REV-ERB agonist suppresses IL-17 production in gamma delta T cells and improves psoriatic dermatitis in a mouse model

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and cellular infiltration. Studies have shown that disease development depends on proinflammatory cytokines, such as interleukin (IL)-23 and IL-17. It has been suggested that IL-23 produced by innate immune cells, such as macrophages, stimulates a subset of helper T cells to release IL-17, promoting neutrophil recruitment and keratinocyte proliferation. However, recent studies have revealed the crucial role of gamma delta T cells in psoriasis pathogenesis as the primary source of dermal IL-17. The nuclear receptors REV-ERBs are ligand-dependent transcription factors recognized as circadian rhythm regulators. REV-ERBs negatively regulate IL-17-producing helper T cells, whereas the involvement of REV-ERBs in regulating IL-17-producing gamma delta T (gamma delta T17) cells remains unclear. Here we revealed the regulatory mechanism involving gamma delta T17 cells through REV-ERBs. gamma delta T17 cell levels were remarkably elevated in the secondary lymphoid organs of mice that lacked an isoform of REV-ERBs. A synthetic REV-ERB agonist, 5R9009, suppressed gamma delta T17 cells in vitro and in vivo. Topical application of SR9009 to the skin reduced the inflammatory symptoms of psoriasiform dermatitis in mice. The results of this study provide a novel therapeutic approach for psoriasis targeting REV-ERBs in gamma delta T17 cells

A new mapping method to estimate exit sites of ventricular arrhythmias using intracardiac echocardiography and M-mode for catheter ablation

Background: Catheter ablation of premature ventricular complexes (PVCs) has been used as a curative therapy in many cases. Intracardiac ultrasound with a magnetic sensor probe has recently become available for catheter ablation. In this study, we assessed a new mapping method, contraction mapping, for determining the optimal ablation sites using intracardiac ultrasound and M-mode. This study sought to assess the accuracy of the new mapping method using intracardiac echocardiography. Methods: Eighteen patients (10 males and eight females; mean age, 63±12 years) with 104 mapping points diagnosed as idiopathic PVCs were included in this study. At the mapping points, the time interval from the onset of the QRS to the onset of the contraction (QRS-c-time) and the local activation time were measured using M-mode with an intracardiac echo probe and using the conventional method. The correlation between the QRS-c-time and local activation time were studied. Results: The QRS-c-time was significantly correlated with the local activation time (activation time=−66.8+0.882 * QRS-c-time, R2=0.728, p<0.0001). Conclusions: Contraction mapping could help determine the local activation time without the delivery of a catheter to the mapping points

Complications and mortality after catheter ablation of ventricular arrhythmias

$\bf Aims$ Catheter ablation of ventricular arrhythmias (VA) has proven to be an effective therapeutic option for secondary arrhythmia prophylaxis. We sought to assess the procedural efficacy, safety and in-hospital mortality of a large patient cohort with and without structural heart disease undergoing VA ablation. $\bf Methods$ A total of 1417 patients (804 patients with structural heart disease) undergoing 1792 endo- and epicardial procedures were analyzed. Multivariable risk factor analysis for occurrence of major complications and intrahospital mortality was obtained and a score to allow preprocedural risk assessment for patients undergoing VA ablation procedures was established. $\bf Results$ Major complication occurred in 4.4% of all procedures and significantly more often in patients with structural heart disease than in structurally normal hearts (6.0 vs. 1.8%). The frequency of these periprocedural complications was significantly different between procedures with sole right ventricular and a combination of RV and LV access (0.5 vs. 3.1%). The most common complication was cardiac tamponade in 46 cases (3.0%). Intrahospital death was observed in 32 patients (1.8%). Logistic regression model revealed presence of ischemic heart disease, epicardial ablation, presence of oral anticoagulation or dual antiplatelet therapy as independent risk factors for the occurrence of complications or intrahospital death, while a history of previous heart surgery was an independent predictor with a decreased risk. Based on this analysis a risk score incorporating 5 standard variables was established to predict the occurrence of complications and intrahospital mortality. $\bf Conclusions$ Safety of VA catheter ablation mainly relies on patient baseline characteristics and the type of access into the ventricles or epicardial space