Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND & AIMS: The aim of this study was to evaluate the efficacy of LT-02, a novel modified-release phosphatidylcholine (PC) formulation, for induction and maintenance of remission in patients with mild to moderate ulcerative colitis (UC) and inadequate response to mesalamine. METHODS: LT-02 was evaluated in a multicenter double-blind, randomized, placebo-controlled study comprising a 12-week induction trial (PCG-2), followed by a 48-week maintenance trial (PCG-4). In PCG-2, patients were randomized 1:1:1 to treatment with 0.8 g LT-02 4 times daily (QID), 1.6 g LT-02 twice daily (BID), or placebo, respectively. All patients continued to take a standard dose of oral mesalamine (≥2.4 g/day). The primary end point in PCG-2 was deep remission. Patients achieving remission at week 12 were randomly assigned 2:1:1 to 1.6 g LT-02 BID, placebo, or 500 mg mesalamine (3 times daily), respectively, in PCG-4; the primary end point was remission at 48 weeks. RESULTS: PCG-2 was terminated early for futility after a prespecified interim analysis; 466 patients (of 762 planned) were randomized. There was no statistically significant difference in deep remission at week 12 (placebo, 13.5%; LT-02 BID, 14.2%; LT-02 QID, 9.7%). In PCG-4, 150 patients (of approximately 400 planned) were randomized. There was no statistically significant difference in remission rates at week 48 (LT-02 BID, 49.3%; mesalamine, 50.0%; placebo, 43.2%). LT-02 was safe. CONCLUSIONS: Despite prior evidence of beneficial effects of PC in phase 2 trials, our induction study with LT-02 in patients with mild to moderate UC was terminated prematurely for futility. Signals of efficacy in maintenance therapy require confirmation in an adequately powered maintenance trial. LT-02 was safe and well-tolerated. CLINICALTRIALS: gov: NCT02280629, NCT02142725.

Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study.

BACKGROUND & AIMS: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. METHODS: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). RESULTS: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. CONCLUSIONS: Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. CLINICALTRIALS: gov number: NCT04033445.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Bowel Urgency in Ulcerative Colitis: Current Perspectives and Future Directions.

Bowel urgency (BU), the sudden or immediate need for a bowel movement, is one of the most common and disruptive symptoms experienced by patients with ulcerative colitis (UC). Distinct from the separate symptom of increased stool frequency, BU has a substantial negative impact on quality of life and psychosocial functioning. Among patients with UC, BU is one of the top reasons for treatment dissatisfaction and one of the symptoms patients most want improved. Patients may not discuss BU often due to embarrassment, and healthcare providers may not address the symptom adequately due to the lack of awareness of validated tools and/or knowledge of the importance of assessing BU. The mechanism of BU in UC is multifactorial and includes inflammatory changes in the rectum that may be linked to hypersensitivity and reduced compliance of the rectum. Responsive and reliable patient-reported outcome measures of BU are needed to provide evidence of treatment benefits in clinical trials and facilitate communication in clinical practice. This review discusses the pathophysiology and clinical importance of BU in UC and its impact on the quality of life and psychosocial functioning. Patient-reported outcome measures developed to assess the severity of BU in UC are discussed alongside overviews of treatment options and clinical guidelines. Implications for the future management of UC from the perspective of BU are also explored.

Characteristics, clinical outcomes and patient-reported outcomes of patients with ulcerative colitis receiving tofacitinib: a real-world survey in the United States and five European countries.

BACKGROUND: To describe variations in treatment patterns, clinical outcomes, patient-reported outcomes (PRO), and physician and patient satisfaction in patients with moderate-to-severe ulcerative colitis (UC) treated with tofacitinib in a real-world setting. METHODS: Data were drawn from the Adelphi UC Disease Specific Programme™, a point-in-time survey of physicians and their consulting patients in the US and Europe. For inclusion in this analysis, gastroenterologists completed medical record forms for the next seven consecutive consulting patients with confirmed UC, plus a further two patient record forms for patients treated with tofacitinib. Those same patients then completed a patient-reported questionnaire. RESULTS: Gastroenterologists (n = 340) provided data for 2049 patients with UC, including 642 patients receiving tofacitinib. Physicians' most frequent reason for choosing tofacitinib was overall efficacy (71.3% of patients). The proportion of patients in remission increased with length of treatment, from 13.7% at [0, 4) weeks to 68.3% at [52+] weeks. Both physicians and patients reported that the Mayo components of stool frequency and blood in stool were reduced with time on treatment. Improvement in symptoms (bloody diarrhea, abdominal pain/cramps, urgency, rectal bleeding, fatigue/tiredness) was reported in the first weeks of treatment, and increased with time. At week [52+], mean score reductions from treatment initiation to current in overall symptom severity, pain, and fatigue were 2.2 (to a current mean score of 1.1), 2.2 (to 0.9), and 2.1 (to 1.0), respectively. Comparing patients at weeks [0, 4) and [52+] (all PROs, p < 0.0001), the increase in EQ-5D-5L index total score was 0.29 points and in SIBDQ total score was 20.5 points; percent reductions in WPAI absenteeism was 34.4%, presenteeism 26.8%, overall work impairment 40.9% and activity impairment was 28.3%. These changes reached the thresholds for minimally clinically important differences. The majority of physicians (91.9%) and patients (93.5%) were satisfied with tofacitinib at week [52+]. CONCLUSION: Patients with moderate-to-severe UC treated with tofacitinib show considerable improvement in symptoms and quality of life from tofacitinib initiation to one year and beyond, with high rates of remission. Physicians and patients report satisfaction with UC control at recommended doses in a mostly biologic experienced population.

International Consensus on Definition of Mild-to-Moderate Ulcerative Colitis Disease Activity in Adult Patients.

Background and Objectives: At present, there is no consensus definition of mild-to-moderate disease activity in patients with ulcerative colitis. The objective of the present study was to establish a reliable definition of mild-to-moderate disease activity in adult patients with ulcerative colitis. Materials and Methods: Twelve physicians from around the world participated in a virtual consensus meeting on 26 September 2022. All the physicians had expertise in the diagnosis and treatment of inflammatory bowel disease. After a systematic review of the literature and expert opinion, a modified version of the RAND/University of California, Los Angeles appropriateness method was applied. A total of 49 statements were identified and then anonymously rated (on a 9-point scale) as being appropriate (scores of 7 to 9), uncertain (4 to 6) or inappropriate (1 to 3). The survey results were reviewed and amended before a second round of voting. Results: Symptom and endoscopic-based measurements are of prime importance for assessing mild-to-moderate ulcerative colitis activity in clinical trials. The experts considered that clinical activity should be assessed in terms of stool frequency, rectal bleeding and fecal urgency, whereas endoscopic activity should be evaluated with regard to the vascular pattern, bleeding, erosions and ulcers. Fecal calprotectin was considered to be a suitable disease activity marker in mild-to-moderate ulcerative colitis. Lastly, mild-to-moderate ulcerative colitis should not have more than a small impact on the patient's daily activities. Conclusions: The present recommendations constitute a standardized framework for defining mild-to-moderate disease activity in clinical trials in the field of ulcerative colitis.

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.

BACKGROUND: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. RESULTS: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Multinational evaluation of clinical decision-making in the treatment and management of mild-to-moderate ulcerative colitis.

OBJECTIVES: To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). METHODS: This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios - active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. RESULTS: A total of 157 individual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52; 93% specialist gastroenterologists) from Europe and North America (25; 45%), South America (19; 34%) and the Middle East, Asia and Australia (12; 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. CONCLUSION: The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history.

[Biologics in inflammatory bowel diseases]. / Biologika bei chronisch-entzündlichen Darmerkrankungen.

BACKGROUND: In addition to conventional anti-inflammatory treatment for chronic inflammatory bowel disease (IBD), there has been an evolution of new treatment options over the past 20 years. Already approved biologics provide multiple treatment alternatives but also make the treatment algorithms more complex. This development results in a substantial improvement in patient care. The ambitious treatment targets are associated with a higher quality of life and the reduction of long-term disability and morbidity. OBJECTIVE: The aim of this article is to give an overview of how biologics can currently be implemented in IBD. In particular, the current clinical management is presented and an outlook on future treatment options with biologics for IBD is provided. MATERIAL AND METHODS: A search was carried out in PubMed and ClinicalTrials.gov and the current German and European guidelines and expert recommendations were evaluated. RESULTS: Since the late 1990s there have been a continuously increasing number of treatment options for IBD. All substances have proven safety and efficacy in large randomized clinical studies and enable increasingly more individualized treatment for patients with IBD. Biologics are currently the standard treatment of choice for moderate to severe inflammatory activity as well as for steroid-refractory or steroid-dependent courses of disease after failure of conventional treatment. CONCLUSION: The diversity of IBD treatment offers increasing treatment options and thus improved patient care; however, as the number of new substances increases treatment becomes more complex. This article summarizes the current and future treatment options for IBD and their integration into current treatment algorithms.

Approaches to Integrating Biomarkers Into Clinical Trials and Care Pathways as Targets for the Treatment of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: There is no consensus on the best way to integrate biomarkers into inflammatory bowel disease (IBD) research and clinical practice. The International Organization for the Study of Inflammatory Bowel Disease aimed to outline biomarker definitions, categories, and operating properties required for their use in registration trials and clinical practice. Using fecal calprotectin as an example, we provide a framework for biomarker development and validation in patients with IBD. METHODS: We reviewed international society guidelines, regulatory agency guidance documents, and standardized reporting guidelines for biomarkers, in combination with publications on fecal calprotectin levels in patients with IBD. We assessed the validity of fecal calprotectin to serve as a surrogate biomarker of IBD activity and outlined a framework for further validation and development of biomarkers. RESULTS: No endpoints have been fully validated as surrogates of risk of disease complications; mucosal healing is the most valid endpoint used to determine risk of disease complications. Fecal level of calprotectin has not been validated as a biomarker for IBD activity because of lack of technical and clinical reliability, assessment of performance when used as a replacement for endoscopy, and assessment of responsiveness to changes in disease states. The level of fecal calprotectin can be used only as a prognostic factor for disease recurrence in patients in remission after medical or surgical treatment. CONCLUSIONS: We reviewed guidelines, regulatory documents, and publications to identify properties required for the development of biomarkers of IBD activity and areas in need of clarification from regulatory agencies and societies. We propose a path forward for research of biomarkers for IBD.

"It ain't over till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a "new normal," and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.

Correction to: Psychosocial distress in acute cancer patients assessed with an expert rating scale.

The article "Psychosocial distress in acute cancer patients assessed with an expert rating scale".

Addendum to S3-Guidelines Crohn's disease and ulcerative colitis: Management of Patients with Inflammatory Bowel Disease in the COVID-19 Pandemic - open questions and answers.

The COVID-19 pandemic is a global outbreak of new onset infections with the SARS-CoV-2 virus. To date, more than 3.4 million people have been infected throughout the world. In Germany, approximately 450,000 patients suffer from inflammatory bowel disease; these patients generally require continuous expert care and support. Against the background of a rapidly accumulating knowledge base on SARS-CoV-2, 68 expert authors of the current DGVS guidelines for Crohn's disease and ulcerative colitis took part in a virtual meeting to compile up-to-date, practice-orientated recommendations aimed at improving the care of patients with IBD. These recommendations address the risk of infection, including the risk for specific patient groups, the possible course of the disease, and consequences for pharmacological and surgical therapies of the underlying disease, as well as general measures for infection prevention and adjuvant prophylactic and therapeutic options.

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. METHODS: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). RESULTS: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5-31.2; P = .021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2-31.2; P = .010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1-31.1; P = .013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. CONCLUSION: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

Indirect comparison of vedolizumab and adalimumab for biologic-naive patients with ulcerative colitis.

AIM: Indirect comparison of efficacy and safety of vedolizumab with adalimumab in biologic-naïve patients with moderate to severe ulcerative colitis (UC). METHODS: Vedolizumab is a gut-selective medication for moderate to severe UC. Since no comparative trials are available for direct comparison of vedolizumab vs adalimumab in UC, a systematic review of literature databases was conducted to identify randomized, placebo-controlled trials of the two drugs in patients with moderate to severe UC after failure of conventional treatment. Studies were screened for eligibility by two reviewers based on predefined inclusion criteria. Bucher's adjusted indirect comparison was used to compare vedolizumab and adalimumab indirectly through placebo as common comparator. RESULTS: One vedolizumab study (GEMINI 1) and three adalimumab studies (ULTRA 1, ULTRA 2 and M10-447) met the eligibility criteria. Baseline characteristics of the included populations were similar in biologic-naïve UC patients across study arms. Although no statistically significant differences between treatments were found for induction efficacy endpoints, there was a trend toward a benefit of vedolizumab over adalimumab. There were also no significant differences between treatments for any maintenance efficacy endpoints, with no clear trend favoring either agent. Vedolizumab exhibited statistically superior maintenance safety compared with adalimumab, with significant reductions in risks of adverse events (relative risk 0.67 [95% confidence interval 0.57-0.80]; p < .0001), serious adverse events (0.20 [0.09-0.42]; p < .0001) and adverse events leading to discontinuation (0.14 [0.05-0.43]; p = .0006). CONCLUSION: This analysis indicates that vedolizumab has comparable efficacy to adalimumab with improved safety in biologic-naïve patients with moderate to severe UC.

Exercise improves functional capacity and lean body mass in patients with gastrointestinal cancer during chemotherapy: a single-blind RCT.

PURPOSE: Although growing evidence underlines the benefits of physical activity as supportive intervention for cancer patients, sparse data are available for exercise in patients with advanced disease stages, in particular for gastrointestinal cancer (GIC) patients who experience specific disease-associated limitations. Thus, the aim of this study is to evaluate the effects of home-based moderate intensity exercise on functional capacity, activities of daily living (ADL) and body composition in patients with advanced GIC during first-line chemotherapy. METHODS: Participants (GIC, UICC III-IV; n = 44) were randomly assigned to home-based physical activity programme of 150 min moderate walking per week or a control group (CG). Functional status (SPPB: gait speed, balance, lower extremity muscle strength), postural sway, chemotherapy-induced peripheral neuropathy, nutritional state (Mini Nutritional Assessment, MNA) and lean body mass were assessed according to established recommendations. All tests were performed before chemotherapy (T0), after two chemotherapy cycles (T1) and after 12 weeks (T2). RESULTS: SPPB changes from T1 to T2 differed between groups with a comparably greater decrease in the CG (p < .05), but no changes or group differences over the whole study period (T0 to T2) were found. Exercise improved postural sway (T0 to T1; T0 toT2) and lean body mass (T1 to T2; T0 to T2) compared to the control group (p < .05). Gait speed, peripheral neuropathy and strength did not differ between groups (p > .05). CONCLUSIONS: Our results indicate that a home-based physical activity improves postural sway and body composition and might stabilize functional capacity in patients with advanced GIC during chemotherapy. Although the other outcomes did not differ between groups, aforementioned effects might contribute to a maintenance of independency in ADL and a better treatment tolerance and thus enhance patients' quality of life.

Serum Hepcidin Levels Predict Intestinal Iron Absorption in Patients with Inflammatory Bowel Disease.

BACKGROUND: Hepcidin has been shown to be inversely associated with iron absorption and the expression of iron transport proteins in healthy females and patients with iron deficiency. Data describing the relationship between hepcidin expression and iron absorption in patients with inflammatory bowel disease (IBD) are lacking. The objective of this study was to assess the relationship between serum concentrations of hepcidin and iron absorption in patients with IBD and iron deficiency by means of an oral iron absorption test. METHODS: This study was conducted as a comparative, single-centered, open clinical trial. After overnight fasting, an oral iron absorption test was performed, serum iron concentrations were measured 60, 90, 120, 180, and 240 minutes. Changes in iron levels between baseline and the 2-hour timepoint were calculated and recorded. RESULTS: Both ferritin and serum hepcidin levels are found to be good predictors of iron malabsorption, with sensitivity and specificity both at levels > 95%. When the two markers are compared, in our analysis, serum hepcidin levels (AUC: 0.817) tended to predict iron malabsorption slightly better than serum ferritin (AUC: 0.788). CONCLUSIONS: The evidence from our study suggests that serum hepcidin levels are a promising predictor of absorptive capacity in patients treated with oral iron compounds.

Perianal fistulas in adult patients with Crohn's disease in Germany - a retrospective cross-sectional analysis of claims data from German sickness funds.

INTRODUCTION: Perianal fistulas (PF) are presumably a frequent extraintestinal manifestation of Crohn's disease (CD), causing significant functional impairment. This study aims to gain representative data on the prevalence, characteristics, and treatment of CD patients suffering from PF in Germany. MATERIALS AND METHODS: A retrospective cross-sectional analysis of claims data from several German company health insurance funds included adult patients with CD and PF in 2015. The dataset comprised in- and outpatient services with diagnoses, drug prescriptions, and other patient data. It is representative for age, gender, and region and allows extrapolation to the total German statutory health insurance (SHI) population. A systematic literature review was conducted to discuss these results in the international context. RESULTS: A CD prevalence of 299 per 100 000 and a PF prevalence in CD patients of 3.4 % was observed in this cross-sectional study. PF are most prevalent in young age groups (< 24 to 39). One-third of patients with PF received biologics and surgery. Surgical procedures were performed in 31.3 % of PF patients in the inpatient setting and in 4.4 % of PF patients in the outpatient setting. All complicated perianal fistula patients received at least 1 inpatient surgery and 44.8 % received biologic therapy. DISCUSSION: This claims data analysis in German patients estimates a CD prevalence in the SHI population that corresponds well to previously reported data. The prevalence rate for PF in CD patients is comparable with a previous cross-sectional German claims data analysis but is markedly lower than cumulative risks reported in longitudinal cohort studies. PF patients are young and treatment intensive with one-third requiring biologic treatment or inpatient surgery.