1.Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease
Teruki MIYAKE ; Shinya FURUKAWA ; Bunzo MATSUURA ; Osamu YOSHIDA ; Masumi MIYAZAKI ; Akihito SHIOMI ; Ayumi KANAMOTO ; Hironobu NAKAGUCHI ; Yoshiko NAKAMURA ; Yusuke IMAI ; Mitsuhito KOIZUMI ; Takao WATANABE ; Yasunori YAMAMOTO ; Yohei KOIZUMI ; Yoshio TOKUMOTO ; Masashi HIROOKA ; Teru KUMAGI ; Eiji TAKESITA ; Yoshio IKEDA ; Masanori ABE ; Yoichi HIASA
Diabetes & Metabolism Journal 2024;48(3):440-448
Background:
Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD.
Methods:
This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%–6.4%, 6.5%–7.4%, and ≥7.5%.
Results:
Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%–6.4%, 6.5%–7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%– 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses.
Conclusion
Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%–7.4%, contributing to NAFLD progression.
2.Multimorbidity of Allergic Diseases Is Associated With Functional Gastrointestinal Disorders in a Young Japanese Population
Yasunori YAMAMOTO ; Shinya FURUKAWA ; Teruki MIYAKE ; Junichi WATANABE ; Yukihiro NAKAMURA ; Yoshihiro TAGUCHI ; Tetsuya YAMAMOTO ; Aki KATO ; Katsunori KUSUMOTO ; Osamu YOSHIDA ; Eiji TAKESHITA ; Yoshio IKEDA ; Naofumi YAMAMOTO ; Yuka SAEKI ; Osamu YAMAGUCHI ; Yoichi HIASA
Journal of Neurogastroenterology and Motility 2024;30(2):229-235
Background/Aims:
Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS.The aim of this study is to determine this issue in young people.
Methods:
A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria.Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire.
Results:
The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018).
Conclusion
Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.
3.The albumin to globulin ratio is associated with clinical outcome in Japanese patients with ulcerative colitis
Sen YAGI ; Shinya FURUKAWA ; Kana SHIRAISHI ; Teruki MIYAKE ; Kazuhiro TANGE ; Yu HASHIMOTO ; Shogo KITAHATA ; Tomoe KAWAMURA ; Tomoyuki NINOMIYA ; Kenichirou MORI ; Seiyuu SUZUKI ; Naozumi SHIBATA ; Hidehiro MURAKAMI ; Katsuhisa OHASHI ; Aki HASEBE ; Hideomi TOMIDA ; Yasunori YAMAMOTO ; Eiji TAKESHITA ; Yoshio IKEDA ; Yoichi HIASA
Annals of Coloproctology 2023;39(2):155-163
Purpose:
The albumin-to-globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC.
Methods:
The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day).
Results:
The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52–14.18 and adjusted OR, 4.97; 95% CI, 2.14–12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56–11.51 and adjusted OR, 5.22; 95% CI, 1.97–14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06–21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found.
Conclusion
Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.
4.Association Between Body Mass Index and Functional Dyspepsia in Young Japanese People
Yasunori YAMAMOTO ; Shinya FURUKAWA ; Junichi WATANABE ; Aki KATO ; Katsunori KUSUMOTO ; Eiji TAKESHITA ; Yoshio IKEDA ; Naofumi YAMAMOTO ; Katsuhiko KOHARA ; Yuka SAEKI ; Yoichi HIASA
Journal of Neurogastroenterology and Motility 2022;28(2):276-282
Background/Aims:
Evidence regarding the association between body mass index (BMI) and functional dyspepsia (FD) in the Asian population is limited.Further, no study has evaluated this issue in young people in Asian and Western populations. Thus, we aim to investigate this issueamong young Japanese people.
Methods:
The study subjects comprised of 8923 Japanese university students. BMI was divided into 4 categories (quartiles) on the basis of thestudy subjects’ distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, overweight, and obesewas BMI < 18.5 kg/m2 , 18.5 ≤ BMI < 25 kg/m2 (reference), 25 kg/m2 ≤ BMI < 30 kg/m2 , and 30 kg/m2 ≤ BMI, respectively. The definition of FD was based on the Rome III criteria.
Results:
The prevalence of FD was 1.9% in this cohort. The lowest BMI was independently associated with FD after adjustment (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.46-3.67); P for trend = 0.001). The lowest BMI was independently associated with FD in women but not in men (OR, 2.94; 95% CI, 1.59-5.77; P for trend = 0.001). Leanness was independently associated with FD in total and in women but not in men (total: adjusted OR, 2.01; 95% CI, 1.40-2.86) and women (OR, 2.19; 95% CI, 1.35-3.45). However,interaction analysis showed no significant difference for sex.
Conclusions
Among young Japanese people, BMI may be independently inversely associated with FD. Leanness may be an independent associated factor for FD in the young Japanese women.
5.Current Treatment Strategy for Superficial Nonampullary Duodenal Epithelial Tumors
Tetsuya SUWA ; Kohei TAKIZAWA ; Noboru KAWATA ; Masao YOSHIDA ; Yohei YABUUCHI ; Yoichi YAMAMOTO ; Hiroyuki ONO
Clinical Endoscopy 2022;55(1):15-21
Endoscopic submucosal dissection (ESD) is the standard treatment method for esophageal, gastric, and colorectal cancers. However, it has not been standardized for duodenal lesions because of its high complication rates. Recently, minimally invasive and simple methods such as cold snare polypectomy and underwater endoscopic mucosal resection have been utilized more for superficial nonampullary duodenal epithelial tumors (SNADETs). Although the rate of complications associated with duodenal ESD has been gradually decreasing because of technical advancements, performing ESD for all SNADETs is unnecessary. As such, the appropriate treatment plan for SNADETs should be chosen according to the lesion type, patient condition, and endoscopist’s skill.
6.Association Between Eating Behavior, Frequency of Meals, and Functional Dyspepsia in Young Japanese Population
Yasunori YAMAMOTO ; Shinya FURUKAWA ; Junichi WATANABE ; Aki KATO ; Katsunori KUSUMOTO ; Teruki MIYAKE ; Eiji TAKESHITA ; Yoshio IKEDA ; Naofumi YAMAMOTO ; Katsuhiko KOHARA ; Syuichi SAHEKI ; Yuka SAEKI ; Yoichi HIASA
Journal of Neurogastroenterology and Motility 2022;28(3):418-423
Background/Aims:
Functional dyspepsia (FD) may be a common digestive disease worldwide and reduces the quality of life of patients. However, only a few studies have investigated the association between eating behavior and FD. The purpose of this cross-sectional study is to examine the association between eating behavior and prevalence of FD in a young Japanese cohort.
Methods:
In this study, we enrolled 8923 Japanese university students. FD is diagnosed based on the Rome III criteria. Eating habits and frequency of meals were investigated using a self-administered questionnaire.
Results:
The FD subjects had a younger mean age, a lower body mass index, and a lower proportion of men compared to the non-FD subjects.An independent positive association between skipping breakfast and/or lunch and FD was found (adjusted ORs were 1.60 [95% CI, 1.10-2.32] for breakfast and 2.52 [95% CI, 1.04-5.18] for lunch). Skipping dinner, extra meals (snacks) or midnight snacks was not associated with FD. The prevalence of FD in subjects eating 1, 2, and 3 meals per day was 4.8%, 2.2%, and 1.7%, respectively. The frequency of meals was independently inversely associated with prevalence of FD (adjusted ORs were 1 per day: 2.72 [95% CI, 1.19-5.42], and 2 per day: 1.69 [95% CI, 1.16-2.43], P for trend = 0.001).
Conclusions
In the young Japanese people, the frequency of meals may be independently inversely associated with prevalence of FD. In particular, skipping breakfast and/or lunch was associated with the prevalence of FD.
7.Actual Use of Internet by Patients with Diabetes to Find Drug Information
Kana MARUYAMA ; Yuki KONDO ; Shinichiro YAMAKADO ; Tadakazu KAJIYA ; Ken YAMAMOTO ; Aya FURUKAWA ; Yoichi ISHITSUKA ; Masayoshi IWAMOTO ; Michiko YAMAMOTO ; Tetsumi IRIE
Japanese Journal of Drug Informatics 2021;23(2):99-108
Objectives: It is important for patients to make correct use of drug information (DI) to promote the proper use of medicines. Many patients use the Internet to find DI, but awareness about the websites of public institutions that provide DI is low. This study aimed to identify the actual use of the Internet for DI and associated problems to inform development of a comprehensive DI website for patients.Method: Patients with diabetes were set as a model case for patients who take medicines and need DI. A questionnaire survey was conducted among patients with diabetes who visited community pharmacies in Kagoshima City from March 2019 to October 2019. The survey covered Internet use, DI needs, methods of sourcing DI, and problems obtaining DI via the Internet.Results: There were 349 valid respondents (median age 64 years), of which 52.1% used the Internet at least once a week. Around half of the Internet users searched for DI on the Internet. More than half of these respondents chose a DI acquisition site because it “appeared at the top of search results” and was “easy to understand.” However, around half of these respondents felt that “there is too much information on the internet and I don’t know what is correct.”Conclusion: This study suggests that older patients with a long history of diabetes use the Internet to obtain DI. However, patients face various problems accessing DI via the Internet. It may be necessary to construct a comprehensive website that is easy to use and enhance public health literacy to support the proper use of medicines by patients.
8.Association between physical function and long-term care in community-dwelling older and oldest people: the SONIC study.
Werayuth SRITHUMSUK ; Mai KABAYAMA ; Kayo GODAI ; Nonglak KLINPUDTAN ; Ken SUGIMOTO ; Hiroshi AKASAKA ; Yoichi TAKAMI ; Yasushi TAKEYA ; Koichi YAMAMOTO ; Saori YASUMOTO ; Yasuyuki GONDO ; Yasumichi ARAI ; Yukie MASUI ; Tatsuro ISHIZAKI ; Hiroshi SHIMOKATA ; Hiromi RAKUGI ; Kei KAMIDE
Environmental Health and Preventive Medicine 2020;25(1):46-46
BACKGROUND:
Preventing the need for long-term care (LTC) by identifying physical function risk factors are important to decrease the LTC burden. The objective of this study was to investigate whether grip strength and/or walking speed, which are components of the frailty definition, are associated with LTC in community-dwelling older and oldest people.
METHODS:
The participants were 1098 community-dwelling older and oldest people who had not received LTC at the baseline. The endpoint was receiving LTC after the baseline survey. The independent variables were grip strength and walking speed, and participants were divided into two groups based on these variables. The confounding factors were age, sex, the Japanese version of the Montreal Cognitive Assessment (MoCA-J), hypertension, diabetes mellitus, stroke, joint diseases, living alone, body mass index, and serum albumin. We calculated the hazard ratio of receiving LTC using the Cox proportional hazard model.
RESULTS:
Among the 1098 participants, 107 (9.7%) newly received LTC during the follow-up. Regarding the physical function, only slow walking speed was significantly correlated with LTC after adjusting for all confounding factors except the MoCA-J score (HR = 1.74, 95% CI = 1.10-2.75, P = .018). However, slow walking speed was still a risk factor for LTC after adjusting for the MoCA-J score and other confounding factors (HR = 1.64, 95% CI = 1.03-2.60, P = .037).
CONCLUSIONS
The findings from this study may contribute to a better understanding of slow walking speed as a factor related to LTC, which might be a criterion for disability prevention and could serve as an outcome measure for physical function in older people.
Aged
;
Aged, 80 and over
;
Exercise
;
Female
;
Humans
;
Independent Living
;
statistics & numerical data
;
Japan
;
Long-Term Care
;
statistics & numerical data
;
Male
;
Proportional Hazards Models
9.Long-term prognosis of Japanese patients with biologic-naïve Crohn’s disease treated with anti-tumor necrosis factor-α antibodies
Rintaro MOROI ; Katsuya ENDO ; Katsutoshi YAMAMOTO ; Takeo NAITO ; Motoyuki ONODERA ; Masatake KUROHA ; Yoshitake KANAZAWA ; Tomoya KIMURA ; Yoichi KAKUTA ; Atsushi MASAMUNE ; Yoshitaka KINOUCHI ; Tooru SHIMOSEGAWA
Intestinal Research 2019;17(1):94-106
BACKGROUND/AIMS: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn’s disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. METHODS: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. RESULTS: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels < 2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. CONCLUSIONS: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.
Adalimumab
;
Antibodies
;
Asian Continental Ancestry Group
;
Biological Products
;
C-Reactive Protein
;
Cohort Studies
;
Crohn Disease
;
Food, Formulated
;
Humans
;
Infliximab
;
Necrosis
;
Prognosis
;
Proportional Hazards Models
;
Retrospective Studies
;
Risk Factors
;
Serum Albumin
10.Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy.
Yusuke MIMURA ; Toshihiko KATOH ; Radka SALDOVA ; Roisin O'FLAHERTY ; Tomonori IZUMI ; Yuka MIMURA-KIMURA ; Toshiaki UTSUNOMIYA ; Yoichi MIZUKAMI ; Kenji YAMAMOTO ; Tsuneo MATSUMOTO ; Pauline M RUDD
Protein & Cell 2018;9(1):47-62
Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.
Animals
;
Antibodies, Monoclonal
;
adverse effects
;
pharmacokinetics
;
therapeutic use
;
Glycosylation
;
Humans
;
Immunoglobulin G
;
chemistry
;
metabolism
;
Protein Engineering
;
methods
;
Receptors, Fc
;
chemistry
;
metabolism
;
Treatment Outcome


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