Low Dietary Flavonoid Consumption Is Associated to Severe Inflammatory Bowel Disease.

Background and Aims: Associations between diet habits and inflammatory bowel disease (IBD) have been widely described. Flavonoids are taken with vegetables, fruits, and green tea. Because of barrier-protective and anti-inflammatory effects, flavonoid consumption (FC) may influence the severity of IBD. The aim of this study was to reveal the role of FC in the course and severity of IBD. Methods: A prospective cohort study including 204 IBD patients (Crohn's disease n = 126, ulcerative colitis n = 78) was conducted between 2016 and 2021. FC was calculated using questionnaires. In addition to standard activity scores and different treatments, a "severity index" was related to individual FC. Differences between groups and odds ratios were analyzed. Results: Inverse correlation (r = -0.0549; P = .01) between FC and severity of IBD was found. Patients were assigned to 3 different severity index ranges: mild, moderate, and severe disease. FC of patients with severe disease (331 ± 330 mg/week) was less than FC of patients with mild (1404 ± 1086 mg/ week) disease (P < .001). The risk of IBD patients with low FC (1000 mg/week) experiencing overall severe disease was 17 times increased (P < .001) compared to patients with high FC (>1000 mg/week). Patients with UC and low FC had a 9.6-times higher risk for disease progression (P < .001). Conclusion: Consumption of dietary flavonoids and the overall severity of IBD are inversely correlated. Patients with mild diseases consume higher amounts of flavonoids than patients with severe diseases. Low dietary flavonoids were related to a considerable risk of severe IBD.

Integrating the Patient Perspective to Validate a Measure of Disease Severity in Inflammatory Bowel Disease: Online Survey of Patients and Their Physicians.

BACKGROUND: The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA). METHODS: In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points. RESULTS: The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC. CONCLUSIONS: The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective.

The performance of an inflammatory bowel disease severity score was compared with self-perceived severity based on an individually linked online survey of patients and their physicians. Agreement and prediction of severe disease were moderate and should be improved by integrating the patients' perspective.

Prospective Evaluation of the Prediction Score for a Mild Course of Crohn's Disease (PreMiCC) in Newly Diagnosed Patients With Crohn's Disease: The PROGNOS Study.

BACKGROUND AND AIMS: The course of Crohn's disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score. METHODS: The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048). RESULTS: A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001). CONCLUSIONS: In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn's disease) successfully predicted this.

In our study of newly diagnosed Crohn's disease patients, we found that around 30% had a mild disease course. We also successfully tested our proposed PreMiCC (prediction score for a mild course of Crohn's disease), which predicts this mild course.

Mesalazine granules promote disease clearance in patients with mild-to-moderate ulcerative colitis.

BACKGROUND: Over the past decade, treatment targets for ulcerative colitis (UC) have become more stringent, incorporating multiple parameters. Recently, the concept of 'disease clearance'-defined as combined clinical, endoscopic, and histological remission-has been proposed as an ultimate endpoint in treating UC. OBJECTIVE: To determine the rates of disease clearance in patients with mild-to-moderate UC treated with different doses of mesalazine granules as induction therapy. METHODS: In a post hoc analysis, data were pooled from four randomised, active-controlled, phase 3 clinical trials in patients with mild-to-moderate UC receiving 8-week induction therapy with mesalazine granules at daily doses of 1.5, 3.0 or 4.5 g. Rates of clinical, endoscopic, and histological remission were determined using stringent criteria and used to calculate rates of the composite endpoints of clinical plus endoscopic remission, endoscopic plus histological remission, and disease clearance (clinical plus endoscopic plus histological remission). RESULTS: A total of 860 patients were included in the analysis. Among the total population, 20.0% achieved disease clearance with mesalazine granules: 13.1% in patients receiving 1.5 g mesalazine granules/day, 21.8% in those receiving 3.0 g/day and 18.9% in those receiving 4.5 g/day. Among patients with moderate UC, 16.8% achieved disease clearance: 7.1% with 1.5 g/day, 18.8% with 3.0 g/day and 16.2% with 4.5 g/day. CONCLUSION: Disease clearance, proposed to be predictive of improved long-term outcomes, can be achieved in a clinically meaningful proportion of mild-to-moderate UC patients treated with mesalazine granules. A daily dose of 3.0 g appears optimal to reach this target.

German guideline diverticular disease/diverticulitis: Part II: Conservative, interventional and surgical management.

Diverticulosis and diverticular disease are ranked among the most common gastroenterological diseases and conditions. While for many years diverticulitis was found to be mainly an event occurring in the elder population, more recent work in epidemiology demonstrates increasing frequency in younger subjects. In addition, there is a noticeable trend towards more complicated disease. This may explain the significant increase in hospitalisations observed in recent years. It is not a surprise that the number of scientific studies addressing the clinical and socioeconomic consequences in the field is increasing. As a result, diagnosis and conservative as well as surgical management have changed in recent years. Diverticulosis, diverticular disease and diverticulitis are a complex entity and apparently an interdisciplinary challenge. To meet theses considerations the German Societies for Gastroenterology and Visceral Surgery decided to create joint guidelines addressing all aspects in a truely interdisciplinary fashion. The aim of the guideline is to summarise and to evaluate the current state of knowledge on diverticulosis and diverticular disease and to develop statements as well as recommendations to all physicians involved in the management of patients with diverticular disease.

German guideline diverticular disease/diverticulitis: Part I: Methods, pathogenesis, epidemiology, clinical characteristics (definitions), natural course, diagnosis and classification.

Diverticulosis and diverticular disease are ranked among the most common gastroenterological diseases and conditions. While for many years diverticulitis was found to be mainly an event occurring in the elder population, more recent work in epidemiology demonstrates increasing frequency in younger subjects. In addition, there is a noticeable trend towards more complicated disease. This may explain the significant increase in hospitalisations observed in recent years. It is not a surprise that the number of scientific studies addressing the clinical and socioeconomic consequences in the field is increasing. As a result, diagnosis and conservative as well as surgical management have changed in recent years. Diverticulosis, diverticular disease and diverticulitis are a complex entity and apparently an interdisciplinary challenge. To meet theses considerations the German Societies for Gastroenterology and Visceral Surgery decided to create joint guidelines addressing all aspects in a truely interdisciplinary fashion. The aim of the guideline is to summarise and to evaluate the current state of knowledge on diverticulosis and diverticular disease and to develop statements as well as recommendations to all physicians involved in the management of patients with diverticular disease.

Novel Budesonide Suppository and Standard Budesonide Rectal Foam Induce High Rates of Clinical Remission and Mucosal Healing in Active Ulcerative Proctitis: a Randomised, Controlled, Non-inferiority Trial.

BACKGROUND AND AIMS: Proctitis is the least extensive type of ulcerative colitis, for which rectal therapy is rarely studied and is underused. This study evaluated the efficacy, safety, and patient's preference of a novel formulation of budesonide suppository 4 mg, compared with a commercially available budesonide rectal foam 2 mg, for the treatment of mild to moderate ulcerative proctitis. METHODS: This was a randomised, double-blind, double-dummy, active-controlled trial. Patients were randomly assigned in a 1:1 ratio to receive either budesonide 4 mg suppository or budesonide 2 mg foam once daily for 8 weeks. The co-primary endpoints were changes from baseline to Week 8 in clinical symptoms, for which clinical remission was defined as having a modified Ulcerative Colitis-Disease Activity Index [UC-DAI] subscore for stool frequency of 0 or 1 and a subscore for rectal bleeding of 0, and mucosal healing, defined as having a modified UC-DAI subscore for mucosal appearance of 0 or 1. Using a more stringent criterion, we additionally analysed deepened mucosal healing, which was defined as a mucosal appearance subscore of 0. Patient's preference, physician's global assessment, and quality of life were also assessed and analysed. RESULTS: Overall, 286 and 291 patients were included in the 4 mg suppository and 2 mg foam groups, respectively. Budesonide 4 mg suppository met the prespecified criterion for non-inferiority to the 2 mg foam in both co-primary endpoints of clinical remission and mucosal healing. Secondary endpoints consistently supported the non-inferiority of the suppository. Trends in favour of the suppository were observed in the subgroup of mesalazine non-responders. More patients reported a preference for the suppository over rectal foam. CONCLUSIONS: In patients with ulcerative proctitis, budesonide 4 mg suppository was non-inferior to budesonide 2 mg foam in efficacy, and both were safe and well tolerated.

Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus.

Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

[Diverticula of the colon: Review of related entities]. / Kolondivertikel und Divertikulitis.

Diverticulosis, Diverticular Disease, and Diverticulitis, comprising different entities, pose increasing burdens for health care systems. The introduction of new scientific knowledge into daily clinical work is challenging for attending physicians. This review is related to case presentations and currently debated questions are discussed such as definitions: Which entities are meant by the term "Diverticular Disease", is "uncomplicated symptomatic Diverticular Disease"(SUDD) reality? To classify diverticula related diseases targeted diagnosis including imaging is necessary. The question is ultrasound or computed tomography, or the combination and in which order?Lastly, open questions of treatment have to be addressed: Outpatient care or hospitalisation, always antibiotics or only in defined situations, relapse prevention, indications to operate upon?The present review comes along with revised German guidelines, which will be published later this year on S3-level.

Prevalence of abnormal Pap smear results in inflammatory bowel disease: a prospective study.

PURPOSE: Development of malignancy is a pending threat for patients with inflammatory bowel disease (IBD). Aim of this study was to analyze cervical dysplasia and infection with human papilloma virus (HPV) in patients with IBD. METHODS: This was a prospective, single center cohort study in Germany. Consecutive IBD patients admitted to the Department of Gastroenterology were sent to Gynecology, where a questionnaire was answered and gynecological examinations including a smear for cytology and HPV were taken. Participants of a general screening program constituted controls. Descriptive statistics, 95% confidence intervals and odds ratios were calculated. RESULTS: A total of 101 patients were recruited of which 99 patients participated. Analysis showed a significant (p = 0.05) difference between the prevalence of abnormal smears in patients with (22%) and without (6%) immunosuppressive therapy, while the latter had cervical abnormalities comparable with healthy controls (5%). All immunosuppressants showed similarly high risks for abnormal smear results. Only 11/99 (11%) patients had positive high-risk HPV tests, which is comparable with general population. CONCLUSION: The prevalence of abnormal cervical smears is higher in IBD patients compared to healthy individuals, but the difference is confined to patients with IBD and immunosuppressive therapy. Annual screening is advisable.

What Are the Most Challenging Aspects of Inflammatory Bowel Disease? An International Survey of Gastroenterologists Comparing Developed and Developing Countries.

BACKGROUND AND AIMS: As inflammatory bowel disease (IBD) becomes more prevalent, the challenges that gastroenterologists face in managing these patients evolve. We aimed to describe the most important challenges facing gastroenterologists from around the world and compare these between those working in developed and developing countries. METHODS: An online questionnaire was developed, and a link distributed to gastroenterologists. Data were analyzed descriptively using Friedman and Wilcoxon matched-pair signed rank tests to compare rankings for responses. Mann-Whitney U tests were used to compare rankings between responses from gastroenterologists from developed and developing countries. Lower scores reflected greater challenges. RESULTS: Of 872 who started, 397 gastroenterologists (45.5%) completed the survey. Respondents represented 65 countries (226 [56.9%] from developed countries). Overall, the challenge ranked most important (smallest number) was increasing IBD prevalence (13.6%). There were significant differences in mean ranking scores for many simple aspects of care for those from developing countries compared to providers from developed countries, such as access to simple IBD treatments (5.52 vs. 6.02, p = 0.01), access to anti-TNF drugs including dose escalation (3.33 vs. 3.93, p < 0.01), access to good stoma care (2.57 vs. 3.03, p < 0.001), access to therapeutic drug monitoring (1.47 vs. 1.84, p < 0.001), and access to care for people from low socioeconomic status (2.77 vs. 3.37, p < 0.001). CONCLUSIONS: Increasing IBD prevalence is seen by gastroenterologists as the greatest challenge facing them. There are significant differences between the IBD challenges facing gastroenterologists from developed and developing countries that reflect inequities in access to health care.

[Diverticular disease. Clinical appearance, conservative treatment, primary and secondary prophylaxis]. / Divertikelkrankheit. Klinisches Erscheinungsbild, konservative Behandlung, Primär- und Sekundärprophylaxe.

Diverticula of the colon are very common and usually asymptomatic but 20% of people with diverticulosis develop symptoms and sometimes also complications, such as diverticulitis with abscesses or perforation and bleeding. In the long-term stenoses or a conglomerate can occur. The treatment depends on the type of diverticular disease, on the knowledge of risk indicators and imaging with sonography or computed tomography (CT). The uncomplicated diverticular disease is treated on an outpatient and conservative basis, while complicated diverticular disease is treated on an inpatient basis and often surgically.

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

OBJECTIVE: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. DESIGN: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. RESULTS: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. CONCLUSION: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

Perianal Fistula-Associated Carcinoma in Crohn's Disease: A Multicentre Retrospective Case Control Study.

BACKGROUND AND AIMS: Carcinoma associated with perianal fistula in Crohn's disease is a pending threat for patients. This study aimed to improve understanding and facilitate development of diagnostic and therapeutic strategies. METHODS: A retrospective case-control study was conducted at four German hospitals. The analysis included 40 patients with proven malignancy associated with perianal Crohn's fistulas and 40 randomly selected controls with fistulizing perianal Crohn's disease. Differences between groups were analysed and multivariate calculations were performed to describe risk factors for oncological outcomes. RESULTS: Histology revealed adenocarcinoma in 33/40 patients and squamous cell carcinoma in 7/40 patients. Compared to fistula patients without carcinoma, patients with malignancies associated with fistula had a diagnosis of Crohn's disease at younger age. Crohn's disease lasted longer in patients with malignancy [25.8 ± 9.0 vs 19.6 ± 10.4; p = 0.006]. Fistula-related findings differed significantly between the two groups. Signs of complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated with fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histological type of cancer, metastatic disease and R1 resection. Overall survival was 45.1 ± 28.6 months and the 5-year survival rate was 65%. CONCLUSIONS: In patients with adenocarcinoma or squamous cell carcinoma associated with perianal fistula in Crohn's disease, fistula characteristics determine the risk of malignancy. Early diagnosis influences outcomes, while treatment of chronic fistula activity may be key to preventing malignancy. Expert multimodal therapy is paramount for successful treatment of perianal fistula-associated malignancies.

[Cost of illness of inflammatory bowel disease in Germany]. / Krankheitskosten chronisch entzündlicher Darmerkrankungen in Deutschland.

INTRODUCTION: The prevalence of inflammatory bowel disease (IBD) in Germany is rising. Due to a disease onset at a young age, direct and indirect costs are important. The aim of the present study is to provide a comprehensive presentation of existing healthcare costs for these diseases in Germany and to compare them by inflation adjustments for 2018. MATERIAL AND METHODS: Performing a systematic literature search, monetary costs were extracted from German and English literature. Quality and relevance of the studies were assessed with a checklist. RESULTS: The average outpatient cost for inflammatory bowel disease amounts between 18 and 87 Euro/pat/30 days, the average inpatient cost was between 1026 and 9083 Euro/case. Depending on the type of calculation, biologicals cause different amounts of cost. Few data are available for direct medical 82 and 618 Euro/pat/30 days, direct non-medical 63 and 84 Euro/pat/30 days and indirect costs 463 and 3493 Euro/pat/30 days. The total costs are about 533 Euro/pat/30 days, related to one year 6485 Euro/pat. CONCLUSION: For the first time, it is possible to compare existing medical costs for IBD in Germany. Current studies feature very heterogeneous methods and study populations of IBD. Depending on the collective, the total costs are up to 6485 Euro/patient/year.

A Multicentre, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of the S1P Receptor Agonist KRP203 in Patients with Moderately Active Refractory Ulcerative Colitis.

BACKGROUND AND AIMS: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the gastrointestinal tract. METHODS: We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0-1 and modified Baron Score 0-1 with rectal bleeding subscore 0. RESULTS: KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. CONCLUSIONS: Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.