Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease

Prolonged operative time of repeat cesarean is a risk marker for post-operative maternal complications

Abstract Background Repeat cesarean delivery (CD) accounts for approximately 15% of all annual deliveries in the US with an estimated 656,250 operations per year. We aimed to study whether prolonged operative time (OT; skin incision to closure) is a risk marker for post-operative maternal complications among women undergoing repeat CD. Methods We conducted a cross-sectional retrospective study in a single tertiary center including all women who underwent repeat CD but excluding those with cesarean hysterectomy. Prolonged OT was defined as duration of CD longer than the 90th percentile duration on record for each specific surgeon in order to correct for technique differences between surgeons. Bi-variate analysis was used to study the association of prolonged OT with each one of the following maternal complications: post-operative blood transfusion, prolonged maternal hospitalization (defined as hospitalization duration longer than 1 week post-CD), infection necessitating antibiotics, re-laparotomy within 7 days post-CD, and re-admission within 42 days post-CD. A multivariate regression analysis was performed controlling for maternal age, ethnicity, parity, number of fetus, gestational age at delivery, trial of labor after cesarean, anesthesia, and number of previous CDs. The adjusted odd ratio was calculated for each complication independently and for a composite adverse maternal outcome defined as any one of the above. Results A total of 6507 repeat CDs were included; prolonged OT was highly associated (P value < 0.000) with: post-operative blood transfusion (4.4% vs. 1.5%), prolonged hospitalization (8.4% vs. 4.0%), infection necessitating antibiotics (2% vs. 1%), and readmission (1.8% vs. 0.8%) when compared to control. The composite adverse maternal outcome was also associated with prolonged OT (20.2% vs. 11.2%, p < 0.000). These correlations remained statistically significant in the multivariate regression analysis when controlling for confounders. Conclusions Among women undergoing repeat CD, prolonged OT (reflecting CD duration greater than 90th percentile for the specific surgeon) is a risk marker for post-operative maternal complications

Real World Cost-Effectiveness Analysis of Population Screening for BRCA Variants among Ashkenazi Jews Compared with Family History-Based Strategies

Identifying carriers of pathogenic BRCA1/BRCA2 variants reduces cancer morbidity and mortality through surveillance and prevention. We analyzed the cost-effectiveness of BRCA1/BRCA2 population screening (PS) in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with two existing strategies: cascade testing (CT) in carrier&rsquo;s relatives (&ge;25% carrier probability) and international family history (IFH)-based guidelines (&gt;10% probability). We used a decision analytic-model to estimate quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratio for PS vs. alternative strategies. Analysis was conducted from payer-perspective, based on actual costs. Per 1000 women, the model predicted 21.6 QALYs gained, a lifetime decrease of three breast cancer (BC) and four ovarian cancer (OC) cases for PS vs. CT, and 6.3 QALYs gained, a lifetime decrease of 1 BC and 1 OC cases comparing PS vs. IFH. PS was less costly compared with CT (&minus;3097 USD/QALY), and more costly than IFH (+42,261 USD/QALY), yet still cost-effective, from a public health policy perspective. Our results are robust to sensitivity analysis; PS was the most effective strategy in all analyses. PS is highly cost-effective, and the most effective screening strategy for breast and ovarian cancer prevention. BRCA testing should be available to all AJ women, irrespective of family history

A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay

Loss of function (LoF) mutations in Optineurin can cause recessive amyotrophic lateral sclerosis (ALS) with some heterozygous LoF mutations associated with dominant ALS. The molecular mechanisms underlying the variable inheritance pattern associated with OPTN mutations have remained elusive. We identified that affected members of a consanguineous Middle Eastern ALS kindred possessed a novel homozygous p.S174X OPTN mutation. Analysis of these primary fibroblast lines from family members identified that the p.S174X mutation reduces OPTN mRNA expression in an allele-dependent fashion by nonsense mediated decay. Western blotting correlated a reduced expression in heterozygote carriers but a complete absence of OPTN protein in the homozygous carrier. This data suggests that the p.S174X truncation mutation causes recessive ALS through LoF. However, functional analysis detected a significant increase in mitophagy markers TOM20 and COXIV, and higher rates of mitochondrial respiration and ATP levels in heterozygous carriers only. This suggests that heterozygous LoF OPTN mutations may not be causative in a Mendelian manner but may potentially behave as contributory ALS risk factors

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease