Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.

Background: Up to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient.

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial.

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC.

Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.

Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.

Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and CKD.

Background: Chronic kidney disease (CKD) is associated with higher risk of myocardial infarction and anemia. Among patients with anemia and CKD who experience myocardial infarction, it remains uncertain if a liberal red blood cell transfusion threshold strategy (hemoglobin cutoff [Hgb] < 10 g/dL) is superior to a restrictive transfusion threshold (Hgb 7-8 g/dL) strategy.

Methods: Among the 3,504 patients enrolled in the Myocardial Ischemia and Transfusion (MINT) trial with non-missing creatinine, we compared baseline characteristics and 30-day and 6-month outcomes of patients without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.

Genetic and environmental influences on alcohol consumption in middle to late life.

Objective: Alcohol use is common in older adults and linked to poor health and aging outcomes. Studies have demonstrated genetic and environmental contributions to the quantity of alcohol consumption in mid-to-late life, but less is known about whether these influences are moderated by sociodemographic factors such as age, sex, and educational attainment. This study sought to better understand sociodemographic trends in alcohol consumption across the second half of the life course and their underlying genetic and environmental influences.

Atrial Fibrillation and Retinal Stroke.

Importance: Atrial fibrillation (AF) is the most common, chronic, cardiac arrythmia in older US adults. It is not known whether AF is independently associated with increased risk of retinal stroke (central retinal artery occlusion), a subtype of ischemic stroke that causes severely disabling visual loss in most cases and is a harbinger of further vascular events.

Objective: To determine whether there is an association between AF and retinal stroke.

Shared Local Oncology Care After Allogeneic Hematopoietic Cell Transplantation: A Randomized Clinical Trial.

Importance: Although sharing care with local oncologists after allogeneic hematopoietic cell transplantation (HCT) has been proposed for patients living far from HCT centers, it is not known whether a shared strategy is safe or improves patient quality of life (QOL).

Objective: To determine the efficacy and safety of sharing follow-up care after HCT between the HCT specialty center and local oncologists.

Design, Setting, And Participants: This was a multicenter collaborative randomized clinical trial of patients undergoing HCT at Dana-Farber Cancer Institute (DFCI)-a high volume HCT center in Boston (Massachusetts)-and 8 local oncology practices.

A Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

Sex-specific risk factors for new-onset heart failure: the PREVEND study at 25 years.

Background And Aims: Current estimates for the lifetime risk to develop heart failure with either a reduced (HFrEF) or preserved ejection fraction (HFpEF) and their associated risk factors are derived from two studies from the USA. The sex-specific lifetime risk and population attributable fraction of potentially modifiable risk factors for incident HFpEF and HFrEF are described in a large European community-based cohort with 25 years of follow-up.

Methods: A total of 8558 participants from the PREVEND cohort were studied at baseline from 1997 onwards and followed until 2022 for cases of new-onset HFrEF (ejection fraction < 50%) and HFpEF (ejection fraction ≥ 50%) by assessment of hospital records.

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.

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.

Biomarkers.

Background: Alzheimer's disease (AD) causes a steady degradation of connections inside the brain. The apolipoprotein E is a protein where one of its subtypes, APOE4, is a major genetic risk factor for developing late onset AD. Using a combination of tensor network PCA (TN-PCA) and bundle analysis, we sought to determine which specific connections differentiate APOE4 individuals relative to non-APOE4 carriers, and whether these changes increase with age.

Biomarkers.

Background: Emerging evidence underscores the significant influence of diet on risk for Alzheimer's disease and related dementias (ADRD). In particular, a Western dietary pattern associates with increased risk for ADRD, with proposed mediation via inflammatory mechanisms, among others. Although a Western dietary pattern associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate Western diet-associated inflammation and neurodegeneration.

Biomarkers.

Background: Heavy alcohol consumption is associated with increased risk for Alzheimer's disease and related dementias (ADRD), with mixed evidence suggesting a dose-dependent nonlinear effect of alcohol on ADRD. Potential mechanisms by which alcohol may promote or attenuate brain pathology need further exploration. Although chronic alcohol consumption associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate alcohol-associated neurodegeneration and cognitive decline.

Public Health.

Background: Little is known about how education in later life is related to cognitive function in older adults. This study assessed whether participating in later-life education was associated with better cognitive function over time and whether the benefits differed by sex, race/ethnicity, and prior education level in a nationally-representative sample of U.S.

Public Health.

Background: Many studies have demonstrated an association between sleep and cognition in older adults. The Long Life Family Study (LLFS) has followed families enriched with longevity since 2006 and has shown that this cohort has slower rates of cognitive decline than their spouse controls and the general public. Understanding how sleep and cognition are related in this population can improve our understanding of the key to long life.

Public Health.

Background: Although visual and hearing impairment have been identified as established risk factors for dementia, evidence was limited on the association of the coexistence of these two sensory impairments with incident dementia, especially in the U.S. The study aimed to examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease.

Public Health.

Background: Pesticide exposure may contribute to cognitive decline, but empirical evidence is limited. We examined high pesticide exposure events (HPEE) in relation to subjective cognitive decline among farmers in the Pesticide and Sense of Smell Study (PASS), a sub-cohort of the Agricultural Health Study (AHS).

Method: This analysis included 2365 predominantly white male farmers from Iowa and North Carolina (aged 70±10 years) who enrolled in AHS from 1993-1997 and participated in PASS in 2020-2021.

Biomarkers.

Background: Postoperative delirium (POD) is characterized by fluctuating attention after surgery and is associated with increased risk of developing Alzheimer's Disease (AD). While the neurophysiological changes that underlie POD and increased risk of AD are unclear, recent data has raised the possibility that an exaggerated brain response to anesthetics may be a biomarker for POD risk and preclinical AD-like pathology. Thus, we examined whether anesthetic-dose-adjusted intraoperative brain activity is associated with POD or preoperative brain vulnerabilities (preclinical AD-like pathology, preoperative inattention) that may contribute to risk of POD (and later AD).

Biomarkers.

Background: Subjective cognitive decline (SCD), or a person's perception of changes in their cognitive abilities, has been identified as a possible early marker of preclinical Alzheimer's disease (AD) in non-Hispanic Whites; however, research is lacking about the clinical utility of SCD in diverse populations. This study investigated the associations of self and informant reports of SCD, plasma biomarker profiles of AD, and objective cognitive performance in Hispanic older adults living in Miami.

Method: Hispanic participants enrolled in the 1Florida Alzheimer's Disease Research Center who completed neuropsychological testing and blood draws for biomarker analysis were eligible.

Biomarkers.

Background: Metabolomics captures net influences of exposome, diet, gut microbiome, and genome, informing about individuality and how we respond to interventions. Applications of metabolomics in pharmacology are starting to enable a Systems Pharmacology approach, where the outcome of a treatment is considered to evolve from effects on complex molecular networks, enabling insights into response variations. We bring the power of these approaches to the study of the MIND, a Mediterranean DASH diet for prevention of cognitive decline.