Pharyngeal Reconstruction Methods to Reduce the Risk of Pharyngocutaneous Fistula After Primary Total Laryngectomy: A Scoping Review

Introduction: The most common early postoperative complication after total laryngectomy (TL) is pharyngocutaneous fistula (PCF). Rates of PCF are higher in patients who undergo salvage TL compared with primary TL. Published meta-analyses include heterogeneous studies making the conclusions difficult to interpret. The objectives of this scoping review were to explore the reconstructive techniques potentially available for primary TL and to clarify which could be the best technique for each clinical scenario. Methods: A list of available reconstructive techniques for primary TL was built and the potential comparisons between techniques were identified. A PubMed literature search was performed from inception to August 2022. Only case-control, comparative cohort, or randomized controlled trial (RCT) studies were included. Results: A meta-analysis of seven original studies showed a PCF risk difference (RD) of 14% (95% CI 8-20%) favoring stapler closure over manual suture. In a meta-analysis of 12 studies, we could not find statistically significant differences in PCF risk between primary vertical suture and T-shaped suture. Evidence for other pharyngeal closure alternatives is scarce. Conclusion: We could not identify differences in the rate of PCF between continuous and T-shape suture configuration. Stapler closure seems to be followed by a lower rate of PCF than manual suture in those patients that are good candidates for this technique

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways