Impact of timing of primary ileocecal resection on prognosis in patients with Crohn's disease.

BACKGROUND: The advantage of early ileocecal resection after Crohn's disease diagnosis is a matter of debate. This study aims to assess the timing of ileocecal resection on prognosis, after correction for possible confounders. METHODS: Patients with Crohn's disease with primary ileocecal resection between 2000 and 2019 were included in a retrospective multicentre cohort. The primary endpoint was endoscopic recurrence (Rutgeerts score ≥i2b) within 18 months. Secondary endpoints were escalation of inflammatory bowel disease medication within 18 months and re-resection during follow-up. The association between timing of ileocecal resection and these endpoints was investigated using multivariable proportional hazard models, corrected for covariates including Montreal classification, postoperative prophylaxis, smoking, indication for surgery, medication before ileocecal resection, perianal fistulas, surgical approach, histology, length of resected segment and calendar year. RESULTS: In 822 patients ileocecal resection was performed after a median of 3.1 years (i.q.r. 0.7-8.0) after Crohn's disease diagnosis. The lowest incidence of endoscopic recurrence, escalation of inflammatory bowel disease medication and re-resection was observed for patients undergoing ileocecal resection shortly after diagnosis (0-1 months). After correction for covariates, patients with ileocecal resection at 0, 4 and 12 months after diagnosis had a cumulative incidence of 35 per cent, 48 per cent and 39 per cent for endoscopic recurrence, 20 per cent, 29 per cent and 28 per cent for escalation of inflammatory bowel disease medication and 20 per cent, 30 per cent and 34 per cent for re-resection, respectively. In the multivariable model ileocolonic disease (HR 1.39 (95 per cent c.i. 1.05 to 1.86)), microscopic inflammation of proximal and distal resection margins (HR 2.20 (95 per cent c.i. 1.21 to 3.87)) and postoperative prophylactic biological and immunomodulator (HR 0.16 (95 per cent c.i. 0.05 to 0.43)) were associated with endoscopic recurrence. CONCLUSION: The timing of ileocecal resection was not associated with a change of disease course; in the multivariable model, the postoperative recurrence was not affected by timing of ileocecal resection.

A genderful research world: rapid review, design, and pilot study of an interactive platform for curated sex and gender health research resources.

BACKGROUND: Integration of sex and gender into health research is best practice for designing and conducting equitable, rigorous scientific research. Many evidence-based resources exist to support researchers in this endeavour, but such resources often remain underutilized as they are difficult to find, are not publicly accessible, or are specific to a particular research phase, context, or population. The development and evaluation of a repository of resources was deemed important to create an accessible platform for promoting sex- and gender-integration in health research. METHODS: A rapid review was conducted of critical resources for conducting sex and gender health research. These were integrated into a prototype website design (the Genderful Research World; GRW) that provided an interactive digital landscape for researchers to access these resources. A pilot study evaluated the GRW website for applicability, desirability, and usability with an international sample of 31 health researchers from various disciplines and career stages. Quantitative data from the pilot study was summarized with descriptive statistics. Qualitative data was summarized narratively and used to identify concrete elements for improvement in a second design iteration. RESULTS: Results of the pilot study revealed that the GRW was considered user friendly and desirable by health researchers and helped them access relevant information. Feedback suggested that providing these resources in a playful way may enhance the experience of the user, particularly given the high 'desirability' scores and that users emphasized the interactive layout as being key to their intention to integrate it into their teaching endeavors. Key feedback from the pilot study (e.g., addition of resources specific to research with transgender populations, revision of website layout) was integrated into the current version of the website: www.genderfulresearchworld.com . CONCLUSIONS: The present research suggests a utility for a repository of resources for integrating sex and gender considerations into research, and that providing a logical, intuitive means of cataloguing and navigating such resources is critical for usability. The results of this study may inform the development of other novel researcher-directed resource curation efforts to address health equity issues and encourage and support health researchers to integrate a sex and gender perspective in their work.

Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population.

AIMS: Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We compared cardiovascular disease (CVD) risk factors and 10-year risk in IBD patients to the general population. METHODS AND RESULTS: In this cross-sectional study, consecutive IBD patients ≥45 years were included. History of ASCVD and CVD risk factors (smoking, hypertension, overweight, hypercholesterolaemia, diabetes, and metabolic syndrome) were assessed. The Systematic COronary Risk Evaluation (SCORE2) algorithm was used to estimate 10-year CVD risk. One to four age/sex-matched controls were derived from the prospective population-based Rotterdam Study cohort. In total, 235 IBD patients were included {56% women, median age 59 years [interquartile range (IQR) 51-66]} and matched to 829 controls [56% women, median age 61 years (IQR 56-67)]. Inflammatory bowel disease patients experienced ASCVD events more often compared with matched controls [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.23-3.27], specifically heart failure (OR 2.02, 95% CI 1.02-4.01) and coronary heart disease (OR 2.01, 95% CI 1.7-3.13). Inflammatory bowel disease patients showed lower odds of overweight (OR 0.48, 95% CI 0.35-0.66) and hypercholesterolaemia (OR 0.45, 95% CI 0.31-0.65) and higher odds of hypertension (OR 1.67, 95% CI 1.19-2.32), as well as higher waist circumference (+4 cm, P = 0.006) and triglyceride levels (+0.6 mmol/L, P < 0.001) as compared with controls. Mean 10-year CVD risk was 4.0% [standard deviation (SD) ±2.6] in 135 IBD patients vs. 6.0% (SD ±1.6) in 506 controls. CONCLUSION: The increased CVD risk in IBD is discrepant with the 10-year CVD risk estimate. Systematic COronary Risk Evaluation may underestimate CVD risk in IBD patients due to differing CVD risk profiles compared with the general population, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of hypertension, abdominal obesity, and hypertriglyceridaemia.

The unfavourable CVD risk profiles in IBD patients compared with the general population are discrepant with the calculated 10-year CVD risk with the SCORE2 algorithm. Cardiovascular disease risk profiles in IBD patients differ from age/sex-matched controls, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of CVD history, hypertension, abdominal obesity, and hypertriglyceridaemia.Systematic COronary Risk Evaluation was comparable between IBD patients and controls; however, the proportion of patients with 10-year CVD risk above the treatment threshold was lower among IBD patients.

Lipid Changes After Induction Therapy in Patients with Inflammatory Bowel Disease: Effect of Different Drug Classes and Inflammation.

BACKGROUND: Dyslipidemia may be an important modifiable risk factor contributing to the increased cardiovascular risk in inflammatory bowel disease (IBD). The lipid metabolism is subject to both systemic inflammation and drug therapy; however, it is unclear if this effect is drug-class dependent. Our aim was to assess lipid changes after IBD induction therapy and evaluate associated factors with a particular focus on drug class and disease activity. METHODS: In this prospective study, consecutive IBD patients starting systemic therapy (eg, corticosteroids, thiopurines, methotrexate, anti-TNF-α agents, vedolizumab, ustekinumab, and tofacitinib) were included. Primary outcomes were changes in total cholesterol, high density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides at week 10. RESULTS: One hundred ninety-eight IBD patients (107 women [54%], median age 36 years; interquartile range [IQR], 27-47) were included: 137 Crohn's disease (67%), 61 ulcerative colitis (29%), and 8 IBD-unclassified (4%). Median C-reactive protein and fecal calprotectin at baseline were 5.1 mg/L (IQR, 1.6-12.0) and 1040 ug/g (IQR, 383-1800), respectively. Relative increases in total cholesterol, HDL-c, and LDL-c were significant after prednisone (+26%, +31%, +12%) and tofacitinib therapy (+20%, +25%, +26%), respectively. Results remained after adjusting for concomitant corticosteroids, cholestyramine, and PSC diagnosis. Changes in clinical scores were inversely correlated with total cholesterol changes (R -186, P = .014), as was CRP with total cholesterol and LDL-c (R -0.292 and R -0.259, P < .001). No correlation was found with FCP. Lipid changes remained after adjusting for age and CRP. CONCLUSIONS: Prednisone and tofacitinib induction therapy significantly increase serum lipid levels, whereas no changes were observed in other drug classes. The observations seem drug-specific inasmuch as adjustment for systemic inflammation did not alter the results.

Prednisone and tofacitinib induction therapy increase lipid levels, whereas no changes are observed for immunomodulators and newer biologics. The observations seem drug-specific on top of control of inflammation. Studies on long-term consequences of IBD drug-induced lipid changes are required.

Systematic review with meta-analysis: effect of inflammatory bowel disease therapy on lipid levels.

BACKGROUND: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes. AIM: To precisely assess the effect of different IBD drug classes on lipid profiles METHODS: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (≤10 weeks) and maintenance (>10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models. RESULTS: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95 ] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNFα treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes. CONCLUSIONS: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNFα agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: epidemiology, pathogenesis and clinical management.

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry.

BACKGROUND: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). AIM: To evaluate effectiveness, safety and use of tofacitinib in daily practice. METHODS: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. RESULTS: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. CONCLUSION: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.