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日本人2型糖尿病患者において、身体活動レベルが高いことは独立して糖尿病網膜症の新規発症リスク低減と関連する。
Get PDFWe assessed the prospective association between baseline levels of physical activity (PA) and the incidence of newly developed diabetic retinopathy (DR) in patients with type 2 diabetes. Data from 1,814 patients with type 2 diabetes without DR were obtained from a Japanese diabetes registry at Tenri Hospital, Nara, Japan. To assess the independent correlations between baseline PA levels and newly developed DR, the participants were divided into five categories based on their PA levels. A Cox proportional hazards model with time-varying exposure information was used and adjusted for potential confounders to assess the independent correlations. At baseline, the mean age, BMI, and hemoglobin A1c levels of the patients were 65.5 years, 24.5 kg/m2, and 7.2% (54 mmol/mol), respectively. After 2 years, newly developed DR was confirmed in 184 patients (10.1%). Patients with newly developed DR had longer duration of type 2 diabetes (14.7 versus 11.0 years, p < 0.0001), higher systolic blood pressure (139.2 versus 135.1 mmHg, p = 0.0012), lower estimated glomerular filtration rate (74.0 versus 77.1 mL/min/1.73 m2, p = 0.0382), greater urinary albumin–creatinine ratio (4.00 versus 2.45 mg/mmol, p < 0.0039), and higher HbA1c levels (7.5 versus 7.2%, p = 0.0006) than those without newly developed DR. The multivariable-adjusted hazard ratios for DR development were 0.87 (95% CI, 0.53–1.40; p = 0.557), 0.83 (95% CI, 0.52–1.31; p = 0.421), 0.58 (95% CI, 0.35–0.94; p = 0.027), and 0.63 (95% CI, 0.42–0.94; p = 0.025)for the second, third, fourth, and fifth PA categories, respectively, compared with the reference category of patients with a mean PA of 0 metabolic equivalent of task-hours/week). Higher PA levels are independently associated with a lower incidence of DR in Japanese patients with type 2 diabetes.博士（医学）・甲第730号・令和2年3月16日Copyright: © 2017 Kuwata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
脳幹部転移性脳腫瘍に対する寡分割定位放射線治療の治療成績
Get PDFBackground: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Methods: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Results: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Conclusions: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.博士（医学）・乙第1450号・令和2年3月16日Copyright © 2019 Elsevier Inc. All rights reserved
プラスミド性キノロン耐性遺伝子を保有するIMP-6産生腸内細菌科細菌でのイノカラムサイズ効果の比較
Get PDFAlmost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened β-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum β-lactamases. All isolates carried one or more PMQRs; aac(6’)-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-β-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.博士（医学）・乙第1463号・令和2年6月30日Copyright: © 2019 Ogawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited
階段昇降試験中に認められる酸素飽和度低下 : 肺切除を予定している患者の術後合併症の予測指標
Get PDFObjective: It is widely accepted that exercise tolerance tests are applicable in perioperative risk assessment for patients who undergo pulmonary resection; however, the relevance of desaturation during the test is unclear. The purpose of this study was to investigate whether the occurrence of desaturation during a stair-climbing test can be a predictor of postoperative complications among patients who will undergo pulmonary resection and are considered "normal risk" according to published guidelines. Methods: Desaturation was defined as a depression of more than 4% points on a pulse oximeter during stair climbing. Among 186 consecutive patients who underwent pulmonary resection, 162 patients who could climb to the 6th floor were selected for the study (excluding 21 patients who could not stair-climb and 3 patients who could not climb from the first floor to the sixth floor). The relationship of desaturation with postoperative complication was investigated using parameters of cardio-pulmonary status associated with additional foci of oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Results: The occurrence ratio of postoperative complications > grade 3 (Clavien-Dindo classification) was 0.75% (1/133) among patients without desaturation and 17.2% (5/29) in patients with desaturation (difference: p = 0.0002). In addition, DS was an indicator of prolonged oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Conclusion: The occurrence of desaturation during a stair-climbing test for patients who will undergo pulmonary resection can be a predictor of postoperative complications among patients who are classified as having normal risk.博士（医学）・乙第1457号・令和2年6月30日© The Japanese Association for Thoracic Surgery 2019© 2019 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in General thoracic and cardiovascular surgery. The final authenticated version is available online at: http://doi.org/10.1007/s11748-019-01153-z.本文の登録不可。本文は以下のURLを参照 "https://doi.org/10.1007/s11748-019-01153-z"（※全文閲覧は学内限定
食道扁平上皮癌における予後因子および腫瘍進展メカニズムとCullin4A高発現との関連性について
No full textBackground: Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown. Methods: We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique. Results: The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels. Conclusions: CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.博士（医学）・乙第1449号・令和2年3月16日© Japan Society of Clinical Oncology 2019This is a post-peer-review, pre-copyedit version of an article published in International journal of clinical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10147-019-01547-2
高齢者の入浴タイミングと夜間血圧低下の関連：自宅での繰り返し実測データを用いた縦断的分析
Get PDFHot water bathing – a Japanese traditional practice – has not been evaluated for its association with night- and sleep-time blood pressure (BP) in large population. In this longitudinal analysis, bathing parameters and ambulatory BP were repeatedly measured for 2 nights in 758 Japanese elderly individuals. Participants were divided into three groups according to tertile values of time soaked in the bathtub (Duration: tertile value, 11 and 15 min), time from bathing-end to bedtime (Time before bedtime: tertile value, 42 and 106 min), and temperature of hot water in the bathtub (Water temp: tertile value, 40.3 and 41.2 °C). Participants’ mean age was 70.9 years, and mean night- and sleep-time systolic BP (SBP) and dipping were 115.1 ± 16.1, 114.2 ± 16.2 mmHg, and 14.2 ± 8.8%, respectively. Multivariable mixed-effect linear regression models adjusted for potential confounding factors suggested that nighttime SBP was significantly lower in the intermediate Time before bedtime group by 1.7 mmHg (95% CI, 0.2–3.1) and in the short group by 1.9 mmHg (95% CI, 0.1–3.7) than that in the long group. Dipping was significantly greater in the intermediate Time before bedtime group by 1.8% (95% CI, 0.7–2.9) and in the short group by 1.8% (95% CI, 0.6–3.1) than that in the long group. These associations were consistent regarding sleep-time SBP. Conversely, Water temp and Duration did not significantly associate with any ambulatory BP parameter. Remarkably, Time before bedtime significantly prolonged with increases in tertiles of Water temp (P for trend = 0.006). In conclusion, the findings of this study revealed that Japanese hot water bathing, especially the short time from bathing-end to bedtime, was associated with lower night- and sleep-time BP and greater dipping in an elderly population.博士（医学）・甲第751号・令和2年9月30日This is a post-peer-review, pre-copyedit version of an article published in Chronobiology international. The final authenticated version is available online at: https://doi.org/10.1080/07420528.2019.1675685
腰椎すべり症における動態X線画像を用いた不安定性評価に対する姿勢の影響
Get PDFStudy design: Prospective clinical study. Purpose: To determine the optimal posture for instability evaluation using flexion-extension X-ray imaging in patients with lumbar spondylolisthesis. Overview of literature: Currently, flexion-extension X-ray imaging is the most practical approach for the evaluation of lumbar instability. In flexion-extension X-ray imaging, achievement of the greatest segmental motion with flexion-extension movement is necessary. However, to our knowledge, currently, there is no standardized posture for determining lumbar instability. Methods: Twenty-three individuals with lumbar spondylosis related to the fourth vertebra underwent flexion-extension X-ray imaging in different postures (standing, sitting, and lateral decubitus positions), lumbar magnetic resonance imaging (MRI), and low back pain Visual Analog Scale (VAS) evaluation on the same day. Intervertebral angle, percent slippage, and intervertebral disc area ratio for different postures during flexion and extension were compared using Tukey's method. The effect of low back pain and the association between MRI facet effusion and these measurements were investigated according to posture. Results: The percent slippage during extension (p=0.036), change in the percent slippage between flexion and extension (p=0.004), and change in the intervertebral angle (p=0.042) were significantly different between the sitting and lateral decubitus positions. There were also significant differences between the standing and lateral decubitus positions in the change in intervertebral angle (p=0.010). In patients with VAS score <40, there were significant differences in the intervertebral angle (p=0.011) between the standing and lateral decubitus positions, percent slippage (p=0.048), and intervertebral disk ratio (p=0.008) between the sitting and lateral decubitus positions. We found no relationship between MRI facet effusion and posture in terms of instability. Conclusions: In this study, intervertebral instability was best evaluated in the lateral decubitus position when using flexion-extension X-ray imaging for patients with fourth lumbar vertebral spondylolisthesis.博士（医学）・甲第754号・令和2年9月30日Copyright Ⓒ 2021 by Korean Society of Spine SurgeryThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited