Survey of Urogynecology Fellows on the Care of Patients with Differences in Sex Development/Intersex Traits.

Introduction And Hypothesis: Patients with differences in sex development or intersex traits (DSD/I) struggle to find clinically competent care in adulthood. We sought to describe the surgical exposure of Urogynecology and Reconstructive Pelvic Surgery (URPS) fellows who had previously trained in ObGyn (URPS-Gyn) to patients with DSD/I and their interest in performing 18 relevant procedures. We hypothesized that most graduating fellows would not have had exposure to many of the surgeries.

A field resource for the glioma cerebrospinal fluid proteome: impacts of resection and location on biomarker discovery.

Background: While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown.

Methods: Aptamer-based proteomics was performed on 147 CSF samples from 74 patients, 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas.

How I Diagnose and Treat Acute Infection-associated Purpura Fulminans.

Purpura fulminans (PF) is a rare but devastating complication of sepsis characterized by a highly thrombotic subtype of disseminated intravascular coagulation (DIC). A medical emergency, PF cases often require the involvement of consultant hematologists to assist with diagnosis and management of patients who are in a highly dynamic and deteriorating clinical situation. Patients who survive past the first 24 to 72 hours often die from complications of unchecked thrombosis rather than from shock, and survivors are usually left with severe scarring and tissue loss.

Pain Coping Skills Training for Patients Receiving Hemodialysis: The HOPE Consortium Randomized Clinical Trial.

Importance: Chronic pain is common among individuals with dialysis-dependent kidney failure.

Objective: To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference.

Design, Setting, And Participants: This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US.

Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: Primary analysis of the ELM-1 study.

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) progressing after chimeric antigen receptor T-cell therapy (CAR T) have dismal outcomes. The prespecified post-CAR T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR T. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression.

High-resolution awake mouse fMRI at 14 tesla.

High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts.

Biomarkers.

Background: In recent efforts to improve early identification, staging, and prediction of risk of persons at risk for vascular contributions to cognitive impairment and dementia (VCID) in relation with small vessel disease (SVD), the MarkVCID consortium has worked to identify and validate fluid- and imaging-based biomarkers for SVD associated with VCID. Free water (FW) measured derived from diffusion tensor imaging and one of the selected neuroimaging biomarker "kits", has been demonstrated to have excellent instrumental validity and to be a sensitive biomarker of cognitive performances. We sought to further examine FW clinical relevance by investigating whether FW predicts cognitive worsening over time.

Biomarkers.

Background: The MarkVCID consortium was established to address the paucity of biomarkers for vascular contributions to cognitive impairment and dementia (VCID), a leading cause of dementia. Plasma neurofilament light (NfL), a neuroaxonal injury marker elevated in several neurological and neurodegenerative diseases, was selected as one of the first biomarkers to be examined. We performed comprehensive instrumental and clinical validation of the Quanterix Simoa NfL assay using the first MarkVCID cohort.

Biomarkers.

Background: Plasma tau phosphorylated at threonine 231 (p-tau231) is a promising novel biomarker of emerging Alzheimer's disease (AD) pathology. We aimed to characterize cross-sectional and longitudinal plasma p-tau231 measurements and estimated ages of biomarker onset in an exceptionally large number of presenilin (PSEN1) E280A (Glu280Ala) mutation carriers and age-matched non-carriers from the Colombian autosomal dominant Alzheimer's disease kindred.

Method: We included a cohort of 722 PSEN1 E280A mutation carriers (mean age 36.

Biomarkers.

Background: Mild Cognitive Impairment (MCI) is the prodromal stage of dementia, including Alzheimer's Disease (AD). Early identification and accurate assessment of MCI are critical for clinical trial enrichment as well as the early intervention of AD. Digital makers offered a unique opportunity for ecologically valid and affordable early detection approaches.

Biomarkers.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Biomarkers.

Background: Peak-width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)-related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD and worse cognitive function. Therefore, we proposed PSMD as a risk stratification biomarker for VCID.

Biomarkers.

Background: Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta-amyloid (Aβ) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at different disease stages appears ideal to developing and evaluating therapeutics.

Biomarkers.

Background: Enlarged perivascular spaces (ePVS) on MRI can signal impaired cerebral fluid clearance and predict dementia risk. Risk factors and biological correlates of ePVS are uncertain partially due to the lack of pathological correlation studies. Repetitive head impacts (RHI) from contact sports might represent one risk factor for ePVS, given their association with vascular pathologies and chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by perivascular p-tau aggregates.

Biomarkers.

Background: In AD, tauopathy and atrophy start in the mesiotemporal lobe, including the amygdala-hippocampal complex. Until recently, subnuclei and subfields within these structures were indistinguishable in-vivo. FreeSurfer 7.

Biomarkers.

Background: This study introduces the Automated High-purity Exosome isolation-based AD diagnostics system (AHEADx). By analyzing and understanding the molecular cargo (proteins and miRNAs) carried by circulating exosomes, researchers found brain-derived exosome (BDE) levels of P-S396-tau, P-T181-tau, and Aβ1-42 are elevated up to 10 years prior to clinical symptoms. Currently, there is no available technology capable of simultaneously isolating and screening exosomal biomarkers for efficient and personalized precision medicine giving early AD diagnosis.

Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.

Objective: Despite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.

Methods: We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty.

Malpractice Liability Exposure and the Sports Medicine Team Physician: Caring for Professional Athletes in the National Football League, Major League Baseball, and National Hockey League.

Background: Orthopaedic surgeons play a critical role in ensuring the health and safety of professional athletes. Despite the privilege of treating elite athletes, there exists great financial exposure to individual physicians in the event of a malpractice lawsuit.

Hypothesis/purpose: The purpose of this study was to evaluate and model malpractice liability exposure of the sports medicine surgeon caring for athletes in the National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) with respect to player position and additional supplemental malpractice insurance needs.

Biomarkers.

Background: Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting-state functional connectivity are associated with reduced β-amyloid (Aβ)-related cognitive decline in cognitively unimpaired older adults, who were predominantly Aβ negative. This suggests that these networks might support cognitive resilience in the face of early AD pathology but it remains unclear whether these effects are apparent in preclinical AD. We investigated whether left-FPCN, right-FPCN, and DMN connectivity moderated the effect of Aβ on cognitive decline using a large multi-site dataset from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.

Biomarkers.

Background: Oxidative stress, which refers to an imbalance between the production of reactive oxygen/nitrogen species (ROS/RNS) and the body's antioxidant defense mechanisms, is implicated in the pathogenesis of various chronic diseases by promoting cellular damage, inflammation, and dysfunction. Numerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the ROS/RNS reactions, particularly quasi-stable oxidized products, have been much less explored.

Method: In this report, we discovered that acetylacetone, a core moiety of curcumins, is a new scaffold for generating chemiluminescence in the presence of oxidants.

Biomarkers.

Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Biomarkers.

Background: Validating the predictive value of plasma markers for Alzheimer's disease, cerebrovascular disease and cognitive dysfunction in older adults representative of primary care settings, is needed to guide prevention and treatment decisions.

Method: At baseline, single molecule array plasma measures of Aβ42/40, pTau217, pTau181, GFAP and NfL were collected from 625 dementia-free participants from the population-based Rotterdam Study (mean age 63 years [range 54-84], 51% women). After a mean follow-up time of seven years [range 5-9], participants underwent amyloid F-florbetaben PET, brain MRI, and cognitive assessment.