Combined Bilateral Salpingo-oophorectomy and Cesarean Delivery in BRCA1/2 Alteration Carriers : A Case Series.

BACKGROUND: The cumulative lifetime risk of ovarian cancer is 16-68% and 11-30% in female BRCA1 and BRCA2 gene alteration carriers, respectively. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only proven way to reduce ovarian cancer mortality. We report a series of patients who underwent risk-reducing surgery at the time of planned obstetric-indicated cesarean delivery. CASES: This is a case series of four women carrying a pathogenic germline BRCA1 or BRCA2 gene alteration who underwent RRSO at the time of cesarean delivery between March 1, 2018, and March 31, 2022. All women were referred during pregnancy to the University College London Hospitals Familial Cancer Clinic for consideration of RRSO at the time of obstetric-indicated cesarean delivery. Women were considered eligible for RRSO if they had a proven pathogenic germline alteration, would have completed childbearing after the cesarean delivery, and were older than age 35 or 40 years with BRCA1 or BRCA2 alterations, respectively. Operating time, blood loss, transfusion requirements, length of hospital stay, complications, and ability to breastfeed were assessed and, where possible, compared with the institutional means for similar patients who underwent cesarean delivery only, to determine whether RRSO was associated with increased morbidity. Women were contacted 11-59 months postprocedure to assess satisfaction. The mean blood loss was 687 mL (range 400-1,000 mL), mean operating time was 68 minutes, mean length of hospital stay was 3 days, and mean change in hemoglobin was -1 g/dL. No patient required a transfusion, had internal organ damage, returned to the operating room, or was readmitted. One of two women with intact breast tissue successfully breastfed, and the other chose to bottle feed. The mean contemporaneous institutional blood loss for cesarean delivery was not significantly different at 681 mL for singleton pregnancies and 872 mL for twin pregnancies. All four women reported a high level of satisfaction with the combined procedure. CONCLUSION: Our results show that RRSO can be performed at the time of cesarean delivery with high patient satisfaction. This approach can be offered to appropriately counseled individuals, with the benefit of avoiding the need for two separate procedures, with potentially reduced patient morbidity and health care costs.

Rapid prototyping for quantifying belief weights of competing hypotheses about emergent diseases.

Emerging diseases can have devastating consequences for wildlife and require a rapid response. A critical first step towards developing appropriate management is identifying the etiology of the disease, which can be difficult to determine, particularly early in emergence. Gathering and synthesizing existing information about potential disease causes, by leveraging expert knowledge or relevant existing studies, provides a principled approach to quickly inform decision-making and management efforts. Additionally, updating the current state of knowledge as more information becomes available over time can reduce scientific uncertainty and lead to substantial improvement in the decision-making process and the application of management actions that incorporate and adapt to newly acquired scientific understanding. Here we present a rapid prototyping method for quantifying belief weights for competing hypotheses about the etiology of disease using a combination of formal expert elicitation and Bayesian hierarchical modeling. We illustrate the application of this approach for investigating the etiology of stony coral tissue loss disease (SCTLD) and discuss the opportunities and challenges of this approach for addressing emergent diseases. Lastly, we detail how our work may apply to other pressing management or conservation problems that require quick responses. We found the rapid prototyping methods to be an efficient and rapid means to narrow down the number of potential hypotheses, synthesize current understanding, and help prioritize future studies and experiments. This approach is rapid by providing a snapshot assessment of the current state of knowledge. It can also be updated periodically (e.g., annually) to assess changes in belief weights over time as scientific understanding increases. Synthesis and applications: The rapid prototyping approaches demonstrated here can be used to combine knowledge from multiple experts and/or studies to help with fast decision-making needed for urgent conservation issues including emerging diseases and other management problems that require rapid responses. These approaches can also be used to adjust belief weights over time as studies and expert knowledge accumulate and can be a helpful tool for adapting management decisions.

An integrated biopsychosocial model of childhood maltreatment and psychosis.

There is now a well-established link between childhood maltreatment and psychosis. It is, however, unclear what the mechanisms are by which this occurs. Here, we propose a pathway linking the experience of childhood maltreatment with biological changes in the brain and suggest a psychological intervention to ameliorate its effects.

Set shifting and reversal learning in borderline personality disorder.

BACKGROUND: People with BPD have been shown in some studies to have structural deficits in regions of the prefrontal cortex. A sensitive test of prefrontal cortex function is the intra-dimensional/extra-dimensional (IDED) set shifting task. This study sought to examine whether people with BPD demonstrate impaired performances on extra-dimensional shift (EDS) and reversal learning aspects of this task similar to those seen in conditions such as schizophrenia and bipolar affective disorder. METHOD: Twenty subjects with BPD and 21 healthy control subjects were administered the IDED task from the Cambridge Neuropsychological Test Automated Battery cognitive test battery. EDS and reversal learning errors were compared between the groups using repeated measures ANOVAs. RESULTS: There was no significant difference between the BPD and control participants in EDS or reversal learning on the IDED task or in stage of the task completed. There was a medium effect size difference (Cohen's d = 0.4) for simple reversal learning and small effect sizes for reversal learning (Cohen' d = 0.17) and IDED shift stages (Cohen's d = 0.2 and -0.3 respectively). CONCLUSIONS: Participants with BPD in this study did not show statistically significant deficits in EDS or reversal learning, although small to medium effect sizes were found. These findings distinguish them from sufferers of schizophrenia and bipolar affective disorder and are in keeping with the idea that BPD is a distinct condition with discrete neuropathological processes.

Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia.

Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper-activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk.