Recent advances in cytokines:Therapeutic implications for inflammatory bowel diseases

Inflammatory bowel diseases(IBDs) are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems.Cytokines are essential mediators between activated immune and non-immune cells,including epithelial and mesenchymal cells.They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells.The physiology of IBD is becoming a very attractive field of research for development of new therapeutic agents.These include cytokines involved in intestinal immune inflammation.This review will focus on mechanisms of action of cytokines involved in IBD and new therapeutic opportunities for these diseases.

Interendoscopist variability in proximal colon polyp detection is twice higher for serrated polyps than adenomas

AIM To assess the interendoscopist variability in the detection of colorectal polyps according to their location and histological type.METHODS This study was a retrospective analysis of prospectively collected data from a regional colorectal cancer(CRC) screening program; 2979 complete colonoscopies from 18 endoscopists were included. Variability in performance between endoscopists for detection of at least one adenoma(A), one proximal adenoma(PA), one distal adenoma(DA), and one proximal serrated polyp(PSP) was assessed by using multilevel logistic regression models.RESULTS The observed detection rates among the 18 endoscopists ranged from 24.6% to 47.6%(mean = 35.7%) for A, from 19.1% to 39.0%(mean = 29.4%) for DA, from 6.0% to 22.9%(mean = 12.4%) for PA, and from 1.3% to 19.3%(mean = 6.9%) for PSP.After adjusting for patient-level variables(sex, age), the interendoscopist detection rates variability achieved a significant level for A, PA, and PSP but not for DA(P = 0.03, P = 0.02, P = 0.02 and P = 0.08, respectively). This heterogeneity, as measured by the variance partition coefficient, was approximately threefold higher for PA(6.6%) compared with A(2.1%), and twofold higher for PSP(12.3%) compared with PA.CONCLUSION These results demonstrate significant interendoscopist variability for proximal polyp particularly for serrated p o l y p s, b u t n o t f o r d i s t a l a d e n o m a d e t e c t i o n. These findings contribute to explain the decreased effectiveness of complete colonoscopies at preventing proximal CRCs and the need to carefully assess the proximal colon during scope procedure.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

BACKGROUND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" strategies.AIM To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52.METHODS CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled.RESULTS Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12(P = 0.012), CRP level < 2.9 mg/L at W12(P = 0.001) and Fcal improvement at W12(Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal(< 100 μg/g)(P = 0.001) were predictive of CFREM at W52. Combined endpoint(CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3(0.36-237.1); P = 0.145]and CRP < 2.9 mg/L(0.77-278.0; P = 0.073).CONCLUSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

Relationship between clinical remission of perianal fistulas in Crohn’s disease and serum adalimumab concentrations:A multicenter cross-sectional study

BACKGROUND Crohn’s disease(CD)is complicated by perianal fistulas in approximately 20%of patients.Achieving permanent fistula closure remains a challenge for physicians.An association between serum anti-tumor necrosis factor-αconcentrations and clinical outcomes in patients with CD has been demonstrated;however,little information is available on serum adalimumab(ADA)concentrations and remission of perianal fistulas in such patients.AIM To study the relationship between serum ADA concentrations and clinical remission of CDassociated perianal fistulas.METHODS This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018.At the time of each serum ADA concentration measurement,we collected information about the patients and their fistulas.The primary study endpoint was clinical remission of fistulas defined as the absence of drainage(in accordance with Present’s criteria),with a PDAI≤4,absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center.We also assessed fistula healing[defined as being in clinical and radiological(magnetic resonance imaging,MRI)remission]and adverse events.RESULTS The study cohort comprised 34 patients who underwent 56 evaluations(patients had between one and four evaluations).Fifteen patients had clinical remissions(44%),four of whom had healed fistulas on MRI.Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not[14(10-16)vs 10(2-15)μg/mL,P=0.01].Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas[11(7-14)vs 10(4-16)μg/mL,P=0.69].The adverse event rate did not differ between different serum ADA concentrations.CONCLUSION We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.