Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

Morphologies and prognostic significance of left ventricular volume/time curves with cardiac magnetic resonance in patients with non-ischaemic heart failure and left bundle branch block

The International Journal of Cardiovascular Imaging - Patients with non-ischaemic systolic heart failure (HF) and left bundle branch block (LBBB) can display a wide or narrow pattern (WP/NP) of the...     

Abdominal aortic aneurysm associated with renal ectopia

This report describes a rare case of concurrent abdominal aortic aneurysm and bilateral renal ectopia. Preoperative work-up included intravenous pyelography and angiography to assess renal function, renal artery anatomy, and ureter position. Conventional surgery was performed without renal protection. No deterioration in postoperative renal function was observed.     

Clinical utility of EUS-guided fine-needle aspiration of mediastinal masses in the absence of known pulmonary malignancy

BACKGROUND: Mediastinal masses represent a diagnostic challenge because of their proximity to numerous critical structures, difficulty of access for tissue sampling, and myriad potential pathologic etiologies. A large, single-center experience with EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of non-lung cancer-related mediastinal masses is presented. METHODS: An EUS database was reviewed and all cases of mediastinal mass or lymphadenopathy encountered between 1994 and 1999 were included. Final diagnoses were determined by EUS-FNA cytology and clinical follow-up. RESULTS: Forty-nine patients were identified (27 women, 22 men; mean age 58.1 years, range 30-89 years). A malignant process was diagnosed in 22 cases (45%) and a benign process in 24 (49%). The EUS-FNA specimen was nondiagnostic in 3 cases (6%). An accurate diagnosis was made in 46 of the 49 patients (94%). No complication was noted. CONCLUSIONS: EUS-FNA is a minimally invasive technique that facilitates detection and tissue sampling of mediastinal masses. It is a safe procedure that can be performed with the patient under conscious sedation in an outpatient setting.     

Klebsiella bacteremia: an analysis of 100 episodes

During a five-year period, 204 patients had klebsiella bacteremia at this institution; these cases constituted 6.6% of the total episodes of bacteremia. The incidence was 2.3 cases per 1,000 admitted patients. A random group of 100 cases was chosen for analysis in the present study. The disease was community acquired in 23%, nosocomially acquired in 77%, unimicrobial in 88%, or part of a polymicrobial bacteremia in 12% of episodes. Three-quarters of the episodes were caused by Klebsiella pneumoniae and the remaining one-quarter, by Klebsiella oxytoca. Portals of entry, in decreasing order of frequency, were urinary, respiratory, and biliary tracts. Twenty-four percent of the Klebsiella isolates were resistant to gentamicin. The most frequent clinical finding (in 96% of the cases) was fever. Shock occurred in 22% and pyogenic metastatic foci, in 5% of the patients. None of the patients had evidence of disseminated intravascular coagulation. Overall mortality was 25%, and factors associated with poor prognosis were inadequacy of antimicrobial chemotherapy, septic shock, type of underlying disease, and clinical condition of the patients.