Inflammatory Intestinal Diseases最新文献

Introduction and objective: Despite the known benefits of physical activity in the management of chronic diseases, the use of exercise as a treatment is relatively underemployed, with many patients reporting their disease to be a barrier. This study aimed to assess physical activity levels, attitudes, and barriers towards exercise in a cohort of patients with inflammatory bowel disease (IBD). In addition, this study aimed to assess possible relationships between physical well-being, psychological well-being, and sociodemographic factors.

Methods: 306 patients >18 years with diagnosed IBD in Dunedin, New Zealand, were approached to participate in this study. Participants who consented completed questionnaires regarding exercise preferences and attitudes, physical activity levels, and psychological well-being.

Results: Seventy-seven patients participated in the study (77/308 = 25%). Sixty-six percent of participants met physical activity guidelines and the median metabolic equivalent minutes/week of 1,027.5 (505.5-2,339.5). Walking was the most preferred activity (30%) followed by water-based exercise (20%). Two-thirds of participants reported their disease limited the amount of physical activity undertaken. Common barriers to participating in physical activity included fatigue (34%) and abdominal pain (20%). Patients with active disease reported higher levels of barriers than those in remission (80 vs. 54%, p = 0.018). Higher physical activity levels were correlated with lower levels of fatigue (p = 0.022-0.046).

Conclusions: While patients with IBD in Dunedin, New Zealand, are physically active, reducing real and perceived barriers is crucial to further increase physical activity in patients with IBD who are in remission or with active disease.

Background: Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints.

Method: Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated.

Results: After RYGB, median calprotectin levels are significantly higher (>188, 104-415 μg/g) than before surgery (40, 19-78 μg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) μg/g before, and >5.9 (1.8-13.6) μg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) μg/g before and <0.23 (0.06-0.33) μg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values.

Conclusion: Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.

Introduction: Intestinal fibrosis, characterized by excessive deposition of extracellular matrix proteins, is a common and severe clinical complication of inflammatory bowel disease (IBD). However, the mechanisms underlying fibrosis remain elusive, and currently, there are limited effective pharmacologic treatments that target the development of fibrosis. Hypoxia is one of the key microenvironmental factors influencing intestinal inflammation and has been linked to fibrosis.

Objective: In the present study, we sought to elucidate the impact of hypoxia on fibrotic gene expression in the intestinal mucosa.

Methods: Human volunteers, IBD patients, and dextran sulphate sodium-treated mice were exposed to hypoxia, and colonic biopsies were collected. The human intestinal epithelial cell line Caco-2, human THP-1 macrophages, and primary human gut fibroblasts were subjected to hypoxia, and changes in fibrotic gene expression were assessed.

Results: Human volunteers subjected to hypoxia presented reduced transcriptional levels of fibrotic and epithelial-mesenchymal transition markers in the intestinal mucosa. IBD patients showed a trend towards a decrease in tissue inhibitor of metalloproteinase 1 protein expression. In mice, hypoxic conditions reduced the colonic expression of several collagens and matrix metalloproteinases. Hypoxic Caco-2 cells, THP-1 cells, and primary gut fibroblasts showed a significant downregulation in the expression of fibrotic and tissue remodelling factors.

Conclusions: Stabilization of hypoxia-inducible factors might represent a novel therapeutic approach for the treatment of IBD-associated fibrosis.

Background: Therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies in conjunction with symptoms, disease history, and investigations can aid decision-making. This study evaluated 1-year outcomes of patients with decisions that were altered on the basis of TDM results, in order to investigate whether outcomes from TDM-based decisions to adjust or stop IFX treatment are durable.

Methods: We retrospectively collected clinical outcomes 12 months post treatment decisions based on proactive TDM. Patients whose initial treatment decisions were altered on the basis of TDM results were compared with those where the decision remained unchanged. Events of interest were inpatient admissions with active inflammatory bowel disease (IBD), further changes to biologic therapy, and IBD-related health-care costs.

Results: Of 189 patients, 54 (28%) had initial treatment decisions altered in the light of TDM results. The 135 patients whose initial decision was not altered in light of TDM results served as the comparator. There were no differences in hospitalization rates or subsequent biologic switches between the altered decision groups and the comparator group. IBD-related health-care costs were higher in those whose initial decision was altered (median GBP 7,912 vs. GBP 6,521; p < 0.0001) due to higher drug costs (median GBP 7,062 vs. GBP 6,012; p < 0.0001).

Conclusion: Our study demonstrates good outcomes from changes to IFX treatment based on TDM. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes but had higher drug-related expenditure than those whose treatment decision was not altered in light of TDM.

Background and aims: The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care.

Methods: We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included.

Results: The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (p = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (p = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9-38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients.

Conclusions: TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

Background: Long-standing ulcerative colitis has been associated with an increased risk of colorectal cancer (CRC). Current guidelines recommend endoscopic CRC screening after 8 years of disease duration. The objectives of our study were to assess the adherence to recommendations and the quality of endoscopic procedure in long-standing ulcerative colitis.

Methods: This is a retrospective cohort study. We selected patients included in the Swiss IBD cohort with a disease duration of ≥8 years and an extension above the rectosigmoid junction. The complementary medical chart review focused on endoscopy and associated histological reports in 8 Swiss centers. Descriptive analyses focused on patients and their colonoscopies.

Results: 309 colonoscopies were conducted among 116 patients with the following characteristics: women 47%, mean age at diagnosis 31 years, and pancolitis disease extent in 65.5% of cases; 38.8% of patients had a first screening colonoscopy <8 years, 13.8% between 8 and 10 years, and 47.4% >10 years. Cecal intubation was performed in 94.5% of cases, and bowel preparation was good to excellent in 61.5% of endoscopies. Chromoendoscopy was used in 7.4% of cases, and the mean withdrawal time was 16.4 min. Dysplasia was found in 6.2% of cases.

Conclusion: Despite current international recommendations, a significant number of patients did not receive a proper endoscopic surveillance. An increased use of chromoendoscopy, monitoring of withdrawal time, and appropriate bowel preparation would increase the quality of CRC screening. The adherence to screening guidelines and endoscopic quality should be promoted and standardized.

Introduction: Protracted exposures to small doses of radiation, even cumulative effective doses (CED) as low as 50-100 mSv, may increase the risk for malignancy. Medical radiation exposure has not been rigorously examined for patients with irritable bowel syndrome (IBS). We examined medical radiation exposure in patients with IBS at a tertiary care center in the USA.

Methods: Patients diagnosed with IBS at our institute from 2009 to 2018 were included in a retrospective cohort study. Medical charts were examined to calculate total and annual CED.

Results: 221 patients were included; mean CED was 40.32 mSv (SD: 54.36). Fifty-nine participants (26.7%) received >50 mSv of CED with 27 participants (12.2%) exceeding 100 mSv. Conventional imaging, nuclear medicine, and fluoroscopy accounted for 74.08, 12.93, and 12.98% of total CED, respectively. CT scans contributed to 66.61% of total CED. Outpatient orders accounted for 37.96% of total CED, while 31.4% of total CED was ordered in the emergency department. Population-specific high total CED was calculated as 105.65 mSv. Multivariable binomial logistic regression model found that comorbid anxiety, chronic pain medication use, and diarrhea-predominant IBS were independently positively associated with population-specific high CED exposure. No significant temporal trend in peri-diagnostic mean CED was found.

Conclusion: Patients with IBS receive high amounts of medical radiation, with 1 in 4 patients reaching at-risk levels of 50 mSv or more. Usage of pain medication at home, comorbid anxiety, and IBS-D are independently linked to an increased risk of high CED.

Background: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody, which binds to α4β7 integrin on T lymphocytes, thus disturbing the interaction with mucosal vascular addressin cell adhesion molecule 1 on the intestinal endothelial cells to interfere with lymphocyte trafficking to the gut.

Summary: Vedolizumab is a safe and effective drug to induce and maintain clinical remission in patients with Crohn's disease (CD) and ulcerative colitis (UC) in both clinical trials and real-world data. Various guidelines recommend vedolizumab as a first- or second-line treatment regimen for steroid-dependent, steroid, or immunomodulator refractory cases of UC and CD; however, it is more effective in anti-TNF-naive patients. The first head-to-head trial (VARSITY trial) comparing the efficacy of vedolizumab to adalimumab has shown better clinical remission and mucosal healing with vedolizumab.

Key messages: In this review, we have discussed guidelines recommendation of vedolizumab use, as well as its safety data, use in special population, in presence of extraintestinal complications, therapeutic drug monitoring, data from Asian patients, along with other evolving concepts. Because of its excellent safety data and low immunogenicity, vedolizumab is an impressive option for patients with prior malignancy and less chance of reactivation of tuberculosis; however, cost remains an issue.

Introduction: Infliximab (IFX) therapy is efficacious for inducing and maintaining symptomatic remission in patients with Crohn's disease (CD), but whether this benefit results in reduced hospitalization rates and therefore may improve patients' quality of life in an economically sensible way is conflicting so far.

Methods: We conducted a noninterventional, multicenter, open-label, prospective study to evaluate the effect of originator IFX treatment on patient-reported outcomes and disease-related hospitalizations in adult CD patients in Germany treated for the first time with IFX according to label.

Results: Two hundred and ninety-four patients were included in the study. We observed a statistically significant reduction in the number of CD-related hospitalizations from the year before baseline (mean 1.00 per patient, SD ± 0.93) to the mean value of the 1st (0.62, SD ± 0.95) and 2nd year (0.32, SD ± 0.75) of the observation period (p < 0.0001). After 3 months of IFX therapy, work productivity and activity increased by an average of 12.6 and 17.1%, respectively. Patient's clinical outcome was markedly improved as the total CD activity index (CDAI) sum score continuously decreased from baseline to month 24 and the mean score of the total inflammatory bowel disease questionnaire (IBDQ) changed substantially from 141 at baseline to 172 after 24 months of IFX treatment. Additionally, the number of work incapacity days declined. Recently, no new safety issues of IFX have been identified.

Conclusion: In this large, prospective, multicenter study on disease-related hospitalization rates, work productivity, capacity for daily activities, and HRQoL in patients with CD, IFX significantly reduces their hospitalization rates and improves work productivity, daily activity, and quality of life over 24 months.

Introduction: Abdominal surgery in patients with Crohn's disease (CD) is challenging, especially in the biologic era. The aim of this study was to evaluate factors associated with increased risk for postoperative complications in CD.

Methods: A retrospective study was conducted with consecutive patients who underwent abdominal surgery for CD from January 2012 to January 2018.

Results: Of 103 patients, 32% had postoperative complications. Gender, age, disease location and phenotype, hemoglobin and albumin levels, previous abdominal surgery, and preoperative optimization did not differ between the groups with or without complications. Thirty-five percent of the patients were under anti-TNF therapy, and this medication was not associated with increased risk for postoperative complications. Time since the onset of the disease was significantly higher in patients with complications (12.9 vs. 9.4, p = 0.04). In multivariate analysis, creation of ostomy and urgent surgery were the only variables independently associated with increased risk for complications (OR 3.2, 95% CI 1.12-9.46 and OR 2.94, 95% CI 0.98-9.09, respectively).

Conclusion: Urgent surgery for CD should preferably be performed in specialized centers, and creation of stoma is not necessarily associated with lower rate of postoperative complications but rather less severe complications.