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包括的凝固/線溶動態に基づく敗血症性DIC（播種性血管内凝固）の病態解明
Get PDFBackground: The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin-antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. Methods: Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma. Results: CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min - max: 0.10 - 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 - 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 - 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 - 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios (ρ = 0.55, p < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios (ρ = 0.71, p < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant. Conclusion: A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals.博士（医学）・甲第786号・令和3年3月15日© 2020. Thieme. All rights reserved.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0040-1713890
Upshaw-Schulman症候群の糸球体障害には補体活性とADAMTS13欠損が関連している可能性がある
Get PDFIntroduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.博士（医学）・甲第792号・令和3年3月15日Copyright © 2018 Elsevier Ltd. All rights reserved
本邦で分離されたカルバペネマーゼ産生肺炎桿菌の分子遺伝学的解析
Get PDFCarbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan.IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance.博士（医学）・乙第1509号・令和3年3月15日Copyright © 2020 Yonekawa et al. This is an open-access article distributed under the terms
of the Creative Commons Attribution 4.0 International license(https://creativecommons.org/licenses/by/4.0/)
僧帽弁閉鎖不全症を伴うまたは伴わない非代償性急性心不全患者の予後に心房細動が与える影響
Get PDFBackground: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.博士（医学）・甲第799号・令和3年9月29日© 2021, THE JAPANESE CIRCULATION SOCIETY
This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0
A Study on Vonoprazan Based Helicobacter Pylori Eradication with in An Aging Community in Nara Prefecture.
Get PDFIntroduction: There are few reports on the efficacy and safety of vonoprazan (P-CAB) based triple eradication therapy in the elderly. In this study, we investigated the efficacy and safety of P-CAB based eradication of Helicobacter pylori (H. pylori) in non-elderly and elderly patients in our community, where the elderly population is high (41.7%). Methods: 205 patients who underwent primary and secondary eradication for H. pylori at our hospital from October 2018 to December 2020, were included in this study. Results: In primary eradication, the success rate for eradication in non-elderly and elderly patients was 96.6% (57 of 59 patients) and 88.7% (110 of 124 patients) respectively (P=0.10). The success rate for eradication in the late-elderly was 90.2% (46 of 51 patients). There was no significant difference compared with non-elderly patients (P = 0.25). The success rates for secondary eradication in non-elderly and elderly patients were 100% (7 of 7 patients) and 66.7% (10 of 15 patients). respectively, with no significant difference between the two groups (P = 0.13). The success rate for eradication in the late-elderly was low (40.0%: 2 of 5 cases). and there was significant difference compared with that in the non-elderly (P < 0.05). In the primary eradication, there was only one case of death from other diseases in the late-elderly patients during the first week after treatment. Discussion: In the elderly, the efficacy of primary eradication was similar to that for the non-elderly, and the frequency of incidental disease was low. Although the efficacy of secondary eradication was lower in the elderly, it was a safe treatment
Prevention of Recidivism Support for Community-Dwelling Forensic Patients: Assessment Items for Changes in The Patient's Condition Preceding The Appearance of Symptoms Developed in The Patient-Nurse Relationship.
Get PDFPrevention of recidivism in community-dwelling forensic patients is an important task for nurses. This study aimed to clarify how assessment items for change in the patient's condition are developed between patients and nurses. It also aimed to clarify assessment items for changes in patients preceding the appearance of symptoms that lead to offending behavior. The processes in the development of assessment items for changes in the patient's condition in the patient-nurse relationship were: "Evaluation of assessment items between patients and nurses", "patient-initiated assessment", and "sharing of assessment results between patients and nurses". The assessment items for changes in the patient's condition were "changes compared with usual life", "identification of difficulties in the patients' lives", and "identification of factors that trigger symptoms"
