1.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.
2.Development of a Training Program on the Proper Use of Over-the-Counter Drugs for Pharmacy Pharmacists
Chie HIRAOKA ; Keiko (Sasaki) AKAGAWA ; Yoshiaki FUJITA ; Yuki ODANAKA ; Atsuhiko SANO ; Mika NAGANUMA ; Tetsuya OGINO ; Hajime KATO ; Akihiro NAKAMURA
Japanese Journal of Social Pharmacy 2022;41(2):155-166
The importance of promoting self-medication is increasing, and the active participation of pharmacies is required to support this. We developed a training program based on the Attention, Relevance, Confidence, and Satisfaction (ARCS) model, which is a motivational design process to train pharmacists who support the proper use of OTC drugs, and for insurance pharmacists who usually perform dispensing work. In the six months of training, we conducted six sessions for insurance pharmacists on the subject of colds and constipation. In addition to conducting lectures and exercises on OTC drugs, we provided pharmacists with an opportunity to practice the training content during their daily work, and discuss solutions to the problems that they encountered. Of the eight participants who attended all workshops and were part of the final evaluation, seven provided OTC drugs after considering whether it was necessary to provide them. A total of six advised patients who came to the pharmacy to have their prescription medications dispensed that there were OTC medications that they should be careful about taking. These results suggest the usefulness of this training program based on the ARCS motivational design model.
3.Differences in the effects of BMI on bone microstructure between loaded and unloaded bones assessed by HR-pQCT in Japanese postmenopausal women
Norifumi FUJII ; Manabu TSUKAMOTO ; Nobukazu OKIMOTO ; Miyuki MORI ; Yoshiaki IKEJIRI ; Toru YOSHIOKA ; Makoto KAWASAKI ; Nobuhiro KITO ; Junya OZAWA ; Ryoichi NAKAMURA ; Shogo TAKANO ; Saeko FUJIWARA
Osteoporosis and Sarcopenia 2021;7(2):54-62
Objectives:
The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women.
Methods:
Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters.
Results:
Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure.
Conclusions
Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.
4.Differences in the effects of BMI on bone microstructure between loaded and unloaded bones assessed by HR-pQCT in Japanese postmenopausal women
Norifumi FUJII ; Manabu TSUKAMOTO ; Nobukazu OKIMOTO ; Miyuki MORI ; Yoshiaki IKEJIRI ; Toru YOSHIOKA ; Makoto KAWASAKI ; Nobuhiro KITO ; Junya OZAWA ; Ryoichi NAKAMURA ; Shogo TAKANO ; Saeko FUJIWARA
Osteoporosis and Sarcopenia 2021;7(2):54-62
Objectives:
The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women.
Methods:
Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters.
Results:
Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure.
Conclusions
Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.
5.Chronic obstructive pulmonary disease severity in middle-aged and older men with steoporosis associates with decreased bone formation
Manabu TSUKAMOTO ; Toshiharu MORI ; Eiichiro NAKAMURA ; Yasuaki OKADA ; Hokuto FUKUDA ; Yoshiaki YAMANAKA ; Ken SABANAI ; Ke-Yong WANG ; Takeshi HANAGIRI ; Satoshi KUBOI ; Kazuhiro YATERA ; Akinori SAKAI
Osteoporosis and Sarcopenia 2020;6(4):179-187
Objectives:
Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.
Methods:
We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers.
Results:
All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors.
Conclusions
The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.
6.Chronic obstructive pulmonary disease severity in middle-aged and older men with steoporosis associates with decreased bone formation
Manabu TSUKAMOTO ; Toshiharu MORI ; Eiichiro NAKAMURA ; Yasuaki OKADA ; Hokuto FUKUDA ; Yoshiaki YAMANAKA ; Ken SABANAI ; Ke-Yong WANG ; Takeshi HANAGIRI ; Satoshi KUBOI ; Kazuhiro YATERA ; Akinori SAKAI
Osteoporosis and Sarcopenia 2020;6(4):179-187
Objectives:
Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.
Methods:
We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers.
Results:
All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors.
Conclusions
The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.
7.Hooks at the Upper Instrumented Vertebra Can Adjust Postoperative Shoulder Balance in Patients with Adolescent Idiopathic Scoliosis: 5 Years or More of Follow-up
Shingo KUROYA ; Tsutomu AKAZAWA ; Toshiaki KOTANI ; Tsuyoshi SAKUMA ; Shohei MINAMI ; Yoshiaki TORII ; Tasuku UMEHARA ; Masahiro IINUMA ; Kenichi MURAKAMI ; Sumihisa ORITA ; Kazuhide INAGE ; Yawara EGUCHI ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Junichi NAKAMURA ; Gen INOUE ; Masayuki MIYAGI ; Wataru SAITO ; Seiji OHTORI ; Hisateru NIKI
Asian Spine Journal 2019;13(5):793-800
STUDY DESIGN: A retrospective cohort study. PURPOSE: This study aims to investigate postoperative shoulder imbalance (PSI) ≥5 years postoperatively in patients who underwent posterior spinal fusion using hooks at the upper instrumented vertebra (UIV) for Lenke type 1 adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: Studies have reported PSI due to excessive correction of the main thoracic curve. METHODS: We examined 56 patients with AIS who underwent a posterior spinal fusion with hooks at the UIV from 2004 to 2010. Of these, we enrolled 14 patients who underwent surgery, at least, 5 years ago. X-rays and Scoliosis Research Society-22 (SRS-22) questionnaire were administered. To evaluate the shoulder balance, T1 vertebral tilt angle (T1 tilt), clavicle angle, and radiographic shoulder height (RSH) were measured. PSI was considered as the absolute value of the postoperative RSH being ≥20 mm. Based on radiographs obtained immediately postoperatively, we divided patients into two groups as follows: the balanced group (absolute value of RSH <20 mm) and imbalanced group (absolute value of RSH ≥20 mm). RESULTS: The frequency of PSI was 28.6% immediately postoperatively, 0% 2 years postoperatively, and 7.1% at the last follow-up. In the balanced group, PSI did not occur even at 2 years postoperatively or at the last follow-up. In the imbalanced group, PSI was improved in all patients 2 years postoperatively and all patients, except one patient, at the last follow-up. No significant differences were noted in the frequency of distal adding-on at 2 years postoperatively or the last follow-up between the balanced group and the imbalanced group. We observed moderate negative correlations between the absolute value of T1 tilt and the SRS-22 pain and satisfaction at the last follow-up. CONCLUSIONS: Hooks at the UIV could adjust the shoulder balance to avoid long-term PSI in patients with AIS.
8.Feasibility of Newly Developed Endoscopic Ultrasound with Zone Sonography Technology for Diagnosis of Pancreatic Diseases.
Yoshiki HIROOKA ; Akihiro ITOH ; Hiroki KAWASHIMA ; Eizaburo OHNO ; Yuya ITOH ; Yosuke NAKAMURA ; Takeshi HIRAMATSU ; Hiroyuki SUGIMOTO ; Hajime SUMI ; Daijiro HAYASHI ; Naoki OHMIYA ; Ryoji MIYAHARA ; Masanao NAKAMURA ; Kohei FUNASAKA ; Masatoshi ISHIGAMI ; Yoshiaki KATANO ; Hidemi GOTO
Gut and Liver 2013;7(4):486-491
BACKGROUND/AIMS: To confirm the feasibility of using newly developed endoscopic ultrasound (EUS) with Zone sonography(TM) technology (ZST; Fujifilm Corp.). METHODS: Seventy-five patients with pancreatic disorders were enrolled: 45 with intraductal papillary mucinous neoplasm; 15 with ductal carcinoma; five with neuroendocrine tumors; three with serous cystic neoplasms; and seven with simple cysts. The endoscopes used were EG-530UR2 and EG-530UT2 (Fujifilm Corp.). Two items were evaluated: visualization depth among four frequencies and image quality after automatic adjustment of sound speed (AASS), assessed using a 5-scale Likert scale by two endosonographers blinded to disease status. Because sound speed could be manually controlled, besides AASS, image quality at sound speeds of 1,440 and 1,600 m/sec were also assessed. RESULTS: In all cases, sufficient images were obtained in the range of 3 cm from the EUS probe. Judgments of image quality before AASS were 3.49+/-0.50, 3.65+/-0.48, respectively. After AASS, A and B scored 4.36+/-0.48 and 4.40+/-0.49 (p<0.0001). There were significant differences in the data before and after AASS and plus 60 m/sec, but no significant difference between the datasets were seen after AASS and at sound speeds manually set for minus 100 m/sec. CONCLUSIONS: EUS with ZST was shown to be feasible in this preliminary experiment. Further evaluation of this novel technology is necessary and awaited.
Endoscopes
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Endosonography
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Humans
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Judgment
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Mucins
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Pancreatic Diseases
9.Relationship between the Noto-Peninsula earthquake and maternal postnatal depression and child-rearing.
Yuri HIBINO ; Jiro TAKAKI ; Yasuhiro KAMBAYASHI ; Yoshiaki HITOMI ; Akemi SAKAI ; Naomi SEKIZUKA ; Keiki OGINO ; Hiroyuki NAKAMURA
Environmental Health and Preventive Medicine 2009;14(5):255-260
OBJECTIVEThe aim of our study was to explore the relationship between a medium-scale earthquake and maternal depression and child-rearing in a depopulated community in the Noto Peninsula of Japan.
METHODSThree months after a major earthquake, self-rating questionnaires were distributed to women who were pregnant at the time of the earthquake or who became pregnant immediately thereafter, and who were receiving care at any of four major hospitals in the most devastated area. A total of 155 women who had given birth returned the completed questionnaire for analysis. Maternal postnatal depression among the participants was assessed using the Edinburgh Postnatal Depression Scale (EPDS).
RESULTSThe EPDS score was significantly associated with decreased "satisfaction with delivery" (beta = -0.28, p = 0.01), increased artificial "lactation" (beta = 0.31, p = 0.002), and increased "trouble with infant care" (beta = 0.47, p < 0.001) in multivariate analysis. It was also significantly associated with increased "anxiety about earthquakes" (beta = 0.30, p = 0.001), and "anxiety about earthquakes" was significantly associated with increased "fear of the earthquake" (beta = 0.20, p = 0.04).
CONCLUSIONSEarthquake-related factors such as "anxiety about earthquakes" and "fear of the earthquake" did not have a direct effect on child-rearing factors; however, they did have a significant relationship with increased EPDS. Based on these results, we conclude that screening strategies for maternal depression in peri- and postnatal women under emergency circumstances are necessary.
10.Effects of the Clinical Pathway in Acute Phase Rehabilitation on Walking Ability Recovery in Elderly Stroke Patients
Kensei NAKAMURA ; Yoshiaki KIM
The Japanese Journal of Rehabilitation Medicine 2008;45(11):750-756
To determine whether the clinical pathway in acute phase rehabilitation contributes to the early recovery of walking ability in elderly stroke patients, we developed a pathway for acute stroke patients over 65 years old who had lower extremity paresis. The pathway goal was to have patients walking within four weeks after the start of physiotherapy. We compared the improvement in walking ability during their stay in the stroke unit, length of stay and discharge destination between the two groups, namely the pre-pathway group that comprised 41 patients admitted before the introduction of the pathway and the post-pathway group that comprised 54 patients admitted after its introduction. In the post-pathway group, 68.5% of the patients achieved the goal, and the days required to achieve the goal were 9.6±6.0 days after the start of physiotherapy. The proportion of patients whose walking ability improved was significantly higher in the post-pathway group than the pre-pathway group (66.7% versus 39.0%, p=0.007). The efficiency of improvement was also higher in the post-pathway group (p=0.024). Logistic regression analysis showed that the use of the pathway was a factor that independently contributed to the improvement of walking ability (odds ratio, 2.80 ; 95% CI, 1.04 to 7.56 ; p=0.042). No significant differences were noted between the two groups in length of stay or discharge destination. From these results, it is suggested that the clinical pathway in acute phase rehabilitation promotes the recovery of walking ability in elderly stroke patients.


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