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Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in crohn’s disease under infliximab therapy

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World Journal of Gastroenterology 2022年第23期28卷 2582-2596页

作者： Wan-Ting Cao Rong Huang shan Liu Yi-Hong Fan Mao-sheng Xu Yi Xu Hui Ni Department of Gastroenterology The First Affiliated Hospital of Zhejiang Chinese Medical UniversityZhejiang Provincial Key Laboratory of Gastrointestinal Diseases PathophysiologyHangzhou 310006Zhejiang ProvinceChina Department of Clinical Evaluation Center The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006Zhejiang ProvinceChina Department of Radiology The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006Zhejiang ProvinceChina Department of Nursing The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina

BACKGROUND Infliximab trough level(ITL)severely affects therapeutic outcomes of crohn’s disease(CD)patients under infliximab(IFX).Recently,frontier research has focused on identifying ITL based on different therapeutic *** previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy,studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and *** To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance *** CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were *** and inflammatory biomarkers were continuously monitored during the *** step I study was conducted from weeks 14 to 54 of IFX *** step II study was conducted from weeks 54 to 108 of IFX *** outcomes were defined as endoscopic activity(crohn’s disease endoscopic index of severity score>2 points or Rutgeerts score>i1)and endoscopic remission(crohn’s disease endoscopic index of severity score≤2 points or Rutgeerts≤i1).Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study *** At week 14,low ITL[odds ratio(OR)=0.666,95%confidence interval(CI):0.514-0.862,Psed the risk of endoscopic activity at week *** week 54,low ITL(OR=0.466,95%CI:0.247-0.877,Psed the risk of endoscopic activity at week *** week 14,ITL≤5.60μg/mL[area under the curve(AUC)=0.83,95%CI:0.73-0.90,P238μg/g

关键词： Infliximab trough level C-reactive protein Fecal calprotectin crohn’s disease Clinical remission Long-term endoscopic outcomes

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Impact of vitamin D on the hospitalization rate of crohn's disease patients seen at a tertiary care center

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World Journal of Gastroenterology 2017年第14期23卷 2539-2544页

作者： Krishna VR Venkata sumant s Arora Feng-Long Xie Talha A Malik Department of Internal Medicine University of Alabama at Birmingham Montgomery Health Center Department of Medicine-Gastroenterology University of Alabama at Birmingham

AIM To study the association between vitamin D level and hospitalization rate in crohn's disease(CD) *** We designed a retrospective cohort study using adult patients(> 19 years) with CD followed for at least one year at our inflammatory bowel disease center. Vitamin D levels were divided into: low mean vitamin D level(s appropriate mean vitamin D level(30-100 ng/m L). Generalized Poisson Regression Models(GPR) for Rate Data were used to estimate partially adjusted and fully adjusted incidence rate ratios(IRR) of hospitalization among CD patients. We also examined IRRs for vitamin D level as a continuous *** Of the 880 CD patients, 196 patients with vitamin D level during the observation period were included. Partially adjusted model demonstrated that CD patients with a low mean vitamin D level were almost twice more likely to be admitted(IRR = 1.76, 95%CI: 1.38-2.24) compared to those with an appropriate vitamin D level. The fully adjusted model confirmed this association(IRR = 1.44, 95%CI: 1.11-1.87). Partially adjusted model with vitamin D level as a continuous variable demonstrated,higher mean vitamin D level was associated with a 3% lower likelihood of admission with every unit(ng/m L) rise in mean vitamin D level(IRR = 0.97, 95%CI: 0.96-0.98). The fully adjusted model confirmed this association(IRR = 0.98, 95%CI: 0.97-0.99). CONCLUsION Normal or adequate vitamin D stores may be protective in the clinical course of CD. However, this role needs to be further characterized and understood.

关键词： crohn’s disease Vitamin D Vitamin D deficiency Hospitalization rate Inflammatory bowel disease

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Establishing a rabbit model of perianal fistulizing crohn's disease

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World Journal of Gastroenterology 2022年第15期28卷 1536-1547页

作者： shuang-shuang Lu Wen-Jia Liu Qiu-Ya Niu Chun-Yan Huo Yu-Qing Cheng En-Jing Wang Rong-Nan Li Fang-Fang Feng Yi-Ming Cheng Rong Liu Jin Huang Gastroenterology Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Graduate school Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Graduate school Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina Medical statistics Center Changzhou UniversityChangzhou 213000Jiangsu ProvinceChina

BACKGROUND crohn’s disease(CD)is a chronic nonspecific intestinal inflammatory *** aetiology and pathogenesis of CD are still *** fistula is the main complication of CD and is a difficult problem to solve at *** main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness ***,an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal *** To improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing crohn’s disease animal model to evaluate new treatment *** Twenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce *** A was treated with an improved equal interval small dose increasing *** dosage of group B was *** days later,the rabbits underwent surgical creation of a transsphincteric ***,three rabbits were randomly selected from each group every 7 d to remove the seton from the *** rabbits were examined by endoscopy every 7 days,and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological *** disease activity index(DAI),colonoscopy and histological scores were *** endoscopic ultrasonography(EUs)was used to evaluate the healing of *** Except for the DAI score,the colonoscopy and histological scores in group A were significantly higher than those in group B(Pseton,all animals had persistent lumens on EUs imaging,showing continuous fullthickness high *** inspection of the fistula showed acute and chronic inflammation,fibrosis,epithelialization and peripheral proctitis of the adjoining *** The improved method of CD colitis induction successfully established a rabbit perianal fistula CD pre

关键词： crohn’s disease Perianal fistula Model Endoscopy Histology

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Neurological manifestations related to crohn’s disease:a boon for the workforce

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Gastroenterology Report 2019年第4期7卷 291-297,I0002页

作者： Reza Nemati somayeh Mehdizadeh Hooman salimipour Ehsan Yaghoubi Zeinab Alipour seyed Masoud Tabib Majid Assadi Department of Neurology Bushehr University of Medical SciencesBushehrIran The Persian Gulf Tropical Medicine Research Center Bushehr University of Medical SciencesBushehrIran Department of Pathology Rasul-e Akram HospitalIran University of Medical SciencesTehranIran Department of Neurology Yasuj University of Medical SciencesYasujIran Department of Gastroenterology and Hepatology Bushehr University of Medical SciencesBushehrIran The Persian Gulf Nuclear Medicine Research Center Bushehr University of Medical SciencesBushehrIran

The neurological manifestations of crohn’s disease and its prevalence are not well ***,we report five patients of confirmed crohn’s disease with different neurological *** neurological presentations include anterior ischemic optic neuropathy,myelopathy,posterior reversible encephalopathy syndrome,chronic inflammatory demyelinating polyneuropathy,and chronic axonal sensory and motor *** manifestations should be kept in mind in the assessment of crohn’s disease.

关键词： crohn’s disease idiopathic inflammatory bowel disease neurological manifestation

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Elaboration and validation of crohn's disease anoperineal lesions consensual definitions

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World Journal of Gastroenterology 2017年第29期23卷 5371-5378页

作者： Clémence Horaist Vincent de Parades Laurent Abramowitz Paul Benfredj Guillaume Bonnaud Dominique Bouchard Nadia Fathallah Agnès sénéjoux Laurent siproudhis Ghislain staumont Manuelle Viguier Philippe Marteau Department of Digestive disease Centre Hospitalier Intercommunal Le Raincy-Montfermeil Department of Proctology Hopital Saint-Joseph Institut Léopold Bellan Department of Proctology and Digestive diseases University Hospital Bichat Department of Digestive diseases Clinique des Cèdres Department of Proctology Hopital Bagatelle Department of Proctology Centre Hospitalier Privé Rennes de Saint-Grégoire Department of Digestive diseases Pontchaillou University Hospital Department of Proctology Clinique St Jean Languedoc AP-HP H0pital Saint Louis Dermatology and Denis Diderot-Paris 7 University sorbonne Universités UPMC Univ Paris 06 75005 Paris France INsERM-ERL 1157 CHU Saint-Antoine 27 75012 Paris France CNRs UMR7203 75012 Paris France APHP Hépatologie et Gastroentérologie Hopital Saint Antoine

To establish consensual definitions of anoperineal lesions of crohn’s (APLOC) disease and assess interobserver agreement on their diagnosis between experts. METHODsA database of digitally recorded pictures of APLOC was examined by a coordinating group who selected two series of 20 pictures illustrating the various aspects of APLOC. A reading group comprised: eight experts from the société Nationale Française de Colo Proctologie group of study and research in proctology and one academic dermatologist. All members of the coordinating and reading groups participated in dedicated meetings. The coordinating group initially conducted a literature review to analyse verbatim descriptions used to evaluate APLOC. The study included two phases: establishment of consensual definitions using a formal consensus method and later assessment of interobserver agreement on the diagnosis of APLOC using photos of APLOC, a standardised questionnaire and Fleiss’s kappa test or descriptive statistics. REsULTsTerms used in literature to evaluate visible APLOC did not include precise definitions or reference to definitions. Most of the expert reports on the first set of photos agreed with the main diagnosis but their verbatim reporting contained substantial variation. The definitions of ulceration (entity, depth, extension), anal skin tags (entity, inflammatory activity, ulcerated aspect), fistula (complexity, quality of drainage, inflammatory activity of external openings), perianal skin lesions (abscess, papules, edema, erythema) and anoperineal scars were validated. For fistulae, they decided to follow the American Gastroenterology Association’s guidelines definitions. The diagnosis of ulceration (κ = 0.70), fistulae (κ = 0.75), inflammatory activity of external fistula openings (86.6% agreement), abscesses (84.6% agreement) and erythema (100% agreement) achieved a substantial degree of interobserver reproducibility. CONCLUsIONThis study constructed consensual definitions of APLOC and the

关键词： crohn’s disease Anoperineal lesions Fistula Interobserver agreement

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Trends and risk factors of elderly-onset crohn’s disease: A nationwide cohort study

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World Journal of Gastroenterology 2020年第4期26卷 404-415页

作者： Jung Min Moon Eun Ae Kang Kyungdo Han seung Wook Hong Hosim soh seona Park Jooyoung Lee Hyun Jung Lee Jong Pil Im Joo sung Kim Department of Internal Medicine Liver Research InstituteSeoul National University College of MedicineSeoul 03080South Korea Department of Biostatistics College of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND The incidence of inflammatory bowel disease(IBD)is increasing in *** risk factors associated with IBD development have been *** To investigate trends and environmental risk factors of crohn’s disease(CD)diagnosed in persons aged≥40 years in south *** Using the National Health Insurance service database,a total of 14060821 persons aged>40 years who underwent national health screening in 2009 were followed up until December *** with newly diagnosed CD were enrolled and compared with non-CD *** was identified according to the International Classification of diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance service *** mean follow-up periods was 7.39 ***,sex,diabetes,hypertension,smoking,alcohol consumption,regular exercise,body mass index,anemia,chronic kidney disease(CKD)and dyslipidemia were adjusted for in the multivariate analysis *** During the follow-up,1337(1.33/100000)patients developed *** in the middle-aged group(40-64 years)had a higher risk than women[adjusted hazard ratio(aHR)1.46,95%confidence interval(CI):1.29-1.66];however,this difference tended to disappear as the age of onset *** the middle-aged group,patients with a history of smoking[(aHR 1.46,95%CI:1.19-1.79)and anemia(aHR 1.85,95%CI:1.55-2.20)]had a significantly higher CD *** the elderly group(age,≥65 years),ex-smoking and anemia also increased the CD risk(aHR 1.68,95%CI:1.22-2.30)and 1.84(95%CI:1.47-2.30,respectively).Especially in the middle-aged group,those with CKD had a statistically elevated CD risk(aHR 1.37,95%CI:1.05-1.79).Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups.[Middle-aged:aHR 0.77(95%CI:0.66-0.89)and aHR 0.73(95% CI:0.63-0.84),respectively][Elderly-group:aHR 0.57(95% CI:0.42-0.78)and aHR 0.84(95%CI 0.67-1.04),respectively].For regular p

关键词： crohn’s disease Aged Environmental Risk factors Epidemiology Nationwide cohort

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Therapeutic strategies in crohn’s disease in an emergency surgical setting

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World Journal of Gastroenterology 2022年第18期28卷 1902-1921页

作者： Maria Michela Chiarello Gilda Pepe Valeria Fico Valentina Bianchi Giuseppe Tropeano Gaia Altieri Giuseppe Brisinda Department of surgery San Giovanni in Fiore HospitalAzienda Sanitaria Provinciale di CosenzaCosenza 87100Italy Emergency surgery and Trauma Center Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of surgery Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Medical and surgical science UniversitàCattolica del Sacro CuoreRome 00168Italy

crohn’s disease(CD)remains a chronic,incurable disorder that presents unique challenges to the *** factors must be considered to allow development of an appropriate treatment *** therapy often precedes or complements the surgical *** indications for operative management of CD include acute and chronic disease complications and failed medical *** surgery comes into play when patients are refractory to medical treatment if they have an obstructive *** colitis,acute obstruction,perforation,acute abscess,or massive hemorrhage represent indications for emergency *** patients are generally in critical conditions and present with intra-abdominal sepsis and a preoperative status of immunosuppression and malnutrition that exposes them to a higher risk of complications and mortality.A multidisciplinary team including surgeons,gastroenterologists,radiologists,nutritional support services,and enterostomal therapists are required for optimal patient care and decision *** of each emergency should be individualized based on patient age,disease type and duration,and patient goals of ***,the recurrent nature of disease mandates that we continue searching for innovative medical therapies and operative techniques that reduce the need to repeat surgical *** this review,we aimed to discuss the acute complications of CD and their treatment.

关键词： crohn’s disease Intestinal obstruction Free perforation Intra-abdominal sepsis Perineal sepsis Acute bleeding

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Proteomics identifies a novel role of fibrinogen-like protein 1 in crohn’s disease

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World Journal of Gastroenterology 2021年第35期27卷 5946-5957页

作者： Xue-Liang sun Li-Chao Qiao Jing Gong Ke Wen Zhi-Zhong Xu Bo-Lin Yang First Clinical Medical College The Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Colorectal surgery Suzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhou 215000Jiangsu ProvinceChina Department of Colorectal surgery Jiangsu Province Hospital of Chinese MedicineNanjing 210029Jiangsu ProvinceChina

BACKGROUND crohn’s disease(CD)is an incurable intestinal disorder with unclear etiology and ***,there is a lack of specific biomarkers and drug targets for CD in clinical *** is essential to identify the precise pathophysiological mechanism of CD and investigate new therapeutic *** To explore a new biomarker and therapeutic target for CD and verify its role in the CD pathological *** Proteomics was performed to quantify the protein profile in the plasma of 20 CD patients and 20 matched healthy *** genes among the selected differentially expressed proteins(DEPs)were detected via the MCODE plugin in Cytoscape *** expression level of one hub gene with an immunoregulatory role that interested us was verified in the inflamed intestinal tissues of 20 CD patients by immunohistochemical *** that,the effects of the selected hub gene on the intestinal inflammation of CD were identified in a CD cell model by examining the levels of proinflammatory cytokines by enzymelinked immunosorbent assays and the expression of the NF-κB signalling pathway by quantitative real-time PCR analysis and Western blot *** Thirty-five DEPs were selected from 393 credible proteins identified by proteomic *** the DEPs,fibrinogen-like protein 1(FGL1),which attracted our attention due to its function in the regulation of the immune response,had 1.722-fold higher expression in the plasma of CD patients and was identified as a hub gene by ***,the expression of FGL1 in the intestinal mucosal and epithelial tissues of CD patients was also upregulated(Ps of FGL1 and NF-κB;the protein expression levels of FGL1,IKKα,IKKβ,p-IKKα/β,p-IκBα,and p-p65;and the concentrations of the proinflammatory cytokines IL-1β,IL-6,IL-17,and TNF-αwere increased(Pstimulation with lipopolysaccharide,which were reversed by knockdown of FGL1 with siRNA transfection(P<0.05).Conve

关键词： crohn’s disease Fibrinogen-like protein 1 Proteomics NF-κB pathway

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Alterations of autophagic and innate immune responses by the crohn’s disease-associated ATG16L1 mutation

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World Journal of Gastroenterology 2022年第26期28卷 3063-3070页

作者： Natsuki Okai Tomohiro Watanabe Kosuke Minaga Ken Kamata Hajime Honjo Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of MedicineOsaka-Sayama 589-8511OsakaJapan

crohn’s disease(CD)is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory *** pro-inflammatory cytokines are produced by macrophages and dendritic cells(DCs)upon sensing the intestinal microbiota by the pattern recognition receptors(PRRs).Impaired activation of PRR-mediated signaling pathways is associated with chronic gastrointestinal inflammation,as shown by the fact that loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene increase the risk of CD *** is an intracellular degradation process,during which cytoplasmic nutrients and intracellular pathogens are *** that impaired reaction to intestinal microbiota alters signaling pathways mediated by PRRs,it is likely that dysfunction of the autophagic machinery is involved in the development of ***,the loss-of-function mutation T300A in the autophagy related 16 like 1(ATG16L1)protein,a critical regulator of autophagy,increases susceptibility to *** studies have provided evidence that ATG16L1 is involved not only in autophagy,but also in PRR-mediated signaling ***16L1 negatively regulates pro-inflammatory cytokine responses of macrophages and DCs after these cells sense the intestinal microbiota by ***,we discuss the molecular mechanisms underlying the development of CD in the T300A ATG16L1 mutation by focusing on PRR-mediated signaling pathways.

关键词： ATG16L1 crohn’s disease Autophagy Innate immunity Cytokine Pattern recognition receptors

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Cerebral magnetic resonance imaging in quiescent crohn's disease patients with fatigue

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World Journal of Gastroenterology 2017年第6期23卷 1018-1029页

作者： sanne van Erp Ece Ercan Perla Breedveld Lianne Brakenhoff Eidrees Ghariq sophie schmid Matthias van Osch Mark van Buchem Bart Emmer Jeroen van der Grond Ron Wolterbeek Daniel Hommes Herma Fidder Nic van der Wee Tom Huizinga Désirée van der Heijde Huub Middelkoop Itamar Ronen Andrea van der Meulen-de Jong Department of Gastroenterology and Hepatology Leiden University Medical Center C.J.Gorter Center Leiden University Medical Center Department of Radiology Leiden University Medical Center Department of Medical statistics Leiden University Medical Center Center for Inflammatory Bowel diseases University of California Los Angeles Department of Gastroenterology and Hepatology University Medical Center Utrecht Department of Psychiatry Leiden University Medical Center Department of Rheumatology Leiden University Medical Center Department of Neuropsychology Leiden University Medical Center Department of Radiology Leiden University Medical CenterLeiden

To evaluate brain involvement in quiescent crohn’s disease (CD) patients with fatigue using quantitative magnetic resonance imaging (MRI).METHODsMultiple MRI techniques were used to assess cerebral changes in 20 quiescent CD patients with fatigue (defined with at least 6 points out of an 11-point numeric rating scale compared with 17 healthy age and gender matched controls without fatigue. Furthermore, mental status was assessed by cognitive functioning, based on the neuropsychological inventory including the different domains global cognitive functioning, memory and executive functioning and in addition mood and quality of life scores. Cognitive functioning and mood status were correlated with MRI findings in the both study *** glutamate + glutamine (Glx = Glu + Gln) concentrations (P = 0.02) and ratios to total creatine (P = 0.02) were found in CD patients compared with controls. significant increased Cerebral Blood Flow (P = 0.05) was found in CD patients (53.08 ± 6.14 mL/100 g/min) compared with controls (47.60 ± 8.62 mL/100 g/min). CD patients encountered significantly more depressive symptoms (P scores related to memory (P = 0.007) and executive functioning (P = 0.02) were lower in CD patients and both scores showed correlation with depression and anxiety. No correlation was found subcortical volumes between CD patients and controls in the Tsub>1sub>-weighted analysis. In addition, no correlation was found between mental status and MRI *** work shows evidence for perfusion, neurochemical and mental differences in the brain of CD patients with fatigue compared with healthy controls.

关键词： Magnetic resonance imaging systemic inflammation Fatigue crohn’s disease Cognition

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