Drug Development.

Background: VY-TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer's disease (AD). Both VY-TAU01 and its parental mouse IgG1 mAb Ab-01 target an epitope in the C-terminus of tau, bind pathological tau with high affinity and selectivity over wild-type tau, block paired helical filament seed-induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J-Tg[Thy1-MAPT*P301S]2541Godt) brain. Ab-01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.

Drug Development.

Background: A traditional method for validating a surrogate endpoint typically involves assessing the correlation between changes in biomarkers and changes in clinical endpoints using Pearson's and/or Spearman's correlation. However, this approach may not provide an accurate representation of the true correlation due to several reasons: (i) it only considers the change from baseline to the last visit and does not use all post-baseline longitudinal data; (ii) the raw change has large variability; (iii) it does remove the within-subject variability. The objective of this presentation is to propose two alternative approaches that overcome these limitations and allow for a more accurate estimation of the true correlation using all available longitudinal data.

Drug Development.

Although amyloid b immunotherapies offer great potential for prevention or delay of symptoms in dominantly inherited AD (DIAD), the mechanism of action of this class of medications does not address the underlying mechanism of most DIAD mutations. Moreover, the need for repeated IV infusions or sub-cutaneous injections with Ab immunotherapies may prove challenging for long-term prevention approaches. The majority of DIAD mutations appear to affect the interaction of the gamma-secretase enzyme with the Amyloid Precursor Protein (APP) making this enzyme an attractive target for disease modification.

Dementia Care Research and Psychosocial Factors.

Background: Rapidly progressive dementia (RPD) is variably defined across published cohorts. A standardized definition is needed to support multicenter studies required to inform the causes of RPD and optimize recognition and management of treatment-responsive causes. An optimal definition will capture the broad spectrum of causes of RPD, adequately differentiate patients with rapid and typically progressive presentations of neurodegenerative disease, and be reliably implemented across healthcare settings and centers.

Dementia Care Practice.

Implementation of amyloid-lowering treatments in clinical care for early symptomatic Alzheimer disease (AD) raises many challenges. The Memory Diagnostic Center (MDC), the dementia specialty practice associated with Barnes-Jewish Hospital/Washington University School of Medicine (BJH/WUSM), has 16 clinicians (12 physicians and 4 advanced practice providers) who see over 2,000 patients with memory disorders per year. BJH is the academic flagship of BJC HealthCare (BJC), an integrated health system in St.

Comparison of Associations of Food Security Instruments and Mediators With Premature All-Cause and Cardiovascular Disease Death in US Adults.

Background: Food insecurity is associated with high morbidity and mortality and is typically measured with the 10-item US Adult Food Security Survey Module. Shorter instruments may capture similar information, but this has not been validated against mortality in general populations.

Methods: A nationally representative sample of individuals aged 20 to 74 years from the US National Health Interview Survey 2011 to 2018 was included, with deaths linked to the National Death Index through 2019.

Predictive value of neutrophil-to-lymphocyte ratio and MELD score for short-term survival of patients with HBV-DeCi.

Objective: The prognostic value of neutrophil-to-lymphocyte ratio (NLR) combined with Model for End-Stage Liver Disease (MELD) score was evaluated for hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi).

Methods: The 30-day mortality of 166 hBV-DeCi patients was examined. Receiver operating characteristic curve analysis and multivariate regression analysis were used to assess the performance of NLR for prediction of poor outcomes.

Trends and disparities in cardiovascular disease-related mortality among adults with myeloproliferative neoplasms in USA.

Aims: We aimed to perform a retrospective cohort study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyse the trends in cardiovascular disease (CVD)-related mortality in patients with myeloproliferative neoplasms (MPNs) from 1999 to 2020.

Methods And Results: We analysed the death certificate data from the CDC WONDER database from 1999 to 2020 for CVD with co-morbid myeloproliferative disorders in the US population. Age-adjusted mortality rates (AAMRs) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population.

Hospital-level volume in extracorporeal membrane oxygenation cases and death or disability at 6 months.

Objective: Extracorporeal membrane oxygenation (ECMO) is a high-risk procedure with significant morbidity and mortality and there is an uncertain volume-outcome relationship, especially regarding long-term functional outcomes. The aim of this study was to examine the association between ECMO centre volume and long-term death and disability outcomes.

Design Setting And Participants: This is a registry-embedded observational cohort study.

Fetal Tetra-Amelia Birth: A Case Report.

Fetal limb anomaly presentation varies greatly. It can present as amelia (complete absence of skeletal part of one or more limb), meromelia (partial absence of skeletal part of one or more limb), phocomelia (only rudimentary limb formed), and minor limb disorders like polydactyly. The complete absence of the four fetal limbs is extremely rare.

Intracranial Gunshot Wounds: An Assessment of Patient Characteristics on Surgical Outcomes.

Background/objective: Intracranial gunshot wounds (GSW) are often fatal, with most patients dying before intervention can occur. Surgical management, when indicated, results in decreased mortality. We sought to assess the neurosurgical outcomes and economic costs of intracranial GSW.

" " Exploring the Experiences of Black and Hispanic Parents following a Congenital Heart Disease Diagnosis.

 Congenital heart disease (CHD) is an important contributor to pediatric morbidity and mortality. Unfortunately, disparities in the diagnosis and treatment of CHD exist across racial and ethnic groups. The objective of this study was to share the experiences of Hispanic and Black families with CHD to better understand their needs.

Automated line-clearing chest tubes reduce postoperative pain and atrial fibrillation after cardiac surgery.

Objective: Recent advancements in chest tube technologies have gained interest for their ability to enhance postoperative recovery via reduction of retained blood syndrome after cardiothoracic surgery. The present study investigates the effect of the Centese Thoraguard automated line-clearance chest tube system on postoperative pain and recovery after cardiac surgery.

Methods: This was a single-center retrospective review of 1771 adult patients undergoing nonemergency cardiac surgery between January 2021 and December 2022.

Superior transseptal versus left atriotomy approaches in isolated mitral valve surgery.

Objective: The superior transseptal approach to mitral valve surgery offers improved exposure compared with left atriotomy; however, concerns remain regarding postoperative arrhythmias and pacemaker placement. This study investigates intraoperative parameters and postoperative outcomes in these approaches.

Methods: Retrospective review of 259 adults undergoing isolated mitral valve repair or replacement over a 10-year period was performed.

Noniatrogenic hypoglycemia: A universal marker for poor outcomes.

Objective: Previous retrospective studies have established a relationship between postoperative hypoglycemia and adverse outcomes after cardiac surgery, but none have accounted for the cause of hypoglycemia.

Methods: A retrospective review was performed of patients who underwent cardiac surgery at a single institution between 2016 and 2021. Patients were categorized as hypoglycemic if they had 1 or more postoperative blood glucose measurement less than 70 mg/dL and normoglycemic otherwise.

Heart transplant survival and the use of donors with intracranial bleeding: United Network for Organ Sharing Registry propensity-score matched analysis.

Objective: The transplantation of hearts from donors who experienced intracranial bleeding (ICB) has been associated with inferior long-term survival in both single-center analyses and, more recently, with the United Network for Ogan Sharing Registry. The purpose of this study was to further explore this relationship through propensity score matching in recipients receiving donor hearts from ICB and non-ICB donors in a large national registry.

Methods: We performed a retrospective cohort analysis of the United Network for Organ Sharing Registry Organ Procurement and Transplantation Network between 2006 and 2018 for adult candidates wait-listed for isolated heart transplantation.

[Research progress on the early warning effectiveness of early warning score in patients with in-hospital cardiac arrest].

In-hospital cardiac arrest (IHCA) is a critical medical issue threatening the survival and prognosis of hospitalized patients, characterized by high incidence, high mortality and poor prognosis. Early warning and intervention for IHCA are urgently needed. The early warning score (EWS) is developed as a point-of-care warning tool for early identification and intervention of hospitalized patients with deteriorating condition.

Intravenous branched-chain amino acid administration for the acute treatment of hepatic encephalopathy: a systematic review and meta-analysis.

Background: Hepatic encephalopathy (HE) is a severe complication of acute hepatic failure requiring urgent critical care management. Branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine have been investigated as potential treatments to improve outcomes in patients with acute HE. However, the effectiveness of BCAA administration during the acute phase remains unclear.

Inflammatory markers link triglyceride-glucose index and obesity indicators with adverse cardiovascular events in patients with hypertension: insights from three cohorts.

Background: Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated.

Methods: This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis.

Association of remote work with tobacco and alcohol use: a cross-sectional study in Japan.

Background: Remote work allows one to work free from workplace policy, but it may negatively affect health-related behaviors such as tobacco product use and alcohol drinking. Our study aimed to investigate the association of remote work with tobacco dependence and hazardous alcohol use.

Methods: This nationwide Internet-based survey was conducted in Japan in February 2023.

Triacylglycerol mobilization underpins mitochondrial stress recovery.

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response.

Medical large language models are vulnerable to data-poisoning attacks.

The adoption of large language models (LLMs) in healthcare demands a careful analysis of their potential to spread false medical knowledge. Because LLMs ingest massive volumes of data from the open Internet during training, they are potentially exposed to unverified medical knowledge that may include deliberately planted misinformation. Here, we perform a threat assessment that simulates a data-poisoning attack against The Pile, a popular dataset used for LLM development.

Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions.