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フィリピンの環境（病院排水・河川）より分離されたカルバペネマーゼ産生腸内細菌科の分子遺伝学的解析
Get PDFThis study aimed to evaluate the prevalence and genetic characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in hospital sewage and river water in the Philippines, which has a typical tropical maritime climate. We collected 83 water samples from 7 hospital sewage and 10 river water sites. CPE were identified using CHROMagar mSuperCARBA, and Gram-negative strains were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) or 16S rRNA gene sequencing. Resistance genes in Enterobacteriaceae strains were identified using PCR and DNA sequencing, and transferability of carbapenemase genes from the CPE was investigated with conjugation experiments. Genotyping was performed using multilocus sequence typing (MLST) for Escherichia coli and Klebsiella pneumoniae Out of 124 Enterobacteriaceae isolates, we identified 51 strains as CPE and divided these into 7 species, 11 E. coli, 14 Klebsiella spp., 15 Enterobacter spp., and 11 others, including 4 additional species. Conjugation experiments via broth mating and using E. coli J53 revealed that 24 isolates can transfer carbapenemase-encoding plasmids. MLST analysis showed that 6 of 11 E. coli isolates belonged to clonal complex 10 (CC10). Of 11 K. pneumoniae strains, 9 unique sequence types (STs) were identified, including ST147. Five types of carbapenemase genes were identified, with the most prevalent being NDM (n = 39), which is epidemic in clinical settings in the Philippines. E. coli CC10 and K. pneumoniae ST147, which are often detected in clinical settings, were the dominant strains. In summary, our results indicate that hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.IMPORTANCE Carbapenemase-producing Enterobacteriaceae (CPE) cause severe health care-associated infections, and their increasing prevalence is a serious concern. Recently, natural ecosystems have been recognized as important reservoirs of antibiotic resistance genes. We investigated the prevalence and genetic characteristics of CPE isolated from the environment (hospital sewage and river water) in the Philippines and found several CPE, including Escherichia coli and other species, with different carbapenemases. The most prevalent carbapenemase gene type was NDM, which is endemic in clinical settings. This study revealed that isolates belonging to carbapenemase-producing E. coli CC10 and K. pneumoniae sequence type 147 (ST147), which are often detected in clinical settings, were dominant in the natural environment. Our work here provides a report on the presence and characteristics of CPE in the environment in the Philippines and demonstrates that both hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.博士（医学）・甲第734号・令和2年3月16日Copyright © 2020 Suzuki et al. This is an openaccess article distributed under the terms of
the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/)
肝線維化に対するファルネソイドX受容体アゴニストとジペプチジルペプチダーゼ-4阻害薬の併用効果
Get PDFAim: Non-alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase-4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH. Methods: Fifty Fischer 344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac-HSCs) were assessed in vitro. Results: Treatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac-HSC proliferation and hepatic transforming growth factor (TGF)-β1, α1(I)-procollagen, and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase-2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet-induced zonula occludens-1 disruption, whereas sitagliptin directly inhibited Ac-HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF-β1 and α1(I)-procollagen mRNA expression and p38 phosphorylation in Ac-HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac-HSC. Conclusions: Treatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac-HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH.博士（医学）・甲第737号・令和2年3月16日© 2019 The Japan Society of HepatologyThis is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.13385], which has been published in final form at [https://doi.org/10.1111/hepr.13385]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions
卵巣子宮内膜症性嚢胞の癌化におけるCD44v9と8-OHdGの発現
Get PDFAim: Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up-regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8-OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC). Methods: A retrospective study was performed at the Department of Gynecology, Nara Medical University hospital from January 2006 to December 2012. Patients with histologically confirmed benign OE (n = 27) and OE harboring areas of CCC (n = 8) were selected. Tissue samples were immunohistochemically analyzed for the presence of CD44v9 and 8-OHdG using avidin-biotin complex method. Results: CD44v9 was located on the cell membrane of endometriotic epithelial cells and expressed in 88.9% (24/27) of benign OE tissues. Only 25.0% (2/8) of benign endometriotic lesions adjacent to CCC was found to stain weakly for CD44v9. Percentage of CD44v9 positive cells was 68.5 ± 20.2% (mean ± standard deviation) of benign OE, 16.7 ± 16.5% of CCC endometriotic tissue (P < 0.001). Compared to benign OE, CCC endometriotic tissue showed a significant increase in the proportion of 8-OHdG expression (77.3 ± 22.5% vs 94.9 ± 3.0%, P = 0.049). A significant negative correlation was observed between CD44v9 status and 8-OHdG nuclear expression (r = -0.458, P = 0.006). Conclusion: Alterations in CD44v9 and 8-OHdG may be associated with malignant transformation of benign OE.博士（医学）・乙第1452号・令和2年3月16日© 2019 Japan Society of Obstetrics and Gynecology.This is the peer reviewed version of the following article: [https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.14093], which has been published in final form at [https://doi.org/10.1111/jog.14093]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions
外来診断を可能にするモバイルテクノロジーを用いた細径子宮鏡の使用実績と診断精度の検討
Get PDFOffice hysteroscopy is a minimally invasive procedure and provides a direct view of the endometrial cavity. This study presents the first report of a novel smartphone‑based ultrathin flexible hysterofiberscopy system (currently known as office diagnostic smart hysterofiberscopy, or Hysmartscopy), for the diagnosis of intrauterine abnormalities. The Hysmartscopy system captures images using a flexible fiberscope (0.8 mm in diameter) coupled with an Apple iPhone 6S™. This study was conducted at the Department of Gynecology of Nara Medical University Hospital from February, 2015 to February, 2019. In total, 22 patients requiring a diagnostic Hysmartscopy for the investigation of intrauterine pathology were included in this study. In the first cohort, Hysmartscopy was performed in the operating room with anesthesia in 17 patients to assess the overall physician's experience during image acquisition, subjective image quality and the ease of use on a 5‑point Likert scale. In the second cohort, 5 subjects further underwent Hysmartscopy without anesthesia to evaluate the feasibility and safety of this system. Images were assessed by two expert gynecological endoscopists blinded to the pathological reports. The Hysmartscopy system revealed good resolutions in the ex vivo image and color resolution. From the beginning of the procedure, the time required to capture a video was <1 min. The ergonomic advantage of this technique enabled the examiners to use direct visualization for image‑guided diagnosis in a hand‑held manner. On average, the quality of the images (4.0/5.0 on a 5‑point Likert scale) may be largely sufficient to detect emergent findings. The diagnostic accuracy of Hysmartscopy was found to be 100% (2/2) for the normal endometrium, 71.4% (5/7) for endometrial polyps, 62.5% (5/8) for submucosal fibroids and 100% (5/5) for endometrial cancer. The diagnostic accuracy of Hysmartscopy was 77.3%. None of the cases had any complications during and after the diagnostic procedures. Thus, the results indicate that Hysmartscopy is a patient‑friendly technique without the need for anesthesia and cervical dilation in an office setting. To the best of our knowledge, this study is first proof of concept pilot study of Hysmartscopy. Hysmartscopy may prove to be a simple, convenient, non‑invasive, accurate and well‑tolerated procedure for the diagnosis of intrauterine abnormalities that can be performed within an outpatient clinic.博士（医学）・乙第1453号・令和2年3月16日Copyright: © Iwai et al. This is an open access article distributed under theterms of CreativeCommons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/)
血漿レニン活性値は、急性心筋梗塞患者の独立した予後予測因子である
No full textBackground: Plasma renin activity (PRA) is associated with cardiovascular events in patients with heart failure (HF), but its prognostic role in acute myocardial infarction (AMI) is unclear. Methods and Results: A total of 878 patients with information on baseline PRA on admission were selected from 1,055 AMI patients who underwent emergency coronary angiography between 2007 and 2016. The patients were divided into 2 groups according to their median PRA (2.0 ng/mL/h). The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiovascular death and hospitalization because of HF. During follow-up (median 4.5±3.1 years), MACE occurred in 108 patients. Kaplan-Meier analysis showed that the high PRA group had significantly lower MACE-free survival than the low PRA group (log-rank P=0.0009). By multivariate analysis, high PRA was an independent predictor of MACE (hazard ratio (HR) 1.573; 95% confidence interval (CI) 1.049–2.396, P=0.0282). Similarly, among 580 patients who had not been previously treated with renin-angiotensin system inhibitors or β-blockers on admission, high PRA was an independent predictor of MACE (HR 1.732; 95% CI 1.010–3.047, P=0.0460). Conclusions: In the studied AMI patients, elevated levels of PRA were independently associated with poor prognosis.博士（医学）・甲第745号・令和2年6月30日日本循環器学会の許諾を得て登録（2020年10月19日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj
Support provided by midwives to parturient women transferred in the intrapartum period from an in-hospital midwifery center to a maternity ward for childbirth.
Get PDF目的：分娩期に院内助産から産科病棟での出産へ移行した産婦への助産師のケアの方向性や支援を明らかにする。方法：助産師10名を対象とし半構造化インタビューを行い、質的帰納的方法で分析した。結果：10個のカテゴリーと25個のサブカテゴリーから構成されていた。院内助産からの転棟（移行）を受けた助産師は、【いつ急な院内助産からの転棟があってもいいような準備】を行い、基本的となる支援として【これまでの経過や産婦の思いへの継続ケア】、【新たに信頼関係を築き、慣れない場でのリラックスを促す】、【疲れている産婦や家族を気遣い、気持ちを前向きにさせる】、【転棟して状況が変わったため、最終目標を一緒に確認し達成を目指す】、【産婦が自分の力で産むと感じられる支援】、医療介入を意識したケアでは【状況や必要な医療介入についての理解・納得度を確認する】、【満足度の高い医療介入となるように医師と連携する】ことを行っていた。【産科病棟の特性による課題がある】ことを感じながらも、【お産が育児に影響することを見通して、より良い出産体験となるように関わる】ことをゴールとしていた。考察：日頃から院内助産からの急な転棟（移行）に備えての準備が支援の土台として重要と考えられた。また出産体験が母子の将来に影響を及ぼすため、良い出産となる支援が必要と考えられた。更に産科病棟の特性による課題から、助産師聞の更なる協力等の必要性が示唆された。PURPOSE: To clarify midwives' views on care and support provided by midwives to parturient women transferred in the intrapartum period from an in-hospital midwifery center to a maternity ward. METHOD: Semi-structured interviews were conducted with 10 midwives and answers were qualitatively and inductively analyzed. RESULTS: The analysis produced 10 categories and 25 sub-categories. Midwives who received transferred patients from in-hospital midwifery centers made “preparations to accommodate patients even if they had suddenly been transferred from an in-hospital midwifery center.” As basic support, midwives “provided continuous care for the parturient woman's progress so far and her feelings,”“built a new relationship of trust and encouraged relaxation in an unfamiliar place,”“ showed consideration for the exhausted parturient woman and her family and fostered a positive attitude,”“confirmed the end goals together with the parturient woman to achieve these goals as a result of the change in situation due to the transfer,” and “supported the parturient woman in feeling able to give birth under her own strength.” Midwives also “confirmed the degree of understanding of, and consent for, the situation and necessary medical intervention” and “coordinated with physicians to ensure highly satisfactory medical intervention” in their provision of care with medical intervention in mind. Furthermore, despite feeling that “issues arising from the characteristics of maternity wards exist,” midwives aimed to “provide care to ensure a better childbirth based on the outlook that childbirth affects subsequent childcare. ”DISCUSSION: Regular preparations for sudden transfers from in-hospital midwifery centers appeared to be an important foundation of support. Furthermore, because the experience of childbirth affects the future of the mother and child, support to ensure a good birth was considered necessary
人工足関節再置換術におけるカスタムメイド全置換型人工距骨の応用
Get PDFBackground: The rate of revision surgery for total ankle arthroplasty (TAA) is higher than for hip and knee arthroplasties. Tibiotalocalcaneal arthrodesis is widely used; however, it requires a large allograft. Thus, the use of a customized total talar prosthesis in combination with the tibial component of TAA (combined TAA) may be an effective strategy for talar component subsidence. This study aimed to evaluate the clinical and radiographic effectiveness of the combined TAA in such revision cases. Methods: Between 2000 and 2015, 10 patients (10 women; 10 ankles) were treated using the combined TAA for revision after standard TAA or combined procedures that included the use of a talar body prosthesis. In 6 patients, the tibial component was concurrently replaced. The median follow-up period was 49 months (interquartile range [IQR], 24.5 to 90 months). The Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale score, a numerical rating scale (NRS) pain score, passive range of motion of the ankle, and the presence of osteophytes and degenerative changes in the adjacent joints were assessed preoperatively and at final postoperative follow-up. Results: The median NRS pain score improved significantly, from 7 (IQR, 6.25 to 8.75) to 2 (IQR, 1 to 3). The median JSSF ankle-hindfoot scale total score improved significantly, from 64 (IQR, 56.25 to 71.5) to 88.5 (IQR, 79.75 to 96). In the subcategories of this scale, the median pain score improved from 20 (IQR, 20 to 27.5) to 35 (IQR, 30 to 40), and the median function score improved from 34 (IQR, 26.5 to 37) to 43.5 (IQR, 39.75 to 46). The median range of motion improved from 29° (IQR, 25.5° to 35°) to 35° (IQR, 31.25° to 43.75°). No significant difference in osteophyte formation was found. Degenerative changes in the adjacent joint were found only in the talonavicular joint. Conclusions: The combined TAA, used in revision for postoperative complications after standard TAA or combined procedures including the use of a talar body prosthesis, was associated with improved objective JSSF ankle-hindfoot scale scores, subjective pain assessment, and range of motion in the ankle. Level of evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.博士（医学）・甲第758号・令和2年12月24日Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article
distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/), where it is permissible to
download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal