Development of a drug allergy alert tiering algorithm for penicillins and cephalosporins.

Introduction: Limited research is available regarding recommendations about which drug allergy alerts (DAAs) in clinical decision support (CDS) systems should interrupt provider workflow. The objective was to evaluate the frequency of penicillin and cephalosporin DAA overrides at two institutions. A secondary objective was to redesign DAAs using a new tiered alerting system based on patient factors.

Joint Physical-Psychosocial Frailty and Risks of All-Cause and Cause-Specific Premature Mortality.

Background: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.

Design: A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort.

B-cell infiltration distinguishes mucosal from skin patterns of rejection in facial vascularized composite allografts.

Rejection monitoring in facial vascularized composite allotransplantation (fVCA) traditionally focuses on skin biopsies. However, mucosal rejection frequently presents with more pronounced signs of immune activity. To explore mechanistic differences between skin and mucosal rejection, rejection and non-rejection biopsies from allograft skin and oral mucosa of nine fVCA recipients were retrospectively analyzed using histology, multiplex immunostaining, and gene expression profiling, with peripheral blood mononuclear cells (PBMCs) quantified via mass cytometry (CyTOF).

Differences in Care and Outcomes in Cardiogenic Shock in Cardiac Intensive Care Units in the United States and Canada: CCCTN Registry Insights.

Background: Mortality in cardiogenic shock (CS) remains high. Significant inter-hospital heterogeneity in critical care therapies have been described, which reflects the lack of high-quality evidence to guide optimal treatment. We aimed to describe differences in practices and clinical outcomes among patients with CS in the United States (US) and Canada.

Sex Differences in Long COVID.

Importance: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain.

Objective: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Combined T1-weighted MRI and diffusion MRI tractography of paraventricular, locus coeruleus, and dorsal vagal complex connectivity in brainstem-hypothalamic nuclei.

Background: Current multimodal neuroimaging plays a critical role in studying clinical conditions such as cardiovascular disease, major depression, and other disorders related to chronic stress. These conditions involve the brainstem-hypothalamic network, specifically the locus coeruleus (LC), dorsal vagal complex (DVC), and paraventricular nucleus (PVN) of the hypothalamus, collectively referred to as the "DVC-LC-PVN circuitry." This circuitry is strongly associated with the norepinephrine (NE) and epinephrine (E) neurotransmitter systems, which are implicated in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress response, and cognitive and emotional behaviors.

Epidemiology of Coronavirus Disease 2019-Associated Fungal Infections in the Intensive Care Unit: A Single-Center Retrospective Study.

Introduction: Invasive fungal disease (IFD) is a morbid superinfection that can arise in critically ill patients with COVID-19 infection. Studies evaluating the full spectrum of COVID-19-associated fungal infections remain limited.

Methods: Single-center retrospective study assessing IFD in patients with COVID-19, hospitalized for ≥ 72 h in the intensive care unit (ICU) between 02/25/20 and 02/28/22 (n = 1410).

Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.

Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.

Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).

Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.

Bacterium-Phage Symbiosis Facilitates the Enrichment of Bacterial Pathogens and Antibiotic-Resistant Bacteria in the Plastisphere.

The plastisphere, defined as the ecological niche for microbial colonization of plastic debris, has been recognized as a hotspot of pathogenic and antibiotic-resistant bacteria. However, the interactions between bacteria and phages facilitated by the plastisphere, as well as their impact on microbial risks to public health, remain unclear. Here, we analyzed public metagenomic data from 180 plastisphere and environmental samples, stemming from four different habitats and two plastic types (biodegradable and nonbiodegradable plastics) and obtained 611 nonredundant metagenome-assembled genomes (MAGs) and 4061 nonredundant phage contigs.

Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.

 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery.

Background: Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes to prioritize drugs in a cell type-dependent manner.

Association between chronic fatigue syndrome/myalgic encephalomyelitis and cardiovascular disease.

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a medical condition characterized by severe and prolonged fatigue that is not relieved by rest or attributed to any underlying medical or psychological condition. Individuals with CFS/ME are considered to have an increased risk of a wide range of comorbid conditions, including cardiovascular disease (CVD). The association between CFS/ME and CVD is not fully understood.

Consensus Recommendations for the Management of Neurosarcoidosis: A Delphi Survey of Experts Across the United States.

Background And Objectives: Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies.

Methods: In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis.

The Impact of Idiopathic Intracranial Hypertension on Cardiovascular Disease Risk Among UK Women: An Obesity-Adjusted Analysis.

Introduction: Idiopathic intracranial hypertension (IIH) is known to elevate cardiovascular disease (CVD) risk, but the extent to which obesity and IIH-specific factors contribute to this risk is not well understood. WE aim to separate the effects of obesity from IIH-specific factors on the risk of stroke and CVD, building on previous findings that indicate a two-fold increase in cardiovascular events in women with IIH compared to BMI-matched controls.

Methods: An obesity-adjusted risk analysis was conducted using Indirect Standardization based on data from a cohort study by Adderley et al.

Quantifying Metagenomic Strain Associations from Microbiomes with Anpan.

Genetic and genomic variation among microbial strains can dramatically influence their phenotypes and environmental impact, including on human health. However, inferential methods for quantifying these differences have been lacking. Strain-level metagenomic profiling data has several features that make traditional statistical methods challenging to use, including high dimensionality, extreme variation among samples, and complex phylogenetic relatedness.

Development of a Paper-Based Disposal Thin-Film Solid-Phase Microextraction Tool for the Quantification of Environmentally Hazardous 4-Chlorophenol in Water.

The presence of chlorinated compounds in water resources presents various environmental and health risks. Therefore, there is a precise need to develop a potential technique for fast and efficient monitoring of chlorinated contaminants in water due to environmental protection and regulation compliance. Here, we designed a paper-based thin-film solid-phase microextraction (TF-SPME) patch to estimate 4-chlorophenol (4-CRP), a widely known environmentally hazardous pollutant in water samples.

Enhanced Stability and Sensitivity for CA-125 Detection Under Microfluidic Shear Flow Using Polyethylene Glycol-Coated Biosensor.

The microfluidic-based point-of-care (POC) diagnostic tool has garnered significant interest in recent years, offering rapid and cost-effective disease detection. There is a growing trend toward integrating microfluidic platforms with biosensors, aligning lab-on-a-chip technologies with POC diagnostic devices. Despite numerous efforts to incorporate biosensors into microfluidic systems, researchers have performed very limited investigations on the stability of biomarker detection when biosensors operate under microfluidic shear flow conditions.

The renin-angiotensin-aldosterone system and salt sensitivity of blood pressure offer new insights in obesity phenotypes.

Objective: Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin-angiotensin-aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes.

Low Utility of Routine Thyroid Function Testing for Bowel Symptoms: A Population-Based Assessment.

Background: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

Aims: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.