Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. METHODS: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. RESULTS: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. CONCLUSIONS: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to remove sludge/stones from the common bile duct (CBD). In a small but clinically important proportion of patients with suspected choledocholithiasis ERCP is negative. This is undesirable because of ERCP associated morbidity. We aimed to map the diagnostic pathway leading up to ERCP and evaluate ERCP outcome. METHODS: We established a prospective multicenter cohort of patients with suspected CBD stones. We assessed the determinants that were associated with CBD sludge or stone detection upon ERCP. RESULTS: We established a cohort of 707 patients with suspected CBD sludge or stones (62% female, median age 59 years). ERCP was negative for CBD sludge or stones in 155 patients (22%). Patients with positive ERCPs frequently had pre-procedural endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) imaging (44% vs. 35%; P = 0.045). The likelihood of ERCP sludge and stones detection was higher when the time interval between EUS or MRCP and ERCP was less than 2 days (odds ratio 2.35; 95% CI 1.25-4.44; P = 0.008; number needed to harm 7.7). CONCLUSIONS: Even in the current era of society guidelines and use of advanced imaging CBD sludge or stones are absent in one out of five ERCPs performed for suspected CBD stones. The proportion of unnecessary ERCPs is lower in case of pre-procedural EUS or MRCP. A shorter time interval between EUS or MRCP increases the yield of ERCP for suspected CBD stones and should, therefore, preferably be performed within 2 days before ERCP.

Effective bowel management in spinal cord injury during inpatient rehabilitation: data from the Dutch spinal cord injury database.

STUDY DESIGN: Retrospective Observational Study. OBJECTIVES: To describe bowel management in individuals with a recently acquired spinal cord injury (SCI) both at admittance and discharge from first inpatient rehabilitation, and to determine factors that contribute to effective bowel management (EBM) at discharge. SETTING: Specialized rehabilitation centers in the Netherlands. METHODS: Data from the Dutch Spinal Cord Injury Database (DSCID) collected between 2015 and 2019 was used. EBM was defined by the variables of stool frequency and fecal incontinence. After univariate analysis, a multivariate regression analysis was conducted. RESULTS: Of 1,210 participants, 818 (68%) did not have EBM at admittance. At discharge, 308 (38%) did still not have EBM (in total 33% of all participants). The odds of having EBM at discharge was 2.82 times higher for participants with ASIA Impairment Scale (AIS) D compared to those with AIS-A (95% CI: 1.38-5.78). Participants with non-traumatic SCI had higher odds of having EBM than those with traumatic SCI (OR: 0.59, 95% CI 0.38-0.91). Use of suppositories, small enema, medication influencing bowel function, and oral laxatives at admittance did not influence EBM significantly at discharge. CONCLUSIONS: Bowel management improves during first inpatient rehabilitation. However, realizing EBM after a recently acquired SCI is a challenge. This endorses the importance of bowel management during inpatient rehabilitation, especially for people with AIS-A and non-traumatic etiology.

Web-based dietary assessment and advice helps inflammatory bowel disease patients to improve their diet quality.

Time to evaluate diet quality and give dietary advice is limited in clinical IBD practice. The Eetscore is a web-based tool that assesses diet quality according to the Dutch dietary guidelines and provides personalised dietary advice. We aimed to assess diet quality of IBD patients using the Eetscore and to study changes in diet quality, health-related quality of life (HRQoL) and clinical disease activity over time. A prospective cohort study was performed in 195 adult IBD patients. Participants were invited to fill out questionnaires (Eetscore-FFQ, short IBDQ and p-HBI/p-SCCAI) at baseline and after 1 and 4 months. The Eetscore calculates diet quality based on 16 food components (10 points per component, total score 0-160; the higher the better) and provides dietary advice per component based on the assessment. At baseline, mean diet quality was 98±19. Diet quality was positively associated with age, female gender and level of education. Component scores were highest for red meat, wholegrain products, and sweetened beverages, and lowest for legumes, nuts, and processed meat. Over time, diet quality increased to 107±21 at 4 months (p<0.001). Each 10-point improvement in diet quality was associated with an increase in HRQoL (ß=0.4 (95%CI 0.02; 0.7), p=0.04). Clinical disease activity did not change. In conclusion, diet quality of IBD patients significantly improved following personalised dietary advice of the Eetscore. Improvement of diet quality was associated with a slight improvement in HRQoL. The Eetscore is a practical and useful tool to monitor and support a healthy diet in IBD patients.

Fecal Microbiota Signatures Are Not Consistently Related to Symptom Severity in Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent functional bowel disorder, but its pathophysiology is still unknown. Although a microbial signature associated with IBS severity has been suggested, its association with IBS severity still remains largely unknown. AIMS: This study aims to assess longitudinal dynamics of fecal microbiota and short-chain fatty acids (SCFAs) in different IBS severity groups and study the association with stool pattern, diet, depression, anxiety, and quality of life (QoL). METHODS: A longitudinal study was performed, including n = 91 IBS patients and n = 28 matched controls. All participants collected fecal samples for microbiota composition and SCFA analysis and completed validated questionnaires regarding IBS severity, stool pattern, depression, anxiety, and IBS-QoL at two timepoints with four weeks in-between. Diet was assessed at the first timepoint. RESULTS: Over time, 36% of IBS patients changed in severity group, and 53% changed in predominant stool pattern. The largest proportion of microbiota variation was explained by the individual (R2 = 70.07%). Microbiota alpha diversity and composition, and SCFAs did not differ between IBS severity groups, nor between IBS and controls. Relative abundances of Bifidobacterium, Terrisporobacter, and Turicibacter consistently differed between IBS and controls, but not between IBS severity groups. Large dynamics over time were observed in the association of microbiota composition with questionnaire data where IBS symptom severity was associated at T1 but not at T2. CONCLUSIONS: Fecal microbiota and SCFA signatures were not consistently associated with IBS severity over time, indicating the importance of repeated sampling in IBS research.

Patient Education Regarding Fasting Recommendations to Shorten Fasting Times in Patients Undergoing Esophagogastroduodenoscopy: A Controlled Pilot Study.

This study evaluated the applicability and efficacy of patient education regarding fasting recommendations to shorten fasting times in patients undergoing esophagogastroduodenoscopy (EGD). A prospective nonrandomized controlled pilot study was performed. The intervention group (IG) was educated by nurses to eat until 6 hours and drink until 2 hours before EGD. The control group (CG) received usual care. Outcomes were applicability as perceived by patients, adherence to fasting recommendations, gastric visibility, and patients' comfort. A total of 109 patients were included of whom 42 were IG patients (37%). Patients' perspectives on fasting, their experienced discomfort, professional support, and circadian rhythm influenced application of fasting recommendations. Adherence to length of fasting from foods improved with 3:14 hours ( p < .001) and from liquids with 5:22 hours ( p < .001) in the IG compared with the CG. Gastric visibility during EGD was better in the IG than in the CG. The IG patients experienced significant less thirst, hunger, headache, and anxiety. To successfully reduce fasting times, fasting education should include positive, individual instructions, which help patients apply the fasting recommendations within their biorhythm. Positive, concrete instructions by nurses shortened fasting times before EGD, which improved gastric visibility and reduced patient discomfort.

Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal-release peppermint oil group had a response (46.8%, P = .170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P = .385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P = .317 and 1.6%, P = .351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P = .016), discomfort (P = .020), and IBS severity (P = .020). Adverse events, although mild, were more common in both peppermint oil groups (P < .005). CONCLUSIONS: In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

Repeated prolonged moderate-intensity walking exercise does not appear to have harmful effects on inflammatory markers in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: The role of exercise in the management of inflammatory bowel disease (IBD) is inconclusive as most research focused on short or low-intensity exercise bouts and subjective outcomes. We assessed the effects of repeated prolonged moderate-intensity exercise on objective inflammatory markers in IBD patients. METHODS: In this study, IBD patients (IBD walkers, n = 18), and a control group (non-IBD walkers, n = 19), completed a 30, 40 or 50 km walking exercise on four consecutive days. Blood samples were taken at baseline and every day post-exercise to test for the effect of disease on exercise-induced changes in cytokine concentrations. A second control group of IBD patients who did not take part in the exercise, IBD non-walkers (n = 19), was used to test for the effect of exercise on faecal calprotectin. Both IBD groups also completed a clinical disease activity questionnaire. RESULTS: Changes in cytokine concentrations were similar for IBD walkers and non-IBD walkers (IL-6 p = .95; IL-8 p = .07; IL-10 p = .40; IL-1ß p = .28; TNF-α p = .45), with a temporary significant increase in IL-6 (p < .001) and IL-10 (p = .006) from baseline to post-exercise day 1. Faecal calprotectin was not affected by exercise (p = .48). Clinical disease activity did not change in the IBD walkers with ulcerative colitis (p = .92), but did increase in the IBD walkers with Crohn's disease (p = .024). CONCLUSION: Repeated prolonged moderate-intensity walking exercise led to similar cytokine responses in participants with or without IBD, and it did not affect faecal calprotectin concentrations, suggesting that IBD patients can safely perform this type of exercise.

Patient experiences with the role of physical activity in inflammatory bowel disease: results from a survey and interviews.

BACKGROUND: Physical activity may affect disease activity in patients with inflammatory bowel disease. We used a survey to investigate this association and performed interviews to get a better understanding of patient experiences, and therefore the nature of this association. METHODS: Patients with Crohn's disease (CD, n = 176) and ulcerative colitis (UC, n = 162) completed the short Crohn's Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI) and the Short Questionnaire to Assess Health-enhancing physical activity (SQUASH). Associations were investigated by multiple linear regression. Semi-structured interviews (7 CD, 7 UC) were conducted to assess patient experiences with the role of physical activity in their disease. RESULTS: The majority of survey participants were in remission (70%) and adhered to the Dutch physical activity guidelines (61%). In Crohn's disease, the total physical activity score was inversely associated with disease activity, even after adjustment for confounders (ß = - 0.375; p = 0.013). No association between physical activity and disease activity was found in ulcerative colitis. Of the interviewees, 86% experienced beneficial effects of physical activity, such as improved general fitness, quality of life and self-image. However, during periods of active disease they struggled to find the motivation and perseverance to be physically active due to physical barriers. CONCLUSIONS: Crohn's disease participants with a higher physical activity level had a lower disease activity. This inverse association was not found in ulcerative colitis. Interviews revealed that IBD patients generally experience beneficial effects from physical activity, although the barriers caused by active disease may put them off to be physically active.

Development and validation of the FiberScreen: A short questionnaire to screen fibre intake in adults.

BACKGROUND: Health effects of dietary fibres are the topic of many studies. Eligibility criteria often include a certain fibre intake, which requires dietary screening during recruitment. However, dietary assessment methods are extensive and burdensome for both the researcher and participant. Therefore, we developed and validated a short questionnaire (FiberScreen) to screen fibre intake. METHODS: The initial five-item questionnaire assessed fruit, vegetable, whole grain, pasta/rice/potato and legume intake. The optimised FiberScreen included 18 items, which further specified intake of the above-mentioned categories, and included nuts and seeds. The FiberScreen was completed during two fibre promoting interventions. In Study A, participants without constipation completed the five-item FiberScreen and a food frequency questionnaire (FFQ) during screening (n = 131), and the 18-item FiberScreen and a FFQ at 3-month follow-up (n = 87). In Study B, 29 constipated participants completed the 18-item FiberScreen at screening and a FFQ during the first study visit. RESULTS: The fibre estimate from the five-item FiberScreen and the FFQ was moderately correlated (r = 0.356, p < 0.001). Importantly, the 18-item FiberScreen and FFQ, when data of both studies were combined, had a strong correlation (r = 0.563, p < 0.001). The 18-item FiberScreen had a lower fibre estimate compared to the FFQ (Δ = 1.2 ± 5.9 g, p = 0.030) but the difference was relatively small. Bland-Altman plots showed a good agreement between the questionnaires. Completion time of the 18-item FiberScreen was 4.2 ± 2 min. CONCLUSIONS: The 18-item FiberScreen is a suitable short screening questionnaire for ranking the fibre intake of adults. The 18-item FiberScreen can help to reduce screening burden for both the participant and researcher.

The association between inflammatory potential of diet and disease activity: results from a cross-sectional study in patients with inflammatory bowel disease.

BACKGROUND: Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn's disease and ulcerative colitis. METHODS: Participants completed a disease activity questionnaire (short Crohn's Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals' diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. RESULTS: The analysis included 329 participants; 168 with Crohn's disease (median sCDAI score 93 [IQR 47-156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1-3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn's disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. CONCLUSIONS: Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn's disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.

A context analysis on how oral care is delivered in hospitalised patients: A mixed-methods study.

AIMS AND OBJECTIVES: To analyse oral care delivery in one hospital through exploring experiences from both nurses' and patients' perspectives and examining patients' oral health. BACKGROUND: Oral health problems are associated with undernutrition and other general health outcomes. Although oral care belongs to the essentials of nursing, it is often neglected. Improving oral health may require behaviour change of both nurses and patients. Defining tailored strategies need a clear view on the context. DESIGN: A context analysis in one hospital using a convergent parallel mixed-methods design was reported following the EQUATOR guidelines using two checklists: COnsolidated criteria for REporting Qualitative research (qualitative research) and STROBE (observational research). METHODS: Semi-structured interviews were conducted with 19 nurses and 11 patients. The topic list was based on the Integrated Change Model. Prospective oral examination was performed among 91 surgical patients using the Oral Health Assessment Tool (OHAT). RESULTS: Nurses acknowledged that they did not prioritise oral care in daily practice. Furthermore, they lacked knowledge and skills to identify and provide care for oral problems. Nurses mentioned helpful resources to perform oral care, like standardised language and instruments. However, they had no access to or were unaware of them. Patients admitted that they did not prioritise oral care due to their sickness during hospitalisation, were unaware of the importance of oral care, but felt responsible for their oral care. The most prominent oral problems identified with the OHAT were unclean mouths (n = 75, 82%), unhealthy gum and tissues (n = 55, 60%) and dry mouth (n = 42, 46%). CONCLUSIONS: This context analysis identified inadequate oral care due to lack of positive attitude and knowledge in both nurses and patients, skills for nurses, and resources. RELEVANCE TO CLINICAL PRACTICE: The behavioural factors indicate strategies for development of a multicomponent intervention to improve oral care in this hospital, nutritional status and general health outcomes.

Patient's Dietary Beliefs and Behaviours in Inflammatory Bowel Disease.

BACKGROUND: The inflammatory bowel disease (IBD) is a chronic lifelong inflammation that may affect the entire gastro-intestinal tract in Crohn's disease and the colon in ulcerative colitis (UC). Diet plays an important role in IBD patients and many of them follow strict diet restriction in order to reduce complaints and prolong remission intervals. The aim of this study was to assess dietary beliefs, dietary behaviour and nutrition knowledge in Dutch adults with IBD to enable considering the patient's perspective on dietary advice. METHODS: A self-administered online questionnaire assessing general characteristics, dietary beliefs and behaviour, nutrition knowledge and sources and dietary advice was devised. The questionnaire was distributed to members of the Dutch Crohn and UC patient association of whom 294 participated in the study. RESULTS: Fifty-nine per cent of the patients valued nutrition to be either more or equally important compared to medication for their treatment and 62% believed diet to be more important in influencing the disease course. Sixty-two per cent reported to be successful in controlling disease symptoms through dietary adaptations. Avoiding certain foods was preferred over eating more beneficial foods or following specific diets (77 vs. 57% and 48% respectively). Dietary supplements were used by 68% of the IBD patients. Although over 71% had received dietary advice mainly by dieticians, 81% stated that the main source of their nutritional knowledge related to IBD was their own experience. CONCLUSION: A subgroup of IBD patients considered diet to be a more important and successful managing tool than medication to relieve their disease symptoms.

Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study.

BACKGROUND: The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are - in hindsight - unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better exclude SCD in these patients and evaluated the value of adding a faecal calprotectin point-of-care (POC) and/or a POC faecal immunochemical test for haemoglobin (FIT) to routine clinical information. METHODS: We used data from a prospective diagnostic study in SCD-suspected patients from 266 Dutch primary care practices referred for endoscopy to develop a diagnostic model for SCD with routine clinical information, which we extended with faecal calprotectin POC (quantitatively in µg/g faeces) and/or POC FIT results (qualitatively with a 6 µg/g faeces detection limit). We defined SCD as colorectal cancer (CRC), inflammatory bowel disease, diverticulitis, or advanced adenoma (>1 cm). RESULTS: Of 810 patients, 141 (17.4 %) had SCD. A diagnostic model with routine clinical data discriminated between patients with and without SCD with an area under the receiver operating characteristic curve (AUC) of 0.741 (95 % CI, 0.694-0.789). This AUC increased to 0.763 (95 % CI, 0.718-0.809; P = 0.078) when adding the calprotectin POC test, to 0.831 (95 % CI, 0.791-0.872; P < 0.001) when adding the POC FIT, and to 0.837 (95 % CI, 0.798-0.876; P < 0.001) upon combined extension. At a ≥ 5.0 % SCD probability threshold for endoscopy referral, 30.4 % of the patients tested negative based on this combined POC-tests extended model (95 % CI, 25.7-35.3 %), with 96.4 % negative predictive value (95 % CI, 93.1-98.2 %) and 93.7 % sensitivity (95 % CI, 88.2-96.8 %). Excluding the calprotectin POC test from this model still yielded 30.1 % test negatives (95 % CI, 24.7-35.6 %) and 96.0 % negative predictive value (95 % CI, 92.6-97.9 %), with 93.0 % sensitivity (95 % CI, 87.4-96.4 %). CONCLUSIONS: FIT - and to a much lesser extent calprotectin - POC testing showed incremental value for SCD diagnosis beyond standard clinical information. A diagnostic strategy with routine clinical data and a POC FIT test may safely rule out SCD and prevent unnecessary endoscopy referral in approximately one third of SCD-suspected primary care patients. Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0694-3 .

Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis.

UNLABELLED: The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4 × ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1 × and 2 × ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97). CONCLUSION: Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC.

Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer.

Gastrointestinal (GI) cancer is responsible for the majority of deaths among all types of cancer. Lifestyle factors may not only be the main risk factor for GI cancer but reactive oxygen species (ROS) may also be involved. The single-nucleotide polymorphisms (SNPs) 609C>T (rs1800566) and 465C>T (rs1131341) in the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene lead to a decline in NQO1 enzyme activity. NQO1 catalyzes the two-electron reduction of quinones to hydroquinones, thereby preventing the formation of ROS. Such polymorphisms in NQO1 may increase the risk of GI cancer. The aim of this study was to evaluate the influence of the SNPs rs1800566 and rs1131341 in the NQO1 gene on the risk of GI cancer in the Netherlands. Real-time polymerase chain reaction techniques were conducted to determine the NQO1 genotypes of 1457 patients with GI cancer and 1457 age- and gender-matched controls in a case-control study. Binary logistic regression analyses showed no statistically significant difference in genotype distributions between patients and controls: odds ratios (ORs) with 95% confidence interval (CI) for rs1800566 were 1.09 (0.93-1.28) and 1.17 (0.77-1.77) for the CT and TT genotypes, respectively. ORs for rs1131341 CT and TT genotypes were 1.21 (0.90-1.63) and 0.54 (0.05-5.94), respectively. For rs1800566, a significant association between the CT genotype and proximal colon cancer was detected (OR=1.60; 95% CI=1.09-2.35). The NQO1*2 T allele of SNP rs1800566 was found associated with an increased risk for proximal colorectal cancer, whereas SNP rs1131341 was rare in our Dutch population and was not associated with GI cancer.

The impact of running on gastrointestinal symptoms in patients with irritable bowel syndrome.

INTRODUCTION: Physical activity has been suggested to alleviate gastrointestinal (GI) symptoms in patients with irritable bowel syndrome (IBS); however, evidence is scarce. Running has become increasingly popular and may be beneficial for patients with IBS. To obtain more insight in the potential application of running as therapy, we aimed to explore the impact of running and its intensity on GI symptoms in patients with IBS. METHODS: Data from a large observational study in runners were used for this nested case-control study, which included 153 runners with IBS and 153 controls. All participants had completed a questionnaire on personal characteristics, running characteristics and GI symptoms. Regarding GI symptoms, the severity of nine symptoms was asked, both at rest and during and/or shortly (up to 3 h) after running. Each symptom could be scored on a scale from 0 (not bothersome) to 100 (very bothersome), resulting in a maximum total score of 900 points. KEY RESULTS: The prevalence and total severity score of GI symptoms were higher in runners with IBS than in controls, both at rest and during running. Among runners with IBS, the median (25th-75th percentile) total severity score during/after running was significantly lower than at rest (118 [50-200] vs. 150 [90-217]), while in controls no significant difference between running and rest was observed. Analyses stratified for running intensity revealed that the beneficial effect in runners with IBS was present when their most intensive training session was moderately intensive or intensive but not very intensive. CONCLUSIONS & INFERENCES: Running, particularly on moderate intensity, could have a beneficial effect on GI symptoms in patients with IBS.

The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study.

BACKGROUND: Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS: This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E+) or gluten-free (E-) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G+) or gluten-free (G-) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS: Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E+G+ (n=21), E+G- (n=21), E-G+ (n=20), or E-G- (n=22). One person in the E+G+ group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E+G+ (16·6 mm [95% CI 13·1 to 20·0]) than for E-G+ (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and E-G- (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for E+G- (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between E+G- and E-G+ (difference 4·7 mm [-1·8 to 11·3], p=0·33), E+G- and E-G- (difference 4·2 mm [-2·2 to 10·7], p=0·47), and E-G+ and E-G- (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the E+G- group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the E-G+ group (vomiting). INTERPRETATION: The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING: Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.

Dietary supplement use is not associated with recurrence of colorectal adenomas: a prospective cohort study.

Diet and lifestyle influence colorectal adenoma recurrence. The role of dietary supplement use in colorectal adenoma recurrence remains controversial. In this prospective cohort study, we examined the association between dietary supplement use, total colorectal adenoma recurrence and advanced adenoma recurrence. Colorectal adenoma cases (n = 565) from a former case-control study, recruited between 1995 and 2002, were prospectively followed until 2008. Adenomas with a diameter of ≥1 cm and/or (tubulo)villous histology and/or with high grade dysplasia and/or ≥3 adenomas detected at the same colonic examination were considered advanced adenomas. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary supplement users (use of any supplement during the past year) compared to nonusers and colorectal adenoma recurrence were calculated using stratified Cox proportional hazard models for counting processes and were adjusted for age, sex, educational level and number of colonoscopies during follow-up. Robust sandwich covariance estimation was used to adjust for the within subject correlation. A number of 165 out of 565 adenoma patients had at least one colorectal adenoma recurrence during a median person-time of 5.4 years and of these, 37 patients had at least one advanced adenoma. One-third of the total study population (n = 203) used a dietary supplement. Compared to no use, dietary supplement use was neither statistically significantly associated with total colorectal adenoma recurrence (HR = 1.03; 95% CI 0.79-1.34) nor with recurrent advanced adenomas (HR = 1.59; 95% CI 0.88-2.87). This prospective cohort study did not suggest an association between dietary supplement use and colorectal adenoma recurrence.