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1.
Intestinal Research ; : 318-327, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1000592

ABSTRACT

Background/Aims@#Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. @*Methods@#This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. @*Results@#Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10). @*Conclusions@#CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

2.
Guillaume Butler-Laporte; Gundula Povysil; Jack A Kosmicki; Elizabeth T Cirulli; Theodore Drivas; Simone Furini; Chadi Saad; Axel Schmidt; Pawel Olszewski; Urszula Korotko; Mathieu Quinodoz; Elifnaz Celik; Kousik Kundu; Klaudia Walter; Junghyung Jung; Amy D Stockwell; Laura G Sloofman; Daniel M Jordan; Ryan C Thompson; Diane Del Valle Del Valle; Nicole Simons Simons; Esther Cheng Cheng; Robert Sebra Sebra; Eric E Schadt; Seunghee Schulze-Kim Shulze-Kim; Sacha Gnjatic Gnjatic; Miriam Merad Merad; Joseph D Buxbaum; Noam D Beckmann; Alexander W Charney; Bartlomiej Przychodzen; Timothy Chang; Tess D Pottinger; Ning Shang; Fabian Brand; Francesca Fava; Francesca Mari; Karolina Chwialkowska; Magdalena Niemira; Szymon Pula; J Kenneth Baillie; Alex Stuckey; Antonio Salas; Xabier Bello; Jacobo Pardo-Seco; Alberto Gomez-Carballa; Irene Rivero-Calle; Federico Martinon-Torres; Andrea Ganna; Konrad J Karczewski; Kumar Veerapen; Mathieu Bourgey; Guillaume Bourque; Robert JM Eveleigh; Vincenzo Forgetta; David Morrison; David Langlais; Mark Lathrop; Vincent Mooser; Tomoko Nakanishi; Robert Frithiof; Michael Hultstrom; Miklos Lipcsey; Yanara Marincevic-Zuniga; Jessica Nordlund; Kelly M Schiabor Barrett; William Lee; Alexandre Bolze; Simon White; Stephen Riffle; Francisco Tanudjaja; Efren Sandoval; Iva Neveux; Shaun Dabe; Nicolas Casadei; Susanne Motameny; Manal Alaamery; Salam Massadeh; Nora Aljawini; Mansour S Almutairi; Yaseen M Arab; Saleh A Alqahtan; Fawz S Al Harthi; Amal Almutairi; Fatima Alqubaishi; Sarah Alotaibi; Albandari Binowayn; Ebtehal A Alsolm; Hadeel El Bardisy; Mohammad Fawzy; - COVID-19 Host Genetics Initiative; - DeCOI Host Genetics Group; - GEN-COVID Multicenter Study (Italy); - Mount Sinai Clinical Intelligence Center; - GEN-COVID consortium (Spain); - GenOMICC Consortium; - Japan COVID-19 Task Force; - Regeneron Genetics Center; Daniel H Geschwind; Stephanie Arteaga; Alexis Stephens; Manish J Butte; Paul C Boutros; Takafumi N Yamaguchi; Shu Tao; Stefan Eng; Timothy Sanders; Paul J Tung; Michael E Broudy; Yu Pan; Alfredo Gonzalez; Nikhil Chavan; Ruth Johnson; Bogdan Pasaniuc; Brian Yaspan; Sandra Smieszek; Carlo Rivolta; Stephanie Bibert; Pierre-Yves Bochud; Maciej Dabrowski; Pawel Zawadzki; Mateusz Sypniewski; Elzbieta Kaja; Pajaree Chariyavilaskul; Voraphoj Nilaratanakul; Nattiya Hirankarn; Vorasuk Shotelersuk; Monnat Pongpanich; Chureerat Phokaew; Wanna Chetruengchai; Katsuhi Tokunaga; Masaya Sugiyama; Yosuke Kawai; Takanori Hasegawa; Tatsuhiko Naito; Ho Namkoong; Ryuya Edahiro; Akinori Kimura; Seishi Ogawa; Takanori Kanai; Koichi Fukunaga; Yukinori Okada; Seiya Imoto; Satoru Miyano; Serghei Mangul; Malak S Abedalthagafi; Hugo Zeberg; Joseph J Grzymski; Nicole L Washington; Stephan Ossowski; Kerstin U Ludwig; Eva C Schulte; Olaf Riess; Marcin Moniuszko; Miroslaw Kwasniewski; Hamdi Mbarek; Said I Ismail; Anurag Verma; David B Goldstein; Krzysztof Kiryluk; Alessandra Renieri; Manuel AR Ferreira; J Brent Richards.
Preprint in English | medRxiv | ID: ppmedrxiv-22273040

ABSTRACT

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights. Author SummaryCOVID-19 clinical outcomes vary immensely, but a patients genetic make-up is an important determinant of how they will fare against the virus. While many genetic variants commonly found in the populations were previously found to be contributing to more severe disease by the COVID-19 Host Genetics Initiative, it isnt clear if more rare variants found in less individuals could also play a role. This is important because genetic variants with the largest impact on COVID-19 severity are expected to be rarely found in the population, and these rare variants require different technologies to be studies (usually whole-exome or whole-genome sequencing). Here, we combined sequencing results from 21 cohorts across 12 countries to perform a rare variant association study. In an analysis comprising 5,085 participants with severe COVID-19 and 571,737 controls, we found that the gene for toll-like receptor 7 (TLR7) on chromosome X was an important determinant of severe COVID-19. Importantly, despite being found on a sex chromosome, this observation was consistent across both sexes.

3.
Article in English | WPRIM (Western Pacific) | ID: wpr-938110

ABSTRACT

Background/Aims@#Functional dyspepsia (FD), one of the functional gastrointestinal disorders, is highly prevalent. Impaired gastric accommodation is proposed as a pathophysiology of FD. In order to assess gastric accommodation, a slow nutrient drinking test was developed. This study aims to evaluate the effectiveness of this slow nutrient drinking test among patients with FD in Japan. @*Methods@#Asymptomatic/healthy participants (n = 26) and those with FD (n = 16), were enrolled. An infusion pump was used to deliver the liquid meal into cups. They were requested to score their meal-related and abdominal symptoms at 5-minute intervals, using a 100 mm visual analog scale. They were instructed to end the test when they felt unable to ingest more or until after 50 minutes. @*Results@#The test ending time was significantly shorter in patients with FD than in healthy participants (22.3 ± 10.6 vs 45.0 ± 7.5 minutes, P < 0.001). The receiver operating characteristic curve indicated that the optimal cutoff time for detecting patients with FD was 30 minutes. The severity of meal-related and abdominal symptoms between healthy participants and those with FD was continuously different. Univariate and multivariate analyses revealed that the presence of symptoms of postprandial distress syndrome contributed to the short test ending time. @*Conclusion@#The 30-minute slow nutrient drinking test is a minimally invasive method of effectively evaluating symptoms of postprandial distress syndrome among patients with FD, in Japan.

4.
Ho Namkoong; Ryuya Edahiro; Koichi Fukunaga; Yuya Shirai; Kyuto Sonehara; Hiromu Tanaka; Ho Lee; Takanori Hasegawa; Masahiro Kanai; Tatsuhiko Naito; Kenichi Yamamoto; Ryunosuke Saiki; Takayoshi Hyugaji; Eigo Shimizu; Kotoe Katayama; Kazuhisa Takahashi; Norihiro Harada; Toshio Naito; Makoto Hiki; Yasushi Matsushita; Haruhi Takagi; Ryousuke Aoki; Ai Nakamura; Sonoko Harada; Hitoshi Sasano; Hiroki Kabata; Katsunori Masaki; Hirofumi Kamata; Shinnosuke Ikemura; Shotaro Chubachi; Satoshi Okamori; Hideki Terai; Atsuho Morita; Takanori Asakura; Junichi Sasaki; Hiroshi Morisaki; Yoshifumi Uwamino; Kosaku Nanki; Yohei Mikami; Sho Uchida; Shunsuke Uno; Rino Ishihara; Yuta Matsubara; Tomoyasu Nishimura; Takanori Ogawa; Takashi Ishiguro; Taisuke Isono; Shun Shibata; Yuma Matsui; Chiaki Hosoda; Kenji Takano; Takashi Nishida; Yoichi Kobayashi; Yotaro Takaku; Noboru Takayanagi; Soichiro Ueda; Ai Tada; Masayoshi Miyawaki; Masaomi Yamamoto; Eriko Yoshida; Reina Hayashi; Tomoki Nagasaka; Sawako Arai; Yutaro Kaneko; Kana Sasaki; Etsuko Tagaya; Masatoshi Kawana; Ken Arimura; Kunihiko Takahashi; Tatsuhiko Anzai; Satoshi Ito; Akifumi Endo; Yuji Uchimura; Yasunari Miyazaki; Takayuki Honda; Tomoya Tateishi; Shuji Tohda; Naoya Ichimura; Kazunari Sonobe; Chihiro Sassa; Jun Nakajima; Yasushi Nakano; Yukiko Nakajima; Ryusuke Anan; Ryosuke Arai; Yuko Kurihara; Yuko Harada; Kazumi Nishio; Tetsuya Ueda; Masanori Azuma; Ryuichi Saito; Toshikatsu Sado; Yoshimune Miyazaki; Ryuichi Sato; Yuki Haruta; Tadao Nagasaki; Yoshinori Yasui; Yoshinori Hasegawa; Yoshikazu Mutoh; Tomonori Sato; Reoto Takei; Satoshi Hagimoto; Yoichiro Noguchi; Yasuhiko Yamano; Hajime Sasano; Sho Ota; Yasushi Nakamori; Kazuhisa Yoshiya; Fukuki Saito; Tomoyuki Yoshihara; Daiki Wada; Hiromu Iwamura; Syuji Kanayama; Shuhei Maruyama; Takashi Yoshiyama; Ken Ohta; Hiroyuki Kokuto; Hideo Ogata; Yoshiaki Tanaka; Kenichi Arakawa; Masafumi Shimoda; Takeshi Osawa; Hiroki Tateno; Isano Hase; Shuichi Yoshida; Shoji Suzuki; Miki Kawada; Hirohisa Horinouchi; Fumitake Saito; Keiko Mitamura; Masao Hagihara; Junichi Ochi; Tomoyuki Uchida; Rie Baba; Daisuke Arai; Takayuki Ogura; Hidenori Takahashi; Shigehiro Hagiwara; Genta Nagao; Shunichiro Konishi; Ichiro Nakachi; Koji Murakami; Mitsuhiro Yamada; Hisatoshi Sugiura; Hirohito Sano; Shuichiro Matsumoto; Nozomu Kimura; Yoshinao Ono; Hiroaki Baba; Yusuke Suzuki; Sohei Nakayama; Keita Masuzawa; Shinichi Namba; Ken Suzuki; Nobuyuki Hizawa; Takayuki Shiroyama; Satoru Miyawaki; Yusuke Kawamura; Akiyoshi Nakayama; Hirotaka Matsuo; Yuichi Maeda; Takuro Nii; Yoshimi Noda; Takayuki Niitsu; Yuichi Adachi; Takatoshi Enomoto; Saori Amiya; Reina Hara; Toshihiro Kishikawa; Shuhei Yamada; Shuhei Kawabata; Noriyuki Kijima; Masatoshi Takagaki; Noa Sasa; Yuya Ueno; Motoyuki Suzuki; Norihiko Takemoto; Hirotaka Eguchi; Takahito Fukusumi; Takao Imai; Munehisa Fukushima; Haruhiko Kishima; Hidenori Inohara; Kazunori Tomono; Kazuto Kato; Meiko Takahashi; Fumihiko Matsuda; Haruhiko Hirata; Yoshito Takeda; Hidefumi Koh; Tadashi Manabe; Yohei Funatsu; Fumimaro Ito; Takahiro Fukui; Keisuke Shinozuka; Sumiko Kohashi; Masatoshi Miyazaki; Tomohisa Shoko; Mitsuaki Kojima; Tomohiro Adachi; Motonao Ishikawa; Kenichiro Takahashi; Takashi Inoue; Toshiyuki Hirano; Keigo Kobayashi; Hatsuyo Takaoka; Kazuyoshi Watanabe; Naoki Miyazawa; Yasuhiro Kimura; Reiko Sado; Hideyasu Sugimoto; Akane Kamiya; Naota Kuwahara; Akiko Fujiwara; Tomohiro Matsunaga; Yoko Sato; Takenori Okada; Yoshihiro Hirai; Hidetoshi Kawashima; Atsuya Narita; Kazuki Niwa; Yoshiyuki Sekikawa; Koichi Nishi; Masaru Nishitsuji; Mayuko Tani; Junya Suzuki; Hiroki Nakatsumi; Takashi Ogura; Hideya Kitamura; Eri Hagiwara; Kota Murohashi; Hiroko Okabayashi; Takao Mochimaru; Shigenari Nukaga; Ryosuke Satomi; Yoshitaka Oyamada; Nobuaki Mori; Tomoya Baba; Yasutaka Fukui; Mitsuru Odate; Shuko Mashimo; Yasushi Makino; Kazuma Yagi; Mizuha Hashiguchi; Junko Kagyo; Tetsuya Shiomi; Satoshi Fuke; Hiroshi Saito; Tomoya Tsuchida; Shigeki Fujitani; Mumon Takita; Daiki Morikawa; Toru Yoshida; Takehiro Izumo; Minoru Inomata; Naoyuki Kuse; Nobuyasu Awano; Mari Tone; Akihiro Ito; Yoshihiko Nakamura; Kota Hoshino; Junichi Maruyama; Hiroyasu Ishikura; Tohru Takata; Toshio Odani; Masaru Amishima; Takeshi Hattori; Yasuo Shichinohe; Takashi Kagaya; Toshiyuki Kita; Kazuhide Ohta; Satoru Sakagami; Kiyoshi Koshida; Kentaro Hayashi; Tetsuo Shimizu; Yutaka Kozu; Hisato Hiranuma; Yasuhiro Gon; Namiki Izumi; Kaoru Nagata; Ken Ueda; Reiko Taki; Satoko Hanada; Kodai Kawamura; Kazuya Ichikado; Kenta Nishiyama; Hiroyuki Muranaka; Kazunori Nakamura; Naozumi Hashimoto; Keiko Wakahara; Sakamoto Koji; Norihito Omote; Akira Ando; Nobuhiro Kodama; Yasunari Kaneyama; Shunsuke Maeda; Takashige Kuraki; Takemasa Matsumoto; Koutaro Yokote; Taka-Aki Nakada; Ryuzo Abe; Taku Oshima; Tadanaga Shimada; Masahiro Harada; Takeshi Takahashi; Hiroshi Ono; Toshihiro Sakurai; Takayuki Shibusawa; Yoshifumi Kimizuka; Akihiko Kawana; Tomoya Sano; Chie Watanabe; Ryohei Suematsu; Hisako Sageshima; Ayumi Yoshifuji; Kazuto Ito; Saeko Takahashi; Kota Ishioka; Morio Nakamura; Makoto Masuda; Aya Wakabayashi; Hiroki Watanabe; Suguru Ueda; Masanori Nishikawa; Yusuke Chihara; Mayumi Takeuchi; Keisuke Onoi; Jun Shinozuka; Atsushi Sueyoshi; Yoji Nagasaki; Masaki Okamoto; Sayoko Ishihara; Masatoshi Shimo; Yoshihisa Tokunaga; Yu Kusaka; Takehiko Ohba; Susumu Isogai; Aki Ogawa; Takuya Inoue; Satoru Fukuyama; Yoshihiro Eriguchi; Akiko Yonekawa; Keiko Kan-o; Koichiro Matsumoto; Kensuke Kanaoka; Shoichi Ihara; Kiyoshi Komuta; Yoshiaki Inoue; Shigeru Chiba; Kunihiro Yamagata; Yuji Hiramatsu; Hirayasu Kai; Koichiro Asano; Tsuyoshi Oguma; Yoko Ito; Satoru Hashimoto; Masaki Yamasaki; Yu Kasamatsu; Yuko Komase; Naoya Hida; Takahiro Tsuburai; Baku Oyama; Minoru Takada; Hidenori Kanda; Yuichiro Kitagawa; Tetsuya Fukuta; Takahito Miyake; Shozo Yoshida; Shinji Ogura; Shinji Abe; Yuta Kono; Yuki Togashi; Hiroyuki Takoi; Ryota Kikuchi; Shinichi Ogawa; Tomouki Ogata; Shoichiro Ishihara; Arihiko Kanehiro; Shinji Ozaki; Yasuko Fuchimo; Sae Wada; Nobukazu Fujimoto; Kei Nishiyama; Mariko Terashima; Satoru Beppu; Kosuke Yoshida; Osamu Narumoto; Hideaki Nagai; Nobuharu Ooshima; Mitsuru Motegi; Akira Umeda; Kazuya Miyagawa; Hisato Shimada; Mayu Endo; Yoshiyuki Ohira; Masafumi Watanabe; Sumito Inoue; Akira Igarashi; Masamichi Sato; Hironori Sagara; Akihiko Tanaka; Shin Ohta; Tomoyuki Kimura; Yoko Shibata; Yoshinori Tanino; Takefumi Nikaido; Hiroyuki Minemura; Yuki Sato; Yuichiro Yamada; Takuya Hashino; Masato Shinoki; Hajime Iwagoe; Hiroshi Takahashi; Kazuhiko Fujii; Hiroto Kishi; Masayuki Kanai; Tomonori Imamura; Tatsuya Yamashita; Masakiyo Yatomi; Toshitaka Maeno; Shinichi Hayashi; Mai Takahashi; Mizuki Kuramochi; Isamu Kamimaki; Yoshiteru Tominaga; Tomoo Ishii; Mitsuyoshi Utsugi; Akihiro Ono; Toru Tanaka; Takeru Kashiwada; Kazue Fujita; Yoshinobu Saito; Masahiro Seike; Yosuke Omae; Yasuhito Nannya; Takafumi Ueno; Tomomi Takano; Kazuhiko Katayama; Masumi Ai; Atsushi Kumanogoh; Toshiro Sato; Naoki Hasegawa; Katsushi Tokunaga; Makoto Ishii; Ryuji Koike; Yuko Kitagawa; Akinori Kimura; Seiya Imoto; Satoru Miyano; Seishi Ogawa; Takanori Kanai; Yukinori Okada.
Preprint in English | medRxiv | ID: ppmedrxiv-21256513

ABSTRACT

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

5.
Clinical Endoscopy ; : 851-856, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-914000

ABSTRACT

Background/Aims@#The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unit is desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay among outpatients. @*Methods@#We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at the Toyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depression during endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100 minutes) were identified using multiple logistic regression analysis. @*Results@#We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested without sedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and non-sedation group was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.014−1.036), female sex (OR, 1.657; 95% CI, 1.220−2.249), and midazolam dose (OR, 1.019; 95% CI, 1.013−1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results for colonoscopy. @*Conclusions@#Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.

6.
Intestinal Research ; : 45-55, 2020.
Article | WPRIM (Western Pacific) | ID: wpr-834396

ABSTRACT

Background/Aims@#PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). @*Methods@#OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. @*Results@#In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. @*Conclusions@#In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

7.
Intestinal Research ; : 69-78, 2020.
Article | WPRIM (Western Pacific) | ID: wpr-834395

ABSTRACT

Background/Aims@#5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. @*Methods@#We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. @*Results@#Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05). @*Conclusions@#In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.

8.
Gut and Liver ; : 619-625, 2020.
Article | WPRIM (Western Pacific) | ID: wpr-833191

ABSTRACT

Background/Aims@#The evaluation of small bowel lesions of Crohn’s disease (CD) using balloon-assisted enteroscopy (BAE) is crucial because mucosal healing is associated with a good prognosis. However, BAE procedures are invasive, requiring sedation or analgesia to reduce the patient’s pain.This study evaluated the clinical usefulness of a novel ul-trathin single-balloon enteroscopy (SBE) procedure for CD. @*Methods@#This single-center retrospective study included 102 CD patients who underwent trans-anal SBE between Janu-ary 2012 and May 2018. Of these patients, 82 underwent enteroscopy using conventional SBE, while 20 underwent ultrathin SBE. Patients were analyzed using propensity score matching, with 20 patients per group. The median duration of the examination, terminal ileum intubation rate, median cecum intubation time, median insertion depth, adverse events, and sedated dose in each group were compared. @*Results@#Before propensity score matching, the conventional SBE group had a larger number of surgical history patients than the ultrathin SBE group (p=0.05). After matching, the two groups did not significantly differ clinically. There were no significant differences in the mean duration of the examina-tion, cecum intubation time, or terminal ileal intubation rate between ultrathin SBE and conventional SBE. The mean in-sertion depth of ultrathin SBE tended to be deeper than that of conventional SBE (p=0.09). The use of ultrathin SBE also reduced the sedative dose during needed for enteroscopy compared with conventional SBE (p=0.005). @*Conclusions@#Novel ultrathin SBE may be less painful for CD patients than conventional SBE.

9.
Intestinal Research ; : 635-640, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-717687

ABSTRACT

Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.


Subject(s)
Humans , Colitis , Colitis, Ulcerative , Colonoscopy , Diagnosis , Fever , Hypersensitivity , Inflammatory Bowel Diseases , Medical Records , Mesalamine , Phenotype , Ulcer
10.
Intestinal Research ; : 384-392, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-715882

ABSTRACT

BACKGROUND/AIMS: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. METHODS: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. RESULTS: Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. CONCLUSIONS: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.


Subject(s)
Humans , Blotting, Western , Candida albicans , Candida , Crohn Disease , Cytokines , Flow Cytometry , Fungi , Healthy Volunteers , In Vitro Techniques , Inflammation , Interleukin-6 , Macrophage Colony-Stimulating Factor , Macrophages , Microbiota , Monocytes , Mucous Membrane , Necrosis , Tumor Necrosis Factor-alpha
12.
Intestinal Research ; : 142-146, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-740013

ABSTRACT

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.


Subject(s)
Humans , Clostridioides difficile , Clostridium , Colitis, Ulcerative , Colonoscopy , Diarrhea , Dysbiosis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Microbiota , Recurrence , Ulcer
13.
Intestinal Research ; : 236-243, 2017.
Article in English | WPRIM (Western Pacific) | ID: wpr-191815

ABSTRACT

BACKGROUND/AIMS: Colonoscopy and computed tomography (CT) are used primarily to exclude organic diseases in patients with irritable bowel syndrome (IBS), rather than to assess the pathophysiology of IBS. We aimed to evaluate colonic dysmotility and morphology in Japanese patients with IBS. METHODS: One hundred eighty-four patients with IBS and 49 asymptomatic controls who underwent colonoscopy in combination with CT colonography or barium enema were retrospectively reviewed between 2008 and 2012. Water-aided colonoscopy was performed without sedation by a single endoscopist. The duration and pattern of colonic movement and cecal intubation time were recorded. To assess colonic morphology, barium enema or CT colonography were performed immediately after colonoscopy. RESULTS: Colonic dysmotility was more frequent in the IBS group (28.8% vs. 2.0% in controls, P<0.001), especially in cases of IBS with diarrhea (IBS-D) (IBS with constipation [IBS-C] 28.8% vs. IBS-D 60.0% vs. mixed IBS [IBS-M] 5.1%, P<0.001). Colonic morphological abnormality was more frequent in the IBS group than in the control group (77.7% vs. 24.5%, P<0.001), especially in IBS-M and IBS-C groups (IBS-C 77.5% vs. IBS-D 48.9% vs. IBS-M 100%, P<0.001). Most patients with IBS with colonic dysmotility had experienced stress related to their symptoms. Cecal intubation time was significantly longer in the IBS group than in the control group (12.1±6.9 minutes vs. 4.6±1.9 minutes, P<0.001). CONCLUSIONS: Unsedated colonoscopy, combined with radiographic findings, can detect colonic dysmotility and morphological abnormality. Technical difficulties observed during cecal intubation may partially explain the pathophysiology of IBS.


Subject(s)
Humans , Asian People , Barium , Colon , Colonography, Computed Tomographic , Colonoscopy , Constipation , Diarrhea , Enema , Intubation , Irritable Bowel Syndrome , Radiography , Retrospective Studies
14.
Intestinal Research ; : 68-74, 2017.
Article in English | WPRIM (Western Pacific) | ID: wpr-47078

ABSTRACT

BACKGROUND/AIMS: Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan. METHODS: We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814). RESULTS: Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels. CONCLUSIONS: The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.


Subject(s)
Humans , Asian People , Colitis, Ulcerative , Colonoscopy , Communicable Diseases , DNA, Complementary , Dysbiosis , Ethics Committees, Research , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Information Services , Informed Consent , Japan , Microbiota , Tissue Donors , Treatment Outcome , Ulcer
15.
Article in English | WPRIM (Western Pacific) | ID: wpr-152286

ABSTRACT

Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel disease and is useful for assessing the disease severity in the colon and terminal ileum, several alternative diagnostic techniques have been developed recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy, and confocal laser endomicroscopy enable assessment of histological inflammation without the need for biopsy. Capsule endoscopy is useful for detection of small intestinal and colonic lesions in both female and male patients. For UC, capsule endoscopy may be useful for evaluating colonic inflammation in patients with a previous poor colonoscopy experience, while it should be used only in Crohn's disease (CD) patients with unexplained symptoms when other examinations are negative. Magnetic resonance enterography (MRE) is particularly useful for detecting transmural inflammation, stenosis, and extraintestinal lesions, including abscesses and fistulas. MRE is also useful when evaluating small and large intestinal lesions, even in cases with severe strictures in which full evaluation of the small bowel would be virtually impossible using other devices. Therefore, the appropriate diagnostic devices for detecting CD lesions in the small and large intestine should be used.


Subject(s)
Humans , Colitis, Ulcerative/diagnosis , Crohn Disease/diagnosis , Cytodiagnosis/trends , Diagnostic Imaging/trends , Endoscopy, Gastrointestinal/trends , Magnetic Resonance Imaging/trends , Microscopy, Confocal/trends , Predictive Value of Tests , Prognosis , Severity of Illness Index
17.
Gut and Liver ; : 689-692, 2015.
Article in English | WPRIM (Western Pacific) | ID: wpr-216098

ABSTRACT

We report herein improved methods for the safe and successful completion of endoscopic papillectomy (EP). Between January 2008 and November 2011, 12 patients underwent double-snare retracting papillectomy for the treatment of lesions of the major duodenal papilla. The main outcomes were en bloc resection rates, pathological findings, and adverse events. All of the patients (mean age, 60.1 years; range, 38 to 80 years) were diagnosed with ampullary adenoma by endoscopic forceps biopsies prior to endoscopic snare papillectomy. En bloc resection by double-snare retracting papillectomy was successfully performed for all lesions (median size, 12.3 mm), comprising six tubular adenomas, one tubulovillous adenoma, three cases of epithelial atypia, one hamartomatous polyp, and one case of duodenitis with regenerative change. Significant hemorrhage and pancreatitis were observed in one case after EP. Adenoma recurrence occurred in three patients during follow-up (median, 28.5 months) at a mean interval of 2 months postoperatively (range, 1 to 3 months). No serious adverse events were observed. Double-snare retracting papillectomy is effective and feasible for treating lesions of the major duodenal papilla. Further treatment experience, including a single-arm phase II study, needs to be accumulated before conducting a randomized controlled study.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenoma/pathology , Ampulla of Vater/pathology , Biopsy , Common Bile Duct Neoplasms/pathology , Dissection/methods , Duodenoscopy/methods , Feasibility Studies , Neoplasm Recurrence, Local , Treatment Outcome
18.
Article in English | WPRIM (Western Pacific) | ID: wpr-116739

ABSTRACT

The incidence and prevalence of inflammatory bowel diseases (IBDs) including ulcerative colitis and Crohn disease are rapidly increasing in Western countries and in developed Asian countries. Although biologic agents targeting the immune system have been effective in patients with IBD, cessation of treatment leads to relapse in the majority of patients, suggesting that intrinsic immune dysregulation is an effect, not a cause, of IBD. Dramatic changes in the environment, resulting in the dysregulated composition of intestinal microbiota or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has upgraded water supply and sewerage systems, as well as dietary habits and antibiotic overuse that are similar to such features found in developed Western countries. The purpose of this review article was to describe the association of diet, particularly Japanese food and microbiota, with IBD.


Subject(s)
Animals , Humans , Asian People , Diet/ethnology , Evidence-Based Medicine , Feeding Behavior/ethnology , Incidence , Inflammatory Bowel Diseases/diagnosis , Intestines/immunology , Japan/epidemiology , Microbiota , Prevalence , Probiotics/therapeutic use , Prognosis , Risk Factors
19.
Gut and Liver ; : 218-222, 2012.
Article in English | WPRIM (Western Pacific) | ID: wpr-19385

ABSTRACT

BACKGROUND/AIMS: A flexible spectral imaging color enhancement system was installed in new capsule software for video capsule endoscopy. Contrast image capsule endoscopy (CICE) is a novel technology using light-emitting diodes selected for the main absorption range of hemoglobin. We assessed the feasibility and diagnostic effi cacy for small bowel surveillance in patients with polyposis syndromes. METHODS: Six patients with polyposis syndromes, four with familial adenomatous polyposis and one each with Cowden syndrome (CS) and Cronkhite-Canada syndrome (CCS) were examined using CICE. We conducted three evaluations to assess the effect on the numbers of the detected polyps; compare polyp diagnostic rates between adenoma and hamartoma; and assess polyp visibility. RESULTS: The numbers of detected polyps and diagnostic accuracy did not differ signifi cantly between pre-contrast and contrast images. However, 50% of the adenomatous polyps displayed enhanced visibility on contrast images. CICE contrast images exhibited clearly demarcated lesions and improved the visibility of minute structures of adenomatous polyps. Hamartomatous polyp micro-structures in patients with CS and CCS were more clearly visualized on contrast than pre-contrast images. CONCLUSIONS: CICE is an effective tool for enhancing the visibility of polyps in patients with polyposis syndrome.


Subject(s)
Humans , Absorption , Adenoma , Adenomatous Polyposis Coli , Adenomatous Polyps , Capsule Endoscopes , Capsule Endoscopy , Hamartoma Syndrome, Multiple , Hemoglobins , Intestinal Polyposis , Polyps
20.
Intestinal Research ; : 317-323, 2012.
Article in English | WPRIM (Western Pacific) | ID: wpr-154839

ABSTRACT

Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-alpha. In addition, the CD14+ macrophages contributed to interferon (IFN)-gamma production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-gamma-positive feedback loop in IBD patients. We also discuss IFN-gamma and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)gammat, the master regulator of Th 17 cells, and are differentiated 'alternative Th 1 cells.' In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-gamma. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD.


Subject(s)
Child , Humans , Antigen-Presenting Cells , Bacteria , Child, Orphaned , Colitis , Colitis, Ulcerative , Crohn Disease , Cytokines , Dendritic Cells , Epithelial Cells , Homeostasis , Inflammatory Bowel Diseases , Interferons , Interleukin-17 , Interleukin-23 , Interleukins , Intestines , Killer Cells, Natural , Lymphocytes , Macrophages , Mucous Membrane , Plastics , T-Lymphocytes , T-Lymphocytes, Helper-Inducer , Tumor Necrosis Factor-alpha
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