Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review.

Introduction: Without disease-modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near-total failure rate in clinical trials suggests that more disease-modifying therapies are on the horizon. In this review, we assess the late-stage pipeline of disease-modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms-groups of candidates that share an underlying biological mechanism of action and general disease target.

Color Fundus Photography and Deep Learning Applications in Alzheimer Disease.

Objective: To report the development and performance of 2 distinct deep learning models trained exclusively on retinal color fundus photographs to classify Alzheimer disease (AD).

Patients And Methods: Two independent datasets (UK Biobank and our tertiary academic institution) of good-quality retinal photographs derived from patients with AD and controls were used to build 2 deep learning models, between April 1, 2021, and January 30, 2024. ADVAS is a U-Net-based architecture that uses retinal vessel segmentation.

Exploring Restaurant Worker Mental Models of Injury and Safety Using Pathfinder Networks.

OCCUPATIONAL APPLICATIONSResults from our exploratory study of restaurant worker mental models of injury and safety emphasize the need for improved occupational safety in the culinary industry through targeted interventions for chefs and managers. The analysis we performed showed that managers possess more integrated and coherent mental models of injury and safety than chefs, reflected in network parameters showing better organization of safety concepts. Kitchen training programs should focus on bridging gaps in safety awareness and mitigating hazards such as burns, cuts, slips, and equipment-related risks.

Crystal structure of Au-pseudocarbyne(C).

Carbyne-related materials permit exploring the potentially extraordinary properties of this long-sought but still elusive carbon allotrope. However, accurate understanding of these materials is challenging. Here we report the crystal structure of a Au-pseudocarbyne, a representative of a possible new family of materials consisting of sp-hybridized carbon chains and stabilizing metal atoms.

A soft thermal sensor for the continuous assessment of flow in vascular access.

Hemodialysis for chronic kidney disease (CKD) relies on vascular access (VA) devices, such as arteriovenous fistulas (AVF), grafts (AVG), or catheters, to maintain blood flow. Nonetheless, unpredictable progressive vascular stenosis due to neointimal formation or complete occlusion from acute thrombosis remains the primary cause of mature VA failure. Despite emergent surgical intervention efforts, the lack of a reliable early detection tool significantly reduces patient outcomes and survival rates.

Automated Detection of Normal Pressure Hydrocephalus Using CT Imaging for Calculating the Ventricle-to-Subarachnoid Volume Ratio.

Background And Purpose: Normal pressure hydrocephalus (NPH) is a diagnostic challenge because its clinical symptoms and imaging appearance resemble normal aging and other forms of dementia. Identifying NPH is essential so that patients can receive timely treatment to improve gait distortion and quality of life. An automated marker of NPH was developed and evaluated on clinical CT images, and its utility was assessed in a large patient cohort.

Women with breast implants have higher adjusted abnormal cardiac testing and coronary angiography but lower coronary intervention.

Background: Breast implants interfere with myocardial perfusion imaging (SPECT) and echocardiographic windows leading to increased false positive results. To validate this concept, we hypothesized that patients with breast implants should have higher positive cardiac testing and coronary angiogram with lower percutaneous coronary intervention (PCI) rates compared to women without a breast implant.

Methods: Using ICD 10 codes for breast implants, abnormal results of cardiac functional study, coronary angiogram, and percutaneous coronary interventions, we evaluated any association between these parameters in adult women with breast implants utilizing the National Inpatient Sample (NIS) database.

A scoping review and consensus recommendations for emergency medical services buprenorphine (EMS-Bupe) programs.

Objectives: Emergency Medical Services (EMS) agencies are beginning to provide low-barrier access to treatment for opioid use disorder (OUD) through the development of EMS buprenorphine (EMS-Bupe) programs. However, evidence-based practices for these programs are lacking. Our aim was to review the current literature on EMS and emergency department (ED) based buprenorphine treatment programs to provide consensus recommendations on the EMS-Bupe program development.

Discovery of Titin and Its Role in Heart Function and Disease.

This review examines the giant elastic protein titin and its critical roles in heart function, both in health and disease, as discovered since its identification nearly 50 years ago. Encoded by the TTN (titin gene), titin has emerged as a major disease locus for cardiac disorders. Functionally, titin acts as a third myofilament type, connecting sarcomeric Z-disks and M-bands, and regulating myocardial passive stiffness and stretch sensing.

Cushing's Disease Clinical Phenotype and Tumor Behavior Vary with Age: Diagnostic and Perioperative Implications.

Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging.

Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes.

Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023.

Risk of Acute Cholecystitis Based on Combination of Patient Age, Patient Sex, Leukocytosis, and Sonographic Murphy Sign.

Objectives: To combine sonographic Murphy sign (SMS) with clinical parameters to effectively stratify patients into risk groups for acute cholecystitis.

Methods: Consecutive emergency department patients from April 1, 2019 to August 31, 2022 with possible acute cholecystitis were grouped using patient age, sex, and white blood cell count to determine the rate of acute cholecystitis found in subgroups. Three distinct clinical risk groups were established and then regrouped by prospective assessment of SMS into three non-imaging risk groups.

A risk-risk tradeoff approach for incorporating the public's risk perceptions into quantitative microbial risk assessment.

In public health, risk experts often define acceptable risk targets without community input. We developed a novel method for applying behavioral microeconomics to integrate individuals' risk preferences into risk assessment. To demonstrate this methodology, we explored a risk-risk tradeoff case scenario: increased asthma risk from increased cleaning and disinfection (C&D) and increased infection risk from decreased C&D for healthcare staff.

Continuing Medical Education Questions: January 2025.

Article Title: ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis.

A scoping review of healthcare effectiveness data and information set (HEDIS) substance use disorder measures.

Introduction: : There is a need to assess the delivery of interventions to improve substance use disorder (SUD) treatment, as measured by the Healthcare Effectiveness Data and Information Set (HEDIS®) metrics. The goal was to characterize published articles reporting HEDIS® SUD measures and recommend future work on applying and investigating SUD HEDIS® metrics and their effect on SUD treatments.

Materials And Methods: The PRISMA-ScR scoping review protocol was used to find published work and investigate the most common reported baseline characteristics, HEDIS® metric outcomes, and knowledge gaps.

A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations.

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples.

Standardization and consensus in the development and application of bone organoids.

Organoids, self-organized structures derived from stem cells cultured in a specific three-dimensional (3D) microenvironment, have emerged as innovative platforms that closely mimic cellular behavior, tissue architecture, and organ function. Bone organoids, a frontier in organoid research, can replicate the complex structures and functional characteristics of bone tissue. Recent advancements have led to the successful development of bone organoids, including models of callus, woven bone, cartilage, trabecular bone, and bone marrow.

Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes.

Introduction: Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods: We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.

Modifying reaction time tasks parameters in the automated IntelliCage identifies heightened impulsivity and impaired attention in the 3xTg-AD model of Alzheimer's disease.

Background: The 3xTg-AD transgenic mouse model of Alzheimer's disease (AD) is an important tool to investigate the relationship between development of pathological amyloid-β (Aβ) and tau, neuroinflammation, and cognitive impairments. Traditional behavioral tasks assessing aspects of learning and memory, such as mazes requiring spatial navigation, unfortunately suffer from several shortcomings, including the stress of human handling and not probing species-typical behavior. The automated IntelliCage system was developed to circumvent such issues by testing mice in a social environment while measuring multiple aspects of cognition.