FOUR QUESTIONS ABOUT ATRIAL FIBRILLATION IN CARDIAC AMYLOIDOSIS. WHY IS THIS ARRHYTHMIA DIFFERENT FROM ALL OTHER ARRHYTHMIAS?

AF is a common arrhythmia in cardiomyopathy, particularly when congestive heart failure is present. The neurohormonal activation in congestive heart failure may trigger fibrotic and other changes in the left atrium and the atrial stretch associated with heart failure may induce further atrial pathology and/ or directly trigger AF (8). By the time that patients with AF develop extensive fibrosis, the arrhythmia has been shown to be associated with a greater difficulty in maintaining sinus rhythm despite attempted ablation procedures.

DOME: Directional medical embedding vectors from electronic health records.

Motivation: The increasing availability of electronic health record (EHR) systems has created enormous potential for translational research. Recent developments in representation learning techniques have led to effective large-scale representations of EHR concepts along with knowledge graphs that empower downstream EHR studies. However, most existing methods require training with patient-level data, limiting their abilities to expand the training with multi-institutional EHR data.

A systematic review and meta-analysis of endovascular treatment of carotid blowout syndrome.

Unlabelled: Carotid Blowout Syndrome (CBS) is a rare and life-threatening condition that necessitates prompt intervention to prevent fatal hemorrhage. This study compares the outcomes of two primary endovascular approaches: reconstructive interventions, which aim to preserve carotid artery function using stents or balloon angioplasty, and deconstructive interventions, which involve vessel occlusion to halt bleeding. A systematic review and meta-analysis were performed by searching multiple databases for relevant studies published from January 2000 to August 2023.

Informative censoring in externally controlled clinical trials: a potential source of bias.

Background: Cancer researchers frequently consider the use of single-arm and randomized controlled clinical trial designs that leverage external data. The literature has reported extensively on how the use of external data can introduce bias through a variety of distortion mechanisms. In this article, we focus on a distortion mechanism that is often overlooked: informative censoring.

Intraoperative FiO and risk of impaired postoperative oxygenation in lung resection: A propensity score-weighted analysis.

Study Objective: To assess whether, in a lung resection cohort with a low probability of confounding by indication, higher FiO is associated with an increased risk of impaired postoperative oxygenation - a clinical manifestation of lung injury/dysfunction.

Design: Pre-specified registry-based retrospective cohort study.

Setting: Two large academic hospitals in the United States.

Rhomboid Intercostal and Subserratus Plane Block for Acute Pain Management after Abdominal Surgeries: A Narrative Review.

Purpose Of Review: The rhomboid intercostal and subserratus plane (RISS) block is an effective, safer alternative for managing postoperative acute pain following abdominal surgeries. The RISS block offers several advantages over traditional approaches, including reduced incidence of puncture-related complications, lower rates of systemic opioid consumption, and more consistent analgesic coverage of lower thoracic dermatomes.

Recent Findings: Despite a favorable safety profile, the RISS block carries potential risks, such as pneumothorax and local anesthetic systemic toxicity, particularly when long-acting anesthetics such as bupivacaine or ropivacaine are used.

Impact of high maternal body mass index on fetal cerebral cortical and cerebellar volumes.

Objectives: Maternal obesity increases a child's risk of neurodevelopmental impairment. However, little is known about the impact of maternal obesity on fetal brain development.

Methods: We prospectively recruited 20 healthy pregnant women across the range of pre-pregnancy or first-trimester body mass index (BMI) and performed fetal brain magnetic resonance imaging (MRI) of their healthy singleton fetuses.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

A Splice Site Variant in SENP7 Results in a Severe Form of Arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder associated with 1/3000 to 1/5000 live births. We report a consanguineous family with multiple affected members with AMC and identified a recessive mutation in the highly conserved splice donor site, resulting in the mis-splicing of the affected exons. SENP7 is a deSUMOylase that is critical for sarcomere assembly and skeletal muscle contraction by regulating the transcriptional program in the skeletal muscle.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

Comparative analysis of injuries related to self-harm, assault, and intimate partner violence: insights from U.S. Emergency Departments (2005-2021).

Background: Emergency departments are on the front lines of non-fatal self-harm injury (SHI). This study identifies patterns in patients presenting to emergency departments with SHI compared with patients presenting with assault and intimate partner violence.

Methods: Using the National Electronic Injury Surveillance System All Injury Program database, we analyzed SHI cases in the emergency department from 2005 to 2021 and examined demographic characteristics, injury mechanism and anatomic location, emergency department disposition and temporal patterns relative to cases involving assault and intimate partner violence.

Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204.

Purpose: In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival.

Updated Geriatrics Competencies for Graduating Medical Students: Training Physicians to Provide Age-Friendly Care.

Purpose: Medical student education in geriatrics is a critical need for every doctor-in-training as the population ages, with fewer than 7,000 geriatricians, and older patients, who now approach 20% of the U.S. population, having unique health care needs.

Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth.

Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.

Incidence of Adjacent Synchronous Ipsilateral Infiltrating Carcinoma and/or Ductal Carcinoma In Situ in Patients Diagnosed with Flat Epithelial Atypia by Core Needle Biopsy (TBCRC 034).

Background: Flat epithelial atypia (FEA), a rare breast proliferative lesion, is often diagnosed following core biopsy (CB) of mammographic microcalcifications. In the prospective multi-institution TBCRC 034 trial, we investigate the upgrade rate to ductal carcinoma in situ (DCIS) or invasive cancer following excision for patients diagnosed with FEA on CB.

Patients And Methods: Patients with a breast imaging reporting and data system (BI-RADS) ≤ 4 imaging abnormality and a concordant CB diagnosis of FEA were identified for excision.

Defining Textbook Outcomes for Minimally Invasive Surgical Resection of Small Gastrointestinal Stromal Tumors (GIST) of the Stomach.

Background: Textbook outcome (TO) has been utilized to assess the quality of surgical care. This study aimed to define TO rates for minimally invasive gastric gastrointestinal stromal tumor (GIST) resections in a bi-institutional cohort.

Methods: Patients with gastric GIST (≤ 5 cm) who underwent laparoscopic or robotic resection (January 2014 to January 2024) were retrospectively identified from two GIST centers.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.

Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is highly comorbid with Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), and the combined AD+LATE-NC is more common than either pathology alone. However, the topographic relationship between tau and TDP-43 in AD+LATE-NC remains unclear.

Method: We analyzed the data from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) participants.

Basic Science and Pathogenesis.

Background: Women are disproportionately affected by Alzheimer's disease (AD) and exhibit greater AD neuropathology than men. Women possess two X chromosomes, with one randomly silenced across each cell for dosage compensation. X chromosome inactivation (XCI) is not complete, and XCI-escaping genes provide a promising avenue of discovery for biological pathways driving sex-specific AD risk.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid-beta and hyperphosphorylated tau (P-tau) proteins in the brain. P-tau accumulates in neurons and is strongly associated with AD severity and affected brain regions. However, only a subset of neurons in AD exhibit tau pathology.