Anemia and Iron Deficiency in Outpatients with Inflammatory Bowel Disease: Ubiquitous Yet Suboptimally Managed.

Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn's and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn's Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that­despite inconsistently measured iron parameters­is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care.

Multiple Switches From the Originator Infliximab to Biosimilars Is Effective and Safe in Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Though a single nonmedical switch from the originator infliximab (IFX) to a biosimilar is considered effective and safe for most patients with inflammatory bowel disease (IBD), very limited data are available on multiple successive switches. METHODS: We performed a prospective multicenter cohort study of adult IBD patients who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3). Patients were assessed at 4 and 12 months since the most recent switch for remission using clinical (physician's assessment) and biochemical (C-reactive protein [CRP], and fecal calprotectin [FC]) measures. Patients discontinuing treatment for ineffectiveness or adverse events before month 12 were imputed as nonremitters. RESULTS: One hundred seventy-six patients (Crohn's disease 71%, ulcerative colitis 27.8%, IBD unclassified 1.2%; group 1, 69; group 2, 80; group 3, 27) were included. At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively. There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups. Infusion reactions occurred in 1.7% of patients (3/176), all in patients with antidrug antibodies from group 2. CONCLUSIONS: Multiple successive switching and switching between biosimilars of IFX seemed to be effective and safe.

Limited diagnostic accuracy and clinical impact of single-operator peroral cholangioscopy for indeterminate biliary strictures.

BACKGROUND: Single-operator peroral cholangioscopy (sPOCS) is considered a valuable diagnostic modality for indeterminate biliary strictures. Nevertheless, studies show large variation in its characteristics and measures of diagnostic accuracy. Our aim was to estimate the diagnostic accuracy of sPOCS visual assessment and targeted biopsies for indeterminate biliary strictures. Additional aims were: estimation of the clinical impact of sPOCS and comparison of diagnostic accuracy with brush cytology. METHODS: A retrospective single-center study of adult patients who underwent sPOCS for indeterminate biliary strictures was performed. Diagnostic accuracy was defined as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The clinical impact of sPOCS was assessed by review of medical records, and classified according to its influence on patient management. RESULTS: 80 patients were included, with 40 % having primary sclerosing cholangitis (PSC). Prior ERCP was performed in 88 %, with removal of a biliary stent prior to sPOCS in 55 %. The sensitivity, specificity, PPV, and NPV for sPOCS visual impression and targeted biopsies were 64 %, 62 %, 41 %, and 84 %, and 15 %, 65 %, 75 %, and 69 %, respectively. The clinical impact of sPOCS was limited; outcome changed management in 17 % of patients. Sequential brush cytology sensitivity, specificity, PPV, and NPV were 47 %, 95 %, 80 %, and 83 %. CONCLUSIONS: The diagnostic accuracy of sPOCS for indeterminate biliary strictures was found to be inferior to brush cytology, with a low impact on patient management. These findings are obtained from a select patient population with a high prevalence of PSC and plastic stents in situ prior to sPOCS.

A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease.

Introduction: Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. Therefore, novel predictive biomarkers are urgently needed that better reflect mucosal disease activity in IBD. The aim of this study was to identify a combination of serum inflammatory biomarkers predictive for endoscopic disease activity. Methods: Serum concentrations of 10 inflammatory biomarkers were analyzed in 118 IBD patients [64 Crohn's disease (CD), 54 ulcerative colitis (UC)] and 20 healthy controls. In a subset of 71 IBD patients, endoscopic disease activity was established. Non-parametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity. Results: Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A, and TNF-α) showed better prediction of IBD disease activity than routine measures (CRP, fecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8, and Eotaxin-1, showing an optimism-adjusted area under the ROC (AuROC) curve of 0.84 (95% CI: 0.73-0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43-0.72, P = 0.32). Conclusion: The combination of SAA, IL-6, IL-8, and Eotaxin-1 reliably predicts endoscopic disease activity in IBD and might be valuable for monitoring disease activity and management of the disease.

Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.

Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

OBJECTIVE: Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. DESIGN: Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2. RESULTS: Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10-13). CONCLUSIONS: We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.

The cardiovascular risk profile of atherosclerotic gastrointestinal ischemia is different from other vascular beds.

BACKGROUND: The distribution of cardiovascular risk factors in patients with chronic gastrointestinal ischemia due to atherosclerosis of the splanchnic vessels (chronic splanchnic syndrome) is not well studied. The aim of this study was to determine the cardiovascular risk factor pattern in patients with chronic splanchnic syndrome. METHODS: From April 2003 to September 2007, atherosclerotic risk factors in consecutive patients with chronic splanchnic syndrome were compared prospectively with the general atherosclerotic risk profile in Western Europe and worldwide risk profile of coronary heart disease, peripheral artery disease, and cerebral vascular disease. RESULTS: Of 376 analyzed patients, 97 were diagnosed with chronic splanchnic syndrome. Data from 90 patients were available for analysis (7 were excluded because of incomplete data). Mean age was 63 years (range 28-86 years), and 74% were female. Fifty-nine percent of the patients had atherosclerotic disease in other vascular beds. Smoking was reported in 57%, and increased bodyweight in 21%. Hypercholesterolemia was present in 53%, hypertension in 62%, and diabetes in 21%. CONCLUSIONS: The atherosclerotic risk profile in patients with chronic splanchnic syndrome differed from other atherosclerotic diseases with a female preponderance, lower incidence of obesity/increased bodyweight, diabetes, hypertension, and hypercholesterolemia. Reduced caloric intake, related to the postprandial pain, may explain the observed differences.

Abdominal symptoms during physical exercise and the role of gastrointestinal ischaemia: a study in 12 symptomatic athletes.

BACKGROUND: Gastrointestinal (GI) symptoms during exercise may be caused by GI ischaemia. The authors report their experience with the diagnostic protocol and management of athletes with symptomatic exercise-induced GI ischaemia. The value of prolonged exercise tonometry in the diagnostic protocol of these patients was evaluated. METHODS: Patients referred for GI symptoms during physical exercise underwent a standardised diagnostic protocol, including prolonged exercise tonometry. Indicators of GI ischaemia, as measured by tonometry, were related to the presence of symptoms during the exercise test (S+ and S- tests) and exercise intensity. RESULTS: 12 athletes were specifically referred for GI symptoms during exercise (five males and seven females; median age 29 years (range 15-46 years)). Type of sport was cycling, long-distance running and triathlon. Median duration of symptoms was 32 months (range 7-240 months). Splanchnic artery stenosis was found in one athlete. GI ischaemia was found in six athletes during submaximal exercise. All athletes had gastric and jejunal ischaemia during maximum intensity exercise. No significant difference was found in gastric and jejunal Pco(2) or gradients between S+ and S- tests during any phase of the exercise protocol. In S+ tests, but not in S- tests, a significant correlation between lactate and gastric gradient was found. In S+ tests, the regression coefficients of gradients were higher than those in S- tests. Treatment advice aimed at limiting GI ischaemia were successful in reducing complaints in the majority of the athletes. CONCLUSION: GI ischaemia was present in all athletes during maximum intensity exercise and in 50% during submaximal exercise. Athletes with GI symptoms had higher gastric gradients per mmol/l increase in lactate, suggesting an increased susceptibility for the development of ischaemia during exercise. Treatment advice aimed at limiting GI ischaemia helped the majority of the referred athletes to reduce their complaints. Our results suggest an important role for GI ischaemia in the pathophysiology of their complaints.

Prevalence of gastrointestinal complaints in runners competing in a long-distance run: an internet-based observational study in 1281 subjects.

OBJECTIVE: To assess the prevalence, risk factors and timing of gastrointestinal (GI) complaints in a large group of runners competing in a long-distance run. GI symptoms indicating GI ischaemia were of specific interest. MATERIAL AND METHODS: A questionnaire was sent by e-mail to 2076 athletes who had competed in a recreational run and 1281 (62% response rate) were returned. Reported GI complaints were related to variables such as age, gender, distance, fluid and food ingestion and running experience. For statistical analyses, chi(2) tests and logistic regression analyses were used. RESULTS: The run was completed by 98% of the runners. Three athletes dropped out because of GI complaints, 45% had at least one GI complaint during running, while 11% of the runners suffered from serious GI complaints during the run, the last mentioned being significantly related to runners who were not familiar with fluid ingestion, those of younger age, female gender and those who did not complete the run. Of the runners, 2.7% had complaints during the first 24 h after the run. This was significantly related to female gender and GI complaints during the run. CONCLUSIONS: The prevalence of GI complaints during and after running was low compared with that reported in other studies, which is partly due to the definition of "symptomatic" used in our study. The risk factors associated with becoming symptomatic were identical to those in other studies. The relationship between complaints during the run and the type of complaints afterwards suggests a role of GI ischaemia in the pathophysiology of running-induced GI symptoms.

Assessment of a new prototype hydrogel CO( 2 ) sensor; comparison with air tonometry.

OBJECTIVE: Gastrointestinal ischemia is always accompanied by an increased luminal CO(2). Currently, air tonometry is used to measure luminal CO(2). To improve the response time a new sensor was developed, enabling continuous CO(2) measurement. It consists of a pH-sensitive hydrogel which swells and shrinks in response to luminal CO(2), which is measured by the pressure sensor. We evaluated the potential clinical value of the sensor during an in vitro and in vivo study. METHODS: The response time to immediate, and stepwise change in pCO(2) was determined between 5 and 15 kPa, as well as temperature sensitivity between 25 and 40 degrees C at two pCO(2) levels. Three sensors were compared to air tonometry (Tonocap) in healthy volunteers using a stepwise incremental exercise test, followed by a period of hyperventilation and an artificial CO(2)-peak. RESULTS: The in vitro response time to CO(2) increase and decrease was mean 5.9 and 6.6 min. The bias, precision and reproducibility were +5%, 3% and 2%, resp. Increase of 1 degrees C at constant pCO(2) decreased sensor signal by 8%. In vivo tests: The relation with the Tonocap was poor during the exercise test. The response time of the sensor was 3 min during hyperventilation and the CO(2) peak. CONCLUSION: The hydrogel carbon dioxide sensor enabled fast and accurate pCO(2) measurement in a controlled environment but is very temperature dependent. The current prototype hydrogel sensor is still too unstable for clinical use, and should therefore be improved.