Dnmt3a-mediated methylation balances memory Th1 and Tfh cell plasticity and functionality.

Following acute viral infection, naïve CD4+ T cells differentiate into T follicular helper (Tfh) and T helper 1 (Th1) cells that generate long-lived memory cells. However, it is unclear how memory Tfh and Th1 cells maintain their lineage commitment. Here we demonstrate that Tfh and Th1 lineages acquire distinct DNA methylation programs that are preserved into memory.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction.

Sex specific analysis of patients with and without reported statin intolerance referred to a specialized outpatient lipid clinic.

Background: Lowering LDL-cholesterol is a fundamental goal for both primary and secondary prevention of atherosclerotic cardiovascular diseases. Our study aims to analyse potential sex disparities regarding the tolerability and effectiveness of lipid-lowering therapy in patients with and without reported statin intolerance who are being treated at a lipid-outpatient clinic.

Methods: From 2017 to 2022, n = 1062 patients (n = 612 men, n = 450 women) at high-risk were referred to our lipid-outpatient clinic because of difficulties in lipid control by primary healthcare providers.

LAG-3 and PD-1 synergize on CD8 T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity.

Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown.

Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure.

Background: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited.

Objectives: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC.

Methods: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging.

[Chest pain and cardiovascular diseases in women : Diagnostics and treatment].

Cardiovascular diseases (CVD) are the leading cause of global mortality not only in men but also in women. The incidence of CVD significantly increases in women, especially after the menopause. Sex and gender differences in the incidence, prevalence and mortality of CVD are due to hormonal, anatomical, and sociocultural differences.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction.

Tet2 deletion in CD4+ T cells disrupts Th1 lineage commitment in memory cells and enhances T follicular helper cell recall responses to viral rechallenge.

Following viral clearance, antigen-specific CD4+ T cells contract and form a pool of distinct Th1 and Tfh memory cells that possess unique epigenetic programs, allowing them to rapidly recall their specific effector functions upon rechallenge. DNA methylation programing mediated by the methylcytosine dioxygenase Tet2 contributes to balancing Th1 and Tfh cell differentiation during acute viral infection; however, the role of Tet2 in CD4+ T cell memory formation and recall is unclear. Using adoptive transfer models of antigen-specific wild type and knockout CD4+ T cells, we find that Tet2 is required for full commitment of CD4+ T cells to the Th1 lineage and that in the absence of Tet2, memory cells preferentially recall a Tfh like phenotype with enhanced expansion upon secondary challenge.

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.

The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background And Aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines.

High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

Background And Aims: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C.

Improvement of obstructive sleep apnea does not rescue left atrial enlargement in obese participants of a multimodal weight reduction program.

The aim of our study was to investigate the effect of obstructive sleep apnea (OSA) and its weight loss related improvement on left atrial (LA) area in individuals with severe obesity participating in a multimodal weight reduction (WR) program. Participants with obesity (body mass index, BMI, 40.2 ± 7.

Reliability Testing of the Mayo Elbow Performance Score in Post-operative Patients.

This study aimed to determine intra-observer and inter-observer reliability of the Mayo Elbow Performance Score (MEPS). Patients undergoing elbow surgery completed a MEPS questionnaire initially and another 2-3 weeks later. During the second interview, patients completed the Oxford Elbow Score (OES) for comparison.

The Incidence of Posterolateral Tibial Plateau and Central Lateral Femoral Condylar Impaction Fractures in a Pediatric and Young Adult Population.

Background: Posterolateral tibial plateau and central lateral femoral condylar impaction fractures are known to occur in the setting of anterior cruciate ligament (ACL) tears. There have been no prior investigations into the incidence and morphology of posterolateral tibial plateau impaction fractures in the setting of ACL injury in a pediatric population.

Methods: Patients between 9 and 22 years of age with knee magnetic resonance imagings (MRIs) performed demonstrating complete or partial ACL tear were included in this study.

Skeletally Immature Patients With Classic Anterior Cruciate Ligament Bone Bruise Patterns Have a Higher Likelihood of Having an Intact Anterior Cruciate Ligament Compared With Skeletally Mature Patients.

Background: The incidence of anterior cruciate ligament (ACL) tears in skeletally immature patients with an ACL bone contusion pattern has been sparsely investigated. The purpose of this study is to investigate whether physeal status has an influence on the likelihood of sustaining an ACL tear when classic bipolar ACL bone bruising pattern is present.

Methods: Magnetic resonance imaging reports were queried for "contusion" on all patients between 6 and 22 years between 2015 and 2019.

Electroconvulsive therapy in a patient with hypertrophic cardiomyopathy: A case report.

The use of electroconvulsive therapy (ECT) in patients with underlying cardiac disease like hypertrophic cardiomyopathy (HCM) remains without satisfactory clinical guidelines. We provide a case report of successful application of ECT in a 43-year-old patient with bipolar disorder and comorbid HCM, including detailed diagnostic information and outlining key clinical considerations.

Safety and short-term outcomes of anatomic vs. reverse total shoulder arthroplasty in an ambulatory surgery center.

Background: A scarcity of literature exists comparing outcomes of outpatient anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA). This study was performed to compare early outcomes between the 2 procedures in a freestanding ambulatory surgery center (ASC) and to determine if the addition of preoperative interscalene nerve block (ISNB) with periarticular liposomal bupivacaine injection (PAI) in the postanesthesia care unit (PACU) would improve outcomes over PAI alone.

Methods: Medical charts of all patients undergoing outpatient primary aTSA or rTSA at 2 ASCs from 2012 to 2020 were reviewed.

Tet2 coordinates with Foxo1 and Runx1 to balance T follicular helper cell and T helper 1 cell differentiation.

In response to various types of infection, naïve CD4 T cells differentiate into diverse helper T cell subsets; however, the epigenetic programs that regulate differentiation in response to viral infection remain poorly understood. Demethylation of CpG dinucleotides by Tet methylcytosine dioxygenases is a key component of epigenetic programing that promotes specific gene expression, cellular differentiation, and function. We report that following viral infection, Tet2-deficient CD4 T cells preferentially differentiate into highly functional germinal center T follicular helper (T) cells that provide enhanced help for B cells.

Usage of the wearable cardioverter-defibrillator during pregnancy.

Background: Pregnancy can trigger or aggravate the risk for life-threating arrhythmias in cardiac diseases. Pregnancy is associated with reluctance for implantable cardioverter-defibrillators (ICD) due to concerns about radiation. Thus, the wearable cardioverter-defibrillator (WCD) might be an option during pregnancy.

Use of a Nanofiber Resorbable Scaffold During Rotator Cuff Repair: Surgical Technique and Results After Repair of Small- to Medium-Sized Tears.

Background: The rate of retear after primary rotator cuff failure remains unacceptably high (up to 36% for small- to medium-sized tears). Augmentation of cuff repair with scaffold devices has been reported to improve healing after cuff repair.

Purpose/hypothesis: To describe the surgical technique of using an interpositional nanofiber scaffold during rotator cuff repair and report on a retrospective series of patients regarding functional outcomes and postoperative healing on magnetic resonance imaging (MRI).

[Novel options to maximize oral lipid lowering treatment : Role of bempedoic acid in combination treatment].

Epidemiological, randomized, controlled, clinical and genetic studies confirm that low-density lipoprotein cholesterol (LDL-C) is a causative factor for atherosclerotic diseases. The current European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) guidelines on the management of dyslipidemia recommend a target LDL-C < 55 mg/dl and at least a 50% reduction in baseline LDL‑C for high-risk patients; however, these target values are often not achieved in routine clinical practice, as shown by recent cross-sectional data from EUROASPIRE or DaVinci. Therefore, combination treatment is recommended, which, as with treatment of blood pressure, can improve the success of treatment.

Gender differences in cardiometabolic health and disease in a cross-sectional observational obesity study.

Background: Beyond the degree of adiposity, the pattern of fat distribution has a profound influence on cardiometabolic risk. It is unclear if sex differences in body fat distribution can potentially explain any sex differences in the prevalence of the metabolic syndrome (MetS) and in individual cardiometabolic risk factors among obese men and women.

Methods: In this cross-sectional analysis, 432 persons from the ongoing Obesity Weight Reduction Study (n = 356 obese, ØBMI 41 ± 8 kg/m, and 76 non-obese, ØBMI 25 ± 3 kg/m), were included.

Tension Hydrothorax After Attempted Arthroscopic Fixation of Greater Tuberosity Fracture in a Trauma Patient: A Case Report.

Case: We report the case of a 27-year-old man who presented after a 30-foot fall with a hemopneumothorax, multiple rib fractures, and left shoulder dislocation with greater tuberosity fracture. During attempted arthroscopic repair, the patient developed pulseless electrical activity arrest as the result of intraoperative tension hydrothorax. We hypothesize that this was caused by a traumatic soft-tissue communication to his shoulder joint from the apex of his lung.