken throughout including blood, needle biopsy, and wedge biopsy were negative.
The patient received four cycles of chemotherapy, consisting of ifosfamide and doxorubicin, followed by surgical resection of the residual tumor. Four months after his initial diagnosis, the patient underwent right hepatic trisegmentectomy along with resection of the right hemidiaphragm and mesh reconstruction. A magnetic resonance imaging scan 10 months after his initial admission revealed no evidence of disease, as did a follow-up CT scan of the chest taken 13 months after admission.


We report an 80-year-old gentleman with a background history of chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade D; Modified Medical Research Council Dyspnoea Scale (mMRC) class III) who was admitted for a right spontaneous secondary pneumothorax. He unfortunately developed extensive SE one day after right chest tube insertion leading to hoarseness of voice, tense palpebral fissures, and tense neck swellings. Computed tomography (CT) of the thorax demonstrated extensive SE together with the presence of pneumomediastinum (Fig. ). CT images also revealed that the tip of the chest tube was seen penetrating through part of his lung parenchyma which is the most likely cause of extensive SE. An urgent cardiothoracic surgery consult was made but unfortunately our patient was deemed unfit for surgery in view of his advanced underlying lung condition with poor lung reserve. He was intubated for airway protection on the fourth day of stay in view of development of stridor (Fig. A). Our patient continued to develop worsening SE despite adequate thoracic drainage via a new chest tube. Earlier attempts of subcutaneous cannula insertions for cutaneous tension release were not successful.
A multidisciplinary team discussion involving physicians, nurses, surgeons, physiotherapists, intensive care doctors, and patient's family members was conducted on the fifth day of hospitalization. It was then decided to insert two NPWTD in patient's subcutaneous tissue via incisions made at left and right anterior chest wall, 5 cm below the clavicle level. Extra precautions were made to ensure that the incisions were made at superior borders of the rib below and approximately 5 cm from the midline to avoid injuries to the intercostal and internal mammary vessels, respectively. The NPWTDs were created by using trimmed sterile sponge to fit the wound shape. The sponge was then wrapped around a modified nasogastric tube containing self-created fenestrations on one end to aid in suction. Sutures were used to secure the sponge on the nasogastric tube. The other non-fenestrated end of the nasogastric tube was connected onto a suction machine. After achieving wound haemostasis, the sponges were carefully inserted into the two subcutaneous incisions and secured by using sterile transparent drapes (Fig. B). Continuous negative pressure of 10 mmHg with sequential increment up to 50 mmHg was used.
Prompt regression of SE was noticed within the first 24 h followed by successful extubation after four days of NPWTD (Fig. B). External pressure and massage were done intermittently to enhance exit of trapped gas. In view of significant improvements, the drains were removed after four days from the date of insertion with no recurrence of SE following removal.


A 31-year-old female, previously healthy, referred from a community hospital with a 4-week history of back pain, associated with bilateral lower limb weakness. No symptoms of paresthesia, urinary retention, or constipation reported. She was on dexamethasone 16 mg/day for 5 days prior to transfer to our hospital with no noticeable clinical improvement.
The patient was unable to stand on the first encounter. Positive findings on neurological examination revealed a muscle power of 2/5 on hip flexion, hip extension, knee flexion, foot dorsiflexion, and plantar flexion bilaterally. Hyperreflexia noted in lower extremities.
An ultrasound-guided biopsy was done at the referring hospital. Pathology was reviewed at our institute, and diagnosis of neuroblastoma was confirmed. MYCN amplification was present indicating unfavorable histology.
Upon arrival of the patient, magnetic resonance imaging (MRI) of the spine was done and indicated severe SCC at the 12th thoracic vertebra (T12) level ().
A positron emission tomography (PET) scan was also done and revealed an 8 × 13 × 15 cm, right FDG-avid suprarenal mass with an SUV uptake of 6.7.
Bone marrow biopsy was also performed and was remarkable for invasion by neuroblastoma cells.
The patient's case was discussed in a multidisciplinary fashion, and she started treatment as high-risk NBL with induction chemotherapy. The first cycle of induction chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide as per the Children's Oncology Group (COG) protocol A3973. The same dose of dexamethasone at 16 mg/day was continued.
She started noticing an improvement in her back pain 24 hours after administering chemotherapy. Neurological examination 72 hours after the first cycle of treatment showed a muscle power of 3/5 on hip flexion, hip extension, knee flexion, foot dorsiflexion, and plantar flexion bilaterally. We evaluated the patient one week after induction, and she was able to stand up and walk with assistance. The plan was to proceed as per the COG A3973 protocol which comprises vincristine, doxorubicin, and cyclophosphamide alternating with cisplatin and etoposide.
The patient continued chemotherapy treatments with further symptomatic improvement.
MRI thoracic spine was repeated after the first and third cycle of chemotherapy showed significant decompression of the spinal cord (Figures and ).
However, few days after cycle 6 of chemotherapy, she developed septic shock and unfortunately passed away shortly afterwards. Axial T2 cuts of thoracic spine MRI at T12 level taken 3 mm below the superior endplate of the vertebra.


An asymptomatic 21-year-old Caucasian woman with no history of diabetes was referred by her obstetrician to an adult diabetologist following the birth of her first baby who was macrosomic (birth weight, 5,140 g; birth weight SD score, 3.24); the baby did not have postnatal hypoglycemia. Blood glucose and glycated hemoglobin (A1C) values at different time points are summarized in .
Clinical features at presentation to the diabetes clinic are summarized in . Initial management comprised dietary changes and regular review. She became pregnant 2 years later and was managed with diet. She gave birth to a healthy baby girl, weighing 3,350 g (body weight SD score, −0.22). On day 6 of life, the baby presented with mild, intermittent hyperglycemia (highest glucose value, 13.1 mmol/L) that did not require glucose-lowering treatment. Genetic analysis revealed that case 1 and her second baby are heterozygous for the ABCC8 missense mutation, p.Arg1183Trp, previously shown to cause TNDM . Postdelivery, case 1 was started on gliclazide 15 mg daily (10% of the standard type 2 diabetes dose) because of rising A1C. Blood glucose monitoring showed fasting hyperglycemia. Her A1C improved from 7.2% (55 mmol/mol) after delivery to 5.9% (41 mmol/mol) at most recent follow up, 6 months after starting gliclazide. She has not reported hypoglycemia, weight gain or other side effects on gliclazide. Capillary glucose testing was not done because she was on oral therapy. The child's diabetes remains in remission needing no treatment, and she is developmentally normal at 4 years of age.


A 39-year-old Caucasian woman was referred to a diabetologist with a 3-month history of polyuria, polydipsia, 3 kg weight loss and cystitis. She had developed diabetes soon after birth requiring twice daily insulin for 12 weeks. Her diabetes subsequently remitted, and she had not required treatment until this presentation. Clinical features are summarized in . Because there was a history of TNDM, genetic analysis was performed, revealing a chromosome 6q24 imprinting abnormality. She started glyburide 2.5 mg/d (25% of the standard type 2 diabetes dose), and her A1C improved to 6.5% (48 mmol/L) after 4 months and 6.7% (50 mmol/L) after 13 months of treatment, with no side effects reported. Her weight increased from 60.5 to 63.8 kg in the first 4 months of treatment, but she lost weight subsequently (63.1 kg after 18 months), and her body mass index remained <25 kg/m2 thereafter. Because she was planning a pregnancy when her diabetes relapsed, she was also reassured that the risk of the same type of diabetes in her children would be no higher than that in the general population.


Patient 1 (IV-1) is 5 years old, and he was born by normal vaginal delivery at full term without any complication. He has one brother and two relatives affected with the same problem. Clinical examination showed that he generally looks well, his head circumference is 45 cm, and his central nervous system shows hypertonia in the lower limbs and brisk deep tendon reflexes. He started speaking and walking at age 2. The CT scan of his brain showed density in the left frontal cerebrospinal fluid, an extra axial lesion, and a left frontal subarachnoid epidermal cyst. His thyroid profile was normal, as was a complete blood count. A sleep EEG record revealed a background of predominately beta waves. Paroxysmal epileptic discharge was noted in IV-1 the affected individuals, primarily in the right central hemisphere proband. The facial appearance of the individuals participated in the study are shown in .


Patient 2 (IV-2) is 3 years and 4 months old, and he was born by normal vaginal delivery at full term without any complication. He showed a delay in speaking and walking. The patient shows hyperactivity, and a MRI examination was normal. EEG record during sleep revealed a background of predominately beta waves. Paroxysmal epileptic discharge was also noted in IV-2 the affected individuals, primarily in the right central hemisphere proband.


A 69-year-old male with past medical history of hypertension, asthma, coronary artery
disease, end-stage renal disease secondary to hypertensive glomerulosclerosis s/p
deceased donor kidney transplant 4 months back presented to the hospital with
productive cough, fever, and anorexia of 2 weeks duration. Vitals on presentation
were temperature of 38.5°C, heart rate of 72/min, blood pressure of 167/62 mm Hg,
and respiratory rate of 22/min with oxygen saturation between 90% and 92% on room
air. On physical examination, he had bibasilar crackles, more prominent on the left.
Laboratory findings revealed an elevated white blood cell count of 15 100/µL, blood
urea nitrogen of 21, and creatinine of 1.9 (baseline creatinine of 1.9-2.0).
Urinalysis was unremarkable. Chest X-ray (CXR) showed a left lower lobe
consolidation. Pan cultures were obtained, and treatment was started with
intravenous vancomycin and piperacillin/tazobactam for empiric coverage. His
posttransplant immunosuppressive regimen of mycophenolate mofetil, tacrolimus, and
prednisone was continued along with other supportive measures. His prophylactic
medications of nystatin, valganciclovir, and trimethoprim-sulfamethoxazole (TMP-SMX)
were discontinued 4 weeks prior to admission after completion of 3-month
posttransplant prophylaxis course. On day 3, 1 out of the 4 blood cultures grew
gram-positive bacilli for which ampicillin was added for better central nervous
system (CNS) penetration to cover Listeria infection as well. The
computed tomography (CT) scan of head and lumbar puncture ruled out any CNS
involvement. On day 7, final report of the blood culture revealed weakly acid-fast
filamentous gram-positive bacteria. On further review of the gram stain and colony
morphology of the organisms, it was identified as Nocardia. The
diagnosis of disseminated nocardiosis secondary to pulmonary source (left lower lobe
pneumonia) was made. Treatment for Nocardia was initiated with
imipenem/cilastatin, and initial antibiotics (vancomycin, piperacillin/tazobactam,
and ampicillin) were discontinued. Despite changing the antibiotics, there was no
significant improvement in his overall clinical condition, and the patient remained
with supplemental oxygen–dependent, persistent cough and with productive phlegm.
Speciation of the organism was consistent with Nocardia
transvalensis, which was resistant to imipenem, bactrim, ceftriaxone,
augmentin, and minocycline. It was reported to be sensitive to linezolid, amikacin,
moxifloxacin, clarithromycin, and tobramycin. Imipenem/cilastatin was discontinued,
and linezolid along with moxifloxacin was initiated on day 14. Within the next 3
days, the patient started showing signs of improvement and was discharged home in a
stable condition. He took linezolid 300 mg daily and moxifloxacin 400 mg daily for
12 months and remained asymptomatic. His follow-up visits were uneventful, and the
patient was asymptomatic. Repeat CXR at the follow-up visit showed resolution of the
pneumonia.