Identification of epicardial connections can improve the success rate of first-pass right pulmonary vein isolation.

Background: Epicardial connections between the right pulmonary vein (PV) and the right atrium have been reported. Objective: The purpose of this study was to evaluate the usefulness of our new pulmonary vein isolation (PVI) strategy with identification of these epicardial connections. Methods: Overall, 235 patients with atrial fibrillation were included. High-density mapping of the left atrium was performed to identify the earliest activation sites (EASs) before PVI in all patients. With our new strategy, if EASs around the right PV carina were identified, we ablated these sites and performed usual first-pass circumferential PVI. The patients were divided into 2 groups according to the ablation strategy. One hundred fifteen patients underwent first-pass PVI without information on EASs (nonanalyzed group), and 78 patients underwent ablation at EASs around the right PV carina in addition to PVI (analyzed group). After first-pass ablation around the PV antrum, remapping was performed. Results: High-density mapping before PVI showed that the prevalence of EASs around the right PV carina was 10.9% in all patients (9.6% in the nonanalyzed group, 12.8% in the analyzed group; P = .74. The first-pass right PVI success rate was higher in the analyzed group than in the nonanalyzed group (93.6% vs 82.6%; P = .04). The radiofrequency application time for PVI was significantly shorter in the analyzed group than in the nonanalyzed group (45.6 ± 1.0 minutes vs 51.2 ± 0.9 minutes; P <.05). Conclusion: Identification of epicardial connections before ablation could improve the success rate of first-pass right PVI.

Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosed during Hospitalization for Cardiac Arrest.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically mediated cardiomyopathy charac-terized by progressive myocardial loss of the right ventricle and its replacement by fibrofatty tissue, causing dyskinesia, aneurysm, and/or arrhythmia. The prevalence of ARVC is estimated to be 1 in 2,000-5,000, with the condition accounting for up to 20% of sudden cardiac deaths in individuals < 35 years old. This report describes the case of 61-year-old Japanese who was diagnosed with ARVC after cardiac arrest (CA) and successful resusci-tation. After the sudden CA, the restoration of spontaneous circulation was achieved with appropriate resusci-tation, followed by the introduction of target temperature management in the intensive care unit. He was diag-nosed with ARVC based on angiography and histology results. An ICD (implantable cardioverter-defibrillator) was implanted, and he was discharged without neurological sequelae 1 month post-CA. ARVC is an important cause of sudden CA, and successfully resuscitated patients with right ventricular dilation should undergo testing to rule out ARVC.

A case of secondary IgA nephropathy accompanied by psoriasis treated with secukinumab.

A 60-year-old man was diagnosed with psoriasis 4 years ago. Treatment with adalimumab (a monoclonal anti-TNF-α antibody) became ineffective 1 year ago, and proteinuria and urinary occult blood were detected. Treatment with topical medicine, ultraviolet therapy, and etretinate resulted in remission of psoriasis, and proteinuria and hematuria also improved. For maintenance of remission, treatment with secukinumab (a human anti-interleukin-17A monoclonal antibody) was initiated. After the induction phase, treatment was changed from once a week to once every 4 weeks. After 5 months, he developed nephritis with kidney dysfunction, hematuria, and severe proteinuria (14 g/g Cr) accompanied by pitting edema. After admission, treatment with secukinumab was continued. Kidney biopsy revealed IgA nephropathy with fibrocellular crescents, and immunofluorescence analysis did not detect galactose-deficient IgA1. With these findings, he was diagnosed as secondary IgA nephropathy associated with psoriasis. Tonsillectomy followed by steroid pulse therapy prevented proteinuria and kidney function. In this case, treatment of refractory psoriasis with secukinumab and tonsillectomy was effective, leading to remission of relapsing secondary IgA nephropathy. Therefore, secukinumab might play an immunological role in the treatment of nephropathy.

Glutathione accelerates osteoclast differentiation and inflammatory bone destruction.

Chronic inflammation associated with bone tissues often destructs bones, which is essentially performed by osteoclasts in the presence of immunoregulatory molecules. Hence, regulating osteoclastogenesis is crucial to develop therapeutics for bone-destructive inflammatory diseases. It is believed that reactive oxygen species (ROS) are involved in receptor activator of NF-κB (RANK) ligand (RANKL)-induced osteoclast differentiation, and, therefore, glutathione (GSH), the most abundant endogenous antioxidant, suppresses osteoclast differentiation and bone resorption by RANKL. Interestingly, GSH also contributes to inflammatory responses, and the effects of GSH on osteoclast differentiation and bone destruction under inflammatory conditions have not yet been determined. Here, we investigated how GSH affects inflammatory cytokine-stimulated osteoclast differentiation in vitro and in a mouse model of inflammatory bone destruction. We found that GSH significantly promoted TNFα-stimulated osteoclast formation, while an inhibitor of GSH synthesis, buthionine sulfoximine, suppressed it. GSH facilitated the nuclear localisation of the nuclear factor of activated T cells c1 (NFATc1) protein, a master regulator of osteoclastogenesis, as well as the expression of osteoclast marker genes in a dose-dependent manner. N-acetylcysteine, a substrate of GSH synthesis, also stimulated osteoclast formation and NFATc1 nuclear localisation. GSH did not suppress cell death after osteoclast differentiation. In mouse calvaria injected with lipopolysaccharide, GSH treatment resulted in a fivefold increase in the osteolytic lesion area. These results indicate that GSH accelerates osteoclast differentiation and inflammatory bone destruction, suggesting GSH appears to be an important molecule in the mechanisms responsible for inflammatory bone destruction by osteoclasts.