Very delayed sinus arrest during complete remission of diffuse large B-cell lymphoma invading right atrium.

peer reviewedDiffuse large B-cell lymphoma (DLBCL)-associated arrhythmias may be due to cardiac involvement or may be chemotherapy-induced. There have been no reports of significant arrhythmias with normal cardiac function occurring during the complete remission of DLBCL. A 57-year-old female, who had had no history of abnormal electrocardiograms (ECGs) in annual medical checkups, was admitted to our hospital because of low-grade fever, night sweats, and weight loss. On admission, ECG revealed a variable rhythm consisting of sinus beats and occasional escape beats. Computed tomography and 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) revealed two masses in the right atrium (RA) and the uterus. Total hysterectomy was performed, and pathological findings were consistent with diffuse large B-cell lymphoma (DLBCL). Chemotherapy (R-CHOP) was initiated. After two chemotherapy cycles, RA tumors disappeared, and bradyarrhythmia simultaneously converted to sinus rhythm without antiarrhythmic drug therapy. Six months after completion of chemotherapy, FDG-PET/CT revealed negative uptake in the RA and the uterus. The patient attained complete remission of DLBCL, but ECG showed bradycardia because of sinus arrest. Our case suggests that DLBCL-induced arrhythmia can occur even after its remission and should be monitored

National survey of catheter ablation for atrial fibrillation: The Japanese catheter ablation registry of atrial fibrillation (J-CARAF)

AbstractTo assess the current status of atrial fibrillation (AF) ablation in Japan, the Japanese Heart Rhythm Society (JHRS) instituted a national registry, the Japanese Catheter Ablation Registry of AF (J-CARAF).MethodsUsing an online questionnaire, the JHRS invited electrophysiology centers in Japan to voluntarily and retrospectively register data regarding the AF ablation procedures performed in September, 2011.ResultsA total of 128 centers submitted data regarding AF ablation procedures in 932 patients (age 62.1±10.4 years; male 76.8%; paroxysmal AF 65.7%, CHADS2 score 1.0±1.0). The majority received oral anticoagulant therapy during and following the procedure (68.9% and 97.5%, respectively). Pulmonary vein isolation (PVI) was performed in 97.5% of the patients; ipsilateral encircling PVI was the preferred technique (79.7%). Three-dimensional (3D) mapping systems and irrigated-tip catheters were used in 94.8% and 87.7% of the procedures, respectively. Ablation methods other than PVI were performed in 78.8% of all the patients and 73.5% of the patients with paroxysmal AF. Acute complications were reported in 6.2% of the patients, but no early deaths were recorded.ConclusionsIpsilateral encircling PVI, using 3D mapping and irrigated-tip catheters, is the standard AF ablation method in Japan. However, adjunctive ablations were performed frequently, even in patients with paroxysmal AF

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

High B-type natriuretic peptide levels predict a hypercoagulable state in otherwise low-risk patients with atrial fibrillation

The D-dimer and B-type natriuretic peptide (BNP) levels in relation to CHADS2 and CHA2DS2–VASc scores in 59 patients with atrial fibrillation who were not receiving anticoagulant therapy were analyzed. Among 19 patients with CHADS2 scores of 0–1, 3 of the 7 patients with elevated BNP levels also had elevated D-dimer levels. Among 8 patients with CHA2DS2–VASc scores of 1, 2 of the 3 patients with elevated BNP levels also had elevated D-dimer levels. Therefore, D-dimer levels can be elevated in low-risk patients when BNP levels are high, and anticoagulation therapy should be considered for these patients