1.Oxidative Stress Markers and the Risk of Incident Stroke and Ischemic Heart Disease: A Case-Cohort Study
Shuai GUO ; Hitomi KIMURA ; Kazumasa YAMAGISHI ; Tomomi KIHARA ; Isao MURAKI ; Yoshihiro KOKUBO ; Isao SAITO ; Hiroshi YATSUYA ; Hiroyasu ISO ; Taiki YAMAJI ; Manami INOUE ; Shoichiro TSUGANE ; Norie SAWADA ; Motoki IWASAKI ;
Journal of Stroke 2026;28(2):273-282
Background:
and Purpose To investigate the association between derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP) and the risk of stroke by subtype, and ischemic heart disease (IHD).
Methods:
We employed a case cohort design consisting of cardiovascular disease cases (n=1,521; stroke, n=1,271; IHD, n=265) and a random sub-cohort (n=4,761) in a large Japanese population-based study. d-ROMs and BAP were measured in plasma samples collected between 1995 and 1999. Hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods according to d-ROMs and BAP quartiles, adjusted for age, sex, area, and potential confounding factors.
Results:
Analysis revealed a positive association between d-ROMs and the risk of total stroke, ischemic stroke, IHD, and the composite outcome of ischemic stroke and IHD. The multivariable HRs and 95% confidence intervals (CIs) for the highest versus lowest quartiles for d-ROMs were 1.34 (95% CI: 1.11–1.63) for total stroke (P for trend<0.001), 1.47 (1.16–1.86) for ischemic stroke (P for trend<0.001), 1.47 (1.02–2.11) for IHD (P for trend=0.072), 1.47 (0.87–2.49) for subarachnoid hemorrhage (P for trend=0.101), and 1.01 (0.72–1.41) for intraparenchymal hemorrhage (P for trend=0.618). In contrast, no significant association was detected between BAP levels and the risk of cardiovascular disease.
Conclusions
Analysis revealed that d-ROMs levels were positively associated with the risk of ischemic stroke and heart disease but not with hemorrhagic stroke.
2.Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer
Mika OKAZAWA-SAKAI ; Shunsuke A. SAKAI ; Ichinosuke HYODO ; Satoshi HORASAWA ; Kentaro SAWADA ; Takao FUJISAWA ; Yasuko YAMAMOTO ; Shogen BOKU ; Yoh HAYASAKI ; Masanori ISOBE ; Daisuke SHINTANI ; Kosei HASEGAWA ; Tomomi EGAWA-TAKATA ; Kimihiko ITO ; Kei IHIRA ; Hidemichi WATARI ; Kazuhiro TAKEHARA ; Hiroshi YAGI ; Kiyoko KATO ; Tatsuyuki CHIYODA ; Kenichi HARANO ; Yoshiaki NAKAMURA ; Riu YAMASHITA ; Takayuki YOSHINO ; Daisuke AOKI
Journal of Gynecologic Oncology 2025;36(3):e38-
Objective:
To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer.
Methods:
This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing.
Results:
Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016).
Conclusion
High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.
3.Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro IWAKI ; Hideki FUJII ; Hideki HAYASHI ; Hidenori TOYODA ; Satoshi OEDA ; Hideyuki HYOGO ; Miwa KAWANAKA ; Asahiro MORISHITA ; Kensuke MUNEKAGE ; Kazuhito KAWATA ; Tsubasa TSUTSUMI ; Koji SAWADA ; Tatsuji MAESHIRO ; Hiroshi TOBITA ; Yuichi YOSHIDA ; Masafumi NAITO ; Asuka ARAKI ; Shingo ARAKAKI ; Takumi KAWAGUCHI ; Hidenao NORITAKE ; Masafumi ONO ; Tsutomu MASAKI ; Satoshi YASUDA ; Eiichi TOMITA ; Masato YONEDA ; Akihiro TOKUSHIGE ; Yoshihiro KAMADA ; Hirokazu TAKAHASHI ; Shinichiro UEDA ; Shinichi AISHIMA ; Yoshio SUMIDA ; Atsushi NAKAJIMA ; Takeshi OKANOUE ;
Clinical and Molecular Hepatology 2024;30(2):225-234
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods:
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results:
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.
4.Effects of a Mouthwash Containing Plant Extracts on Gingivitis and Halitosis
Koji HATTORI ; Akiko WATANABE ; Hiroshi TAKAGI ; Naokazu HOTTA ; Youichi YASHIRO ; Ryoma GOTO ; Noritaka SAWADA ; Genta YAMAMOTO ; Akio MITANI ; Seiji HASEGAWA
Japanese Journal of Complementary and Alternative Medicine 2023;20(1):1-8
Mouthwash is used to support brushing because it is distributed throughout the oral cavity. In this study, we examined the efficacy of a mixture of three hot water extracts (from Hordeum vulgare L, Apocynum venetum L, and Brasenia schreberi J. F. Gmel) for the purpose of developing an effective mouthwash. The mixture suppressed enhanced tumor necrosis factor α and matrix metalloproteinase 3 gene expression by Porphyromonas gingivalis lipopolysaccharide stimulation in human gingival fibroblasts. Furthermore, human studies using a mouthwash containing the plant extracts (MW) improved gingival index and bleeding on probing in the gum, and reduced the concentration of methyl mercaptan, which causes bad breath, in the mouth. These findings suggest that continued use of MW has positive effects on gingival inflammation and halitosis, and is useful for maintaining oral health.
5.Efficacy and Safety of Bolus 5-Fluorouracil and L-Leucovorin as Salvage Chemotherapy for Oral Fluoropyrimidine-Resistant Unresectable or Recurrent Gastric Cancer: A Single Center Experience.
Tetsuhito MURANAKA ; Satoshi YUKI ; Yoshito KOMATSU ; Kentaro SAWADA ; Kazuaki HARADA ; Yasuyuki KAWAMOTO ; Hiroshi NAKATSUMI ; Naoya SAKAMOTO
Journal of Gastric Cancer 2016;16(3):177-181
PURPOSE: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. MATERIALS AND METHODS: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital. The bolus 5-FU and l-leucovorin regimen consisted of intravenous l-leucovorin (250 mg/m²/2 h) and bolus 5-FU (600 mg/m²) administered once weekly followed by a 2-week rest period; each cycle was repeated every 8 weeks. RESULTS: A total of 14 patients were identified. The disease control rate was 35.7%. The median progression-free survival was 1.6 months (95% confidence interval [CI], 1.3~2.0 months), and the median overall survival was 6.3 months (95% CI, 4.7~7.9 months). No patient died from treatment-related causes. The most common severe adverse event associated with bolus 5-FU and l-leucovorin was neutropenia, which occurred in 21.4% of patients. CONCLUSIONS: Bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. We are planning a multi-center prospective phase II trial to evaluate the efficacy and safety of bolus 5-FU and l-leucovorin treatment for pre-treated unresectable or recurrent GC to confirm the results of this limited, retrospective study.
Disease-Free Survival
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Drug Therapy*
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Fluorouracil*
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Humans
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Leucovorin
;
Medical Records
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Neutropenia
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Prospective Studies
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Retrospective Studies
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Stomach Neoplasms*
6.Successful Repair of a Traumatic Aortic Isthmus Pseudoaneurysm Concomitant with Right Diaphragmatic Hernia
Taisuke Nakayama ; Masashi Kano ; Shingo Isshiki ; Takashi Tominaga ; Hiroshi Ishitoya ; Katsuhiko Hiratani ; Takahiro Sawada ; Hirotsugu Kurobe ; Tetsuya Kitagawa ; Takaki Hori
Japanese Journal of Cardiovascular Surgery 2011;40(3):94-97
A 24-year-old woman underwent successful repair of a traumatic pseudoaneurysm of the aortic isthmus concomitant with right diaphragmatic hernia which developed after a traffic accident, and the steering wheel of the crashed car was considered responsible for both lesions. Due to the right diaphragmatic hernia, she could breathe mainly with the left lung only. The aortic isthmus aneurysm was considered to be a pseudoaneurysm, and because of the potential risk of rupture, we performed urgent aortic surgery. Prior to a left thoracotomy, we anastomosed an 8-mm prosthetic graft to the right axillary artery. When the left lung was collapsed in order to perform a femoro-femoral bypass, the SpO2 level of her right index finger and her cerebral rSO2 markedly decreased. Therefore, we administered additional perfusion via the right axillary artery, which provided sufficient oxygen to the upper body and brain. The patient underwent Marlex mesh reinforcement of the right diaphragmatic hernia 30 days after grafting, and is doing well 1 year postoperatively.
7.Results of Abdominal Examinations by Sonography at Hokkaido Koseiren-Affiliated Facilities over the Past 10 Years
Akikazu NAGANUMA ; Yasufumi TODA ; Norio KONDO ; Kazuhisa MATSUMOTO ; Hidenori SAWADA ; Shunsuke NAKAYA ; Shunichi NAKAMURA ; Takahiro YAMAGISHI ; Hiroshi AZUMA ; Kazurou KUBOTA ; Masakazu KURITA ; Akimichi IMAMURA
Journal of the Japanese Association of Rural Medicine 2010;59(2):92-96
The Association of Radiologists under the umbrella of the Hokkaido Prefectural Federation of Agricultural Cooperatives for Health and Welfare (Hokkaido Koseiren) set up in 2003 a committee with the aim of improving the accuracy of mass health examinations. Recently, the committee reviewed the results of abdominal examinations by sonography performed at the eight hospitals affiliated with the Koseiren during fiscal 2006 that ended March 31, 2007. Of those individuals who underwent thorough health checkups, 91.3% had their abdomen examined by ultrasound. Something anomalous was detected in 68.1% of the examinees and 4.5% needed to undergo closer checkups, the rate of response to which was 74.5%. The detection ratio of cancer by ultrasonography was worked out at 0.048%. The ratio of patients requiring a closer exam to the total and the cancer detection ratio varied widely from hospital to hospital. The wide dispersion was ascribable to the difference in the standard of judgment for indicating closer examinations and the difference in the number of examinees so far as the cancer detection ratio was concerned, from hospital to hospital. A look at the primary findings of anomalies revealed that fatty liver topped the list accounting for 27.4% followed by cholelithiasis with 3.6%. From this, we realized that the abdominal examinations by sonography served to detect cancer and lifestyle-induced health problems as well. Organ-wise, the cancer cases found during the period from 1998 to 2009 broke down as follows: kidney (79 cases), liver (40 cases), pancreas (30 cases), gall bladder (24 cases), others (8 cases) and spleen (none). The cancer detection ratio per year ranged from 0.03 to 0.05% during the period.
8.Study on Effective and Safe Cancer Chemotherapy for Outpatients (Part1): Influence of Establishment of the Outpatient Cancer Chemotherapy Unit on Effective Usage of Hospital Beds
Eiji YONEYAMA ; Satoru MASE ; Hiroshi YOSHIDA ; Yuji OHIRA ; Hironobu NIINOMI ; Kazuhisa TSUZUKI ; Mizuho MURAKOSHI ; Kazuyuki NAKAMURA ; Makiko ARAI ; Kazuhisa SAWADA ; Akio KATSUMI
Journal of the Japanese Association of Rural Medicine 2008;57(1):1-7
Although the Outpatient Cancer Chemotherapy (OCC) Unit was established with in Anjo-Kosei Hospital in 2006, its real worth remains to be elucidated. To address this, the following subjects were examined;effective usage of hospital beds changes in the number of outpatients given to chemotherapy, length of hospitalization, the number of patients transferred by ambulance to the hospital, hospital occupancy rate, and the number of frequently used chemotherapy regimens.Since the establishment of the OCC Unit, the number of patients transferred by ambulance has increased and length of hospitalization has gradually decreased, accompanied by the increase in the number of outpatients treated at the OCC Unit. Additionally, no significant change was observed in the hospital occupancy rate. Furthermore, of the frequently used chemotherapy regimens, nine regimens were available for 62.4% of the total number of outpatients of the OCC Unit.These results indicated the useful effect of the establishment of the OCC Unit on the usage of hospital beds, and provided significant information helpful in promoting the effective and safe chemotherapy for outpatients in the OCC Unit.
Chemotherapy-Oncologic Procedure
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Unit
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seconds
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Outpatients
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Malignant Neoplasms
9.Separate Perfusion of the Upper and Lower Body under Different Temperatures during Thoracoabdominal Aortic Aneurysm Repair in a Patient with Low Left Ventricular Function
Kiyohito Yamamoto ; Hisato Itou ; Yasuhiro Sawada ; Takane Hiraiwa ; Hiroshi Hata
Japanese Journal of Cardiovascular Surgery 2006;35(4):217-221
A 79-year-old man was admitted for thoracoabdominal aortic aneurysm repair. He had already twice undergone coronary artery bypass grafting, 19 and 2 years previously. The value of the ejection fraction of the left ventricle was 36%, measured by ventriculography; and transthoracic echocardiography revealed moderate aortic valve regurgitation. In the presence of aortic valve regurgitation or coronary artery disease, myocardial perfusion under hypothermic fibrillatory arrest may be significantly impaired. Therefore, to maintain a beating heart we used separate perfusions of the upper and lower body that enabled individual temperature control of each organ. The femoral and axillary arteries were cannulated, and a long cannula was inserted into the right common femoral vein and positioned in the right atrium. Cardiopulmonary bypass was established, and the upper body was mildly cooled until the pharyngeal temperature was 33°C, while the lower body was cooled until the bladder temperature reached 20°C. Mild hypothermia of the upper body maintained the beating heart, and deep hypothermia in the lower body provided adequate protection to the spinal cord. Furthermore, in a case of aortic valve regurgitation and low left ventricular function, left ventricular venting is essential for the heart. However, it was difficult to insert the venting tube through the apex of the left ventricle or through the left inferior pulmonary vein; therefore, we selected the left main pulmonary artery for left ventricular venting, and maintained a non-working beating heart. After cardiopulmonary bypass was discontinued, cardiac function was good although a bleeding tendency became apparent. Postoperatively, the maximum dose of dopamine we needed was only 3γ. There were no remarkable complications and the patient was discharged on postoperative day 30. This experience suggests that pulmonary artery venting and separate perfusion of the upper and lower body to individually control organ temperatures is a useful procedure for thoracoabdominal aortic aneurysm repair in patients with low left ventricular function.
10.Multi-Center Randomized Controlled Trial of Acupuncture and Moxibustion for Rheumatoid Arthritis
Daichi KASUYA ; Tetsuji SAWADA ; Hideyuki ISOBE ; Seigou AKAO ; Makoto KIKKAWA ; Kumiko TAKATA ; Satoru YAMAGUCHI ; Hiroshi OMATA ; Kazuhiko YAMAMOTO
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2005;68(4):193-202
We evaluated the efficacy, usefulness and safety of acupuncture and moxibustion treatment in rheumatoid arthritis, by the randomized, parallel-group, multi-center study with the drug-treated outpatient group as the control. The endpoints, important in the clinical assessment of acupuncture treatment, included the improvement criteria in ACR core set variables and the Japanese version of the Arthritis Impact Measurement Scales Version 2 (AIMS-2), a system of evaluation of the QOL of patients with RA.
Regarding intervention (therapy), a therapy chart for each stage of disease was drawn up to give local and systemic treatment in consideration of the patient's activity and disability in each stage of rheumatoid arthritis, so that generally consistent therapy adapted to the patient's condition would be provided. Result 1. Patients eligible for analysis were 80 patients of A-group (drug therapy group) (80 females, 2 males, 2dropped) and 90 patients of B-group (drug plus acupuncture and moxibustion group), total 170 patients. 2. Patients who satisfied the improvement criteria in ACR core set variables (improved patients) were 8 of 80 patients in A-group and 20 of 90 patients in B-group. The improvement rate was significantly higher for B-group treated by drug plus acupuncture and moxibustion versus A-group, with P=0.04 in 2×2 table chi square test. 3. In QOL change investigated by AIMS-2 questionnaire, the improvement occurred significantly more frequently in the drug plus acupuncture and moxibustion group, with difference between groups at 12 months after the initiation of clinical study at P=0.001. 4. Changes in the subjects included in AIMS-2 questionnaire: Improvement was significantly more frequent in the drug plus acupuncture and moxibustion group versus drug therapy group in respect to the ability to walk, finger function, housework, sociableness, pain, mood, and the degree of subjective improvement. In the present randomized, parallel-group, multicenter study, a significant improvement was detected in the drug plus acupuncture and moxibustion group versus the drug therapy group in the aforesaid respect, which suggested that the use of acupuncture and moxibustion combined with the conventional therapy would prevent deterioration of physical functions, improve blood circulation, stabilize mental status, and thereby contribute to the improvement of QOL in patients with rheumatoid arthritis.


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