Making lemonade with lemons: a multicenter effort to improve outpatient sleeve gastrectomy amid the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic impacted healthcare delivery worldwide. Resource limitations prompted a multicenter quality initiative to enhance outpatient sleeve gastrectomy workflow and reduce the inpatient hospital burden. OBJECTIVES: This study aimed to determine the efficacy of this initiative, as well as the safety of outpatient sleeve gastrectomy and potential risk factors for inpatient admission. SETTING: A retrospective analysis of sleeve gastrectomy patients was conducted from February 2020 to August 2021. METHODS: Inclusion criteria were adult patients discharged on postoperative day 0, 1, or 2. Exclusion criteria were body mass index ≥60 kg/m2 and age ≥65 years. Patients were divided into outpatient and inpatient cohorts. Demographic, operative, and postoperative variables were compared, as well as monthly trends in outpatient versus inpatient admission. Potential risk factors for inpatient admission were assessed, as well as early Clavien-Dindo complications. RESULTS: Analysis included 638 sleeve gastrectomy surgeries (427 outpatient, 211 inpatient). Significant differences between cohorts were age, co-morbidities, surgery date, facility, operative duration, and 30-day emergency department (ED) readmission. Monthly frequency of outpatient sleeve gastrectomy rose as high as 71% regionally. An increased number of 30-day ED readmissions was found for the inpatient cohort (P = .022). Potential risk factors for inpatient admission included age, diabetes, hypertension, obstructive sleep apnea, pre-COVID-19 surgery date, and operative duration. CONCLUSION: Outpatient sleeve gastrectomy is safe and efficacious. Administrative support for extended postanesthesia care unit recovery was critical to successful protocol implementation for outpatient sleeve gastrectomy within this large multicenter healthcare system, demonstrating potential applicability nationwide.

Breast Cancer Predisposition Genes and Synthetic Lethality.

BRCA1 and BRCA2 are tumor suppressor genes with pivotal roles in the development of breast and ovarian cancers. These genes are essential for DNA double-strand break repair via homologous recombination (HR), which is a virtually error-free DNA repair mechanism. Following BRCA1 or BRCA2 mutations, HR is compromised, forcing cells to adopt alternative error-prone repair pathways that often result in tumorigenesis. Synthetic lethality refers to cell death caused by simultaneous perturbations of two genes while change of any one of them alone is nonlethal. Therefore, synthetic lethality can be instrumental in identifying new therapeutic targets for BRCA1/2 mutations. PARP is an established synthetic lethal partner of the BRCA genes. Its role is imperative in the single-strand break DNA repair system. Recently, Olaparib (a PARP inhibitor) was approved for treatment of BRCA1/2 breast and ovarian cancer as the first successful synthetic lethality-based therapy, showing considerable success in the development of effective targeted cancer therapeutics. Nevertheless, the possibility of drug resistance to targeted cancer therapy based on synthetic lethality necessitates the development of additional therapeutic options. This literature review addresses cancer predisposition genes, including BRCA1, BRCA2, and PALB2, synthetic lethality in the context of DNA repair machinery, as well as available treatment options.

The maternal microbiome modulates fetal neurodevelopment in mice.

'Dysbiosis' of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly associated with abnormalities in brain function and behaviour of the offspring4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during critical prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small molecules in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioural tasks, but no overt differences in many other sensorimotor behaviours. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.