Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition-A Prospective Multicenter Study.

BACKGROUND: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.

Factors Associated with Response to Systemic Corticosteroids in Active Ulcerative Colitis: Results from a Prospective, Multicenter Trial.

BACKGROUND: Among patients with ulcerative colitis, 30-50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. RESULTS: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. CONCLUSION: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

Hematopoietic Stem Cell Transplantation in Refractory Crohn's Disease: Should It Be Considered?

Hematopoietic stem cell transplantation (HSCT) is widely used in benign and malignant hematological diseases. During the last decade, HSCT, mainly autologous, also gained increasing attention in the treatment of refractory autoimmune diseases. Crohn's disease (CD) is an inflammatory bowel disease leading to transmural inflammation potentially affecting all parts of the luminal gastrointestinal tract. Despite improving therapeutic options, including various biologics, some patients are refractory to all lines of available conservative therapy, leading to increased morbidity and reduced quality of life. Apart from surgery, HSCT might be a reasonable treatment alternative for refractory CD patients. This review aims to describe the current role of HSCT in CD and discusses the procedure, the correct patient selection, the clinical efficacy from initial remission to following relapse rates, and complications of this treatment.

Mixed lymphocytic and collagenous inflammation of the entire gastrointestinal tract under therapy with serotonin and norepinephrine reuptake inhibitors.

Drug-induced injury to the gastrointestinal tract has gained growing significance in recent years, and the list of causative medications keeps expanding. Herein, we present the case of a 45-year-old female with major depressive disorder treated with two serotonin and norepinephrine reuptake inhibitors (venlafaxine and duloxetine). She developed nausea and weight loss. Endoscopic evaluation of the upper and lower gastrointestinal tract rendered grossly normal mucosa in all segments. Histological examination, however, revealed lymphocytic esophagitis, collagenous gastritis, celiac disease-like intraepithelial lymphocytosis of the duodenum, and incomplete collagenous colitis. Gastrointestinal side effects of psychoactive drugs are largely underrecognized. This is the first report of a mixed lymphocytic and collagenous pattern of injury affecting esophagus, stomach, duodenum, and colon triggered by combined treatment with venlafaxine and duloxetine. In patients with unclear symptoms, obtaining biopsies from mucosa that is normal upon endoscopic inspection may render decisive clues for clinical management.

Treatment persistence of ustekinumab and vedolizumab in IBD patients is independent of prior immunogenicity to anti-TNFs: a retrospective study.

BACKGROUND AND AIMS: Immunological treatment failure of anti-TNF therapy negatively influences treatment persistence of a second anti-TNF in IBD patients. So far it is unknown if this effect is also observed for other monoclonal antibodies. We assessed the influence of immunogenicity to anti-TNFs on treatment persistence of subsequent ustekinumab and vedolizumab therapy. METHODS: IBD patients with and without immunogenicity to anti-TNFs (undetectable trough levels and antibody titers ≥20 ng/mL) and subsequent ustekinumab (UST) and/or vedolizumab (VDZ) therapy were included in this retrospective, single-center study. The Kaplan-Meier method with the log-rank test and Cox proportional hazards were used as statistical methods. RESULTS: One hundred patients (Crohn's disease: 62, Ulcerative colitis: 31, IBD unclassified: 7) with 127 treatment lines (62 with UST, 65 with VDZ) were included in the analysis. Immunogenicity to previous anti-TNFs did not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy (UST: Log rank: p = .95, Immunogenicity: HR for treatment discontinuation: 0.97 [95% CI 0.31-3.04]; VDZ: p = .65, HR: 0.85 [0.41-1.75]; total cohort [UST and VDZ]: p = .62, HR: 0.86 [0.47-1.57]). Azathioprine co-treatment did not lengthen treatment persistence (UST: Log rank: p = .77, azathioprine: HR: 1.20 [0.34-4.27]; VDZ: p = .92, HR: 0.58 [0.17-1.99]; total cohort: p = .79, HR: 1.10 [0.55-2.20]). In this anti-TNF experienced cohort, patients with ustekinumab remained longer on treatment than patients receiving vedolizumab (Log rank: p = .005, UST: HR: 0.43 [0.23-0.79]). CONCLUSIONS: Immunogenicity to anti-TNFs does not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy.

Practical application of breath tests in disorders of gut-brain interaction.

Frequently occurring diseases of disordered gut-brain interactions are the irritable bowel syndrome and functional dyspepsia. Breath tests are noninvasive and are used to monitor a variety of gastrointestinal functions or conditions. Their general principle is the oral application of a test substance, the metabolism of which results in a substrate that can be measured in expiratory air. Clinically used breath tests use carbohydrates or stable 13C-enriched substrates. This review will focus on two questions, which breath tests are relevant for initiating treatments and which breath tests are useful for assessing treatment response? Recently published guidelines have described breath tests in detail and the recommendations for their use will be based on recommendations of these guidelines.

Risks in Management of Enteral Nutrition in Intensive Care Units: A Literature Review and Narrative Synthesis.

Critically ill patients in the intensive care unit (ICU) have a high risk of developing malnutrition, and this is associated with poorer clinical outcomes. In clinical practice, nutrition, including enteral nutrition (EN), is often not prioritized. Resulting from this, risks and safety issues for patients and healthcare professionals can emerge. The aim of this literature review, inspired by the Rapid Review Guidebook by Dobbins, 2017, was to identify risks and safety issues for patient safety in the management of EN in critically ill patients in the ICU. Three databases were used to identify studies between 2009 and 2020. We assessed 3495 studies for eligibility and included 62 in our narrative synthesis. Several risks and problems were identified: No use of clinical assessment or screening nutrition assessment, inadequate tube management, missing energy target, missing a nutritionist, bad hygiene and handling, wrong time management and speed, nutritional interruptions, wrong body position, gastrointestinal complication and infections, missing or not using guidelines, understaffing, and lack of education. Raising awareness of these risks is a central aspect in patient safety in ICU. Clinical experts can use a checklist with 12 identified top risks and the recommendations drawn up to carry out their own risk analysis in clinical practice.