Lymphatic System Development and Function.

Purpose Of Review: This review delves into recent advancements in understanding generalized and organ-specific lymphatic development. It emphasizes the distinct characteristics and critical anomalies that can impair lymphatic function. By exploring developmental mechanisms, the review seeks to illuminate the profound impact of lymphatic malformations on overall health and disease progression.

Congenital Vascular and Lymphatic Diseases.

Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.

ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection.

Viral myocarditis, an inflammatory disease of the heart, causes significant morbidity and mortality. Type I interferon (IFN)-mediated antiviral responses protect against myocarditis, but the mechanisms are poorly understood. We previously identified A Disintegrin And Metalloproteinase domain 9 (ADAM9) as an important factor in viral pathogenesis.

Endothelial cell expression of a STING gain-of-function mutation initiates pulmonary lymphocytic infiltration.

Patients afflicted with Stimulator of interferon gene (STING) gain-of-function mutations frequently present with debilitating interstitial lung disease (ILD) that is recapitulated in mice expressing the STING mutation (VM). Prior radiation chimera studies revealed an unexpected and critical role for non-hematopoietic cells in initiating ILD. To identify STING-expressing non-hematopoietic cell types required for the development of ILD, we use a conditional knockin (CKI) model and direct expression of the VM allele to hematopoietic cells, fibroblasts, epithelial cells, or endothelial cells.

Effectiveness of Tofacitinib in Patients With Ulcerative Colitis: A Nationwide Veterans Administration Cohort Study.

Introduction: There is paucity of data on the effectiveness and safety of tofacitinib among elderly patients with ulcerative colitis (UC).

Methods: Through a retrospective cohort study among the US National Veterans Affairs Healthcare System, we evaluated effectiveness among the elderly (≥65) and young (<65) patients with UC initiated on tofacitinib.

Results: Among 158 patients (53 elderly, 105 young), effectiveness at 12 months was 50.

Expression of a STING Gain-of-function Mutation in Endothelial Cells Initiates Lymphocytic Infiltration of the Lungs.

Unlabelled: Patients afflicted with STING gain-of-function mutations frequently present with debilitating interstitial lung disease ( ) that is recapitulated in mice expressing the STING mutation ( ). Prior radiation chimera studies revealed an unexpected and critical role for non-hematopoietic cells in the initiation of ILD. To identify STING-expressing non-hematopoietic cell types relevant to ILD, we generated a conditional knock-in ( ) model in which expression of the VM allele was directed to hematopoietic cells, fibroblasts, epithelial cells, or endothelial cells.

Quantitative analysis of metabolic fluxes in brown fat and skeletal muscle during thermogenesis.

Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice.

Incidence of Pneumonia, Related Hospitalization, and Mortality Among Younger Unvaccinated IBD Patients in a Nationwide Cohort.

Background And Goals: Community Acquired Pneumonia (CAP) is among the most common infections among Inflammatory Bowel Disease (IBD) patients. Our aim was to determine the absolute and relative risk of CAP, related hospitalization, and death among younger (age < 65) unvaccinated IBD patients exposed and unexposed to immunosuppressive medications.

Materials And Methods: We conducted a retrospective cohort study among a nationwide cohort of younger IBD unvaccinated patients in the VAHS.

Interaction between Age and Primary Site on Survival Outcomes in Primary GI Melanoma over the Past Decade.

Background: Primary malignant melanomas of the Gastrointestinal mucosa are uncommon. Most cases of gastrointestinal (GI) melanomas are secondary, arising from metastasis at distant sites. The purpose of this study is to assess to what extent the interaction between independent prognostic factors (age and tumor site) of primary GI melanoma influence survival.

Interaction between age and gender on survival outcomes in extramedullary multiple myeloma over the past two decades.

Background: Extramedullary multiple myeloma (MM) (EMM) is a rare and aggressive subentity of MM that can be present at diagnosis or develop anytime during the disease course. There is a paucity of data on the clinical characteristics and overall epidemiology of EMM. Furthermore, there is a scarcity of data on how the interaction of age and gender influences the survival of EMM.

Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib.

Lymphangiectasia, an anomalous dilation of lymphatic vessels first described in the 17th century, is frequently associated with chylous effusion, respiratory failure, and high mortality in young patients, yet the underlying molecular pathogenesis and effective treatments remain elusive. Here, we identify an unexpected causal link between MAPK activation and defective development of the lymphatic basement membrane that drives lymphangiectasia. Human pathological tissue samples from patients diagnosed with lymphangiectasia revealed sustained MAPK activation within lymphatic endothelial cells.

A Rare Case of Junctional Bradycardia Secondary to Oral Phenytoin.

Phenytoin is a commonly used anti-seizure agent, which stabilizes neuronal membranes by blocking voltage-gated sodium channels to inhibit the propagation of action potentials during convulsions. However, phenytoin has also been shown to have antiarrhythmic effects as it can prolong the effective refractory period of ventricular pacemaker cells. Adverse cardiac effects such as junctional bradycardia are usually seen with intravenous use.

Safety of Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease.

Background And Aims: Patients with inflammatory bowel disease [IBD] have an increased risk of contracting herpes zoster [HZ] infection. However, vaccination rates for HZ are low among IBD patients. A contributing factor may be fear of an IBD flare associated with vaccination.

The impact of IBD medications on risk of pneumonia and pneumonia-related hospitalisation: a nationwide cohort study of 56 410 IBD patients.

Background: There are limited data on the incidence of pneumonia and pneumonia-related hospitalisation in the IBD population, and on any association of IBD medications with such outcomes.

Aims: To evaluate the impact of IBD medications on the risk of pneumonia, pneumonia-related hospitalisations and death.

Methods: We conducted a retrospective cohort study of IBD patients from the nationwide Veteran Affairs (VA) dataset.

Efficacy of Recombinant Zoster Vaccine in Patients With Inflammatory Bowel Disease.

Background & Aims: Individuals with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. Although the efficacy of recombinant zoster vaccine (RZV) is high among immunocompetent individuals, little is known about its effect among immunosuppressed individuals with IBD.

Methods: We conducted a retrospective cohort study among individuals in the national Veterans Affairs Healthcare System diagnosed with IBD on or before January 3, 2018, the earliest date of RZV vaccinations.