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BRAT1-related neurodevelopmental disorders are characterized by heterogeneous phenotypes with varying levels of clinical severity. Since the discovery of BRAT1 variants as the molecular etiology of lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498), these variants have also been identified in patients with milder clinical forms including neurodevelopmental disorder with cerebellar atrophy and with or without seizures (NEDCAS, OMIM 618056), epilepsy of infancy with migrating focal seizures (EIMFS), and congenital ataxia (CA). This study aims to examine the consequences and pathogenicity of a novel homozygous splice site variant in BRAT1 in a patient presenting with migrating focal seizures since birth without prominent rigidity. The patient was born from a consanguineous marriage and has had seizures since the neonatal period. He presented with dysmorphic features, pontocerebellar hypoplasia, and migrating focal seizures. Despite supportive treatment, his symptoms rapidly progressed to intractable myoclonic seizures, bouts of apnea and bradycardia, and arrest of head growth, with no acquisition of developmental milestones. Clinical exome sequencing yielded a novel homozygous splice variant in BRAT1. Genetic analysis based on reverse transcription of the patient's RNA followed by PCR amplifications performed on synthesized cDNA and Sanger sequencing was undertaken, and the functional effect of a BRAT1 variant on splicing machinery was demonstrated for the first time. The severe clinical presentation of migrating focal seizures and pontocerebellar hypoplasia in the absence of rigidity further expands the genotypic and phenotypic spectrum of BRAT1-related neurodevelopmental disorders.

Background: Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), in which pulmonary involvement often predominates, is a multisystem granulomatous, necrotizing vasculitis that affects small and medium-sized vessels. In this study we evaluated various radiological findings of pulmonary GPA and focused on spiculated pulmonary lesions invading the pulmonary fissure, pleura or diaphragm mimicking malignancy., Methods: This retrospective study included 48 patients, aged 28-73 (mean, 47.3) years, who showed either histopathological diagnosis of GPA (n = 39) or elevated levels of the cytoplasmic anti-neutrophilic cytoplasmic antibody serum marker (n = 9) between January 2003 and December 2013. All patients received a chest computed tomography (CT), and the types of pulmonary lesions were defined and evaluated., Results: Among the 48 patients, 33 had abnormal pulmonary findings on CT. The most commonly detected pulmonary lesion types were nodules and masses (n = 126) observed in 24 patients. Cavitation, necrosis, spiculation and invasion of the fissure, pleura or diaphragm were observed in 14, 9, 10 and 6 patients, respectively. Consolidation was found in 14 patients and thickening of bronchial wall in 8 patients., Conclusions: Pulmonary lesion types of GPA have a wide spectrum, potentially mimicking a high number of diseases including malignancy, infection and noninfectious inflammatory diseases. A spiculated lung lesion invading the fissure, pleura or diaphragm is mostly present in malignancy, but it can be also seen in GPA.

The diseases affecting the trachea and main bronchi can be categorized into congenital or acquired abnormalities and also into focal or diffuse diseases. Major congenital bronchial abnormalities cover accessory cardiac bronchus and tracheal bronchus. Tracheobronchial strictures, such as post-intubation and post-infectious stenosis and tracheobronchial neoplasms are regarded as focal diseases, whereas tracheobronchomegaly, relapsing polychondritis, tracheobronchopathia osteochondroplastica, amyloidosis, granulomatosis with polyangiitis, tracheobronchomalacia, saber-sheath trachea and tracheobronchitis associated with ulcerative colitis are examples of diffuse diseases. Computed tomography (CT) is the best non-invasive method for evaluation of tracheobronchial lesions. In this pictorial review we aimed to demonstrate CT features of central airway diseases.

Purpose: Our aim was to investigate the role of computed tomography pulmonary angiography (CTPA) in the diagnosis of right ventricular dysfunction (RVD) and massive pulmonary thromboembolism (PTE)., Materials and Methods: We retrospectively involved a total of 61 patients. In CTPAs, pulmonary arterial obstruction index (PAOI), right ventricular/left ventricular diameter ratio (RV/LV), and superior vena cava (SVC) diameters were calculated, followed by echocardiography (ECHO), and clinical results were evaluated based on the reports available., Results: CTPA findings that included PAOI, RV/LV ratio, and SVC diameter were, respectively, 54.9 ± 22.7 %, 1.58 ± 0.51, and 20.3 ± 0.2 mm in patients with RVD on ECHO, whereas corresponding values were, respectively, 37.8 ± 24.2 %, 1.32 ± 0.47, and 18.4 ± 3.3 mm in those without RVD (respectively, p = 0.006, p = 0.038, and p = 0.026). PAOI was 63.3 ± 22.0 % in patients among whom massive PTE was detected and 43.1 ± 23.9 % in the group without massive PTE (p = 0.01). As for mortality; given an RV/LV ratio >1.0, this ratio had 100 % sensitivity and 35.6 % specificity, whereas given a PAOI of ≥50 %, sensitivity and specificity were 83.3 % and 57.8 %, respectively., Conclusion: We concluded that in the patients with PTE, PAOI ≥50 % and RV/LV >1.0 in CTPA could be helpful to demonstrate RVD.

Background: Reduced soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) levels follow declining renal function, are strongly associated with endothelial dysfunction and predict cardiovascular events in nondialyzed chronic kidney disease patients. In contrast, elevated levels of sTWEAK predict poor survival in hemodialysis (HD) patients. Recent evidence suggests a role for sTWEAK in the pathophysiology of vascular calcification. The aim of the study was to investigate plausible links between sTWEAK, atherosclerosis, arterial stiffness and vascular calcification in HD patients., Methods: Coronary artery calcification score (CACs) determined by multislice computed tomography, arterial stiffness by pulse wave velocity (PWV) and carotid artery intima-media thickness (CA-IMT) by carotid Doppler ultrasonography were assessed in 131 long-term prevalent HD patients. sTWEAK levels were measured by ELISA (Bender MedSystems, Vienna, Austria)., Results: Mean serum sTWEAK level was 237.0 ± 147.5 pg/mL (range 78-937). sTWEAK level was inversely correlated with CA-IMT at a borderline significance (r=-0.168, p=0.05). Neither carotid-radial PWV nor carotid-femoral PWV values correlated with sTWEAK. sTWEAK level was higher in patients with severe vascular calcification (CACs ≥400) compared to patients with CACs <400 (264.5 ± 146.8 pg/mL vs. 205.04 ± 122.4 pg/mL, p=0.02).The association between sTWEAK and vascular calcification persisted after multivariate adjustment., Conclusions: There exists a weak inverse correlation between sTWEAK and carotid atherosclerosis and a positive correlation with coronary artery calcification in long-term HD patients. Our data give support for a role for sTWEAK in the pathogenesis of vascular injury in HD patients.

OBJECTIVES: To review the computed tomography (CT) findings of common and uncommon high-attenuation pulmonary lesions and to present a classification scheme of the various entities that can result in high-attenuation pulmonary abnormalities based on the pattern and distribution of findings on CT. BACKGROUND: High-attenuation pulmonary abnormalities can result from the deposition of calcium or, less commonly, other high-attenuation material such as talc, amiodarone, iron, tin, mercury and barium sulphate. CT is highly sensitive in the detection of areas of abnormally high attenuation in the lung parenchyma, airways, mediastinum and pleura. The cause of the calcifications and other high-attenuation conditions may be determined based on the location and pattern of the abnormalities within the lung parenchyma and knowledge of the associated clinical features. RESULTS: We have presented a diagnostic approach based on the presence and distribution of five main patterns of high-attenuation conditions on CT: (1) small hyperdense nodules, (2) large calcified nodules or masses, (3) high-attenuation linear or reticular pattern, (4) high-attenuation consolidation and (5) high attenuation extraparenchymal lesions. CONCLUSIONS: Some high-attenuation pulmonary abnormalities have characteristic CT findings suggesting the correct diagnosis. In other diseases, a combination of clinical features and radiological findings can significantly improve diagnostic accuracy.