研究者業績

阿江 竜介

アエ リュウスケ  (Ryusuke Ae)

基本情報

所属
自治医科大学 地域医療学センター公衆衛生学部門 教授
学位
医学(2016年6月 自治医科大学)

研究者番号
70554567
J-GLOBAL ID
201401017187488735
researchmap会員ID
B000237506

【略歴】

2003年に自治医科大学卒業。

兵庫県で地域医療に従事。

2013年より自治医科大学教員(現所属)。

 

【専門医資格】

総合内科専門医 (日本内科学会)

老年病専門医・指導医 (日本老年医学会)

上級疫学専門家 (日本疫学会)

社会医学系専門医・指導医 (社会医学系専門医協会)


論文

 116
  • Hiroya Masuda, Yu Yamamoto, Ryusuke Ae
    Cureus 2025年2月22日  
  • Koki Kosami, Masanari Kuwabara, Akira Okayama, Ryusuke Ae
    Nutrients 17(1) 2024年12月30日  
    Background/Objectives: Obesity is associated with food intake, drinking, and nutrition. It is necessary to examine the association between body mass index (BMI), body weight changes, and the incidence of hypertension, focusing on potential sex differences. Methods: A retrospective two-point cohort study was conducted using data from the Japanese Specific Health Checkup program from 2011 to 2013. Multivariable logistic regression analyses were employed to assess associations between BMI, weight change, and hypertension onset, adjusting for age, sex, and lifestyle factors, including smoking, drinking, and exercise. Results: In total, 397,181 participants were analyzed. A higher BMI was linked to a higher risk of hypertension, with an odds ratio (OR) of 1.11 (95% confidence interval [CI]: 1.11-1.12) for both sexes. Women aged 40-65 showed higher ORs than men. Weight gain was associated with developing hypertension, with an OR (95% CI) of 1.09 (1.09-1.10) in men and 1.08 (1.07-1.08) in women. This association held across all BMI levels, even among individuals without obesity, with the effect being generally stronger in men. Conclusions: Both BMI and weight change contribute to the development of hypertension among the Japanese healthy population, with differences based on sex. Weight reduction may reduce the risk of hypertension for individuals with and without obesity, emphasizing the importance of weight stability through food and nutrition control, particularly for women.
  • Masanari Kuwabara, Ryusuke Ae, Koki Kosami, Mehmet Kanbay, Ana Andres-Hernando, Ichiro Hisatome, Miguel A Lanaspa
    Hypertension research : official journal of the Japanese Society of Hypertension 2024年12月3日  
    Uric acid, the final product of purine metabolism, plays a significant role in hypertension Research on uric acid has advanced significantly, particularly regarding its links to hypertension and cardiovascular disease (CVD). Our 2023 review covered the relationship between uric acid, hypertension; and CVD, however, numerous new studies have emerged since then. This paper provides an update, summarizing recent findings over the past two years on hyperuricemia and its association with hypertension, preeclampsia, arteriosclerosis, kidney disease, sleep-disordered breathing, CVD, and so on. Hyperuricemia, often driven by reduced uric acid excretion or increased production, is influenced by genetic factors and lifestyle habits, including high-purine foods, alcohol, and fructose intake. While hyperuricemia has been proposed to contribute to hypertension and CVD through mechanisms like inflammasome activation and oxidative stress, its causal role remains debated. Further clinical and basic science studies on hyperuricemia and purine metabolism are necessary to clarify its impact on CVD and guide therapeutic approaches.
  • Sotaro Takaki, Tohru Kobayashi, Masanari Kuwabara, Naoto Kato, Koki Kosami, Ryusuke Ae
    Archives of disease in childhood 109(12) 1029-1034 2024年11月19日  
    OBJECTIVES: To identify clinical characteristics of patients with non-refractory Kawasaki disease (KD), which were defined as those who successfully responded to the standard initial intravenous immunoglobulin (IVIG) treatment (2 g/kg/day, single infusion) without any secondary or later additional specific treatments, and to investigate the factors associated with the development of coronary artery (CA) complications in patients with non-refractory KD. DESIGN: Retrospective cohort study. SETTING: Hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: A total of 122 489 patients who developed KD across Japan during 2011-2018. MAIN OUTCOME MEASURES: CA abnormalities identified after acute illness of KD (defined as CA sequelae). RESULTS: A total of 69 735 patients with non-refractory KD were identified, of which 672 (0.96%) experienced CA sequelae. Among patients with non-refractory KD, the presence of CA abnormalities identified at initial echocardiographic assessment was strongly associated with CA sequelae (adjusted OR (95% CI): 37.8 (31.9 to 44.7)). CA sequelae was also associated with male patients, infants (<12 months old), older patients (≥60 months old) and patients who received delayed initial IVIG treatment (>7 days from KD onset). Subgroup analyses demonstrated that delayed initial IVIG treatment was significantly associated with the development of CA sequelae in both patients with and without CA abnormalities identified at initial echocardiographic assessment. CONCLUSIONS: Approximately 1% of patients with non-refractory KD may develop CA sequelae. Our findings highlight the importance of initial echocardiographic assessment and early initiation of IVIG treatments for patients with KD.
  • Masanari Kuwabara, Ichiro Hisatome, Ryusuke Ae, Koki Kosami, Yuhei Aoki, Ana Andres-Hernando, Mehmet Kanbay, Miguel A. Lanaspa
    Nutrition, Metabolism and Cardiovascular Diseases 103796-103796 2024年11月  
  • Toshiaki Nonaka, Ryusuke Ae, Koki Kosami, Hiroya Tange, Miho Kaneko, Takehiro Nakagaki, Tsuyoshi Hamaguchi, Nobuo Sanjo, Yoshikazu Nakamura, Tetsuyuki Kitamoto, Yoshiyuki Kuroiwa, Kensaku Kasuga, Manabu Doyu, Fumiaki Tanaka, Koji Abe, Shigeo Murayama, Ichiro Yabe, Hideki Mochizuki, Takuya Matsushita, Hiroyuki Murai, Masashi Aoki, Koji Fujita, Masafumi Harada, Masaki Takao, Tadashi Tsukamoto, Yasushi Iwasaki, Masahito Yamada, Hidehiro Mizusawa, Katsuya Satoh, Noriyuki Nishida
    Diagnostics 14(21) 2424-2424 2024年10月30日  
    Background/Objectives: Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann’s criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan. Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann’s criteria were calculated by comparing diagnoses with those made by the JPDS Committee. Results: Of the 786 included cases, Hermann’s criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann’s criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as “definite” by both criteria. Conclusions: The findings suggest that Hermann’s criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.
  • Masanori Ogawa, Ryusuke Ae, Teppei Sasahara, Keiko Omi
    BMC nursing 23(1) 724-724 2024年10月8日  
    BACKGROUND: New employees often exhibit stress reactions to changes in their environment and some of these may result in resignations. Employees in medical institutions are no exceptions. Considering the shortage of nurses in Japan, countermeasures are needed against the resignation of newly graduated nurses. Many studies have indicated that multifaced factors affect the resignation of newly graduated nurses. Even though individual characteristics are important factors in this regard, training and support for newly graduated nurses do not focus on the nurses' characteristics. The purpose of this study is to examine the characteristics influencing the early resignation of newly graduated nurses and suggest ways to support them and prevent their early resignation based on their characteristics. METHODS: With the approval of the Ethics Committee, various characteristics of 353 newly graduated nurses (personality, interpersonal relationships, trait anxiety, nurse orientation, desire to be a nurse, and self-proclaimed academic ability) were assessed using a transactional analysis, the State-Trait Anxiety Inventory, and self-reporting numerical rating scales. The characteristics of those who resigned within 1 year (case group) and those who did not (control group) were compared using chi-square test and logistic regression analysis. RESULTS: Our sample of 353 participants included 32 nurses from the case group and 304 nurses from the control group. Most participants showed similar personality traits. However, the control group had a significantly lower percentage with negative self, strong trait anxiety, negative self and strong trait anxiety, and low orientation compared to the case group. Our logistic regression analysis showed that strong trait anxiety and low nurse orientation are significantly related with the early resignation of nurses. CONCLUSIONS: The early resignation of newly graduated nurses may be prevented by understanding their characteristics at the time of gaining employment and implementing early intervention programs, such as education programs to reduce anxiety, and helping those with strong trait anxiety and low nurse orientation to find meaning in work.
  • Tsuneari Takahashi, Ryusuke Ae, Tatsuya Kubo, Yuya Kimura, Mikiko Handa, Katsushi Takeshita
    Cureus 16(2) e54239 2024年2月  
    PURPOSE: To assess how intraoperative macroscopical anterior cruciate ligament (ACL) findings affect perioperative procedures, biomarkers, and postoperative anterior-posterior (AP) laxity and range of motion (ROM) after cruciate-retaining (CR) total knee arthroplasty (TKA) and to determine how chronic ACL deficiency may affect postoperative inflammatory biomarker, AP laxity, and ROM. METHODS: A total of 121 patients with varus knee osteoarthritis without a history of ACL injury who underwent ATTUNE® (DePuy Synthes, Warsaw, IN) CR TKA were analyzed. Intraoperative ACL findings were stratified into intact, damaged, and diminished, according to the tension by probing, synovial coverage, and vascularity. C-reactive protein (CRP) levels were examined at one, seven, and 14 days after surgery. Knee AP laxity measurements using Kneelax 3 (Monitored Rehab Systems, Haarlem, The Netherlands) and postoperative knee ROM were also compared. RESULTS: One-way ANOVA showed significant differences in CRP levels examined one day after surgery observed between the three groups (8.4 (3.8), 9.8 (4.3), and 13.2 (7.7) mg/dL, respectively; P = 0.018), with post hoc analysis showing that CRP levels one day after surgery were significantly greater in the diminished group than in the intact and damaged groups (P = 0.012 and 0.023, respectively). AP laxity in 30° of knee flexion was observed between the three groups (5.4 (2.3), 5.8 (2.5), and 7.1 (2.8) mm, respectively; P = 0.039), with post hoc analysis showing that AP laxity in 30° of knee flexion was significantly greater in the diminished group than in the intact group (P = 0.038). Knee ROM showed no significant differences. CONCLUSION: Intraoperative ACL diminishment was associated with higher CRP one day after surgery and midrange AP laxity one year after surgery.
  • Gaku Ota, Yuji Kaneda, Yoshitaka Maeda, Kosuke Oiwa, Ryusuke Ae, Mikio Shiozawa, Hisanaga Horie, Naohiro Sata, Hiroshi Kawahira
    Cureus 2024年1月8日  
  • Tsuneari Takahashi, Kazuhisa Hatayama, Ryusuke Ae, Tomohiro Saito, Mikiko Handa, Yuya Kimura, Katsushi Takeshita
    Technology and health care : official journal of the European Society for Engineering and Medicine 2023年11月9日  
    BACKGROUND: Total knee arthroplasty (TKA) alleviates pain and improves daily living activities in individuals with end-stage osteoarthritis of the knee. However, up to 20% of patients have sub-optimal outcomes after TKA. OBJECTIVE: No studies have clarified the intraoperative factors that affect postoperative range of motion (ROM) after cruciate-retaining (CR) TKA. Thus, this study aims to clarify these factors. METHODS: Patients with knee osteoarthritis with varus knee deformity who underwent CR-TKA between May 2019 and December 2020 were included in this study. One year after surgery, patients were stratified into two groups based on knee flexion: Group F (over 120∘) and Group NF (below 120∘). Patient backgrounds including age, body mass index, hip knee angle, preoperative range of motion for both extension and flexion, intraoperative center joint-gap measurements of 0∘, 30∘, 45∘, 60∘, 90∘, and 120∘ of knee flexion using a tensor, intraoperative anterior-posterior (AP) laxity measurements of 30∘ and 90∘ of knee flexion using an instrumental laximeter were compared between the groups. Univariate analyses between the groups were used to construct the initial model. The receiver operating characteristic curve was also analyzed. The predictive variables included in the final model were selected by stepwise backward elimination. RESULTS: Intraoperative AP laxity with 30∘ of knee flexion smaller than 10.8 mm was a significant positive prognostic factor (OR: 1.39, 95% CI: 1.08-1.79, P= 0.011) of postoperative ROM over 120∘ of knee flexion one year after surgery. The sensitivity, specificity, PPV, and NPV were 70.9%, 82.4%, 92.9%, and 46.7%, respectively. CONCLUSION: Intraoperative AP laxity smaller than 10.8 mm was a significant positive predictive factor for obtaining knee flexion greater than 120∘ one year after surgery when using CR-TKA and its PPV was high up to 92.9%.
  • Yuji Kaneda, Yuki Kimura, Akira Saito, Ryusuke Ae, Hiroshi Kawahira, Naohiro Sata
    Cureus 15(9) e44771 2023年9月  
    Introduction Postoperative pancreatic fistula (POPF) is a critical complication occurring with a high incidence after distal pancreatectomy. To minimize the risk of POPF, we developed an innovative pancreas ligation device capable of closing the pancreatic stump without causing traumatic injury to the pancreatic duct and artery. We conducted an ex vivo follow-up study to compare the pressure resistance of the pancreas ligation device with that of a regular linear stapler. Materials and methods The pancreases were excised from 20 pigs and divided into two groups: ligation group (n = 10) and stapler group (n = 10). Distal pancreatectomy was performed, and the pancreatic stump was closed using either a pancreas ligation device or a regular linear stapler. The main pancreatic duct was cannulated with a 4-French catheter connected to a cannula and syringe filled with contrast medium. Using fluoroscopy detection, pressure resistance was defined as the maximum pressure without leakage from the pancreatic stump. Results No significant differences were found between the two groups regarding sex, age, body weight, or pancreatic thickness. In the ligation group, no leakage was observed at the stump in any pancreas. However, in the stapler group, six of 10 pancreases showed leakage at the staple line or into the parenchyma. Pressure resistance was significantly higher in the ligation group than in the stapler group (median: 42.8 vs. 34.3 mmHg, P = 0.023). Conclusions These findings suggest the effectiveness of a pancreas ligation device in reducing the incidence of POPF after distal pancreatectomy. Our ligation device is expected to be a useful alternative to a linear stapler for pancreatic stump closure.
  • Tatsuya Kubo, Tsuneari Takahashi, Akihiro Saitsu, Ryusuke Ae, Hitoshi Sekiya, Katsushi Takeshita
    Arthroscopy, sports medicine, and rehabilitation 5(3) e629-e635 2023年6月  
    PURPOSE: To investigate whether the biomechanical properties of the healed superficial medial collateral ligament (sMCL) repaired by augmentation vary depending on the material properties of the suture augmentation. METHODS: In 8 of 10 porcines (16 hindlimbs), the sMCL was detached from the femoral attachment using a scalpel under intubated general anesthesia. sMCL repair was performed using an ultra-high-molecular-weight polyethylene (UHMWPE) tape for the right hindlimbs and polyester tape (PE) for the left hindlimbs. They were sacrificed at 4 weeks postoperatively. The remaining 2 animals were assigned to the native control group (left and right hindlimb; n = 4). All connective tissues and suture augmentation, except for the repaired sMCL, were removed, and their biomechanical properties were evaluated. RESULTS: No significant differences were observed in the upper yield load (PE group, 247.4 ± 116.0 N; UHMWPE group, 279.9 ± 95.7 N; and sham group, 231.6 ± 50.6 N; P = .70), maximum yield load (PE group, 310.1 ± 166.1 N; UHMWPE group, 334.6 ± 95.2 N; and sham group, 290.9 ± 42.3 N; P = .84), linear stiffness (PE group, 43.3 ± 16.5 N/mm; UHMWPE group, 52.0 ± 28.2 N/mm; and sham group, 44.7 ± 7.2 N/mm; P = .66), and elongation at failure (PE group, 9.4 ± 4.3 mm; UHMWPE group, 9.1 ± 2.7 mm; and sham group, 10.1 ± 2.1 mm; P = .89). Statistical analysis of failure modes showed no significant difference between the groups (P = .21). CONCLUSIONS: The material properties of suture augmentation used for sMCL repair did not significantly influence length changes during cyclic loading, postoperative structural properties, or failure modes. CLINICAL RELEVANCE: The results of this study provide valuable information regarding the efficacy of suture augmentation repair regardless of the materials used.
  • Yu Otsu, Ryusuke Ae, Masanari Kuwabara
    Hypertension research : official journal of the Japanese Society of Hypertension 2023年5月12日  
  • Takanori Miura, Tsuneari Takahashi, Jun Watanabe, Yuki Kataoka, Ryusuke Ae, Hidetomo Saito, Katsushi Takeshita, Naohisa Miyakoshi
    BMC Musculoskeletal Disorders 24(1) 2023年4月24日  
    Abstract Background Mechanically aligned total knee arthroplasty (MATKA) is a well-established procedure. Kinematically aligned TKA (KATKA) has been proposed to restore and preserve pre-arthritic knee anatomy. However, normal knee anatomy varies widely, and there have been concerns regarding restoring unusual anatomy. Accordingly, restricted KATKA (rKATKA) was introduced to reproduce constitutional knee anatomy within a safe range. This network meta-analysis (NMA) aimed to evaluate the clinical and radiological outcomes of the surgeries. Methods We performed a database search on August 20, 2022, which included randomized controlled trials (RCTs) comparing any two of the three surgical TKA techniques for knee osteoarthritis. We conducted a random-effects NMA within the frequentist framework and evaluated confidence in each outcome using the Confidence in Network Meta-Analysis tool. Results Ten RCTs with 1,008 knees and a median follow-up period of 1.5 years were included. The three methods might result in little to no difference in range of motion (ROM) between methods. In patient-reported outcome measures (PROMs), the KATKA might result in a slight improvement compared with the MATKA (standardized mean difference, 0.47; 95% confidence interval [CI], 0.16–0.78; very low confidence). There was little to no difference in revision risk between MATKA and KATKA. KATKA and rKATKA showed a slight valgus femoral component (mean difference [MD], -1.35; 95% CI, -1.95–[-0.75]; very low confidence; and MD, -1.72; 95% CI, -2.63–[-0.81]; very low confidence, respectively) and a slight varus tibial component (MD, 2.23; 95% CI, 1.22–3.24; very low confidence; and MD, 1.25; 95% CI, 0.01–2.49; very low confidence, respectively) compared with MATKA. Tibial component inclination and hip–knee–ankle angle might result in little to no difference between the three procedures. Conclusions KATKA and rKATKA showed similar ROM and PROMs and a slight variation in the coronal component alignment compared with MATKA. KATKA and rKATKA are acceptable methods in short- to mid-term follow-up periods. However, long-term clinical results in patients with severe varus deformity are still lacking. Surgeons should choose surgical procedures carefully. Further trials are warranted to evaluate the efficacy, safety, and subsequent revision risk.
  • Masanari Kuwabara, Takahide Kodama, Ryusuke Ae, Mehmet Kanbay, Ana Andres-Hernando, Claudio Borghi, Ichiro Hisatome, Miguel A Lanaspa
    Hypertension research : official journal of the Japanese Society of Hypertension 2023年4月18日  
    A direct relationship between serum uric acid levels and hypertension, cardiovascular, renal and metabolic diseases has been reported in many basic and epidemiological studies. Among these, high blood pression is one of the most common features associated with hyperuricemia. In this regard, several small-scale interventional studies have demonstrated a significant reduction in blood pressure in hypertensive or prehypertensive patients on uric acid-lowering drugs. These observation or intervention studies have led to affirm that there is a causal relationship between uric acid and hypertension. While the clinical association between uric acid and high blood pressure is notable, no clear conclusion has yet been reached as to whether lowering uric acid is beneficial to prevent cardiovascular and renal metabolic diseases. Recently, several prospective randomized controlled intervention trials using allopurinol and other uric acid-lowering drugs have been reported, and the results from these trials were almost negative, suggesting that the correlation between hyperuricemia and cardiovascular disease has no causality. However, it is important to note that in some of these recent studies there were high dropout rates and an important fraction of participants were not hyperuricemic. Therefore, we should carry caution in interpreting the results of these studies. This review article presents the results of recent clinical trials using uric acid-lowering drugs, focusing on hypertension and cardiovascular and renal metabolic diseases, and discusses the future of uric acid therapy.
  • Kazuo Nakamichi, Yoshiharu Miura, Toshio Shimokawa, Kenta Takahashi, Tadaki Suzuki, Nobuaki Funata, Masafumi Harada, Koichiro Mori, Nobuo Sanjo, Motohiro Yukitake, Kazuya Takahashi, Tsuyoshi Hamaguchi, Shoko Izaki, Satoru Oji, Jin Nakahara, Ryusuke Ae, Koki Kosami, Souichi Nukuzuma, Yosikazu Nakamura, Kyoichi Nomura, Shuji Kishida, Hidehiro Mizusawa, Masahito Yamada, Masaki Takao, Hideki Ebihara, Masayuki Saijo
    Viruses 15(4) 2023年4月14日  
    Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.
  • 小佐見 光樹, 阿江 竜介, 中村 好一, 牧野 伸子, 青山 泰子, 松原 優里, 浜口 毅, 山田 正仁, 水澤 英洋
    Journal of Epidemiology 33(Suppl.1) 164-164 2023年2月  
  • 小佐見 光樹, 阿江 竜介, 中村 好一, 牧野 伸子, 青山 泰子, 松原 優里, 浜口 毅, 山田 正仁, 水澤 英洋
    Journal of Epidemiology 33(Suppl.1) 164-164 2023年2月  
  • Masanari Kuwabara, Michikazu Nakai, Yoko Sumita, Yoshitaka Iwanaga, Ryusuke Ae, Takahide Kodama, Ichiro Hisatome, Naoyuki Kamatani
    Frontiers in pharmacology 14 1289386-1289386 2023年  
    Objectives: This study investigates the impact of xanthine oxidase inhibitors (XOI) on mortality in patients with cardiovascular diseases. XOI withdrawal has been reported to increased mortality risk due to rapid adenosine triphosphate (ATP) deficiency. This study aims to determine whether XOI treatment reduces mortality and whether XOI withdrawal increases mortality. Methods: This is a real-world database study using the Japanese Registry of All Cardiac and Vascular Diseases (J-ROAD). We analyzed 1,648,891 hospitalized patients aged 20-90 with acute coronary syndrome or heart failure. In the first study, mortality rates were compared between patients without urate-lowering agents (n = 1,292,486) and those with XOI agents (n = 315,388, excluding 41,017 on other urate-lowering agents). In the second study, mortality rates were compared between the XOI continuous medication group (n = 226,261) and the XOI withdrawal group (n = 89,127). Results: After multiple adjustments, XOI treatment group showed significantly lower mortality compared with that without any urate-lowering agent (odds ratio (OR), 0.576, 95% confidence interval (CI), 0.567-0.587, p < .001). In the sub-analysis, the group with allopurinol (OR, 0.578; 95% CI, 0.557-0.600), febuxostat (OR, 0.610; 95% CI, 0.599-0.622), and topiroxostat (HR, 0.545; 95% CI, 0.473-0.628) showed lower OR of mortality compared with that without any urate-lowering agent. XOI withdrawal group led to significantly higher death rates compared to XOI continuous group (19.8% vs. 0.03%; p < .001). Conclusion: XOI treatment for patients with cardiovascular diseases is associated with reduced mortality. Conversely, XOI withdrawal is linked to elevated mortality risk. This emphasizes the importance of both prescribing and discontinuing XOI carefully to optimize patient outcomes.
  • Ryusuke Ae, Nobuko Makino, Masanari Kuwabara, Yuri Matsubara, Koki Kosami, Teppei Sasahara, Yosikazu Nakamura
    JAMA Pediatrics 176(12) 1217-1224 2022年12月1日  査読有り筆頭著者責任著者
    IMPORTANCE: Global studies have reported that the incidence of Kawasaki disease (KD) declined during the COVID-19 pandemic. These studies suggest that the global pandemic and its accompanying mitigation measures may provide an important opportunity to explore the hypothesis of a KD pathogenesis. OBJECTIVE: To compare changes in KD incidence in Japan before and after the start of the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using the data set from Japan's 26th nationwide KD survey that obtained information on patients who were diagnosed with KD in Japan from January 1, 2019, through December 31, 2020. MAIN OUTCOMES AND MEASURES: Kawasaki disease incidence rates were calculated by referring to the national population data in the vital statistics data for Japan. RESULTS: A total of 28 520 patients were identified (16 236 male individuals [56.9%]; median [IQR] age, 26 [14-44] months). A total of 17 347 patients were diagnosed with KD in 2019 and 11 173 were diagnosed in 2020, representing a 35.6% reduction in the number of patients diagnosed in 2020 compared with the previous year. Patient distributions for days of illness at the first hospital visit were almost identical in 2019 and 2020, suggesting that the decrease in KD incidence likely was not associated with pandemic-related delays in seeking treatment. The proportion of patients diagnosed with KD who were younger than 12 months was significantly larger in 2020 than in 2019 (21.6% vs 19.4%; P < .001). Compared with KD incidence among younger patients, the incidence among those 24 months and older declined rapidly after initiation of COVID-19 special mitigation measures, with a greater percentage reduction (58.3% reduction in July), but rebounded faster after the end of the special mitigation period. By contrast, the incidence among patients younger than 12 months declined moderately after the initiation of the special mitigation period, with a lower percentage reduction (40.3% reduction in October), and rebounded at a later phase. CONCLUSIONS AND RELEVANCE: In this cohort study, the number of patients diagnosed with KD decreased by approximately one-third across Japan in 2020, with no indication that parents avoided a hospital visit. Differences in KD incidence reduction patterns before and after the initiation of COVID-19 pandemic mitigation measures were found in patients with KD aged younger than 12 months compared with those 24 months or older, suggesting a potential KD pathogenesis involving transmission among children.
  • Ryusuke Ae, Yoshihide Shibata, Tohru Kobayashi, Koki Kosami, Masanari Kuwabara, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Hiroya Masuda, Yosikazu Nakamura
    Pediatric Cardiology 44(1) 153-160 2022年9月19日  査読有り筆頭著者責任著者
    No studies have assessed differences between the Japanese and Z score criteria in the echocardiographic detection sensitivity of coronary artery (CA) abnormalities using large-scale data containing samples from multiple facilities engaged in daily clinical practices of Kawasaki disease (KD). We analyzed data from the 25th Japanese nationwide KD survey, which identified 30,415 patients from 1357 hospitals throughout Japan during 2017-2018. Hospitals were classified according to their use of Z score criteria. We assessed differences in hospital and patient background factors and compared the prevalence of CA abnormalities among groups using the Z score criteria. Multivariable logistic regression analyses were performed to evaluate differences in the detection sensitivity for CA abnormalities. The Z score criteria were more likely to be utilized in larger hospitals with more pediatricians and cardiologists. Even after controlling for potential confounders, detection sensitivities by the Z score criteria were significantly higher than by the Japanese criteria in patients with CA dilatations (adjusted odds ratio (95% confidence interval) 1.77 (1.56-2.01)) and aneurysms (1.62 (1.17-2.24)). No significant difference was found in patients with giant CA aneurysms. Compared with the Japanese criteria, the Z score criteria were significantly more sensitive for detecting patients with CA dilatations regardless of age, and for those with CA aneurysms only in patients aged ≤ 1 year. Our results indicate that differences in the detection sensitivity for CA abnormalities between the Z score and the Japanese criteria were dependent on the CA size and patient age.
  • Hiroya Masuda, Ryusuke Ae, Taka-Aki Koshimizu, Koki Kosami, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Yosikazu Nakamura
    Clinical Rheumatology 2022年7月7日  査読有り筆頭著者責任著者
    INTRODUCTION/OBJECTIVES: Serum alanine aminotransferase (ALT) elevation is considered a risk factor for resistance to initial intravenous immunoglobulin (IVIG) treatment in patients with Kawasaki disease (KD). However, serum ALT levels change dramatically during acute KD illness. We tested the hypothesis that risk assessment for initial IVIG resistance based on serum ALT elevation may differ by examination day after KD onset. METHODS: We analyzed 18,492 population-based patients who developed KD throughout Japan. First, we epidemiologically evaluated the serum ALT variation at 1‒10 days after disease onset. Second, we conducted multivariable logistic regression to determine the association between serum ALT level and initial IVIG resistance according to timing of initial hospital visit by stratifying the patients into an early group (1‒5 days after onset) and a late group (6‒10 days after onset). RESULTS: Serum ALT rapidly increased after KD onset, peaked at day 4 of illness, and then declined regardless of IVIG responsiveness. The adjusted odds ratio (OR) increased with increasing serum ALT in the early group (adjusted OR [95% CI]: 1.44 [1.25-1.66], 1.94 [1.65-2.28], and 2.22 [1.99-2.48] for serum ALT 50-99, 100-199, and ≥ 200 IU/L, respectively; reference ALT level: 1-49 IU/L). No significant association was observed in the late group. CONCLUSIONS: The findings indicate that risk assessment for initial IVIG resistance based on serum ALT level may only be reliable for patients with KD who visit hospitals during early illness, specifically 1-5 days after disease onset. Key Points Serum alanine aminotransferase level differed markedly according to examination days after Kawasaki disease onset. Serum alanine aminotransferase level declined toward normal range after day 5 of illness regardless of intravenous immunoglobulin responsiveness. Elevated serum alanine aminotransferase level was no longer a significant risk factor for initial intravenous immunoglobulin resistance when measured on delayed hospital visits. Risk assessment for initial intravenous immunoglobulin resistance based on serum alanine aminotransferase level may only be reliable for patients who visit hospitals during early illness, specifically 1-5 days after disease onset.
  • 松原 優里, 小佐見 光樹, 阿江 竜介, 青山 泰子, 石川 鎮清, 牧野 伸子, 中村 好一
    医学教育 53(Suppl.) 195-195 2022年7月  
  • Shinsuke Hoshino, Yoshihide Shibata, Jun Matsubayashi, Ryusuke Ae
    The Journal of Pediatrics 2022年7月  査読有り最終著者
  • Taiki Matsubayashi, Miho Akaza, Yuichi Hayashi, Tsuyoshi Hamaguchi, Katsuya Satoh, Koki Kosami, Ryusuke Ae, Tetsuyuki Kitamoto, Masahito Yamada, Takayoshi Shimohata, Takanori Yokota, Nobuo Sanjo
    Journal of the neurological sciences 437 120265-120265 2022年6月15日  査読有り
    Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges. Clinical records, magnetic resonance imaging (MRI), and changes in EEG were compared between three groups (LPD in MM1/classic, CSSED in MM1/classic, and focal epileptiform discharge in MM2c). Three (37.5%) and five (62.5%) patients with MM1/classic sCJD were classified into the LPD and CSSED groups, respectively. Patients in the LPD group were accompanied by cortical hyperintensities at the corresponding areas on MRI, while those in the CSSED group showed hyperintensities on MRI at unassociated cortical areas. Follow-up EEG of three (100%) patients in the LPD group and four (80%) in the CSSED group showed transitions to GPDs. All patients with MM1/classic sCJD showed myoclonus on initial EEG, and the symptomatic side was opposite to the hemisphere showing LPDs or higher-amplitude central sagittal epileptiform activity. The periodicity after these EEGs likely contributes to the diagnostic confidence of physicians when patients are in the very early stages of MM1/classic sCJD.
  • Yosikazu Nakamura, Yuri Matsubara, Koki Kosami, Ryusuke Ae, Teppei Sasahara, Yasuko Aoyama, Soichi Koike, Shizukiyo Ishikawa, Nobuko Makino
    Pediatrics International 2022年6月14日  査読有り
  • Ryusuke Ae, Yoshihide Shibata, Toshiki Furuno, Teppei Sasahara, Yosikazu Nakamura, Hiromichi Hamada
    International Journal of Environmental Research and Public Health 19(11) 2022年6月6日  査読有り筆頭著者責任著者
    The study tested the hypothesis that human mobility may be a potential factor affecting reductions in droplet-transmissible pediatric infectious diseases (PIDs) during the coronavirus disease-2019 (COVID-19) pandemic mitigation period in 2020. An ecological study was conducted using two publicly available datasets: surveillance on infectious diseases collected by the Japanese government and COVID-19 community mobility reports presented by Google. The COVID-19 community mobility reports demonstrated percentage reductions in the movement of people over time in groceries and pharmacies, parks, and transit stations. We compared the weekly trends in the number of patients with droplet-transmissible PIDs identified in 2020 with those identified in the previous years (2015-2019) and assessed the correlations between the numbers of patients and percentage decreases in human mobility during 2020. Despite experiencing their peak seasons, dramatic reductions were found in the numbers of patients with pharyngoconjunctival fever (PCF) and group A streptococcal (GAS) pharyngitis after the tenth week of 2020. Beyond the 20th week, no seasonal peaks were observed in the number of patients with all PIDs identified in 2020. Significant correlations were found between the percentage decreases in human mobility in transit stations and the number of patients with hand-foot-and-mouth disease (Pearson correlation coefficient [95% confidence interval]: 0.65 [0.44-0.79]), PCF (0.47 [0.21-0.67]), respiratory syncytial virus infection (0.45 [0.19-0.66]), and GAS pharyngitis (0.34 [0.06-0.58]). The highest correlations were found in places underlying potential human-to-human contacts among adults. These findings suggest that reductions in human mobility for adults might contribute to decreases in the number of children with droplet-transmissible PIDs by the potential prevention of adult-to-child transmission.
  • Tsuneari Takahashi, Kazutaka Sugimoto, Ryusuke Ae, Tomohiro Saito, Yuya Kimura, Tatsuya Kubo, Mikiko Handa, Katsushi Takeshita
    Technology and health care : official journal of the European Society for Engineering and Medicine 30(5) 1147-1154 2022年5月13日  査読有り
    BACKGROUND: Total knee arthroplasty (TKA) is a widely performed procedure to alleviate pain and restore function of patients with end-stage knee osteoarthritis. OBJECTIVE: The study aim was to determine if tibia-first (TF) total knee arthroplasty (TKA) using a novel computer-assisted surgery (CAS) system can yield better anterior and posterior (AP) knee stability. METHODS: Patients with knee osteoarthritis with obvious varus knee who met the indication for and underwent TKA from May 2019 to November 2020 were included. Forty-one measured resection (MR)-TKAs and 32 TF-TKAs were compared. The varus-valgus ligament balance and joint tension at a joint center-gap setting equal to the tibial-baseplate thickness were measured, and appropriate polyethylene inserts with 0∘, 30∘, 45∘, 60∘, 90∘, and 120∘ of knee flexion were placed. A Kneelax 3 arthrometer was used to measure knee AP laxity in the postoperative anesthetized patients with 30∘ and 90∘ of knee flexion. RESULTS: The horizontal gap balance was significantly closer in the TF-TKA group than the MR-TKA group for 0∘, 30∘, 45∘, and 60∘ of knee flexion. In contrast, no significant differences were observed for 90∘ and 120∘ of knee flexion. No significant differences in joint-gap tensions among all knee-flexion angles were observed. Translation was significantly smaller in the TF-TKA group than the MR-TKA group for AP laxity with 30∘ of knee flexion (8.8 ± 2.9 mm vs. 10.7 ± 3.1 mm, P= 0.0079). In contrast, no significant AP laxity was observed with 90∘ of knee flexion (7.2 ± 2.8 mm vs. 7.2 ± 3.5 mm). CONCLUSION: TF-TKA using a novel CAS system provided better AP knee stability with close to horizontal gap balances.
  • H Takada, R Ae, M Ogawa, T Kagomoto
    Occupational Medicine (Oxford, England) 72(3) 207-214 2022年4月19日  査読有り責任著者
    BACKGROUND: Few studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health. AIMS: To test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs' mental health. METHODS: This cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs' mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms. RESULTS: Of the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54-1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10-2.63], P < 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10-2.52], P < 0.01) or colleagues/supervisors (3.19 [2.22-4.58], P < 0.001) were significantly more likely to have depressive symptoms. CONCLUSIONS: Being a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.
  • Koki Kosami, Ryusuke Ae, Tsuyoshi Hamaguchi, Nobuo Sanjo, Tadashi Tsukamoto, Tetsuyuki Kitamoto, Masahito Yamada, Hidehiro Mizusawa, Yosikazu Nakamura
    Journal of neurology, neurosurgery, and psychiatry 2022年4月6日  査読有り責任著者
    BACKGROUND: No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset. METHODS: We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)). RESULTS: Of 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu. CONCLUSIONS: Methionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.
  • 阿江 竜介, 屋代 真弓, 松原 優里, 小佐見 光樹, 牧野 伸子, 中村 好一, 川崎病全国調査担当グループ(特定非営利活動法人川崎病研究センター)
    小児科診療 85(3) 391-396 2022年3月  査読有り筆頭著者責任著者
    川崎病全国調査は1970年から2年に1回の間隔で実施されてきた。今回、2021年に実施された第26回調査の結果について、過去の調査結果と比較しつつ以下の項目に分けて報告した。1)患者数・罹患率の年次推移。2)月別患者数の推移(2017〜2020年の比較)。3)患者の地域分布。4)診断の確実度。5)心障害。6)初回免疫グロブリン治療。7)初回免疫グロブリン不応例への追加治療。8)主要6症状とBCG接種部位の発赤。9)新型コロナウイルスPCR検査を受けた患者の割合と検査結果。
  • Yuya Kimura, Tsuneari Takahashi, Ryusuke Ae, Katsushi Takeshita
    Geriatric orthopaedic surgery & rehabilitation 13 21514593221082785-21514593221082785 2022年  査読有り
    Introduction: Arterial injury following total knee arthroplasty (TKA) can be life-threatening. There are some anatomical variations in the popliteal artery (PA) and its branches. In most cases, the PA branches into the anterior tibial artery (ATA) and posterior tibial artery (PTA), which are usually distal to the height of tibial resection in TKA. However, some cases show that the PA branches into the ATA and PTA proximal to the height of tibial resection in TKA. This study aimed to assess the distance from the posterior cortex of the proximal tibia to the anterior wall of the PA or ATA at the height of the tibial cut line, during TKA in the distal and proximal branch groups. Methods: 129 patients (6 patients in the proximal branch group and 123 patients in the distal branch group) were enrolled for this study. For prediction of the distance from the posterior cortex of the proximal tibia to the anterior wall of the PA or ATA, preoperative sagittal and coronal magnetic resonance images and postoperative radiographs were evaluated. Results: The distance between the posterior cortex of the proximal tibia and the anterior wall of the PA or ATA at the height of the tibial cut line was 1.8 ± 1.1 mm in the proximal branch group and 6.1 ± 2.6 mm in the distal branch group, which was significantly closer in the proximal group (P < .05). Discussion: The rate of proximal branching was 4.7%. This study clarified that the proximal branching of the ATA from PA significantly decreased the distance between the posterior cortex of the proximal tibia and the anterior wall of the artery. Conclusions: The proximal branch group has a high risk for arterial injury as the artery may be close to the saw, and appropriate retraction should be performed.
  • Tsuneari Takahashi, Ryusuke Ae, Koki Kosami, Kensuke Minami, Meiwa Shibata, Tatsuya Kubo, Katsushi Takeshita
    Telemedicine reports 3(1) 49-54 2022年  査読有り責任著者
    Background: Hospital-related coronavirus disease 2019 (COVID-19) infection is of utmost concern among patients and health care workers. Expanding the use of telemedicine may be required in daily outpatient practice; however, the acceptance of telemedicine use is still low, especially among older patients. In an orthopedic practice, no studies have investigated potential factors that can contribute to changes in the acceptance of using telemedicine. Focusing on older outpatients with knee osteoarthritis (KOA), we hypothesized that a drastic surge in the number of patients with COVID-19 could trigger changes in attitudes regarding the acceptance of telemedicine use. Methods: A baseline survey was conducted after the first wave of the COVID-19 pandemic in Japan to obtain information on the willingness to use telemedicine among patients aged ≥70 years who regularly consulted an orthopedic surgeon for KOA. A follow-up survey was subsequently conducted during the third wave of the pandemic period to assess changes in the acceptance of telemedicine use in response to the rapidly increasing number of patients with COVID-19. We compared the difference in acceptance of telemedicine use and knee pain status between the baseline and follow-up surveys. Results: In the baseline survey, 11 of 43 patients (25.6%) responded that they would be willing to use telemedicine. In the follow-up survey, patients' acceptance of telemedicine did not change, with the exact same number and percentage of patients who were willing to use telemedicine as in the baseline survey, despite that ∼20% of patients reported improvement in their knee pain status. Discussion: Our findings indicate that older outpatients with KOA did not change their willingness to accept use of telemedicine, even with a drastically increased risk of hospital-related transmission of a potentially fatal infectious disease when visiting a hospital. The acceptance of telemedicine use among older patients might not be less sensitive to external environmental factors but instead might be more sensitive to patients' personal factors, such as anxiety for information technology and resistance to changes in their lifestyle.
  • Dai Akine, Teppei Sasahara, Kotaro Kiga, Ryusuke Ae, Koki Kosami, Akio Yoshimura, Yoshinari Kubota, Kazumasa Sasaki, Yumiko Kimura, Masanori Ogawa, Shinya Watanabe, Yuji Morisawa, Longzhu Cui
    Antibiotics (Basel, Switzerland) 11(1) 2021年12月29日  査読有り
    A high prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) may call for monitoring in geriatric long-term care facilities (g-LTCFs). We surveyed the distribution of ESBL-causative gene types and antimicrobial susceptibility in ESBL-PE strains from residents in g-LTCFs, and investigated the association between ESBL-causative gene types and antimicrobial susceptibility. First, we analyzed the types of ESBL-causative genes obtained from 141 ESBL-PE strains collected from the feces of residents in four Japanese g-LTCFs. Next, we determined the minimum inhibitory concentration values for alternative antimicrobial agents against ESBL-PE, including β-lactams and non-β-lactams. Escherichia coli accounted for 96% of the total ESBL-PE strains. Most strains (94%) contained blaCTX-M group genes. The genes most commonly underlying resistance were of the blaCTX-M-9 and blaCTX-M-1 groups. Little difference was found in the distribution of ESBL-causative genes among the facilities; however, antimicrobial susceptibility differed widely among the facilities. No specific difference was found between antimicrobial susceptibility and the number of ESBL-causative genes. Our data showed that ESBL-PEs were susceptible to some antimicrobial agents, but the susceptibility largely differed among facilities. These findings suggest that each g-LTCF may require specific treatment strategies based on their own antibiogram. Investigations into drug resistance should be performed in g-LTCFs as well as acute medical facilities.
  • Joseph Y Abrams, Ryusuke Ae, Ryan A Maddox, Lawrence B Schonberger, Yosikazu Nakamura, Ermias D Belay
    Pediatrics international : official journal of the Japan Pediatric Society 64(1) e15112 2021年12月27日  査読有り責任著者
    BACKGROUND: Kawasaki disease (KD) can result in severe coronary artery abnormalities (CAAs). Corticosteroids added to initial standard intravenous immunoglobulin (IVIG) treatment may decrease the risk for these complications. Different corticosteroid regimens (single-day high dose pulse vs multiple lower doses) may contribute to the discrepant results of prior studies. METHODS: Using data from the 22nd, 23rd , and 24th Japanese nationwide KD surveys (2011-2016), we identified KD patients who did not have CAAs at first presentation and who were treated with either pulse or multiple-dose corticosteroids as part of their initial treatment. Occurrence of subsequent CAAs and treatment failure were compared between the treatment regimens and adjusted odds ratios were calculated controlling for sex, age group, illness day at first treatment, survey, and recurrent KD. RESULTS: There were 782 KD patients who received pulse corticosteroid treatment and 4,817 who received multiple dose treatment. Patients receiving multiple dose treatment were less likely to develop CAAs (5.5% vs 8.3%, OR 0.64; 95% CI: 0.48-0.85) or treatment failure (21.4% vs 41.6%; OR: 0.38; 95% CI: 0.33-0.45). Adjusted analyses showed similar protective effects of multiple-dose treatment against CAAs (OR: 0.67, 95% CI: 0.51-0.90) and treatment failure (OR: 0.39, 95% CI: 0.33-0.46). CONCLUSIONS: Multiple-dose corticosteroid combination treatment resulted in substantially improved outcomes in KD patients compared to pulse treatment. For patients who may be at elevated risk of treatment failure or CAA, use of multiple-dose corticosteroids in conjunction with IVIG is likely to provide considerable clinical benefit.
  • Ryusuke Ae, Teppei Sasahara, Akio Yoshimura, Koki Kosami, Shuji Hatakeyama, Kazumasa Sasaki, Yumiko Kimura, Dai Akine, Masanori Ogawa, Kenji Hamabata, Longzhu Cui
    Scientific Reports 11(1) 21607-21607 2021年11月3日  筆頭著者責任著者
    Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with < 2 months residence at study onset or new admission during the study period. Three analyses were performed: (1) ESBL-E carriage statuses in Cohort 1 and Cohort 2; (2) changes in ESBL-E carriage statuses 3-12 months after the first testing and ≥ 12 months after the second testing; and (3) lengths of positive ESBL-E carriage statuses. Compared with the residents in Cohort 1, a significantly larger proportion of residents in Cohort 2 were positive for ESBL-E carriage (28.0% in Cohort 1 vs 40.0% in Cohort 2). In the subsequent testing results, 18.3% of residents who were negative in the first testing showed positive conversion to ESBL-E carriage in the second testing, while no patients who were negative in the second testing showed positive conversion in the third testing. The maximum length of ESBL-E carriage was 17 months. The findings indicated that some residents acquired ESBL-E through potential cross-transmission inside the LTCFs after short-term residence. However, no residents showed positive conversion after long-term residence, which indicates that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures could improve the ESBL-E prevalence in geriatric LTCFs.
  • Takao Kojo, Ryusuke Ae, Koki Kosami, Shizukiyo Ishikawa, Ichiro Innami
    Preventive medicine 153 106857-106857 2021年10月20日  査読有り責任著者
    Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40-89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1-3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%-63%, while the percentage of patients with 1-3 risk factor(s) was 71-83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.
  • Shuhei Hiyama, Tomohiro Matsumura, Tsuneari Takahashi, Ryusuke Ae, Katsushi Takeshita
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2021年9月24日  査読有り
    BACKGROUND: There is a need for a novel therapeutic strategy for an earlier prediction of long bone union failure as compared to previous methodologies. This study aimed to determine whether a combination of two diagnostic tools would result in a more accurate diagnosis of delayed union. METHODS: The inclusion criteria were as follows: patients with tibial shaft fracture who underwent treatment with intramedullary nailing (IMN) as definitive internal fixation (IF). The study included a total of 114 patients with 116 tibial shaft fractures treated with IMN as definitive IF. Radiographic apparent bone gap (RABG) and nonunion risk determination score (NURDS) can be used to predict nonunion. However, this study aimed to determine whether combination of RABG and NURDS could help deduce a more accurate prediction of delayed union. RESULTS: The union rate was found to be 85% (99 fractures), the delayed union rate was found to be 15% (17 fractures), and the rate of nonunion requiring additional surgical intervention was estimated to be 4% (5 out of the 17 delayed union cases). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RABG were found to be 82.3%, 76.0%, 36.8%, and 96.2%, respectively, when an RABG cutoff value of 5.0 mm was applied to our patient cohort. The sensitivity, specificity, PPV, and NPV of NURDS were found to be 47.1%, 82.0%, 30.8%, and 90.1%, respectively, when a NURDS cutoff value of 8.0% was applied to our patient cohort. When RABG and NURDS were above their respective cutoff values, the sensitivity and PPV were estimated to be 90.0% and 56.3%, respectively. When RABG and NURDS were below their respective cutoff values, the specificity and NPV were estimated to be 90.1% and 98.5%, respectively. CONCLUSIONS: The combination of RABG and NURDS evaluation immediately after surgery helps surgeons identify patients who are at a high risk of delayed union, facilitating careful monitoring of these patients and consideration of additional treatments.
  • Masaki Iguchi, Tsuneari Takahashi, Tomohiro Matsumura, Ryusuke Ae, Shuhei Hiyama, Mitsuharu Nakashima, Katsushi Takeshita
    Injury 2021年9月23日  査読有り責任著者
    INTRODUCTION: The AO/OTA classification for diagnosing femoral trochanteric fractures (31A fractures) was revised in 2018. No studies have investigated whether the addition of CT to radiographic diagnosis improves the inter-rater reliability of classifying 31A fractures with the current AO/OTA criteria. The study aimed to test the hypothesis that the addition of three-dimensional CT (3D-CT) to radiographic diagnosis would improve diagnostic reliability. METHODS: A retrospective review was conducted to assess the diagnostic reliability of classification of 31A fractures with current AO/OTA criteria. Radiographs and 3D-CT images from 89 cases were assessed. Major fracture types (A1, A2, and A3) and subgroups were diagnosed by nine orthopedic surgeons who were classified into three groups (high-, intermediate-, and low-experience) according to their clinical experience. Anterior-posterior and lateral radiographs were provided to diagnose fracture type (first assessment). After a 6-week interval, radiographs and 3D-CT images of all cases were evaluated by each rater (second assessment). Fleiss's Kappa was used to determine inter-rater reliability. RESULTS: In the first assessment, the Kappa value indicated fair inter-rater reliability in all groups (high-experience group: κ = 0.296, 95% confidence interval [CI] 0.239-0.352; intermediate-experience group: κ = 0.367, 95% CI 0.305-0.428; low-experience group: κ = 0.304, 95% CI 0.246-0.362). With the addition of 3D-CT (second assessment), reliability improved from fair to moderate in the high- and intermediate-experience groups (κ = 0.483, 95% CI 0.428-0.539 and κ = 0.409, 95% CI 0.352-0.466, respectively). By contrast, reliability remained fair in the low-experience group (κ = 0.322, 95% CI 0.322-0.431). The inter-rater reliability of diagnosing subgroup fracture types improved for A2.3 and A3.1 in all three groups and for A3.2 and A3.3 in the intermediate- and low-experience groups. CONCLUSION: The current AO/OTA classification revised in 2018 provided fair reliability in diagnosing femoral trochanteric fractures in all three surgeon groups. The addition of 3D-CT to radiographic image evaluation improved reliability in high- and middle-expertise groups. The addition of 3D-CT to radiographic evaluation often improved the diagnostic reliability for unstable fractures, although there was some variation among fracture subgroups.
  • 小川 真規, 阿江 竜介, 笹原 鉄平, 秋根 大
    産業衛生学雑誌 63(5) 154-161 2021年9月  
  • 小川 真規, 阿江 竜介, 笹原 鉄平, 秋根 大
    産業衛生学雑誌 63(5) 154-161 2021年9月  
  • Yuji Kaneda, Yuki Kimura, Akira Saito, Hideyuki Ohzawa, Ryusuke Ae, Hiroshi Kawahira, Alan K Lefor, Naohiro Sata
    Cureus 13(9) e18238 2021年9月  査読有り
    Introduction Although new techniques and devices have been introduced, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high. To reduce the risk of POPF, we developed an innovative ligation band and conducted this pilot study to assess the possibility of reducing the incidence of POPF and pancreatic necrosis after distal pancreatectomy. Methods Distal pancreatectomy was performed in three pigs. In two animals, ligation of the pancreas was performed while maintaining arterial blood flow to the stump, and in one animal, the arterial blood flow was occluded. After ligation, the pancreas was sharply divided. Animals were sacrificed seven days later, and the remnant pancreas was assessed histologically. POPF was defined as amylase in ascites > 3x the preoperative serum amylase level. The following equation was used to quantify the extent of necrotic tissue: necrotic tissue residual rate = necrotic tissue area/ cross-sectional area. Results All animals survived, and no POPF developed. For two animals in which arterial blood flow to the stump was maintained, necrotic tissue residual rates at the ligation line were 24% and 31%. At the pancreatic stump, necrotic tissue residual rates were 37% and 50%. In the animal in which arterial blood flow to the stump was occluded, the necrotic tissue residual rate at the ligation line was 83% and that at the pancreatic stump was 78%, both higher than that in animals in which arterial blood flow was maintained. In all animals, there was no injury to pancreatic tissue at the ligation line. Conclusion The pancreas ligation band can potentially prevent POPF after distal pancreatectomy by atraumatic ligation, and the band ligates the pancreatic stump while maintaining arterial blood flow and limiting pancreatic necrosis.
  • Hiroya Masuda, Ryusuke Ae, Taka-Aki Koshimizu, Masami Matsumura, Koki Kosami, Kanako Hayashida, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Yosikazu Nakamura
    Clinical rheumatology 41(1) 137-145 2021年8月7日  査読有り筆頭著者責任著者
    INTRODUCTION/OBJECTIVES: Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) identified after acute Kawasaki disease (KD). However, the serum sodium distribution corresponding to the reference intervals differs between infants (< 1 year of age) and older children. We hypothesized the association of serum sodium level with CAL complications differs between infants and older patients with KD. METHODS: We analyzed 21,610 population-based patients who developed KD throughout Japan during 2013-2014. We performed multivariable logistic regression analyses to evaluate the association between serum sodium and CAL complications. Additionally, we stratified the serum sodium distribution associated with CAL complications by infants and older patients. RESULTS: CALs were identified in 158 (3.6%) infants and 302 (1.8%) older patients. Infants were more likely to develop CALs when within the normal sodium range compared with older patients (75% vs. 29%), whereas most older patients developed CALs with a sodium level lower than the reference interval. Serum sodium ≤ 130 mEq/L indicated significantly higher risk for development of CALs in both groups (adjusted odds ratio [95% confidence intervals] = 3.21 [1.65-6.25] in infants and 1.74 [1.18-2.57] in older patients). CONCLUSIONS: Serum sodium distribution associated with CAL complications differed greatly between infants and older patients. Older patients developed CALs with sodium levels lower than the reference interval; however, among infants, hyponatremia was not necessarily a risk factor for developing coronary artery lesion. When considering risk assessments for CALs using serum sodium levels, infants with KD should be distinguished from older patients. Key Points • Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) among patients with Kawasaki disease. • However, the serum sodium distribution corresponding to the reference intervals differs between infants (< 1 year of age) and older children. • Most infants developed CALs within the normal sodium range, whereas older patients developed at a range lower than the reference interval. • These findings highlight that when considering risk assessments for CALs using serum sodium levels, infants should be distinguished from older patients.
  • Ryusuke Ae, Yoshihide Shibata, Koki Kosami, Yosikazu Nakamura, Hiromichi Hamada
    The Journal of pediatrics 239 50-58 2021年7月26日  査読有り筆頭著者責任著者
    OBJECTIVE: To assess the epidemiologic association between Kawasaki disease and common pediatric infectious diseases (PIDs) identified during the coronavirus disease 2019 (COVID-19) pandemic period to confirm whether the infection-triggered theory is a plausible hypothesis for the pathogenesis of Kawasaki disease. STUDY DESIGN: A retrospective epidemiologic study was conducted using datasets obtained from Web-based surveillance of Kawasaki disease and PIDs in Japan. We compared weekly numbers of patients who developed Kawasaki disease and specific PIDs between 2020 and 2017-2019 and evaluated the association between the percent reduction in the number of patients with these diseases. RESULTS: A total of 868 patients developed Kawasaki disease in 2020. During the social distancing period in 2020, the number of patients with Kawasaki disease was approximately 35% lower than in 2017-2019. Time from the onset of Kawasaki disease until the first hospital visit did not differ significantly among the examined years. The proportion of older children with Kawasaki disease decreased more than that of infants with Kawasaki disease (age <1 year), resulting in a significant difference in the proportion of infant patients between 2020 and 2017-2019 (24% vs 19%; P < .01). The number of patients with incomplete Kawasaki disease was unchanged from that of previous years. The weekly percent reduction in patient numbers differed between Kawasaki disease and PIDs during 2020, with no strong correlation between the 2 diseases. CONCLUSIONS: Our data indicate that parents of patients with Kawasaki disease did not avoid hospital visits during the COVID-19 pandemic period. The findings indicate the possibility that triggering Kawasaki disease might be associated with presently unidentified respiratory pathogen(s) that potentially might be acquired from both within and outside the household.
  • Kanako Hayashida, Ryusuke Ae, Hiroya Masuda, Koki Kosami, Masami Matsumura, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Yosikazu Nakamura
    The Pediatric infectious disease journal 40(6) 531-536 2021年6月1日  査読有り筆頭著者責任著者
    BACKGROUND: Some patients with Kawasaki disease (KD) have siblings who developed the same disease. Using a large-scale epidemiologic dataset, the present study aimed to determine the clinical characteristics of this population. METHODS: We analyzed 89,725 patients diagnosed with KD during 2011-2018 who were registered in the nationwide Japanese KD survey database. Multivariable logistic regression analyses were performed to determine factors associated with sibling history of KD. RESULTS: Of the 89,725 patients, 1777 (2%) had sibling history of KD. Annual prevalence ranged from 1.5% to 2.3% during the study period and showed a tendency toward an increasing trend. Patients with recurrent KD and parental history of KD were significantly associated with sibling history of KD (adjusted odds ratio [95% confidence interval] = 2.15 [1.82-2.54] and 2.64 [2.02-3.47], respectively). Although patients with a sibling history of KD were significantly associated with initial intravenous immunoglobulin treatment resistance (1.14 [1.02-1.28]), no significant association was found between sibling history and coronary artery abnormality development. Among patients with a sibling history of KD, male patients were less likely to have recurrent KD than female patients (0.68 [0.49-0.96]). CONCLUSIONS: The significant association between sibling history and parental history may indicate genetic susceptibility to KD onset. Among those with a sibling history, recurrent KD was more likely to occur in female patients. Further studies focusing on this population may contribute toward identification of the cause of KD onset.
  • Ryusuke Ae, Ryan A Maddox, Joseph Y Abrams, Lawrence B Schonberger, Yosikazu Nakamura, Masanari Kuwabara, Nobuko Makino, Koki Kosami, Yuri Matsubara, Daisuke Matsubara, Teppei Sasahara, Ermias D Belay
    Journal of the American Heart Association 10(7) e019853 2021年4月6日  査読有り筆頭著者責任著者
    Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.
  • Hiroya Masuda, Ryusuke Ae, Taka-Aki Koshimizu, Masami Matsumura, Koki Kosami, Kanako Hayashida, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Yosikazu Nakamura
    Pediatric cardiology 42(4) 969-977 2021年4月  査読有り筆頭著者責任著者
    A giant coronary artery (CA) aneurysm is a potentially fatal cardiac complication resulting from Kawasaki disease (KD). We aimed to identify epidemiologic characteristics and potential risk factors associated with giant CA aneurysms identified after acute KD. We analyzed 90,252 patients diagnosed with KD from 2011 to 2018, using data obtained in nationwide KD surveys conducted in Japan. Multivariable logistic regression analyses were performed to evaluate potential risk factors associated with subsequent giant CA aneurysm complications (defined as lumen size ≥ 8 mm), adjusting for all potential factors. Giant CA aneurysms were identified in 144 patients (0.16%) after acute KD. The annual prevalence ranged from 0.07 to 0.20% during the study period. In the multivariate analyses, male sex (adjusted odds ratio 2.09 [95% confidence interval 1.41-3.11], recurrent KD (1.90 [1.09-3.33]), IVIG administration at 1-4 days of illness (1.49 [1.04-2.15]) and ≥ 8 days after KD onset (2.52 [1.38-4.60]; reference, 5-7 days), detection of CA dilatations and aneurysms at initial echocardiography (4.17 [1.85-5.41] and 46.5 [28.8-74.8], respectively), and resistance to IVIG treatment (6.09 [4.23-8.75]) were significantly associated with giant CA aneurysm complications identified after acute KD. The annual prevalence of giant CA aneurysms identified after acute KD did not increase during the study period. Patients with larger CA abnormalities detected at initial echocardiography were independently associated with progression to giant CA aneurysm complications after acute KD regardless of the number of days from onset at treatment initiation.
  • Akio Yoshimura, Teppei Sasahara, Ryusuke Ae, Koki Kosami, Dai Akine, Masanori Ogawa, Kenji Hamabata, Shuji Hatakeyama, Yuji Morisawa, Longzhu Cui
    Biocontrol science 26(4) 207-210 2021年  
    Influenza outbreaks at geriatric long-term care facilities (g-LTCFs) can be deadly and their prevention is important. However, the factors influencing disease transmission in g-LTCFs remain controversial. In this descriptive study, we tried to identify the potential risk factors influencing influenza outbreaks that occurred in different influenza seasons within a single g-LTCF with 100 residents in Gunma Prefecture. We reviewed the detailed facility records for all influenza cases in both residents and staff between January 2012 and June 2020. Facility preventive measures were also reviewed. We found that community meals may have been a potential source of transmission leading to the outbreaks. When influenza infection is noted, implementation of strict preventive measures and restriction of meal provision to resident rooms may help to prevent disease transmission and the development of an outbreak. Such measures may also be useful to prevent the transmission of other serious droplet-borne diseases within g-LTCFs.
  • Masanori Ogawa, Ryusuke Ae, Teppei Sasahara, Dai Akine
    Sangyo eiseigaku zasshi = Journal of occupational health 63(5) 154-161 2020年12月25日  査読有り
    OBJECTS: The number of workers dispatched to developing countries has increased recently. The sanitary conditions in these countries are different from those in developed countries and from what the workers are used to. Therefore, health control, especially infection control, is an important consideration for working there. In this study, we investigate workers' needs as well as the occupational physicians' skills concerning working in developing countries. We propose a more effective education system for health control. METHODS: Regarding workers who have lived in developing countries, we surveyed the company profiles, duration of stay, vaccination status, infectious education, medical assistance, and satisfaction with infection control strategies of their employer companies. Regarding occupational physicians, we surveyed their profiles, their experiences in consultation, and advice from/to the workers dispatched to developing countries as well as their suggestive advice for staying there. RESULTS: Factors that contributed to workers' satisfaction with their employment companies were prior education and health consulting services in addition to company size. Many occupational physicians believed that this kind of information should be supplied but they did not have the confidence to provide it. CONCLUSIONS: Workers who are dispatched overseas should receive prior education and access to health consulting services. It is necessary for information providers such as occupational physicians to be knowledgeable in travel medicine.
  • Teppei Sasahara, Koki Kosami, Akio Yoshimura, Ryusuke Ae, Dai Akine, Masanori Ogawa, Yuji Morisawa
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27(2) 329-335 2020年12月16日  査読有り責任著者
    INTRODUCTION: Hand hygiene is crucial for infection control in long-term care facilities for elderly (LTCFEs), because it can be easily implemented in the low-resource settings of LTCFEs. This study investigated the actual status of hand hygiene adherence in LTCFEs, identified the factors inhibiting its appropriate implementation, and evaluated the effectiveness of a hand hygiene promotion program. METHODS: In this before-and-after study, participants were staff members (n = 142) at two LTCFEs in Gunma Prefecture, Japan. We modified the World Health Organization's "five moments for hand hygiene" and assessed participants' hand hygiene adherence rates in four situations: (1) Before touching around a resident's mucous membrane area; (2) Before medical practice or clean/aseptic procedures; (3) After body fluid exposure/risk or after touching around a resident's mucous membrane area; and (4) After touching a resident's contaminated environments. The study was divided into four phases. In Phase 1, participants self-assessed their hand hygiene adherence using a questionnaire. In Phase 2, we objectively assessed participants' pre-intervention adherence rates. In Phase 3, an intervention comprising various hand hygiene promotion measures, such as education and hands-on training on hand hygiene practices and timings, was implemented. In Phase 4, participants' post-intervention adherence rates were objectively measured. RESULTS: Although most participants reported high hand hygiene adherence rate in the self-assessment (93.1%), the pre-intervention evaluation revealed otherwise (16.8%). Participants' post-intervention adherence rates increased for all four situations (77.3%). CONCLUSION: The intervention program helped increase participants' hand hygiene adherence rates, indicating its effectiveness. Similar interventions in other LTCFEs may also improve adherence rates.

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