Summary We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival ‘neuronal’ subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, lncRNA, and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma-in-situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.

Early experience with laparoscopic partial nephrectomy is promising. Laparoscopic partial nephrectomy offered the advantages of less operative time, decreased operative blood loss and a shorter hospital stay. When applied to patients with a single renal tumor 7 cm or less, laparoscopic partial nephrectomy was associated with additional postoperative morbidity compared to open partial nephrectomy. However, equivalent functional and early oncological outcomes were achieved.

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Previous genetic studies of the nematode Caenorhabditis elegans identified three important components of the cell death machinery. CED-3 and CED-4 function to kill cells, whereas CED-9 protects cells from death. Here CED-9 and its mammalian homolog Bcl-xL (a member of the Bcl-2 family of cell death regulators) were both found to interact with and inhibit the function of CED-4. In addition, analysis revealed that CED-4 can simultaneously interact with CED-3 and its mammalian counterparts interleukin-1beta-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases.

the presence of diabetes mellitus or other comorbid emphysematous infections of the urinary tract. RESULTSIn all, 102 published papers, including 135 cases of EC, were reviewed; the median patient age was 66 years, 64% were women and 67% had diabetes mellitus. Most cases were diagnosed using plain films of the abdomen (84%), although more recently, computed tomography was the primary imaging method. Escherichia coli was the most commonly isolated organism. Most patients were treated with medical management alone (90%), while 10% of infections were treated with a combination of medicine and surgery. The overall death rate was 7%. CONCLUSIONSEC is the most common and typically the least severe gas-forming infection of the urinary tract. Prompt diagnosis and treatment is warranted to prevent the potential morbidity and mortality of this infectious condition.

The second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology.Here we report comparisons of analytic and diagnostic performance. Of 1,248 ill inpatient infants, 578 (46%) had diseases of unknown etiology. 213 infants (37% of those eligible) were enrolled within 96 h of admission. 24 infants (11%) were very ill and received ultrarapid whole-genome sequencing (urWGS). The remaining infants were randomized, 95 to rWES and 94 to rWGS. The analytic performance of rWGS was superior to rWES, including variants likely to affect protein function, and ClinVar pathogenic/likely pathogenic variants (p < 0.0001). The diagnostic performance of rWGS and rWES were similar (18 diagnoses in 94 infants [19%] versus 19 diagnoses in 95 infants [20%], respectively), as was time to result (median 11.0 versus 11.2 days, respectively). However, the proportion diagnosed by urWGS (11 of 24 [46%]) was higher than rWES/rWGS (p ¼ 0.004) and time to result was less (median 4.6 days, p < 0.0001). The incremental diagnostic yield of reflexing to trio after negative proband analysis was 0.7% (1 of 147). In conclusion, rapid genomic sequencing can be performed as a first-tier diagnostic test in inpatient infants. urWGS had the shortest time to result, which was important in unstable infants, and those in whom a genetic diagnosis was likely to impact immediate management. Further comparison of urWGS and rWES is warranted because genomic technologies and knowledge of variant pathogenicity are evolving rapidly.

Lower preoperative glomerular filtration rate, solitary kidney, older age, gender, tumor size and longer ischemic interval all predicted lower glomerular filtration rate after partial nephrectomy. Therefore, duration of renal ischemia is the strongest modifiable surgical risk factor for decreased renal function after partial nephrectomy, and efforts to limit ischemic time and injury should be pursued in open and laparoscopic partial nephrectomy.