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非心臓手術における、術前の蛋白尿と術後急性腎障害の関連: 奈良AKIコホート研究
Get PDFBackground: Little is known about the association between pre-operative proteinuria and post-operative acute kidney injury (AKI) in noncardiac surgery. Methods: This is a retrospective cohort study. Adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data for analyses or pre-operative dialysis were excluded. Exposure of interest was pre-operative proteinuria, defined as (+) or more by dipstick test. The outcome variable was post-operative AKI, defined by Kidney Disease: Improving Global Outcomes criteria, within 1 week after surgery. Multivariable logistic regression analyses were performed. Results: Among 5168 subjects, 309 (6.0%) developed AKI. Pre-operative proteinuria was independently associated with post-operative AKI, with an odds ratio (OR) [95% confidence interval (CI)] of 1.80 (1.30-2.51). A sensitivity analysis restricted to elective surgery yielded a similar result. As proteinuria increased, the association with AKI became stronger [OR (95% CI) 1.14 (0.75-1.73), 1.24 (0.79-1.95), 2.75 (1.74-4.35) and 3.95 (1.62-9.62) for urinary protein (+/-), (+), (2+) and (3+), respectively]. Subgroup analyses showed proteinuria was especially associated with post-operative AKI among subjects with renin-angiotensin system inhibitors, other anti-hypertensives, hypoalbuminemia or impaired renal function (P for interaction = 0.05, 0.003, 0.09 or 0.02, respectively). Conclusions: In noncardiac surgery, pre-operative proteinuria was independently associated with post-operative AKI. Subjects with proteinuria should be managed with caution to avoid AKI peri-operatively.博士（医学）・甲第777号・令和3年3月15日© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.This is a pre-copyedited, author-produced version of an article accepted for publication in Nephrology dialysis transplantation following peer review. The version of record Nephrology Dialysis Transplantation, Volume 35, Issue 12, December 2020, Pages 2111–2116, is available online at: https://doi.org/10.1093/ndt/gfz269
大腸癌肝転移におけるCD200発現の臨床的意義
Get PDFBackground: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). Methods: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. Results: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy. Conclusions: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM.博士（医学）・乙第1497号・令和3年3月15日© 2021. Society of Surgical Oncology.© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Annals of Surgical Oncology. The final authenticated version is available online at: https://doi.org/10.1245/s10434-020-09471-w
犬モデルにおける ex vivo および in vivo 遺伝子治療のための代替遺伝子導入技術の開発
Get PDFIntroduction: Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A. Here we investigated the efficacy and safety of the technologies in canine model. Especially, validations of technical procedures of the gene transfers for dogs were focused. Methods: Green fluorescence protein (GFP) gene were transduced into normal beagle dogs by ex vivo and in vivo gene transfer techniques. For ex vivo gene transfer, blood outgrowth endothelial cells (BOECs) derived from peripheral blood of normal dogs were transduced with GFP gene using lentivirus vector, propagated, fabricated as cell sheets, then implanted onto the omentum of the same dogs. For in vivo gene transfer, normal dogs were subjected to GFP gene transduction with non-viral piggyBac vector by liver-targeted hydrodynamic injections. Results: No major adverse events were observed during the gene transfers in both gene transfer systems. As for ex vivo gene transfer, histological findings from the omental biopsy performed 4 weeks after implantation revealed the tube formation by implanted GFP-positive BOECs in the sub-adipose tissue layer without any inflammatory findings, and the detected GFP signals were maintained over 6 months. Regarding in vivo gene transfer, analyses of liver biopsy samples revealed more than 90% of liver cells were positive for GFP signals in the injected liver lobes 1 week after gene transfers, then the signals gradually declined overtime. Conclusions: Two types of gene transfer techniques were successfully applied to a canine model, and the transduced gene expressions persisted for a long term. Toward clinical application for hemophilia patients, practical assessments of therapeutic efficacy of these techniques will need to be performed using a dog model of hemophilia and FVIII (or FIX) gene.博士（医学）・乙第1517号・令和3年12月21日© 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
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Construction of Knowledge in Nursing Education: Theoretical Foundation of Inquiry-Based Learning.
Get PDF学習者中心教育の必要性は認識されているが、看護教育現場では伝統的な教師中心型教育が依然として主流である原因の一つは、20世紀以前の情報の稀少性である。情報が多量な21世紀において、教師が特権的に情報を提供するのではなく、学習者が情報を選択する自律的学習が教育の中心となるべきである。伝統的には知識が伝達可能なものとされてきたが、構築主義に基づく探究型学習は、知識を個人が構築するものと位置付ける。さらに、看護が人間の健康全体を関心事とするため、科目ごとの知識の伝達ではない包括的な視点と探究を必要とする。21世紀の看護師に求められる分析的かつ柔軟に考える能力と「絶え間ない改造」による包括的な理解力の育成のためには、アクティブな学習者中心型教育への変換、特に問い (question) を学習経験の始まりとするInquiry-Based Learning (探究基盤型学習) が看護教育には適しているのではないか
長母趾屈筋と長趾屈筋の分枝形態は超音波画像診断装置にて評価できる
Get PDFPurpose: Flexor hallucis longus (FHL) and flexor digitorum longus (FDL) tendons are frequently used in surgery. Therefore, it is necessary to evaluate the chiasma plantare formation preoperatively. The development of ultrasonography (US) may help the chiasma plantare formation evaluation. The purpose of this study is to prove the usefulness of the US method using cadavers. Methods: Eleven cases (twenty-two ankles) were obtained from Asian adult cadavers. At first, we evaluated and compared the chiasma plantare formation using US. Later, we evaluated that using the findings after dissection as type A (connection from FHL to FDL of the second toe), type B (connection from FHL to the second and third toes), type C (connection from FHL to the second through fourth toes), or type D (connection from FHL to all lesser toes). Results: Chiasma plantare formation was classified as types A and B in fifteen and seven ankles, respectively. After dissection, chiasma plantare formation was classified as types A, B, and C in fourteen, six, and two ankles, respectively. Therefore, there was an 86% similarity between the two methods. Conclusions: Chiasma plantare formation can be reliably and noninvasively evaluated using US. This may be useful for preoperative rehabilitation or surgical procedure planning.博士（医学）・甲第782号・令和3年3月15日© 2021. Springer-Verlag France SAS, part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Surgical and radiologic anatomy. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00276-020-02630-4
握力は、糖尿病患者の心血管イベントの独立した予測因子である
Get PDFDiabetes mellitus (DM) is associated with an increased incidence of cardiovascular events and an elevated prevalence of sarcopenia. However, the relationship between cardiovascular events and sarcopenia in patients with DM remains unclear. This study examined this relationship and investigated the predictors of cardiovascular events in this population.This study enrolled 161 patients with DM and no history of cardiovascular diseases who were admitted to our hospital for the treatment of DM between September 2012 and December 2015. Patients were divided into sarcopenia and non-sarcopenia groups, and were followed until March 2019. The primary endpoint was major adverse cardiovascular events (MACE).The mean age was 65.9 ± 1.8 years old and the mean follow-up period was 4.1 ± 0.8 years. The log-rank test indicated that MACE differed significantly between the two groups (P < 0.0001). Multivariate Cox hazard analysis identified the cardio-ankle vascular index (CAVI) and handgrip strength as independent predictors of MACE (hazard ratio [HR] = 1.18, P = 0.039; and HR = 0.70, P = 0.016, respectively).Handgrip strength is an indicator of sarcopenia in diabetic patients, and together with CAVI it was independently associated with the incidence of MACE. This suggests that the handgrip strength test might be useful in the management of patients with DM at high risk of cardiovascular outcomes.博士（医学）・乙第1493号・令和3年3月15日© 2021 by the International Heart Journal Association発行元であるインターナショナル・ハート・ジャーナル刊行会の許諾を得て登録（2021年6月23日付）ジャーナル公式サイト（J-STAGE内）：https://doi.org/10.1536/ihj.20-67
食道切除後の臨床経過に対する無症候性腎機能障害の影響
Get PDFPurpose: Recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with an increased risk of postoperative complications after esophagectomy; however, it remains unclear whether asymptomatic renal dysfunction affects the postoperative course after esophagectomy. Methods: The subjects of this retrospective study were 177 patients who underwent esophagectomy between May, 2009 and December, 2018. Renal function was evaluated based on the pretreatment estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the eGFR cut-off value of 55 ml/min per 1.73 m2. Results: There were 17 patients in the low eGFR group and 160 patients in the normal group eGFR group. The rate of severe complications was significantly higher in the low eGFR than in the normal eGFR group. A low eGFR was the only significant complication risk factor identified; however, there were no marked differences in mortality or survival between the low and normal eGFR groups. Conclusion: Our findings demonstrate that pretreatment asymptomatic renal dysfunction may be a significant risk factor for severe morbidity after esophagectomy.博士（医学）・乙第1494号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02118-z
乳癌術前化学療法において腋窩リンパ節転移が陰性化するための効果予測因子の検討
Get PDFPurpose: We investigated the role of tumor-infiltrating lymphocytes (TILs) in pretreatment primary breast cancer to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with clinical node-positive disease (cN +). Methods: The subjects of this study were 60 patients with cN + , who received NAC followed by breast surgery with axillary lymph node dissection (ALND). We conducted a semi-quantitative assessment of TILs in pretreatment primary tumors and their association with clinicopathological factors and axillary lymph node metastasis. Results: We observed a higher number of TILs in tumors with negative hormone receptors, positive human epidermal growth factor receptor 2, or high Ki67. TILs were associated with a favorable response to NAC in primary tumors. The rate of axillary pathologic complete response (Ax-pCR) was significantly higher in patients with a high number of TILs than in patients with a low number of TILs (72.0% versus 17.1%, p < 0.001). In multivariable analysis, a high number of TILs was a significant predictor of Ax-pCR as well as of pCR of the primary tumor after NAC. Importantly, all patients with HER2-positive tumors in the high TILs group showed Ax-pCR on ALND. Conclusion: TILs in pretreatment primary breast cancer had the potential to predict therapeutic efficacy of NAC in patients with clinical node-positive disease.博士（医学）・乙第1498号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02157-6