Faculty Profiles - MITSUHASHI Toshiharu

Papers - MITSUHASHI Toshiharu

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Assessing Vulnerability to Surges in Suicide-Related Tweets Using Japan Census Data: Case-Only Study. Reviewed International journal

Toshiharu Mitsuhashi

JMIR formative research 7 e47798 2023.8

Authorship：Lead author,　Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: As the use of social media becomes more widespread, its impact on health cannot be ignored. However, limited research has been conducted on the relationship between social media and suicide. Little is known about individuals' vulnerable to suicide, especially when social media suicide information is extremely prevalent. OBJECTIVE: This study aims to identify the characteristics underlying individuals' vulnerability to suicide brought about by an increase in suicide-related tweets, thereby contributing to public health. METHODS: A case-only design was used to investigate vulnerability to suicide using individual data of people who died by suicide and tweet data from January 1, 2011, through December 31, 2014. Mortality data were obtained from Japanese government statistics, and tweet data were provided by a commercial service. Tweet data identified the days when suicide-related tweets surged, and the date-keyed merging was performed by considering 3 and 7 lag days. For the merged data set for analysis, the logistic regression model was fitted with one of the personal characteristics of interest as a dependent variable and the dichotomous exposure variable. This analysis was performed to estimate the interaction between the surges in suicide-related tweets and personal characteristics of the suicide victims as case-only odds ratios (ORs) with 95% CIs. For the sensitivity analysis, unexpected deaths other than suicide were considered. RESULTS: During the study period, there were 159,490 suicides and 115,072 unexpected deaths, and the number of suicide-related tweets was 2,804,999. Following the 3-day lag of a highly tweeted day, there were significant interactions for those who were aged 40 years or younger (OR 1.09, 95% CI 1.03-1.15), male (OR 1.12, 95% CI 1.07-1.18), divorced (OR 1.11, 95% CI 1.03 1.19), unemployed (OR 1.12, 95% CI 1.02-1.22), and living in urban areas (OR 1.26, 95% CI 1.17 1.35). By contrast, widowed individuals had significantly lower interactions (OR 0.83, 95% CI 0.77-0.89). Except for unemployment, significant relationships were also observed for the 7-day lag. For the sensitivity analysis, no significant interactions were observed for other unexpected deaths in the 3-day lag, and only the widowed had a significantly larger interaction than those who were married (OR 1.08, 95% CI 1.02-1.15) in the 7-day lag. CONCLUSIONS: This study revealed the interactions of personal characteristics associated with susceptibility to suicide-related tweets. In addition, a few significant relationships were observed in the sensitivity analysis, suggesting that such an interaction is specific to suicide deaths. In other words, individuals with these characteristics, such as being young, male, unemployed, and divorced, may be vulnerable to surges in suicide-related tweets. Thus, minimizing public health strain by identifying people who are vulnerable and susceptible to a surge in suicide-related information on the internet is necessary.

DOI： 10.2196/47798

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Effects of indium exposure on respiratory symptoms: a retrospective cohort study in Japanese workers using health checkup data. Reviewed International journal

Toshiharu Mitsuhashi

PeerJ 8 e8413 2020

Authorship：Lead author,　Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Background: Indium compounds are known health hazards for lung cancer and interstitial pneumonia. Furthermore, they are related to emphysema, alveolar proteinosis, and cholesterol granuloma. In Japan, laws were revised in 2013 to tighten regulations on indium exposure in workplaces. However, its impact on the health of workers who handle indium has not been evaluated. This study aimed to investigate whether subjective respiratory symptoms in these workers have reduced after the 2013 amendment in the regulations. Methods: The subjects were workers from certain areas of Japan who had undergone health checkups between January 1, 2013, and June 30, 2015. Indium-handling and non-handling workers were categorized into the exposed and less-exposed groups, respectively. Based on the findings of health checkups during this period, the hazard ratio of subjective respiratory symptoms (cough, sputum production, shortness of breath, and palpitation) and its 95% confidence intervals (CIs) were calculated with the less-exposed group as the reference. The Prentice-Williams-Peterson model was used for calculation, and a model that adjusted for coarse analysis and potential confounding factors was adopted. Results: Overall, 2,561 workers (from 22 companies) who underwent 6,033 health checkups were included. The total person-years were 2,562.8 years, and 162 outcome events occurred. The hazard ratios of the exposed group were 1.65 (95% CI [1.14-2.39]: p = 0.008) and 1.61 (95% CI [1.04-2.50]: p = 0.032) in the crude and adjusted models, respectively. Conclusion: Indium-handling workers had a high hazard of the subjective respiratory symptoms than non-indium -handling workers despite stricter regulations on indium exposure in workplaces. This indicates the need for further changes to the legislation to protect the health of workers exposed to harmful substances in workplaces. Further studies including larger diverse cohorts are needed to validate our findings.

DOI： 10.7717/peerj.8413

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Effects of two-week e-learning on eHealth literacy: a randomized controlled trial of Japanese Internet users. Reviewed International journal

Toshiharu Mitsuhashi

PeerJ 6 e5251 2018

Authorship：Lead author,　Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Background: The Internet is widely used as a source of information by people searching for medical or healthcare information. However, information found on the Internet has several drawbacks, and the ability to consume accurate health information on the Internet (eHealth literacy) is increasingly important. This study's goal was to clarify the extent to which eHealth literacy is improved after e-learning in a randomized controlled trial. Methods: Data were collected on 301 Japanese adults through an online survey. Participants were assigned to the intervention (e-learning about eHealth literacy) group or the control group in a 1:1 ratio. The intervention group included 148 participants, and 153 participants were in the control group. The participants provided information at baseline on demographic characteristics, self-rated health, and frequency of Internet searching. The eHealth Literacy Scale (eHEALS), which was the main measure of eHealth literacy, and data on secondary outcomes (the Healthy Eating Literacy Scale and skill for evaluating retrieved search results) were obtained at baseline and at follow-up. The score difference was calculated by subtracting the score at baseline from the score at follow-up. Linear regression analysis and multinomial regression analysis were performed using the differences in score as the dependent variables and the intervention as the explanatory variable. Intention-to-treat analysis was employed. Results: The results from participants who responded to all of the questions both times were analyzed (134 in the intervention group and 148 in the control group). eHEALS increased 1.57 points due to the intervention effect (Δ score change = 1.57; 95% CI [0.09-3.05]; p = 0.037). Skills for evaluating retrieved search results improved more in the intervention group than in the control group (relative risk ratio = 2.47; 95% Confidence Interval: 1.33, 4.59; p = 0.004). There were no large differences at baseline between the intervention and control groups in the eHEALS, Healthy Eating Literacy scale, or skill for evaluating retrieved search results. However, at follow-up, the intervention group had improved more than the control group on both the eHEALS and skill for evaluating retrieved search results. Discussion: eHealth literacy improved after the e-learning, as evidenced by the change to the eHEALS scores and increased skill for evaluating retrieved search results. There was no significant effect of e-learning, which did not include content on healthy eating, on the Healthy Eating Literacy Scale scores. This indicates that scores did not increase much due to effects other than e-learning, as is sometimes seen with the Hawthorne effect. Although it was statistically significant, the effect size was small. Therefore, future research is necessary to verify the clinical implications. In sum, this study suggests that e-learning is an effective way to improve eHealth literacy.

DOI： 10.7717/peerj.5251

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Maternal working hours and early childhood overweight in Japan: a population-based study. Reviewed International journal

Toshiharu Mitsuhashi, Etsuji Suzuki, Soshi Takao, Hiroyuki Doi

Journal of occupational health 54 ( 1 ) 25 - 33 2012

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC OCCUPATIONAL HEALTH

OBJECTIVES: There has been a growing concern that maternal employment could have adverse or beneficial effects on children's health. Although recent studies demonstrated that maternal employment was associated with a higher risk of childhood overweight, the evidence remains sparse in Asian countries. We sought to examine the relationship between maternal working hours and early childhood overweight in a rural town in Okayama Prefecture. METHODS: In February 2008, questionnaires were sent to parents of all preschool children aged ≥3 yr in the town to assess maternal working status (working hours and form of employment), children's body mass index, and potential confounders. Childhood overweight was defined following the age and sex-specific criteria of the International Obesity Task Force. Odds ratios (ORs) and 95% confidence intervals (CIs) for childhood overweight were estimated in a logistic regression. We used generalized estimating equations with an exchangeable correlation matrix, considering the correlation between siblings. RESULTS: We analyzed 364 preschool children. Adjusting for each child's characteristics (age, sex), mother's characteristics (age, obesity, educational attainment, smoking status, and social participation), and family's characteristics (number of siblings), children whose mothers work <8 h/day had a substantially lower risk for being overweight (OR: 0.28, 95% CI: 0.09, 0.93) compared with children of non-working mothers, whereas the relationship was less pronounced among children whose mothers work ≥8 h/day (OR: 0.71, 95% CI: 0.19, 2.68). We observed similar patterns in a stratified analysis by the form of maternal employment. CONCLUSION: Short maternal working hours are associated with a lower odds of early childhood overweight.

DOI： 10.1539/joh.11-0100-OA

Web of Science

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[Utilization, needs, and related factors for e-learning and its application to education and training in occupational safety and health among enterprises in Japan]. Reviewed

Toshiharu Mitsuhashi, Soshi Takao, Akizumi Tsutsumi, Norito Kawakami

Sangyo eiseigaku zasshi = Journal of occupational health 48 ( 5 ) 183 - 91 2006.9

Authorship：Lead author Language：Japanese Publisher：(公社)日本産業衛生学会

In order to know utilization, needs, and related factors for e-learning and its application to education and training in occupational safety and health (OSH) among enterprises in Japan, a questionnaire survey was conducted of enterprises randomly selected from those with 1,000 or more employees and those with 999 or less (500 for each). Data from 134 (56 and 78, respectively) enterprises were analyzed (response rate, 13%). Among total enterprises, 19% had introduced and 16% planned to introduce e-learning. However, only 7% of larger enterprises and less than 3% of smaller enterprises used e-learning for education and training in OSH. On the other hand, 80-90% of enterprises responded positively to considering the use of e-learning for education and training on various OSH topics for various users. Highly rated merits of e-learning were "can use whenever", "can use anywhere"; and its highly rated obstacles were "cost", "individual PC not available", "insufficient information on efficacy". However, the merit "can monitor training" was significantly associated with the use/plan of e-learning. "Good contents not available" was more frequent among enterprises which used/planned e-learning. The study indicated a greater need for e-learning based OSH education and training, despite a currently low rate of its use. Improvement of e-learning platforms and contents, reduction of cost, and improvement of e-learning infrastructure at work may be needed to facilitate the use of e-learning in OSH.

DOI： 10.1539/sangyoeisei.48.183

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Elevated pulse pressure and risk of chronic kidney disease by hypertension status: A longitudinal study in Japanese adults

Yukari Okawa, Toshiharu Mitsuhashi

2025.3

Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis

Yuki Fujii, Kazuyuki Matsumoto, Akihiro Matsumi, Kazuya Miyamoto, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Toshiharu Mitsuhashi, Motoyuki Otsuka

Journal of Clinical Medicine 2025.3

Acetic Acid-Indigo Carmine Chromocolonoscopy for Proximal Serrated Lesions: A Randomized, Three-Arm Colonoscopy Study. International journal

Hideaki Kinugasa, Sakiko Hiraoka, Sayo Kobayashi, Minoru Matsubara, Teruya Nagahara, Reiji Higashi, Kensuke Takei, Masayasu Ohmori, Takashi Nakamura, Takao Tsuzuki, Shouichi Tanaka, Ryosuke Hirai, Junki Toyosawa, Yuki Aoyama, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Takehiro Tanaka, Toshiharu Mitsuhashi, Motoyuki Otsuka

The American journal of gastroenterology 2025.3

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Aggressive colorectal cancer (CRC) frequently originates from serrated lesions (SLs), particularly in the proximal colon, which are challenging to detect using standard screening colonoscopy. Although duplicate examinations or chromocolonoscopies are recommended for detecting proximal SLs, evidence from randomized trials is limited. We evaluated the effectiveness of tandem colonoscopy with an acetic acid-indigo carmine mixture (AIM) for detecting SLs in the proximal colon compared to white-light imaging (WLI) and indigo carmine (IC). METHODS: This three-arm, multicenter, randomized controlled trial involving nine institutions enrolled patients undergoing colonoscopy and assigned them randomly to the WLI, IC, or AIM group. The primary outcomes were the SL-detection rate (SDR) of proximal lesions during the second examination (SDR2nd) and SL additional rate (SAR). Secondary outcomes included the detection and additional rates of other polyps, factors contributing to SAR, and complications. RESULTS: Between 2021 and 2024, 1,319 participants with 1,267 polyps were included in the analysis. With AIM, the SDR2nd and SAR were significantly higher compared to WLI or IC (WLI vs. AIM: 2.7% vs. 14.0%, p<.001; IC vs. AIM: 7.9% vs. 14.0%, p=.002, and WLI vs. AIM: 22.4% vs. 69.3%, p<.001; IC vs. AIM: 45.8% vs. 69.3%, p=.001). AIM conferred a higher adenoma-detection rate (ADR)2nd than with WLI (10.5% vs. 24.7%; p<.001) and was an independent factor for SAR (odds ratio [95% confidence interval]: 7.79 [3.76-17.08]). No major adverse events were observed. CONCLUSIONS: AIM significantly improved proximal colon SDRs and outperformed WLI and IC. The relationship between SDR and CRC incidence warrants further investigation.

DOI： 10.14309/ajg.0000000000003411

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A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD. International journal

Wataru Kitamura, Keiko Fujii, Mitsuru Tsuge, Toshiharu Mitsuhashi, Hiroki Kobayashi, Chihiro Kamoi, Akira Yamamoto, Takumi Kondo, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Nobuharu Fujii, Yoshinobu Maeda

Annals of hematology 2025.2

Language：English Publishing type：Research paper (scientific journal)

Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.

DOI： 10.1007/s00277-025-06269-2

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The Asia-Pacific Body Mass Index Classification and New-Onset Chronic Kidney Disease in Non-Diabetic Japanese Adults: A Community-Based Longitudinal Study from 1998 to 2023

Yukari Okawa, Toshiharu Mitsuhashi, Toshihide Tsuda

Biomedicines 2025.2

Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children. International journal

Kensuke Uraguchi, Naomi Matsumoto, Toshiharu Mitsuhashi, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

Cureus 17 ( 1 ) e77709 2025.1

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma. METHODS: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as "longer dinner-to-bed time" (>120 minutes), "shorter dinner-to-bed time" (≤120 minutes or less), and "irregular dinner-to-bed time." Modified Poisson regression with robust variance was used to estimate risk ratios (RRs). RESULTS: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR) = 1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR = 1.13; 95% CI, 1.04-1.22). CONCLUSION: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER.

DOI： 10.7759/cureus.77709

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Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial

Masaya Abe, Keiko Fujii, Nobuharu Fujii, Toshiharu Mitsuhashi, Takuya Fukumi, Yuichi Sumii, Maiko Kimura, Tomohiro Urata, Takumi Kondo, Fumio Otsuka, Yoshinobu Maeda

Hematology, Transfusion and Cell Therapy 2024.12

Subjective global assessment for nutritional screening and its impact on surgical outcomes: A prospective study in older patients with colorectal cancer. International journal

Fuminori Teraishi, Yusuke Yoshida, Ryohei Shoji, Nobuhiko Kanaya, Yuki Matsumi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Shunsuke Kagawa, Rie Tamura, Yoshikazu Matsuoka, Hiroshi Morimatsu, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

Langenbeck's archives of surgery 409 ( 1 ) 356 - 356 2024.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Our perioperative management center provides preoperative intervention and functional and nutritional assessments for colorectal cancer patients aged over 75 years. This study evaluated the associations of preoperative nutritional status with postoperative outcomes and prognosis in colorectal cancer patients aged 75 years or older. METHODS: This was a prospective, observational study of 71 colorectal cancer patients aged 75 years or older who underwent surgery between July 2020 and September 2022. The Subjective Global Assessment (SGA) was evaluated as a nutritional index. The patients were classified into three groups: SGA-A (well nourished), B (moderately malnourished), and C (severely malnourished), and the correlations with postoperative outcomes and prognosis were examined. RESULTS: The median age of the 71 patients (34 males, 37 females) was 78 (75-92) years, and their median body mass index (BMI) was 22.3 (13.4-31.9) kg/m2. Forty-eight patients had colon cancer, and 23 had rectal cancer. On the SGA, 28 patients were SGA-A, 25 SGA-B, and 18 SGA-C. The SGA-B/C group had significantly higher BMI (p < 0.01) and more ICU admissions (p = 0.02). The G8 score was significantly lower (p = 0.03) in the SGA-B/C group, suggesting coexisting functional decline. In terms of postoperative outcomes, the SGA-B/C group had a significantly longer postoperative hospital stay (p = 0.04). The 3-year OS rates for all stages were 100% in the SGA-A group and 49.7% in the SGA-B/C group (p = 0.03), while the 3-year OS rates for patients excluding Stage IV were 100% in the SGA-A group and 68.5% in the SGA-B/C group, not significantly different (p = 0.14). The 3-year RFS rate was 95.5% in the SGA-A group and 65.3% in the SGA-B/C group (p = 0.15). CONCLUSION: The SGA is a promising nutritional index associated with short-term outcomes in older patients undergoing colorectal cancer surgery. The SGA can be assessed in a few minutes during an outpatient visit, making it useful for routine clinical use.

DOI： 10.1007/s00423-024-03548-w

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The required experience of open pancreaticoduodenectomy before becoming a specialist in hepatobiliary and pancreatic surgeons: a multicenter, cohort study of 334 open pancreaticoduodenectomies. International journal

Tomokazu Fuji, Yuzo Umeda, Kosei Takagi, Masayoshi Hioki, Ryuichi Yoshida, Yoshikatsu Endo, Kazuya Yasui, Daisuke Nobuoka, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

BMC surgery 24 ( 1 ) 366 - 366 2024.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Open pancreaticoduodenectomy (OPD) is an essential surgical procedure for expert hepato-biliary-pancreatic (HBP) surgeons. However, there is no standard for how many surgeries must be performed by a surgeon in training before they are considered to have enough experience to ensure surgical safety. METHODS: Cumulative Sum (CUSUM) analysis was performed using the surgical data of OPDs performed during the training period of board-certified expert surgeons of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. RESULTS: Fourteen HBP surgeons participated in this study and performed 334 OPDs during their training period. The median (interquartile range) values for operative time, blood loss, and length of hospital stay were 455 (397-519) minutes, 450 (234--716) ml, and 28 (21-38) days, respectively. CUSUM analysis showed inflection points at 20 surgeries performed for operative time. After 20 procedures, operative time was significantly shorter (461 min vs. 425 min, p = 0.021) and blood loss was significantly lower (470 ml vs. 340 ml, p = 0.038). No significant differences between within 20 and after 21 procedures were found in the complication rate (53% vs. 48%, p = 0.424) and rate of in-hospital deaths (1.5% vs.1.4%. p = 0.945). Up to 20 surgeries, PDAC and another malignant tumor had longer operative time than benign/low malignant diseases (486 min vs. 472 min vs. 429 min, p < 0.001), and higher blood loss (500 ml vs. 502 ml vs. 355 ml, p < 0.001). Mortality rate was higher at PDAC cases (5% vs. 0% vs. 0%, p = 0.01). After the 21 procedures, these outcomes were improved and no differences in by primary disease were observed. Multivariable analysis showed that within 20 surgeries were independent risk factors of longer operative time (HR2.6, p = 0.013) and higher blood loss (HR2.0, p = 0.049). CONCLUSIONS: To stabilize the surgical outcome of OPD for malignant disease, at least 20 surgeries should be performed at a certified institution during surgeon training. TRIAL REGISTRATION: Clinical trial number: Not applicable.

DOI： 10.1186/s12893-024-02677-9

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In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan

Naomi Matsumoto, Takashi Mitsui, Tomoka Kadowaki, Toshiharu Mitsuhashi, Tomoya Hirota, Hisashi Masuyama, Takashi Yorifuji

European Journal of Pediatrics 184 ( 1 ) 2024.11

Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53–1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10–0.96 and aRR: 0.37, 95% CI: 0.14–0.98, respectively).

Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups.

<table><tbody> <tr> <td colspan="2">What is known:• Long-term health and developmental outcomes of IVF-conceived children remain inconsistent across studies and populations, despite the widespread use of this technology.</td> </tr> <tr> <td colspan="2">What is new:• A nationwide population-based cohort study in Japan did not show adverse effects of IVF on long-term child health and development through age 9.• These findings provide reassurance about the safety of IVF, while indicating the need for careful monitoring in specific subgroups such as preterm and multiple births.</td> </tr> </tbody></table>

DOI： 10.1007/s00431-024-05883-y

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Other Link： https://link.springer.com/article/10.1007/s00431-024-05883-y/fulltext.html

Dyslipidemia and development of chronic kidney disease in non-diabetic Japanese adults: a 26-year, community-based, longitudinal study

Yukari Okawa, Toshiharu Mitsuhashi

2024.10

Publisher：Cold Spring Harbor Laboratory

Follow-up studies evaluating the relationship between dyslipidemia and chronic kidney disease (CKD) in non-diabetic populations are limited. This longitudinal study (1998–2024) examined whether the prevalence of dyslipidemia is associated with the subsequent development of CKD in non-diabetic Japanese adult citizens of Zentsuji, Kagawa Prefecture, Japan. Dyslipidemia was defined as low-density lipoprotein cholesterol concentrations ≥140 mg/dL, high-density lipoprotein cholesterol concentrations <40 mg/dL, and/or triglyceride concentrations ≥150 mg/dL. Participants were considered to have developed CKD if their estimated glomerular filtration rate was <60 mL/min/1.73 m². The proportional hazard assumptions were violated. Therefore, the Weibull accelerated failure-time model was selected using the Akaike and Bayesian information criteria. The final cohort included 5970 participants, 41.6% of whom were men. The mean follow-up was 7.09 years. After the follow-up, 1890 (31.7%) participants developed CKD. Participants with dyslipidemia had a 5% shorter survival time (95% confidence interval: 3%–7%) to incident CKD compared with those without dyslipidemia in the full model. High-density lipoprotein cholesterol concentrations <40 mg/dL and triglyceride concentrations ≥150 mg/dL also reduced the survival time to CKD onset by 5%–6%. Our results provide further evidence that controlling the lipid profile to an appropriate range may prevent the future onset of CKD.

DOI： 10.1101/2024.10.25.24315968

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Kinetics of SARS-CoV-2 antibody titers after booster vaccinations during an Omicron surge in Japan

Naomi Matsumoto, Ayako Sasaki, Tomoka Kadowaki, Toshiharu Mitsuhashi, Soshi Takao, Takashi Yorifuji

Vaccine 42 ( 21 ) 126156 - 126156 2024.8

Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients. International journal

Mitsuru Tsuge, Eiki Ichihara, Kou Hasegawa, Kenichiro Kudo, Yasushi Tanimoto, Kazuhiro Nouso, Naohiro Oda, Sho Mitsumune, Goro Kimura, Haruto Yamada, Ichiro Takata, Toshiharu Mitsuhashi, Akihiko Taniguchi, Kohei Tsukahara, Toshiyuki Aokage, Hideharu Hagiya, Shinichi Toyooka, Hirokazu Tsukahara, Yoshinobu Maeda

International journal of molecular sciences 25 ( 15 ) 2024.7

Language：English Publishing type：Research paper (scientific journal)

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

DOI： 10.3390/ijms25158370

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Comprehensive geriatric assessment as an indicator of postoperative recovery in older patients with colorectal cancer. International journal

Fuminori Teraishi, Ryohei Shoji, Yoshitaka Kondo, Shunsuke Kagawa, Rie Tamura, Yoshikazu Matsuoka, Hiroshi Morimatsu, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

Journal of geriatric oncology 101837 - 101837 2024.7

Risk factors and treatment strategies for cholecystitis after metallic stent placement for malignant biliary obstruction: a multicenter retrospective study. International journal

Akihiro Matsumi, Hironari Kato, Taiji Ogawa, Toru Ueki, Masaki Wato, Masakuni Fujii, Tatsuya Toyokawa, Ryo Harada, Yuki Ishihara, Masahiro Takatani, Hirofumi Tsugeno, Naoko Yunoki, Takeshi Tomoda, Toshiharu Mitsuhashi, Motoyuki Otsuka

Gastrointestinal endoscopy 100 ( 1 ) 76 - 84 2024.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Cholecystitis can occur after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction (MBO), but the best treatment option for cholecystitis has not been determined. Here, we aimed to identify the risk factors of cholecystitis after SEMS placement and determine the best treatment option. METHODS: Incidence, treatments, and predictive factors of cholecystitis were retrospectively evaluated in 1084 patients with distal MBO (DMBO) and 353 patients with hilar MBO (HMBO) who underwent SEMS placement at 12 institutions from January 2012 to March 2021. RESULTS: Cholecystitis occurred in 7.5% of patients with DMBO and 5.9% of patients with HMBO. The recurrence rate was significantly lower (P = .043) and the recurrence-free period significantly longer (P = .039) in endoscopic procedures than in percutaneous procedures for cholecystitis treatment. EUS-guided gallbladder drainage (EUS-GBD) was better in terms of technical success, procedure time, and recurrence-free period than endoscopic transpapillary gallbladder drainage. Obstruction across the cystic duct orifice by tumor (P = .015) and by stent (P = .037) were independent risk factors for cholecystitis in DMBO. Cases with multiple SEMS placements (odds ratio [OR], 11; 95% confidence interval [CI], 0.68-190; P = .091) and with gallbladder stones (OR, 2.3; 95% CI ,0.92-5.6; P = .075) had a higher risk for cholecystitis in HMBO. CONCLUSIONS: The incidences of cholecystitis after SEMS placement for DMBO and HMBO were similar. EUS-GBD is the optimal treatment option for patients with cholecystitis after SEMS placement for MBO.

DOI： 10.1016/j.gie.2024.02.019

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