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Pachychoroid neovasculopathy と加齢黄斑変性症における血漿 von Willebrand 因子に焦点を当てた解析
Get PDFPachychoroid neovasculopathy (PNV) is a new concept of macular disorder. Some cases diagnosed as age-related macular degeneration (AMD) have been re-diagnosed as PNV. However, the biological features of PNV are still uncertain. The purpose of this study was to compare PNV and AMD by analyses focusing on von Willebrand factor (VWF) and complement factor H (CFH). Ninety-seven patients who were previously diagnosed with treatment naïve AMD were enrolled in this study. They were re-classified as either PNV or AMD based on the clinical criteria and 33 patients were classified as PNV and 64 patients as AMD. We examined the clinical data, analyzed VWF multimer and two genetic polymorphisms (I62V and Y402H) in the CFH. PNV group was significantly younger than AMD group (P = 0.001). In both I62V and Y402H, there were no significant differences between PNV and AMD while the recessive homozygous (AA) was found only in PNV group in I62V. The presence of unusually large VWF multimers (UL-VWFMs) and subretinal hemorrhages were significantly higher in PNV than in AMD (P = 0.045, P = 0.020, respectively). Thus, the residual UL-VWFMs may result in platelet thrombosis and hemorrhages in the choriocapillaris of PNV. In conclusion, our results suggest the biological differences between PNV and AMD.博士（医学）・甲第832号・令和4年3月15日© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
頭蓋骨形成術後の手術部位感染予防のための80％エタノール溶液に保存した自家骨移植片の有効性。後方視的コホート研究
Get PDFBackground: Surgical site infection (SSI) is common following cranioplasty after decompressive craniectomy (DC). The aim of this study was to assess the risk of SSI following cranioplasty in terms of the preservation method of autogenous bone graft (ABG), comparing preservation in 80% ethanol versus the standard method of subcutaneous ABG preservation. Material and methods: The patients who underwent cranioplasty using ABGs after DC between 2008 and 2019 were retrospectively reviewed. SSIs were compared between patients whose ABG was preserved in 80% ethanol (group A) and those whose ABG was preserved subcutaneously (group B) using inverse probability of treatment weighting (IPTW) based on propensity scores to balance measurable confounders including elderly age, sex, expanded polytetrafluoroethylene, stroke, interval to cranioplasty, and diabetes mellitus. Results: Total number of 127 patients consisted of 56 in group A and 71 in group B. SSI after cranioplasty occurred in five patients each in groups A and B (8.9% vs. 7%, p = 0.748). IPTW analysis demonstrated that preservation in 80% ethanol was associated with a lower risk of SSI (odds ratio: 0.239, 95％ confidence interval: 0.0615–0.927, p = 0.039). Conclusion: The simple and less-invasive method of preserving ABGs in 80% ethanol for cranioplasty after DC might be potentially safe from an SSI perspective.博士（医学）・乙第1526号・令和4年3月15日© 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND licens(https://creativecommons.org/licenses/by-nc-nd/4.0/)
子宮頸がん検診管理方式における米国、豪州、欧州と日本の現状
No full text子宮頸がん検診管理方式における米国、豪州、欧州と日本の現状について解説する。米国では2020年4月に公開されたASCCP(American Society for Colposcopy and Cervical Pathology）ガイドライン2019が子宮頸がん検診管理方式における根幹をなすものであり、世界の標準となる指針である。豪州では細胞診による検診が2017年12月よりHPV(human papillomavirus）検査単独へ変更した。欧州ではHPV検査単独から開始とするガイドラインがあるものの国ごとに管理方式の差異を認めた。日本の現状として、頸部細胞診HSILのみでは治療が容認されないことと、生検でCIN2の場合の取扱いが世界と異なった。子宮頸がん検診管理方式における世界の潮流として、初回スクリーニングとしてHPV検査を優先したのちにHPV陽性者に対象を絞り細胞診を実施する流れがあり、細胞診HSILに対する即時の診断的LEEP(loop electrosurgical excision procedure）治療の容認を認めた。世界と日本の間には子宮頸がん検診管理方式に乖離を認めるものの、今後はその乖離を近づけることが肝要と考える
自閉スペクトラム症における幼少期逆境体験と白質微小構造障害の関連性についての検討
Get PDFIndividuals with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs) than typically developed (TD) children. Since multiple lines of studies have suggested that ACEs are related to myelination in the frontal lobe, an exposure to ACEs can be associated with white matter microstructural disruption in the frontal lobe, which may be implicated in subsequential psychological deficits after the adulthood. In this study, we investigated the relationship between ACEs and microstructural integrity on frontal lobe-related white matter tracts using diffusion tensor imaging in 63 individuals with ASD and 38 TD participants. Using a tractography-based analysis, we delineated the uncinate fasciculus (UF), dorsal cingulum (Ci), and anterior thalamic radiation (ATR), which are involved in the neural pathology of ASD, and estimated each diffusion parameter. Compared to the TD participants, individuals with ASD displayed significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the left ATR. Then, ASD individuals exposed to severe ACEs displayed higher RD than those exposed to mild ACEs and TD participants in the left ATR. Moreover, the severity of ACEs, particularly neglect, correlated with lower FA and higher RD in the left UF and ATR in individuals with ASD, which was not observed in TD participants. These results suggest that an exposure to ACEs is associated with abnormality in the frontal lobe-related white matter in ASD.博士（医学）・甲第843号・令和4年6月29日Copyright © 2022 Yoshikawa, Kitamura, Matsuoka, Takahashi, Ishida, Kishimoto, Yasuno, Yasuda, Hashimoto, Miyasaka, Kichikawa, Kishimoto and Makinodan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY: https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
複雑先天性心疾患患者における心房細動の病因 : より良い治療戦略のために
Get PDFBackground: The demographics of patients with congenital heart disease (CHD) and atrial fibrillation (AF) differ significantly from the general population. The etiology and treatment strategy for AF in CHD patients have been investigated but are to date inconclusive. Methods: To determine the etiology of AF in CHD and to seek a better treatment strategy, we retrospectively evaluated the atrial overload in 42 complex CHD cases with normal atrial arrangements and AF (age 25; range, 9-66 years) and the impact of a reduction in the atrial overload on the atrial rhythm. Results: Cardiac defect diagnoses varied, with 17% of the patients having a persistent left superior vena cava (PLSVC). In regard to the volume overload, the frequencies of an overload in the right atrium (RA), left atrium (LA), or both, were 50 %, 23%, and 10%, respectively (p = 0.015). Other sustained supraventricular tachycardias were observed in 29 patients (69%) before and after the onset of AF. Among these 29 patients, 26 had intra-atrial reentrant tachycardia. Fifteen patients (36%), 10 of whom had chronic AF, died during the follow-up including 3 with arrhythmias and 10 because of heart failure. Fourteen (33%) patients had no AF at the last follow-up due to medical interventions, 8 of which underwent solely an RA-sided catheter ablation and/or surgical RA overload reduction. Conclusions: AF in complex CHD with a normal atrial arrangement correlates with a higher RA-sided overload than an LA-sided and exhibits a high incidence of PLSVCs, high comorbidity of intra-atrial reentrant tachycardias, and high mortality rate. In a substantial number of patients, RA-sided interventions were effective in controlling AF. To effectively manage AF in complex CHD it is essential to understand each individual's hemodynamics and consider hemodynamic interventions.博士（医学）・甲第853号・令和4年9月28日© 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology
NDBを用いた新たな患者追跡手法の開発
Get PDFThe National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is a comprehensive database containing health insurance claim information. The structure of the NDB complicates long-term cohorts for two main reasons. First, the NDB data are stored on a per-claim basis. Second, the NDB is a billing-focused record structure. Therefore, the objective of this study was to use ID0 to modify the data structure to allow for long-term cohorts, provided that the data volume is not increased and the runtime per data year is maintained within one month. The NDB uses two primary keys (ID1 and ID2) made from hash values that mask personally identifiable information. ID0 is our recently developed key from ID1 and ID2, which improves patient-matching efficiency with excellent long-term tracing performance. Our study used claim data with filing dates between April 2013 and March 2016 to trace hospitalizations of one month or longer, including outpatient care, in three steps. In Step 1, claims were transferred to a CD-record format. As some diagnosis procedure combination (DPC) claim records contain a mixture of overlapping comprehensive and piece-rate data, we sorted and reorganized them. In Step 2, pharmacy and medical outpatient claims were integrated using the ID0 key, the medical institution code for issuing a prescription, and the prescription issue date. In Step 3, the transferred data were combined and converted from consecutive hospitalization days into sequences based on ID0, the medical institution code, and hospital ward classification. Consequently, the size of the originally extracted comma-separated variable dataset for three years (approximately 10.5 TB) was reduced to an approximately 6 TB main database file that was usable for processing. The process took approximately three months. With similar conventional methods, the data size was 30 times larger, and it took more than seven months to process a year's worth of data. In addition, to demonstrate the application of this method, we conducted a six-year mortality cohort for all Japanese citizens. Our technique makes it easy to perform follow-up and longitudinal cohort surveys while accurately tracing patient data in large-scale medical claims databases.博士（医学）・甲第854号・令和4年12月22日Copyright: ©2022 The Author(s). This is an open
access article distributed under the terms of the
Creative Commons BY 4.0 International (Attribution) License (https://
creativecommons.org/licenses/by/4.0/legalcode), which permits the
unrestricted distribution, reproduction and use of the article provided
the original source and authors are credited
柿タンニンは新型コロナウイルスに対する抗ウイルス効果を持ち、シリアンハムスターモデルにおける新型コロナウイルス感染症の重症度および感染伝播を抑制する
Get PDFCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the world. Inactivating the virus in saliva and the oral cavity represents a reasonable approach to prevent human-to-human transmission because the virus is easily transmitted through oral routes by dispersed saliva. Persimmon-derived tannin is a condensed type of tannin that has strong antioxidant and antimicrobial activity. In this study, we investigated the antiviral effects of persimmon-derived tannin against SARS-CoV-2 in both in vitro and in vivo models. We found that persimmon-derived tannin suppressed SARS-CoV-2 titers measured by plaque assay in vitro in a dose- and time-dependent manner. We then created a Syrian hamster model by inoculating SARS-CoV-2 into hamsters' mouths. Oral administration of persimmon-derived tannin dissolved in carboxymethyl cellulose before virus inoculation dramatically reduced the severity of pneumonia with lower virus titers compared with a control group inoculated with carboxymethyl cellulose alone. In addition, pre-administration of tannin to uninfected hamsters reduced hamster-to-hamster transmission of SARS-CoV-2 from a cohoused, infected donor cage mate. These data suggest that oral administration of persimmon-derived tannin may help reduce the severity of SARS-CoV-2 infection and transmission of the virus.博士（医学）・甲第817号・令和4年3月15日© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
たこつぼ症候群におけるカテコラミンと機械的サポートの効果
Get PDFObjective: This study aimed to reveal the clinical characteristics of patients with severe Takotsubo syndrome (TTS) who needed catecholamine support (CS) or mechanical support (MS) and to identify factors associated with serious illness and in-hospital mortality. Methods: This was a nationwide retrospective study that used claims data from the Japanese registry of all cardiac and vascular diseases and the diagnosis procedure combination registry, from April 2012 to March 2016. The patients with TTS were divided into severe TTS and mild TTS groups. The severe group was defined as patients who needed CS and/or MS. Results: Among 6169 patients with TTS, 1148 (18.6%) had severe TTS. No significant difference in age was found between the two groups; however, the number of female patients was significantly lower in the severe group than in the mild group. Among 130 patients who underwent MS, 22 and 108 patients required MS alone and both MS and CS, respectively. The 30-day mortality rate was significantly higher in the severe group than in the mild group (11.4% vs 2.6%, p<0.01) and increased with age. Of the patients with severe TTS, 65.6% died within 7 days. Multivariable analysis showed that male sex (OR 1.22, p=0.03), higher Charlson scores (OR 1.11, p<0.01), comorbid pneumonia (OR 1.68, p<0.01), comorbid sepsis (OR 6.02, p<0.01) and ambulance use (OR 2.01, p<0.01) were associated with severe TTS. Conclusions: The rate of severe TTS was 18.6% among 6169 patients registered in the Japanese nationwide database, and the 30-day mortality was higher in patients with severe TTS than in those with mild TTS (11.4% vs 2.6%).博士（医学）・甲第822号・令和4年3月15日© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.This article has been accepted for publication in Heart, 2022 following
peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/heartjnl-2021-319904
骨転移を有する泌尿器科がんに特化した予後予測スコアリングモデル(B-FOM model)の外部検証および他のスコアリングモデルとの予後予測精度の比較
Get PDFObjective: We previously developed genitourinary (GU) cancer-specific scoring system for prediction of survival in patients with bone metastasis (the Bone-Fujimoto-Owari-Miyake [B-FOM] scoring model) based on five prognostic factors: the type of primary tumor (prostate cancer (PCa) vs renal cell carcinoma (RCC) and PCa vs urothelial carcinoma (UC)), poor performance status (PS), visceral metastasis, high Glasgow-prognostic score (GPS), elevated neutrophil-to-lymphocyte ratio (NLR). The aim of this study was to externally validate and further improve the performance of the B-FOM score. Methods: The external validation cohort comprised 309 patients with GU cancer with bone metastasis from multiple institutions. Clinical factors were analyzed using Kaplan-Meier method and COX regression hazard model. Performance of a modified B-FOM score was compared to that of other scoring models by the Kaplan-Meier method and the area under the curve (AUC) of receiver operating characteristic curves. Results: The median follow-up period of development and validation cohort were 25 and 17 months, respectively. Kaplan-Meier curve demonstrated that the type of primary tumor (RCC and UC vs PCa), poor PS, presence of visceral metastasis, high GPS, elevated NLR were significantly associated with shorter cancer-specific survival. Risk groups were successfully stratified by the modified B-FOM score classification. Moreover, the AUC of the modified B-FOM scoring model for predicting mortality at 6, 12, and 24 months were 0.895, 0.856, and 0.815, respectively, which were the highest among evaluated models. Conclusions: The B-FOM scoring model is a simple and accurate prediction tool. By using this scoring model at the time of the diagnosis of bone metastasis in patients with GU cancers, an individualized optimal treatment strategy can be selected.博士（医学）・甲第835号・令和4年3月15日© 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license(https://creativecommons.org/licenses/by-nc-nd/4.0/)
切除およびラジオ波凝固療法が適応外と判断された肝細胞癌症例に対する経動脈的化学塞栓療法と放射線療法の併用療法の効果
Get PDFPurpose: The local control rate of trans-arterial chemoembolization (TACE) for the patients with hepatocellular carcinoma (HCC) was unsatisfactory compared to resection or radiofrequency ablation (RFA). We performed radiation therapy after TACE to increase the control rate in our institution. The purpose of this study was to evaluate the efficacy and toxicity of the TACE and radiotherapy combination in HCC patients ineligible for resection or RFA. Material and Methods: Between January 2017 and April 2020, 33 patients with HCC ineligible for resection or RFA were treated with a combination of TACE and radiation therapy. Eight patients were initial cases, and 25 were recurrent or residual cases. A total dose of 40-60 Gy in 5-20 fractions was delivered to the 50-90% isodose line. Results: The median follow-up period was 16 months (range, 6-47 months); objective response rate, 66.7%; and the 1- and 2-year overall survival rates, 72.7% and 62.5%, respectively. The objective response rate of HCCs <5 cm was 79.2%; the 1- and 2-year overall survival rates, 91.7% and 62.5%, respectively; median progression-free survival, 13.5 months (range, 3-47 months), and the 1- and 2-year local progression-free survival rates, 95.8% and 85.7%, respectively. There was one case each of grade 2 radiation esophagitis and ascites after three months of irradiation. Conclusion: The combination of TACE and radiation therapy shows good local control and acceptable toxicity, particularly in HCCs <5 cm and may be a good treatment option.博士（医学）・甲第837号・令和4年3月15