記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/00005053-200203000-00006

記述言語：英語   出版者・発行元：Journal of Microbiology, Immunology and Infection  

Background/Purpose: Recent large-scale epidemiological studies have revealed significant temporal associations between certain viral infections and the subsequent development of Kawasaki disease (KD). Despite these associations, definitive laboratory evidence linking acute or recent viral infections to KD cases remains elusive. The objective of this study is to employ a molecular epidemiological approach to investigate the temporal association between viral infections and the development of KD. Methods: We analyzed 2460 patients who underwent the FilmArray® Respiratory Panel test between April 2020 and September 2021. Results: Following the application of inclusion criteria, 2402 patients were categorized into KD (n = 148), respiratory tract infection (n = 1524), and control groups (n = 730). The KD group exhibited higher positive rates for respiratory syncytial virus (RSV), human rhinovirus/enterovirus (hRV/EV), parainfluenza virus (PIV) 3, and adenovirus (AdV) compared to the control group. Additionally, coinfections involving two or more viruses were significantly more prevalent in the KD group. Notably, RSV-positive, hRV/EV-positive, and PIV3-positive KD patients exhibited a one-month delay in peak occurrence compared to non-KD patients positive for corresponding viruses. In contrast, AdV-positive KD cases did not show a one-month delay in peak occurrence. Moreover, anti-RSV, anti-PIV3, and anti-AdV antibody-positive rates or antibody titers were higher in RSV-, PIV3-, and AdV-positive KD cases, respectively, compared to non-KD cases with the same viral infections. Conclusion: Recent infection with RSV, PIV3, or AdV, occasionally in conjunction with other viruses, may contribute to the pathogenesis of KD as infrequent complications.

DOI： 10.1016/j.jmii.2024.07.001

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

DOI： 10.1007/s10384-024-01100-3

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記述言語：英語   出版者・発行元：PLoS ONE  

Traumatic spinal cord injury (TSCI) causes an insult to the central nervous system, often resulting in devastating temporary or permanent neurological impairment and disability, which places a substantial financial burden on the health-care system. This study aimed to clarify the up-to-date epidemiology and demographics of patients with TSCI treated at the largest SCI center in Japan. Data on all patients admitted to the Spinal Injuries Center with TSCI between May 2005 and December 2021 were prospectively collected using a customized, locally designed SCI database named the Japan Single Center Study for Spinal Cord Injury Database (JSSCI-DB). A total of 1152 patients were identified from the database. The study period was divided into the four- or five-year periods of 2005–2009, 2010–2013, 2014–2017, and 2018–2021 to facilitate the observation of general trends over time. Our results revealed a statistically significant increasing trend in age at injury. Since 2014, the average age of injury has increased to exceed 60 years. The most frequent spinal level affected by the injury was high cervical (C1-C4: 45.8%), followed by low cervical (C5-C8: 26.4%). Incomplete tetraplegia was the most common cause or etiology category of TSCI, accounting for 48.4% of cases. As the number of injuries among the elderly has increased, the injury mechanisms have shifted from high-fall trauma and traffic accidents to falls on level surfaces and downstairs. Incomplete tetraplegia in the elderly due to upper cervical TSCI has also increased over time. The percentage of injured patients with an etiology linked to alcohol use ranged from 13.2% (2005–2008) to 19% (2014–2017). Given that Japan has one of the highest aging populations in the world, epidemiological studies in this country will be very helpful in determining health insurance and medical costs and deciding strategies for the prevention and treatment of TSCI in future aging populations worldwide.

DOI： 10.1371/journal.pone.0298836

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

進行性ホルモン感受性前立腺癌(HSPC)に対するゴナドトロピン放出ホルモン(GnRH)アンタゴニスト単独療法と、GnRHアゴニストとビカルタミド併用による複合アンドロゲン遮断療法(CAB)の有効性と安全性を、無作為化非盲検多施設共同試験(KYUCOG-1401試験)で比較した。患者200例を登録し、A群(GnRHアンタゴニスト単独療法後にビカルタミドを追加)またはB群(GnRHアゴニストとビカルタミド併用によるCAB)に無作為化した。A群100例、B群98例を解析した。主要評価項目の前立腺特異抗原(PSA)無増悪生存期間(PFS)はB群で有意に長かった(ハザード比:1.40、95%CI:1.01～1.95、p=0.041)。副次評価項目のCAB治療不成功までの期間はA群の方がわずかに長かった(ハザード比:0.80、95%CI:0.59～1.08、p=0.146)。X線画像上のPFSおよび全生存期間に有意な群間差は認められなかった。60週時に血清テストステロン値が去勢レベルに達しなかった患者の割合はA群の方が高かった(p=0.046)。血清骨代謝マーカー値や脂質マーカー値に有意な群間差はなかった。注射部位反応の発生率はA群の方が高かった。以上より、進行性HSPCに対するGnRHアゴニストとビカルタミドを併用したCABは、GnRHアンタゴニスト単独療法よりも有効な治療法である可能性が示唆された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Preventive Cardiology  

Aims Exercise intolerance is a clinical feature of patients with heart failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line examination for assessing exercise capacity in patients with HF. However, the need for extensive experience in assessing anaerobic threshold (AT) and the potential risk associated with the excessive exercise load when measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This study aimed to use deep-learning approaches to identify AT in real time during testing (defined as real-time AT) and to predict peak VO2 at real-time AT. Methods and results This study included the time-series data of CPET recorded at the Department of Cardiovascular Medicine, Kyushu University Hospital. Two deep neural network models were developed to: (i) estimate the AT probability using breath-by-breath data and (ii) predict peak VO2 using the data at the real-time AT. The eligible CPET contained 1472 records of 1053 participants aged 18–90 years and 20% were used for model evaluation. The developed model identified real-time AT with 0.82 for correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error (MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25 mL/kg/min for MAE. Conclusion Deep-learning models for real-time CPET analysis can accurately identify AT and predict peak VO2. The developed models can be a competent assistant system to assess a patient’s condition in real time, expanding CPET utility.

DOI： 10.1093/eurjpc/zwad375

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14–2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

DOI： 10.1038/s41598-023-51085-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical and Translational Immunology  

Objectives: The objectives of this study were to investigate the pathophysiology of Kawasaki disease (KD) from immunological and oxidative stress perspectives, and to identify real-time biomarkers linked to innate immunity and oxidative stress in KD. Methods: We prospectively enrolled 85 patients with KD and 135 patients with diverse conditions including immune, infectious and non-infectious diseases for this investigation. Flow cytometry was used to analyse the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. Additionally, oxidative stress levels were evaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxidant capacity measured by a free radical elective evaluator system. Results: During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, reflecting the indirect detection of circulating innate immune molecular patterns. Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. Notably, the surface expression of CD14 on monocytes was restored concurrently with responses to intravenous immunoglobulin and infliximab treatment in KD. Furthermore, d-ROM levels in patients with KD were significantly elevated compared with patients with infectious and non-infectious diseases. Following intravenous immunoglobulin treatment, oxidative stress levels decreased in patients with KD. Conclusion: Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients. The interplay between inflammation and oxidative stress likely plays a crucial role in the development of KD.

DOI： 10.1002/cti2.1482

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Urology  

Objectives: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). Methods: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. Results: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01–1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59–1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. Conclusions: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.

DOI： 10.1111/iju.15371

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

冠動脈ステント留置術を受けた冠動脈疾患の患者をスタチン(S)またはSとエゼチミブの併用(S+E)で治療するCuVIC試験から、治療前と6～8ヵ月追跡調査後の非責任病変の血管内超音波(IVUS)画像が得られた79症例(S群39名、S+E群40名)を抽出し解析した。治療期間後のS+E群のLDL-コレステロール(LDL-C)値はS群と比べて有意に低かった。S+E群ではコレステロール吸収のマーカーであるcampesterol、オキシステロール(β-epoxycholesterol、4β-hydroxycholesterol、27-hydroxycholesterol)も低かった。IVUS解析でS+E群のプラーク退縮率はS群と比べて大きかった。campesterolおよび27-hydroxycholesterolの低下はプラーク退縮と正相関し、LDL-Cの低下は相関しなかった。

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Trials  

Background: We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study. Methods: This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO–quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled. Discussion: This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia. Trial registration: This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021.

DOI： 10.1186/s13063-023-07468-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nutrients  

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n = 207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis”. Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

DOI： 10.3390/nu15132997

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記述言語：英語   出版者・発行元：Nature Publishing Group  

安静時心拍数(RHR)と心血管イベント(心、脳、腎血管疾患または関連死)の関連について検討した。EMPATHY(The standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY)試験に参加した網膜症合併2型糖尿病患者4746名を、ベースライン時のRHR(中央値76、四分位範囲69～85bpm)で4群に分け、心血管イベントの発生率を比較した。RHR高値群ほど低年齢であり、BMI、血圧、HbA1c、eGFR、喫煙率、糖尿病合併症の有病率が高かった。Cox比例ハザードモデルによる解析の結果、RHR高値は心血管イベントと有意に関連し、RHR 60～69bpm群に対する70～79bpm群および≧80bpm群の多変量調整ハザード比は、それぞれ1.50(95%CI 1.03～2.20)および1.62(1.11～2.36)であった(P<0.05)。心血管イベントリスクはRHRが70bpm以上であれば同様に高い傾向にあり、両者間に線形関係はみられなかった。

記述言語：英語   出版者・発行元：Hypertension Research  

A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR (< 60, 60–69, 70–79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70–79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03–2.20; and hazard ratio 1.62, 95% CI 1.11–2.36; respectively) compared to a RHR of 60–69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60–69 bpm. [Figure not available: see fulltext.].

DOI： 10.1038/s41440-023-01178-1

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Circulation: Arrhythmia and Electrophysiology  

DOI： 10.1161/CIRCEP.122.011579

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Psychiatry  

Backgrounds: Hikikomori, pathological social withdrawal, is becoming a crucial mental health issue in Japan and worldwide. We have developed a 3-day family intervention program for hikikomori sufferers based on Mental Health First Aid (MHFA) and Community Reinforcement and Family Training (CRAFT). This study aims to confirm the effectiveness of the 3-day program by a randomized controlled trial. Methods: This study was registered on the UMIN Clinical Trials Registry (UMIN000037289). Fifteen parents were assigned to the treat as usual (TAU) group (TAU only; Age Mean, 65.6; SD, 7.8), and 14 to the Program group (program + TAU; Age Mean, 67.9; SD, 8.6). This study was discontinued due to the COVID-19 pandemic; the recruitment rate was 36.3% of our target sample size of 80. Results: Perceived skills improved temporally and stigma temporally worsened in the TAU group. Confidence decreased and attitude showed no change in both groups. Aggressive behaviors of hikikomori sufferers were significantly worsened in the Program group; however, no serious domestic violence was reported. In the TAU group, Avoidance and irregular life patterns were improved. Activity levels were worsened in both groups. Two participants (16.7%) in the Program group and one participant (7.7%) in the TAU group reported actual behavioral changes (e.g., utilizing support). Conclusion: We could not draw general conclusions on the effectiveness of the program due to the study discontinuation. Nevertheless, this study indicates the necessity for revision of the program to improve family members’ confidence in engaging with hikikomori sufferers, with safer approaching by families.

DOI： 10.3389/fpsyt.2022.1029653

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Urology  

Objectives: In children with a first Escherichia coli-induced febrile urinary tract infection (fUTI), routine voiding cytourethrography (VCUG) is not recommended for detecting vesicoureteral reflux (VUR). Meanwhile, the sensitivity of renal and bladder ultrasound (RBUS) for detecting VUR is insufficient. Aiming to implement VCUG properly for children with a first E. coli-induced fUTI, we attempted to construct a predictive scoring system for the early screening of VUR. Methods: This study enrolled patients aged <2 years of age hospitalized for their first E. coli-induced fUTI during the period when VCUG was implemented for all patients (2007–14, non-selective group [n = 111]) and only for those with VUR-suspected RBUS findings, bacteremia or acute focal bacterial nephritis (2016–19, selective group [n = 102]). We evaluated the accuracy of the current criteria and the VUR predictive score constructed using data from the non-selective group. Results: In the non-selective group, 32 patients had VUR (29%). In the selective group, 20 of 45 VCUG-tested patients had VUR (44%). Among 57 patients not undergoing VCUG in the selective group, 8 had a recurrence of fUTI, 3 of whom were diagnosed with VUR. In the non-selective group, 9 patients with VUR did not fulfill the current criteria and the VUR predictive score consisting of young age, female sex, prolonged fever, hypoproteinemia, hyponatremia and hyperglycemia, showed higher sensitivity, specificity than the current criteria. Conclusions: The current imaging/bacteriological criteria were ineffective in screening for VUR in patients with their first E. coli-induced fUTI. The VUR predictive score can be an accurate indicator for implementing VCUG.

DOI： 10.1111/iju.15041

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1183/13993003.00380-2022

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本動脈硬化学会  

Aim: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial. Methods: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6–8 months of follow-up. Results: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S ＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (−6.14% vs. −1.18% for each group, p =0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression. Conclusions: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

DOI： 10.5551/jat.63507

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

大腸菌による初回発熱性尿路感染症(fUTI)の患児に対し排尿時膀胱尿道造影(VCUG)を適切に行う目的で、膀胱尿管逆流症(VUR)の予測スコアの構築を試みた。全例にVCUGを行った期間(2007～2014年)ならびにVURを疑う腎・膀胱超音波(RBUS)所見を認める場合にのみVCUGを行った期間(2016～2019年)に初回fUTIにより入院した2歳未満の患児それぞれ111例(非選択群)、102例(選択群)を対象とした。非選択群では32例(29%)がVURと診断された。選択群ではVCUGを行った45例中20例(44%)がVURと診断され、VCUGを行わなかった57例中8例がfUTI再発をきたし、うち3例がVURと診断された。非選択群でVURと診断された患児のうち9例は、RBUS所見に基づいた現在のVCUG実施基準を満たさなかった。非選択群のデータを用いた多変量ロジスティック回帰分析により6因子(低年齢、女性、発熱の持続、低タンパク血症、低ナトリウム血症、高血糖)を選択し、VUR予測スコアを作成した。その結果、現在のVCUG実施基準に比べてVUR検出の感度および特異度が高かった。

記述言語：英語   出版者・発行元：Journal of the Neurological Sciences  

Objective: The current study sought to develop a new indicator for disease progression rate in amyotrophic lateral sclerosis (ALS). Methods: We used a nonparametric method to score diverse patterns of decline in the percentage of predicted forced vital capacity (%FVC) in patients with ALS. This involved 6317 longitudinal %FVC data sets from 920 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database volunteered by PRO-ACT Consortium members. To assess the utility of the derived scores as a disease indicator, we examined changes over time, the association with prognosis, and correlation with the Risk Profile of the Treatment Research Initiative to Cure ALS (TRICALS). Our local cohort (n = 92) was used for external validation. Results: We derived scores ranging from 35 to 106 points to construct the FVC Decline Pattern scale (FVC-DiP). Individuals' FVC-DiP scores were determined from a single measurement of %FVC and disease duration at assessment. Although the %FVC declined over the disease course (p < 0.0001), the FVC-DiP remained relatively stable. Low FVC-DiP scores were associated with rapid disease progression. Using our cohort, we demonstrated an association between FVC-DiP and the survival prognosis, the stability of the FVC-DiP per individual, and a correlation between FVC-DiP scores and the TRICALS Risk Profile (r2 = 0.904, p < 0.0001). Conclusions: FVC-DiP scores reflected patterns of declining %FVC over the natural course of ALS and indicated the disease progression rate. The FVC-DiP may enable easy assessment of disease progression patterns and could be used for assessing treatment efficacy.

DOI： 10.1016/j.jns.2022.120389

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Darbepoetin alfa (DA) is used to treat anemia in lower-risk (IPSS low or int-1) myelodysplastic syndromes (MDS). However, whether mutations can predict the effectiveness of DA has not been examined. The present study aimed to determine predictive gene mutations. The primary endpoint was a correlation between the presence of highly frequent (≥ 10%) mutations and hematological improvement-erythroid according to IWG criteria 2006 by DA (240 μg/week) until week 16. The study included 79 patients (age 29–90, median 77.0 years; 52 [65.8%] male). Frequently (≥ 10%) mutated genes were SF3B1 (24 cases, 30.4%), TET2 (20, 25.3%), SRSF2 (10, 12.7%), ASXL1 (9, 11.4%), and DNMT3A (8, 10.1%). Overall response rate to DA was 70.9%. Multivariable analysis including baseline erythropoietin levels and red blood cell transfusion volumes as variables revealed that erythropoietin levels and mutations of ASXL1 gene were significantly associated with worse response (odds ratio 0.146, 95% confidence interval 0.042–0.503; p = 0.0023, odds ratio 0.175, 95% confidence interval 0.033–0.928; p = 0.0406, respectively). This study indicated that anemic patients who have higher erythropoietin levels and harbor ASXL1 gene mutations may respond poorly to DA. Alternative strategies are needed for the treatment of anemia in this population. Trial registration number and date of registration: UMIN000022185 and 09/05/2016.

DOI： 10.1007/s12185-022-03414-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncologist  

Background: Osimertinib is one of the standard first-line treatments for advanced non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations, because it achieves significantly longer progression-free survival (PFS) than conventional first-line treatments (hazard ratio: 0.46). However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remain unclear. Methods: This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. The primary endpoint was 1-year PFS rate; secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety. Results: Thirty-eight patients were included in the analysis. The 1-year PFS rate was 59.4% (95% confidence interval [CI], 46.1%-72.7%), which did not meet the primary endpoint (the threshold 1-year PFS rate of 50% predicted using data from the NEJ003 study). The most common grade 3/4 adverse events were rash/dermatitis acneiform/ALT increased/hypokalemia (2 patients, 5%). Seven patients developed pneumonitis (17.5%). There were no other cases of treatment discontinuation due to adverse events other than pneumonitis. Conclusion: Although this study did not meet the primary endpoint, osimertinib was tolerable for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer.

DOI： 10.1093/oncolo/oyac193

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Lung Cancer  

Background: Renal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel. Patients and Methods: Previously treated NSCLC patients were randomly allocated (1:1) to receive docetaxel (60 mg/m²) on day 1 or nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function. Results: Among the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mL/min, n = 49 for docetaxel and n = 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of >50 to ≤80 mL/min, n = 133 for docetaxel and n = 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population. Conclusion: Nab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment.

DOI： 10.1016/j.cllc.2022.08.011

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記述言語：英語   出版者・発行元：(一社)日本血液学会  

低リスク骨髄異形成症候群(MDS)の貧血に対する持続型赤血球造血刺激因子製剤ダルベポエチンアルファ(DA)の効果を予測するための遺伝子変異について検討した。主要評価項目は、DA(240μg/週)投与開始後16週目の高頻度(10%以上)遺伝子変異と国際ワーキンググループクライテリア2006による血液学的改善-赤血球反応の相関であった。低リスクMDS患者79例(年齢29～90歳)を対象とした。頻繁に変異していた(10%以上)遺伝子は、SF3B1(24例、30.4%)、TET2(20例、25.3%)、SRSF2(10例、12.7%)、ASXL1(9例、11.4%)、DNMT3A(8例、10.1%)であった。DAに対する全奏効率は70.9%であった。ベースラインの血清エリスロポエチン(EPO)値および赤血球輸血量を変数として含む多変量解析の結果、EPO値およびASXL1遺伝子の変異は、奏効率の悪化と有意に関連していた(オッズ比0.146、95%CI 0.042～0.503、p=0.0023;オッズ比0.175、95%CI 0.033～0.928、p=0.0406)。以上より、EPO濃度が高く、ASXL1遺伝子変異を保有する貧血のMDS患者は、DAに対する反応性が不良である可能性が示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Cancer Research and Clinical Oncology  

Purpose: This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years. Methods: The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic. Results: In both age groups, the proportion of missing items was low (< 3%). Cronbach’s α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item (“maintaining purpose”) of the EORTC QLQ-ELD14 worsened (− 6.14 ± 29.20, standard response of mean > 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the “global health status/QOL” and “summary score” of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%. Conclusion: The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer.

DOI： 10.1007/s00432-022-04414-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Translational Lung Cancer Research  

Background: Thyroid transcription factor-1 (TTF-1) expression in advanced non-squamous non-small cell lung cancer (NSCLC) has been associated with the efficacy of pemetrexed plus platinum chemotherapy. However, the relation between TTF-1 expression and efficacy of the combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors plus pemetrexed and platinum chemotherapy, a standard first-line treatment regimen for advanced non-squamous NSCLC, has remained unclear. Methods: We retrospectively evaluated TTF-1 expression in tumor tissue of patients with advanced or recurrent non-squamous NSCLC treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting. Clinical characteristics and pathological data for each patient were assessed, and progression-free survival (PFS) was evaluated. Bias due to patient background was minimized by application of inverse probability of treatment weighting (IPTW) analysis. Results: A total of 122 patients, 75 (61.5%) of whom were positive for TTF-1 immunostaining in tumor specimens, was included in this multicenter study. At the time of analysis, 89 (73.0%) patients had experienced progression events and 44 (36.1%) had died [median follow-up 14.6 months (range, 0.53–29.5 months)]. PFS was longer for TTF-1-positive patients than for TTF-1-negative patients [median, 12.2 vs. 6.0 months; hazard ratio (HR) =0.63 (95% CI: 0.37–1.06); log-rank P=0.028]. IPTW-adjusted PFS was significantly longer for TTF-1-positive than for TTF-1–negative patients [HR =0.62 (95% CI: 0.46–0.83); log-rank P=0.024]. Conclusions: TTF-1 expression in advanced non-squamous NSCLC can serve as a basis for prediction of PFS in patients treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting.

DOI： 10.21037/tlcr-22-393

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC Cancer  

Background: First-line treatment of nonsquamous non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with immune checkpoint inhibitors (ICIs). However, phase III studies of combinations of cytotoxic chemotherapy and ICIs have included only patients with maintained organ function, not those with renal impairment. Methods: Cytotoxic chemotherapy–naïve advanced nonsquamous NSCLC patients aged 20 years or older with impaired renal function (creatinine clearance of 15 to 45 mL/min) are prospectively registered in this single-arm phase II study and receive combination therapy with carboplatin, nanoparticle albumin-bound (nab-) paclitaxel, and atezolizumab. Individuals with known genetic driver alterations including those affecting EGFR, ALK, ROS1, BRAF, MET, RET, and NTRK are excluded. We plan to enroll 40 patients over 2 years at 32 oncology facilities in Japan. The primary end point is confirmed objective response rate. Discussion: If the study demonstrates efficacy and safety of carboplatin/nab-paclitaxel/atezolizumab, then this combination regimen may become a treatment option even for nonsquamous NSCLC patients with impaired renal function. Trial registration: Registered with Japan Registry for Clinical Trials on 25 February 2021 (jRCTs071200102).

DOI： 10.1186/s12885-022-10056-x

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

わが国の矯正施設では近年摂食障害(ED)の受刑者が増加し,女子刑務所などの現場では対応に大変苦慮している.重篤で一般刑務所では対応困難な症例は,医療刑務所に移送される.北九州医療刑務所(以下,当所)では,患者の受け入れを2012年5月より開始し集約的な治療を行ってきた.【目的】当所に入所した100人の神経性やせ症(AN)女性患者を分類し比較することにより,その病態理解を進める.【方法】矯正施設初回入所以前の,EDの病歴と覚醒剤乱用歴の有無により,「ED病歴(+)覚醒剤歴(-)」群,「ED病歴(-)覚醒剤歴(-)」群,「覚醒剤歴(+)ED病歴(+)」群,「覚醒剤歴(+)ED病歴(-)」群に分類し,人口統計学的,臨床的,心理社会的データの比較を行った.【結果】大多数を占めたのは「ED病歴(+)覚醒剤歴(-)」群(n=74)であり,若くして典型的なEDを発症しきわめて長い病歴をもった,重症遷延性神経性やせ症(SEAN)であった.「ED病歴(-)覚醒剤歴(-)」群(n=13)は,中高年になり逮捕や収容を契機にEDを出現させていた.「覚醒剤歴(+)ED病歴(-)」群(n=9)は,矯正施設収容以後に,ほぼ矯正施設内限定でEDの症状を出現させていた.「ED病歴(-)覚醒剤歴(-)」群と「覚醒剤歴(+)ED病歴(-)」群は非典型的なEDの病像を示し,やせ願望は比較的軽度であった.重篤で長いED病歴をもつ「ED病歴(+)覚醒剤歴(-)」群においても,矯正施設初回入所以前にED治療を受けた者は,約半数にすぎなかった.【考察】ANの女性受刑者は均一の集団ではなく,治療や対応はそれぞれの病態に適合させる必要があるため,これらの分類は治療のために有益である.「ED病歴(+)覚醒剤歴(-)」群は,数の多さからもEDの典型性や重篤性からも臨床的に特に重要である.医療刑務所のAN患者の病態や治療について,今後も系統的多面的に研究を進め,報告する予定である.(著者抄録)

記述言語：英語   出版者・発行元：ESMO Open  

The authors regret that despite our best care and attention, we have discovered one error in text and corresponding errors in Table 3 and Supplementary Table S2. 1) One error, placed in the “Toxicity” paragraph in Results section has now been corrected as follows:“Radiation pneumonitis, the most clinically important toxicity, occurred in 14 (82%; grade 1) and 2 (12%; grade 2) patients; …”. 2) In Table 3, number and proportion of those with any grade radiation pneumonitis in CRT phase have also been corrected as “16 (94)”.3) Supplementary Table S2 has also been corrected, according to the former correction of number of patients who had pneumonitis events from 14 to 16.The authors would like to apologize for any inconvenience caused.

DOI： 10.1016/j.esmoop.2022.100532

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記述言語：英語   出版者・発行元：公益社団法人 日本医師会 / 日本医学会  

DOI： 10.31662/jmaj.2021-0227

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ Open  

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH. Methods and analysis The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH. Ethics and dissemination This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results. Trial registration number NCT04730037. Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021.

DOI： 10.1136/bmjopen-2022-061225

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：(公社)日本医師会  

肺癌患者を対象とした前向き研究を実施し、発熱性好中球減少症に対するシタフロキサシン(STFX)の有効性および安全性について検討した。低リスク(MASCCスコア>21)発熱性好中球減少症肺癌患者26例(男性19例、中央値70.0歳)を対象にSTFXを投与した。主要評価項目は奏効率(有害事象を伴わない連続5日間の発熱停止と定義)、副次評価項目は72時間後、7日目、14日目での発熱の有無および安全性とした。その結果、14例(53.85%)で主要評価項目の達成が認められた。STFX以外の抗菌薬投与は2例でのみ認められた。奏効率を微生物変化や重篤な合併症を伴わない発熱性好中球減少症からの回復と定義した場合の奏効率は91.67%であった。72時間後、7日後、14日後に発熱が認められなかった割合は、それぞれ53.84%、86.36%、77.78%であった。有害事象は8例に認められたが、いずれも重篤ではなかった。以上から、STFX投与が肺癌患者における低リスク発熱性好中球減少症に対して有用である可能性が示唆された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Cardiology  

Background: In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. Methods: We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. Results: Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/ mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5-29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low-low BNP group (baseline <35 pg/mL and 12-month <35 pg/mL), low-high BNP group as well as high-high BNP group was associated with cardiovascular events (HR: low-high, 2.05 [P = 0.004]; high-high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High-low BNP group tended to be associated with non-renal cardiovascular events (HR vs low-low: 2.05 [P = 0.056]). Conclusions: BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

DOI： 10.1016/j.ijcard.2022.03.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：eBioMedicine  

BACKGROUND: We conducted an exploratory study to assess the safety tolerability, and anti-fibrotic effects of PRI-724, a CBP/beta-catenin inhibitor, in patients with hepatitis C virus (HCV)- and hepatitis B virus (HBV)-induced cirrhosis.

METHODS: This multicentre, open-label, non-randomised, non-placebo-controlled phase 1/2a trial was conducted at three hospitals in Japan. Between July 27, 2018, and July 13, 2021, we enrolled patients with HCV- and HBV-induced cirrhosis classified as Child-Pugh (CP) class A or B. In phase 1, 15 patients received intravenous infusions of PRI-724 at escalating doses of 140, 280, and 380 mg/m2/4 h twice weekly for 12 weeks. In phase 2a, 12 patients received the recommended PRI-724 dose. The primary endpoints of phases 1 and 2a were the frequency and severity of adverse events and efficacy in treating cirrhosis based on liver biopsy. This study was registered at ClinicalTrials.gov (no. NCT03620474).

FINDINGS: Three patients from phase 1 who received the recommended PRI-724 dose were evaluated to obtain efficacy and safety data in phase 2a. Serious adverse events occurred in three patients, one of which was possibly related to PRI-724. The most common adverse events were diarrhoea and nausea. PRI-724 did not decrease hepatic fibrosis with any statistical significance, either by ordinal scoring or measurement of collagen proportionate area at 12 weeks; however, we observed statistically significant improvements in liver stiffness, Model for End-stage Liver Disease score, and serum albumin level.

INTERPRETATION: Intravenous administration of 280 mg/m2/4 h PRI-724 over 12 weeks was preliminarily assessed to be well tolerated; however, further evaluation of anti-fibrotic effects in patients with cirrhosis is warranted.

FUNDING: AMED, Ohara Pharmaceutical.

DOI： 10.1016/j.ebiom.2022.104069

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1183/13993003.00380-2022

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Cancer  

Background: Human epidermal growth factor receptor 2 (HER2) mutations are present in-3% of patients with non-small cell lung cancer (NSCLC), with exon-20 insertions accounting for-90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody-cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations.Patients and methods: Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR). Results: Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0-55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade >3 being low.Conclusion: T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations. Clinical trial number: JapicCTI-194620 (c) 2021 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejca.2021.11.021

Web of Science

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41440-021-00734-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1210/clinem/dgab450

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ehf2.13556

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/bmjopen-2020-047003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jtho.2021.03.027

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.esmoop.2021.100191

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2176/nmc.oa.2020-0388

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/vaccines9080839

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/HJH.0000000000002823

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Psychological Research  

Hikikomori (a severe form of social withdrawal) is a serious mental health issue. A family approach is the initial step to support hikikomori; thus effective family intervention programs are warranted. We recently developed a 5-day family intervention program (120 min weekly) based on Mental Health First Aid (MHFA) and Community Reinforcement and Family Training (CRAFT). In the present study, we modified the 5-day program to a 3-day program (180 min fortnightly), and examined the effectiveness of the 3-day program using a single-arm procedure. Data of 23 parents (four fathers and 19 mothers; age = 62.0 ± 9.1 years) were analyzed. Mental health conditions among participants themselves improved at the 4-month follow-up, but the confidence in hikikomori support declined and stigma toward mental health problems did not change. However, short-term improvements in perceived skills in approaching hikikomori sufferers were detected. Hikikomori sufferers’ actual behavioral changes, such as social participation or utilization of support, were also observed (six out of 20 hikikomori sufferers). Preliminary effectiveness was confirmed for the 3-day program. Further revision of the program and a validation study with controls are required.

DOI： 10.1111/jpr.12368

Web of Science

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejca.2021.02.019

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neuromodulation  

Objectives: We sought to evaluate whether the cutaneous silent period (CSP) could be an electrophysiological indicator reflective of the effects of therapy for Parkinson's disease (PD), including anti-PD medications or deep brain stimulation (DBS). Material and Methods: We recorded the CSP in 43 patients with PD prior to and following the administration of medication during a pre-DBS evaluation (30 cases) and the “on” and “off” states of subthalamic nucleus DBS (13 cases). The CSP was elicited from the abductor pollicis brevis muscle by an electrical stimulation of the index finger that was 2, 4, and 15 times stronger than the sensory threshold (ST). We measured changes in latencies, including the onset, duration, and end of CSP, and waveform scores from 0 to 3. The correlation between the CSP score and unified PD rating score part III (UPDRS-III) also was assessed. Results: The onset latency and duration of CSP were significantly different between high- (15ST) and low-strength stimulations (2ST and 4ST). However, there were no significant latency changes (onset, duration, end of CSP) before and after receiving medication, or during the on and off state of the DBS. Anti-PD medications substantially increased the CSP waveform score only in the 4ST state. However, the waveform score significantly increased in all stimuli states during the DBS-on state. Both medication and the DBS-on state decreased the UPDRS-III. Nevertheless, there was no statistically significant correlation between the UPDRS-III and CSP waveform scores. Conclusion: Different onset latencies and the duration of CSP between low- and high-strength stimuli support the hypotheses proposing two different reflex pathways. Despite being independent from the UPDRS-III, the CSP may be an electrophysiological indicator reflective of the changes in inhibitory activity to the spinal α-motoneuron in response to anti-PD medications and DBS.

DOI： 10.1111/ner.13454

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21873/anticanres.14907

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/blood-2020-134483

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12185-020-02941-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-020-00763-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cllc.2020.03.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/hyp.76.suppl_1.P199

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejca.2020.04.014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.lungcan.2019.01.008

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10549-019-05256-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.clcc.2018.07.004

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00417-018-4122-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.13820

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-21260-w

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-018-25890-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Chemoradiation regimens of greater efficacy are needed for patients with locally advanced non–small cell lung cancer (NSCLC). Patients and methods: In a phase I study, escalating doses of weekly nab-paclitaxel (40 or 50 mg/m
²
) were administered along with weekly carboplatin at an area under the curve (AUC) of 2 mg mL
^–1
min and concurrent radiotherapy with 60 Gy in 30 fractions to patients with locally advanced NSCLC. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. In a phase II study, nab-paclitaxel was administered at the recommended dose (RD) together with carboplatin and radiation. Results: In the phase I study, one of six patients experienced dose-limiting toxicity (leukopenia of grade 3 requiring a second consecutive skip in the administration of weekly chemotherapy) with nab-paclitaxel at 50 mg/m
²
, which was therefore determined to be the RD. Fifty-six patients treated at the RD were evaluable for safety and efficacy. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60.7%) and neutropenia (28.6%). No treatment-related deaths occurred during the study period. The objective response rate was 76.8% (95% confidence interval [CI], 64.2–85.9%), median progression-free survival was 11.8 months (60% CI, 10.6–16.2 months; 95% CI, 8.2–20.8 months), and median overall survival was not reached. Conclusion: Our results reveal encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel at 50 mg/m
²
and carboplatin at an AUC of 2 in patients with locally advanced NSCLC.

DOI： 10.1016/j.lungcan.2018.09.014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background A global multicenter study demonstrated superiority of carboplatin + nab-paclitaxel (PTX) therapy compared to carboplatin + PTX in terms of response rate (RR) and non-inferiority in terms of progression free survival (PFS) and overall survival (OS) in untreated patients with stage IIIB/IV non-small cell lung cancer; no clinical findings have so far been reported on maintenance therapies with nab-PTX. The aim of this study was to determine the efficacy and safety of maintenance therapy with nab-PTX following carboplatin + nab-PTX combination therapy. Methods Carboplatin (AUC 6) was administered on Day 1; and nab-PTX 100 mg/m² on Days 1, 8, and 15, and dosing was repeated in 4 courses of 4 weeks each. In patients with clinical response was observed at the end of the 4th course, nab-PTX maintenance therapy was repeated. Results Out of 39 patients included in the efficacy analysis, 19 (48.7%) patients completed the induction therapy and 15 (38.5%) were transitioned to maintenance therapy. The median PFS in the maintenance phase was 6.5 (90%CI 1.4–11.4) months. The median OS in 15 patients was 12.6 (95%CI: 7.4-not reached). Grade ≥ 3 toxicities observed in more than 5% of patients were neutropenia (55.0%), anemia (15.0%), and febrile neutropenia (5.0%), with no increase during the maintenance phase. Conclusions Although statistically significance was not demonstrated presumably due to a limited transition rate from induction to maintenance phase, nab-PTX was suggested to be a useful treatment option following the induction therapy with nab-PTX in patients with advanced NSCLC.

DOI： 10.1007/s10637-018-0617-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.legalmed.2017.12.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naïve MDD, which are particularly important for early intervention in depression. Methods: As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naïve MDD patients, based on metabolome/lipidome analysis. Results: Plasma tryptophan and kynurenine levels were significantly lower in MDD group (N = 15) compared to healthy controls (HC) group (N = 19), and plasma tryptophan was the significant biomarker to identify MDD group (area under the curve = 0.740). Lower serum high density lipoprotein-cholesterol (HDL-C) was the predictive biomarker for severity of depression in MDD group (R² = 0.444). Interestingly, depressive symptoms were variously correlated with plasma tryptophan-kynurenine and lipid related metabolites. Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs) were significantly correlated in MDD group, but not in HC group. Limitations: This study had small sample size, and we did not use the multiple test correction. Conclusions: This is the first study to suggest that not only tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood biomarkers for first-episode drug-naïve MDD patients. The present study sheds new light on early intervention in clinical practice in depression, and further clinical studies especially large-scale prospective studies are warranted.

DOI： 10.1016/j.jad.2018.01.014

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non–small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab-paclitaxel (100 mg/m
²
on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed in arm B by single-agent administration of nintedanib (150 mg twice daily). The present trial is the first randomized controlled study for the treatment of NSCLC associated with IPF. The goal of the study is to demonstrate that nintedanib combined with carboplatin plus nab-paclitaxel prolongs the interval to acute exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone.

DOI： 10.1016/j.cllc.2017.06.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.17-555

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0187878

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.13309

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/JAHA.116.005370

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pcn.12500

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00520-016-3482-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/ATVBAHA.116.308388

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/CAD.0000000000000562

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Nanoparticle albumin-bound (nab) paclitaxel is a promising new therapeutic agent for all histologic types of non–small-cell lung cancer (NSCLC). We recently performed a phase 2 study of weekly nab-paclitaxel in patients with previously treated advanced NSCLC, finding promising activity and acceptable toxicity for this regimen. We have now designed a randomized phase 3 intergroup study (J-AXEL, UMIN000017487) to examine the clinical benefit and safety of nab-paclitaxel compared to docetaxel in patients with previously treated advanced NSCLC. Patients and Methods Patients are randomized to receive either docetaxel (60 mg/m² on day 1 every 3 weeks, control arm) or nab-paclitaxel (100 mg/m² on days 1, 8, and 15 every 3 weeks, experimental arm), with each drug being administered until disease progression or unacceptable toxicity. The study will evaluate the noninferiority of nab-paclitaxel relative to docetaxel for the primary end point of overall survival. Conclusion If the primary objective is achieved, this study will provide evidence for a new alternative treatment option for patients with previously treated advanced NSCLC.

DOI： 10.1016/j.cllc.2016.08.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18632/oncotarget.14698

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/annonc/mdw531

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/2168479017739267

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0167016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/1759-7714.12360

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00381-016-3041-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.clim.2016.03.015

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jiac.2016.01.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cllc.2015.08.004

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2016/1745108

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10067-015-3049-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00330-014-3496-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.14814/phy2.12387

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18632/oncotarget.4058

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jmri.24454

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0110527

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10147-013-0516-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1126/scitranslmed.3009430

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5551/jat.19109

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.exphem.2013.11.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00262-014-1554-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.humpath.2014.05.012

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.13-216

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/JAHA.113.000174

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fnhum.2013.00403

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt056

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-12-1149

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejca.2012.11.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.54.33

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5551/jat.13862

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00280-012-2023-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1182/blood-2012-02-408864

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3171/2012.8.JNS112073

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-11-1406

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejrad.2011.02.056

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/07481187.2011.553323

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-11-0887

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13340-011-0032-0

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10557-011-6309-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10557-011-6315-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-5448.2010.00708.x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1365-2265.2011.03980.x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.humpath.2010.08.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ibd.21365

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/HYPERTENSIONAHA.110.157032

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/PAS.0b013e318205df36

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study was designed to analyze the subcellular localization of E-cadherin and β-catenin both of which play a critical role in cell-cell adhesion in uterine carcinosarcoma (UCS). We performed an immunohistochemical reaction analysis of the subcellular localization of E-cadherin and β-catenin proteins in 46 cases of UCSs consisting of 28 UCSs with heterologous sarcoma and 18 UCSs with homologous sarcoma and compared their clinicopathological features. In most UCSs, membranous expression of E-cadherin and β-catenin was completely lost in sarcomatous components, but it was preserved in carcinomatous components. Nuclear β-catenin expression was observed significantly more frequently in sarcomatous components (31/46, 67.4%) than in carcinomatous components (22/46, 47.8%; P=0.0025). In sarcomatous components, nuclear β-catenin expression was found significantly more frequently in heterologous sarcoma (23/28, 82.1%) than in homologous sarcoma (8/18, 44.4%; P=0.0279). The stage was the only independent prognostic significant factor. These results suggest that reduced membranous expression of E-cadherin and β-catenin may contribute to the biphasic morphology of UCS. Furthermore, although the precise mechanism is unclear, nuclear β-catenin expression in sarcomatous components may also be associated with biphasic morphology and heterologous sarcomatous differentiation.

DOI： 10.1007/s00428-010-1002-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jts.20589

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00428-010-0959-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1365-2141.2010.08249.x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5551/jat.2899

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/hr.2009.96

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000195719

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/BRS.0b013e31818f924d

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jts.20337

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11604-007-0189-4

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.M608383200

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/gut.2006.109157

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1227/01.NEU.0000255341.03157.00

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/01.sla.0000219017.78611.49

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.genhosppsych.2006.02.007

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1086/504444

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jamcollsurg.2005.10.019

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00776-005-0887-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00127-004-0727-7

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Mental Influence of Sexual Trauma on Victims: From the Results of An Investigation of Female College Students in Japan

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

会議種別：口頭発表（一般）  

国名：日本国  

DAWN JAPN study 2005 (4) Relationship between stage changes and initiation of insulin treatment for patients with Type 2 Diabetes

会議種別：口頭発表（一般）  

国名：日本国  

DAWN JAPAN study 2005 (2) Is Insulin therapy introduced to patients with Type 2 diabetes in a timely manner?

会議種別：口頭発表（一般）  

国名：日本国  

DAWN JAPAN Study 2005 (1) REALITY OF TREATMENT OF PATIENTS WITH TYPE 2 DIABETES IN JAPAN

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語