Attenuation correction of myocardial SPECT by scatter-photopeak window method in normal subjects

金沢大学医薬保健研究域Objective: Segmentation with scatter and photopeak window data using attenuation correction (SSPAC) method can provide a patient-specific non-uniform attenuation coefficient map only by using photopeak and scatter images without X-ray computed tomography (CT). The purpose of this study is to evaluate the performance of attenuation correction (AC) by the SSPAC method on normal myocardial perfusion database. Methods: A total of 32 sets of exercise-rest myocardial images with Tc-99 m-sestamibi were acquired in both photopeak (140 keV ± 10%) and scatter (7% of lower side of the photopeak window) energy windows. Myocardial perfusion databases by the SSPAC method and non-AC (NC) were created from 15 female and 17 male subjects with low likelihood of cardiac disease using quantitative perfusion SPECT software. Segmental myocardial counts of a 17-segment model from these databases were compared on the basis of paired t test. Results: AC average myocardial perfusion count was significantly higher than that in NC in the septal and inferior regions (P < 0.02). On the contrary, AC average count was significantly lower in the anterolateral and apical regions (P < 0.01). Coefficient variation of the AC count in the mid, apical and apex regions was lower than that of NC. Conclusions: The SSPAC method can improve average myocardial perfusion uptake in the septal and inferior regions and provide uniform distribution of myocardial perfusion. The SSPAC method could be a practical method of attenuation correction without X-ray CT. © 2009 The Japanese Society of Nuclear Medicine

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

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

Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016&ndash;March 2018) and post-AST (April 2018&ndash;March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (&beta; = &minus;0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (&gt;8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum &beta;-lactamases and AmpC) (95% confidence interval, 1.030&ndash;2.818, 1.067&ndash;66.667, 1.057&ndash;2.782, 0.168&ndash;0.742, and 1.382&ndash;5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders

Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016–March 2018) and post-AST (April 2018–March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (β = −0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (>8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum β-lactamases and AmpC) (95% confidence interval, 1.030–2.818, 1.067–66.667, 1.057–2.782, 0.168–0.742, and 1.382–5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders