SUBRETINAL DRUSENOID DEPOSITS AND SOFT DRUSEN: Are They Markers for Distinct Retinal Diseases?

PURPOSE: Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases. METHODS: One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. RESULTS: There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 ± 18 vs. 69 ± 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038). CONCLUSION: Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.

"When to Nuss? patient age as a risk factor for complications of minimally invasive repair of pectus excavatum: a systematic review and meta-analysis".

PURPOSE: The optimal age for minimally invasive repair of pectus excavatum (MIRPE) is unclear; this study investigates the differences in complication rates among different age groups undergoing repair. METHODS: PubMed and Embase databases were searched from inception to October 2020. To assess age as a risk factor for complications, odds ratios from relevant studies were analyzed using the Mantel-Haenszel method with a random-effects model for younger vs older patients. Specific complication rates were compared between the two cohorts using a chi-squared test. RESULTS: Of the 4448 studies retrieved, 25 studies stratified complication data by age groups. From these studies, ten studies compared groups at ages < 18 and ≥ 18 and four studies compared ages < 20 and ≥ 20, and one study compared ages < 19 and ≥ 19. These fifteen studies reported on 5978 patients, with 1188 complications, for a complication rate of 19.87%. Older patients were more likely to have complications in a pooled analysis of studies comparing older vs younger patients (OR = 1.66, 95% CI = 1.28-2.14, heterogeneity I2 = 49%). Specifically, older patients were significantly more likely to experience pneumothorax, pleural effusion, wound infection, bar displacement, and reoperations. CONCLUSION: Increased age is a risk factor for complications of MIRPE. This supports repair of pectus excavatum prior to late adolescence.

Prevention of Postoperative Constipation in Urogynecology Patients: A Systematic Review.

IMPORTANCE: Constipation is common after pelvic surgery, and studies suggest that surgeons underestimate the negative impact of constipation on patients. Patients undergoing pelvic reconstructive surgery are a unique population requiring special consideration in the prevention and management of constipation. OBJECTIVE: This study aimed to systematically review the literature to identify evidence for prevention of postoperative constipation with medications or fiber in patients undergoing reconstructive pelvic surgery. STUDY DESIGN: A structured literature search was performed of five databases (MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library) from inception to June 2022 for studies of postoperative laxative or fiber use in adult patients undergoing benign pelvic reconstructive surgery. Studies of preoperative bowel preparation and nonsurgical patients were excluded. Data on postoperative constipation were extracted for a qualitative analysis of the literature. Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to assess the quality of evidence. RESULTS: We identified 86 references after deduplication. Only 4 studies with a total of 344 patients were eligible for inclusion in the review. The included studies were all randomized controlled trials assessing time to first bowel movement with the earliest published in 2010. Laxative use decreased constipation more than placebo. Multiple-agent laxative use appeared to decrease bothersome constipation more than single-agent docusate. Preoperative fiber did not decrease constipation. By Grading of Recommendations Assessment, Development, and Evaluation criteria, all four studies provide moderate-quality evidence. CONCLUSIONS: Few studies have investigated laxative regimens in patients after urogynecologic surgery. The available literature is moderate quality and suggests benefit of multiple-agent treatment over docusate only or no treatment.

Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast.

In yeast, actin cables are F-actin bundles that are essential for cell division through their function as tracks for cargo movement from mother to daughter cell. Actin cables also affect yeast lifespan by promoting transport and inheritance of higher-functioning mitochondria to daughter cells. Here, we report that actin cable stability declines with age. Our genome-wide screen for genes that affect actin cable stability identified the open reading frame YKL075C. Deletion of YKL075C results in increases in actin cable stability and abundance, mitochondrial fitness, and replicative lifespan. Transcriptome analysis revealed a role for YKL075C in regulating branched-chain amino acid (BCAA) metabolism. Consistent with this, modulation of BCAA metabolism or decreasing leucine levels promotes actin cable stability and function in mitochondrial quality control. Our studies support a role for actin stability in yeast lifespan, and demonstrate that this process is controlled by BCAA and a previously uncharacterized ORF YKL075C, which we refer to as actin, aging and nutrient modulator protein 1 (AAN1).