Dose T2-weighted short TI inversion recovery images on cardiac magnetic resonance reflect disease activity in cardiac involvement of sarcoidosis patients?

The 76th Annual Scientific Meeting of the Japanese Circulation Society 2012年03月18日 Fukuok

Can late gadolinium enhancement on cardiovascular magnetic resonance describe cardiac involvement in patients with systemic sarcoidosis and/or suspect of cardiac involvement of sarcoidosis with cardiac symptoms?

2011 SCMR/Euro CMR Joint Scientific Sessions Nice, France. 3-6 February 201

Value of late gadolinium enhancement by magnetic resonance in patients with cardiac sarcoidosis: characteristic findings and clinical utility

73rd Annual Scientific Meeting of the Japanese Circulation Society 2009年03月 Osak

Impact of renal dysfunction on the choice of diagnostic imaging, treatment strategy, and outcomes in patients with stable angina

We investigated the interaction between the prognostic impact of a decrease in eGFR and the choice of initial diagnostic imaging modality for coronary artery disease. Out of 2878 patients who enrolled in the J-COMPASS study, 2780 patients underwent single photon emission computed tomography (SPECT), coronary computed tomography (CT) angiography, or coronary angiography (CAG) as an initial diagnostic test. After excluding patients with routine hemodialysis or lacked serum creatinine levels, 2096 patients in the non-decreased eGFR group (eGFR ≥ 60 ml/min/1.73 m²) and 557 patients in the decreased eGFR group (eGFR < 60 ml/min/1.73 m²) were analyzed in this study. Major adverse cardiac events, including death, myocardial infarction, heart failure hospitalization, and late revascularization, were followed, with a median follow-up duration of 472 days. SPECT or CAG was preferable to CT in patients in the decreased eGFR group (p < 0.0001 and p = 0.0024, respectively). There was a marginally significant interaction between the prognostic impact of a decrease in eGFR and the choice of diagnostic imaging modality (interaction-p = 0.056). A decrease in eGFR was not associated with a poor outcome in patients who underwent CT, while a decrease in eGFR was associated with poor outcomes in patients who underwent SPECT or CAG. In conclusion, the prognostic impact of a decrease in eGFR tended to be different among the initial imaging modalities

Association of coronary revascularisation after physician-referred non-invasive diagnostic imaging tests with outcomes in patients with suspected coronary artery disease: a post hoc subgroup analysis

Objective: We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease. Design: A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study. Setting: Multiple centres in Japan. Participants: From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata. Primary and secondary outcome measures: Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ2 test, Student’s t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis. Results: A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p<0.0001; CT stratum: 6.1 vs 0.8%, log-rank p=0.0001), there was no interaction between the risk of revascularisation and the imaging strata (SPECT stratum: adjusted HR (95% CI), 4.25 (1.86–9.72); CT stratum: 4.13 (1.16–14.73); interaction: p=0.97). Conclusion: The association of revascularisation with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion

Value of late gadolinium enhancement by magnetic resonance in patients with cardiac sarcoidosis: characteristic findings and clinical utility

73rd Annual Scientific Meeting of the Japanese Circulation Society 2009年03月 Osak

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