Patient 5 is a 8-year old boy. He is the first child of healthy, non-consanguineous parents. His family history is positive for intellectual disability and microcephaly. He was born at 29,2 WG because of premature rupture of membranes (PROM). Because of his prematurity, he was admitted to neonatal intensive care: he had pneumothorax, respiratory distress and retinopathy of prematurity (ROP). When the patient came to our attention, he had intellectual disability, spastic tetraparesis, strabism and craniofacial dysmorphism: microcephaly, protruding ears, prominent nasal bridge, short philtrum, micrognathia and spaced teeth. Brain MRI showed periventricular leukomalacia, polymicrogyria and dilatation of lateral ventricles. Heart and abdominal ultrasounds were reported normal.


Patient 7 is a 2-year old boy, the first child of non-consanguineous parents, born at 36,1 WG by cesarean delivery. His mother has intellectual disability, thyroid hypoplasia and hypothyroidism, reason why she had performed array-CGH, showing a 1q21.1 deletion.
He has dysmorphic features (sloping forehead, prominent occiput, flat nasal bridge, long philtrum, thin upper lip, large mouth, protruding tongue), congenital hypothyroidism and ectopic urethral meatus. The ultrasound study did not document thyroid hypoplasia. Brain and abdominal ultrasounds were reported normal.


A 27-year-old female patient with a past medical history of HIV infection and uterine fibroids presented to our infectious diseases clinic for establishment of care. The patient has been diagnosed with HIV infection two years ago but unfortunately was lost to follow-up and was never treated. She had no complaints at this visit and her clinical exam was unremarkable. HIV viral load was obtained that revealed 1,117,895 copies per microliter (mL) with a CD4 count of 230/mL. The patient was started on Genvoya (Gilead Sciences, Inc., CA) (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide). The patient was not taking any other medications.
One month later, the patient presented to the emergency department with generalized fatigue, dizziness, and menorrhagia. The patient reported that for the past one week, she had been having heavy menstrual bleeding with large clots and multiple soaked pads. She also noticed easy bruisability and gum bleeding. On initial examination, the patient was very pale. She had a blood pressure of 115/70 mmHg, temperature of 98°F, respiratory rate of 17/minute, and heart rate of 110/minute. Dermatological exam showed diffuse petechiae and purpura all over her body. There was no lymphadenopathy or hepatosplenomegaly. Cardiovascular and respiratory exam were unremarkable.
On initial laboratory evaluation, the patient was found to have a hemoglobin level of 4.3 g/dL from a baseline 11.4 g/dL. Her platelet count was decreased to 4000/cubic millimeter (cmm) from a value of 200,000/cmm just one month prior. Her coagulation profile including protime (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), white blood cell count, basic metabolic panel, and liver function tests were within normal limits. Peripheral blood smear showed normocytic normochromic anemia and severe thrombocytopenia.
The patient was hospitalized for further management. Genvoya was continued. The patient was emergently transfused two units of platelets and also two units of packed red cells. Platelet count improved slightly to 6000/cmm upon repeat testing with minimal improvement in menorrhagia.
Infectious disease and hematology consults were requested. After a multidisciplinary meeting, it was determined that given the patient's degree of severe thrombocytopenia, inappropriate response to platelet transfusion and rapid decline after initiation of antiretroviral treatment, the diagnosis of IRIS was likely. Further platelet transfusions were withheld and oral dexamethasone at a dose of 40 mg daily was initiated. With this intervention, her vaginal bleeding subsided and platelet counts began to improve. Four days later, on the day of discharge, patient's platelet count had improved to 223,000/cmm. At two-week follow-up, her platelet count had remained stable.


An abdominal US examination revealed an SMAA of unknown aetiology in an asymptomatic 26-year-old woman. Initial CTA confirmed the presence of an aneurysm with a diameter of 2.2 cm, originating from the proximal part of the superior mesenteric artery (SMA). Clinical workup included a detailed history, physical examination and blood analysis, including complete blood cell count, coagulation studies and biochemical analysis. There was no history of infectious or inflammatory diseases and no history of trauma; pancreatitis, alcohol abuse, liver disease and neoplasm were also excluded. The only known risk factor was a history of an intracranial aneurysm that found on her grandmother’s autopsy.
After a multidisciplinary consensus, taking into consideration patient’s age, pregnancy planning, aneurysmal size, location and literature data, endovascular management with a covered stent was proposed. Informed consent from the patient was obtained before the procedure.
Due to a large size of the introducer sheath (9 Fr), required for the available covered stent implantation (Bard, Fluency®, 8×20 mm), the femoral approach was chosen. Digital subtraction angiography (DSA) confirmed previous findings (). Selective SMA catheterisation was performed with the use of a curved guiding catheter and a stiff guidewire (Amplatz stiff®, Cook) that was placed distally in a branch of the SMA. Heparin (5000 IU) was administered into the SMA. An introducer sheath (9 Fr, 55 cm, Brite tip®, Cordis) was advanced into the SMA ostium and a self-expandable covered stent was implanted. A control DSA showed persistent aneurysmal sack filling (). Single femoral approach, a stiff guidewire and a large sheath distorted the anatomy, resulting in an incomplete aneurysmal neck covering. Alternatively, only a rigid, stainless steel covered stent was available and therefore the procedure was terminated. The patient was discharged from the hospital on the following day without clinical signs of complications.
Two weeks later, CTA confirmed persistent aneurysmal perfusion due to incomplete neck coverage; the patient was still asymptomatic.
A multidisciplinary board consisting of a vascular a surgeon, cardiologist and interventional radiologists decided to opt for a second endovascular intervention. A longer covered stent with lower crossing profile was selected; we decided to preserve the stump of the SMA for a potential conversion to open surgery.
A left transaxillary approach was used for anatomy preservation and an 8-Fr straight guiding catheter (55 cm, Brite tip®, Cordis) was introduced into the SMA. Balloon, expandable cobalt-chromium covered stent (E-ventus BX®, Jotec, 8×50 mm) was placed in the SMA, covering the aneurysmal neck (). A control DSA confirmed a complete exclusion of the aneurysm.
Complete aneurysmal exclusion and a patent covered stent were confirmed on control US three weeks later, and the patient was free of any signs of bowel ischaemia. Due to the transaxillary approach and 8-Fr sheath used, there was a mild median nerve damage periprocedurally that resolved in the following three months. No additional clinical signs of complications were noted during the follow-up period and an control US examination, performed 11 months later, showed a completely excluded aneurysm and a patent covered stent.


A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis presented to our hospital with worsening bilatateral leg swelling and facial puffiness of 1 month’s duration, accompanied by oliguria. She had no frothy urine or hematuria. She did not have exertional breathlessness or orthopnea, and she had no history suggestive of a cardiac or hepatic cause of edema. She was not diabetic or hypertensive. Her rheumatoid arthritis had been diagnosed 8 months earlier, when she presented with bilateral symmetrical polyarthritis involving the small joints of her hands with significant morning stiffness of 2 hours’ duration. Her rheumatoid factor was positive at a high titer. She was commenced on methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs, with good symptom control achieved.
Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. No malar rash, vasculitic rash, or distal gangrene was seen. She had evidence of mild synovitis of the small joints of the hands bilaterally with no deformities. No generalized lymphadenopathy or hepatosplenomegaly was noted. Her pulse rate was 90 beats per minute; her blood pressure was 170/100 mmHg; and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex and normal heart sounds. A fundus examination did not reveal papilledema. Her lungs were clear with equal breath sounds bilaterally. The results of the rest of the examination were normal. Her laboratory investigation results are provided in Table .
A diagnosis of crescentic glomerular nephritis was made. The patient was started on atorvastatin, enalapril, and diuretics. Intravenous methylprednisolone 1 g was given for 3 consecutive days, followed by 1 mg/kg oral prednisolone. She was started on intravenous cyclophosphamide 500 mg every 2 weeks for a total of six doses. She gradually had increasing urine output and was symptomatically better, with improving renal function. Her serum creatinine level was 110 μmol/L at her last clinic visit after 3 months of treatment.


A previously healthy 10-month-old female was found by her mother after waking in the morning to have slow, labored breathing. She was unresponsive to voice and tactile stimulation. This prompted a call to 911. On arrival, emergency medical services personnel noted that the infant was non-arousable, bradypneic, and stridorous, with a blood oxygen saturation of 80% on room air. She was transported to the emergency department of a regional hospital, where orotracheal intubation was immediately performed. Her blood pressure on arrival was 93/53 mmHg (mean arterial pressure 66 mmHg). Neurologic examination revealed 1 mm hyporeactive pupils bilaterally, global hypertonia, and hyperreflexia. A non-contrast computed tomography (CT) scan of the head was obtained. Arterial blood gas demonstrated a combined metabolic and respiratory acidosis (pH 7.15, PaCO2 29, PaO2 103, 10). Additional laboratory evaluation revealed mild transaminitis (aspartate aminotransferase 100 IU/L, normal = 8–50 IU/L; alanine aminotransferase 55 IU/L, normal = 7–45 IU/L) and leukocytosis (31,000/mm3, normal = 6,000–11,000/mm3). A broad differential diagnosis of respiratory failure of unknown origin was proposed, and treatment was pursued for possible allergic reaction or meningitis with two doses of epinephrine (0.085 mg), methylprednisolone (2 mg/kg), diphenhydramine (2 mg/kg), and a meningitic dose of ceftriaxone. The patient was then transferred to our tertiary care center.
On admission, workup was expanded with a full toxicology panel, which was positive for oxycodone and its metabolite, oxymorphone. Of note, elevated transaminases raised concern for acetaminophen toxicity; however this was ruled out by a negative result on the toxicology panel. A diagnosis of respiratory failure secondary to opiate ingestion and overdose was established. A total of four doses of naloxone (0.1 mg/kg i.v. push each) were administered with improvement in level of consciousness and reduction of ventilator support that allowed extubation. Continuous naloxone infusion was administered for 5 h thereafter. Results of initial neuroimaging were reviewed and revealed extensive symmetric bilateral cerebellar hypoattenuation (Figure A). The patient was admitted to the pediatric intensive care unit and was placed under close observation with frequent neurological exams.
On the third day of hospitalization, she became obtunded, with hyporeactive pupillary reflexes, hypertonia, hypertension, and ocular bobbing. Emergent magnetic resonance imaging (MRI) of the brain was obtained. The MRI demonstrated a pattern of symmetric restricted diffusion in the cerebellar hemispheres (Figure A), right parietal lobule, the heads of the caudate nuclei bilaterally and the right putamen. Additionally, hydrocephalus, elevation of the tectum, cerebellar tonsillar herniation, and an area of increased susceptibility weighted imaging signal in the left perirolandic area were present which suggested hemorrhagic transformation of an infarct.
The patient was taken emergently to the operating room for placement of an external ventricular drain, suboccipital craniectomy, and a C1 laminectomy. A significant portion of the edematous and ischemic cerebellar hemispheres and tonsils were resected bilaterally, thereby decompressing the posterior fossa and cervicomedullary junction.
A postoperative magnetic resonance angiography (MRA) of the head and neck showed normal anterior and posterior circulations. A full coagulopathy workup and echocardiography were unremarkable. No other visceral or musculoskeletal injuries were noted, and an investigation by the child abuse team provided no evidence for physical abuse. After an uneventful postoperative course, the patient was discharged on postoperative day 11.
Follow-up at 33 months of age (23 months after presentation) demonstrated an active, engaged child who spoke in full sentences. She was able to ambulate, jump, and climb stairs with alternating feet but had mild spasticity and internal rotation of her left leg with gait and occasional dystonic posturing of the left upper extremity.


A 25-month-old male with a history of mild reactive airway disease and sickle cell trait was noted by his mother to be breathing slowly and erratically 2 h after being laid down for a nap. Emergency medical services were called and paramedics encountered a pulseless, apneic patient. Cardiopulmonary resuscitation was immediately initiated. Return of spontaneous circulation was achieved in the ambulance on route to our institution’s emergency department.
On arrival, physical examination revealed an afebrile toddler, unresponsive to voice or noxious stimulation with agonal respirations, a blood oxygen saturation of 93% with bag-mask-assisted ventilation, and a blood pressure of 99/65 mmHg (mean arterial pressure 76 mmHg). Neurologic examination demonstrated 3 mm, non-reactive pupils and global hyperreflexia. Orotracheal intubation was performed emergently. Initial laboratory evaluation revealed normal electrolytes (Na+ 138 mEq/L, K+ 4.9 mEq/L, Cl− 104 mEq/L, Ionized Ca2+ 5.2 mEq/L), leukocyte count (11,100/mm3), venous blood gases (pH 7.37, PvCO2 44, PvO2 47, 25.7), and serum lactate (0.9 mmol/L). Upon further interrogation, the patient’s mother reported the presence of prescription opiates (extended release morphine) in the household, which she uses for pain control secondary to frequent sickle cell anemia crises. A total of two doses of naloxone (0.1 mg/kg i.v. push each) were administered, after which the patient regained pupillary reactivity and began moving all four extremities spontaneously. A urine toxicology panel was obtained, which was positive for morphine.
A non-contrast head CT was obtained (Figure B), which revealed acute hydrocephalus and extensive, symmetric bilateral cerebellar hemispheric hypoattenuation consistent with severe cerebellar edema that resulted in compression of the fourth ventricle and displacement of the midbrain and pons superiorly. Cervicomedullary junction compression secondary to cerebellar tonsillar herniation was also noted. Neurosurgery was consulted and the patient was emergently taken to the operating room for the placement of an external ventricular drain, suboccipital craniectomy, and a C1 laminectomy. A significant portion of the edematous and ischemic cerebellar hemispheres and tonsils were resected bilaterally, thereby decompressing the posterior fossa and cervicomedullary junction.
A brain MRI obtained on postoperative day 1 demonstrated cerebellar and cervicomedullary junction decompression, with extensive restricted diffusion in the remaining cerebellar parenchyma (Figure B). Multifocal areas of diffusion restriction were also noted bilaterally in the anterior cerebral artery-middle cerebral artery and middle cerebral artery-posterior cerebral artery watershed territories involving portions of the frontal, occipital, and temporal lobe white matter. An MRA/MR venogram demonstrated no craniocervical or intracranial arterial abnormalities or evidence of cortical or dural venous sinus thrombosis. The patient was extubated on postoperative day 5. Assessment at postoperative day 18 demonstrated an easily arousable child, with spontaneous eye opening, equally round and reactive pupils, and with purposeful movements of all four extremities.
Outpatient follow-up at 29 months of age (3 months after presentation) demonstrated an active child speaking in full sentences. He was able to ambulate independently, albeit with a slightly widened base of support, and mild left lower extremity spasticity which did not limit his ability to climb or descend stairs with rail support.


A 40-year-old Romanian woman, housewife, was referred to the psychiatry outpatient service by general practitioner, with a history of depressed mood, disturbed sleep for the past four years, and complaints that she had a snake inside her body. Her symptoms initially led to diagnosis of anxiety, somatization, and depression. She was treated in primary care with antidepressants, antipsychotics, and anxiolytics, with no response. Her medical history included gastritis, a distal left leg fracture with three surgical interventions (last one five years ago), and a pituitary microadenoma which had been revealed by brain computerized tomography- (CT-) scan but was not confirmed by posterior brain magnetic resonance imaging (MRI). Blood works, including endocrine tests, were normal. At the psychiatric evaluation, the patient was conscious, cooperative, and anxious. She had slow, hesitant speech due to language barrier, however a coherent one. She reported “a snake squeezing around her body, starting in her left leg and spreading to the rest of her body, up to the neck.” This occurred during night time and did not let her sleep. No other delusions or perceptions alterations were revealed. The Ekbom syndrome was considered as a diagnostic hypothesis and the patient was medicated with risperidone and trazodone. Patient returned to the second assessment with no improvements. She was slightly irritable and she verbalized frustration since the treatment showed no result. After careful reconstruction of clinical history, a further detailed analysis of her complaints was performed. Finally, the patient said that she had complained of a feeling like a snake squeezing her body, but not of a true snake. When questioned, the patient described a feeling of something crawling under the skin and a feeling of pins and needles that started in her distal left leg, spread to left thigh, left hemibody, and left side of her neck. The symptoms occurred every night and lasted minutes. No change of consciousness was reported by the patient or by her husband, who has observed several episodes per night. The diagnosis of somatosensory Jacksonian seizures was considered. An anticonvulsant ex juvantibus treatment with levetiracetam was started. In two weeks, the symptoms were greatly reduced in intensity and frequency, allowing the patient to sleep. An EEG study was prescribed but yet not performed due to patient's departure to Romania. The patient was referred to neurologist for further observation and etiological clarification of her epilepsy.


A 55-year-old woman, teacher, was referred to psychiatrist by general practitioner who described her symptoms as hallucinations and mood instability with frequent crying and laughing. She was treated with various antidepressants and herbal medications with no response. Her medical and familiar history was otherwise unremarkable. A brain CT-scan was normal.
At the psychiatric evaluation, the patient was conscious and cooperative; her speech was coherent and her mood was euthymic. During analysis of her complaints, she reported that, since her thirties, she had visual and auditory hallucination, saw images of “teeth laughing,” and heard some sounds described as “noises without any sense that I can't understand,” which lasted up to 5 minutes. The patient added that she also cried and laughed frequently, but she did not associate this with changes of her mood or with any other reason. She described it as an uncontrolled behavior, mentioning “it's a stupid laugh.” The patient was accompanied by her boyfriend, who described short laughing and crying episodes, through a few minutes, with no apparent reason. During the initial assessment, we observed two spontaneous crying episodes that lasted 1-2 minutes, with no reason.
EEG and conventional MRI were asked. Antiepileptic treatment with oxcarbazepine was prescribed.
Within a month, the patient was reevaluated with positive response to treatment; the symptoms had remitted completely. Cerebral MRI was within normal limits. Routine EEG showed unspecific slow activity (theta wave) predominantly in frontotemporal area of the left hemisphere.
The patient was referred to neurologist for further assessment.


A 63-year-old woman, housewife, was referred to psychiatric service by general practitioner due to anxiety disturbance and nocturnal visual hallucinations. The patient was medicated with antidepressants and anxiolytics without benefit. Her medical history included diabetes mellitus, hypertension, hyperlipidemia, thyroid goiter, and cervical disc hernia. There was no relevant family history or drug abuse.
Routine EEG, cerebral CT, and analysis (including thyroid function) were normal.
At the psychiatric evaluation, the patient was conscious, oriented, and cooperative. She was anxious, with an apprehensive facial expression. The speech was coherent and focused on her health problems and on her difficulty of having a good night sleep.
When asked to detail her complaints, it emerged that patient's symptoms had started at the age of 35 years. She mentioned “visual hallucinations during her sleep” of which she only remembered that “there was something terrible.” Her husband mentioned that every night, during the sleep, the patient suddenly became agitated. He described screaming, fear, bizarre movements of feet and legs, more rarely, movements of upper extremities and, very rarely, complex motor behavior as getting out of bed with posterior falling down (no generalized seizures observed), and perplexity if awakened. These episodes were stereotypic and lasted about 5–10 minutes. No aggressive behavior was observed. No eventual trigger factors were identified.
The patient also mentioned that in daytime she felt anxious due to the fear of falling asleep and repeating the same symptoms; that is why she complained of her “fear to be alone.”
An anticonvulsant treatment with oxcarbazepine was started. Within one week, symptoms remitted completely, allowing her to a good night sleep, which the patient considered an unequivocal improvement. She still mentioned anxiety and fear of being alone; for that, an antidepressant (escitalopram in low dose) was added. One month later, no night episodes occurred; anxiety symptoms also remitted.
The patient was referred to neurologist for further observation, exams, and etiological clarification.


A 75-year-old woman was referred to our hospital with intraventricular hemorrhage (Fig. ) caused by hypertensive choroid plexus hemorrhage. She had a history of hearing loss from childhood. Cranial magnetic resonance (MR) imaging at age 73 years for screening of dementia demonstrated ventricular enlargement (Fig. A). On admission, she had mild conscious disturbance (Glasgow Coma Scale [GCS] 12: E = 4, V = 3, M = 5), gait disorder, and difficulty in feeding herself. She had short neck and low posterior hairline (Fig. A,B).


An 80-year-old Japanese woman was admitted to our hospital because of a 2-day history of fever. She had no relevant medical history except for hypertension, for which she had been prescribed amlodipine (5 mg/day). She was taking no other medications. She was a nonsmoker and nondrinker. She caught a cold 10 days before admission and recovered 1 week later. Four days before admission, she experienced general malaise without a fever. Two days before admission, she suddenly developed a fever (38.7°C) with left ventral neck pain. She was examined by her home doctor and prescribed oral cefdinir (300 mg/day), but her fever persisted. She was then admitted to our hospital.
On admission, her height was 141 cm, weight was 47 kg, body temperature was 38.0°C, and blood pressure was 126/62 mmHg. Her heart rate was 90 beats/min with a regular rhythm. A physical examination showed no major abnormalities except for mild and tender swelling of the left anterior region of the neck. Chest and abdominal X-ray films and an electrocardiogram were normal. Laboratory tests showed a high WBC count of 23.4 × 109 cells/L (reference range, 3.5–9.0 × 109 cells/L), lactate dehydrogenase concentration of 243 U/L (reference range, 124–222 U/L), blood urea nitrogen concentration of 21.1 mg/dL (reference range, 8–20 mg/dL), creatinine concentration of 1.16 mg/dL (reference range, 0.46–0.79 mg/dL), and CRP concentration of 19.41 mg/dL (reference range, 0.00–0.14 mg/dL). The fasting plasma glucose and hemoglobin A1c concentrations were 5.3 mmol/L (reference range, 3.9–5.5 mmol/L) and 5.5% (reference range, <6.0%), respectively, indicating the absence of diabetes. Urinary findings were normal. Rapid antigen tests for influenza, pneumococcus, and mycoplasma were negative. Thyroid function tests showed a decreased thyroid-stimulating hormone concentration of 0.18 mU/L (reference range, 0.35–4.94 mU/L) and increased free T4 concentration of 3.06 ng/dL (reference range, 0.70–1.48 ng/dL). Ultrasonography revealed an enlarged thyroid gland with a heterogeneous texture and multiple confluent nodules that were not well-circumscribed and were predominantly hypoechoic, suggesting preexisting adenomatous goiter. Notably, a round, heterogeneous, hypoechoic lesion without a distinct capsule, which was obviously different from the other goiter nodules, was observed in the left lobe of the thyroid gland; it measured approximately 26 × 22 mm (Fig. A). Plain CT of the neck also showed multiple nodules in the thyroid gland but provided no further information regarding the inside of the nodules. Based on these findings, US-guided FNAB targeting a hypoechoic lesion was performed to discriminate between AST and subacute thyroiditis soon after admission. Although FNAB did not yield pus, cultures of the thyroid aspirate needle washout, blood, urine, and sputum were carried out. Although the definitive diagnosis was unclear on admission, oral prednisolone (30 mg/day) was prescribed due to suspicion for subacute thyroiditis. Intravenous administration of aminobenzylpenicillin (8 g/day) was simultaneously performed because the possibility of AST was not completely negated.
On day 2, Gram-positive cocci were detected from the blood culture samples, and administration of the oral prednisolone was discontinued. The patient's general status improved, and she became afebrile on day 4. On day 5, the Gram-positive cocci detected from the blood culture samples were identified as S. agalactiae. Notably, S. agalactiae was also detected from the culture samples of the thyroid aspirate needle washout on admission. The urine culture revealed a small amount of Escherichia coli (1.0 × 104/mL) and S. agalactiae (1.0 × 103/mL); the sputum culture detected no remarkable pathogenic bacteria. All of the S. agalactiae strains detected from blood, biopsy needle washout, and urine showed the same antibiotic sensitivity. Gynecologic and urologic evaluations revealed no significant abnormalities. Vaginal secretion culture was performed on day 5, but S. agalactiae was not detected. Cytological examination of the FNAB samples on admission revealed an abundance of inflammatory cells, including polymorphonuclear leukocytes and lymphocytes (Fig. A), and no remarkable cellular atypia of the follicular epithelial cells (Fig. B). Accordingly, we diagnosed the patient with AST due to S. agalactiae infection. Ultrasonography of the thyroid gland on day 6 revealed that the hypoechoic lesion inside the left lobe had slightly increased in size (29 × 27 mm) and that the internal echogenicity was lower than that on day 1 (Fig. B). The patient's left neck pain resolved and her WBC count normalized on day 10, and her CRP concentration normalized on day 14. Administration of intravenous aminobenzylpenicillin was discontinued on day 14, and she was discharged from our hospital on day 16.
US examination was repeated 1 month after discharge. The size of the hypoechoic lesion was markedly reduced (17 × 15 mm) (Fig. C), and the thyroid function test results had also normalized. An otolaryngology evaluation and barium swallow failed to reveal a pyriform sinus fistula. At the time of this writing, the patient had been followed up for 6 months with normal thyroid function and no recurrence of AST.


A 67-year-old male who was diagnosed with lower rectal cancer underwent laparoscopic partial ISR with creation of a diverting ileostomy in July 2009. The pathological analysis indicated that the tumor staging was stage I (pT2N0M0 according to the 7th edition UICC) with negative resection margins. He did not receive adjuvant chemotherapy or radiotherapy. The ileostomy was reversed in August 2009, and he did well clinically for more than 4 years. In April 2014, although he was asymptomatic, laboratory blood tests showed signs of mild inflammation (WBC, 11,200 /μL; C-reactive protein, 2.2 mg/dL). Computed tomography (CT) scan revealed the presence of a small amount of extraluminal air between the prostate and rectum, adjacent to the coloanal anastomosis (Fig. ), which had not been observed on the previous follow-up CT scans. Both colonoscopy and cystoscopy were unable to detect a recurrent tumor or fistula on the anastomosis, but the presence of an anastomotic-urethral fistula was confirmed when orally administered medicinal charcoal was detected in the urine (Fig. ). He underwent reestablishment of an ileostomy, which has not been reversed for more than 1 year because the fistula remains.


A 44-year-old female went to a hospital in December 2007 complaining of anal bleeding. She was diagnosed with internal hemorrhoids, and she was treated using an aluminum potassium sulfate and tannic acid (ALTA) injection. However, her anal bleeding continued and she was admitted to our hospital because lower rectal cancer was additionally detected by colonoscopy. She underwent laparoscopic partial ISR with creation of a diverting ileostomy in July 2008, and the pathological analysis indicated that the tumor staging was stage I (pT2N0M0) with negative resection margins. She received adjuvant chemotherapy (UFT and leucovorin) for 12 months, and the ileostomy was reversed in November 2008. In September 2009, 14 months after ISR, she suddenly experienced a discharge of gas and feces from her vagina. CT and magnetic resonance imaging (MRI) revealed that an anastomotic-vaginal fistula existed at the right anterior side of the coloanal anastomosis (Fig. ). Colposcopy revealed a pin-hole fistula on the posterior wall of the vagina (Fig. ), and the biopsy from the fistula was not indicative of malignancy. She underwent reestablishment of an ileostomy, and subsequent follow-up CT and MRI showed no local recurrence for more than 1 year. The ileostomy was reversed in October 2010, and she has been alive without recurrence for more than 6 years.


A 74-year-old man who was diagnosed with lower rectal cancer underwent laparoscopic partial ISR in August 2007. The pathological analysis indicated that the tumor staging was stage 0 (pTisN0M0) with negative resection margins. In December 2007, 4 months after ISR, he presented with pneumaturia and fecaluria. Contrast enema revealed that an anastomotic-urethral fistula existed (Fig. ), and cystoscopy identified that it was located at the distal edge of the prostate (Fig. ). He underwent reestablishment of an ileostomy. The ileostomy was then reversed in January 2010 after the closure of anastomotic-urethral fistula was confirmed. He has been alive without recurrence for more than 7 years.


A 68-year-old woman who had undergone right hepatic lobectomy for hilar cholangiocarcinoma at the age of 60 years was diagnosed with lower rectal cancer with two liver metastases in February 2013. She underwent laparoscopic subtotal ISR for rectal cancer, and then, 1 month later, she underwent partial hepatic resection for liver metastases. The pathological findings indicated that the tumor staging was stage IV (pT3N0M1) with negative resection margins and that curative resection could be achieved. In December 2013, 9 months after ISR, she presented with anal pain and purulent perineal discharge. Colonoscopy and CT scan revealed that an anastomotic-perineal fistula existed on the right anterior side of the coloanal anastomosis (Fig. ), and then, she underwent reestablishment of an ileostomy. In February 2014, CT scan showed several metastases in the lung and she has received systemic chemotherapy for more than 2 years.


A 19-year-old male professional basketball player presents with pain to the lateral border of his left foot. The symptoms commence immediately after perceiving a snap to the left foot while attempting to jump. Forced inversion or flexion of the foot during injury is denied. Radiographs confirm a transverse stress fracture of the fifth metatarsal (
). Upon clinical examination, bilateral pes cavus and hindfoot varus alignment including peek-a-boo heel sign is observed (
). The patient is scheduled for intramedullary screw fixation with a 4.5-mm cannulated screw.
The surgical procedure was performed in regional anesthesia. The fracture was identified using a fluoroscan C-arm, and a small incision was made proximal to the base of the fifth metatarsal. An intramedullary guidewire was inserted into the fifth metatarsal and placed across the fracture site. The guidewire was then overdrilled protecting the soft tissue and tendon attachment with a drill sleeve. Counterpressure was placed along the longitudinal axis of the fifth metatarsal, and a correct length screw was inserted and tightened. All threads were placed distal to the fracture site. The screw head was embedded into the cortical part of the styloid process of the fifth metatarsal, avoiding screw head irritation (
). Fracture stability was ensured. The incision was closed with a single suture. The patient was equipped with a controlled ankle motion boot for 4 weeks, and nonweight-bearing for 14 days was advised.
The patient was assessed after 5 and 10 weeks after surgery, and radiographs of the fracture site were obtained (
). After 5 weeks after surgery, the patient was free of symptoms during functional activity and upon clinical examination. Return to competitive sport was permitted. After 10 weeks after surgery, radiographs demonstrated complete fracture consolidation, and the patient was free of symptoms during competitive sport and upon clinical examination. The patient was equipped with a varus unloading orthotic insert to reduce the risk of fracture recurrence. Hardware removal was not indicated.


A 68-year-old woman visited our department for foot drop on the right side after an embolectomy in July 2015. The cause of the foot drop was diagnosed by an electrodiagnostic study as common peroneal neuropathy, with a complete axonotmesis state at the fibular head level. A physical examination revealed that the motor power of the ankle dorsiflexion was nil, and the gait pattern was a steppage gait with the assistance of a single cane. She already had a conventional AFO for foot drop but rarely used it because it was heavy and uncomfortable both outdoors and indoors. She agreed to participate in our 3D printing study.


An 82-year-old man with a history of gout, hypercholesterolemia, and multiple nonmelanoma skin cancers was referred to our dermatology clinic for evaluation of pruritic lesions affecting the skin of the bilateral posterior arms for several weeks. He had no personal or family history of psoriasis or atopic dermatitis and denied any new contact exposures, new detergents, or starting any new medications or supplements. His daily medications included the following: allopurinol 300 mg, hydrochlorothiazide 25 mg, aspirin 81 mg, pravastatin 20 mg, and colchicine 0.6 mg. The patient had been on pravastatin therapy for hypercholesterolemia for over 5 years. Several months before onset of the rash his pravastatin had been increased from 10 mg to 20 mg daily.
Clinical examination revealed scaly, confluent, well-circumscribed erythematous plaques on the extensor surfaces of the upper arms extending to the forearms with no other lesions noted on skin exam (Figures and ). Evaluation of the nails did not reveal any significant findings. A 4 mm punch biopsy was obtained from the forearm for routine histological evaluation. Given the psoriasis-like appearance, the patient was prescribed triamcinolone ointment 0.025%.
The biopsy () revealed compact orthokeratosis and significant spongiosis with a perivascular lymphocytic infiltrate, consistent with an eczematous process. There was no evidence of acanthosis or psoriasiform epidermal hyperplasia. At the patient's follow-up appointment two weeks later, the lesions had spread to his anterior thighs and lower back. He was experiencing significant distress due to the pruritus and appearance of the rash and was treated with 40 mg intramuscular triamcinolone acetonide 0.1% solution. One month later, there was no improvement of his symptoms and alternative treatment options including phototherapy and nonsteroidal immunosuppressive therapy were considered. The patient was started on oral methotrexate, 10 mg weekly, as his schedule was unable to accommodate phototherapy. Further studies including complete blood count, metabolic panel, thyroid hormone, prostate specific antigen, serum protein electrophoresis, hepatitis B and hepatitis C, rapid plasma reagin, and autoimmune panel were unrevealing. Fungal culture and skin scraping for microscopic evaluation for dermatophyte were negative.
Despite an 8-week course of methotrexate, there was no improvement of his lesions. Finally, the patient underwent a trial off his pravastatin to rule out the statin as an etiologic agent. In collaboration with his primary care provider, the patient was switched to cholestyramine for cholesterol management and, after 8 weeks, his cutaneous lesions resolved. The patient was tapered off methotrexate and there was no recurrence of his lesions.


The patient was a woman aged 53 years with an abdominal mass that caused left popliteal and femoral vein thrombosis. She claimed stepwise enlargement of the abdomen and initially thought she had put on weight. However, when swelling progressed in her left leg, she was admitted to an internal medicine clinic. Her condition was diagnosed as DVT and she was referred to us upon finding an abdominal mass in her abdominal ultrasound (USG) examination. Abdominal enlargement and distension were observed, and abdominal USG revealed a 40×50 cm abdominopelvic mass, probably originating from her left ovary, with multiple septations and solid areas. Tumor markers (CA 19-9, CA 125) were within the normal range. A malignant ovarian tumor was initially suspected because of the size, and a positron-emission tomography-computerized tomography (PET-CT) was performed. The PET-CT revealed an enormous heterogenic mass with low metabolic activity in the left ovary, a 5×5 cm mass in the right ovary, and bilateral urinary stasis. A laparotomy with midline incision revealed a smooth-surfaced mass that filled the entire abdomen originating from the left ovary and confirmed the 5×5 cm mass in the right ovary (). A detailed pelvic examination was performed because of the risk of borderline potential, and it did not indicate metastases. There was minimal free fluid in the pouch of Douglas. The patient had hypotension and bradycardia, and we quickly decided to operate in the lateral position to prevent hemodynamic derangements. The ovarian masses were sent for frozen sectioning. A hysterectomy and bilateral salpingo-oophorectomy was performed because of the giant size of the cystic mass, the presence of a contralateral ovarian mass, and the patient’s age. The cystic mass weighed 27 kg. The masses were diagnosed as benign ovarian MCA.


A woman aged 41 years was admitted to a state hospital with pelvic pain, urinary burning, and vaginal bleeding. The patient was referred to our hospital after a cervical biopsy revealed cervical squamous cell carcinoma. On our physical examination, we observed an exophytic necrotic mass measuring 8x9 cm confined to the cervix with no parametrial invasion. According to the International Federation of Gynecology and Obstetrics classification, we established the diagnosis as stage 1b-2 cervical cancer. We excised the mass through the vagina route and performed a type 3 radical hysterectomy (Wertheim) with pelvic-paraaortic lymph node dissection followed by radiotherapy. In the fifth month after surgical treatment, we observed a 2x3-cm ulcerated nodular vulvar lesion (). The lesion in the vulva was excised following abdominopelvic computerized tomography (CT) imaging, which revealed no significant pathology. The biopsy specimen showed squamous cell carcinoma (). A paclitaxel and carboplatin combined chemotherapy protocol was used. Following 2 cycles of chemotherapy, positron emission tomography-CT revealed diffuse metastases in the abdominopelvic site. Despite and alternative protocol (gemcitabine and bevacizumab) administration, there was no response. The patient died in the 11th month of the postoperative period.


A woman aged 54 years who was post-menopausal presented with vaginal bleeding that had persisted for 3 months. A vaginal examination revealed a cervical mass measuring 1x1.5 cm. Histologic examination of the mass showed cervical squamous cell carcinoma. A Wertheim operation was performed and there was no lymph node involvement and the mass had negative surgical borders (stage 1b-1). A Papanicolaou smear was obtained from the vaginal cuff 3 months later and the result was negative. The patient presented with severe abdominal pain, which was localized along the incisional scar region of her umbilicus five months after the primary surgical treatment. Abdominal CT revealed an umbilical mass measuring 4x4.5 cm in diameter (). We considered that the fixed mass was inoperable; it included all layers of the umbilical wall and extended from umbilicus to the upper anterior abdominal wall with massive adhesions. We performed a partial resection of the mass and pathologic examination revealed metastatic squamous cell carcinoma. Two cycles of chemotherapy, including paclitaxel-carboplatin in the first cycle and bevacizumab-gemcitabine in the second cycle, and radiotherapy was administered. The patient died in the 11th month of her medication.


A young adult female patient (20-year-old) attended the clinic of restorative dentistry specialization course, complaining of dissatisfaction with the shape, staining, and fractures of composite resin restorations. The patient's history showed no extractions, previous orthodontic treatment, or implants. Clinical examination revealed a composite resin on the left lateral microdontic incisor, a prosthetic implant on the right lateral incisor, and hypoplastic stains on the central incisors and maxillary and mandibular canines. In addition, the gingival concave arch was irregular but gingival inflammation was not observed. The composite resin restorations of lateral incisors also were not maintaining adequate width-to-height ratio. Radiographic examination confirmed the presence of the implant and the health of adjacent tissues (Figures and ). Models and photographs were prepared for case study. A diagnostic wax-up was done on the maxillary arch model ().
Initial prophylaxis (CleanJoy, Cuxhaven, Germany) and scaling of the teeth were indicated prior to the surgical procedure. Despite the patient's periodontal health, it was still necessary to reconstruct gingival harmony. After four weeks, surgery was performed to increase the clinical crowns of the teeth. Probing with a millimeter probe was performed, and surgery was performed with an electric scalpel (Deltronix Bo 1300, Ribeirão Preto, São Paulo, Brazil), without the need for bone contouring. Gingivectomy was performed to achieve the desired gingival margin position, thus, improving the width-to-height ratio of dental crowns. Sutures were not needed. Following the surgical procedure, oral diclofenac sodium 100 mg was administered for 3 days. Dental prophylaxis was achieved 30, 60, and 90 days after surgery. Postoperative follow-up was done after 3 months ().
Dental bleaching was then performed in the dental office. A labial retractor (Arcoflex, FGM, Joinville, Brazil) was added to improve visibility and protection of soft tissues. The gingival barrier (Polaoffice Powder, SDI, Victoria, Australia) was applied and photopolymerized according to the manufacturer's recommendation. A buccal mirror was used to determine whether there were regions lacking the barrier, to avoid damage to the soft tissues. The 35% hydrogen peroxide bleaching gel kit (Polaoffice Powder, SDI, Victoria, Australia) was applied according to the manufacturer's instructions. The powder and liquid were mixed well to be homogenized in a gel of suitable viscosity. With the aid of a microapplicator, the product was placed on the buccal surfaces of the teeth, except for the maxillary lateral incisors that had restorations. The application was done without the addition of light. At the end, the gel was removed with suction and the aid of a piece of gauze. The teeth were washed, and this procedure was repeated two more times; that is, the gel was applied 3 times in that session. Four weeks of home bleaching with 10% carbamide peroxide was recommended (Pola Night, SDI, Victoria, Australia) ().
After two weeks for the color to stabilize, the final color was selected. The absolute isolation of the operative field was performed by means of a Hygienic rubber dam sheet (Coltene/Whaledent AG, Altstätten, Switzerland). Polytetrafluoroethylene (TDV, Pomerode, Santa Catarina, Brazil) tape was initially placed on the lateral incisors to prevent acid conditioning of these teeth.
The enamel surfaces of the central incisors and canines were conditioned with phosphoric acid over the teeth to avoid the application of resin over unconditioned areas. The surfaces were then dried, the adhesive (Futurabond, VOCO) was applied by means of a regular-sized microbrush (Coltene/Whaledent AG, Altstätten, Switzerland), and polymerization was carried out according to the manufacturer's instructions. Amaris resin in the TL color (Voco, Cuxhaven, Germany) was applied freehand, that is, without the aid of a silicone wall, with the aid of a CompoRoller spatula (Kerr, Orange, CA, USA). Only this resin color was used to reshape the teeth and cover the hypoplastic stains. Each increment was polymerized at the time recommended by the manufacturer, continuously and as closely as possible to the material without, however, touching the resin. In a subsequent session, the finishing and polishing of the resins were done with the Super Tray (Kerr, Orange, CA, USA) kit.
Temporary restorations with bisacrylic resin (Structur 3, Voco, Cuxhaven, Germany) were made on the lateral incisors (). The molding was done with the double-wire technique on the lateral microdontia (Sure-Cord, Sure Dent Corporation, Gyeonggi-do, Korea) simultaneously with the addition of reaction silicone (Variotime, Heraeus Kulzer, Hanau, Germany). The ceramic was prepared with the E.max injected system (Ivoclar Vivadent, Schaan, Liechtenstein) in the color BL4 and applied to the ceramic for intrinsic incisal characterization ().
The material used for the cementation of the ceramics on the lateral incisors was Bifix SE self-adhesive cement (Voco, Cuxhaven, Germany) in opaque white (WO) (). Prophylaxis with prophylactic paste was done prior to cementation. Neighboring teeth were protected with a Teflon strip (TDV, Santa Catarina, Brazil). The self-adhesive cement selected was inserted inside the restorations and placed in position. Excesses were removed with dental floss and a microbrush, and the cement was polymerized as recommended by the manufacturer.
After cementation, the occlusal contacts were checked and adjusted. The results can be seen in Figures and .


A 62-year-old Caucasian man with a history of lung cancer and recurrent pyelonephritis was admitted for work up for possible endocarditis because of fevers and Pseudomonas bacteremia. He had none of the previously mentioned risk factors for Pseudomonas endocarditis. One month prior to admission, he was treated in another state for pyelonephritis and prostatitis with piperacillin-tazobactam (1–3 days), followed by an unknown fluoroquinolone (approximately 10–14 days). Urine culture results from those events were not available. On admission, his serum chemistries, liver associated enzymes, and creatinine were normal. His complete blood count was notable for a hemoglobin of 11 g/dl (13–18 g/dl), and a hematocrit of 37% (40–52%). Computerized tomography of the chest abdomen and pelvis revealed diffuse emphysematous changes, small bilateral pleural effusions, minimal abdominal ascites, and a wedge-shaped zone of diminished attenuation in the right kidney. Treatment with gentamicin and cefepime was initiated. The P. aeruginosa isolated from his bloodstream was susceptible to ceftazidime (minimum inhibitory concentration (MIC) =4 μg/ml), cefepime (2 μg/ml), ciprofloxacin (<0.25 μg/ml), piperacillin-tazobactam (8 μg/ml; zone diameter > 21 mm), ticarcillin-clavulanate (32 μg/ml), gentamicin (2 μg/ml), tobramycin (<1 μg/ml), amikacin (</=2 μg/ml), imipenem (2 μg/ml), and meropenem (0.5 μg/ml). On HD-2, infectious diseases consultation was obtained, and therapy was changed to 2 g cefepime every 8 h, plus 7 mg/kg of tobramycin daily. Subsequently, blood cultures became negative and transesophageal echocardiogram revealed a mobile mass on the aortic valve and severe aortic regurgitation. On HD-11, the patient underwent aortic valve replacement, and P. aeruginosa was isolated from the excised valve tissue. Unexpectedly, the valve isolate was resistant to ceftazidime (>/=64 μg/ml), cefepime (MIC 32 μg/ml), piperacillin-tazobactam (128 μg/ml, zone diameter 21 mm); and ticarcillin-clavulanate (128 μg/ml). MICs to all the other previously mentioned antibiotics were the same as the MICs of bloodstream isolate. Both the valve and blood isolates were tested on the same platform (Vitek ®2, bioMérieux, France), with the same card-AST GN69 (bioMérieux, France) from the same lot (5,890,118,103), using the same inoculation protocols. Furthermore, all results for piperacillin–tazobactam are confirmed with supplemental disk diffusion (Kirby–Bauer) testing before being released. The zone diameter of piperacillin-tazobactam on the blood isolate was >21 mm (sensitive) and 12 mm (resistant) on the valve isolate, which were concordant with the Vitek 2 results. We debated whether the bloodstream or the excised valve isolate should dictate the choice of β-lactam, replaced the cefepime with meropenem, and continued the tobramycin.
To assess genetic relatedness and resistance gene content, both isolates underwent whole-genome sequencing (WGS) on a MiSeq bench-top sequencer (Illumina, San Diego, CA) using methods described previously and ResFinder [, ]. On HD14 In preparation for sequencing, both isolates were thawed, re-cultured on the same media (MacConkey agar (Millipore-Sigma, Temecula, CA)), and simultaneously tested on the same platform using the same card from the same lot as was used in the previous tests. Unexpectedly, the cefepime MIC of the valve isolate had decreased from 32 μg/ml–4 μg/ml, and the piperacillin-tazobactam MICs had fallen from >128 to 8 μg/ml. In the interest of antimicrobial stewardship, and cognizant of the fact that in one series more than 50% of the patients who started with a fully carbapenem susceptible isolate had a >/=4-fold increase in carbapenem MIC during carbapenem therapy [], we again debated the optimum β-lactam and whether cefepime should replace meropenem for the remaining 3.5 weeks of therapy.
WGS revealed that the valve and bloodstream isolates were identical –differing by only one nucleotide in the cheA gene, resulting in truncation and inactivation of CheA which is involved with motility and chemotaxis [, ]. Both isolates belonged to multi-locus sequence type (ST) 162 and contained the same set of resistance genes (bla
ADC35
, aph(3′)-II, blaOXA
, catB7, and fosA). There are very few reports of P. aeruginosa ST-162. Of those reports available, ST162 has been associated with Klebsiella pneumonia carbapenemase producing strains in Argentina, and a VIM-2 producing strain in Algeria [, ] At the whole-genome level, the isolates in our patient were most closely related to reference strains PA_O1 and PA_O581, followed by strain PA_LESB58 (Fig. ). PA_O1 is a spontaneous chloramphenicol-resistant mutant derived from of the original strain that had been isolated in 1954 from a wound in Melbourne, Australia [, ]. PA_O581 is an alginate producing mucoid strain isolated from the sputa of cystic fibrosis patients in Scotland [, ]. PA_LESB58 is the hyper-virulent ‘Liverpool Epidemic Strain’ from an outbreak in pediatric cystic fibrosis clinic in England. PA_LESB58 is a strain that overproduces pyocyanin and other quorum sensing exoproducts and has been associated with transmissibility, dominance over other P. aeruginosa populations in CF airways, increased morbidity and mortality, and causing infections in healthy parents (and a pet cat) of children with cystic fibrosis [–]. In light of this potential for increased virulence, and the uncertainty of the resistance profiles, meropenem and tobramycin were continued. Two months after completing 6 weeks of total antibiotic therapy, the patient had no evidence of endocarditis and was doing well.


A 50-year-old woman of Amhara ethnicity, para III, abortion I (induced), presented to our out-patient department with the complaint of excessive hair on her face of 4 years’ duration. The hair growth was on her face and lower abdomen; it had gradually increased in amount despite frequent shaving. Her menopause started 7 years ago. She had no vaginal bleeding or discharge; she had no abdominal or pelvic pain. She did her daily chores normally as before but the hair growth over her face affected the quality of her personal life and work life.
Her weight was 65 kg with a body mass index (BMI) of 29.8 kg/m2. Her vital signs were in the normal range and there were no abnormal findings from tests of her chest and cardiovascular system. She had hair on her upper lip, chin, and lower abdomen with a modified Ferriman–Gallwey score of 10, which is mild hirsutism (Fig. ). An abdominal examination revealed no abnormality. On pelvic examination, her uterus was normal sized. Since she was obese we failed to detect an adnexal mass that was later detected by ultrasound; her right ovary measured 5 × 4 cm. Her left ovary was normal and no ascites or cul-de-sac fluid was seen. No signs of virilization were found in the form of clitoromegaly, frontal baldness, loss of female body contours, increased muscularity, or atrophy of the breast. She had normal complete blood count, electrolytes, and renal and liver function tests. However, her low-density lipoprotein (LDL) and total cholesterol were raised. Hormonal assays revealed: elevated serum testosterone level, 254 ng/dl; normal cancer antigen (CA) 125, 12.65 u/l; and follicle-stimulating hormone (FSH) was 0.74 miu/ml. Other tests for tumor markers and computed tomography (CT) were not performed as they were not available in our hospital. An endometrial biopsy was done and the result was inconclusive. She was counseled to undergo exploratory laparotomy but she declined. After 10 months, she presented to our out-patient department with a complaint of vaginal bleeding of 18 days’ duration, which was minimal initially and subsequently became excessive with dark clotted blood. She does not have a family history of breast or ovarian cancer. She had stable vital signs and upon pelvic examination a 10 by 15 cm right adnexal non-tender, firm, mobile mass was detected. Sonographic evaluation revealed a 12 by 15 cm right adnexal cystic mass with echo debris, thick walled, and it had minimal cul-de-sac fluid collection which was consistent with malignant ovarian tumor. An exploratory laparotomy was performed with a finding of 400 ml ascites and a 20 by 30 cm right ovarian mass with ruptured capsule. Her left ovary and uterus were normal; there was no seeding into peritoneum, omentum, or other intra-abdominal organs. A total abdominal hysterectomy, bilateral salpingo-oophorectomy, resection of the mass, infracolic omentectomy, and right pelvic lymph node sampling was performed and a specimen sent for histopathology (Fig. ). The result of pathology was AGCT (section from the ovarian mass showed solid insular trabecular patterns and microfollicles formed by proliferation of round to spindle-shaped cells having coffee bean-appearing nuclear grooves and inconspicuous nucleoli in fibrocollagenous stroma, frequent mitotic figures were seen) with normal appearing uterus and cervix, and reactive sinus histiocytosis was seen in the lymph nodes. Her postoperative course was uneventful, her hematocrit was 38%, and she was discharged on postoperative day 5. She was followed-up every month for the first 3 months and then every 3 months. She took five cycles of chemotherapy at a medical oncology unit: bleomycin, etoposide, and cisplatin (BEP). She had more than seven visits after the surgery and chemotherapy. All investigations including complete blood count, liver function tests, and renal function tests were normal. She has no abdominal or pelvic pain, and neither does she have a bowel complaint or a urinary complaint. The hair growth is significantly reduced from before and she does not need to shave her facial hair. Her physical performance is good and she is able to do her daily activities as before. An ultrasound was done once during her follow-up and was normal.


Here, we present a 52-year-old Chinese woman. 6 years before her admission, she began to feel a depressive mood, inferiority and desperation, as well as insomnia, retardation, and social withdrawal. She lacked interest in doing anything and rarely felt happy. She lost any desire to prepare meals for her family and complained constantly. She reported having thoughts about suicide but never attempted it. She and her family did not act on these symptoms, so the patient never sought or received medical treatment. One month before her admission, the depressed mood exacerbated. She felt hopeless, worthlessness, guilt, and had recurrent suicidal ideation. At the same time, she developed into delusions, feelings of reference and persecution, and auditory hallucinations in the form of commentary, repetitive speaking about inappropriate sexual relations, death and the dead body. She also exhibited abnormal behaviors including irrational laughter, yelling, cursing and praising God. Although her consciousness was not disturbed, she occasionally failed to recognize her husband or daughters. Her appetite and sleep were poor.
She underwent hysterectomy, bilateral salpingo-oophorectomy and postoperative radio-chemotherapy to treat cervical carcinoma 6 years ago. The patient reported never drinking or smoking, and she was allergic to pollen. She had worked as a kindergarten teacher, but she stopped working after giving birth. Her husband did not live with the patient and daughters. She had no family history of mental disorders.
Her vital signs were stable, and no abnormal physical or neurological signs were detected at admission. Blood and urine tests were routine, blood glucose and liver and renal functions were normal, and no evidence of infection was found. Antithyroglobulin antibody was 273.80 IU/ml (reference value<115), antithyroperoxidase antibody was 596.10 IU/ml (reference value<34), free triiodothyronine was 3.35 pmol/L (reference value 3.60–7.50). Electroencephalography (EEG), electrocardiogram, and transcranial Doppler ultrasound results were normal. Antinuclear antibody (ANA) was detected in serum at a titer of 1:1000, while antibodies against Extractable nuclear antigen (ENA) or cardiolipin were not detected in serum. Brain MRI revealed several small ischemic foci in bilateral frontal lobes. The patient can’t finish the cognitive testing due to non-cooperation when admission. She and her family members denied any abuse of alcohol or illicit substances. Her family history was negative for mental illness.
The patient was diagnosed with severe major depressive disorder with psychotic features, based on the Structured Clinical Interview in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). She was treated with venlafaxine (75 mg every morning, increased 5 days later to 150 mg), lorazepam (0.5 mg every night), olanzapine (5 mg every morning, 15 mg every night), and electroconvulsive therapy (on two occasions). 5 days later, she slept well, but her mood still depressed and presented delusions of persecution, auditory hallucinations, abnormal behaviors continued. After she had spent one week in the hospital, her condition suddenly worsened: she began to talk nonsense loudly, she felt disoriented, and she did not recognize family members or her environment. She became restless and drank water repeatedly throughout the night. The next morning she suddenly stopped speaking. These symptoms continued to alternate over the course of each day.
This rapidly and dramatically changing disease course led us to organize a consultation with the neurology department. Neurological examination gave no remarkable findings, and lumber puncture was advised. CSF analysis showed no remarkable abnormalities in pressure, appearance, cells, proteins, glucose, chloride, IgG synthesis rate, or results of smear culturing for bacteria, tubercle bacilli, and fungi. The CSF was assayed for autoimmune encephalitis antibodies at Peking Union Medical College Hospital. Cell based assay was used to detect the antibodies of NMDAR, CASPR2, AMPA1-R, AMPA2-R, LGI1 and GABA2-R, and immunoblotting was used to detect the antibodies of Hu, Ri, Yo, PNMA2 (Ma2/Ta), and CV2/CRMP2 [, ]. The results indicated the presence of specific IgG antibodies against NR1 in NMDAR at a titer of 1:100 (Cut-off value 1:10). The other antibodies including CASPR2, AMPA1-R, AMPA2-R, LGI1, GABA2-R, Hu, Ri, Yo, PNMA2 (Ma2/Ta), and CV2/CRMP2 were negative. The patient was diagnosed with concurrent anti-NMDAR encephalitis and severe major depressive disorder with psychotic features.
At 15 days after hospitalization, the patient was transferred to the neurology department for further treatment. She was given intravenous methylprednisolone (1000 mg daily for 5 days) and immunoglobulin (20 g daily for 5 days), as well as venlafaxine (75 mg every morning), lorazepam (0.5 mg every night) and olanzapine (5 mg every night). During 2 weeks of treatment, her disorientation, behavioral disturbances, hallucinations, and delusions gradually disappeared. She was discharged still in a depressive mood; she was not talkative and showed obvious social withdrawal behavior.
2 months later, she was re-admitted to the neurology department as normal follow-up. Her emotional state, appetite and sleep were good. No cognitive or behavioral abnormalities were found. Lumber puncture was conducted a second time, and CSF analysis revealed the presence of specific IgG antibodies against NR1 in NMDAR at a reduced titer of 1:10. She was prescribed oral medications (venlafaxine 75 mg every morning, lorazepam 0.5 mg every night, olanzapine 5 mg every night) and followed up on an outpatient basis.


A 12-year-old boy was admitted to the Santa Maria Hospital of Terni on 27 September 2016, due to a three-day history of fever (38 °C) and vomiting with acute presentation. Approximately two weeks before, the child had suffered from an episode of mild fever associated with abdominal pain and diarrhea that spontaneously resolved in a few days. In addition, in the previous three months, the child had complained of fatigue and loss of appetite several times; the previous history was negative. A mild reduction in body weight, of approximately 2 kg, was noted. Finally, in the last year, the parents had noticed mild but significant hyperpigmentation of the skin and mucous membranes, without giving it any importance. The child was previously well, suffering no significant diseases. His physical and neurological development was always considered within the normal range. There was no family history of severe clinical problems, including autoimmune diseases.
shows a picture of the boy at the time of admission. Physical examination revealed a patient in mediocre general condition, with a body weight of 35 kg (28° centile), a height of 150 cm (50° centile), and a body mass index of 15 (10° centile). Marked darkening of the skin, particularly on the palms and areolae, was evident. Subcutaneous fat tissue was reduced. No pathological findings of the upper and lower respiratory tract, heart, abdomen, or central or peripheral central nervous system were detected. His blood pressure was 110/60 mmHg, which is within the normal range for his age. Laboratory evaluation revealed no abnormalities of white or red blood cell counts (5320/µL; normal values, 4000–10,000/µL and 4,390,000/µL, respectively), no anemia (Hb 12.8 g/dL; normal values, 12–16 g/dL), no increase in serum concentrations of acute phase reactants (C reactive protein, 0.20 mg/dL; normal values <0.65 mg/dL and procalcitonin <0.05 ng/mL), hyponatraemia (124 mEq/L; normal values, 135–145 mEq/L) and hypochloraemia (93 mEq/L; normal values 100–110 mEq/L), mild hyperkalaemia (5.2 mEq/L; normal values, 3.5–5 mEq/L), borderline hypoglycaemia (69 mg/dL; normal values 70–110 mg/dL), and slight increases in blood urea nitrogen (53 mg/dL, normal values 10–50 mg/dL), serum creatine phosphokinase (909 UI/L; normal values 0–171 UI/L), and serum uric acid (9.5 mg/dL; normal values, 4.8–8.7 mg/dL). His ammonia levels, arterial blood gas, and blood lactate were within the normal range.
Immunological evaluations revealed normal serum IgA (81 mg/dL; normal values, 70–400 mg/dL), IgG (716 mg/dL; normal values, 700–1600 mg/dL), and IgM levels (47 mg/dL; normal values, 40–280 mg/dL), as well as negative anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-mitochondrial antibodies, extractable nuclear antigen screening, anti-thyroglobulin antibodies, anti-thyroperoxidase antibodies, and anti-phospholipid antibodies. However, a marked increase in IgA anti-transglutaminase (129 U/mL; normal values, <4 U/mL) and anti-endomysium (positive with a titre of 1/80) antibodies was found. A genetic study with polymerase chain reaction (PCR) DNA amplification and inverse hybridization testing alleles DQA1*05, DQB1*02, and DQB1*03:01 revealed the presence of HLA haplotypes DQ2 and DQ8. Duodenal biopsy could be spared according to the 2012 ESPGHAN CD diagnostic guidelines as anti-tranglutaminase antibodies were elevated over 10 times the normal range (129 UI/mL; normal values, <4 UI/mL), confirmed by the positivity of anti-endomisium antibodies and by the compatible HLA aplotypes.
Beginning with the clinical and laboratory data [,], celiac disease was diagnosed. In addition, primary AD was suspected. The diagnosis of CD and AD occurred quite late because the previous history of this child was negative and the parents did not give much importance at the symptoms that occurred in the last year. This was confirmed by low values of morning cortisol (0.8 µg/dL) and dehydroepiandrosterone sulfate (16.2 µg/dL), with adrenocorticotropic hormone (ACTH) concentrations of 1250 pg/mL. No abnormalities in adrenal gland morphology were found in abdominal ultrasonography and magnetic resonance tomography images. The child was treated with intravenous saline solution starting with a bolus of 300 mL over 2 h, followed by a maintenance dose of 1600 mL every 24 h. Serum electrolyte concentrations were evaluated every hour in order to ensure the maintenance of normal values. Normalization of the child’s electrolyte values was established within 3 h and the infusion was discontinued after 48 h.
On the second day of observation, further evaluation of the patient’s adrenal function was planned. The basal aldosterone and renin concentrations were evaluated. The renin level was high (19.10 ng/mL/h), whereas the aldosterone level was low (3.30 pg/mL). The serum ACTH level was lower than the previous day, but higher than the normal values (from >1250 pg/mL on day 1 to 477 pg/mL on day 2; normal values, <46 pg/mL). In addition, ACTH administration only marginally increased the cortisol concentrations at 30 (0.8 µg/dL) and at 60 min (0.6 µg/dL; normal values, 4.3–23.0 µg/dL). A 5-h Synacthen stimulation test confirmed adrenal insufficiency, as serum cortisol values did not reach the minimum normal values at various times of evaluation. The basal cortisol level was undetectable (<50 nmol/L) and failed to rise following Synacthen administration: the 60-min value was <600 nmol/L and the 5-h value was <1000 nmol/L.
Considering the simultaneous co-existence of AD and CD, cortisone acetate was administered at 25 mg at 8 a.m. and 12.5 mg at 4 p.m., and a gluten-free diet was initiated, instructing the patient and his parents on how to follow it correctly. The child was discharged from the hospital after four days, and the follow-up was planned. Thirty days following discharge, the evaluation revealed that the skin hyperpigmentation had almost completely disappeared. The adrenal insufficiency was no longer present (serum sodium, 135 mEq/L, potassium 4.4 mEq/L, chloride 101 mEq/L, glucose 93 mg/dL) and only a small dose of cortisone acetate (37.5 mg/die) was required to maintain normal serum electrolyte and cortisol concentrations. The compliance to the gluten-free diet was confirmed by the patient and his family and was also associated with a significant increase in body weight, of 1.5 kg. The anti-transglutaminase antibodies were dosed at the one-month follow-up control, and were found to still be high (121 UI/mL).


A 14-month-old girl with a body weight of 7.7 kg was admitted to our pediatric intensive care unit (PICU) in acute polyuric renal failure including severe hypernatremia, hyperchloremia, hyperkalemia, hyperuricemia, and metabolic acidosis. Clinically she was irritable and appeared only mildly dehydrated. Her heart rate on admission was 150 beats per minute with an arterial blood pressure of 83/43 (63) mmHg. Renal ultrasound on admission revealed bilateral nephrocalcinosis type IIa. Her laboratory findings on admission are summarized in . The girl was treated with tacrolimus after liver transplantation 7 months prior to admission for extrahepatic biliary atresia. Renal ultrasound before liver transplantation showed a normal finding. She was discharged home from a former hospital stay 8 days prior to this admission with the recommendation for 800 ml Nutrini Energy MultiFibre® () a day in addition to complementary feeding. Against medical advice she drank no additional water. Therefore, her calculated water deficit over the last 8 days was 23.6% of her body weight (). In PICU the high protein diet was interrupted and the girl was intravenously rehydrated. The average diuresis in the first 12 hours after admission was 8.1 ml/kg/hour. Additionally, bicarbonate was administered and the antihypertensive therapy with enalapril was paused for 2 days. Under these therapeutic measures the renal function recovered and the serum electrolytes returned to normal values. After reinstating feeding with Nutrini MultiFibre plus oral bicarbonate instead of Nutrini Energy MultiFibre the child was transferred to the normal ward. On day 9 after admission she was discharged home. At the time of discharge the patient's serum urea and creatinine values were within the normal range, her glomerular filtration rate assessed by serum cystatin C was 76 ml/min/1.73 sqm. In the later course immunosuppression was changed from tacrolimus monotherapy to low-dose tacrolimus plus mycophenolate mofetil.


A 22-year-old nonsmoker, nonalcoholic male from a middle-class family in the midwestern part of Nepal was referred to our tertiary center with intermittent fever, pain in the left lower chest, occasional nausea and vomiting, anorexia, and weight loss of three-week duration. Symptoms did not improve with two weeks of broad-spectrum oral and then parenteral antibiotics at a local hospital. Fever was associated with chills and rigors. Left lower chest pain was continuous with radiation to the left shoulder. There was no associated cough, shortness of breath, altered bowel or bladder habits, jaundice, headache, vomiting, joint pain, or any skin nodules. There was no history of drug abuse or sexual promiscuity. There was no history of diabetes mellitus and no past or family history of TB.
On examination, the patient's body temperature was 102°F, pulse was 100 beats per minute, and respiratory rate was 16 breaths per minute and regular. Chest examination showed tenderness in the left infra-axillary region and normal bilateral vesicular breath sounds without any additional sounds. Cardiovascular examination revealed normal heart sounds without murmur. Abdominal examination showed a soft, tender left upper quadrant with Traube's space dullness; however, the spleen and liver were not palpable. Complete blood count, liver and renal function tests, posteroanterior chest X-ray, and echocardiography were normal. Erythrocyte sedimentation rate (ESR) using Wintrobe's method was elevated at 58 mm per hour. Purified protein derivative (PPD) was 12 mm. Sputum samples on three consecutive days were negative for acid-fast bacillus (AFB). Spot serological tests for human immunodeficiency virus, hepatitis B, and hepatitis C were nonreactive. Three consecutive bacterial blood cultures and a urine culture showed no growth. Serologic tests for malaria, leptospirosis, brucellosis, and leishmaniasis were negative. Ultrasound of the abdomen () revealed a 5.3 × 4.0 × 3.5 cm hypoechoic lesion at the lower pole of the spleen that was in communication with a similar lesion of an approximately 40 ml collection at the perisplenic area. Likewise, a 3.9 × 3.0 × 2.8 cm collection at the superior pole of the spleen was in communication with a similar collection at the perisplenic area. Contrast-enhanced computed tomography of the abdomen () showed two perisplenic hypodense collections of 6.9 × 5.1 × 3.2 cm at the inferior pole and 5.2 × 4.0 × 3.0 cm at the superior pole of the spleen having connections with similar splenic parenchymal collections, suggestive of multiple splenic abscesses with perisplenic extensions. The patient did not improve with three weeks of empiric parenteral broad-spectrum antibiotics.
Diagnostic and therapeutic ultrasound-guided aspiration removed approximately 30 ml of pus which was sent for microbiological and molecular examination for MTB. The pus was negative for AFB staining; however, PCR for MTB was positive. Gram's stain revealed no bacteria, and routine 72-hour bacterial culture showed no microorganism growth.
Diagnosis of primary splenic tuberculosis was made, and as per directly observed treatment, short course (DOTS), ATT category I was initiated for 6 months. One week after starting ATT, the patient improved clinically with fever resolution and an increase in appetite. The patient was then discharged on ATT. On follow-up, the patient had clinically improved and gained weight. Serial ultrasounds of the abdomen showed a gradual decline in the abscess sizes. Upon completion of six months of ATT, the patient was clinically asymptomatic and had normal ESR, and ultrasound of the abdomen () showed normal spleen.


A 24-year-old male presented to our emergency department with worsening cough, fever, and chills of one-day duration. The patient reported cough for one week that progressively worsened, with mucoid phlegm associated with low-grade fever, chills, and shortness of breath of 1-day duration. He denied hemoptysis, gastrointestinal symptoms, and chest pain and reported no bird exposure, skin rash, arthralgia, recent travel, or sick contacts. His medical history was significant for mild persistent asthma and schizophrenia. He had no prior surgeries and had resided in a psychiatric facility for 2 years with no occupational exposure to chemicals or toxins. He was a former polysubstance abuser and was in abstinence for 2 years. He denied smoking cigarettes, using illicit drugs, or abusing alcohol and had no reported allergies. His medications included divalproex sodium, clozapine, zolpidem, albuterol, and fluticasone aerosol inhaler. He had a negative tuberculin skin test 6 months prior to admission for the current complaint.
A physical examination revealed a young man of average built, with a temperature of 100.4 F, pulse rate of 78/min, respiratory rate of 20/min, and blood pressure of 110/66 mmHg; he also showed 96% saturation on ambient air. He appeared lethargic, with no conjunctival pallor, cyanosis, nuchal rigidity, skin eruptions, or palpable lymphadenopathy. Bilateral air entry was evident on auscultation of lungs, with fine rales on the right side. A precordial examination revealed normal heart sounds, with no murmur, rub, or gallop. An abdominal exam revealed no organomegaly, and a neurological examination showed no motor or sensory neurological deficits. An initial laboratory examination showed neutrophilic leukocytosis (white blood cell count, 18,000/mm3 with 74% neutrophils) and elevated blood urea nitrogen (25 mg/dL) with lactic acidosis (2.5 mmol/L). He had no anemia (hemoglobin, 13.5 g/dL), thrombocytopenia (157,000/μL), or renal failure (creatinine, 0.6 mg/dL). A urine toxicology screen was negative for any drugs. His initial chest radiograph showed right upper lobe consolidation (). He was admitted to the hospital for pneumonia, which was managed with vancomycin, piperacillin-tazobactam, and azithromycin. Further evaluation by chest computed tomography (CT) showed a thick-walled, right upper lobe cavitary lesion (). Fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) was performed to test for associated infections or noninfectious processes. A transbronchial biopsy of the lung showed diffuse lymphocytic infiltrates. Cultures for common bacteria, Mycobacterium tuberculosis, and fungi were negative, as were cultures for respiratory syncytial virus, influenza viruses, parainfluenza viruses, adenoviruses, and vasculitis workup as shown in . Serology performed to detect other infections indicated a cold agglutinin titer of 1 : 320 and an M. pneumoniae IgM antibody titer of 1 : 1,280. At this point, antibiotic treatment with oral azithromycin was continued and the remaining antibiotics were discontinued. The patient's condition did not improve clinically, so levofloxacin was started and the patient was discharged to the psychiatric facility on oral medication for 2 weeks. Follow-up chest radiograph two months later showed right upper lobe scarring and improvement in consolidation (). Follow-up CT scan two months later showed foci with ground glass opacity in the anterior right upper lobe of the lung surrounding a 9.9 mm nodular density and three months later showed complete resolution of the cavitary lesion without sequelae (Figures and ); the antibody titer for M. pneumoniae IgM was also reduced (1 : 160) 3 months later.


A 35-year-old African American woman presented to the Emergency Department with progressive shortness of breath. She was found to be hypoxic via home pulse oximeter with an oxygen saturation of 80%. The patient's dyspnea first started two months prior to admission when she was diagnosed and treated for community acquired pneumonia at an outpatient clinic. Her dyspnea progressed despite repeated admissions to community hospitals, during which she had extensive diagnostic tests including pulmonary function tests (PFTs), bronchoscopy, electromyography (EMG), echocardiogram, and computed tomography (CT) scans of the chest. PFTs showed a restrictive pattern with a decreased vital capacity of 21%. Bronchoscopy, EMG, and echocardiogram did not lead to a definitive diagnosis. The chest CT showed nonspecific dense bibasilar consolidation (). During each hospitalization, she was managed with antibiotics and steroids for presumed pneumonia with asthma exacerbation. Her most recent admission was one week prior to presentation at which time she was discharged with home oxygen and a CPAP machine.
Past medical history included mild persistent asthma treated with albuterol and budesonide-formoterol, postpartum hypertension treated with hydralazine 10 mg PO every 8 hours and chlorthalidone 25 mg PO daily, environmental allergies treated with cetirizine as needed, gastroesophageal reflux disease treated with esomeprazole, prolactinoma treated with cabergoline, and irritable bowel syndrome. Family and social history were noncontributory.
Review of systems was significant for fevers, chills, productive cough, chest tightness, nausea, abdominal pain, decreased appetite, lower back pain, fatigue, diffuse joint pain, and numbness and tingling of her hands and feet. In the Emergency Department, her oxygen saturation dropped into the 70s on room air with a heart rate of 103 bpm. All other vital signs were stable and within normal limits. On physical examination, the patient appeared to be in moderate distress, gasping for air between words. Crackles were audible in bilateral lower lobes. There was diminished diaphragmatic excursion and abdominal paradox was noted. The remainder of the physical exam was normal. Complete metabolic panel was normal. She had a leukocytosis of 28.6 ∗ 109/L and anemia with hemoglobin and hematocrit of 11.6 g/dL and 35.8%, respectively. Further work-up to support a diagnosis of HIL included ANA, ssDNA, and dsDNA, all of which were negative. ANCA and ACE were also normal. Anti-histone antibodies were elevated at 2.8 units (>1.5 is positive) and her N-acetyltransferase 2 (NAT2) genotype was found to be “intermediate acetylator.”
After a thorough review of the medical history, it was apparent that the onset of symptoms began four weeks after the initiation of hydralazine for hypertension that developed a few weeks postpartum. On day 2 of admission, a presumptive diagnosis of hydralazine-induced lupus (HIL) with pneumonitis was made. Hydralazine was discontinued and pyridoxine 25 mg PO once daily was started for paresthesias. Prednisone 60 mg PO once daily was started due to pulmonary involvement with plans for a prolonged taper. The patient experienced symptomatic improvement within three days of hydralazine discontinuation experiencing improvement in arthralgias and paresthesias and shortness of breath.
After discharge, the patient presented to her outpatient family medicine clinic for follow-up. She reported that her breathing was 80% improved and that she was ambulating without oxygen. She had a repeat chest CT which showed complete resolution of the previous bilateral basilar consolidations ().


A 15-year-old male patient was admitted to our clinic with a complaint of scrotal pain persisting for an hour. Physical examination revealed tenderness and painful right spermatic cord, epididymis, and testicle. There was no sign of scrotal erythema or swelling. The right testicle was located slightly above the oblique position. Laboratory examinations including liver, kidney, and urine analysis were all normal. On ultrasonographic evaluation, there was a heterogeneity and slight increase in the size of the right testicle. Although there was a normal parenchymal blood flow in the left testicle, color Doppler imaging revealed the absence of blood flow in the parenchyma of the right testicle. The patient immediately underwent axial T2-weighted and diffusion-weighted MRI. Magnetic resonance imaging examinations of the patient were performed with a 1.5 T MRI system. A multislice axial plane with a single shot, echo planar spin echo sequence (b: 50 sec/mm2, 400 sec/mm2, and 800 sec/mm2 and ADC) technique was performed for the DWI. Twisted right spermatic cord was observed on axial T2-weighted images (). The right testicle had significantly increased signal intensity on DWI and low apparent diffusion coefficient (ADC) values compared to the left testicle (Figures and ). The patient was diagnosed with testicular torsion based on clinical and radiological findings. Approximately 540 degrees of external manual detorsion was applied to the right testicle, which resulted in immediate relief of the patient's pain. After preoperative external detorsion, symmetrical parenchymal blood flow in the right testicle compared to the left testicle was observed on color Doppler imaging. MRI scan was repeated approximately half an hour later after the preoperative external detorsion and recovery of the twisted right spermatic cord was observed. The pathological signal changes in the right testicle on DWI and ADC maps detected before preoperative external detorsion disappeared and the signal intensities of the left and right testicles were almost equal (Figures and ). The patient underwent transscrotal orchidopexy procedures the following day. The intraoperative findings demonstrated no twisted spermatic cord but revealed vascular congestion in the testicle and spermatic cord, which confirmed the diagnosis of prior torsion. The testicle was preserved and found to be viable. The testicle was attached to the scrotum using the appropriate method.


A 4-year-old girl with a large sellar and suprasellar tumour developed chronic euvolemic hyponatremia due to SIADH. The diagnosis was established after brain MRI and CT scan were performed for neuro-psychomotor development delay, visual loss and hyponatremia. The neurosurgical biopsy revealed a low grade ganglioglioma, so neither chemotherapy nor radiotherapy were proposed. Once the diagnosis was made, regular endocrinological and oncological follow-up was established.
At diagnosis, the patient had asymptomatic hyponatremia (serum sodium ranging from 127 to 131 mmol/L), central precocious puberty, for which a treatment with LHRH-analogue was begun, and severe hypothalamic obesity.
At age 8 years, she had a grand mal seizure episode. Serum sodium level at admission to the Emergency Department was 122 mmol/L. Brain MRI and CT scan did not show any increase of the tumour mass size. Electroencephalogram showed non-specific metabolic wave alterations, thus the pathogenesis of the grand mal seizure was attributed to hyponatremia. Pituitary-thyroid and pituitary-adrenal axis functionality was normal. SIADH was confirmed by clinical and laboratory findings (body weight stable at 35 kg, arterial blood pressure 115/80 mmHg, urinary output 1300 mL/24 h, plasma sodium 133 mmol/L (reference range 135-145), plasma osmolality 265 mOsm/kg, urea 30 mg/dL (reference range 20-80), creatinine 0.30 mg/dL (reference range 0.25-0.85), copeptin 16.6 pmol/L (reference range 3-8), urine sodium 144 mmol/L, urine osmolality 502 mOsm/kg).
The acute episode was treated with intravenous phenobarbital and hypertonic saline solution and with orally administered levetiracetam at discharge. As chronic hyponatremia became symptomatic over time, tolvaptan was started in a dose of 3.75 mg/day (0.1 mg/kg/day, weight 35 kg), then increased to 7.5 mg ().
No other seizure episode was observed and levetiracetam withdrawal was decided after 8 months. Actually, after 3 years of treatment, serum sodium levels are nearly normal ranging from 133 to 137 mmol/L and the tolvaptan dosage is 11.25 mg/day (0.32 mg/kg/day). No severe hyponatremia has been registered despite the increase in the size of the tumour mass and central adrenal insufficiency onset.


This 5-year-old boy developed chronic euvolemic hyponatremia due to SIADH after neurosurgical partial removal of a hypothalamic-chiasmatic astrocytoma. Post-surgical chemotherapy regimen treatment was started and an endocrinological follow-up was established to evaluate hypothalamic-pituitary axis functionality. At this time, he had asymptomatic hyponatremia with serum sodium levels ranging from 123 mmol/L to 130 mmol/L. As he developed central hypothyroidism and secondary adrenal insufficiency, a substitutive treatment for these conditions was started. He also developed central precocious puberty for which a LHRH-analogue treatment was started. At age 8 years, after the beginning of a second chemotherapy regimen treatment due to tumour size increase, hyponatremia became symptomatic with headache, nausea, asthenia, and seizures which persisted after chemotherapy withdrawal. Corticosteroid dosage increase (oral cortone acetate 40-50 mg/m2/day), mineralocorticoid treatment (oral fludrocortisone, 0.1 mg/day), and salt supplement (oral NaCl 3 g/day) were not sufficient to maintain serum sodium at acceptable levels, thus we started low-dose tolvaptan treatment (3.75 mg/day, 0.05 mg/kg/day, weight 83 kg) with prompt normalization of serum sodium (136-141 mmol/L) as shown in .
After 3 months, the tolvaptan dosage has been increased to 7.5 mg (0.09 mg/kg/day), the corticosteroid dosage was reduced to a substitutive range (10-15 mg/m2/day), the mineralocorticoid treatment and the supplemented salt were discontinued, with serum sodium levels remaining stable at 135-144 mmol/L.


A 45-year-old female complained of gross diminution of vision in the left eye (LE) on awakening 20 days before. She had a similar history of sudden onset painless diminution of vision in the right eye (RE) two months before. She had diabetes, hypertension, and anemia with chronic kidney disease. She was on hemodialysis bi-weekly for the last 3 years. She gave a history of dialysis a day prior to both of the episodes of acute visual loss. She had no history of headache, pain on extra-ocular movements, limb-weakness, transient ischemic attacks, fever, myalgia, jaw claudication, seizures or focal neurological deficit.
On examination, best-corrected visual acuity (BCVA) was 6/60 in RE and hand movements close to face (HMCF) with accurate projection of rays in LE. Intraocular pressure was 14 and 15 mm of Hg in RE and LE, respectively. LE had grade 1 relative afferent pupillary defect (RAPD). Anterior segment examination of both eyes (BE) was normal. Fundus examination in RE showed optic disc pallor with obliteration of cup and sheathing of vessels around the disc suggesting secondary optic atrophy (Figure 1A ) with arteriolar attenuation and arterio-venous (A-V) crossing changes. Fundus examination of LE showed pallid disc edema with flame-shaped retinal haemorrhages in the peri-papillary region, attenuation of the retinal arterioles, and arterio-venous crossing changes without any background diabetic retinopathy (Figure 1B ).
Humphery’s visual field testing in RE showed severely depressed field. Field examination in LE was not possible due to profound visual loss. Fundus fluorescein angiography (FFA) of LE showed delayed filling of the disc especially superior part in the early phase and staining of disc in the late phase (Figure 2 ).
Her blood pressure was 110/80 mmHg. Ambulatory blood pressure monitoring showed a drop in nocturnal blood pressure with diastolic reading dipping to 55 mmHg. There was no evidence of any neurological deficit. Her haemoglobin level was 9.5 g/dl. Her blood urea was 78 mg/dl and serum creatinine was 6.2 mg/dl. Serum electrolytes and other routine biochemical tests were within the normal range. Contrast enhanced computer tomography of the head revealed normal study.
Based on the above findings, she was diagnosed as having secondary optic atrophy following NA-AION in RE and fresh NA-AION in LE. She was started on oral steroid 80 mg/day with close monitoring of blood sugar levels and blood pressure. Steroids were tapered over 8 weeks. Despite these measures, there was no improvement of vision in LE. At last follow-up at 6 months, best corrected visual acuity was 6/60 in RE and HMCF in LE with BE showing secondary optic atrophy.


A 74-year-old woman was referred to our hospital and admitted for progressive speech and language difficulties. The patient was unable to recall the names of things or persons and was unable to communicate with others for about 1 year prior to admission, though she was able to shop and do housework without difficulty. She had no significant medical history; however, regarding her family history, her elder brother had developed word-finding difficulty with verbal paraphasia and right-hand limb-kinetic apraxia at the age of 62 years of age, and was diagnosed with CBS at 69 years of age. He had frontal lobe signs such as forced grasping, total aphasia, and right-limb kinetic apraxia; moreover, brain magnetic resonance imaging (MRI) demonstrated frontal and temporal lobar atrophy dominantly affecting the left side (Fig. ). The patient’s brother and parents had passed away; therefore, we could not obtain their detailed clinical information.
Neurological findings indicated that our patient was lucid, but showed thought laziness. The cranial nerves, including those related to eye movement, were normal. The patient had normal muscle tonus and did not show muscle weakness or involuntary movement, but all extremity tendon reflexes were slightly increased. There was no evidence of sensory impairment or cerebellar ataxia. It was noted that speech required significant effort, was slow and non-fluent, and showed anarthria and aphasia. The patient’s Mini-Mental Scale Examination score was 4/30.
Language function was assessed using the Western Aphasia Battery (WAB) Japanese edition once and SLTA (standard language test of aphasia) two times within 2 months. The scores of WAB subtests were as follows: spontaneous speech, 13 points; auditory verbal comprehension, 5.5 points; repetition, 0 points; naming, 0 points; reading, 4.3 points; writing, 2.2 points; praxis, 6.8 points; and construction, drawing, block design & calculation, 6.6 points. Raven’s score was 25/37 (average ± standard deviation: 26.9 ± 5.4). Aphasia quotient was 36.8. The results of SLTA were similar to those of WAB. Naming, writing, and repetition were impaired. However, auditory verbal comprehension and reading concerning words and short sentences were relatively preserved. Spatial perception and visual perception were also normal. Verbal comprehension via visual perception was approximately normal. Therefore, it is likely that auditory verbal comprehension was complemented by visual perception. Constructional dysfunction, limb-kinetic apraxia, ideational apraxia, and motor apraxia were not observed. Laboratory blood examinations did not reveal any particular abnormalities that could have caused cognitive dysfunction. Cell counts and protein concentrations in the patient’s cerebrospinal fluid were within normal ranges, and concentrations of tau protein (282 pg/mL) and phosphorylated tau protein (31.3 pg/mL or lower) were also normal. Brain MRI demonstrated cerebral atrophy dominantly affecting the left frontotemporal lobes (Fig. ).
Clinically, the main patient symptoms were difficulty in verbal expression and non-fluent aphasia in the absence of visual memory impairment or behavioral abnormalities. On this premise, the patient was diagnosed with PPA according to Mesulam’s criteria []. Furthermore, the aphasia was classified as non-fluent progressive aphasia because, while speech itself required effort, the patient retained knowledge about objects and the ability to understand words. Brain MRI demonstrated cerebral cortical atrophy dominantly affecting the left frontal and temporal lobes, consistent with previous reports of non-fluent aphasia [, ]. Thus, FTLD was diagnosed according to the patient’s clinical symptoms. Since the patient’s elder brother had been diagnosed with CBS, and similar familial cases of FTLD due to GRN and microtubule-associated protein tau gene (MAPT) mutations had been reported [], we performed genetic analyses on the patient.
Genomic deoxyribonucleic acid (DNA) was extracted from peripheral leukocytes isolated from the patient. The exon/intron boundary of GRN was amplified by polymerase chain reaction (PCR) according to a previously reported method [] and the PCR products were sequenced in both directions. Briefly, blood was collected into a PAXgene® RNA tube, total ribonucleic acid (RNA) was extracted from the sample, and cDNA was prepared from total RNA by a reverse transcriptase reaction. cDNA was then amplified by reverse transcriptase–polymerase chain reaction (RT-PCR) (forward primer: 5′-ACCCAGGCTGTGTGCTG-3′; reverse primer: 5′-GACAGCCTCTGGGATTGGAC-3′) and the gene expression of GRN was analyzed. Then, the amplified PCR product was extracted and its sequence was analyzed.
The genetic examination identified a novel mutation (c.1118_1119delCCinsG) in exon10 of GRN, which was thought to cause a frameshift mutation (p.Pro373ArgX38). No pathological mutations of MAPT were identified. The GRN mRNA sequence was analyzed by RT-PCR; however, a mutant allele product was not detected, suggesting degradation of the mutant allele by the nonsense-mediated RNA decay system. Accordingly, haploinsufficiency due to reduced expression of progranulin was considered to be a possible pathogenic mechanism of FTLD in these cases (Fig. ).


A healthy right hand dominant 26-year-old male presented to the emergency department after sustaining a direct blow to his left wrist with a hockey stick while playing Lacrosse. His wrist was swollen, deformed, and positioned in supination. A complete neurological exam of his left upper extremity revealed decrease sensation over the first three digits. The vascular exam was normal with a good palpable radial pulse.
Initial radiographs demonstrated a distal radius fracture associated with a severe DRUJ volar dislocation. The ulna was positioned anterior to the radius with a complete overlap of the ulna over the radius (). Despite a trial of closed reduction and immobilization performed in the emergency department under conscious sedation, the DRUJ failed to reduce. A computed tomography was then performed for preoperative planning which confirmed the significant volar dislocation of the ulna (). Informed consent was obtained from the patient to publish this case report.