Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Bulgaria: An Internet-Based Survey.

BACKGROUND: The global pooled prevalence of gastroesophageal reflux disease (GORD) is approximately 14% and varies significantly according to the country. More population-based studies are needed in regions lacking epidemiological data on the prevalence of GORD, such as Eastern Europe, particularly Bulgaria. This current study aimed to evaluate the prevalence of GORD in Bulgaria and assess the risk factors associated with this disorder. METHODS: An internet-based health survey was sent to Bulgarian adults. Individuals were invited to complete an online questionnaire on general and gastrointestinal health. The aim of the study was not explicitly stated. The survey collected data on sociodemographic and behavioral characteristics, validated questions to assess GORD, diagnostic questions based on Rome IV criteria to assess irritable bowel syndrome (IBS) and functional dyspepsia (FD), and questions about antisecretory drugs usage. RESULTS: Data were collected from 1,896 individuals (mean age = 35.5 years, SD = 11.7, 73.1% females). The prevalence of GORD in the study population was 27.5%, while 57.29% of all GORD patients taking PPIs had PPI-refractory GORD. Age (p = 0.02), body mass index (BMI) (p < 0.001), marital status (p = 0.03), occupation (p < 0.001), sexual problems (p < 0.001), FD (p < 0.001), and IBS (p < 0.001) were significantly associated with GORD prevalence. Patients with FD (p < 0.001; OR 5.38), IBS (p = 0.03; OR 1.07), and with higher BMI (p < 0.001, OR 1.05) were at an increased risk of having GORD. CONCLUSIONS: The first data on GORD prevalence in the adult population in Bulgaria have been reported. Disorders of gut-brain interaction have a significant impact on the prevalence of GORD.

Coordinated Multi-Language Translation of A Validated Symptom Questionnaire for Carbohydrate Intolerances: A Practical Structured Procedure.

BACKGROUND AND AIMS: Validated questionnaires help to minimize diagnostic bias, to standardize symptom assessment and to achieve comparability between studies and centers. In a recent European guideline the adult and the pediatric carbohydrate perception questionnaires (aCPQ and pCPQ), were recommended to be used for the diagnosis of carbohydrate intolerances in adult and pediatric patients. The implementation of this guideline into clinical practice makes availability of validated translations a necessity. METHODS: Clinical experts who recognized the need for these questionnaires to be available in their own language participated in the translation process. The tasks were assigned and a workflow following a predefined procedure based on recommendations of the Rome foundation was developed. The procedure had 5 phases: foundation, nomination, translation, revision, cognitive debriefing. RESULTS: Within eight months the aCPQ was translated into Bulgarian, French, Hungarian, Italian, Polish, Romanian, Russian and Slovenian language and the pCPQ into Dutch, French and Romanian. This expands the population which can be served with the aCPQ from 160 million to over 500 million Europeans. The reach of pCPQ expanded from 92 million to 193 million Europeans. CONCLUSIONS: We report the development and implementation of a centrally organized process of translation of validated questionnaires, following a predefined procedure based on recommendations of the Rome foundation. This structured procedure may aid future efforts to standardize and harmonize the translation of validated questionnaires.

Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.

Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr.

Diagnosis and management of irritable bowel syndrome-like symptoms in ulcerative colitis.

Both ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) conditions that show some typical features. Persistent GI symptoms typical for IBS are observed in patients with diagnosed UC. Both IBS and UC are characterised by dysregulation of the enteric nervous system, alterations in the gut flora, low-grade mucosal inflammation, and activation of the brain-gut axis. Therefore, it appears that there may be some overlap between the two conditions. It is rather difficult to tell if the lower gastrointestinal symptoms are secondary to coexisting IBS or a hidden UC condition.

Biomarkers in Irritable Bowel Syndrome: Biological Rationale and Diagnostic Value.

BACKGROUND: Patients with irritable bowel syndrome (IBS) usually suffer from nonspecific and overlapping signs that hamper the diagnostic process. In line with this, biomarkers specific for IBS could be of great benefit for diagnosing and managing patients. In IBS, the need is for apparent distinguishing features linked to the disease that improve diagnosis, differentiate from other organic diseases, and discriminate between IBS subtypes. SUMMARY: Some biomarkers are associated with a possible pathophysiologic mechanism of IBS; others are used for differentiating IBS from non-IBS patients. Implementation of IBS biomarkers in everyday clinical practice is critical for early diagnosis and treatment. However, our knowledge about their efficient use is still scarce. Key Messages: This review discusses the biomarkers implemented for IBS diagnosis and management, such as blood (serum), fecal, immunological, related to the microbiome, microRNAs, and some promising novel biomarkers associated with imaging and psychological features of the disease. We focus on the most commonly studied and validated biomarkers and their biological rationale, diagnostic, and clinical value.

European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus.

INTRODUCTION: Measurement of breath hydrogen (H2 ) and methane (CH4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline. METHODS: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H2 -CH4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria. RESULTS: The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H2 -CH4 -breath tests in these indications and recommends approaches to mitigate these issues. CONCLUSION: This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.

Increased prevalence of gastrointestinal symptoms and disorders of gut-brain interaction during the COVID-19 pandemic: An internet-based survey.

BACKGROUND: Quarantine with social distancing has reduced transmission of COVID-19; however, fear of the disease and these remedial measures cause anxiety and stress. It is not known whether these events have impacted the prevalence of gastrointestinal (GI) symptoms and disorders of brain-gut interaction (DGBI). METHODS: An online platform evaluated the prevalence of GI symptoms during the COVID-19 pandemic. Data collection utilized validated questionnaires and was fully anonymized. Findings were compared with identical data acquired in 2019. The association of results with stress and anxiety was analyzed. RESULTS: Data were collected from 1896 subjects May - August 2019 to 980 non-identical subjects May - June 2020. GI symptoms were reported by 68.9% during the COVID-19 lockdown compared with 56.0% the previous year (p < 0.001). The prevalence of irritable bowel syndrome (26.3% vs. 20.0%; p < 0.001), functional dyspepsia (18.3% vs. 12.7%; p < 0.001), heartburn (31.7% vs. 26.2%, p = 0.002), and self-reported milk intolerance (43.5% vs. 37.8% p = 0.004) was higher during the pandemic. Many individuals reported multiple symptoms. Anxiety was associated with presence of all GI symptoms. High levels of stress impacted functional dyspepsia (p = 0.045) and abdominal pain (p = 0.013). The presence of DGBI (p < 0.001; OR 22.99), self-reported milk intolerance (p < 0.001; OR 2.50), and anxiety (p < 0.001; OR 2.18) was independently associated with increased GI symptoms during COVID-19 pandemic. CONCLUSIONS: The prevalence of GI symptoms was significantly higher during the COVID-19 lockdown than under normal circumstances the previous year. This increase was attributable to increased numbers of patients with DGBI, an effect that was associated with anxiety.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

Gastrointestinal mucosal immunity and COVID-19.

As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.

The public's attitude towards doctors' use of Twitter and perceived professionalism: an exploratory study.

INTRODUCTION: Medical professionals use social media to interact with other healthcare professionals, discuss medical issues and promote healthcare information. These platforms have tremendous power to promote healthcare messages but also have potential to damage the profession if used inappropriately. It is currently unknown how others perceive medical doctors' Twitter activity and, therefore, we conducted an online survey exploring these views. METHODS: We used a Google Forms questionnaire consisting of 21 questions, which we distributed on Twitter, exploring doctors', patients', the public's and other healthcare professionals' views of doctors' Twitter activities. We investigated factors that were associated with mistrust by univariate and multivariate analysis. RESULTS: Seven-hundred and twenty-six respondents completed the survey. By univariate analysis, a higher proportion of non-doctors reported witnessing unprofessional behaviour and potential breaches of patient confidentiality compared with doctors (p<0.01). In addition, a significantly higher proportion of non-doctors felt that doctors' Twitter accounts should be monitored by both their employer and regulator when compared with doctors. By multivariate analysis, the main predictor of mistrust in the profession were those that had previously witnessed unprofessional behaviour (odds ratio 2.70; 95% confidence interval 2.08-3.33; p<0.01). CONCLUSION: There are discrepancies in how doctors and non-doctors view Twitter activity and significant mistrust in the profession was brought about by doctors' Twitter activity. To help limit this, adherence to current guidelines set out by the General Medical Council and British Medical Association is vital and doctors should be cautious about how their Twitter activity is professionally perceived by others before posting.

Screening for hereditary transthyretin amyloidosis in Bulgaria.

Transthyretin amyloid (ATTR) amyloidosis is a rare disorder with an adult-onset defined by the accumulation of misfolded fibrils predominantly in peripheral nerves, the heart, and the digestive tract. The disease is characterized by two forms - hereditary (ATTRv) or acquired (ATTRwt). Various point mutations in the transthyretin gene induce the hereditary form of the disease. For finding new cases of ATTR amyloidosis and proper screening, the establishment of a multidisciplinary team and a Centre of Excellence (CoE) is essential. CoE provides regular education and training for better diagnosis and treatment. In the current review, we focus on the importance of having a multidisciplinary team and CoE, the screening strategy for ATTR amyloidosis in Bulgaria, and assessments performed when a patient is first suspected of having this rare disease.

Serum Levels of Fibroblast Growth Factor 19 Correlate with the Severity of Diarrhea and Independently from Intestinal Inflammation in Patients with Inflammatory Bowel Disease or Microscopic Colitis.

BACKGROUND: In chronic diarrhea patients, massive over-reporting symptom-based criteria for functional bowel disorders are pitfalls. There is currently no objective biomarker that may provide a correct correlation with the severity of chronic diarrhea. To clarify the role of fibroblast growth factor-19 (FGF-19) as a biomarker of objective measurements of the severity of diarrhea in comparison with a patientreported outcome, based on the Bristol Stool Form (BSF) Scale. METHODS: Consecutive 100 patients with chronic diarrhea underwent standard investigations with laboratory tests, fecal calprotectin (FC), endoscopy with biopsies, and serum FGF-19. All patients and 14 healthy controls completed a diary recording, BSF, and stool frequency. RESULTS: We found that irritable bowel syndrome with diarrhea (IBS-D) n = 21/23 (91%) reported a high number on BSF ≥6, compared to patients with inflammatory bowel diseases (IBD) 56/77 (72%) with BSF ≥ 6 (P = .011). FGF-19 median serum levels were significantly lower in Microscopic colitis (0.010 pg/mL) and IBD patients (0.009 pg/mL) compare to IBS-D (266.9 pg/mL) and high levels in healthy subjects (463 pg/mL) (P < .001). Strong inverse correlation of FGF-19 with the stool frequency/day and stool index was found (r = -0.800, P < .001; r = -0.739, P < .001), independently from disease activity (r = -0.718, P = .001; r = -0.792, P = .001). CONCLUSION: Serum FGF-19 can become a new biomarker for evaluating the severity of diarrhea with objectively and independently from intestinal inflammation. FC and FGF-19 are predictive biomarkers for the organic cause of diarrhea.

Young age and short duration of the disease are associated with more frequent relapses in inflammatory bowel disease patients.

AIMS: To evaluate the effects of the clinical predictors such as age, duration of disease, sex, and smoking on the frequency of relapses in IBD patients. METHODS: This study recruited 289 IBD (133 with CD and 156 with UC) patients. All were followed-up for 36 months for relapses of the disease. We defined as frequently relapsing (≥1/year) patients with at least one relapse per year and as infrequently relapsing those with less than one relapse per year (<1/year). We assessed the effect of the clinical predictors: age, duration of disease, sex, and smoking on the frequency of relapses in IBD patients. RESULTS: Sixty-four (48.1%) of the CD patients were frequently relapsing and 69 (51.9%) were infrequently relapsing. There was a significant association between the age and the frequency of relapse (p=0.001; OR 0.964; 95% CI 0.941-0.987, p=0.002) and between the duration of the disease and frequency of relapse (p<0.001; OR 0.740, 95% CI 0.655-0.837, p<0.001). Seventy-two (46.2%) of the UC patients were frequently relapsing and 84 (53.8%) were infrequently relapsing. There was a significant association between the age and the frequency of relapse (p=0.001; OR 0.964, 95% CI 0.941-0.987, p=0.002) and between the duration of the disease and frequency of relapse (p<0.001; OR 0.740, 95% CI 0.655-0.837, p<0.001). CONCLUSION: We demonstrate in a relatively significant cohort of IBD patients that young age and short duration of the disease are associated with more frequent relapses.

Small intestinal bacterial overgrowth and non-alcoholic fatty liver disease diagnosed by transient elastography and liver biopsy.

BACKGROUND: We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non-alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non-significant or no liver fibrosis. METHODS: NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum. RESULTS: Patients with non-alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07-37.37), 2.50 (1.16-5.37) and 27.6 (6.41-119), respectively). The most commonly isolated were gram-negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae. CONCLUSION: In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well-investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.

Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations.

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases. Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists. This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.

Biopsy Sampling in Upper Gastrointestinal Endoscopy: A Survey from 10 Tertiary Referral Centres Across Europe.

BACKGROUND: Guidelines give robust recommendations on which biopsies should be taken when there is endoscopic suggestion of gastric inflammation. Adherence to these guidelines often seems arbitrary. This study aimed to give an overview on current practice in tertiary referral centres across Europe. METHODS: Data were collected at 10 tertiary referral centres. Demographic data, the indication for each procedure, endoscopic findings, and the number and sampling site of biopsies were recorded. Findings were compared between centres, and factors influencing the decision to take biopsies were explored. RESULTS: Biopsies were taken in 56.6% of 9,425 procedures, with significant variation between centres (p < 0.001). Gastric biopsies were taken in 43.8% of all procedures. Sampling location varied with the procedure indication (p < 0.001) without consistent pattern across the centres. Fewer biopsies were taken in centres which routinely applied the updated Sydney classification for gastritis assessment (46.0%), compared to centres where this was done only upon request (75.3%, p < 0.001). This was the same for centres stratifying patients according to the OLGA system (51.8 vs. 73.0%, p < 0.001). More biopsies were taken in centres following the MAPS guidelines on stomach surveillance (68.1 vs. 37.1%, p < 0.001). Biopsy sampling was more likely in younger patients in 8 centres (p < 0.05), but this was not true for the whole cohort (p = 0.537). The percentage of procedures with biopsies correlated directly with additional costs charged in case of biopsies (r = 0.709, p = 0.022). CONCLUSION: Adherence to guideline recommendations for biopsy sampling at gastroscopy was inconsistent across the participating centres. Our data suggest that centre-specific policies are applied instead.