The Impact of Addiction Consultation and Medication for Opioid or Alcohol Use Disorder on Hospital Readmission.

Background: Patients with substance use disorder (SUD) are frequently hospitalized and readmitted. Hospitalization is an opportunity for treatment initiation, including medications for alcohol (MAUD) and opioid use disorder (MOUD). Addiction consult teams are one model for increasing hospital-based SUD treatment.

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: The term rapidly progressive dementia (RPD) may be applied to patients with precipitous declines in cognitive function resulting in dementia within one year or complete incapacitation within two-years of symptom onset. Although most patients present with subacute, progressive declines, selected patients develop complete incapacitation within seven days of symptom onset. The differential diagnosis and clinical characteristics of patients with abrupt-onset dementia are not known.

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.

Basic Science and Pathogenesis.

Background: Data from human and model organism studies suggest that genetic background influences susceptibility and resilience to Alzheimer's Disease (AD) neuropathology. We previously showed that, wild-derived PWK/PhJ (PWK) mice carrying the APP/PS1 transgene (PWK.APP/PS1) exhibit cognitive and synaptic resilience compared to traditionally-studied B6.

Basic Science and Pathogenesis.

Background: Previously, we found that germline C3 deletion protected cognition and hippocampal synapses in aged APP/PS1dE9 mice, despite increasing Aß plaques. Here, we crossed our C3 inducible conditional mouse model to APP knockin mice to determine whether global C3 lowering in an adult amyloid mouse model would be protective.

Methods: C3;Rosa26-Cre-ERT2 (C3iKO) mice were crossed to C3;APP mice to generate APP;C3iKO mice, which received 75 mg/kg tamoxifen (TAM; n = 16) or corn oil (CO; n = 15) for 5 days at 3.

Basic Science and Pathogenesis.

Background: Anti-amyloid antibodies have been associated with amyloid-related-imaging-abnormalities (ARIA) in AD patients, causing vasogenic edema and microhemorrhages, especially in ApoE4 carriers. Here, we compared recombinant 3D6-L, a murine version of bapineuzumab, and an isotype control IgG2a monoclonal antibody (mAb) to investigate potential mechanisms, including complement activation, involved in these side effects (ARIA-H or microhemorrhages) following passive immunization.

Method: Plaque-rich 16.

Basic Science and Pathogenesis.

The short introduction will highlight what we have learned about amyloid related imaging abnormalities (ARIA) since 2011 and the critical questions that remain to be elucidated. In particular, we need to better understand the risk factors and mechanisms that underlie the relatively rare symptomatic cases. We will highlight the importance of bi-directional translational research to bring insights from the laboratory to the clinic and findings from clinical trials back to the bench.

Basic Science and Pathogenesis.

Background: The prevalence of Alzheimer's disease (AD) pathologies in people with Down syndrome (DS) is nearly 100%. In DS, overexpression of APP (on chr21) is associated with increased production of amyloid beta (Aβ) and the formation of phosphorylated tau (ptau) tangles. In the general population, women exhibit higher burdens of ptau compared to age-matched men with AD.

Basic Science and Pathogenesis.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impact (RHI) although little is known about its molecular pathogenesis. Previous studies of single neurons showed that private somatic mutations increase both during normal aging and in neurodegenerative disorders, and show diverse mutational patterns.

Method: We applied two orthogonal single-nucleus whole-genome sequencing (snWGS) methods to neurons isolated from the prefrontal cortex of 15 individuals with CTE, and 4 individuals with RHI but no CTE diagnosis, and compared mutational rates and spectra with neurons from neurotypical controls and Alzheimer's disease (AD).

Basic Science and Pathogenesis.

SORL1 (SORLA, LR11) is a large (2214 residue), multi-domain type 1 integral membrane protein that is the product of the SORL1 gene. In neurons, where it is highly expressed, SORL1 functions as both a substrate of and a cargo receptor for the retromer multi protein complex that is a master regulator of protein trafficking out of the early endosome. The SORL1-Vps26b retromer, in particular, is dedicated to the recycling of cell surface proteins, including APP and AMPA receptor subunit GLUA1, back to the plasma membrane.