Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria.

OBJECTIVE: The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. METHODS: This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. RESULTS: Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23). CONCLUSION: Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

Concurrent uterine surgery and uptake of hormone therapy in patients undergoing bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications.

OBJECTIVE: This study aimed to analyze factors associated with concurrent uterine surgery in patients undergoing bilateral salpingo-oophorectomy (BSO) for risk reducing or therapeutic purposes. Additionally, trends in surgical choice and uptake of post-operative hormone therapy (HT) were examined. METHODS: A 10-year retrospective study was conducted on patients who underwent risk-reducing or therapeutic BSO at one institution. Multinomial regression analysis of patient and case characteristics was performed evaluating associations with surgery type (BSO, BSO and hysterectomy, or BSO and endometrial sampling). Trends in surgery type and uptake of HT post operatively are described. RESULTS: Among the study sample of 643 patients, 140 (22%) patients underwent therapeutic BSO for a history of hormone receptor (HR) positive breast cancer, while the remainder underwent risk-reducing BSO due to a pathogenic variant and/or family history. Pathogenic variants included BRCA1 (141, 40%) BRCA2 (173, 49%), and Lynch syndrome genes (15, 4%). Regression analysis revealed significant associations between concurrent hysterectomy and Black race (RR = 3.55, CI = 1.51-8.38, p = 0.004), history of HR positive breast cancer (RR = 1.88, CI = 1.03-3.42, p = 0.04), and surgeon (Surgeon 1, RR = 2.43, CI = 1.36-4.35, p = 0.003). Among eligible patients under age 51, 36% initiated HT. Over the study period, concurrent hysterectomy rates declined while endometrial sampling increased. CONCLUSIONS: Rates of hysterectomy declined over the study period and slightly more than one-third of eligible patients utilized post-operative HT. Further research on concurrent uterine surgery is needed to establish standardized treatment recommendations in the risk-reducing and therapeutic BSO population. Additionally, education regarding the benefits of postoperative HT in eligible patients is warranted.

Postpartum depression, mode of delivery, and indication for unscheduled cesarean delivery: a retrospective cohort study.

OBJECTIVES: To examine the relationship between postpartum depression (PPD), mode of delivery (MOD), and indication for unscheduled cesarean delivery (uCD). METHODS: Patients with antenatal and postpartum Edinburgh Postnatal Depression Scale (EPDS) scores were compared by MOD and indication for uCD if applicable. Patients with an antenatal EPDS>12 were excluded to ascertain the incidence of new depression. The primary outcome was EPDS≥13 by MOD. The secondary outcome was EPDS≥13 by indication for uCD. RESULTS: Seven hundred and thirty eight patients met inclusion criteria. There were statistically significant differences in MOD by age, race, BMI, and multi-gestation pregnancy. Patients delivered via uCD had a higher rate of peripartum complications and NICU admission. There were no differences in medical comorbidities or use of psychiatric medications by MOD. There was no difference in EPDS by MOD. The rate of PPD was higher in patients with uCD for non-reassuring fetal heart tones (NRFHT) compared to other indications for uCD (p=0.02). CONCLUSIONS: While there was no difference in the incidence of PPD by MOD, the incidence of PPD was higher among patients delivered via uCD for NRFHT. These findings may have implications for patient counseling, post-operative mental health surveillance, and support of postpartum patients.

Perinatal depression before and during the COVID-19 pandemic in New York City.

BACKGROUND: Quarantining and isolation during previous pandemics have been associated with higher levels of depression symptomatology. Studies in other countries found elevated rates of anxiety and/or depression among pregnant people during the COVID-19 pandemic compared with prepandemic rates. New York City was the initial epicenter of the pandemic in the United States, and the effects of the pandemic on perinatal depression in this population are not well known. OBJECTIVE: This study aimed to evaluate the rates of perinatal depression before and during the COVID-19 pandemic. STUDY DESIGN: This is a single-center retrospective cohort study of patients screened for perinatal depression with the Edinburgh Postnatal Depression Scale at 2 private academic practices in New York City. This screen is done in these practices at the time of the glucose challenge test and at the postpartum visit. Patients aged ≥18 years who completed a screen at a postpartum visit and/or glucose challenge test from February 1, 2019 to July 31, 2019 and from February 1, 2020 to July 31, 2020 were identified, and the 2019 and 2020 groups were compared. The primary outcome was a positive screen, defined as ≥13 and ≥15 for postnatal and prenatal screens, respectively. Secondary outcomes included monthly changes in rates of positive screens and factors associated with perinatal depression. Data were analyzed using Mann-Whitney U test, chi-square, or Fisher exact test, and univariate and multivariate analyses with P<.05 defined as significant. RESULTS: A total of 1366 records met the inclusion criteria; 75% of the prepandemic (2019) records were included, as opposed to 65% of pandemic (2020) records due to a lower screen completion rate in the pandemic cohort. The 2020 cohort had a higher proportion of Hispanic patients (P=.003) and higher rates of diabetes mellitus (P=.007), preterm labor (P=.03), and current or former drug use (P<.001). The 2019 cohort had higher rates of hypertension (P=.002) and breastfeeding (P=.03); 4.6% of the 2020 cohort had a suspected or confirmed COVID-19 infection. There was no difference in perinatal depression between the 2019 and 2020 cohorts (2.8% vs 2.6%; P>.99). This finding persisted after adjusting for baseline differences (adjusted odds ratio, 0.89; 95% confidence interval, 0.38-1.86; P=.76). There were no differences in rates of positive Edinburgh Postnatal Depression Scale by month. Several risk factors were associated with a positive screen, including being unmarried (P<.001), pulmonary disease (P=.02), depression (P<.001), anxiety (P=.01), bipolar disorder (P=.009), and use of anxiolytics (P=.04). CONCLUSION: There were no differences in the rates of perinatal depression between the periods before and during the COVID-19 pandemic. The rate of perinatal depression in this cohort was below the reported averages in the literature. Fewer women were screened for perinatal depression in 2020, which likely underestimated the prevalence of depression in our cohort. These findings highlight potential gaps in care in a pandemic setting.

Tracking Electron Uptake from a Cathode into Shewanella Cells: Implications for Energy Acquisition from Solid-Substrate Electron Donors.

While typically investigated as a microorganism capable of extracellular electron transfer to minerals or anodes, Shewanella oneidensis MR-1 can also facilitate electron flow from a cathode to terminal electron acceptors, such as fumarate or oxygen, thereby providing a model system for a process that has significant environmental and technological implications. This work demonstrates that cathodic electrons enter the electron transport chain of S. oneidensis when oxygen is used as the terminal electron acceptor. The effect of electron transport chain inhibitors suggested that a proton gradient is generated during cathode oxidation, consistent with the higher cellular ATP levels measured in cathode-respiring cells than in controls. Cathode oxidation also correlated with an increase in the cellular redox (NADH/FMNH2) pool determined with a bioluminescence assay, a proton uncoupler, and a mutant of proton-pumping NADH oxidase complex I. This work suggested that the generation of NADH/FMNH2 under cathodic conditions was linked to reverse electron flow mediated by complex I. A decrease in cathodic electron uptake was observed in various mutant strains, including those lacking the extracellular electron transfer components necessary for anodic-current generation. While no cell growth was observed under these conditions, here we show that cathode oxidation is linked to cellular energy acquisition, resulting in a quantifiable reduction in the cellular decay rate. This work highlights a potential mechanism for cell survival and/or persistence on cathodes, which might extend to environments where growth and division are severely limited.IMPORTANCE The majority of our knowledge of the physiology of extracellular electron transfer derives from studies of electrons moving to the exterior of the cell. The physiological mechanisms and/or consequences of the reverse processes are largely uncharacterized. This report demonstrates that when coupled to oxygen reduction, electrode oxidation can result in cellular energy acquisition. This respiratory process has potentially important implications for how microorganisms persist in energy-limited environments, such as reduced sediments under changing redox conditions. From an applied perspective, this work has important implications for microbially catalyzed processes on electrodes, particularly with regard to understanding models of cellular conversion of electrons from cathodes to microbially synthesized products.