The Crohn＇s disease activity index （CDAI） has been commonly used to assess the effects of treatment with different agents in Crohn＇s disease （CD）. However, these studies may be compromised, if the results compar...The Crohn＇s disease activity index （CDAI） has been commonly used to assess the effects of treatment with different agents in Crohn＇s disease （CD）. However, these studies may be compromised, if the results compared to a placebo or standard therapy group （in the absence of a placebo） substantially differ from the expected response. In addition, significant concerns have been raised regarding the reliability and validity of the CDAI. Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded, even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD. Finally, many CDAI endpoints are open to subjective interpretation and have the potential for manipulation. This is worrisome as there is the potential for significant financial gain, if the results of a clinical trial appear to provide a positive result. Physicians caring for patients should be concerned about the positive results in clinical trials that are sponsored by industry, even if the trials involve respected centers and the results appear in highly ranked medical journals.展开更多
BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive asse...BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.展开更多
BACKGROUND Perianal fistulas pose dual challenges to Crohn's disease(CD)patients.Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of peria...BACKGROUND Perianal fistulas pose dual challenges to Crohn's disease(CD)patients.Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD.AIM To determine the accuracy of endoanal ultrasound(EUS)and shear wave elastography(SWE)for evaluating perianal fistulizing CD(PFCD)activity.METHODS This was a retrospective cohort study.A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups:Non-anal fistula group(n=23),low-activity perianal fistulas[n=19,perianal disease activity index(PDAI)≤4],high-activity perianal fistulas(n=25,PDAI>4)based on the PDAI.All patients underwent assessments including EUS+SWE,pelvic magnetic resonance[pelvic magnetic resonance imaging(MRI)],C-reactive protein,fecal calprotectin,CD activity index,PDAI.RESULTS The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%,and there was good consistency in the classification of perianal fistulas(Kappa=0.752,P<0.001).Significant differences were observed in the blood flow Limberg score(χ^(2)=8.903,P<0.05)and shear wave velocity(t=2.467,P<0.05)between group 2 and 3.Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD(Magnifi-CD)score(r=-0.676,P<0.001),a weak negative correlation with the PDAI score(r=-0.386,P<0.05),and a weak correlation between the Limberg score and the PDAI score(r=0.368,P<0.05).CONCLUSION EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients.It may be the ideal tool to assess PFCD activity objectively for management strategies.展开更多
AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive p...AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P < 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorption, upper GI involvement, perianal disease, and extra- intestinal manifestations. On multiple regression analysis, male gender and ileo-colonic disease were independent factors associated with increased IP. Gender, location, behavior of the disease and upper GI involvement could explain up to 23% of variability in IP (R2 = 0.23). CONCLUSION: IP was increased in 36% of patients with CD. Male gender and an ileo-colonic disease were the independent factors associated with increased IP.展开更多
AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed a...AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnairebased on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn’s disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.展开更多
Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The ai...Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine.Methods:Consecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.The median follow-up was 81 months,and all the data were analyzed in January 2021.The primary outcome was the need for step-up treatment,which included the use of corticosteroids,immunomodulatory,or surgery during admission and follow-up.Data were analyzed using the c2 or Fisher exact test,Spearman test,t-test,and ManneWhitney U test.Results:Totally,65 patients were enrolled,of whom 12(18.5%)needed step-up treatment due to nonresponse to mesalazine.The UCEIS score,MES,and the ulcerative colitis disease activity index(UCDAI)score were significantly higher in patients who had nonresponse to mesalazine(UCEIS score:6.92±0.69 vs.4.45±1.17,p<0.001;MES:2.67±0.49 vs.2.15±0.69,p=0.024;UCDAI score:9.33±1.87 vs.6.70±2.38,p=0.002).In the multivariate analysis,the UCEIS score(OR=25.65,95%CI:3.048 e45.985,p=0.003),UCDAI score(OR=1.605,95%CI:1.144e2.254,p=0.006),and C-reactive protein level(OR=1.056,95%CI:1.006e1.108,p=0.026)were independent risk factors of nonresponse.The area under the ROC curve of UCEIS was 0.95,with a sensitivity of 100%and specificity of 84.6%,a cut-off value of 6,which outperformed the MES with an area under the ROC curve of 0.70.When the UCEIS score≥6,60%of patients eventually needed step-up treatment.Conclusions:The UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine.The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score≥6.展开更多
Capsule endoscopy(CE)is a recently developed diagnostic method for diseases of the small bowel that is non-invasive,safe,and highly tolerable.Its role in patients with inflammatory bowel disease has been widely valida...Capsule endoscopy(CE)is a recently developed diagnostic method for diseases of the small bowel that is non-invasive,safe,and highly tolerable.Its role in patients with inflammatory bowel disease has been widely validated in suspected and established Crohn’s disease(CD)due to its ability to assess superficial lesions not detected by cross-sectional imaging and proximal lesions of the small bowel not evaluable by ileocolonoscopy.Because CE is a highly sensitive but less specific technique,differential diagnoses that can simulate CD must be considered,and its interpretation should be supported by other clinical and laboratory indicators.The use of validated scoring systems to characterize and estimate lesion severity(Lewis score,Capsule Endoscopy Crohn’s Disease Activity Index),as well as the standardization of the language used to define the lesions(Delphi Consensus),have reduced the interobserver variability in CE reading observed in clinical practice,allowing for the optimization of diagnoses and clinical management strategies.The appearance of the panenteric CE,the incorporation of artificial intelligence,magnetically-guided capsules,and tissue biopsies are elements that contribute to CE being a promising,unique diagnostic tool in digestive tract diseases.展开更多
BACKGROUND We have previously demonstrated that the first wave of the coronavirus disease 2019(COVID-19)pandemic caused exacerbations in ulcerative colitis(UC)patients,probably through psychological and physical stres...BACKGROUND We have previously demonstrated that the first wave of the coronavirus disease 2019(COVID-19)pandemic caused exacerbations in ulcerative colitis(UC)patients,probably through psychological and physical stress.However,successive waves of the COVID-19 pandemic continuously followed the first.The effects of this chronic stress on the disease condition in UC patients are of interest.AIM To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave.METHODS Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020,the period of the first wave of the COVID-19 pandemic.In this study,an identical group of 289 UC patients was evaluated using UC-disease activity index(UC-DAI),endoscopic mucosal appearance score,and Matts pathological grade scoring.RESULTS Of the 289 UC patients included in the study in 2020,10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022,making three groups for 2020,2021 and 2022.No significant differences in characteristics were found among the three groups.UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic,but significantly recovered in 2021 and remained stable in 2022.Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022.CONCLUSION Disease activity of UC patients recovered in 2021 and remained stable in 2022,aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.展开更多
Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7...Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.展开更多
AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned t...AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/- 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-kappa B p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 +/- 0.026 vs 0.380 +/- 0.022, 0.492 +/- 0.026 vs 0.355 +/- 0.005, 0.492 +/- 0.026 vs 0.327 +/- 0.015, respectively, P < 0.05 for TLR9; and 0.436 +/- 0.041 vs 0.326 +/- 0.022, 0.436 +/- 0.041 vs 0.293 +/- 0.006, 0.436 +/- 0.041 vs 0.265 +/- 0.017, respectively, P < 0.05 for NF-kappa B p65). CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-kappa B p65 in UC rats. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic technology.METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-...AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic technology.METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis(IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16 S r RNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16 S rR NA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups(P < 0.001) and IPAA groups(P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC(r =-6.591, P < 0.01),was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis.CONCLUSION Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.展开更多
BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the v...BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.展开更多
AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the re...AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.展开更多
BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission an...BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission and patients without inflammatory bowel disease(non-IBD patients)were treated with fistulodesis,a method including curettage of fistula tract,flushing with acetylcysteine and doxycycline,Z-suture of the inner fistula opening,fibrin glue instillation,and Zsuture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks.Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included.The primary end point was fistula healing,defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients,with a total of 22 fistulae.After 24 wk,all fistulae were healed in 4 non-IBD and 2 CD patients(overall 30%)and fistula remained closed until the end of follow-up at 10-25 mo.In a secondary per-fistula analysis,7 out of 22 fistulae(32%)were closed.Perianal disease activity index(PDAI)improved in patients with fistula healing.Low PDAI was associated with favorable outcome(P=0.0013).No serious adverse events were observed.CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure.Overall success rates is at 30%comparable to other similar techniques.A trend for better outcomes in patients with low PDAI needs to be confirmed.展开更多
Background There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease(IBD)in the pediatric population.However,the results are contradictory.Therefore,we have conducte...Background There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease(IBD)in the pediatric population.However,the results are contradictory.Therefore,we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD.Methods We carried out a systematic search in databases from inception until 20 January 2022.We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity,inflammatory factors,and vitamin D and calcium levels in pediatric patients with IBD.Random effects models were used to combine the data.The main outcomes were then analyzed using weight mean difference(WMD)and respective 95%confidence interval(CI).Results Fifteen treatment arms met the eligibility criteria and were included.Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxy vitamin D3[25(OH)D3](pooled WMD of 17.662 ng/mL;CI 9.77-25.46;P<0.001),calcium(pooled WMD of 0.17 mg/dL;CI 0.04-0.30;P=0.009),and inflammatory factors including C-reactive protein(CRP)(pooled WMD of-6.57 mg/L;CI-11.47 to-1.67;P=0.009)and erythrocyte sedimentation rate(ESR)(pooled WMD of-7.94 mm/h;CI-12.65 to-3.22;P=0.001)levels.In addition,this effect was greater for vitamin D levels at doses greater than 2000 IU,and when follow-up duration was more than 12 weeks.Conclusion This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH)D3,calcium,and inflammatory factors in children and adolescents with IBD.展开更多
BACKGROUND With the wide application of immune checkpoint inhibitors(ICIs)in cancer treatment,immune-related adverse events occur frequently,involving almost all organs and systems.The incidence of ICI-associated arth...BACKGROUND With the wide application of immune checkpoint inhibitors(ICIs)in cancer treatment,immune-related adverse events occur frequently,involving almost all organs and systems.The incidence of ICI-associated arthritis(IA)is unknown.In most cases,IA is not serious and non-lethal.Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression.Here,we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma,causing permanent withdrawal of pembrolizumab,but the patient remained in complete remission(CR)20 mo after the development of IA.CASE SUMMARY An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo.He was finally diagnosed with advanced pulmonary adenocarcinoma,with programmed cell death 1 ligand 1 expression of 70%.The patient responded to pembrolizumab treatment and achieved CR,but IA occurred after the 5th cycle of pembrolizumab administration.Although non-steroidal antiinflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed,arthralgia and joint swelling occurred.The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal.Clinical Disease Activity Index(CDAI)score,a traditional measure of arthritis activity,was 43.Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk.The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab.A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR.CONCLUSION This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.展开更多
AIM To summarize the current consensus on the defnition of remission and the endpoints employed in clinical trials.METHODSA bibliogragraphic search was performed from 1946 to 2016 sing online databases （National Libr...AIM To summarize the current consensus on the defnition of remission and the endpoints employed in clinical trials.METHODSA bibliogragraphic search was performed from 1946 to 2016 sing online databases （National Library of Medicine’s PubMed Central Medline, OVID SP MEDLINE, OVID EMBASE, the Cochrane Library and Conference Abstracts） with key words： （“ulcerative colitis”） AND （“ulcerative colitis endoscopic index of severity” OR “UCEIS”） AND （“remission”） as well as （“ulcerative colitis”） AND （“ulcerative colitis disease activity index”） OR “UCDAI” OR “UC disease activity index” OR “Sutherland index”） AND （“remission”）.RESULTSThe search returned 37 and 116 articles for the UCEIS and UCDAI respectively. For the UCEIS, 12 articles were cited in the final analysis of which 9 validation studies have been identified. Despite the UCEIS has been more extensively validated in all three aspects （validity, responsiveness and reliability）, it has been little employed to monitor disease in randomised clinical trials. For the UCDAI, 37 articles were consider-ed for the final analysis. Although the UCDAI is only partially validated, 29 randomised clinical trials were acknowledged to use the UCDAI to determine endpoints and disease remission, though no clear protocol was identifed.CONCLUSIONAlthough the UCEIS has been more widely validated than the UCDAI, it has not been refected in the moni-toring of disease activity in clinical trials. Conversely, the UCDAI has been used in numerous large clinical trials to defne their endpoints and disease remission, however, it is challenging to determine the best possible outcomes due to a lack of homogeneity of the clinical trial protocols. Before determining a gold standard index, international agreement on remission is urgently needed to advance patient care.展开更多
OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucl...OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome formation.METHODS:The UC model was established with male C57BL/6J as the animal model.Bodyweight,Disease Activity Index(DAI),colon length and weight were detected.Furthermore,colonic histology was performed by hematoxylin-eosin(HE)staining.interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),myeloperoxidase(MPO)and superoxide dismutase(SOD)were performed by enzyme-linked immunosorbent assay.Cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS)mRNA expression were conducted by real-time quantitative polymerase chain reaction(RT-qPCR).NF-κB,inhibitor of NF-κBα(iκBα),Phosphorylated inhibitor of NF-κBα(p-iκBα),caspase-1,NLRP3 and Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)protein expression were conducted by Western blotting.RESULTS:Compared with UC model group,Bodyweight was significantly increased in QCS treatment.At the same time,DAI was significantly decreased in QCS treatment.Colon length and weight and colonic histology were significantly improved in QCS treatment.Furthermore,the expression of IL-1β,IL-6,TNF-α,MPO,SOD,COX2,and iN OS were significantly decreased in QCS treatment.Finally,the expression of NF-κB signaling pathway-related proteins NF-κB,iκBα,p-iκBα,and the expression of NLRP3 inflammasome related proteins caspase-1,NLRP3 and ASC were significantly decreased in QCS treatment.CONCLUSION:Traditional Chinese drug QCS could treat UC by inhibiting the NF-κB signaling pathway and NLRP3 inflammasome formation in mice.展开更多
Background：Conventional magnetic resonance imaging （MRI） is the preferred neuroimaging method in the evaluation ofneuropsychiatric systemic lupus erythematosus （NPSLE）.The purpose of this study was to investigate...Background：Conventional magnetic resonance imaging （MRI） is the preferred neuroimaging method in the evaluation ofneuropsychiatric systemic lupus erythematosus （NPSLE）.The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE,to screen for the value of conventional MRI in NPSLE.Methods：A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study.All patients were classified into different groups according to MRI abnormalities.Both clinical and immunological features were compared between MRI abnormal and normal groups.One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index （SLEDAI） score for MRI abnormalities.Multivariate logistic regression analysis investigated the correlation between immunological features,neuropsychiatric manifestations,and MRI abnormalities.Results：Thirty-six NPSLE patients （61%） showed a variety of MRI abnormalities.There were statistically significant differences in SLEDAI scores （P 〈 0.001）,incidence of neurologic disorders （P =0.001）,levels of 24-h proteinuria （P =0.001） and immunoglobulin M （P =0.004）,and incidence of acute confusional state （P =0.002）,cerebrovascular disease （P =0.004）,and seizure disorder （P =0.028） between MRI abnormal and normal groups.In the MRI abnormal group,SLEDAI scores for cerebral atrophy （CA）,cortex involvement,and restricted diffusion （RD） were much higher than in the MRI normal group （P 〈 0.001,P =0.002,P =0.038,respectively）.Statistically significant positive correlations between seizure disorder and cortex involvement （odds ratio [OR] =14.90;95% confidence interval [CI],1.50-151.70;P =0.023） and cerebrovascular disease and infratentorial involvement （OR =10.00;95% CI,1.70-60.00;P =0.012） were found.Conclusions：MRI abnormalities in NPSLE,especially CA,cortex involvement,and RD might be markers of high systemic lupus erythematosus activity.Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.展开更多
The role of interleukin 25 （IL-25） in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 （rIL-25） in the development of dextran sulfate sod...The role of interleukin 25 （IL-25） in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 （rIL-25） in the development of dextran sulfate sodium （DSS）- induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 ＋tg of rIL-25 or PBS. Then disease activity index （DAI）, histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4＋/CD8＋ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS ＋ rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS ＋ rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4＋/CD8＋ T cells between the DSS ＋ rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular ＆ Molecular Immunology. 2008;5（6）：425-431.展开更多
文摘The Crohn＇s disease activity index （CDAI） has been commonly used to assess the effects of treatment with different agents in Crohn＇s disease （CD）. However, these studies may be compromised, if the results compared to a placebo or standard therapy group （in the absence of a placebo） substantially differ from the expected response. In addition, significant concerns have been raised regarding the reliability and validity of the CDAI. Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded, even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD. Finally, many CDAI endpoints are open to subjective interpretation and have the potential for manipulation. This is worrisome as there is the potential for significant financial gain, if the results of a clinical trial appear to provide a positive result. Physicians caring for patients should be concerned about the positive results in clinical trials that are sponsored by industry, even if the trials involve respected centers and the results appear in highly ranked medical journals.
文摘BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.
基金the Major Project of Department of Education of Anhui Province of China,No.2023AH040396.
文摘BACKGROUND Perianal fistulas pose dual challenges to Crohn's disease(CD)patients.Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD.AIM To determine the accuracy of endoanal ultrasound(EUS)and shear wave elastography(SWE)for evaluating perianal fistulizing CD(PFCD)activity.METHODS This was a retrospective cohort study.A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups:Non-anal fistula group(n=23),low-activity perianal fistulas[n=19,perianal disease activity index(PDAI)≤4],high-activity perianal fistulas(n=25,PDAI>4)based on the PDAI.All patients underwent assessments including EUS+SWE,pelvic magnetic resonance[pelvic magnetic resonance imaging(MRI)],C-reactive protein,fecal calprotectin,CD activity index,PDAI.RESULTS The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%,and there was good consistency in the classification of perianal fistulas(Kappa=0.752,P<0.001).Significant differences were observed in the blood flow Limberg score(χ^(2)=8.903,P<0.05)and shear wave velocity(t=2.467,P<0.05)between group 2 and 3.Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD(Magnifi-CD)score(r=-0.676,P<0.001),a weak negative correlation with the PDAI score(r=-0.386,P<0.05),and a weak correlation between the Limberg score and the PDAI score(r=0.368,P<0.05).CONCLUSION EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients.It may be the ideal tool to assess PFCD activity objectively for management strategies.
文摘AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P < 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorption, upper GI involvement, perianal disease, and extra- intestinal manifestations. On multiple regression analysis, male gender and ileo-colonic disease were independent factors associated with increased IP. Gender, location, behavior of the disease and upper GI involvement could explain up to 23% of variability in IP (R2 = 0.23). CONCLUSION: IP was increased in 36% of patients with CD. Male gender and an ileo-colonic disease were the independent factors associated with increased IP.
文摘AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnairebased on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn’s disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.
基金the Natural Science Foundation of Zhejiang Province(LQ21H030010&Q19H030064)Medical Health Science and Technology Project of the Zhejiang Provincial Health Commission(2021417815).
文摘Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine.Methods:Consecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.The median follow-up was 81 months,and all the data were analyzed in January 2021.The primary outcome was the need for step-up treatment,which included the use of corticosteroids,immunomodulatory,or surgery during admission and follow-up.Data were analyzed using the c2 or Fisher exact test,Spearman test,t-test,and ManneWhitney U test.Results:Totally,65 patients were enrolled,of whom 12(18.5%)needed step-up treatment due to nonresponse to mesalazine.The UCEIS score,MES,and the ulcerative colitis disease activity index(UCDAI)score were significantly higher in patients who had nonresponse to mesalazine(UCEIS score:6.92±0.69 vs.4.45±1.17,p<0.001;MES:2.67±0.49 vs.2.15±0.69,p=0.024;UCDAI score:9.33±1.87 vs.6.70±2.38,p=0.002).In the multivariate analysis,the UCEIS score(OR=25.65,95%CI:3.048 e45.985,p=0.003),UCDAI score(OR=1.605,95%CI:1.144e2.254,p=0.006),and C-reactive protein level(OR=1.056,95%CI:1.006e1.108,p=0.026)were independent risk factors of nonresponse.The area under the ROC curve of UCEIS was 0.95,with a sensitivity of 100%and specificity of 84.6%,a cut-off value of 6,which outperformed the MES with an area under the ROC curve of 0.70.When the UCEIS score≥6,60%of patients eventually needed step-up treatment.Conclusions:The UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine.The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score≥6.
文摘Capsule endoscopy(CE)is a recently developed diagnostic method for diseases of the small bowel that is non-invasive,safe,and highly tolerable.Its role in patients with inflammatory bowel disease has been widely validated in suspected and established Crohn’s disease(CD)due to its ability to assess superficial lesions not detected by cross-sectional imaging and proximal lesions of the small bowel not evaluable by ileocolonoscopy.Because CE is a highly sensitive but less specific technique,differential diagnoses that can simulate CD must be considered,and its interpretation should be supported by other clinical and laboratory indicators.The use of validated scoring systems to characterize and estimate lesion severity(Lewis score,Capsule Endoscopy Crohn’s Disease Activity Index),as well as the standardization of the language used to define the lesions(Delphi Consensus),have reduced the interobserver variability in CE reading observed in clinical practice,allowing for the optimization of diagnoses and clinical management strategies.The appearance of the panenteric CE,the incorporation of artificial intelligence,magnetically-guided capsules,and tissue biopsies are elements that contribute to CE being a promising,unique diagnostic tool in digestive tract diseases.
文摘BACKGROUND We have previously demonstrated that the first wave of the coronavirus disease 2019(COVID-19)pandemic caused exacerbations in ulcerative colitis(UC)patients,probably through psychological and physical stress.However,successive waves of the COVID-19 pandemic continuously followed the first.The effects of this chronic stress on the disease condition in UC patients are of interest.AIM To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave.METHODS Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020,the period of the first wave of the COVID-19 pandemic.In this study,an identical group of 289 UC patients was evaluated using UC-disease activity index(UC-DAI),endoscopic mucosal appearance score,and Matts pathological grade scoring.RESULTS Of the 289 UC patients included in the study in 2020,10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022,making three groups for 2020,2021 and 2022.No significant differences in characteristics were found among the three groups.UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic,but significantly recovered in 2021 and remained stable in 2022.Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022.CONCLUSION Disease activity of UC patients recovered in 2021 and remained stable in 2022,aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.
文摘Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.
基金Supported by Scientific and Technological Project of Educational Department of Liaoning Province,China,No.L2011166
文摘AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/- 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-kappa B p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 +/- 0.026 vs 0.380 +/- 0.022, 0.492 +/- 0.026 vs 0.355 +/- 0.005, 0.492 +/- 0.026 vs 0.327 +/- 0.015, respectively, P < 0.05 for TLR9; and 0.436 +/- 0.041 vs 0.326 +/- 0.022, 0.436 +/- 0.041 vs 0.293 +/- 0.006, 0.436 +/- 0.041 vs 0.265 +/- 0.017, respectively, P < 0.05 for NF-kappa B p65). CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-kappa B p65 in UC rats. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
基金Supported by Academician Jie-Shou Li Intestinal Barrier Research Foundation,No.LJS_201008
文摘AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic technology.METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis(IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16 S r RNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16 S rR NA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups(P < 0.001) and IPAA groups(P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC(r =-6.591, P < 0.01),was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis.CONCLUSION Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.
基金Supported by Wenzhou Science and Technology Bureau,No.Y2020296.
文摘BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.
文摘AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.
文摘BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.AIM To challenge and novel minimally invasive treatment options are needed.METHODS Patients with Crohn’s disease(CD)in remission and patients without inflammatory bowel disease(non-IBD patients)were treated with fistulodesis,a method including curettage of fistula tract,flushing with acetylcysteine and doxycycline,Z-suture of the inner fistula opening,fibrin glue instillation,and Zsuture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks.Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included.The primary end point was fistula healing,defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients,with a total of 22 fistulae.After 24 wk,all fistulae were healed in 4 non-IBD and 2 CD patients(overall 30%)and fistula remained closed until the end of follow-up at 10-25 mo.In a secondary per-fistula analysis,7 out of 22 fistulae(32%)were closed.Perianal disease activity index(PDAI)improved in patients with fistula healing.Low PDAI was associated with favorable outcome(P=0.0013).No serious adverse events were observed.CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure.Overall success rates is at 30%comparable to other similar techniques.A trend for better outcomes in patients with low PDAI needs to be confirmed.
基金This research was supported by grant No.1401-1-249-57731 from the Tehran University of Medical Sciences.
文摘Background There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease(IBD)in the pediatric population.However,the results are contradictory.Therefore,we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD.Methods We carried out a systematic search in databases from inception until 20 January 2022.We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity,inflammatory factors,and vitamin D and calcium levels in pediatric patients with IBD.Random effects models were used to combine the data.The main outcomes were then analyzed using weight mean difference(WMD)and respective 95%confidence interval(CI).Results Fifteen treatment arms met the eligibility criteria and were included.Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxy vitamin D3[25(OH)D3](pooled WMD of 17.662 ng/mL;CI 9.77-25.46;P<0.001),calcium(pooled WMD of 0.17 mg/dL;CI 0.04-0.30;P=0.009),and inflammatory factors including C-reactive protein(CRP)(pooled WMD of-6.57 mg/L;CI-11.47 to-1.67;P=0.009)and erythrocyte sedimentation rate(ESR)(pooled WMD of-7.94 mm/h;CI-12.65 to-3.22;P=0.001)levels.In addition,this effect was greater for vitamin D levels at doses greater than 2000 IU,and when follow-up duration was more than 12 weeks.Conclusion This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH)D3,calcium,and inflammatory factors in children and adolescents with IBD.
文摘BACKGROUND With the wide application of immune checkpoint inhibitors(ICIs)in cancer treatment,immune-related adverse events occur frequently,involving almost all organs and systems.The incidence of ICI-associated arthritis(IA)is unknown.In most cases,IA is not serious and non-lethal.Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression.Here,we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma,causing permanent withdrawal of pembrolizumab,but the patient remained in complete remission(CR)20 mo after the development of IA.CASE SUMMARY An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo.He was finally diagnosed with advanced pulmonary adenocarcinoma,with programmed cell death 1 ligand 1 expression of 70%.The patient responded to pembrolizumab treatment and achieved CR,but IA occurred after the 5th cycle of pembrolizumab administration.Although non-steroidal antiinflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed,arthralgia and joint swelling occurred.The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal.Clinical Disease Activity Index(CDAI)score,a traditional measure of arthritis activity,was 43.Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk.The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab.A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR.CONCLUSION This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.
文摘AIM To summarize the current consensus on the defnition of remission and the endpoints employed in clinical trials.METHODSA bibliogragraphic search was performed from 1946 to 2016 sing online databases （National Library of Medicine’s PubMed Central Medline, OVID SP MEDLINE, OVID EMBASE, the Cochrane Library and Conference Abstracts） with key words： （“ulcerative colitis”） AND （“ulcerative colitis endoscopic index of severity” OR “UCEIS”） AND （“remission”） as well as （“ulcerative colitis”） AND （“ulcerative colitis disease activity index”） OR “UCDAI” OR “UC disease activity index” OR “Sutherland index”） AND （“remission”）.RESULTSThe search returned 37 and 116 articles for the UCEIS and UCDAI respectively. For the UCEIS, 12 articles were cited in the final analysis of which 9 validation studies have been identified. Despite the UCEIS has been more extensively validated in all three aspects （validity, responsiveness and reliability）, it has been little employed to monitor disease in randomised clinical trials. For the UCDAI, 37 articles were consider-ed for the final analysis. Although the UCDAI is only partially validated, 29 randomised clinical trials were acknowledged to use the UCDAI to determine endpoints and disease remission, though no clear protocol was identifed.CONCLUSIONAlthough the UCEIS has been more widely validated than the UCDAI, it has not been refected in the moni-toring of disease activity in clinical trials. Conversely, the UCDAI has been used in numerous large clinical trials to defne their endpoints and disease remission, however, it is challenging to determine the best possible outcomes due to a lack of homogeneity of the clinical trial protocols. Before determining a gold standard index, international agreement on remission is urgently needed to advance patient care.
基金Supported by the National Key Research and Development Program(Grant 2018YFC1705403):Clinical Effect Evaluation of Chinese Medicine on Moderately Active Ulcerative ColitisNatural Science Foundation of Tianjin(Grant18JCYBJC26000):Study on the Mechanism of Qingchi San Treating Ulcerative Colitis By Regulating Gut Microflora+1 种基金Scientific Research Program of Tianjin Education Commission(Grant 2017KJ155):based onγδT-NLRP3 Inflammasome-Caspase PathwayQingchi San Regulates Gut Microflora to Treat UC。
文摘OBJECTIVE:To investigate the efficacy of Qingchi San(青赤散,QCS),a preparation of Traditional Chinese Medicine,on ulcerative colitis(UC)in mice by inhibiting the nuclearfactor-kappa B(NF-κB)signaling pathway and nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain-containing 3(NLRP3)inflammasome formation.METHODS:The UC model was established with male C57BL/6J as the animal model.Bodyweight,Disease Activity Index(DAI),colon length and weight were detected.Furthermore,colonic histology was performed by hematoxylin-eosin(HE)staining.interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),myeloperoxidase(MPO)and superoxide dismutase(SOD)were performed by enzyme-linked immunosorbent assay.Cyclooxygenase 2(COX2)and inducible nitric oxide synthase(iNOS)mRNA expression were conducted by real-time quantitative polymerase chain reaction(RT-qPCR).NF-κB,inhibitor of NF-κBα(iκBα),Phosphorylated inhibitor of NF-κBα(p-iκBα),caspase-1,NLRP3 and Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)protein expression were conducted by Western blotting.RESULTS:Compared with UC model group,Bodyweight was significantly increased in QCS treatment.At the same time,DAI was significantly decreased in QCS treatment.Colon length and weight and colonic histology were significantly improved in QCS treatment.Furthermore,the expression of IL-1β,IL-6,TNF-α,MPO,SOD,COX2,and iN OS were significantly decreased in QCS treatment.Finally,the expression of NF-κB signaling pathway-related proteins NF-κB,iκBα,p-iκBα,and the expression of NLRP3 inflammasome related proteins caspase-1,NLRP3 and ASC were significantly decreased in QCS treatment.CONCLUSION:Traditional Chinese drug QCS could treat UC by inhibiting the NF-κB signaling pathway and NLRP3 inflammasome formation in mice.
基金This study was supported by the Provincial Natural Science Foundation of Shandong
文摘Background：Conventional magnetic resonance imaging （MRI） is the preferred neuroimaging method in the evaluation ofneuropsychiatric systemic lupus erythematosus （NPSLE）.The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE,to screen for the value of conventional MRI in NPSLE.Methods：A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study.All patients were classified into different groups according to MRI abnormalities.Both clinical and immunological features were compared between MRI abnormal and normal groups.One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index （SLEDAI） score for MRI abnormalities.Multivariate logistic regression analysis investigated the correlation between immunological features,neuropsychiatric manifestations,and MRI abnormalities.Results：Thirty-six NPSLE patients （61%） showed a variety of MRI abnormalities.There were statistically significant differences in SLEDAI scores （P 〈 0.001）,incidence of neurologic disorders （P =0.001）,levels of 24-h proteinuria （P =0.001） and immunoglobulin M （P =0.004）,and incidence of acute confusional state （P =0.002）,cerebrovascular disease （P =0.004）,and seizure disorder （P =0.028） between MRI abnormal and normal groups.In the MRI abnormal group,SLEDAI scores for cerebral atrophy （CA）,cortex involvement,and restricted diffusion （RD） were much higher than in the MRI normal group （P 〈 0.001,P =0.002,P =0.038,respectively）.Statistically significant positive correlations between seizure disorder and cortex involvement （odds ratio [OR] =14.90;95% confidence interval [CI],1.50-151.70;P =0.023） and cerebrovascular disease and infratentorial involvement （OR =10.00;95% CI,1.70-60.00;P =0.012） were found.Conclusions：MRI abnormalities in NPSLE,especially CA,cortex involvement,and RD might be markers of high systemic lupus erythematosus activity.Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.
基金supported by a grant from the Natural Science Foundation of Liaoning province, China (No. 20072101)
文摘The role of interleukin 25 （IL-25） in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 （rIL-25） in the development of dextran sulfate sodium （DSS）- induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 ＋tg of rIL-25 or PBS. Then disease activity index （DAI）, histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4＋/CD8＋ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS ＋ rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS ＋ rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4＋/CD8＋ T cells between the DSS ＋ rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular ＆ Molecular Immunology. 2008;5（6）：425-431.
