Physician-Patient Communication about Novel Drugs and High-Risk Medical Devices.

Background: After a new drug or medical device is approved by the US Food and Drug Administration (FDA), physician-patient communication about benefits and risks is critical, including whether the product was approved through an expedited pathway based on limited evidence. In addition, physician reporting of drug- and device-related adverse events in real-world use is necessary to have a complete safety profile. We studied physician-reported communication and safety-reporting practices related to drugs and devices.

RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Bridging silicon and carbon worlds with digital twins and on-chip systems in drug discovery.

This perspective discusses the convergence of digital twin (DT) technology and on-the-chip systems as pivotal innovations in precision medicine, substantially advancing drug discovery. DT leverages extensive health data to create dynamic virtual patient models, enabling predictive insights and optimized treatment strategies. Concurrently, on-the-chip systems from the Carbon world replicate human biological processes on microfluidic platforms, providing detailed insights into disease mechanisms and pharmacological interactions.

Effectiveness of Virtual Care Team Guided Management of Hospitalized Patients with HFrEF by Ethnicity.

Background: IMPLEMENT-HF demonstrated a virtual team-based care strategy was safe and improved prescription of guideline directed medical therapy (GDMT) in hospitalized patients with heart failure and reduced ejection fraction (HFrEF). We evaluated differences in efficacy and safety outcomes by ethnicity in IMPLEMENT-HF.

Methods: IMPLEMENT-HF evaluated a provider-facing virtual team-based care strategy vs.

Readmission outcomes after acute coronary syndrome among patients with myeloproliferative neoplasms.

Background And Aims: Myeloproliferative neoplasms (MPNs) are associated with arterial thrombosis, including acute coronary syndrome (ACS). Prior studies have suggested similar in-hospital mortality among patients with MPN compared to those without. However, post-ACS outcomes have not been thoroughly evaluated.

The Need for a Cancer Exposome Atlas: A Scoping Review.

Background: Despite advances in understanding genetic susceptibility to cancer, much of cancer heritability remains unidentified. At the same time, the makeup of industrial chemicals in our environment only grows more complex. This gap in knowledge on cancer risk has prompted calls to expand cancer research to the comprehensive, discovery-based study of non-genetic environmental influences, conceptualized as the "exposome.

Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies.

Background: Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk.

Longitudinal Assessment of Pain in Rheumatoid Arthritis: Increases in Pain and Their Relationship to Functional Declines and Medication Changes.

Objective: Electronic health applications (apps) allow patients with rheumatoid arthritis (RA) to report patient-reported outcomes (PROs) between visits. However, almost no data exist on patients' report of pain between visits and how that correlates with change in function and/or modifications to medication.

Methods: Patients with RA from one rheumatology practice provided data as part of a study of an app.

Trends in Sudden Cardiac Death Among Adults Aged 25 to 44 Years in the United States: An Analysis of 2 Large US Databases.

Background: Sudden cardiac death (SCD) in early adults aged 25 to 44 years represents an important and unexpected cause of death. We assessed trends in SCD-related mortality in the United States from 1999 to 2020 among early adults to determine differences by sex, ethnoracial groups, urbanization, and census region.

Methods And Results: Mortality data were retrieved from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) data set from 1999 to 2020.

Drinking pattern and time lag of alcohol consumption with colorectal cancer risk in US men and women.

Background: Association between light to moderate alcohol consumption and colorectal cancer (CRC) incidence remains understudied, especially regarding drinking pattern, beverage type and temporal aspects.

Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to CRC diagnosis were estimated among 137,710 participants. Estimates based on remote (eg, >10 years before follow-up) and recent (eg, the preceding 10 years before follow-up) alcohol intake, using different cutoffs (eg, 8, 10, 12 years, etc) and mutual adjustment, enabled separating independent effects and investigating time lag of alcohol-CRC association.

Associations between phenotypes of childhood and adolescent obesity and incident hypertension in young adulthood.

Objectives: We investigated whether empirically derived childhood obesity phenotypes were differentially associated with risk of hypertension in young adulthood, and whether these associations differed by sex.

Methods: Data came from 11,404 participants in the Growing Up Today Study, a prospective cohort study in the US established in 1996. We used a childhood obesity phenotype variable that was previously empirically derived using latent class analysis.

Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors.

The trafficking dynamics of uromodulin (UMOD), the most abundant protein in human urine, play a critical role in the pathogenesis of kidney disease. Monoallelic mutations in the UMOD gene cause autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), an incurable genetic disorder that leads to kidney failure. The disease is caused by the intracellular entrapment of mutant UMOD in kidney epithelial cells, but the precise mechanisms mediating disrupted UMOD trafficking remain elusive.

Lithium Use During Pregnancy in 14 Countries.

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

Shared Genetics of Migraine and Gastrointestinal Disorders Implicates Underlying Neurologic Mechanisms Yet Heterogeneous Etiologies.

Background And Objectives: Migraine is strongly comorbid with irritable bowel syndrome (IBS), one of several gastrointestinal (GI) conditions that are distinguished by symptomatic profiles that are partly overlapping. Potential shared mechanisms of migraine and the GI conditions were investigated by assessing shared genetics on a genome-wide basis.

Methods: Analyses leveraged genome-wide summary statistics from large-scale genetic studies for migraine, including by aura status, IBS, peptic ulcer disease (PUD), gastrointestinal reflux (GERD), functional dyspepsia (FD), diverticular disease (DD), and the immune-related inflammatory bowel disease (IBD) or its constituents, ulcerative colitis (UC) and Crohn disease (CD).

AnVILWorkflow: A runnable workflow package for Cloud-implemented bioinformatics analysis pipelines.

Advancements in sequencing technologies and the development of new data collection methods produce large volumes of biological data. The Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) provides a cloud-based platform for democratizing access to large-scale genomics data and analysis tools. However, utilizing the full capabilities of AnVIL can be challenging for researchers without extensive bioinformatics expertise, especially for executing complex workflows.

Measuring the association between diagnostic errors and neighborhood disadvantage.

Patients who reside in areas of high neighborhood disadvantage have poorer health outcomes; the mechanisms for this disparity are complex. We sought to determine if there was an association between neighborhood disadvantage and diagnostic error among a cohort of adult inpatients who experienced either an ICU transfer or in-hospital death. Using a sample of 527 patients from seven geographically diverse academic medical systems, we compared diagnostic error rates to patients' neighborhood disadvantage levels as measured by the Area Deprivation Index, a validated composite measure of socioeconomic status.

Lateral epiglottic collapse in obstructive sleep apnea is associated with laterally directed pharyngeal collapse.

Study Objectives: Epiglottic collapse can obstruct the airway in obstructive sleep apnea (OSA) patients in an anteroposterior (E-ap) or lateral direction (E-lat). The present study investigates the concept that lateral or concentric pharyngeal collapse patterns may remodel the epiglottis and predispose it to lateral collapse. To do so, we hypothesized that the presence of-any form of laterally directed pharyngeal collapse, e.

Etiology of prostate cancer with the TMPRSS2:ERG fusion: A systematic review of risk factors.

The most common somatic alteration in primary prostate cancer is the TMPRSS2:ERG gene fusion, which may be caused or promoted by distinct etiologic factors. The objective of this systematic review was to assess epidemiologic evidence on etiologic factors for prostate cancer by tumor TMPRSS2:ERG fusion status in human populations. Of 3071 publications identified, 19 cohort or case-control studies from six distinct study populations were included in this systematic review.

Reproductive factors and expression of stem cell markers in women with incident benign breast disease.

Reproductive factors are well-established risk factors for breast cancer. The prevailing hypothesis suggested that stem cell changes may be the key underlying mechanisms, but epidemiological evidence has been notably scarce. Herein we examined the relationship between reproductive risk factors and the expression of well-established stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy non-cancerous samples.