Anal defecatory function in ulcerative colitis patients after total proctocolectomy and ileal pouch-anal anastomosis: a prospective cohort study.

BACKGROUND: Total proctocolectomy (TPC) followed by ileal pouch-anal anastomosis (IPAA) remains the only viable option whenever different treatment modalities fail in patients with ulcerative colitis (UC). OBJECTIVE: Prospective cohort pre/post study examining the anal defecatory function and competence in UC patients undergoing TPC plus IPAA using high-resolution anorectal manometry (HR-ARM). PATIENTS: Patients undergoing TPC and IPAA were enrolled in the study and subjected to HR-ARM prior to and 6 months after surgery. The anal resting, squeeze and push pressures were recorded, together with the rectal sensation and the rectal balloon expulsion test. The number of bowel movements, symptoms/signs related to fecal incontinence, as well as the IBDQ-32 quality of life questionnaires were documented during both HR-ARM visits. RESULTS: A total of 20 consecutive UC patients were recruited in our study. The mean (SD) number of bowel movements before the TPC plus IPAA was 10.1 (2.8), while the same number after the pouch surgery was 7.7 (3.1) [ P  = 0.01]. Symptoms or signs of fecal incontinence were noted in one of our patients prior to the operation; however, none of our patients reported any such symptoms after the pouch surgery. The median (IQR) IBDQ-32 questionnaire scores before and after surgery were 121.5 (13.5) and 142.5 (16.0) respectively. At the same time, the anorectal function remained intact since both the anal resting and squeeze pressures were not significantly changed. CONCLUSION: UC patients subjected to TPC-IPAA exhibit improved bowel movements and a normal anal defecatory function and competence post-surgery.

Sedation during endoscopic procedures: a Hellenic Society of Gastroenterology Position Statement.

Administration of sedation by non-anesthesiologists during gastrointestinal endoscopy remains highly controversial in Greece. The aim of this set of 16 position statements prepared by experts in the field on behalf of the Hellenic Society of Gastroenterology is to aid gastroenterologists in their everyday clinical practice and provide evidence for the best use of drugs for the sedation of patients who undergo an endoscopy. The statements address issues such as the level of sedation required, the best drugs used, their mode of action, their side-effects and possible ways to counter their action, and were adopted if at least 80% of all participants agreed upon them.

The ulcerative colitis narrative Greece survey: patients' and physicians' perspective on quality of life and disease management.

Background: Using data from the ulcerative colitis (UC) narrative Greece survey, part of a global survey of patients and physicians, we aimed to identify the impact of UC on patients' lives and to compare patients' and gastroenterologists' responses to questions relating to communication during the management of UC in our country. Methods: The survey was conducted online by The Harris Poll, and included 95 patients and 51 gastroenterologists. Eligible were adult UC patients who had seen a gastroenterologist in the past 12 months and had at some time taken a prescription medication (excluding those who had only ever taken 5-aminosalicylates). Patients with mild UC were capped at 20% of total survey respondents to focus the survey on patients with moderate-to-severe disease. Results: The mean time between first experienced symptoms and diagnosis of UC was 0.89 years. Most patients (82%) considered their UC to be in remission, while 98% felt satisfied with their communication with their treating gastroenterologist. However, the disease affected patients' daily life and employment adversely, with 78% reporting their UC to be mentally exhausting. Although nearly 7 in 10 physicians (69%) reported having taken steps to improve their communication skills, many patients (60%) wished they had more time at appointments with their physician, while 44% still felt uncomfortable talking about their sex life and personal relationships. Conclusions: Greek UC patients appear to be satisfied with their physicians and their disease management. Gaps in patient-physician communication relating to quality of life, emotional, and sexual/relationship concerns need to be addressed.

Prevalence of inflammatory bowel disease in young Greek Army male recruits from 2006 to 2018: a 13-year retrospective study from a tertiary center.

BACKGROUND: The prevalence and incidence of inflammatory bowel diseases (IBDs) vary among countries. Data regarding prevalence of IBD in Greece are limited or outdated. METHODS: We reviewed the medical records of IBD patients from a population of 551,808 Greek Army recruits in a 13-year period (2006-2018). Study population consisted of males 18-37 of age from Northwest, Central Greece (including Attica), Peloponnese, and Aegean Sea Islands. Age, disease distribution, pharmaceutical treatment and IBD-related surgery at the time of patients' admission were recorded. RESULTS: The prevalence of IBD among male recruits during the studied period was 0.15% (839/551 808, 95% confidence interval 0.14-0.16%). Of these, 448 (53.4%) had Crohn's disease (CD) and 391 (46.6%) ulcerative colitis (UC). Although 32.1% of CD patients had been treated with biologics, most often infliximab (60% of them), azathioprine was the most common as monotherapy (27% of patients). Among UC patients, mesalamine was the most often prescribed treatment (64.2%), whereas treatment with biologics as monotherapy or in combination with azathioprine was used in a ratio 1:2 compared to CD patients. A gradual reduction in steroid use was noted from 2006 to 2018, coinciding with the advent and increasing use of biologics. IBD-related surgery had been performed in 8% and 2.8% of CD and UC patients, respectively. CONCLUSION: The prevalence of IBD in Greek male recruits was 0.15% with a slight CD predominance. Remarkable changes in therapeutic trends were noted with an increasing use of biologics and reduced prescription of steroids, especially for CD.

Response to Anti-α4ß7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline.

BACKGROUND: Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4ß7, vedolizumab, in patients with active ulcerative colitis (UC). METHODS: Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. RESULTS: In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a "core" mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. CONCLUSIONS: Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Informed consent in inflammatory bowel disease: a necessity in real-world clinical practice.

In modern medicine, any medical intervention has to be supported by a patient's informed consent. Challenges to this process include the specificity and complexity of medical information being provided, the patient's ability to comprehend the information, the medical uncertainty of the outcomes, and the physician's legal concerns. Important elements of the consent process are respect for the patient's autonomy and self-determination, appropriate disclosure and verification of their understanding, and voluntariness. In inflammatory bowel disease (IBD), pharmaceutical treatment carries significant risks, making discussion and illustration of the treatment critical for decision making. This review aims to emphasize the importance of the informed consent process in routine IBD clinical practice, and suggests an appropriate way of informing patients about the medical treatment on offer. The information that has to be comprehensively presented before consent includes: i) treatment goal; ii) basic characteristics of treatment (route and timetable of drug administration, drug efficacy, adverse events); and iii) consequences of staying untreated. The IBD physician's main concerns must include ensuring not only that the information being provided is detailed and objective, but also that the decision-making process is shared with the patient. Ultimately, the process of obtaining informed consent in real-world clinical practice is undoubtedly of great importance, for both upholding the principles of medical ethics and avoiding legal conflicts.

Management of Patients with Inflammatory Diseases during the COVID-19 Pandemic.

Patients with various inflammatory diseases of the gastrointestinal tract, skin, liver, kidneys, and musculoskeletal system-connective tissues, often undergo different anti-inflammatory therapies to maintain remission and avoid serious and/or life-threatening complications. Available data so far show an increased rate of hospitalization in such patients during the COVID19 pandemic. The key points of our position statement are summarized below: Patients with inflammatory diseases who receive moderate or high-risk anti-inflammatory therapies might be considered as an increased risk group for severe COVID-19 and appropriate measures should be taken in order to protect them. Initiation of immuno-suppressive/modulatory therapies should be done with caution, taking into account the severity of the underlying inflammatory disease, the type of anti-inflammatory treatment, and the risk of exposure to the SARS-CoV-2 virus. Discontinuation of anti-inflammatory therapies in patients who have not been exposed to or infected with the SARS-CoV-2 virus is not recommended. In patients who become infected with SARS-CoV-2, anti-inflammatory therapies should be discontinued, except in special cases. Specialty physicians should actively participate in the Interdisciplinary Teams caring for patients with inflammatory diseases during COVID19 infection.

Prevalence of Clostridium difficile infection among hospitalized inflammatory bowel disease patients in Greece.

BACKGROUND: Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), which is associated significantly with disease severity. We aimed to determine the rates of CDI among hospitalized IBD patients in major tertiary referral hospitals in Greece. PATIENTS AND METHODS: A retrospective analysis was carried out of stool cultures from hospitalized patients investigated for diarrhea, during 2016, tested for CDI with glutamate dehydrogenase (GDH) and toxins A and B. RESULTS: In total, 6932 patients were tested for CDI; 894 were positive for GDH (12.89%) and 339 were also positive for C. difficile toxin (4.89%). The prevalence of CDI among all hospitalized patients was 1.6/1000 patient-days. Among these, there were 401 IBD patients, and 62 were positive for GDH (15.46%) and 30 were also positive for C. difficile toxin (7.48%). The prevalence of CDI in IBD patients was 2.5/1000 patient-days, significantly higher than in non-IBD hospitalized patients (30/401 vs. 309/6531, P=0.013). Among the 30 IBD patients (ulcerative colitis=18, Crohn's disease=12) with CDI, six were receiving biologics, three were on corticosteroids [one combined with azathioprine (AZA) and one combined with 5-ASA], nine were on AZA monotherapy and 12 were on 5-ASA monotherapy. The prevalence of CDI among patients receiving AZA monotherapy was significantly higher than in patients receiving other medications (9/68 vs. 21/333, P=0.047). Mild CDI (n=28) was treated with metronidazole and/or vancomycin, whereas severe CDI (n=2) was treated with vancomycin. CONCLUSION: The prevalence of CDI is higher in hospitalized IBD patients than those without IBD and AZA monotherapy increases the risk of CDI.

Identification of serum proteome signature of irritable bowel syndrome: Potential utility of the tool for early diagnosis and patient's stratification.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence, and great heterogeneity of symptoms. Numerous factors are correlated with IBS development; however, the pathophysiology is not yet clear. In addition, there is no appropriate diagnostic tool available. The aim of this study was the identification of protein expression alterations in IBS patients compared to healthy individuals. Serum samples from 30 IBS patients (10 with IBS-Diarrhea, 10 IBS-Constipation and 10 IBS-Mixed) and 10 healthy individuals were subjected to proteomic analysis by 2-dimensional gel electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by matrix-assisted laser desorption tandem time-of-flight mass spectrometer and the results were confirmed by Western blot analysis. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was overexpressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. IBS-D group overexpressed immunoglobulin light chain Lambda (LAC3) and apolipoprotein E (APOE), IBS-C group overexpressed apolipoprotein H (APOH) and collagen alpha-1 (XIV) chain (COEA1), and IBS-M group and healthy individuals overexpressed retinol-binding protein 4 (RET4). Our results show a different serum protein profile of IBS patients compared to healthy controls. Understanding the role of these eight proteins which are differently expressed in IBS patients, may contribute to a better clarification of IBS pathogenesis and to patient's stratification. SIGNIFICANCE: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence and great heterogeneity of symptoms without any appropriate diagnostic tool available. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was expressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. Our results show that there is a different serum proteome signature in IBS compared to healthy individuals, as well as in IBS subgroups that could be used in the future for patient's stratification and as a diagnostic tool.

Proton pump inhibitor and selective serotonin reuptake inhibitor therapy for the management of noncardiac chest pain.

INTRODUCTION: Although gastroesophageal reflux disease is the main cause of noncardiac chest pain (NCCP), proton pump inhibitors (PPIs) benefit a minority of patients. Our prospective study evaluated the effect of PPI and selective serotonin reuptake inhibitors on the different subtypes of NCCP characterized by impedance-pH monitoring. METHODS: All NCCP patients underwent impedance-pH monitoring and on the basis of the results, those with abnormal distal esophageal acid exposure received PPIs twice daily (group A), those with a positive symptom index for chest pain received citalopram 20 mg and PPI once daily (group B), and those with a negative symptom index for chest pain received citalopram 20 mg once daily (group C). Therapy was administered for 12 weeks and treatment success was defined as complete disappearance of chest pain. RESULTS: From March 2015 to March 2016, 63 patients were included (group A=9, group B=18, group C=36). After 12 weeks of therapy, complete resolution of chest pain was noted in 8/9 (88.9%) group A, 13/18 (72.2%) group B, and 24/36 (66.7%) group C patients. CONCLUSION: Combined impedance-pH monitoring identifies different subtypes of NCCP patients who can receive tailored management. Targeted therapy with PPIs and/or citalopram offers complete symptom relief in the great majority of them.

Proteomics and irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a gastrointestinal disease that according to Rome IV criteria is subdivided into four subtypes. The pathophysiology of this disease is not well understood due to numerous factors playing multiple roles in disease development, such as diet, stress and hormones. IBS has a variety of symptoms and overlaps with many other gastrointestinal and non-gastrointestinal diseases. Area covered: This review aims to present an overview of implementation of proteomics in experimental studies in the field of IBS. Expert commentary: Proteomics is commonly used for biomarker discovery in and has also been extensively used in IBS research. The necessity of a sensitive and specific biomarker for IBS is apparent, but despite the intensive research performed in this field, an appropriate biomarker is not yet available.

Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF.

AIM: To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine. METHODS: In a prospective, multicenter, one-year study biologic naïve patients aged 25-65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls). Before and at weeks 12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell-lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before treatment was also associated with mucosal healing. RESULTS: Of 67 patients, 58 (86.6%) received combination and 9 (13.4%) anti-TNFα monotherapy. Overall 29 (43.3%) patients achieved mucosal healing; rates were higher in patients receiving combination therapy vs. monotherapy (p=0.03) and in azathioprine naïve vs. exposed patients in the combination group (p=0.01). Mucosal healing was associated with lower pre-treatment mucosal expression of transcription factor Th1-Tbet (p<0.05) and higher expression of Th17-Rorc (p<0.05). CONCLUSIONS: Mucosal healing was associated with combination therapy, especially in biologic and azathioprine-naïve patients and pre-treatment mucosal expression of specific Th specific transcripting factors (Tbet and Rorc).

Simethicone adjunct to polyethylene glycol improves small bowel capsule endoscopy imaging in non-Crohn's disease patients.

BACKGROUND: Currently, there is no standardized protocol for bowel preparation before small bowel capsule endoscopy (SBCE). This study aimed to investigate the effect of simethicone combined with polyethylene glycol (PEG) on the visualization quality (VQ) of the SBCE in patients with or without known or suspected Crohn's disease (CD). METHODS: This observational, prospective, single-center study included consecutive patients undergoing a SBCE between 2007 and 2008. Patients received either a standard bowel cleansing preparation of 2 L PEG and 80 mg simethicone orally 12 and 1 h before SBCE respectively (Group A) or only PEG (Group B). VQ, based on scores for luminal bubbles in frames taken from the small intestine, examination completeness, SBCE diagnostic yield, gastric and small bowel transit times were recorded. RESULTS: Of the 115 patients finally included (Group A, n=56 and Group B, n=59) the cecum was visualized in 103 (89.6%). Simethicone overall improved the VQ in the proximal [OR: 2.43 (95%CI: 1.08-5.45), P=0.032] but not in the distal bowel segment (P=0.064). Nevertheless, this effect was not observed in patients undergoing SBCE for either known or suspected CD. CONCLUSION: Simethicone as an adjunct to PEG for bowel preparation in patients undergoing SBCE significantly improved the VQ in non-CD patients.

DNA methylation changes in inflammatory bowel disease.

The cause of inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, remains a mystery but evidence is accumulating that complex interactions between the genetic background and the gut microbiota of the host and environmental factors associated with rapid industrialization and westernized life styles may underlie its pathogenesis. Recent epigenetic studies have suggested that interactions between environment and host DNA may play a leading role in the phenotypical expression of both diseases, explaining amongst others the differences in disease expression in monozygotic twins. DNA methylation is the most studied epigenetic modification and during the last decade its correlation to IBD pathogenesis has been well established. Genes from different molecular pathways have been studied but till now there is no standardized database of methylated genes in IBD. Thus, a thorough and in depth study of DNA methylation, its potential relation to IBD and its interaction with the available pharmaceutical armamentarium is of great interest.

Inflammatory bowel disease: Greek patients' perspective on quality of life, information on the disease, work productivity and family support.

BACKGROUND: The aim of this study was to identify inflammatory bowel disease (IBD) patients' perspectives regarding everyday life issues. METHODS: From October 2010 till April 2011, 1,181 IBD patients completed an anonymous questionnaire through the internet (827 cases) or at the outpatient clinic of the participating centers (354 cases), aiming to identify: a) the impact of disease on social life, emotional status and work productivity; b) the source of disease information; and c) the level of support from family members and friends. RESULTS: Fifty-five percent of the patients reported that IBD interferes with their social life, while 65% felt stressed, 60% depressed and 19% tired because of it. Disease information (physician/ internet) was reported only by 31%, while 26% admitted not discussing their therapy with their gastroenterologist. Forty percent felt that the health service they receive is not satisfactory, with 76% desiring more gastroenterologists, 67% more outpatient clinics, 49% more dieticians and 42% more psychologists specialized in IBD. IBD interfered with working capacity in 40% of the participants, while 57% needed time off of work (ranging from 1-20 days per year). One of three patients (32%) has not informed his work environment about the disease; however, 88% had the support of their family and friends for coping with it. CONCLUSIONS: Greek IBD patients claim that health-related social life, emotional status and work productivity are severely affected by their disease, whereas they complain about lack of information regarding the therapy. These unmet demands call for immediate action by healthcare providers and society.