There is evidence that inflammatory bowel diseases(IBD)combine both inflammation and coagulation in their pathogenesis and clinical manifestations.Although platelets(PLT)are well known for their role ...in hemo stasis,there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions.IBD are associated with several alterations of PLT,including number shape,and function,and these abnormalities are main ly attributed to the highly activated state of circulating PLT in IBD patients.When PLT activate,they increase in size,release a great variety of bio-active inflamma tory and procoagulant molecules/particles,and express a variety of inflammatory receptors.These inflamma tory products may represent a part of the missing link between coagulation and inflammation,and can be considered as possible IBD pathogenesis instigators.In clinical practice,thrombocytosis is associated both with disease activity and iron deficiency anemia.Controlling inflammation and iron replacement in anemic patient usually leads to a normalization of PLT count.The aim of this review is to update the role of PLT in IBD and present recent data revealing the possible therapeutic implications of anti-PLT agents in future IBD remedies.
Background & Aims Adalimumab is an efficacious therapy for active Crohn's disease, but long-term data are scarce. We conducted an observational study to assess the long-term clinical benefit of ...adalimumab in patients who failed to respond to infliximab, specifically focusing on the influence of trough serum concentration and antibodies against adalimumab on clinical outcome. Methods A total of 168 patients with Crohn's disease treated with adalimumab in a tertiary center were included in a prospective follow-up program. Trough serum concentration and antibodies against adalimumab were measured at predefined time points using enzyme-linked immunosorbent assays. Results A total of 71% and 67% of patients responded by weeks 4 and 12, respectively; among them, 61.5% demonstrated sustained clinical benefit until the end of follow-up (median interquartile range, 20.4 11.7–30.0 months). Of the 156 patients receiving maintenance therapy, 102 (65.4%) had to step up to 40 mg weekly and 60 (38.5%) eventually stopped adalimumab therapy mainly due to loss of response. Significantly lower adalimumab trough serum concentrations were measured throughout the follow-up period in patients who discontinued therapy as compared with patients who stayed on adalimumab. Antibodies against adalimumab were present in 9.2% of the patients and affected trough serum concentration. Serious adverse events occurred in 12% of the patients. Conclusions Introduction of adalimumab after failure of infliximab therapy resulted in a sustained clinical benefit in two thirds of patients during a median follow-up period of almost 2 years. Discontinuation was directly related to low adalimumab trough serum concentration, which was observed more frequently in patients who developed antibodies against adalimumab.
Cold snare polypectomy is an established method for the resection of small colorectal polyps; however, significant incomplete resection rates still leave room for improvement. We aimed to assess the ...efficacy of cold snare endoscopic mucosal resection (CS-EMR), compared with hot snare endoscopic mucosal resection (HS-EMR), for nonpedunculated polyps sized 6 - 10 mm.
This study was a dual-center, randomized, noninferiority trial. Consecutive adult patients with at least one nonpedunculated polyp sized 6 - 10 mm were enrolled. Eligible polyps were randomized (1:1) to be treated with either CS-EMR or HS-EMR. Both methods involved submucosal injection of a methylene blue-tinted normal saline solution. The primary noninferiority end point was histological eradication evaluated by postpolypectomy biopsies (noninferiority margin - 10 %). Secondary outcomes included occurrence of intraprocedural bleeding, clinically significant postprocedural bleeding, and perforation.
Among 689 patients screened, 155 patients with 164 eligible polyps were included (CS-EMR n = 83, HS-EMR n = 81). The overall rate of histological complete resection was 92.8 % in the CS-EMR group and 96.3 % in the HS-EMR group (difference 3.5 %; 95 % confidence interval CI - 4.15 to 11.56), showing noninferiority of CS-EMR compared with HS-EMR. CS-EMR was shown to be noninferior both for polyps measuring 6 - 7 mm (CS-EMR 93.3 %; HS-EMR 100 %; 95 %CI - 7.95 to 21.3) and those of 8 - 10 mm (92.5 % vs. 94.7 %, respectively; 95 %CI - 7.91 to 13.16). Rates of intraprocedural bleeding were similar between the two groups (CS-EMR 3.6 %, HS-EMR 1.2 %;
= 0.30). No clinically significant postprocedural bleeding or perforation occurred in either group.
CS-EMR appears to be a valuable modification of the standard cold snare technique, obviating the need to use diathermy for nonpedunculated colorectal polyps sized 6 - 10 mm.
Background
Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety ...within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy.
Aims
We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes.
Methods
Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response.
Results
We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes.
Conclusions
Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.
Patients with ulcerative proctitis represent a sub-group of ulcerative colitis patients with specific characteristics. Disease-related symptoms, endoscopic findings and patient's personality ...perspectives create a difficult-to-assess condition in certain cases.
To summarize available evidence on the management of refractory ulcerative proctitis and provide insights in treatment options.
/Conclusion: Topical therapy plays a central role due to the location of the disease. However, well-established treatment options may become exhausted in a considerable proportion of ulcerative proctitis patients, indicating the need to advance to more potent therapies in order to induce and maintain clinical response and remission in these refractory cases. Systemic corticosteroids, thiopurines, calcineurin inhibitors, biologic agents and small molecules have all been tested with variable success rates. Investigational interventions as well as surgical procedures are kept as the ultimate resort in multi-treatment resistant cases. Identifying early prognostic factors that herald a disabling disease progression will help in optimizing treatment and avoiding surgery.
The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and ...loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways.
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