Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

Background: Vascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking.

Methods: This multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications.

Association of DDX5/p68 protein with the upstream erythroid enhancer element (EHS1) of the gene encoding the KLF1 transcription factor.

EKLF/KLF1 is an essential transcription factor that plays a global role in erythroid transcriptional activation. Regulation of KLF1 is of interest, as it displays a highly restricted expression pattern, limited to erythroid cells and its progenitors. Here we use biochemical affinity purification to identify the DDX5/p68 protein as an activator of KLF1 by virtue of its interaction with the erythroid-specific DNAse hypersensitive site upstream enhancer element (EHS1).

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs), conferring a predisposition to life-threatening COVID-19 pneumonia. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52/IκBδ).

Viral Glomerulopathy.

Background: The association between viral infections and glomerular diseases, commonly known as "viral glomerulopathies," has been described in various clinical scenarios for decades. Despite advancements in diagnostic tools, it remains challenging to establish a causative link fully.

Summary: Data from mouse models have substantiated clinical observations and implicate direct viral infection in the pathogenesis of viral glomerulopathy, particularly in human immunodeficiency virus-associated nephropathy.

Proteome Analysis for Inflammation Related to Acute and Convalescent Infection.

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions.

Mind + Machine: ChatGPT as a Basic Clinical Decisions Support Tool.

Background Generative artificial intelligence (AI) has integrated into various industries as it has demonstrated enormous potential in automating elaborate processes and enhancing complex decision-making. The ability of these chatbots to critically triage, diagnose, and manage complex medical conditions, remains unknown and requires further research. Objective This cross-sectional study sought to quantitatively analyze the appropriateness of ChatGPT (OpenAI, San Francisco, CA, US) in its ability to triage, synthesize differential diagnoses, and generate treatment plans for nine diverse but common clinical scenarios.

Benign inoperable tracheal stenosis in COVID versus non-COVID patients at the pandemic epicenter: a case series.

Background: The COVID-19 pandemic has exponentially expanded the number of patients requiring treatment for chronic respiratory failure. One consequence is an increase in the number of patients requiring intubation and mechanical ventilation. Benign inoperable tracheal stenosis presents a challenge, especially in COVID-19 patients.

Clinical Benefit of Bempedoic Acid in Randomized Clinical Trials.

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

Background & Aims: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota.

Methods: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan.

Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study.

Background: Growing evidence indicates that anhedonia is a multifaceted construct. This study examined the possibility of identifying subgroups of people with anhedonia using multiple reward-related measures to provide greater understanding the Research Domain Criteria's Positive Valence Systems Domain and pathways for developing treatments.

Methods: Latent profile analysis of baseline data from a study that examined the effects of a novel kappa opioid receptor (KOR) antagonist drug on measures and biomarkers associated with anhedonia was used to identify subgroups.

A rare case of concurrent mitral and aortic valve aneurysms in the setting of infective endocarditis.

Key Clinical Message: Mitral valve aneurysm is a rare imaging finding most caused by infective endocarditis. The concurrent presence of an aortic valve aneurysm is unique and foretells a severe presentation that would require valve replacement during the same admission.

Abstract: A 42-year-old male patient presented with intermittent fever, night sweats, and weight loss for 2 months.

Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population.

Previous studies suggested that severe epilepsies, e.g., developmental and epileptic encephalopathies (DEEs), are mainly caused by ultra-rare de novo genetic variants.

Targeting transcriptional kinase of CDK7 halts proliferation of multiple myeloma cells by modulating the function of canonical NF-kB pathway and cell cycle regulatory proteins.

Multiple myeloma (MM) is an incurable plasma cell neoplasm. Despite several effective frontline therapeutic regimens, including Bortezomib (BTZ), relapse is almost inevitable; therefore, better therapeutic modalities to improve the outcomes are needed. Cyclin-dependent kinases (CDKs) are an essential constituent of the cellular transcriptional machinery and tumors including MM are critically dependent on transcription to maintain their oncogenic state.

Mast cell activation and degranulation in acute artery injury: A target for post-operative therapy.

The increasing incidence of cardiovascular disease (CVD) has led to a significant ongoing need to address this surgically through coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). From this, there continues to be a substantial burden of mortality and morbidity due to complications arising from endothelial damage, resulting in restenosis. Whilst mast cells (MC) have been shown to have a causative role in atherosclerosis and other vascular diseases, including restenosis due to vein engraftment; here, we demonstrate their rapid response to arterial wire injury, recapitulating the endothelial damage seen in PCI procedures.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry.

Background: Elevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk.

Objectives: The authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event.

Methods: The authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD.

Socioeconomic and racial disparities in source-apportioned PM levels across urban areas in the contiguous US, 2010.

Fine particulate matter (PM) air pollution exposure is associated with short and long-term health effects. Several studies found differences in PM exposure associated with neighborhood racial and socioeconomic composition. However, most focused on total PM mass rather than its chemical components and their sources.

Codeine prescription pattern and treatment responses in patients with chronic cough: a routinely collected institutional database analysis.

Background: Codeine has been long used as an antitussive drug in several countries. However, a prescription pattern of codeine, such as dose or treatment duration, has not been reported in detail. Furthermore, there is few scientific evidence on the efficacy and safety.

Identification of a genomic DNA sequence that quantitatively modulates KLF1 transcription factor expression in differentiating human hematopoietic cells.

The onset of erythropoiesis is under strict developmental control, with direct and indirect inputs influencing its derivation from the hematopoietic stem cell. A major regulator of this transition is KLF1/EKLF, a zinc finger transcription factor that plays a global role in all aspects of erythropoiesis. Here, we have identified a short, conserved enhancer element in KLF1 intron 1 that is important for establishing optimal levels of KLF1 in mouse and human cells.

Teclistamab versus real-world physician's choice of therapy in triple-class exposed relapsed/refractory multiple myeloma.

We compared the effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC) in triple-class exposed relapsed/refractory multiple myeloma. MajesTEC-1 eligibility criteria were applied to the RWPC cohort. Baseline covariate imbalances were adjusted using inverse probability of treatment weighting.