Increase of Cardiac Autoantibodies Against Beta-2-adrenergic Receptor During Acute Cellular Heart Transplant Rejection.

Background: Acute cellular rejection (ACR) in heart transplant (HTx) recipients may be accompanied by cardiac cell damage with subsequent exposure to cardiac autoantigens and the production of cardiac autoantibodies (aABs). This study aimed to evaluate a peptide array screening approach for cardiac aABs in HTx recipients during ACR (ACR-HTx).

Methods: In this retrospective single-center observational study, sera from 37 HTx recipients, as well as age and sex-matched healthy subjects were screened for a total of 130 cardiac aABs of partially overlapping peptide sequences directed against structural proteins using a peptide array approach.

Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease.

Background: Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children.

Methods And Results: The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416).

Resveratrol used as nanotherapeutic: a promising additional therapeutic tool against hormone-sensitive, hormone-insensitive and resistant prostate cancer.

Prostate cancer is one of the most common cancers in men. Despite the development of diverse therapeutic agents for different types and stages, the progression or spread of the disease is inevitable. Another problem is the development of resistance of cancer cells to available therapeutics.

Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic.

Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE-SPECT ESUS Trial.

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.

Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.

Brugada syndrome (BrS) is an inherited and rare cardiac arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. Different genes have been linked to BrS. The majority of mutations are located in the gene, and the typical abnormal ECG is an elevation of the ST segment in the right precordial leads V1 to V3.

Impact of Atrial Fibrillation on Outcome in Takotsubo Syndrome: Data From the International Takotsubo Registry.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS.

Activation of Adenosine Monophosphate-Activated Protein Kinase Reduces the Onset of Diet-Induced Hepatocellular Carcinoma in Mice.

The worldwide obesity and type 2 diabetes epidemics have led to an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD covers a spectrum of hepatic pathologies ranging from simple steatosis to nonalcoholic steatohepatitis, characterized by fibrosis and hepatic inflammation. Nonalcoholic steatohepatitis predisposes to the onset of hepatocellular carcinoma (HCC).

Clinical Predictors and Prognostic Impact of Recovery of Wall Motion Abnormalities in Takotsubo Syndrome: Results From the International Takotsubo Registry.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study.

A Therapeutic Silencing RNA Targeting Hepatocyte TAZ Prevents and Reverses Fibrosis in Nonalcoholic Steatohepatitis in Mice.

Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. The transcriptional coactivator with PDZ-binding motif (TAZ; encoded by WW domain-containing transcription regulator 1 []) is up-regulated in hepatocytes in NASH liver from humans and has been shown to causally promote inflammation and fibrosis in mouse models of NASH.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry.

Incidence and Clinical Impact of Recurrent Takotsubo Syndrome: Results From the GEIST Registry.

Background Current literature only reports variable information from single-center studies on the recurrence rate, the complications, and the outcome of patients with Takotsubo syndrome ( TTS) experiencing recurrent TTS . Therefore, a detailed description of clinical characteristics, predictors, and the prognostic impact of patients with TTS and recurrences in a multicenter registry is needed. Methods and Results We analyzed 749 patients with TTS from 9 European centers being part of the international, multicenter GEIST (German Italian Stress Cardiomyopathy) Registry.

Inhibitor of DNA binding proteins: implications in human cancer progression and metastasis.

Inhibitor of DNA binding (ID) proteins are a class of helix-loop-helix (HLH) transcription regulatory factors that act as dominant-negative antagonists of other basic HLH proteins through the formation of non-functional heterodimers. These proteins have been shown to play critical roles in a wide range of tumor-associated processes, including cell differentiation, cell cycle progression, migration and invasion, epithelial-mesenchymal transition, angiogenesis, stemness, chemoresistance, tumorigenesis, and metastasis. The aberrant expression of ID proteins has not only been detected in many types of human cancers, but is also associated with advanced tumor stages and poor clinical outcome.

Long-Term Follow-Up of Patients With Short QT Syndrome: Clinical Profile and Outcome.

Background Short QT syndrome ( SQTS ) is a rare inheritable disease associated with sudden cardiac death. Data on long-term outcomes of families with SQTS are limited. Methods and Results Seventeen patients with SQTS in 7 independent families (48% men; median age, 42.

Congenital diaphragmatic hernia in a case of Cat eye syndrome.

Our findings extend the phenotypic spectrum of Cat eye syndrome, a disorder with wide clinical variability. The potentially life-threatening complications of congenital diaphragmatic hernia should be considered in genetic counseling and prenatal diagnostic.

Phase 3, single-arm, multicenter study of dabigatran etexilate for secondary prevention of venous thromboembolism in children: Rationale and design.

Background: Anticoagulant therapy for venous thromboembolism (VTE) in children is largely based on treatment recommendations for adults. However, differences in both physiology (ie, renal maturation and drug excretion) and developmental hemostasis must be considered when treating children, as such differences could affect dose appropriateness, safety and efficacy.

Objectives: To address these concerns, a study was designed to evaluate the safety of dabigatran etexilate in children requiring secondary thrombus prevention in whom an initial VTE was associated with an identified risk factor that persisted after the acute VTE treatment period.

Design and rationale for the DIVERSITY study: An open-label, randomized study of dabigatran etexilate for pediatric venous thromboembolism.

Background: The current standard of care (SOC) for pediatric venous thromboembolism (VTE) comprises unfractionated heparin (UFH), or low-molecular-weight heparin (LMWH) followed by LMWH or vitamin K antagonists, all of which have limitations. Dabigatran etexilate (DE) has demonstrated efficacy and safety for adult VTE and has the potential to overcome some of the limitations of the current SOC. Pediatric trials are needed to establish dosing in children and to confirm that results obtained in adults are applicable in the pediatric setting.

Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism.

Background: The incidence of venous thromboembolism (VTE) in children has been increasing. Anticoagulants are the mainstay of treatment but are associated with bleeding events that may be life-threatening. Idarucizumab is a fragment antigen-binding (fab) that provides immediate, complete, and sustained reversal of dabigatran's anticoagulant effects in adults.

Strengthening health data on a rare and heterogeneous disease: sarcoma incidence and histological subtypes in Germany.

Background: The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries.

Loss of epithelial cell adhesion molecule (EpCAM) in infiltrative basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common type of skin cancer and expresses high protein levels of the epithelial cell adhesion molecule (EpCAM, syn. CD326). Though BCCs only rarely metastasize, infiltrative and destructive growth do occur.