Corrigendum: Application of a multispecies probiotic reduces gastro-intestinal discomfort and induces microbial changes after colonoscopy.

[This corrects the article DOI: 10.3389/fonc.2022.1078315.].

[Reflux symptoms and upper abdominal pain: Reflux, Gastritis and whatever could be behind it]. / Sodbrennen und Oberbauchschmerzen: Reflux, Gastritis und was noch infrage kommt.

Reflux symptoms and upper abdominal pain are very common symptoms in general population. Both symptoms are visceral and thus cannot be linked to an organ or a disease. Diagnostic work-up revealed organic disease in up to 30%, when patients present with dyspeptic symptoms. Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) represent the most frequent and important disorders in western countries, when diagnostic work-up is done in patients with reflux symptoms and abdominal pain.

Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes.

BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis - Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

[Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice]. / Häufige Magen-Darm-Beschwerden: Management der funktionellen Dyspepsie und des Reizdarm-Syndroms in der Praxis.

Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice Abstract: Functional dyspepsia (FD) and irritable bowel syndrome (IBS), two common gastrointestinal entities with overlapping symptoms, should be diagnosed according to Rome IV criteria. This includes one or more of the following symptoms: in FD, postprandial fullness, early satiation, epigastric pain or burning; in IBS, recurrent abdominal pain associated with defecation, change in frequency of stool or form of stool. To exclude structural diseases, attention should be paid to alarm symptoms. As far as treatment is concerned, a stepwise scheme proves to be effective for both diseases. Step 1: doctor-patient discussion with explanation of diagnosis and prognosis as well as clarification of therapy goals; lifestyle adaptations; use of phytotherapeutics; step 2: symptom-oriented medication: for FD, PPIs or prokinetics; for IBS, antispasmodics, secretagogues, laxatives, bile acid sequestrants, antidiarrheals, antibiotics, probiotics; step 3: visceral analgesics (antidepressants).

Menthacarin, a Proprietary Peppermint Oil and Caraway Oil Combination, Improves Multiple Complaints in Patients with Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review summarizes published data on Menthacarin, the proprietary combination of peppermint oil and caraway oil, in the treatment of functional gastrointestinal disorders. Efficacy was assessed by meta-analysis of placebo-controlled trials. METHODS: We searched PubMed, the Cochrane Library, and the manufacturer's information system for clinical studies investigating the safety and efficacy of Menthacarin. Efficacy analyses included change from baseline of epigastric pain and general improvement of the patients' condition. RESULTS: Five randomized trials involving 580 patients were found, demonstrating significant effects of Menthacarin on symptoms of functional dyspepsia (FD) compared to placebo or similar effects compared to a reference drug. Seven other studies reported favorable results on therapeutic application in FD patients with concomitant Helicobacter pylori infection, in irritable bowel syndrome (IBS), and on tolerability in FD patients from 12 years of age. Three trials in FD with 249 patients were eligible for meta-analysis. Results demonstrate a significant reduction in pain intensity (standardized mean difference: 0.80; 95% confidence interval (CI): 0.39-1.21) and in item 2 of the Clinical Global Impression Scale (risk ratio: 2.65; 95% CI: 1.81-3.87) for Menthacarin. CONCLUSIONS: Menthacarin was shown to be effective and safe for the treatment of FD and represents a promising option for symptoms of IBS.

The Process of Developing a Disease Activity Index in Microscopic Colitis.

BACKGROUND AND AIMS: Patient-reported outcome measures [PROMs] aim to measure patients' perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. METHODS: The European Microscopic Colitis Activity Index [E-MCAI] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n = 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n = 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. RESULTS: Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. CONCLUSIONS: The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies.

Application of a multispecies probiotic reduces gastro-intestinal discomfort and induces microbial changes after colonoscopy.

Even after decades of research and pharmaceutical development, cancer is still one of the most common causes of death in the western population and the management of cancer will remain a major challenge of medical research. One of the most common types of cancer is colorectal cancer (CRC). Prevention by detection of early-stage precursors is the most reliable method to prevent CRC development. In dependence of age, familial predisposition, and other risk factors the preventative routine screening for CRC by colonoscopy should be performed at least twice in intervals of about ten years. Although colonoscopy is a life-saving clinical examination reducing both incidence and mortality of CRC significantly, it has still a bad reputation in the population as an uncomfortable procedure with unpleasant side effects lasting sometimes over days to weeks. These effects are most likely caused by the bowel preparation before colonoscopy, which is crucial for a successful colonoscopy with high quality. Beside pain, bleeding and other rare but severe complications of colonoscopy, cleaning of the intestinal mucosa alters the gut microbiome significantly and consistently. Abdominal pain, cramps, diarrhea, nausea, bloating, and constipation are common adverse events which can continue to affect patients for days or even weeks after the procedure. In this multicenter, placebo controlled, double blind clinical trial, we investigated the effect of an intervention with a multispecies probiotic formulation for 30 days on the adverse events due to bowel preparation. We show that the treatment of participants with the multispecies probiotic formulation decreases the number of days with constipation significantly, and reduced pain, bloating, diarrhea, and general discomfort. 16S based amplicon analyses reveal recovery of administered probiotic strains from stool samples and differences in alpha diversity dynamics with higher variability in the probiotic group compared to the placebo group. In conclusion, the probiotic ameliorates the side effects after colonoscopy and might be an important supplement to increase acceptance of this life-saving preventative examination. Further, we present here for the first time that probiotic intervention of only 30 days affects alpha diversity parameters in stool samples.

[The gastroenterology during the first and second wave of corona pandemic - two surveys by the working group of the guiding gastroenterologic clinicians (ALGK)]. / Die Gastroenterologie in der ersten und zweiten Corona-Welle ­ zwei Umfragen der Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte (ALGK).

BACKGROUND: An evaluation of the non-university hospitals in Germany with regard to the actual and follow-up working condition, alterations and perspectives during the Corona-crisis is missing. The working group of the guiding gastroenterologic clinicians (ALGK) comprises more than 70% of the head physicians of gastroenterological units leading to representative informations. METHODS: The ALGK conducted two surveys among its members in 2020 during the first and 2021 during the second Corona-wave. 369 members with correct email adresses were contacted. The first survey included 17 and the second survey 21 questions. RESULTS: 58 % of the respondent represented primary and standard care hospitals, 36 % secondary care hospitals, 6 % tertiary hospitals of maximum care, 43 % communal, 38 % confessional and 18 % private hospitals. 87 % of the respondent reported about cancellation of the hospital appointments by the patients (87 %/85 %). In the second survey, appointment cancellation by the physican (58 % vs. 84 %), reduction of emergency cases (16 % vs. 29 %), postponement of diagnostic or therapeutic appointments (85 % vs. 99 %) and reduction of programmed inpatient (65 vs. 91 %) or outpatient treatment (15 % vs. 84 %) were lesser compared to the first survey. Mean reduction of endoscopic procedures per unit were 337/month to 151/month (55 %) for diagnostic endoscopy, 174/month to 84/month (52 %) for therapeutic endoscopy and 56/month to 7/month (87,5 %) for prevention colonoscopy. The comparison between hospital operators revealed more reports on staff to be under quarantine, more very strong or strong feeling of psychological stress, more fear of corona-infection and more suspicion of ambulatory maintenance in gastroenterology in private hospitals. Willingness for vaccination was very high among physicians and nursing staff (92 %/89 %) and not different between the hospital operators. 38 % of the repsondent reported on the fear of existential risk of their hospital because of the Corona-crisis. CONCLUSION: The two ALGK surveys give a reprensentative picture of the situation of non-university gastroenterological units during Corona-pandemic in Germany.

Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial.

BACKGROUND AND AIMS: Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi. METHODS: Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8. RESULTS: Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase. CONCLUSIONS: Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.

[Quality management in the field of gastroenterology - Proposals of the Quality Commission of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) for Outpatient and Inpatient Quality Assurance]. / Qualität in der Gastroenterologie ­ "Vorschläge der Kommission Qualität der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten zur ambulanten und stationären Qualitätssicherung".

The quality of the medical care depends on numerous factors that can often be influenced by the doctor itself. It is a great challenge to follow the constant scientific progress in practice. Scientific standards in gastroenterology are defined in DGVS guidelines and regularly revised. The implementation of evidence-based recommendations in practice remains challenging. On the basis of the DGVS guidelines, the Quality Commission has therefore developed a selection of quality indicators with particular relevance using standardized criteria, the broad implementation of which could contribute to improved patient care in gastroenterology.

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis ­ Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

[Bile acid diarrhea, stepchild of chronic diarrhea - prevalence, diagnosis and treatment. Update 2021]. / Chologene Diarrhö, Stiefkind der chronischen Diarrhö ­ Prävalenz, Diagnostik und Therapie. Update 2021.

Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.

European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations.

INTRODUCTION: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

[Treatment of IBS with Lactobacillus plantarum 299v: Therapeutic success increases with length of treatment - real-life data of a non-interventional study in Germany]. / Reizdarmbehandlung mit Lactobacillus plantarum 299v: Längere Einnahme verstärkt Behandlungserfolg ­ Ergebnisse einer nichtinterventionellen Studie.

INTRODUCTION: The treatment of irritable bowel syndrome (IBS) in clinical practice is frequently challenging. Modulation of the intestinal microbiome as a treatment option is becoming more and more important. The effectiveness of a bacterial strain, Lactobacillus plantarum 299v (LP299V), was previously investigated in placebo-controlled clinical trials in patients with IBS over 4 weeks. The aims of the present non-interventional study were therefore to investigate tolerability and effectiveness of LP299V under everyday conditions and to gain information on long-term treatment. METHODS: Data on tolerability and effectiveness of LP299V (1 capsule/day; 1 × 1010 CFU) were prospectively collected in 25 centers in 221 patients with IBS. The maximal treatment duration was 12 weeks. The survey was carried out using symptom diaries and medical assessments. Changes in frequency and severity of symptoms were compared to baseline and defined the primary endpoint. RESULTS: During the 12-week treatment, a significant and continuous reduction of overall symptom score (p < 0.05) was observed. In addition, a significant reduction of severity (S) and frequency (H) of individual symptoms, such as abdominal pain (S: - 67 %, H: - 51 %), flatulence (S: - 61 %, H: - 63 %), diarrhea (S: - 70 %, H: - 32 %) and constipation (S: - 79 %, H: - 6 %) was observed. Urgency and feeling of incomplete evacuation were significantly decreased (p < 0.001). Additionally, quality of life increased significantly (mental well-being: + 110 %, influence on everyday life: -67 %, p < 0.01). Self-assessment identified that long-term treatment with LP299V was tolerated well by 94 % of patients. CONCLUSION: In real life, LP299V significantly alleviates the global symptoms of IBS in patients. In order to achieve the maximum effect, long-term use of LP299V (as here 12 weeks) appears to be indicated and is well tolerated.

Distribution of histopathological features along the colon in microscopic colitis.

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. METHODS: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. RESULTS: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. CONCLUSIONS: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.