Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

Purpose: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.

Methods: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.

Results: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively.

Disease duration in autosomal dominant familial Alzheimer disease: A survival analysis.

Objective: To use survival modeling to estimate disease duration in autosomal dominant familial Alzheimer disease (ADAD) and ascertain whether factors influencing age at onset also affect survival.

Methods: Symptomatic mutation carriers (201 presenilin 1 [] and 55 amyloid precursor protein []) from ADAD families referred to the Dementia Research Centre, between 1987 and 2019, were included. Survival was assessed with respect to age at onset, year of birth, ε4 status, cognitive presentation, and sex using multilevel mixed-effects Weibull survival models.

Genetic testing in dementia - utility and clinical strategies.

Techniques for clinical genetic testing in dementia disorders have advanced rapidly but remain to be more widely implemented in practice. A positive genetic test offers a precise molecular diagnosis, can help members of an affected family to determine personal risk, provides a basis for reproductive choices and can offer options for clinical trials. The likelihood of identifying a specific genetic cause of dementia depends on the clinical condition, the age at onset and family history.

Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.

Objectives: Mortality associated with sickle cell disease (SCD) is high in many low- and middle-income countries (LMICs). Hydroxyurea, a medicine to effectively manage SCD, is not widely available in resource-constrained settings. We identified and synthesised the reported implementation outcomes for the therapeutic use of hydroxyurea for SCD in these settings.

Sex Differences in the Longitudinal Course and Outcome of Bipolar Disorder in Youth.

Objective: Despite substantial literature on sex differences in adults with bipolar disorder (BD), little is known about this topic in youth; this study examines sex differences in mood symptomatology and psychiatric comorbidity in prospectively followed youth with BD.

Methods: A subsample of the Course and Outcome of Bipolar Youth study (N = 370; female n = 199, male n = 171) enrolled October 2000-July 2006 (age at intake = 7-17.11 years) who met DSM-IV criteria for bipolar I disorder (BD-I; n = 221), bipolar II disorder (BD-II; n = 26), or operationalized BD not otherwise specified (BD-NOS; n = 123) with ≥ 4 years follow-up was included.

Reducing CO Emissions from U.S. Steel Consumption by 70% by 2050.

The steel sector emits 25% of global industrial greenhouse gases, and the U.S. is the world's second-largest steel consumer.

The age-dependent associations of white matter hyperintensities and neurofilament light in early- and late-stage Alzheimer's disease.

Neurofilament light (NFL) is an emerging marker of axonal degeneration. This study investigated the relationship between white matter hyperintensities (WMHs) and plasma NFL in a large elderly cohort with, and without, cognitive impairment. We used the Alzheimer's Disease Neuroimaging Initiative and included 163 controls, 103 participants with a significant memory concern, 279 with early mild cognitive impairment (EMCI), 152 with late mild cognitive impairment (LMCI), and 130 with Alzheimer's disease, with 3T MRI and plasma NFL data.

Sleep Disturbances in Young Adults with Childhood Traumatic Brain Injury: Relationship with Fatigue, Depression, and Quality of Life.

Objective: This study assessed the consequences of childhood traumatic brain injury (TBI) on sleep, fatigue, depression, and quality of life (QoL) outcomes and explored the relationships between these variables at 20 years following childhood TBI.

Participants: We followed up 54 young adults with mild, moderate, and severe TBI, and 13 typically developing control (TDC) participants, recruited at the time of TBI.

Methods: Sleep was assessed with the Pittsburgh Sleep Quality Index and actigraphy.

Are trainees working in obstetrics and gynecology confident and competent in the care of frail gynecological oncology patients?

Introduction: Older patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients.

Quantitative detection and staging of presymptomatic cognitive decline in familial Alzheimer's disease: a retrospective cohort analysis.

Background: Understanding the earliest manifestations of Alzheimer's disease (AD) is key to realising disease-modifying treatments. Advances in neuroimaging and fluid biomarkers have improved our ability to identify AD pathology in vivo. The critical next step is improved detection and staging of early cognitive change.

Implementation outcomes of policy and programme innovations to prevent obstetric haemorrhage in low- and middle-income countries: a systematic review.

Globally, obstetric haemorrhage (OH) remains the leading cause of maternal mortality. Much of the associated mortality is ascribed to challenges surrounding deployment of innovations rather than lack of availability. In low- and middle-income countries (LMICs), where the burden is highest, there is a growing interest in implementation research as a means to bridge the 'know-do' gap between proven interventions and their reliable implementation at scale.

Recurrent spontaneous coronary artery dissection in a middle-aged male athlete patient: a case report.

Background: Spontaneous coronary artery dissection (SCAD) is a rare condition, mainly affecting young women. Cases in male patients are rare, especially with recurrence.

Case Summary: A 59-year-old male non-elite athlete presented as an ST-elevation myocardial infarction following a 5-km run.

Measuring cortical mean diffusivity to assess early microstructural cortical change in presymptomatic familial Alzheimer's disease.

Background: There is increasing interest in improving understanding of the timing and nature of early neurodegeneration in Alzheimer's disease (AD) and developing methods to measure this in vivo. Autosomal dominant familial Alzheimer's disease (FAD) provides the opportunity for investigation of presymptomatic change. We assessed early microstructural breakdown of cortical grey matter in FAD with diffusion-weighted MRI.

The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study.

Background: Lynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention; it also enables cascade testing of relatives. A growing consensus supports LS screening in EC; however, the expected proportion of test positives, and optimal testing strategy is uncertain.

Assessment of mismatch repair deficiency in ovarian cancer.

Background: Hereditary causes of ovarian cancer include Lynch syndrome, which is due to inherited pathogenic variants affecting one of the four mismatch repair genes involved in DNA repair. The aim of this study was to evaluate tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years.

Methods: Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, promoter methylation testing followed by constitutional testing for Lynch syndrome.

Neuroimaging in paediatric mild traumatic brain injury: a systematic review.

Neuroimaging is being increasingly applied to the study of paediatric mild traumatic brain injury (mTBI) to uncover the neurobiological correlates of delayed recovery post-injury. The aims of this systematic review were to: (i) evaluate the neuroimaging research investigating neuropathology post-mTBI in children and adolescents from 0-18 years, (ii) assess the relationship between advanced neuroimaging abnormalities and PCS in children, (iii) assess the quality of the evidence by evaluating study methodology and reporting against best practice guidelines, and (iv) provide directions for future research. A literature search of MEDLINE, PsycINFO, EMBASE, and PubMed was conducted.

Delineating the Nature and Correlates of Social Dysfunction after Childhood Traumatic Brain Injury Using Common Data Elements: Evidence from an International Multi-Cohort Study.

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase.

Validation of an adapted instrument to measure female genital fistula-related stigma.

Female genital fistula results in severe physical, psychological, and social sequelae. Qualitative research confirms stigma pervasiveness; however, no quantitative instrument exists to measure fistula-related stigma. We adapted an existing HIV-related stigma instrument to fistula-related stigma and assessed its reliability and validity.

Impact of stent thickness on clinical outcomes in small vessel and bifurcation lesions: a RAIN-CARDIOGROUP VII sub-study.

Background: The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population.

Methods: All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.

A mismatch in care: results of a United Kingdom-wide patient and clinician survey of gynaecological services for women with Lynch syndrome.

Objective: To describe the current testing practice, referral pathways and gynaecological services available to women with Lynch syndrome (LS) in the UK.

Design: Cross-sectional nationwide survey of gynaecological oncologists and women with LS.

Setting: United Kingdom.

Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database.

Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome.

Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT.

BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: A cohort study.

Background: An association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit.

Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.

Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD).