A 28-year-old white woman presented to our emergency department with dyspnea, edema of the lower limbs, and weight gain of 11 kg in the last 2 weeks. Her respiratory frequency was 20 breaths/minute, her heart rate was 82 beats/minute, her blood pressure was 98/65 mmHg, and her oxygen saturation was 100% on room air. Her body temperature was 36.7 °C.
The patient was alert and cooperative; in no acute distress; and orientated to person, place, and time. An examination of her lungs revealed clear auscultation and percussion without rales, wheezing, or diminished breath sounds. A cardiac examination revealed normal S1 and S2 and no S3, S4, or murmurs; the rhythm was regular. She had no cyanosis or pallor. Her extremities were warm and well perfused with distinctive edema of the lower limbs. Her strength and sensation were symmetric and intact throughout. Her abdomen had positive bowel sounds and was soft, nondistended, and nontender.
The patient’s white blood cell count was 9600/μl, and her C-reactive protein level was 0.3 mg/dl. Her serum creatinine was within the normal range (0.9 mg/dl). On further evaluation, her serum albumin was decreased to 8.4 g/L, and urinalysis revealed proteinuria of 16 g/g creatinine.
The patient was not taking any medication at the time of presentation. She was a housewife and had one son.
For further evaluation, echocardiography was performed, revealing a 3×3-cm mass in the right ventricle, which was suspected to be a myxoma (Fig. ). Therefore, cardiac surgeons extracted the mass on the same day by using a minimally invasive technique. Histological examination yielded a relatively fresh thrombus and no signs of atypical cells or malignancy. Deep vein thrombosis of the legs could be excluded by color Doppler sonography. The patient had no clinical or echocardiographic signs of pulmonary embolism.
After discussing the urine findings with the patient, she reported an episode of proteinuria at the age of 7 years and again at 13 years, both of which were treated with steroids and chlorambucil. A kidney biopsy was not performed in childhood.
Because we suspected a very late recurrence of minimal change glomerulonephritis, and owing to the patient’s concomitant anticoagulation therapy, which was started after the surgery because of nephrotic syndrome, a kidney biopsy was again not performed. Treatment with oral steroids (1 mg/kg body weight) was immediately initiated. The patient’s proteinuria disappeared within 4 weeks, her weight went back to normal, and her serum albumin level 6 weeks later was also normal (35.9 g/L).


A male patient, aged 32 years, sought psychiatric care for psychotic symptoms. At that time he worked as a doorman and misinterpreted the intentions of a resident of the building, imagining that she was in love with him. He approached the resident in her apartment and she was startled, verbally assaulting him. The effects of this encounter began to manifest in total insomnia. In a few days he presented symptoms of acute confusion, with behavioral disorganization (throwing himself on the floor and standing around doors for no apparent reason), psychomotor agitation, time disorientation, disturbances in recent memory, irritability, hostility, loose association of ideas, and delusions (e.g., that the army was after him for not having enlisted at the proper age). These symptoms remitted after 3 months of clozapine therapy 200 mg/day (olanzapine and aripiprazole having had no effect). The patient is currently not on antipsychotic medication.
The patient's clinical history has been marked by poor social performance. He has often been mistaken about the intentions of girls at the psychosocial center he usually attends, which has become his only social activity. He reports occasional derogatory auditory hallucinations and hyperesthesia in the scalp. When he develops insomnia or more frequent hallucinations, he takes clozapine (200 mg/day).
He was born, without complications, by cesarean section. He first spoke at the age of three and has always been withdrawn socially. In childhood he had untreated attention deficit symptoms and failed three years of elementary school. At the age of 10, he began experiencing bilateral hand tremors and difficulties with fine motor coordination, for which he began physiotherapy and consulted a neurologist. His mother has always characterized him as clumsy. At age 18, he began having delusions, auditory hallucinations, increasing social isolation, and behavioral disorganization, for which he was hospitalized. At age 28, he was diagnosed with a psychotic depressive episode (with derogatory auditory hallucinations). His symptoms improved with use of risperidone, and for the next 4 years he remained asymptomatic without medication.
In physical examination at age 32, he presented bilateral positional and intention hand tremors, which were worse on the left side, hypertelorism, broad forehead and high hair implantation (), pectus carinatum (), scalp changes compatible with cutis verticis gyrata (), and a slight imbalance in tandem gait.
We did not apply psychological tests for the diagnosis of autism; however, we used the diagnostic criteria of DSM-5 299.00 with level of severity one and intellectual disability. MRI revealed anteriorization and enlargement of the anterior-posterior diameter of the frontal sinus, reduction of the maxillary antrum (with hypopneumatization), scalp anomaly compatible with cutis verticis gyrata, probable small cyst of the pineal gland, subtle proptosis of the eyes, prominent cerebrospinal fluid spaces along the optic nerve sheaths, reductions in brain parenchyma incompatible with age (prominent in the posterior parietal regions), and FLAIR hyperintensities of white matter in the occipital horns, atria, posterior horns of the lateral ventricles, part of the corona radiata, and semioval centers, as well as in deep white matter of the superior, middle, and inferior frontal gyrus, the postcentral gyrus, and the upper and lower parietal lobes (). These changes in white matter presented no restrictions on diffusion or increased signal intensity with contrast enhancement, which raised the possibility of metabolic changes after discussion with the radiologist. Following this line of reasoning, we ordered adult tests for metabolic errors, beginning with those that could account for this image pattern, the physical examination, and the psychiatric history.
Due to the lesions with demyelinating characteristics, recurrent stress-triggered psychotic syndrome, pectus carinatum, and hypopneumatization of the sinus, the possibility of alpha-mannosidosis and Krabbe's disease was suggested. These hypotheses were excluded by the enzymatic assays. Due to the physical characteristics, psychiatric history, and cutis verticis gyrata, the possibility of a syndromic genetic disease was suggested.
The karyotype was normal. Comparative genomic hybridization by oligonucleotide arrangement (microarray) showed a deletion of approximately 151 kb in the long arm of chromosome 7, which involved band 7q31-32 (). This deletion is intragenic in the CADPS2 gene, involving exons 3 through 9. Mutation searches performed in the patient's mother and sister were negative by the same method. Since the father is deceased, it could not be determined whether the patient had a de novo mutation.


A 52-year-old Japanese woman was diagnosed as having advanced BC with a sensitive estrogen receptor and without human epidermal growth factor receptor 2. This diagnosis took place about 3 years prior to the admission described in the present report. She received four courses of combination therapy with epirubicin, cyclophosphamide, and fluorouracil (ECF) for 6 months, and then eight courses of docetaxel (DTX) for 10 months. After these two regimens, a malignant pleural effusion developed; therefore, the disease was considered progressive. After DTX treatment, the patient received two estrogen receptor inhibitors, tamoxifen for 6 months, fulvestrant for 4 months, and an aromatase inhibitor (letrozole) for 11 months. Despite this, the patient’s BC metastasized to the liver; the attending physician therefore considered the disease progressive and began treatment with eribulin. Five days after she began her second treatment with eribulin, she was admitted to our hospital for dyspnea.
Upon admission, her initial vital signs included a body temperature of 37.5 °C and an oxygen saturation of 88% in room air. A physical examination revealed fine crackles in both lower lung fields. Her laboratory test results were as follows: white blood cells—1200 cells/µL (neutrophils—600 cells/µL); serum lactate dehydrogenase (LDH)—749 IU/L (normal: 119–229 IU/L); serum sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) level—3782 U/mL (normal: < 500 U/mL); serum surfactant protein-D (SP-D)—158 ng/mL (normal: < 110 ng/mL); serum C-reactive protein (CRP)—3.9 mg/dL (normal: < 0.3 mg/dL); and plasma (1-3)-beta-d-glucan—12 pg/mL (normal: < 20 pg/mL). The patient was negative for serum antibodies associated with connective tissue diseases. Furthermore, her sputum, urine, and blood cultures yielded no microbial growth, and she was negative for a rapid flu test, cytomegalovirus antigen, Mycoplasma antigen in the pharynx, and Streptococcus pneumoniae and Legionella antigen in the urine.
A chest radiograph (Fig. b) showed consolidation in the right lower lung field, and a chest high-resolution computed tomography (HRCT) scan showed consolidation with air bronchograms along the bronchovascular bundles in both lower lobes (Fig. b). Prior to the admission described in the present study, the patient had no pre-existing interstitial shadow on her chest radiograph (Fig. a) and HRCT (Fig. a). Moreover, she showed no evidence of heart or renal failure; that is, her brain natriuretic peptide and creatinine levels were within the normal range.
A year before the admission described in the present report, the patient was prescribed brotizolam, tramadol, loxoprofen, and famotidine to treat insomnia, chronic gastritis, and carcinomatous pain. Upon admission, we treated her with the antibiotic cefepime for 5 days, as well as with carbocysteine and dextromethorphan hydrobromide hydrate for sputum and cough. However, her respiratory symptoms and radiological findings were not improved by this treatment. Five days after her admission, we performed a bronchoalveolar lavage (BAL) in the right B4 bronchus. The total cell count, lymphocyte, neutrophil, eosinophil, and macrophage percentages, and CD4/CD8 ratio values in the BAL fluid (BALF) were 10.8 × 105 cells/mL (normal range: 0.7–2.0 × 105 cells/mL), 13, 2, 0, 85%, and 0.63 (normal range: 1.5–3.2), respectively. The polymerase chain reaction (PCR) assay of the BALF for Pneumocystis jirovecii was negative.
Based on these findings, including the clinical course and chest HRCT, we concluded that the patient had developed IP, specifically organized pneumonia (OP), and we therefore initiated treatment with prednisolone (1 mg/kg/day), gradually decreasing the dosage every 2 weeks. The patient’s respiratory condition and chest radiograph findings (Fig. c) had improved after 2 weeks of prednisolone treatment.


In April 2015 a 45 years old male who had undergone a metallic prosthetic valve replacement 10 years ago presented to a medical unit at Teaching Hospital, Kandy, Sri Lanka with fever for 5 days duration. There was no history of intravenous drug abuse. He had a diastolic murmur at the apex with muffled metallic sound of prosthetic valves and examination of the optic fundi revealed a Roth’s spot in the right eye. Investigations showed a leukocyte count of 10,000/µl with thrombocytopenia (platelet count of 117,000/µl) and elevated C reactive protein (CRP). Urine analysis showed red cells with red cell casts and urine culture was negative. Blood cultures yielded Staphylococci which were resistant to methicillin and sensitive to vancomycin with an MIC of 0.25 µg/ml. Transthoracic echocardiogram showed two mobile vegetations (10.3 × 3.7 mm and 12.4 × 1.3 mm in size) attached to prosthetic mitral valve and further a transoesophageal echocardiogram confirmed these findings. He was started on intravenous vancomycin, gentamicin and oral rifampicin.
Despite the intravenous antibiotics with adequate vancomycin trough serum levels he remained bacteremic with continuing fever and persistent isolation of MRSA in blood cultures, and high levels of CRP. On the fifth day of admission, patient complained of severe headache and computed tomography (CT) scan of head revealed a subarachnoid haemorrhage and a intracranial haemorrhage possibly following rupture of mycotic aneurysms (Fig. ). At that moment patient was considered for surgical treatment as he had persistent bacteraemia along with multiple embolic events. However, considering the suggestions of the multi-disciplinary team (microbiologist, neurosurgeon and cardiothoracic surgeon) the decision was made to continue the total course of antibiotics while planning for an early surgery since there was no urgent or emergency indication for a surgery. A second surgery at this point would have been more difficult and operating on an infected field carries a high risk of postoperative complications. Moreover since the patient was having intracranial haemorrhage he was at a significant risk of mortality and adverse outcome during as well as after an early surgery. In addition to the previous antibiotics he was started on oral co-trimoxazole as well. On day 15 of hospitalization there was a failure in settling the fever and resolution of bacteremia.
Fifteen days after admission, his antibiotic regimen was modified with linezolid/cipro initiation while all other antibiotics were stopped since there was no response to the treatment. He was started on intravenous linezolid 600 mg 8 hourly. Intravenous ciprofloxacin was also added to linezolid. Subsequently the patient developed frequent ventricular ectopics and Holter study revealed a heavy burden of ventricular ectopics including short runs of nonsustained ventricular tachycardia. With the opinion of the consultant electrophysiologist, he was loaded with intravenous amiodarone for which there was a reduction in the ectopic burden and he was then maintained on oral amiodarone. By this time a gradual reduction of the height of the fever spikes was noticed indicating a response to the new course of antibiotics, and after 7 days of linezolid treatment the temperature became normal and CRP level improved. Blood culture became negative on day 9 of linezolid treatment. He was continued on intravenous linezolid and ciprofloxacin for a total of 4 weeks and then converted to oral linezolid and ciprofloxacin to complete the total duration of antibiotics of 6 weeks. The patient didn’t develop any significant adverse drug reaction to the treatment. The follow up transthoracic echocardiogram revealed no vegetations and to-date the patient is being regularly followed up at our clinic with no further complications.


A 28-year-old white male with a history of CF (homozygous for the F508del mutation), CF-related diabetes (CFRD), and pancreatic insufficiency presented for evaluation of low bone density. Dual energy X-ray absorptiometry (DXA) scan showed low bone density with a significant decline in BMD compared to a previous scan obtained four years prior, as follows:Femoral neck: Z-score −2.6, decline in BMD by 13.3% over the preceding four years Total hip: Z-score −2.3, decline in BMD by 11.2% PA spine: Z-score −1.8, decline in BMD by 11.1%
The patient reported no significant oral or inhaled glucocorticoid use, delayed puberty, tobacco or alcohol use, or other risk factors for low bone density. He was compliant with pancreatic enzymes. He endorsed excellent dietary calcium intake, and his 25-hydroxyvitamin D (25[OH]D) level was at goal 57 ng/mL on cholecalciferol 3000 IU daily. His BMI at the time of evaluation was 22.1 kg/m2, which had improved after starting insulin for treatment of CFRD several months before. He reported a possible rib fracture occurring earlier in the year, though this was not confirmed on X-ray. Pertinent family history included an aunt with celiac disease.
Laboratory evaluation showed normal parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase, renal function, and morning testosterone level. Screening tests for celiac disease showed a total immunoglobulin A (IgA) of 375 ng/dL (reference range 69–309 mg/dL) and an elevated anti-tissue transglutaminase (TTG) IgA level of 195.09 U/mL (reference range 0–15 U/mL). He was also found to have significant iron deficiency with a low ferritin level of 6 ug/L (reference range 20–300 ug/L) and a low transferrin saturation of 5%. He underwent endoscopy with duodenal biopsies, and pathology revealed villous blunting with intraepithelial lymphocytosis consistent with celiac disease. A gluten-free diet was recommended for treatment. Follow-up DXA scans after initiation of treatment are not yet available given that the diagnosis of celiac disease was made within the past year.


A 28-year-old white male with a history of CF (homozygous for the F508del mutation), pancreatic insufficiency, and progressive pulmonary decline over the preceding 6 months presented for evaluation of bone health prior to lung transplantation. Pretransplant screening DXA scan showed low bone mineral density (BMD) with femoral neck Z-score −2.6, total hip Z-score −2.3, and PA spine Z-score −2.2. As with the first case, the patient reported no prior significant oral or inhaled glucocorticoid use, delayed puberty, or significant tobacco or alcohol use. He endorsed reduced physical activity over the year prior to his evaluation related to his advanced lung disease. He had never suffered any fractures. He reported robust dairy intake every day, but he had persistent vitamin D deficiency (25[OH]D level 26 ng/mL) despite being compliant with ergocalciferol 50,000 IU twice weekly. His BMI was low at 18.8 kg/m2, and he reported longstanding difficulty with weight gain despite taking pancreatic enzymes with all meals and snacks. He denied any family history of celiac disease or other autoimmune or gastrointestinal disorders.
Laboratory evaluation showed normal PTH, calcium, phosphorus, alkaline phosphatase, renal function, and morning testosterone level. Total IgA was 729 mg/dL and TTG IgA level was elevated at 82.60 U/mL. The patient was evaluated by gastroenterology but was deemed too ill to undergo confirmatory testing with endoscopy and duodenal biopsy. He was empirically started on a gluten-free diet. Shortly thereafter, he underwent lung transplantation and was treated with intravenous zoledronic acid to prevent bone loss and fractures in the posttransplant period.


A 51-year-old woman presented to our clinic with signs and symptoms of hyperthyroidism. Asymmetric hypertrophy of the thyroid gland at the right side was determined by inspection. A larger nodule with regular margins was palpated in the right lobe by physical examination. Suppressed serum thyroid-stimulating hormone (TSH = 0.03 µIU/mL) and high free thyroxin (FT4 = 2.42 ng/dL) levels were determined by biochemical analysis. Ultrasound of the thyroid gland revealed the absence of the left lobe and a 33 × 25 mm hypoechoic solid nodule with a cystic component in the right lobe. Thyroid nuclear scan with Tc-99 m pertechnetate showed that the left lobe was not visualized (agenesis) and further revealed a larger, hot, autonomous, hyperactive solitary nodule in the right lobe (Figure ). Cervical magnetic resonance imaging (MRI) revealed the absence of the left lobe and isthmus of the thyroid gland, and a 26 x 23 mm solid nodule with a central cystic component. The solitary nodule was iso-hypointense in T1AG and heterogeneously hyperintense in T2AG. The diagnosis was toxic adenoma in the right lobe in this patient with TH (absence of the left lobe). The patient preoperatively received antithyroid medical treatment with thyromazol. Antithyroid drugs were used until the operation under the control of thyroid function tests. We totally excised the remaining right lobe, including the large, hyperactive solid nodule. Right superior and inferior parathyroid glands and also the recurrent laryngeal nerve (RLN) were identified at the usual anatomical position. They were fully exposed and preserved during thyroid surgery. Pre- and postoperative laryngoscopy showed normal vocal cords functions. Thyroid surgery was performed under the guidance of intraoperative nerve monitoring that wave amplitudes after pre- and post-dissection stimulation of the vagus nerve (V1: 654 µV and V2: 1249 µV) and RLN (R1: 1652 µV and R2: 1750 µV) showed functional integrity of laryngeal nerves. Postoperative period was uneventful. The patient was discharged on the second postoperative day. The pathological report showed that the size of the right lobe is 50 × 40 × 35 mm, which contained a solid nodule (30 × 25 × 25 mm). The histopathological diagnosis was follicular nodular disease. The patient is euthyroid with LT4 (150 µg/day) replacement.


Case 1 is a fetus of a 28-year-old woman, primigravida, who conceived naturally. The previous medical history of the woman was normal, and there was no family history of congenital anomalies. The mother did not have abnormal signs and symptoms, and she denied teratogenic exposure. The serologic test for TORCH infection diseases (including Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex virus) was negative. The sonographic screening at 13 weeks’ gestation revealed enlarged nuchal translucency thickness (NT), increased intracranial translucency (IT) diameter, absent nasal bone. Ventricular septal defect was suspected as well. Follow-up scannings were performed at 16 and 21 gestation weeks. Major anomalies, Dandy–Walker malformation (Fig. ), congenital heart defects [atrioventricular septal defect (Fig. ), double outlet right ventricle and mild pulmonary artery stenosis] were identified. Other sonographic markers and other minor anomalies were detected as well, including absent nasal bone, short femur and humerus length, arachnoid cyst, small stomach bubble, and irregular spinal alignment.
Noninvasive prenatal test showed a low risk of trisomy 13, 18, 21 and common sex chromosome aneuploidies. Subsequently amniocentesis was carried out to further identify chromosomal anomalies. Conventional G-band karyotype and fluorescence in situ hybridization (FISH) analysis revealed normal karyotypes. Then, chromosomal microarray analysis (CMA) using SNP-array (Affymetrix CytoScan 750K Array, Santa Clara, California) was performed, which finally demonstrated no copy number variations but loss of heterozygosity on long arm of chromosome 22 [ISCN: arr(hg19) 22q11.1q13.33(16,888,899–51,157,531)x2 hmz] (Fig. ).
Considering the major structural and genotype anomalies, the parents decided to terminate the pregnancy at 22 weeks’ gestation. This woman delivered a healthy child in the next year.


Case 2 is a fetus of a 27-year-old woman, primigravida, who conceived naturally. Her medical and family history was normal. Teratogenic exposure was denied. No complaint of specific symptoms by the mother during the pregnancy. The first-trimester sonographic screening at 13 weeks’ gestation revealed isolated enlarged NT. Further detailed sonographic examination was carry out at 17 and 21 weeks’ gestation, and no structural anomalies were found, while thickened nuchal fold and ascites (Fig. ) were detected. Then, ascites was reduced gradually, but polyhydramnios appeared in the follow-up scannings between 27 and 31 weeks’ gestation.
This fetus received amniocentesis for the purpose of reducing amniotic fluid volume, checking the ascites and performing prenatal diagnostic testing. Conventional G-band karyotype analysis revealed 46 normal chromosomes with a small supernumerary marker chromosome (sSMC) (Fig. ). The results of amniotic test for TORCH infection and fetal ascites culture and biochemical examination were negative. Considering no major karyotypic or structural anomalies were identified so far, the parents decided to carry on the pregnancy. The baby was born prematurely at 33 weeks’ gestation with a bell-shaped small thorax (Fig. ) and died within a day. CMA using SNP-array (Affymetrix CytoScan 750K Array) was then performed, no copy number variations were detected, but the long arm of chromosome 14 was detected by loss of heterozygosity [ISCN:arr[hg19]14q11.2q32.33(20,520,197–107,279,475)x2 hmz] (Fig. ).
Karyotype analysis of these 2 parents showed that they are normal individuals. Linkage analysis by polymerase chain reaction (PCR)-based Sequence-Tagged Site (STS) marker showed that the segmental isodisomy of both cases was of paternal origin.


A 66-year-old male, physician, was admitted to our institute with a left atrial tumor
suggesting a myxoma. He had a history of esophagectomy with retrosternal gastric
tube reconstruction for adenocarcinoma of gastroesophageal junction, twenty years
previously. He was asymptomatic, and the left atrial mass was incidentally
discovered by an echocardiogram study during a preoperative evaluation for an
ophthalmologic procedure. He had a normal physical examination, without heart murmur
or arrhythmia, as well as normal values of laboratory tests.
Preoperative transthoracic echocardiography showed normal ventricular and mitral
function and a heterogeneous mass in the left atrium attached to the interatrial
septum. A heart magnetic resonance imaging (MRI) was performed to establish the
anatomic relations among the heart, the gastric tube and the sternum (). The MRI demonstrated an intracardiac
lobular mass in the left atrium (2-3 cm in size) attached to the left atrial septum,
as well as the relationship between the intrathoracic structures. As it was an
unusual case, this imaging study was crucial in order to make the decision for the
best surgical approach, which was made after a heart surgery team discussion. The
right anterolateral thoracotomy was the approach of choice.
For surgical access, a right anterolateral thoracic incision was made and the
pectoralis major muscle was divided. After the pleural space opening through the
fourth intercostal space, it was possible to observe the gastric tube adjacent to
the posterior sternum portion, as well as many adherences between the lung and the
gastric tube (). Through cautious
bluntly dissection we have obtained a wide view of the lateral portion of the
pericardium (). About 20 mm anterior
to the right phrenic nerve, a longitudinal pericardium incision was made and it
allowed an adequate exposure of the heart and the great vessels ().
Moderate hypothermic (28ºC) cardiopulmonary bypass (CPB) was established with left
femoral artery cannulation and venous cannulas placed in the superior and inferior
vena cava. The aortic cross-clamping was performed in a standard manner. After the
administration of cardioplegic solution in the aortic root, a longitudinal left
atriotomy was performed with a good exposure of the tumor, which had a macroscopic
aspect of an intracardiac myxoma ().
It was possible to resect the entire tumor without any injury to the interatrial
septum (). The patient was easily
weaned from CPB and the incision was closed. The CPB and the arterial cross-clamp
times were 40 minutes and 26 minutes, respectively.
The patient had an uneventful postoperative course, with a length of stay in the
intensive care unit of 36 hours. The predischarge transthoracic echocardiography
demonstrated a normal biventricular function, with a complete resection of the tumor
and an intact interatrial septum. The patient was discharged to home on
postoperative day 5, and the histopathologic exam confirmed the diagnosis of myxoma.
After nineteen months of follow-up, medical surveillance shows no complication
().


A 74-year-old man was admitted to our hospital with symmetric hyperkeratotic skin changes for a 7-month duration. Clinical manifestation showed hyperkeratotic plaques, first affecting the oral mucosa, face, and fingers then extending to palms, soles, and trunk. Meanwhile, the patient also complained of heartburn and felt bloated after meals during the last 2 months. The patient had no other obvious medical history. He denied any history of similar diseases in his family. The patient was a common farmer around the countryside and often planted in farmland under the sun. He lived in the southeast of China. He was married and reported no drug abuse history. He drank alcohol occasionally and was a former smoker.
On physical examination, hyperkeratotic plaques were observed in the oral mucosa, face, fingers, palms, soles, and trunk (Fig. ). No lesions were detected in the wrinkles of the neck, armpits, groin, and other parts of the body. The other physical and neurological examinations were unremarkable. Serum carcinoembryonic antigen (CEA) was 100.30 μg/L (normal range 0 to 5), and carbohydrate antigen 199 (CA199) was 250.98 u/mL (normal range 0 to 40). Other laboratory findings were within normal range, and no other clinically significant findings were noted.
A biopsy of skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer, and some dermal papillae were projected upward in the form of finger-like projections (Fig. ). Furthermore, an esophagogastroduodenoscopy was performed. A histopathological examination of the gastric mucosa showed dilated branching tubules of varying diameter and presence of acinar structure. In addition, the malignant glands invaded fibrous stroma, and individual neoplastic cells were columnar or cuboidal, with the varying degree of nuclear atypia from middle to high grade (Fig. ). An endoscopic ultrasound was performed to determine the depth of invasion and lymph node metastasis, which led to the diagnosis of gastric cardia tubular adenocarcinoma and TNM classification (T4N2M0). The patient was detected with lymph node metastasis in the abdominal cavity by a computed tomography scan.
The diagnosis of MAN associated with gastric adenocarcinoma (T4N2M0) was given. Palliative surgery was recommended to relieve symptoms and improve life quality of the patient. Then the patient was transferred to the department of gastrointestinal surgery for tumor resection and lymphadenectomy. A subsequent slight improvement was seen in the skin condition. Unfortunately, the patient died of cancer cachexia 3 months later.


The 39-year-old male was treated for HCV genotype 1a between weeks 4 and 16 of incarceration (12 weeks of ledipasvir and sofosbuvir). Four weeks after the therapy was finished, the patient returned a negative polymerase chain reaction (PCR) result.
The patient describes a single episode of shared injecting with a known HCV-positive contact. The episode is described with some clarity, approximately 4–6 weeks after the negative PCR result. Bleach had been accessed, and a well-described method of flushing the injecting equipment with diluted bleach was used. The patient was receiving a stable dose of 95 mg methadone at the time.
He had been in custody for 7 months when the health service was notified that the HCV PCR result was positive. That result related to a test taken in week 30 of the period of incarceration. The genotype was reported as a mixed infection of genotype 3 and genotype 1 or 6—clearly distinct from the sample taken at pre-treatment. Given the significance of that result, the sample was retested and confirmed. Liver function tests and full blood count were normal.


A 32-year-old man was referred to the outpatient clinic of the Department of Endocrinology and Metabolism in Mugla Sitki Kocman University Training and Research Hospital with complains of excessive weight gain and muscle weakness. The patient gained 8 kgs in 12 months. He had a history of PV for 12 years. He used clobetasol propionate (CP) 0.05% ointment continuously at 150 mg/week for the past 12 years and stopped the steroid ointment treatment a month ago by himself. On physical examination, he had a moon face appearance with truncal obesity, buffalo hump, hirsutism, and purple striae in the axilla, periumbilical, and inguinal region (). Numerous erythematous, scaly psoriatic plaques were located on the shoulders, all extremities, dorsum of hands, and feet and at the intertriginous areas ().
Vital signs revealed an arterial blood pressure of 130/80 mmHg, pulse rate 75/min, height 172 cm, weight 85 kg, and body mass index 28.7 kg/cm2. On laboratory studies, liver and kidney function tests and fasting blood glucose were within normal limits. The following were found: morning adrenocorticotropic hormone (ACTH): 17 : 53 pg/ml (N: 7.2–63.3); morning basal cortisol: 3.83 mg/dL (N = 6.24–18.0). Other anterior hypophyseal hormones were as follows: thyroid stimulating hormone (TSH): 2.77 μ/ml (N: 0.27–4.2); fT4: 17.6 pmol/L (N: 12–22); fT3: 7.26 pmol/L (N: 3.1–6.8); prolactin: 7.34 ng/ml (N: 4.04–15.2); follicle stimulated hormone (FSH): 3.81 mIU/mL; luteinizing hormone (LH): 2.7 mIU/mL; total testosterone: 2.77 ng/mL (N: 2.9–8.36). 1 μg ACTH stimulation test was performed to evaluate hypophyseal-adrenal axis and there was insufficient response to the test (peak cortisol level 7.7 mg/dL). Clinical symptoms and laboratory findings of the patient suggested the diagnosis of ICS due to the prolonged use of a high-potent TS with subsequent ACTH deficiency. The patient had osteopenia on dual energy X-ray absorptiometry (DEXA) scan of the spine. The topical steroid was ceased, and methotrexate (10 mg/week) for psoriatic plaques and hydrocortisone acetate (20 mg/m2/d) were prescribed in order to prevent adrenal insufficiency. Calcium and vitamin D supplementation were given for osteopenia. Calcipotriene ointment and moisturizing lotion treatment were also started.


A 55-year-old woman was admitted to the Vascular Surgery Department of our hospital for ultrasonographic examination of suspected LMS in the left common femoral vein. Seven months previously, the patient had begun to experience edema and pain in the left leg, and underwent a rapid ultrasonographic evaluation in the emergency department of our hospital. Based on the ultrasonography, thrombus in the left common femoral vein and superficial femoral vein was diagnosed. The patient was administered anticoagulation therapy, with no improvement of the status of the lower limb. Before anticoagulation therapy, coagulation factors, fibrinogen level, and C-reactive protein (CRP) level were normal. During anticoagulation therapy, prothrombin time was 20.4 s (reference value, 9.6–12.8 s) and International Normalized Ratio was 1.8 s (reference value, 0.86–1.14 s), while other laboratory data, including fibrinogen level, thrombin time, activated partial thrombin time, and CRP level, were normal. She underwent a repeat ultrasonographic examination after 7 months, which confirmed that a tumor, rather than a blood clot, had involved the left external iliac vein, common femoral vein, deep femoral vein, and superficial femoral vein. Physical examination revealed a mass with a diameter of approximately 2 cm in the left inguinal region, which could not be pushed, mild cyanosis, and swelling of the left leg.
The first ultrasonographic examination (Philips IU22; Bothell, WA; probe L9-3, 3–9 MHz; venous condition) performed 7 months previously in the emergency department had revealed dilation of the common femoral vein (diameter, 18 mm), as well as a hypoechoic mass in the lumens of the left external iliac vein, common femoral vein, deep femoral vein, and superficial femoral vein. Color Doppler flow imaging revealed no color flow signal in the lumen of the common femoral vein. Thus, the patient was diagnosed as having DVT.
In the second examination, we used a multimodal ultrasonographic imaging approach (Philips IU22; probes C5-1, 1–5 MHz; L9-3, 3–9 MHz; L12-5, 5–12 MHz; superficial condition). High-resolution gray-scale images further revealed a dilation of the common femoral vein (diameter, 25 mm), as well as a hypoechoic mass in the lumens of the left external iliac vein, common femoral vein, deep femoral vein, and superficial femoral vein (Fig. A and B). Color Doppler flow imaging showed rich color spots and linear blood flow signals in the hypoechoic mass (Fig. C and D). Pulsed-wave Doppler imaging detected low- and high-resistance arterial flow, peak systolic velocity (PSV): 14.0 cm/s, end diastolic velocity (EDV): 7.02 cm/s, resistance index (RI): 0.50 (Fig. E) and PSV: 18.9 cm/s, EDV: 0 cm/s, RI: 1.00 (Fig. F), respectively. CEUS revealed rapid, heterogeneous, high levels of enhancement in the arterial phase (Fig. A and B) and the low levels of enhancement in the venous phase (Fig. C), after injection of 2.4 mL of the contrast agent, SonoVue (Bracco, Milan, Italy). These findings confirmed that the initially diagnosed blood clot was actually a tumor in the vein.
After the second ultrasonographic examination, the patient underwent contrast-enhanced CT (CECT) for confirmation, which revealed a partial enlargement of the left external iliac vein and common femoral vein due to a heterogeneous mass of soft tissue density filling their lumens. The mass showed an obvious heterogeneous enhancement in the arterial and venous phases (Fig. A and B).
During surgery, we found a mass extending from the left external iliac vein to the common femoral vein bifurcation, causing an obvious enlargement of the lumens of the involved veins (Fig. A). When the above veins were opened longitudinally, a fish flesh-like, solid substance was found in the lumens (Fig. B). The tumor originated from the deep femoral vein and involved the left external iliac vein, common femoral vein, deep femoral vein, and the upper section of the superficial femoral vein. The mass was not closely adhered to the venous wall of the left external iliac vein or common femoral vein nor to the upper section of the superficial femoral vein. Pathologic examination identified the mass as LMS rather than a blood clot (Fig. A and B). The tumor was removed successfully, and autologous saphenous vein replacement was performed.


A 30-year-old woman was admitted to our Internal Medicine Department because of a continuous remittent fever (up to 40°C) present for a month, profuse sweating, pelvic girdle arthralgia and myalgia, and sore throat with dry cough. The patient always lived in Trapani and did not travel recently. She had been in her usual health until a month before admission in Trapani Hospital, where laboratory tests showed neutrophilic leukocytosis, normochromic normocytic anemia, erythrocyte sedimentation rate (ESR) of 120 mm/h, C-reactive protein (CRP) of 193 mg/L; negative results for ANA, ANCA, anti-dsDNA antibodies, AMA and rheumatoid factor (RF) 0; CA 125 of 44 u/mL; absence of IgM anti-EBV and anti-CMV; and negative Widal and Wright test and of oval, vivax, falciparum plasmodium serodiagnosis. Whole-body computed tomography (CT) showed modest liver and spleen volume increase and para-aortic and common iliac artery lymphadenopathy (max 2 cm), while sternal bone marrow aspiration showed reactive hyperplasia. Esophagogastroduodenoscopy (EGDS) revealed an enlarged ampulla of Vater with mild plasmacytic infiltrate and rare lamina propria eosinophilic granulocytic infiltrate in histologic examination. The empirical antibiotic therapy with amoxicillin–clavulanate, ceftriaxone, levofloxacin, teicoplanin, and gentamicin was ineffective. Her medical history includes surgical treatment of left femoral hernia when she was 10 years.
On admission, blood pressure was 110/70 mmHg, heart rate 80 beats per minute, respiratory rate 16 breaths per minute, body temperature 38.5°C, and oxygen saturation 92%, while the patient was breathing ambient air. She was pale with nonpruritic, evanescent, macular, erythematous (salmon-pink) rash (Fig. ) alert and oriented, pharyngeal erythema. Cardiac examination revealed 2/6 ejection murmur on aortic area. Abdomen was treatable with the lower liver and spleen borders of the 2 cm below the costal margin. Severe pelvic girdle pain with stiffness, functional limitation, and myalgia was present as well – the overall level of disease activity on a visual analog scale (VAS) was 3.
The laboratory data were as follows: total leukocyte count, 19,000/mm3 (4000–10,000 mm3); differential leukocyte count: neutrophils, 88% (40–80), and lymphocytes, 14% (20–40); hemoglobin, 6 g/dL (women's normal range: 12–16); platelets, 740,000/mm3 (150,000–400,000/mm3); erythrocyte sedimentation rate (ESR), 106 mm/h (RR 0–43 mm/h); CRP, 214 mg/L (RR <5 mg/L); ferritin, 342 ng/mL (RR 8–252 ng/mL); serum iron, 2 mg/dL (RR 50–170 mg/dL); aspartate aminotransferase (AST), 43 U/L (RR 10–31 IU/L); alanine aminotransferase (ALT), 79 IU/L (RR 10–34 IU/L); alkaline phosphatase (ALP), 205 IU/L (RR 30–120 IU/L); g-glutamyl transferase (GGT), 277 IU/L (RR 3–38 IU/L); antinuclear antibodies (ANA), 1:80 (absence); anti-dsDNA antibodies and extractable nuclear antigen (ENA) antibodies negative; rheumatoid factor (RF), 12.5 IU/L (RR 0–25 IU/L); anticitrullinated protein antibodies (ACPAs), 0 U/mL (RR 0–6.9 U/mL); Quantiferon TB GOLD TEST: indeterminate (negative); and blood and urine cultures: negative. Additional laboratory markers are shown in Table .
ECG highlighted nonspecific anterolateral repolarization disorders. Echocardiogram (Fig. ) showed diffuse transmural hyperechoic aspect of myocardium and small circumferential pericardial detachment with hyperechoic aspect of the pericardium, more evident on right sections. Head, chest, abdomen and pelvis contrast-enhanced CT was similar to the previous.
The admission diagnosis to our department was fever of unknown origin ; nevertheless, clinical presentation, patient's age, and positivity of Yamaguchi's criteria led to a working diagnosis of adult-onset Still's disease , , . Specifically, she fulfilled the four major Yamaguchi's criteria – fever >39°C, ≥1 week; arthralgias >2 weeks; nonpruritic, evanescent, macular, erythematous (salmon-pink) rash; WBC > 10,000 (>80% granulocytes); and five of the five minor ones – sore throat, lymphadenomegaly, hepatosplenomegaly, abnormal liver functional tests, and negative rheumatoid factor/antinuclear antibodies (<1:100) .
Adult-onset Still's disease is an exclusion diagnosis among infectious, neoplastic, and rheumatic diseases ; the last two were excluded by CT, EGDS, tumor markers, and negative autoimmune pattern.
During the workup of FUO with severe anemia, assuming AOSD, in a patient living in a leishmaniasis endemic area, we performed revaluation of sternal bone marrow aspiration searching and detecting amastigotes (Figure ). Therefore, an anti-Leishmania antibody titer (indirect immunofluorescence assay method) was requested showing 1:160, while polymerase chain reaction (PCR) with specific primers confirmed the presence of Leishmania spp. .
Leishmania infantum, responsible for visceral disease in the Mediterranean region with a reservoir in the domestic dog, could be the causative agent of patient's disease. In fact, patient lived near a cemetery frequented by stray dogs. Therefore, the patient was treated with intravenous liposomal amphotericin B (3 mg/kg IV once daily), replaced by pentamidine isethionate (4 mg/kg IV every other day), dexamethasone (6 mg IV), and promethazine prophylaxis for angioedema and wheezing appearance. A promptly clinical improvement followed this latter treatment.
The following gradual corticosteroid anaphylactic prophylaxis reduction led to a relapse of remittent fever (peak 40°C), sweating, arthralgia, myalgia, evanescent, macular, erythematous (salmon-pink) rash, dry cough, and persistent elevation of inflammatory markers. This symptom relapse excludes reactive arthritis and led to an AOSD diagnosis, according to Yamaguchi's criteria . Therefore, prednisone (1 mg/kg PO) was associated, following the diagnosis of secondary AOSD. The patient was treated with twenty pentamidine isethionate doses and a month of steroid therapy with slow taper off. Peripheral blood anti-Leishmania antibodies and PCR and sternal bone marrow aspiration resulted negative at the end of specific therapy. Her overall condition and laboratory results significantly improved, ESR and CRP normalized (Table ), and myocardial hyperechogenicity and pericardial effusion reduced.
The final clinical and pathological diagnosis was as follows: adult-onset Still's disease caused by visceral leishmaniasis.
At one-year follow-up, the patient was in healthy condition.


A 21-year-old man with complex congenital heart disease was referred for catheter ablation after presenting to the emergency room with palpitations and dizziness. A regular narrow complex tachycardia at 176 bpm was terminated upon administration of intravenous adenosine. Over the preceding 2 years, he complained of rapid and regular palpitations of sudden onset that spontaneously resolved within 15 min. He was born with left atrial isomerism (including polysplenia), interruption of the inferior vena cava with azygous vein continuation, bilateral superior vena cavae, double-outlet right ventricle with a hypoplastic left ventricle, common atrium, complete unbalanced AV septal defect, and D-malposed great arteries. He underwent a staged Norwood surgical approach, culminating in a Kawashima-type Fontan. His surgeries included bilateral Glenn shunts (i.e., anastomoses of superior vena cavae to the pulmonary artery), Damus-Kaye-Stansel (i.e., anastomosis of the pulmonary artery stump to the aortic root), and a nonfenestrated intracardiac tunnel connecting a confluence of suprahepatic veins to the pulmonary artery. The global ejection fraction of his univentricular heart was 48% by cardiac magnetic resonance (CMR) imaging.
Under conscious sedation, an electrophysiological study was performed with three-dimensional electroanatomic mapping (CARTO 3, Biosense Webster, Johnson & Johnson, South Diamond Bar, CA) and CMR image integration. Considering the lack of venous access, only two catheters were used. A 6-French decapolar reference catheter (Livewire, St. Jude Medical/Abbott, Menlo Park, CA) was inserted through the right internal jugular vein into the intracardiac tunnel in order to record atrial far-field signals (Fig. ). Secondly, an 8-French radiofrequency ablation catheter (Navistar RMT Thermocool, Biosense Webster) was steered into the heart by remote magnetic guidance (Epoch Solution, Stereotaxis, St. Louis, MO) using a retrograde aortic approach (Fig. B).
Electrophysiological testing revealed the presence of two distinct AV nodes, that is, superior and inferior, each with decremental properties, discrete His-bundle electrograms, and separate patterns of ventricular activation (Fig. ). The governing rhythm spontaneously transitioned from one AV nodal pathway to the other. The superior AV conduction system was associated with an HV interval of 58 msec, an AV node effective refractory period of 350 msec at a drive train of 600 msec, and an antegrade Wenckebach cycle length of 370 msec. Corresponding values for the inferior AV conduction system were as follows: HV 40 msec, effective refractory period 430 msec, and Wenckebach cycle length 450 msec. A sling of conduction tissue, so-called Mönckeberg's sling, connected the two AV conduction systems, as schematically portrayed in Figure . Signals along the sling were characterized by high-frequency potentials that preceded local ventricular activation. Conduction across the superior AV node resulted in pre-excitation of the inferior AV nodal pathway (HV 21 msec) via Mönckeberg's sling. Conduction across the sling was bidirectional, with activation across the inferior AV node associated with pre-excitation of the superior AV conduction pathway (HV 24 msec).
Sustained antidromic and orthodromic twin AV nodal reentrant tachycardia was induced by atrial extrastimuli under an isoproterenol infusion. During each tachycardia, entrainment mapping at high output from superior and inferior AV nodal pathway sites confirmed that they were both components of the circuit. Electroanatomic mapping of the clinical tachycardia with image integration is shown in Figure A. The tachycardia coursed antegrade across the superior AV nodal pathway, down Mönckeberg's sling, and retrograde through the inferior AV node. The inferior AV node was targeted for irrigated radiofrequency ablation considering its less robust conduction properties. As shown in Figure B, ablation was performed in sinus rhythm with spontaneous conduction across the inferior AV nodal pathway. Successful elimination of the inferior AV node was marked by a transition of the QRS axis from superior to inferior as conduction shifted to the superior AV nodal pathway. During a 30-minute observation period on and off isoproterenol, no tachycardia was inducible and no inferior AV node conduction occurred spontaneously or could be provoked by adjacent atrial pacing. At 7 months of follow-up, the patient remains arrhythmia free with no evidence of inferior AV node conduction.


A 22-year-old woman presented to the Neurosurgery clinic in Nobel Teaching Hospital with a history of slow progressive but painless swelling over her left neck, ongoing for the last 6 months. She was also experiencing some difficulty while swallowing. She denied history of trauma, any episodes suggestive of transient ischemic attacks or paroxysmal episodes of severe headache, flushing or chest pain. She did not have major surgery or medical illnesses in the past, or any significant family history.
Local examination revealed a pulsatile swelling on her left neck. There was no audible bruit over the swelling. The patient then underwent a CT angiography, which revealed a well-defined large (> 8 cm) heterogeneous and hyperdense soft tissue lesion; showing intense arterial enhancement at the level of carotid bifurcation (
). It was causing significant compression and displacement of a long segment of the internal carotid artery (ICA) and external carotid artery (ECA), encasing a broad area of the ICA and ECA ( Shamblin Grade 3) (
). The lesion was getting vascular supply from both the ICA and ECA branches (
). These findings were all highly suggestive of a carotid body tumor.
Ultrasound imaging of the abdomen to assess adrenal glands was normal. 24-hour urine vanillylmandelic acid (VMA) and plasma metanephrines were within normal range.
The patient was thoroughly counseled regarding her condition and the need for operative management. The risks associated with the surgery, including intra-operative uncontrolled bleeding, lower cranial nerve palsy, ischemic stroke and even death, were detailed. Anaesthetic precautionary measures were implemented to reduce the risk of hypertensive crisis (during tumor manipulation) and hypotensive episodes (following tumor removal), by administering antihypertensive drugs and fluid support, respectively. After ensuring temporary carotid control with vascular loops, sub-adventitial dissection of the lesion was carried out starting from the common carotid caudally and then progressing cranially towards the bifurcation and its branches (
). The major vascular supplies were sequentially isolated, ligated and divided. A venous graft from the long saphenous vein was prepared for repair in case of inadvertent tears within the carotid or any of its branches. The internal jugular vein and the vagus nerve within the carotid sheath, and the hypoglossal nerve were all selectively isolated and well preserved. The lesion was completely excised and sent for histopathological analysis. There was only one instance of temporary bradycardia throughout the procedure. Patient made an uneventful recovery with no lower cranial nerve deficits or any vascular insults. The histology from the lesion revealed a characteristic Zellballen pattern, highly suggestive of a Paraganglioma (
). The patient has been for regular follow-ups in the last 4 months, with complete resolution of her previous symptoms. She has been advised for lifelong periodic visits.


Our patient is a 69-year-old Japanese man. At the age of 55 years, he underwent a medical assessment for occasional left abdominal pain. A left suprarenal mass was discovered by abdominal computed tomography (CT), and he was referred to our hospital. The tumor was 4 cm in size at that time, and no hormonal production had been detected (plasma renin activity (PRA), 0.5 ng/mL/h; plasma aldosterone concentration (PAC), 105 pg/mL; aldosterone/renin ratio (ARR), 210; the load test of furosemide in the standing position (PRA of 2.3 ng/mL/h, PAC of 236 pg/mL, ARR of 102.6); normal catecholamine and cortisol levels). Consequently, a diagnosis of a non-functional adrenal tumor was determined. The patient did not want to undergo surgery and was followed without surgical excision. The follow-up at our hospital continued for 5 years, and the tumor size (4.5 × 3.8 cm) did not appear to be increasing (the CT scan from the final visit is shown in Fig. ).
At the age of 65 years, he experienced an acute myocardial infarction and was taken to another hospital. Afterwards, he periodically visited the hospital for cardiac function assessments and hypertension treatment. At the age of 69 years, he was referred to our hospital because of a left suprarenal mass identified on abdominal CT (Fig. ) as part of a regular medical examination for ischemic heart disease and hypertension. He was admitted to our hospital for a detailed evaluation because the tumor had increased in size (5.8 × 5.2 cm). On admission, he was apparently in good health with no symptoms. He had been taking an antihypertensive drug (Amlodipine besylate 2.5 mg/day). A physical examination revealed no significant findings. His blood pressure was 136/76 mmHg. The laboratory data are shown in Table . The complete blood count and blood biochemistry tests were within normal ranges. The endocrinological data were within the normal range except for abnormal PRA and ARR values. The PAC was within the normal range (66 pg/mL), but PRA was reduced (0.2 ng/mL/h), resulting in an increased ARR (330).
To evaluate autonomous secretion of aldosterone and suppression of renin, load tests of captopril or furosemide in the standing position were carried out according to guidelines []. In Japan, if the ARR is high, at least 2 of 3 confirmation tests are recommended to make a definitive diagnosis (load tests of captopril or furosemide in the standing position, or saline) before attempting localization by adrenal vein sampling (AVS) []. No increase in renin activity was observed in the load tests, indicating autonomous secretion of aldosterone.
AVS with ACTH stimulation indicated that the PAC in both adrenal veins was markedly high (Fig. ). The PAC/cortisol ratio in both adrenal veins did not show laterality. These data demonstrate that both adrenal glands exhibited high and autonomous secretion of aldosterone, which is usually diagnosed as idiopathic hyperaldosteronism (IHA).
On CT scan (Fig. ), the left suprarenal mass was mostly circumscribed with a partial irregularity, and it was a homogenous mass (20~40 HU) with a density similar to that of the kidney (30~50 HU). The imaging diagnosis of the CT scan by the radiologist indicated an adrenal tumor. On magnetic resonance imaging (MRI), the tumor showed a low signal intensity on T1-weighted images (WI) (Fig. ) and heterogeneous signal intensity on T2-WI (Fig. ). Together with the results of MRI, the radiologist suggested that the tumor was a schwannoma.
Surgery was performed because of the possibility of malignancy, and a left supra-renal tumor was resected. On gross pathological examination (Fig. ), a clearly demarcated tumor (6.5 × 4.8 × 4.2 cm, 111 g) was observed with the adrenal gland and fat tissue. Histologically, the tumor was a typical schwannoma (Fig. ) and consisted of two different patterns of Antoni A and B components [] without defined nuclear atypias. The Antoni A area had a high cellular density component characterized by closely packed spindle-shaped tumor cells with nuclear palisading, forming Verocay bodies, whereas the Antoni B area had a relatively low cellular density component with myxoid stroma. According to the immunohistochemical examination, the spindle-shaped tumor cells were strongly and diffusely positive for S-100 (Fig. ). Based on these histological findings, the tumor was diagnosed as a typical benign schwannoma.
Although the patient’s abdominal mass was a schwannoma adjacent to the adrenal gland, the preoperative examination could not detect whether the lesion was responsible for autonomous aldosterone hypersecretion. Therefore, we performed a histological analysis of the adrenal gland (Fig. ). The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase [, ]), demonstrating “paradoxical hyperplasia” [, ] (Fig. ). Multiple CYP11B2-positive adrenocortical micronodules were detected in the resected adrenal gland (Fig. ), and these micronodules were negative for CYP11B1 (Fig. ). These histological findings demonstrated that the lesion responsible for autonomous aldosterone hypersecretion in the present case was derived from unilateral adrenocortical micronodules [] rather than diffuse hyperplasia (DH) [].
The postoperative course of the patient was uneventful. The patient is presently well and has shown no signs of recurrence of the schwannoma as of 6 months after the operation. His blood pressure is 110–130/70–90 mmHg with the administration of an antihypertensive drug (Amlodipine besylate 2.5 mg/day). His blood biochemistry data, including potassium, are within the normal range. His endocrinological data are also within the normal range, including the PAC (25.5 pg/mL), PRA (0.5 ng/mL/h) and ARR (51.0).


A 59-year-old woman with a history of irritable bowel syndrome and protein aversion, which led to a preferential vegetarian diet, was admitted for elective reparative surgery to treat rectal prolapse and enterocele. Her postoperative course was complicated by bowel perforation (requiring small bowel resection and end ileostomy), fecal peritonitis, intra-abdominal abscesses, septic shock, respiratory failure, tracheostomy, critical illness myopathy, protein-caloric malnutrition, and altered mental status (AMS). The patient provided written informed consent to publish these findings.
The patient's daily spontaneous awakening trials during her intensive care unit (ICU) course showed a positive evaluation on the Confusion Assessment Method for the ICU, score of +3 on the Richmond Agitation and Sedation Scale, and inability to follow 2-step commands, which led to an initial diagnosis of delirium. After standard delirium treatment was unsuccessful, further ICU investigation yielded normal renal, thyroid, and liver function. However, she had a markedly elevated ammonia level (100 mcmol/L, normal 0–30). Noncontrast head computed tomography and magnetic resonance imaging of the brain were negative for acute intracranial process.
Electroencephalography showed no evidence of nonconvulsive status epilepticus. Urine orotic acid and plasma amino acid panel were ordered to investigate her unexplained hyperammonemia. Her urine orotic acid level was elevated (3.2 mmol/mol creatinine, normal 0.4–1.2) but the plasma glutamine (normal 371–957 nmol/ml), ornithine (normal 38–130 nmol/ml), citrulline (normal 17–46 nmol/ml), arginine (normal 30–120 nmol/ml), and argininosuccinic acid (normal <2 nmol/ml) were within normal ranges. Nitrogen scavengers were not initiated at this time since there were no abnormalities in the rest of the urea cycle panel, ammonia began to trend down, and her mental status subsequently improved.
Because of prolonged mechanical ventilation and weaning failure, the patient received a standard polymeric enteral formula with a modular protein supplement. This was transitioned to an isotonic enteral formula after her ileostomy output increased. Her enteral nutrition was inconsistent during her ICU stay because of intestinal perforation, multiple planned procedures, intermittent high doses of vasopressors, and fluctuating doses of propofol.
On day 25 in the hospital, she was transferred to the step-down unit at her baseline mental state. Her appetite remained poor as she continued to experience bloating, nausea, and high gastric residual volume resulting in intermittent enteral and oral feeding. Trials of antiemetics, appetite stimulants, nutrition supplements, and diet adjustments were unsuccessful.
In the days approaching discharge, she had acute neurologic changes overnight, including visual hallucinations, hyperreflexia, clonus, generalized high-frequency low-amplitude tremors, nystagmus, and delirium. During the same night, she received the longest period of continuous enteral feeding since admission.
After this sudden neurologic decline on the step-down unit, OTC deficiency as a diagnosis was investigated further and empiric treatment was immediately initiated. Urine organic acid and acylglycines, quantitative plasma amino acid, and quantitative plasma acylcarnitine panels were ordered to screen for inborn errors of metabolism. This additional testing confirmed increased orotic acid, low citrulline, and elevated ammonia levels. The constellation of elevated urine orotic acid, low citrulline, persistent hyperammonemia with normal liver function, ketonuria, feeding difficulty, and neurologic changes were so highly suspicious of OTC deficiency; a confirmation of diagnosis by means of liver biopsy was not performed.


A young male aged 8 years 7 months presented with the following dentofacial problems:
Lip Biting Habit → Open bite, incompetent Lips,
Tongue Thrust, ↑ Overjet, Median Maxillary Diastema,
Tongue Pressure Prevents Maxillary Laterals from Eruption.
The parents’ and patient’s chief complaint was the anterior open bite and facial disharmony.
His medical history was good and free from any relevant health problems.
In view of the pretreatment records and clinical examination, interceptive orthodontics treatment was recommended using removable Hawley appliance with screening device and habit breaker as shown in Fig. ().
Phase I early treatment was successful and further follow up confirmed parents’ and patient’s satisfaction. A retention protocol was established to maintain future stability (Fig. ).
A female aged 8 years, 2 months, presented with Class I malocclusion and pleasant facial features.
Extra-oral examination: The patient had a rounded, symmetric face with incompetent lips where the lower lip is tucked behind the maxillary incisors forcing them labially and the mandibular incisors lingually (Fig. ). Her past medical history was free from any health problem.
Intra-oral examination revealed the following features (Fig.
Anterior open bite with normal Cl I Occlusion
Increased Overjet (Max Incisors Protruded)
Tongue thrust & atypical swallowing pattern
Lower lip entrapped under upper lip at rest
Lower anterior arch crowding
Lower anterior gingival recession
Oro-nasal breather
Distorted occlusal plane
Panoramic Radiograph (Fig.
-Early Mixed Dentition Phase with normally developing dentition-
-Lower anteriors + 4 1st molars erupted and roots are completed,
-Max Right Lateral did not erupt yet
-Max left lateral is partially erupting.
-All other teeth are present except third molars.
The patient's chief complaint was a lack of incising ability with anterior teeth and abnormal lip seal.
-Early Orthodontic Treatment (Lingual Arch) Started at 21 Oct 1999- (Phase I) (Figs. -)
Start of Fixed Tongue Crib + TPA (Goshgarian)
Ant Teeth Eruption & Crowding Resolved (Nov 2000)
Early Treatment Finished at 22 July 2002
1st Phase Treatment Duration 2 Ys + Lower Arch Development
Diphasic Treatment of AOB & Narrow Maxilla (Fig. ).
A female Aged 7y 5M, presented with pleasant face, AOB, incompetent lips, gummy smile, tongue thrust, narrow maxilla and convex mild dolichoface. Her medical history is free from any health problems.
Sequence of Phase I Treatment: RPE (Haas Appliance); Followed by Hawley Retainer with Tongue Guard for Stability (retention), ready to receive Phase II Treatment (Figs. -).
After three years post retention facial & occlusal features (October 2008) (Fig. ).
Female: (Age 13 Y + 2 M) 2004, Early Adult Orthodontic Treatment of Anterior Open Bite Cephalometric Analysis (Jarabak & McNamara) (Figs. -).
Problem Listing: Records: 5 February 2005
Anterior Open bite - Distorted Occ Plane
Mild Crowding - Buccal Crossbite
Tendency Dolichoface - Pleasant Facial Esthetics
Etiology
Tongue Thrust Habit
Mild Oro-Nasal Breathing? Resolved Prior to Treatment
Orthosurgical Correction of Anterior Open Bite
Adult Female 27Y old with sequence of comprehensive ortho treatment of occlusion.
Major Extra-Oral Findings (Figs. , ).
Long Face Syndrome
Gummay Smile
Anterior Open Bite
Class III Malocclusion
Mandibular dental deviation to the left 4mm
Incompetent Lips
Narrow alar bases
Intra-Oral Examination
Complex open bite (5mm)
Bilateral Buccal Crossbite
Distorted Occlusal Plane
Midline Deviation
Class III Malocclusion (Right full unit; left half unit)
Moderate Max Crowding & minimal crowding in the lower arch
Zero Overjet
In addition to radiographic examination (Fig. ).
The patient was treated with presurgical alignment and postsurgical treatment and evaluated with cephalometric analysis to improve the treatment (Figs. -).
The skeletal and dentoalveolar complexities of the case necessitated a combined consultation and treatment planning with the maxillofacial surgeon. To restore normal facial esthetics and occlusion; the following schedule was agreed upon:
Presurgical comprehensive orthodontic treatment including removal of the lower wisdom teeth;
LeFort 1 osteotomy with superior positioning of the maxilla and bilateral sagittal split osteotomy of the mandible to restore normal lip-teeth relationship and reduce the increased facial height; and
Postsurgical orthodontic care to settle the occlusion and maintain future stability of the treatment outcome.


A 79-year-old woman with no history of trauma presented with pain in her right arm that had persisted for one month. Her medical case history revealed that, for the past 6 years, she had received 35 mg/week alendronate as treatment for osteoporosis. Plain radiographs showed a transverse fracture in the proximal third of her ulna, and cortical thickening was observed at the fracture site (). A baseline dual-energy X-ray absorptiometry (DXA) scan showed that her femoral neck bone mineral density (BMD) was 0.34 g/cm2. Blood tests indicated that her serum calcium, phosphate, and alkaline phosphatase levels were in the normal ranges. The patient was diagnosed with an atypical fracture of the ulna. The patient discontinued her alendronate regimen, and surgical treatment for her fracture was planned. Because the fracture site appeared similar to pseudarthrosis, a 5 mm area of the sclerotic bone was resected from the fracture site (), and an autologous corticocancellous iliac bone graft was inserted at the resection site and fixed with a locking plate (). She was given teriparatide daily for osteoporosis, and low-intensity pulsed ultrasound (LIPUS) was done after surgery. LIPUS was done once a day for 1 year, and bone union was observed 1 year after the surgery ().


An 89-year-old woman complained of acute pain in her left arm after she lightly hit her elbow on a shelf. For the past nine years, she had been treated with 17.5 mg/week risedronate. Plain radiographs showed a transverse fracture in the proximal third of her ulna (). DXA revealed that her femoral neck BMD was 0.57 g/cm2, and blood tests showed normal results. The patient was diagnosed with an atypical fracture of the ulna. The risedronate was discontinued, and she was treated surgically. The sclerotic region was resected (), and an iliac bone graft was inserted followed by rigid fixation with a locking plate (). Daily teriparatide treatment was administered for the patient's osteoporosis, and an LIPUS was done once a day for one year. Bone union was observed 1.5 years after the surgery ().


A 44-year-old Asian woman presented to our institution with right flank pain. She reported recurrent right flank pain during menstruation of 4 years’ duration. Shortly after onset, she visited an emergency center and was diagnosed with right hydroureteronephrosis on the basis of computed tomography (CT) at another hospital (Fig. ). She underwent balloon dilation of the right distal ureter. Her right hydronephrosis was relieved, and the final diagnosis was idiopathic right distal ureteral stricture (Fig. ). She subsequently had mild cyclic right flank pain and visited numerous physicians, including gynecologists, but the cause of her symptoms was not diagnosed. Two weeks before visiting our hospital, her right flank pain was acutely aggravated during menstruation. She visited another hospital and was diagnosed on the basis of ultrasonography (US) and CT with right hydronephrosis due to right distal ureter stricture; however, her hydronephrosis resolved after 1 week (Fig. ).
The patient denied any menstrual cycle irregularities or history of endometriosis; chronic disease; allergies; hospitalizations; or past surgical history, including abdominal and gynecological surgeries. The result of a comprehensive review of systems was negative. Routine laboratory test results, including urinalysis, were all within normal limits. Transabdominal US revealed improved right hydronephrosis (Fig. ) compared with the previous CT findings. On transvaginal US, the uterus was deviated to the right with a nodular lesion at the right uterosacral ligament; the right ovary was attached to the uterus, with no apparent cystic lesion (Fig. ). Magnetic resonance imaging (MRI) showed a 2.8-cm heterogeneous mass in the right uterine wall with a tiny implant in the serosa of the posterior uterine wall. Mild wall thickening with delayed enhancement and mild dilation of the right distal ureter were observed, suggesting fibrotic change around the right distal ureter (Fig. ). These radiologic findings were consistent with ureteral DIE.
Diagnostic laparoscopy revealed narrowing of the distal right ureter between the right uterosacral ligament and right ovary, with adhesions caused by DIE (Fig. ). Dense adhesive fibrotic bands around the right distal ureter were dissected after resection of the right uterosacral ligament (Fig. ). Resection of the ipsilateral uterine artery crossing the distal part of the ureter was performed with ureterolysis to its most distal segment (Fig. ). A double-J stent was inserted into the right ureter to prevent possible obstruction. The pathologic report confirmed DIE of the right uterosacral ligament. The patient also received gonadotropin-releasing hormone agonists and is now free of symptoms.


A 71-year-old woman developed muscle pain and weakness in both thighs in 2014. The symptoms gradually progressed, and she was admitted to our hospital for work-up in August 2016.
Physical examinations revealed normal blood pressure of 105/65 mm Hg and body temperature of 36.7°C. Manual muscle testing score of her neck flexor tendons, biceps, triceps, quadriceps, and iliopsoas muscles showed muscle weakness (neck flexor tendons; 2, biceps, triceps, quadriceps, and iliopsoas muscles; bilaterally 4). Gowers’ sign was positive. The findings of ocular, lung, cardiovascular, abdominal, other neurological, joints and skin examination were normal. She had no history of statin treatment.
Laboratory tests revealed elevated levels of serum creatinine kinase (384 IU/L, normal range: 50–170 U/L), aldolase (6.2 IU/L, normal range: 2.7–5.9 IU/L), lactate dehydrogenase (314 U/L, normal range: 120–220 U/L), IgG (2603 mg/dL, normal range: 870–1700 mg/dL), IgA (721 mg/dL, normal range: 93–393 mg/dL), and IgG4 (313 mg/dL, normal range: 4.8–105 mg/dL). While serum erythrocyte sedimentation rate level was elevated (112 mm/h, normal range: 0–15 mm/h), serum C-reactive protein level was within normal range (0.04 mg/dL, normal range: 0–0.35 mg/dL). Other blood tests, including blood counts, serum levels of electrolyte, creatinine, IgE, and blood glucose were within normal range. Anti-nuclear antibody was positive with the titer of 1:1240 (homogeneous and speckled patterns). Antiaminoacyl-tRNA synthetase, anti-RNP, anti-dsDNA antibody, and anti-Sm antibodies were all negative.
Fat-suppressed T2-weighted magnetic resonance imaging showed high intensity (Fig. ), and needle electromyography showed spontaneous fibrillations and positive sharp waves in bilateral femoral quadriceps, suggesting the presence of myopathies. Positron-emission tomography-computed tomography demonstrated no abnormal accumulation of fluoro-2-deoxyglucose, or malignant tumor, or typical organ involvement for IgG4-RD, including lacrimal glands, salivary glands, pancreas, bile duct, kidney, aorta, and retroperitoneum.
Histological examination of her left quadriceps revealed mononuclear inflammatory cells that surrounded and invaded muscle fibers (Fig. A and B). Those inflammatory cells were positive for CD8 (Fig. C), and MHC class I antigen was extensively expressed on the surface of almost all muscle fibers (Fig. D). Scattered necrotic and regenerating muscle fibers as well as variations in muscle fiber size were characteristic of inflammatory myopathy (Fig. A and B). Infiltration of inflammatory cells at perivascular sites and perifascicular atrophy were not observed. While CD138, IgG, and IgG4 immunostaining (Fig. E–G) revealed that over 40% of infiltrated IgG positive plasma cells were IgG4+ cells, the important findings for IgG4-RD of storiform fibrosis and obliterative phlebitis were not found (Fig. H).
We diagnosed her with PM based on the Bohan and Peter classification criteria.[ Although she also met the 2011 comprehensive diagnostic criteria for IgG4-RD,[ IgG4-RD was unlikely since she had no swelling or masses in systemic organs, the affected lesion was only muscle without typical sites for IgG4-RD, and the findings of muscles showed necrotic and regenerating muscle fibers but not storiform fibrosis and obliterative phlebitis. Treatment with 40 mg/day of prednisolone decreased muscle enzyme levels and improved muscle weakness.


A 34-year-old female patient, with a history of laser epithelial keratomileusis, visited our clinic for diplopia and ocular motility disorder after removal of an epidermoid tumor at the prepontine cistern of the brain because of right 6th nerve palsy. At her initial visit, her best-corrected visual acuity (BCVA) was 20/20 for both eyes. An alternate cover test showed 45 prism-diopter esotropia and 3 prism-diopter hypertropia in the right eye. The patient was diagnosed with paralytic strabismus, and we planned to observe her for about two to three months to check changes in the amount of deviation. However, as the patient failed to visit outpatient clinic since then, further follow-up was unavailable. She revisited at 6 months after the development of her first symptom. Following 6 months of observation, angle of deviation did not improve, and 0.2 cm3 of botulinum toxin (2.5 international units) were injected into the right medial rectus (RMR). After 6 days, she visited our clinic complaining of decreased visual acuity of her right eye. The BCVA and intraocular pressure (IOP) for her right eye were found to be 20/50 and 15 mmHg, respectively. Based on funduscopic examination, a retinal hole was located 4 DD (disc diameter) inferonasally from the optic disc, and both preretinal and vitreous hemorrhages were present in front of the lesion (Fig. ). Optical coherence tomography (OCT) examination revealed subretinal fluid nasal to the fovea, but central fovea was attached (Fig. , ). The patient was diagnosed with RRD with macula off, but because of small subretinal fluid and tiny retinal break, we decided to observe it first. Barrier laser photocoagulation around the retinal hole was performed (Fig. ). However, the patient’s visual acuity continued to decrease without improvement of vitreous hemorrhage, and at 12 weeks after botulinum toxin injection, a newly developed tractional membrane from macula to inferonasal periphery was noted, suggesting PVR development (Fig. , ). An alternate cover test presented 30 prism-diopter right esotropia. 19 weeks following RMR botulinum toxin injection, she received PPV, membranectomy, peeling of the internal limiting membrane, and endolaser barrier photocoagulation. After 4 months, her visual acuity improved to 20/20, and only 4 prism-diopter of right hypertropia and 3 prism-diopter of exotropia were noted. Vitreous opacity and the epiretinal membrane were completely removed (Fig. , ). Serious adverse complications, including endophthalmitis, retinal re-detachment, and increased IOP, were not observed.


The proband, a 35-year old man, was referred to us for a 20-year history of pain and limitation in mobility of multiple joints and a one-year history of worsening symptoms. He developed kyphosis at the age of 11. The patient endorsed pain in his palms, wrists and elbow joints without the presence of a rash or erythematous swelling. Subsequently, he progressed to develop pain and restricted movements in his hip and ankle joints that was associated with limited motion with squatting. A suspected diagnosis of congenital spondyloepiphyseal dysplasia was made at another hospital, and the doctor recommended he follow up without any therapy. The patient noted pain in his hips and knee joints, and he had difficulty in standing and sitting. The patient developed claudication and was only treated with occasional painkillers instead of systemic therapy.
At the age of 34, the patient was unable to walk without a crutch due to the pain and severely restricted motion in his hip joints after becoming very tired. At a local hospital, a laboratory test showed a normal erythrocyte sedimentation rate (2 mm/h), and tests for HLA-B27 remained negative. A radiograph of his hips showed sacroiliitis. The patient was suspected to have ankylosing spondylitis, and he was referred to our institution for further evaluation.
Examination of the spine showed an abnormal spinal curvature with limited range of motion in the cervical spine. Flexion contractures of the elbows and knees were observed, and there was limited range of motion in the elbows, shoulders, knees and ankles. The Patrick test and occiput-to-wall distance test were positive. The rest of his physical examination was unremarkable.
Radiological findings revealed the following: a reduced interarticular space of the hip joints with bilateral femoral neck aseptic necrosis (Fig. ); enlargement of the interphalangeal joints (Fig. ); osteosclerosis and irregular contour of the joint surface and narrowing of the spaces in the knee joints (Fig. ); herniated disks in the thoracolumbar spine with lumbar spine hyperplasia (Fig. ) and platyspondyly of the cervical spine (Fig. ).
The rest of his five family members including his parents, wife and son did not have any evidence of skeletal dysplasia. Subsequently, the diagnosis of ankylosing spondylitis was challenged, and PPD was strongly suspected. A genetic analysis was carried out, following the CARE guidlines. We found that the proband carried a frameshift mutation (c.670dupA) and a nonsense mutation (c.756C > A, p.Cys252*) in exon 4 of WISP3 (Fig. ), which have been reported previously [, ]. Furthermore, the frameshift mutation (c.670dupA) was found in the paternal allele (Fig. ), and the nonsense mutation (c.756C > A, p.Cys252*) was found in the maternal allele (Fig. ). The son of the proband was found to carry the frameshift mutation (c.670dupA) inherited from his grandfather (Fig. ).
A diagnosis of PPD was confirmed in the proband after combining the clinical characteristics and the results from the genetic analysis. Furthermore, genetic counseling was given for the son, who was told that he would not be affected by PPD in the future.


A 46-year-old male with a history significant for atrial fibrillation, dilated aortic root, and bicuspid aortic valve with severe aortic regurgitation (AR) presented to the operating room for elective aortic valve replacement, aortic root replacement, and Maze procedure. His preoperative transthoracic echocardiogram (TTE) was notable for normal biventricular function, severe AR, and a possible patent foramen ovale (PFO). No details about the coronary sinus were provided on the TTE report. Intraoperatively, the patient underwent an uneventful induction of general anesthesia. Transesophageal echocardiography (TEE) was then performed and confirmed the preoperative findings with the exception that there was no PFO identified. Other notable findings, however, were also discovered on TEE. During placement of a central venous catheter in the right internal jugular vein, TEE was used to visualize the guidewire. It was noted at this time that the right SVC appeared small ().
In addition, the coronary sinus was observed to be significantly dilated, measuring 2.1 cm in the deep midesophageal 4-chamber view () and 3.3 cm in the midesophageal 2-chamber view ().
These echocardiographic findings raised suspicion for a PLSVC. A left-sided intravenous line was in place so a bubble study was attempted. Injection of agitated saline showed bubbles appearing in the coronary sinus prior to entering the right atrium ( in Supplementary Material), although the study was limited by the relatively low number of bubbles. The suspicion for a PLSVC was communicated to the surgical team given the possible implications for retrograde cardioplegia administration. However, at that time, they were not able to visually identify a PLSVC.
The patient was cannulated for CPB. Given the severe aortic insufficiency, retrograde was preferred over antegrade cardioplegia. Once CPB was established, retrograde cardioplegia administration was attempted but there was difficulty achieving pressurization of the coronary sinus. Since the patient was on CPB by this time, a more thorough visual examination of the coronary sinus was possible without hemodynamic instability. Further inspection by the surgical team confirmed that there indeed was a PLSVC in continuity with the coronary sinus and antegrade cardioplegia was used to arrest the heart while carefully monitoring the left ventricle for distention using TEE. The heart was successfully arrested and the patient underwent MAZE along with aortic valve and root replacement. The patient was weaned from CPB uneventfully and was taken to the intensive care unit postoperatively. No intervention was performed for the PLSVC.


A 58-year-old man presented to his primary care physician with vague abdominal pain, constipation, and one year of urinary hesitancy. Abdominopelvic CT scan revealed a complex, lobulated, enhancing, intraperitoneal mass measuring 18 × 19 × 10 cm, extending from the umbilicus to the level of the superior acetabulum (). He underwent resection of the mass, including small bowel and partial bladder resection in January 2013. Pathology confirmed complete resection (R0) of high-grade GIST originating from the proximal jejunum, stage IIIB (pT4a, pNx). The tumor was spindle-cell subtype, with the mitotic rate of 8/10 HPF, and necrosis. Immunohistochemistry (IHC) showed membrane positivity for CD117, beta-catenin, vimentin, and smooth muscle actin (SMA). Mutational analysis demonstrated no mutations in the c-Kit proto-oncogene or platelet-derived growth factor receptor alpha (PDGFRA). Risk of recurrence was determined to be 90% [–]. He began imatinib mesylate 400 mg daily postoperatively. No evidence of tumor recurrence was detected over three years postoperatively. The patient tolerated imatinib well, except for mild diarrhea (grade 1 CTCAE) [].
In May 2016, surveillance CT revealed a 3.5 × 2.8 cm left lower quadrant mass abutting the sigmoid colon (). IM dosage was empirically increased from 400 mg to 800 mg daily, but repeat imaging in July 2016 showed disease progression. The left lower quadrant lesion had grown in size to 4.0 × 3.3 × 3.2 cm, with extrinsic compression on the sigmoid colon, with a 2.4 × 2.1 × 2.5 cm periumbilical lesion. Additionally, a new right upper quadrant lesion was noted, approximately 5.3 × 3.7 × 2.1 cm. In late July 2016, diagnostic laparoscopy was performed (detecting a right lower quadrant peritoneal nodule), followed by laparotomy, small bowel resection, resection of right upper quadrant lesion, sigmoidectomy, and resection of right lower quadrant peritoneal nodule (). The pathology revealed high-grade GIST with negative margins and absence of c-Kit mutation. Molecular profiling and next-generation sequencing (NGS) of the recurrent disease indicated susceptibility to sunitinib based on the presence of wild-type (WT) c-Kit. Accordingly, the patient was switched from imatinib to sunitinib. Follow-up CT in May 2017 showed no signs of tumor recurrence, with patient follow-up at three-month intervals [].


A 50-year-old woman presented to our center with dyspepsia from three months prior to evaluation. Past medical history was unremarkable. The physical examination was normal. Upper gastrointestinal endoscopy was performed for evaluation of cause of dyspepsia. Endoscopy identified a firm submucosal yellow lesion, measuring approximately 10 mm and located 30 cm distal from the incisor teeth (). The stomach and duodenum were normal. Biopsies by forceps were taken from the esophageal lesion. The histologic assessment was in favor of GCT.
Endoscopic ultrasonography (EUS) was performed by linear echo with frequency of 10 MHZ. EUS identified a submucosal lesion with a diameter of 12 mm. It was a nonhomogeneous hyperechoic solid lesion with clear border with no extension to muscularis layer and without mediastinal adenopathies ().
The patient was considered for endoscopic resection of lesion. After deep sedation with intravenous Propofol (Lipuro-1%), submucosal injection of 5 ml diluted epinephrine solution (0.01 mg/ml) with 0.5 ml methylene blue was done using a sclerotherapy needle (ENDO-FLEX-Germany). After creation of the submucosal fluid bulging, the resection of lesion was performed using a monofilament rotatable polypectomy snare (Boston; 20 mm; output setting: cut 40 watts; coagulation 40 watts) without any complication (). The resected specimen was removed by basket. The size of specimen was 12 × 5 mm with yellow color (). The specimen was fixed in 10% formalin and transferred to the lab for histologic assessment.
In histologic examination, the diagnosis of GCT was confirmed. Histological analysis of specimen revealed nests of medium-sized cells with abundant eosinophilic granular cytoplasm with bland looking nuclei without any atypia or pleomorphism ().
Follow-up endoscopy 9 months after removal of tumor showed complete healing of the site of resection in esophagus.


A 41-year-old male with hypertension, ventricular tachycardia (VT) status post biventricular implantable cardioverter defibrillator (ICD), and non-ischemic cardiomyopathy with end-stage heart failure (left ventricular ejection fraction 10%) was admitted with decompensated heart failure. The patient was treated with diuresis and ionotropic support. Eleven days later, the patient received an LVAD Heartmate II (Thoratec, Pleasanton, California). On postoperative day 25, the patient experienced severe chest pain followed by multiple ICD shocks. Telemetry confirmed VT (Figure ). Medical therapy was initiated followed by intubation and sedation for incessant VT. Echocardiogram showed unobstructed LVAD cannula flow at the apex, severe right ventricular dilation, and hypokinesis; the aortic valve did not open during systole (Figure ). Coronary angiography illustrated a large thrombus burden in the left coronary sinus extending to the left main and proximal left anterior descending (LAD) artery (Figure ). A six French contralateral support (CLS) guiding catheter (Boston Scientific, Marlborough, Massachusetts, US) and a Prowater guidewire (Abbott Vascular, Santa Clara, CA, US) were advanced (Figure ). Aspiration thrombectomy was performed and multiple passes were made without success; thus, rheolytic thrombectomy was attempted, which was again unsuccessful. The guide catheter was advanced into the left main and aspiration was performed with a 20 cc syringe, yielding 1-2 x 6-8 mm pieces of organized thrombus, without improvement in the distal flow. Intra-coronary tPA injection, with repeated rheolytic thrombectomy, resulted in near resolution of the thrombus (Figure ) except at the distal LAD (Figure ). The patient was extubated the next day and remained free of chest pain and VT. He was later discharged with heart-failure clinic follow-up.


The first patient is a 44-year-old male, involved in a motor vehicle accident, who sustained a severe traumatic brain injury resulting in an acute subdural hematoma, intraparenchymal and subarachnoid hemorrhages. An emergent decompressive craniotomy was performed at a community hospital and no specific vascular lesions of the MMA were appreciated intra-operatively. Consequently, the patient was referred to our tertiary care center for evaluation of vascular injuries discovered on computed tomography (CT)e angiography. Cerebral angiography revealed two traumatic pseudoaneurysms of the right MMA. The decision was made to treat the MMA aneurysms using endovascular Onyx 18 embolization per standard technique, with excellent results.


The second patient is a 56-year-old male that sustained a frontal bone fracture with severe cerebral edema following a motorcycle collision. Field resuscitation and intubation were completed prior to arrival to the emergency department. Initial survey showed a large scalp laceration, periorbital ecchymosis, scattered chest and abdominal abrasions, multiple orthopedic fractures, which required surgical fixation as well as extensive intra-abdominal injuries, which required a laparotomy and repair. An external ventriculostomy drain was placed for cerebrospinal fluid diversion and intracranial pressure monitoring. Critical care management was done for eight days and the patient was extubated. Follow-up CT Angiography showed bilateral carotid artery dissection and various other traumatic vascular lesions that were treated according to standard guidelines. Follow-up angiography performed one year later revealed a right-sided traumatic unruptured middle meningeal artery aneurysm in addition to persistent right-sided internal carotid artery (ICA) dissection with an enlarging pseudoaneurysm. The decision was made to treat both lesions concurrently. The right MMA aneurysm was treated with transcatheter embolization using Onyx 34, with excellent angiographic results. The ICA pseudoaneurysm was treated using overlapping pipeline embolization. Figure shows the pre- and post-intervention cerebral angiograms.
Neither patient experienced any intraoperative or immediate postoperative complications. The first patient remained mechanically ventilated in the perioperative period and his respiratory status steadily improved. He was discharged several days later to an acute rehabilitation facility. There was no recurrence of any of the lesions at 10-month follow-up angiography. The second patient tolerated the procedure well and was discharged home the next day in stable condition. Follow-up angiography one year later showed no recurrence of lesions post-embolization.


A 49-year-old female presented with nausea, vomiting, and weight loss. Full blood count revealed a white blood cell count of 238.0 × 109/L, hemoglobin of 7.7 g/dL, and platelets of 746 × 109/L. Bone marrow morphology revealed granulocytic hyperplasia with increased megakaryocytes and <1% myeloblasts. Cytogenetics detected the t(9;22) translocation with molecular analysis demonstrating high levels of e13a2 BCR-ABL1 transcripts, consistent with a diagnosis of chronic-phase CML with a low-risk Sokal score. She commenced imatinib 400 mg oral daily with transient toxicities of nausea and increased susceptibility to infections but overall tolerated imatinib well, achieving a major molecular response (MMR) of BCR-ABL1/ABL1 0.09% on the International Scale (IS) at 20 months (). BCR-ABL1 transcripts became undetectable (<0.001% IS) at 40 months with optimal adherence and a good quality of life. After BCR-ABL1 transcripts became undetectable, monitoring intervals were extended to six months. Rising transcript levels resulted in loss of MMR at 105 months, peaking at a BCR-ABL1/ABL1 IS of 3.43%, almost nine years after starting imatinib (). After adherence was assured, ABL1 KD mutation analysis was performed as previously described [, ] and detected the Y253H (c.757T > C; NM_005157.5) mutation. The time between loss of MMR and mutation detection was six months. The patient then switched to bosutinib 500 mg oral daily [], reduced to 400 mg oral daily after gastrointestinal toxicities, which resulted in an MMR within three months (BCR-ABL1/ABL1 IS 0.02%). The BCR-ABL1 transcript level continues to decline () with continued frequent monitoring advocated.