How achievable are STRIDE-II treatment targets in real-world practice and do they predict long-term treatment outcomes?

Objective: The second iteration of the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) initiative recommends use of the Simple Endoscopic Score for Crohn's disease (SES-CD) as a treatment target for patients with CD. We aimed to assess whether the STRIDE-II endoscopic endpoints are achievable and whether the degree of mucosal healing (MH) affects long-term outcomes. Design/method: We performed a retrospective observational study between 2015 and 2022. Patients with CD who had baseline and follow-up SES-CD scores after biological therapy initiation were included. The primary outcome was treatment failure, defined as the need for: (1) change of biological therapy for active disease (2) corticosteroid use (3) CD-related hospitalisation or (4) surgery. We compared rates of treatment failure with the degree of MH achieved. Patients were followed up until treatment failure or study end (August 2022). Results: 50 patients were included and followed up for median 39.9 (34.6-48.6) months. Baseline characteristics: 62% male, median age 36.4 (27.8-43.9) years, disease distribution (L1: 4, L2: 11, L3: 35, perianal: 18). The proportion of patients achieving STRIDE-II end-points were: SES-CD≤2-25 (50%) and >50% reduction in SES-CD-35 (70%). Failure to achieve SES-CD≤2 (HR 11.62; 95% CI 3.33 to 40.56, p=0.003) or >50% improvement in SES-CD (HR 30.30; 95% CI 6.93 to 132.40, p<0.0001) predicted treatment failure. Conclusion: Use of SES-CD is feasible in real-world clinical practice. Achieving an SES-CD≤2 or a greater than 50% reduction, as set out by STRIDE-II, is associated with reduced rates of overall treatment failure including CD-related surgery.

Management of orofacial granulomatosis.

Orofacial granulomatosis is a chronic relapsing-remitting inflammatory condition that shares a similar phenotypic presentation to some other granulomatous diseases, particularly Crohn's disease. However, subtle clinical and pathological differences justify it as a separate disease entity. Previous studies have assessed the effectiveness of interventions used in the management of orofacial granulomatosis. This article reviews the management options available. A literature search was conducted to identify studies, in English, which assessed the effect of non-pharmacological and pharmacological interventions in the treatment of orofacial granulomatosis. The interventions were categorised into dietary modification, pharmacological (topical, intralesional and systemic therapy), surgery and psychological. A combination of interventions is often required to effectively manage each patient. There is convincing evidence that diet plays a role in disease severity. In patients where dietary manipulation alone is unsuccessful, topical, intralesional and/or systemic treatment may be considered to manage the condition.

A retrospective cohort study: pre-operative oral enteral nutritional optimisation for Crohn's disease in a UK tertiary IBD centre.

BACKGROUND: Low-quality evidence suggests that pre-operative exclusive enteral nutrition (E/EN) can improve postoperative outcomes in patients with Crohn's disease (CD). It is not standard practice in most centres. AIMS: To test the hypothesis that pre-operative EN in patients undergoing ileal/ileocolonic surgery for CD is associated with improved postoperative outcome. METHODS: We performed a single centre retrospective observational study comparing surgical outcomes in patients receiving pre-operative EN (≥600 kcal/day for ≥2 weeks) with those who received no nutritional optimisation. Consecutive adult patients undergoing ileal/ileocolonic resection from 2008 to 2020 were included. The primary outcome was postoperative complications <30 days. Secondary outcomes included EN tolerance, specific surgical complications, unplanned stoma formation, length of stay, length of bowel resected, readmission and biochemical/anthropometric changes. RESULTS: 300 surgeries were included comprising 96 without nutritional optimisation and 204 optimised cases: oral EN n = 173, additional PN n = 31 (4 of whom had received nasogastric/nasojejunal EN). 142/204 (69.6%) tolerated EN. 125/204 (61.3%) initiated EN in clinic. Patients in the optimised cohort were younger at operation and diagnosis, with an increased frequency of penetrating disease and exposure to antibiotics or biologics, and were more likely to undergo laparoscopic surgery. The optimised cohort had favourable outcomes on multivariate analysis: all complications [OR 0.29; 0.15-0.57, p < 0.001], surgical complications [OR 0.41; 95% CI 0.20-0.87, p = 0.02], non-surgical complications [OR 0.24 95% CI 0.11-0.52, p < 0.001], infective complications [OR 0.32; 95% CI 0.16-0.66, p = 0.001]. CONCLUSIONS: Oral EN was reasonably well tolerated and associated with a reduction in 30-day postoperative complications. Randomised controlled trials are required to confirm these findings.

Depression, anxiety, and stress among inflammatory bowel disease patients during COVID-19: A UK cohort study.

BACKGROUND AND AIM: Patients with chronic diseases are believed to be at increased risk of mental health conditions during the COVID-19 pandemic. We aimed to assess the incidence of psychological morbidity in inflammatory bowel disease (IBD) patients during the COVID-19 pandemic, explore for association with risk of severe COVID-19 and other factors, and establish patients' interest in psychological support. METHODS: A survey including the Patient Health Questionnaire-9, General Anxiety Disorder-7, and Perceived Stress Scale tools for depression, anxiety, and stress was administered to IBD patients from a tertiary center in London, United Kingdom, in June 2020. RESULTS: Two hundred seventy-four patients responded to the survey (57% response rate), with 271 (99%) completing it. Moderate-severe depression was observed in 61 (22.5%), while 49 (18%) had moderate-severe anxiety; 39 (14%) had both diagnoses. Mean (SD) stress score was 16.2 (7.4). There was no association between degree of severe COVID-19 risk and psychological morbidity. Flare symptoms and fatigue were associated with worse psychological morbidity, while accessibility of information regarding COVID-19 risk and reducing that risk was protective for depression (odds ratio [OR] 0.56 [0.33-0.94], P = 0.03), anxiety (OR 0.62 [0.4-0.96], P = 0.03), and stress (standardized ß-coefficient -0.15 [-0.28 to -0.03], P = 0.02). Seventy-nine (30%) respondents were interested in receiving psychological support during the pandemic, while 200 (76%) expressed interest beyond the pandemic. CONCLUSIONS: Although depression, anxiety, and stress among IBD patients during the pandemic were common, their frequency was similar to pre-pandemic rates and recent general population levels. Ensuring easy access to personalized risk information with targeted psychological support may mitigate psychological burden as patients reintegrate into society and deal with future COVID-19 waves.

An observational study of switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with first or second switch.

BACKGROUND: Biologics account for a significant cost in inflammatory bowel disease (IBD) management; however, switching from infliximab originator to its biosimilars has enabled cost saving without compromising disease control. The effects on IBD activity and infliximab trough levels of a second switch to another biosimilar are, however, uncertain. AIMS: To assess the effects on disease activity and infliximab trough levels associated with switching from infliximab biosimilar CT-P13 to another biosimilar SB2 and compare outcomes in those switching for the first and second time. METHODS: IBD patients on CT-P13, including some previously switched from originator, were prospectively followed during a switch to SB2. C-reactive protein (CRP), trough infliximab level and clinical disease activity indices were collected at baseline, Infusion 3 or 4 ('early' after switch), and 1 year. RESULTS: One hundred eighty-six patients (n = 99 second switch) on stable infliximab dosing underwent switching. Compared with baseline, there was no significant change in CRP, clinical disease activity scores or median trough infliximab level at the early time point among first-switch (baseline vs early: 5.7 vs 6.6 µg/mL, P = 0.05) and second-switch (4.3 vs 4.9 µg/mL, P = 0.07) patients nor at 1 year (median infliximab trough levels, baseline vs 1 year, in first-switch [5.7 vs 5.7 µg/mL, P = 0.37] and second-switch [4.3 vs 4.7 µg/mL, P = 0.06] patients). The proportion of patients in clinical remission did not significantly change at the early (92% vs 91% at baseline, P = 0.75) or 1 year (95% vs 91% at baseline, P = 0.16) time points. There was no significant difference in time to loss of response between patients switching for the first or second time (P = 0.69). CONCLUSIONS: Switching from one infliximab biosimilar to another had no adverse impact on infliximab trough levels, and clinical and biochemical disease activity, regardless of whether switching for the first or second time.

The effects of COVID-19 on IBD prescribing and service provision in a UK tertiary centre.

BACKGROUND: To quantify the effects of COVID-19 on our inflammatory bowel disease (IBD) unit, including service provision, prescribing practices and use of therapeutic drug monitoring (TDM). METHODS: We performed a single centre retrospective observational cohort study. Data was extracted from our IBD database, electronic patient records and radiology/endoscopy reporting systems between 16/3/20-17/4/20 and the corresponding period in 2019. RESULTS: A similar number of patients commenced biologic therapy before COVID-19 (n = 37) and during the pandemic (n = 36). Patients in the pre-COVID-19 cohort were older (median 36 vs 29 years, P = 0.009) with a longer median disease duration (9.3 vs 5.2 years, P = 0.02). During COVID-19 there was a nonsignificant increase in prescribing of vedolizumab (8/37, 22% vs 14/36, 39%, P = 0.13) and a higher proportion of patients were anti-TNF-naïve (3/17, 18% vs 18/24, 74%, P = 0.0004). There was a reduction in use of concomitant immunomodulators (22/29, 76% vs 4/34, 12%, P < 0.0001) and increased biologic use in thiopurine-naïve patients (3/37, 8% vs 15/36, 42%, P = 0.001). Use of TDM fell by 75% (240 vs 59 tests). Outpatient appointments fell by 68% and were conducted via telemedicine. MRI scanning, endoscopy, luminal surgery and inpatient numbers fell by 87%, 85%, 100% and 82% respectively. IBD Clinical Nurse Specialist and Pharmacist helpline contacts increased by 76% and 228% respectively. CONCLUSIONS: We observed prescribing differences during COVID-19, bypassing the initiation of immunomodulators and/or anti-TNF therapy in favour of vedolizumab with a reduction in immunomodulator prescribing. We also observed a rapid reorganisation of service provision, including a shift towards telemedicine and online solutions.

Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic.

OBJECTIVE: To determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services. METHODS: Internet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020. RESULTS: Respondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4-7.5 and median 3, IQR 2-4) to the point of survey (median 2, IQR 1-4.8 and median 2, IQR 1-3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery. CONCLUSIONS: IBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.

Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO-LEVEL study.

BACKGROUND: Significant associations between serum golimumab concentrations and favourable outcomes have been observed during both induction and maintenance therapy in ulcerative colitis (UC). However, data regarding optimal therapeutic serum golimumab concentration thresholds are limited. AIMS: To identify optimal serum golimumab concentration thresholds during induction and maintenance treatment with golimumab. METHODS: GO-LEVEL was an open label, phase IV study that included a prospective cohort of UC patients commencing golimumab, as well as a cross-sectional cohort receiving maintenance treatment. Patients commencing induction for active UC (defined as a simple clinical colitis activity index [SCCAI] >5 in addition to a raised faecal calprotectin [FC] >59µg/g or, raised C-reactive protein [CRP] [>5mg/L] or, Mayo endoscopic disease activity 2 or 3) were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare or during remission. Combined clinical-biochemical remission was defined as SCCAI ≤2 and FC <250µg/g. Serum golimumab concentrations were measured using a commercially available ELISA (LISATRACKER, Theradiag). RESULTS: Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined clinical-biochemical remission at week 6. The median serum golimumab concentration of those in combined clinical-biochemical remission was significantly higher than those who were not (5.0 vs 3.1 µg/mL, respectively, P = 0.03). Receiver operating characteristic (ROC) curve analysis demonstrated 3.8 µg/mL as the optimal threshold (sensitivity 0.71, specificity 0.65, area under curve [AUC] 0.72, positive predictive value [PPV] 0.59 and negative predictive value [NPV] 0.79). Sixty-three patients were included in the maintenance cohort; 31 (49%) were in combined remission, 32 (51%) were not. The median serum golimumab concentration of those in combined remission was significantly higher (2.9 vs 2.1 µg/mL, respectively, P = 0.01). ROC curve analysis demonstrated 2.4 µg/mL as the optimal threshold (sensitivity 0.68, specificity 0.66, AUC 0.68, PPV 0.65 and NPV 0.66). CONCLUSIONS: GO-LEVEL (NCT03124121) offers further evidence regarding golimumab's exposure-response relationship. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested therapeutic thresholds of 3.8 µg/mL at week 6 and 2.4 µg/mL during maintenance.

Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response.

BACKGROUND: Despite the proven efficacy of vedolizumab (VDZ) for ulcerative colitis (UC) and Crohn's disease (CD), suboptimal response is commonly encountered. However, data regarding the effectiveness of dose intensification (by interval shortening) to achieve response are limited. OBJECTIVES: We evaluated the effectiveness of dose intensification at achieving response in patients with a previously suboptimal response to VDZ. Additionally, we aimed to identify predictors of response to this strategy. METHODS: We performed a retrospective cohort study of patients who underwent VDZ dose intensification for suboptimal response. Clinical disease activity was evaluated at the point of dose intensification (baseline) and at weeks 12 and 24. Response was defined as Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) reduction of ≥3, and remission as HBI <5 or SCCAI <3. RESULTS: A total of 36 patients received dose intensification to 4-weekly infusions: 18 CD, 14 UC and 4 inflammatory bowel disease-unclassified (analysed in the UC group). Median SCCAI scores fell from 6 (range 0-11) at baseline to 4 (0-6, p=0.008) at week 24, while HBI scores did not change significantly (4 (0-27) and 3 (0-8), p=0.092). Overall median C reactive protein (CRP) fell from 6 mg/L (1-23) to 2 mg/L (1-17, p=0.011). Of 20 patients with clinically active disease at baseline, 10 (50%) responded, of whom 4 (20%) achieved remission at week 24. Univariate analysis demonstrated low baseline CRP (p=0.045) and response at week 12 (0.020) were associated with week 24 response. CONCLUSIONS: Our findings demonstrate VDZ dose intensification to be effective at achieving clinical response in half of patients. Low baseline CRP and response at week 12 are potential predictors of week 24 response.

Validation and Investigation of the Operating Characteristics of the Ulcerative Colitis Endoscopic Index of Severity.

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a novel instrument to evaluate endoscopic disease activity. It has been demonstrated to outperform the more widely used Mayo endoscopic score (MES) in predicting long-term prognosis, including the need for colectomy. Despite its potential benefits, many clinicians still prefer to use MES because its operating characteristics are better defined and its grades are more readily applicable to clinical decision-making. The aims of our study were to quantify the UCEIS cutoff most closely associated with the need for treatment escalation and to perform a validation exercise using MES and clinical, biochemical, and histological measures of disease activity. METHODS: Endoscopies performed in UC patients between November 2016 and January 2018 were retrospectively reviewed. Agreement between the UCEIS and MES was quantified using Kappa (κ) statistics. A UCEIS cutoff for treatment escalation was calculated using chi-square, receiver operating characteristic curve, and area under the curve (AUC) analyses. The Pearson correlation coefficient was used to compare linear relationships between UCEIS and clinical (Simple Clinical Colitis Activity Index [SCCAI]), biochemical (C-reactive protein [CRP]), and histological (Nancy Histological Index [NHI]) activity. RESULTS: Two hundred one (56%) procedures documented both UCEIS and MES, demonstrating substantial agreement (κ = 0.713; P < 0.001). Treatment was escalated after 199 (56%) procedures. Receiver operating characteristic curve analysis of need for treatment escalation showed the highest sensitivity and specificity for UCEIS ≥4 (0.80 and 0.93, respectively; AUC, 0.93). Of 170 patients with a UCEIS ≥4, treatment was escalated in 159 (94%), but not for 11 (6%). Of 185 patients with a UCEIS ≤3, 40 (22%) were escalated, whereas 145 (78%) were not (P < 0.001). UCEIS correlated strongly with NHI (0.723; P < 0.001), moderately with SCCAI (0.671; P < 0.001), and weakly with CRP (0.279; P < 0.001). CONCLUSIONS: A UCEIS ≥4 was significantly associated with treatment escalation. This cutoff could therefore be used to support clinical decision-making based on endoscopic findings. Strong and moderate correlations were found between UCEIS and histological and clinical disease activity, respectively, whereas a weak correlation was found with CRP.10.1093/ibd/izy325_Video_1 izy325.video1 5849933952001.

Current Practices in Ileal Pouch Surveillance for Patients With Ulcerative Colitis: A Multinational, Retrospective Cohort Study.

BACKGROUND AND AIMS: There are no universally accepted guidelines regarding surveillance of ulcerative colitis [UC] patients after restorative proctocolectomy and ileal pouch-anal anastomosis [IPAA]. There also exists a lack of validated quality assurance standards for performing pouchoscopy. To better understand IPAA surveillance practices in the face of this clinical equipoise, we carried out a retrospective cohort study at five inflammatory bowel disease [IBD] referral centres. METHODS: Records of patients who underwent IPAA for UC or IBD unclassified [IBDU] were reviewed, and patients with <1-year follow-up after restoration of intestinal continuity were excluded. Criteria for determining the risk of pouch dysplasia formation were collected as well as the use of pouchoscopy, biopsies, and completeness of reports. RESULTS: We included 272 patients. Median duration of pouch follow-up was 10.5 [3.3-23.6] years; 95/272 [35%] had never undergone pouchoscopy for any indication; 191/272 [70%] had never undergone pouchoscopy with surveillance as the specific indication; and 3/26 [12%] high-risk patients had never undergone pouchoscopy. Two cases of adenocarcinoma were identified, occurring in the rectal cuff of low-risk patients. Patients under the care of surgeons appeared more likely to undergo surveillance, but rates of incomplete reporting were higher among surgeons [78%] than gastroenterologists [54%, p = 0.002]. CONCLUSIONS: We observed wide variation in surveillance of UC/IBDU-IPAA patients. In addition, the rate of neoplasia formation among 'low-risk' patients was higher than may have been expected. We therefore concur with previous recommendations that pouchoscopy be performed at 1 year postoperatively, to refine risk-stratification based on clinical factors alone. Reports should document findings in all regions of the pouch and biopsies should be taken.

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

Differences in inflammatory bowel disease phenotype between South Asians and Northern Europeans living in North West London, UK.

OBJECTIVES: The incidence and prevalence of inflammatory bowel disease (IBD) is increasing throughout Asia. Since the 1950s, there has been substantial migration from South Asia (India, Pakistan, and Bangladesh) to the United Kingdom. The aim of this study was to define the clinical phenotype of IBD in UK South Asians living in North West London, and to compare the results with a white Northern European IBD cohort. METHODS: The phenotypic details of 367 South Asian IBD patients (273 ulcerative colitis (UC) and 94 Crohn's disease (CD)), undergoing active follow-up in five North West London hospitals, were compared with those of 403 consecutively collected white Northern European IBD patients (188 UC and 215 CD). RESULTS: The phenotype of IBD differed significantly between the two populations. 63.0% of South Asian UC patients had extensive colitis compared with 42.5% of the Northern European cohort (P < 0.0001). Proctitis was uncommon in South Asian UC patients (9.9 vs. 26.1% in Northern European patients, P<0.0001). In the South Asian CD cohort, disease location was predominantly colonic (46.8%). CD behavior differed significantly between the groups, with less penetrating disease compared with Northern Europeans (P=0.01) and a reduced need for surgery (P=0.003). CONCLUSIONS: The phenotype of IBD in South Asians living in North West London is significantly different from that of a white Northern European IBD cohort. Knowledge of ethnic variations in disease phenotype may help to identify key genetic, environmental, and behavioral factors contributing to the development of IBD.

The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis.

OBJECTIVES: Hypnotherapy is effective in several diseases with a psychosomatic component. Our aim was to study the effects of one session of hypnosis on the systemic and rectal mucosal inflammatory responses in patients with active ulcerative colitis (UC). METHODS: In total, 17 patients with active UC underwent a 50-min session of gut-focused hypnotherapy. Before and after each procedure, the systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor-alpha (TNF-alpha) and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell number, platelet activation, and platelet-leukocyte aggregate formation. Rectal inflammation was assessed by mucosal release of substance P (SP), histamine, IL-13 and TNF-alpha, reactive oxygen metabolite production, and mucosal blood flow. Eight patients with active UC underwent a control procedure. RESULTS: Hypnosis decreased pulse by a median 7 beats per minute (bpm) (P= 0.0008); it also reduced the median serum IL-6 concentration by 53% (P= 0.001), but had no effect on the other systemic variables assessed. Hypnosis reduced rectal mucosal release of SP by a median 81% (P= 0.001), histamine by 35% (P= 0.002) and IL-13 by 53% (P= 0.003), and also, blood flow by 18% (P= 0.0004). The control protocol had no effect on any of the variables assessed. CONCLUSIONS: Hypnosis reduced several components of the systemic and mucosal inflammatory response in active ulcerative colitis toward levels found previously in the inactive disease. Some of these effects may contribute to the anecdotally reported benefits of hypnotherapy and provide a rationale for controlled trials of hypnotherapy in UC.

New flow cytometric technique for the evaluation of circulating endothelial progenitor cell levels in various disease groups.

Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and play a role in vascular repair and re-endothelialisation of injured blood vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in the general population. It is not clear at present whether and how the numbers of circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the flow cytometric analysis of whole blood by using a novel cocktail of monoclonal antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non-progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs. We analysed 250 patients with varying stages of uraemia, 36 patients with inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress syndrome and compared this to 74 healthy controls. Using flow cytometry we were able to measure the circulating levels of EPCs, with a result available within hours of the sample being obtained. Circulating EPC numbers vary in different patient groups and healthy controls. In uraemic patients, irrespective of disease severity, there are lower numbers of circulating EPC numbers compared to normal controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means of monitoring patients and shows a reduction in circulating EPCs in uraemic patients; this abnormality may be a target of novel therapies.

The effect of acute psychologic stress on systemic and rectal mucosal measures of inflammation in ulcerative colitis.

BACKGROUND & AIMS: Recent studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Our aim was to study the effects of acute psychologic stress on systemic and rectal mucosal inflammatory responses in patients with inactive ulcerative colitis (UC). METHODS: Twenty-five patients with inactive UC and 11 healthy volunteers (HV) underwent an experimental stress test. Ten patients with UC and 11 HV underwent a control procedure. Before and after each procedure, systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor (TNF)-alpha and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell numbers, platelet activation, and platelet-leukocyte aggregate (PLA) formation. In patients with UC, rectal mucosal inflammation was assessed by TNF-alpha, IL-13, histamine and substance P release, reactive oxygen metabolite (ROM) production, mucosal blood flow (RMBF) and histology. RESULTS: Stress increased pulse (P < .0001) and systolic BP (P < .0001). In UC, stress increased LPS-stimulated TNF-alpha and IL-6 production by 54% (P = .004) and 11% (P = .04), respectively, leukocyte count by 16% (P = .01), NK cell count by 18% (P = .0008), platelet activation by 65% (P < .0001), PLA formation by 25% (P = .004), mucosal TNF-alpha release by 102% (P = .03), and ROM production by 475% (P = .001) and reduced rectal mucosal blood flow by 22% (P = .05). The control protocol did not change any of the variables measured. There were no differences between the responses of the patients with UC and HV. CONCLUSIONS: Acute psychologic stress induces systemic and mucosal proinflammatory responses, which could contribute to exacerbations of UC in ordinary life.