New insights into the pathogenesis of Crohn's disease: are they relevant for therapeutic options?

During the last few years significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A genetic susceptibility to Crohn's disease has been proven by identification of variations as risk factor NOD2/CARD15. Functional data on NOD2/CARD15 and NF-kappaB activation indicate that an inflammatory reaction of the intestinal mucosa, as an immediate response of the innate immune system, may be necessary for the maintenance of gut homeostasis. Crohn's disease is now also discussed as an impaired and inadequate immune reaction and no longer only as a hyper-responsiveness of the mucosal immune system. Data on NOD2/CARD15 expression suggest that macrophages and epithelial cells could be the locus of the primary pathophysiological defect and that T-cell activation might just be a secondary effect inducing chronification of the inflammation, perhaps as backup mechanism to insufficient innate immunity. In addition to NOD2/CARD15 there are more "innate" pathways by which commensal and pathogenic bacteria can directly be hindered to invade the human body (such as interaction with Toll like receptors, TLRs and defensins). The "germ-concept" and the "genetic concept" of IBD pathophysiology are converging. However, more time is needed until these important insights in IBD pathogenesis will make their way into routine diagnostic procedures and treatment of patients with IBD

Serum protein electrophoresis : an underused but very useful test

Serum protein electrophoresis is used in clinical practice to identify patients with multiple myeloma and other serum protein disorders. It is an inexpensive and easy-to-perform screening procedure. Electrophoresis separates serum proteins based on their physical properties and identifies morphologic patterns in response to acute and chronic inflammation, various malignancies, liver or renal failure, and hereditary protein disorders. For gastroenterologists, the use of serum protein electrophoresis may be helpful in the diagnosis of both common diseases with unusual presentations and rare disorders with typical presentations. Therefore, it represents an ideal screening tool

Diagnosis and outcome of oesophageal Crohn's disease

BACKGROUND AND AIMS: Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS: A total of 40 patients were reported [22 males, mean (±SD, range) age at oesophageal CD diagnosis: 25 (±13.3, 10-71) years and mean time of follow-up: 67 (±68.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (±5.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION: In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.info:eu-repo/semantics/publishedVersio

High altitude journeys, flights and hypoxia: any role for disease flares in IBD patients?

The importance of environmental factors in the pathogenesis including their disease-modifying potential are increasingly recognized in inflammatory bowel disease (IBD) patients, largely driven by the perception that the prevalence and incidence of IBD are on the rise within the last few years, especially in non-western countries. One of those factors is believed to be hypoxia. The role of hypoxia as a modifying or even causative factor in the genesis and maintenance of inflammation has been increasingly elucidated in recent years. Hypoxia is believed to be a main inducing factor of inflammation. This has been studied in different animal experiments as well as in humans exposed to hypoxia. In several studies - mainly in mice - animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future

Air suctioning during colon biopsy acquisition reduces bacterial contamination

Background and Aim: Contamination of endoscopy suites with bacteria during procedures is of concern particularly through droplets during handling of biopsy specimens. It has been advocated that suctioning while removing the biopsy forceps could help to reduce potentially hazardous bioaerosols. The aim of the present study was to evaluate the efficacy of air suctioning during removal of the biopsy forceps. Materials and Methods: Airborne bacteria were collected by an impactor air-sampler (MAS-100). Fifty liters of air were collected continuously for 30 seconds at a 30 cm distance from the colonoscope suction channel. Room air samples were taken in the endoscopy suite in the morning prior to the beginning of the endoscopy program, during colonoscopy with a sham biopsy in the descending colon with and without suctioning and at the end of the procedure day. Standard 90 mm Petri dishes containing a selective medium for gram-positive cocci (CNA blood agar) were used with the impaction sampler and colony forming units/m3 (cfu) were determined. Results: Measurements were performed at fifty consecutive colonoscopies. Prior to the beginning of the endoscopy program, the bioaerosol burden in the colonoscopy suite reached a mean of 4.2 cfu/m3. During colonoscopies performed without suctioning at biopsy the bioaerosol burden increased to 29.4 cfu/m3 whereas this burden increased only to 15.1 cfu/m3 when the suctioning was applied during removal of the biopsy forceps. The difference in bioaerosol burden between suctioning and no suctioning was highly significant (p < 0.0005). At the end of the procedure day the airborne bacteria count dropped to 15.6 cfu/m3. The analysis of the colonies on the CNA blood agar identified predominantly enterococci. Staphylococci spp. and other gram-positive bacteria were rarely isolated. Conclusion: The present study indicates that the bioaerosol burden during handling of biopsy specimens is not neglectable but can be reduced by the simple habit of applying suctioning during acquisition of biopsies. This practice might be an important infection-control measure during gastrointestinal endoscopies

Expression patterns of TNFα, MAdCAM1 and STAT3 in intestinal and skin manifestations of inflammatory bowel disease

Background: Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear. Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis). A semiquantitative score (0-100%) was used for evaluation. Results: TNFα was upregulated in intestinal biopsies from active Crohn`s disease (CD) vs. controls (36.2 vs. 12.1, p<0.001), but not ulcerative colitis (UC: 17.9). NFκB however was upregulated in intestinal biopsies from both active CD and UC (43.2 and 34.5 vs. 21.8, p<0.001 and p=0.017). TNFα and NFκB were overexpressed in skin biopsies from EN, PG and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, while it was upregulated in active UC vs. controls (57.5 vs. 35.4, p=0.003). STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, while a similar upregulation was seen in skin biopsies from EN (84.7 vs. 22.3, p<0.001) and PG (60.5 vs. 22.3, p=0.011), but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls. Conclusions: Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1 support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab

Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial

OBJECTIVE: To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms. DESIGN: Randomised controlled crossover study. PARTICIPANTS: 20 healthy adults (14 men) aged 23-58. INTERVENTIONS: Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium (13)Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order. MAIN OUTCOME MEASURES: Cumulative percentage dose of (13)C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales). RESULTS: Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of (13)C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, -0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference -0.40, -0.01 to -0.79; P<0.046). No difference in dyspeptic symptoms was present. CONCLUSIONS: Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT00943696

Cytomegalovirus disease in inflammatory bowel disease: epidemiology and disease characteristics in a large single-centre experience

BACKGROUND Patients with inflammatory bowel disease (IBD) show an increased risk of developing cytomegalovirus (CMV) disease because of immunosuppressive medication and malnutrition. Here, we aimed to investigate the prevalence and clinical characteristics of CMV disease in our cohort of IBD patients. PATIENTS AND METHODS We carried out a retrospective analysis of 1023 IBD patients treated at our IBD clinic at the University Hospital Zurich between 2007 and 2014. CMV disease was defined as a positive immunohistochemistry for CMV and 14 patients were identified. RESULTS The prevalence of CMV disease in our IBD cohort was 1.37%. Twelve patients had ulcerative colitis and two had Crohn's disease with colonic involvement. All patients who developed CMV disease received immunosuppressive medication or, as in one case, had HIV infection. The most used immunosuppressive medications were steroids and azathioprine. The most common therapeutic strategy was the consecutive use of ganciclovir and valganciclovir. Ten patients recovered and two were treatment refractory; among these, one required colectomy and two had a relapse. CONCLUSION CMV disease may influence the clinical course of IBD. There is probably an association between CMV disease and IBD-specific medication. Risk factors, epidemiology and therapeutic strategy need to be further investigated

Effect of distance to specialist care for the diagnosis and disease outcome of inflammatory bowel disease in the Swiss inflammatory bowel disease cohort study

Background: Inflammatory bowel disease (IBD) needs early interventions and an individual specialist-patient relationship. Distance from a tertiary IBD center might affect patient's disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods: Patient's home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: 35 km (group 3). Results: Our study included in total 408 IBD patients [234 Crohn's disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups. Conclusions: Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland

Prevalence of extraintestinal manifestations in paediatric patients with Inflammatory Bowel Disease : results from the Swiss IBD Cohort Study

Background: There is a paucity of data from large cohort studies on the prevalence and type of extraintestinal manifestations in pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and type of EIM in pediatric patients with inflammatory bowel disease (IBD). Methods: Data from patients enrolled in the Pediatric Swiss IBD Cohort Study (P-SIBDCS) were analyzed. Since 2008 the P-SIBDCS collects data on patients aged 2-17 from hospitals and private practices across Switzerland. Results of continuous data are reported as median and interquartile range