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Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.
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Objective To evaluate the role of infliximab trough levels(IFX-TL)and C reactive protein(CRP)concentration in prediction secondary loss of response(LOR)to infliximab(IFX)in patients with Crohn′s disease(CD)during IFX maintenance therapy since 14 weeks after induced treatment.Methods From November 2015 to October 2016,43 CD patients received IFX treatment were enrolled.IFX was initially given at zero,two,and six weeks at 5 mg/kg as induced therapy,and then the same dose was given every eight weeks as long-term maintenance treatment.Serum IFX-TL and CRP concentration were measured at 14thweek after the first IFX injection.The disease activity of CD was assessed by the Harvey-Braddshaw index.According to the follow-up results,the enrolled patients were divided into LOR group and continuous response group,and then the differences in IFX-TL and CRP concentrations at the 14thweek after induced therapy were compared between two groups.Mann-Whitney U test and receiver operating characteristic(ROC)curve were performed for statistical analysis.Results After a median 54 weeks of follow-up,18(41.9%)of 43 CD patients achieved a sustained response to IFX therapy,while 11 patients(25.6%)were LOR to IFX therapy.At the 14thweek after induced therapy,serum IFX-TL of LOR group was 2.30 μg/mL(0.52 μg/mL,2.92 μg/mL),which was lower than that of continuous response group(5.10 μg/mL(3.54 μg/mL,9.34 μg/mL)),and the difference was statistically significant(Z= -3.236,P=0.001).The CRP concentration of LOR group was 3.10 mg/L (0.38 mg/L,21.70 mg/L),which was higher than that of continuous response group(0.51 mg/L(0.27 mg/L, 1.50 mg/L)),and the difference was statistically significant(Z= -1.732,P=0.015).The results of ROC curve analysis indicated that at 14thweek after induced therapy the area under curve(AUC)value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864(95% confidence interval(CI)0.728 to 0.999),sensitivities were 83.3% and 81.8%,specificities were 94.4% and 54.5%,cut-off values of accuracies were 3.115 μg/mL and 5.93 mg/L.Conclusion IFX-TL<3.115 μg/mL and CRP concentration>5.93 mg/L at 14thweek since IFX induced therapy might be used as effective predictors of LOR in CD patients during maintenance therapy.
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Background:With the extensive use of infliximab (IFX)in treatment of patients with Crohn's disease (CD),some of the patients had losing of response to IFX treatment. The specific mechanism is not clear yet,and may be related to the formation of antibodies to infliximab (ATI). However,there is no report on the positivity rate of ATI in China so far. Aims:To investigate the clinical effects of serum IFX trough levels (IFX-TLs)and ATI in CD patients treated with IFX. Methods:A total of 76 CD patients receiving IFX treatment from Jan. 2016 to Mar. 2017 at Shanghai Renji Hospital were enrolled. Serum IFX-TLs and ATI were detected. CD patients were divided into active stage group and remission group according to CDAI score,and serum IFX-TLs,ATI,C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR) levels were analyzed. Results:Of the 76 patients with CD,positive ATI was found in 2 patients (2. 6%). Forty-five (59. 2%)patients were in remission,while 31 (40. 8%)in active stage. No significant differences in IFX-TLs [2. 84 (1. 30,4. 96)μg/ mL vs. 4. 08 (1. 29,6. 72)μg/ mL,P =0. 484],ATI [8. 00 (5. 27,14. 89)ng/ mL vs. 7. 00 (4. 40, 25. 00)ng/ mL,P = 0. 454]were found between active CD and remission CD. Serum CRP,ESR levels were significantly increased in active CD than in remission CD (P = 0. 038,P = 0. 009). Logistic regression analysis showed that activity of CD was related to CRP (OR = 6. 082,95% CI:1. 348-27. 436,P = 0. 019),but not related to IFX-TLs,ATI and ESR (P > 0. 05). Conclusions:The activity of CD may be correlated with CRP,but not with IFX-TLs,ATI and ESR.
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Background:Reactivation of hepatitis B virus (HBV)in the context of immunosuppressive therapy is serious. Biological agents are known having the effect to increase the risk of HBV reactivation in patients with inflammatory bowel disease (IBD)who are seropositive for HBsAg and/ or HBcAb. Aims:To study the HBV reactivation in IBD patients with HBV infection who are treated with infliximab (IFX)in China. Methods:A retrospective study was conducted between March 2014 and March 2017 in Shanghai Renji Hospital. Consecutive IBD patients who were seropositive for HBcAb and treated with IFX were enrolled. The clinical and follow-up data were analyzed and the changes in viral replication and liver function were recorded. Results:Of the 194 IBD patients treated with IFX,28 had active or prior HBV infection. The overall prevalence of HBV infection was 14. 4%,and that of active infection was 4. 6% . The mean number of IFX treatment course was 6. 96 ± 3. 47,and the mean follow-up period was (15. 32 ± 10. 47)months. Fifteen patients (53. 6%)received prophylactic antiviral treatment,one with lamivudine and 14 with entecavir. Ten patients (35. 7%) received synergistic treatment with immunosuppressants,of which,one (10. 0%)with active HVB infection (HBsAg positive and HBV-DNA negative)suffered HBV reactivation. In this reactivation case,lamivudine antiviral prophylaxis was used initially and the reactivation was resolved when entecavir was used instead of lamivudine. Conclusions:IBD patients receiving IFX treatment should be screened for HBV infection. In patients who are seropositive for HBsAg and/ or HBcAb, prophylactic antiviral agents with low resistance rate is recommended for preventing HBV reactivation when IFX and immunosuppressants are synergistically used.
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Background:Reactivation of hepatitis B virus (HBV)in the context of immunosuppressive therapy is serious. Biological agents are known having the effect to increase the risk of HBV reactivation in patients with inflammatory bowel disease (IBD)who are seropositive for HBsAg and/ or HBcAb. Aims:To study the HBV reactivation in IBD patients with HBV infection who are treated with infliximab (IFX)in China. Methods:A retrospective study was conducted between March 2014 and March 2017 in Shanghai Renji Hospital. Consecutive IBD patients who were seropositive for HBcAb and treated with IFX were enrolled. The clinical and follow-up data were analyzed and the changes in viral replication and liver function were recorded. Results:Of the 194 IBD patients treated with IFX,28 had active or prior HBV infection. The overall prevalence of HBV infection was 14. 4%,and that of active infection was 4. 6% . The mean number of IFX treatment course was 6. 96 ± 3. 47,and the mean follow-up period was (15. 32 ± 10. 47)months. Fifteen patients (53. 6%)received prophylactic antiviral treatment,one with lamivudine and 14 with entecavir. Ten patients (35. 7%) received synergistic treatment with immunosuppressants,of which,one (10. 0%)with active HVB infection (HBsAg positive and HBV-DNA negative)suffered HBV reactivation. In this reactivation case,lamivudine antiviral prophylaxis was used initially and the reactivation was resolved when entecavir was used instead of lamivudine. Conclusions:IBD patients receiving IFX treatment should be screened for HBV infection. In patients who are seropositive for HBsAg and/ or HBcAb, prophylactic antiviral agents with low resistance rate is recommended for preventing HBV reactivation when IFX and immunosuppressants are synergistically used.
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Objective To evaluate the impact of total parenteral nutrition(TPN)on nutrition status and inflammatory markers in hospitalized fasted patients with inflammatory bowel disease(IBD).Methods A retrospective study was performed and 82 hospitalized fasted IBD patients [male/female=58/24,(39.4±14.5)years] who received TPN entered the study.Among them,38 patients had ulcerative colitis(UC)and 44 patients suffered from Crohn`s disease(CD).Clinical data(gender,age,duration of disease,history of disease,prednisone,immuno-suppressor,and antibiotics)were obtained from medical records.Nutritional parameters,C-creative protein(CRP),and erythrocyte sedimentation rate(ESR)before and after TPN were also obtained.Average caloric supplementation by TPN was(4 437.3±1 199.1)kJ/d and the nitrogen amount was(9.9±1.7)g/d.Median PN length was 15 days(7-54 days).67 IBD patients received a TPN formula with glutamine(≥14 d,25 patients vs.0-14 d,42 patients)and 15 IBD subjects received TPN without glutamine.Malnutrition was diagnosed by body mass index(BMI)and serum albumin level.Results The prevalence of undernutrition was 90.2％(74/82)in the study population.CD patients had a significantly longer history of disease [84(3-288)months vs.24(1-324)months,P<0.001] and a significantly lower BMI [(15.6±1.8)kg/m2 vs.(19.1±3.5)kg/m2,P<0.001] compared with those in UC patients.TPN improved nutritional parameters [serum albumin:(28.7±6.6)g/L before TPN vs.(31.7±5.8)g/L after TPN,P<0.001;pre-albumin:(174.1±85.5)mg/L before TPN vs.(227.2±82.8)mg/L after TPN,P<0.001].Conclusions TPN improves nutritional status in hospitalized fasted IBD patients.However,prospective randomized controlled trials are required to estimate the role of low-to-middle dosage of glutamine in IBD patients.
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Assessment mode is a bottleneck in medical education reform nowadays.Although traditional assessment tools,such as written examination,are still widely used in medical education assessments,they have obvious limitations.With the enhancement of requirements in physicians' abilities,assessments on some basic abilities of physicians are still insufficient.The United States and Europe not only focus on the curriculum reform but also the development of appropriate assessment tools,therefore,some new assessment tools are invented.These assessment tools are applicable to the formative assessment and are student-centered,being able to promote the development of education and provide new options for medical education assessments.
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Objective To analyze the consistency of transcutaneous perianal ultrasonography (TPUS) and pelvic magnetic resonance imaging (MRI) in diagnosing perianal lesions of Crohn's disease (CD), and to evaluate the value of transcutaneous perianal ultrasonography in detecting perianal lesions of CD. Methods A cohort of 102 patients diagnosed as Corhn's disease were enrolled from August 2008 to August 2010. Perianal abscess and fistula of these CD patients was diagnosed by ultrasonography and MRI system. Statistics was performed with SPSS 11.5 software for X2 test. The consistency was analyzed with Kappa test. Results The mean onset time of perianal lesions in CD was -0.443 year (95％CI:-1.659～0.773 year) before typical symptoms showed up. There was no significant difference in detecting perianal lesions of CD between transcutaneous perianal ultrasonography and pelvic magnetic resonance imaging (P ＝ 0.706, Kappa ＝ 0.541). If pelvic magnetic resonance imaging was considered as the golden standard in detecting perianal lesions of CD,the sensitivity (Sen), specificity (Spe), Youden's index, positive predictive value (PPV) and negative predictive value (NPV) of TPUS were 72.73％, 82.61％, 0.55, 66.67％ and 86.36％ respectively.Furthermore, there was no significant difference between transcutaneous perianal ultrasonography and pelvic magnetic resonance imaging in detecting perianal abscess ( P ＝ 0.706, Kappa ＝ 0.496) and fistula (P＝0.655, Kappa＝0.546) of CD. Conclusions Perianal lesions occur in the entire course of CD. There was favorable consistency between transcutaneous perianal ultrasonography and pelvic magnetic resonance imaging in detecting perianal abscess and fistula of CD. Transcutaneous perianal ultrasonography can be used as an additional method in detecting and evaluting perianal lesions of CD.
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Objective To investigate the expression of CD40-CD154 co-stimulatory pathway in peripheral circulation and intestinal mucosa in patients with inflammatory bowel disease (IBD),the difference between the expression of CD40-CD154 in patients with IBD and that in healthy controls,and the correlation between CD40-CD154 levels and disease activity. Methods A total of 62 patients with Crohn's disease (CD),64 patients with ulcerative colitis (UC) and 56 healthy controls were enrolled. Enzyme-Linked Immuno Sorbent Assay (ELISA),SYBR-green real time PCR and immunohistochemical assay were respectively applied to evaluate expression of CD40-CD154 in plasma,mononuclear cells of peripheral blood and intestinal mucosa. Results Levels of CD40 (P=0. 000) and CD154 (P=0. 001) in plasma,mononuclear cells of peripheral blood and intestinal mucosa were significantly higher in patients with CD and UC than in healthy controls. However,no correlation between disease activity and CD40-CD154 expression in peripheral circulation or intestinal mucosa was detected (P ＞ 0. 05 ). Conclusion CD40-CD154 pathway activation is found in plasma,peripheral blood mononuclear cells and intestinal mucosa in patients with IBD,but is not correlated with disease activity.
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Objective To investigate the expression of CD27-CD70 co-stimulatory pathway in peripheral circulation and intestinal mucosa of patients with inflammatory bowel disease, and to find the difference between the expression of CD27-CD70 in patients with inflammatory bowel disease and in healthy controls. Methods A total of 62 patients with Crohn's disease, 64 patients with ulcerative colitis and 56 healthy controls were enrolled. Enzyme-linked immunosorbent assay was applied to evaluate plasma CD27-CD70 protein expression in patients with inflammatory bowel disease and healthy controls. SYBR-green real time PCR was applied to access CD27-CD70 mRNA expression in peripheral blood mononuclear cells in patients with inflammatory bowel disease and healthy controls.And CD27-CD70 protein expression in intestinal mucosa was determined by immunohitochemistry.Results Plasma levels of CD27 (P=0. 025) and CD70 (P=0. 000) were significantly higher in patients with Crohn's disease than in healthy controls. However, CD27 (r= 0. 055, P= 0. 673) and CD70 (r= 0. 024, P = 0. 852) were not significantly associated with endoscopic disease activity in patients with Crohn's disease. Similarly, CD27 (P=0. 001) and CD70 (P=0. 000) were significantly higher in patients with ulcerative colitis than in healthy controls. And CD27 (r=0. 077, P=0. 547)and CDT0 (r=0.021, P=0. 869) were not significantly associated with endoscopic disease activity in patients with ulcerative colitis. Moreover, CD27 and CD70 mRNA expression in peripheral blood mononuclear cells were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000), and immunostaining indicated that CD27 and CD70 expression in intestinal mucosa were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000). Conclusions CD27-CD70 pathway activated in plasma, peripheral blood mononuclear cells and intestinal mucosa of patients with inflammatory bowel disease. However,plasma levels of CD27 and CD70 can not reflect endoscopic disease activity.