Proceedings of the Tenth Annual Beef Cattle Short Course.

91 p

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Modeling Long-Term Trends in Russet Burbank Potato Growth and Development in Wisconsin

Improving understanding and prediction of the potato (Solanum tuberosum) tuber size over the growing season is important due to its effects on crop price and marketing. Several models have been proposed to describe potato growth and development, but are based on short-term data and have little use for predicting yields or in-season management decisions. This analysis uses long-term data collected from 1979 to 1993 in central Wisconsin to describe growth and development of the Russet Burbank potato variety. This paper describes average number of potato tubers per plant and tuber length as influenced by thermal time and stem number per plant over 14 years. For each plant variable, data analysis uses multivariate techniques to fit a hierarchical logistic model with parameters potentially depending on stem number per plant. Analysis finds that the average number of potato tubers and average tuber length were affected by thermal time and stem number per plant. Estimated models are biologically relevant, provide an understanding of seasonal thermal variability and stem number per plant effects on average tuber set and growth, and can be used to describe yearly variation in average potato growth and development. Increased understanding of potato growth in response to thermal time and stem number per plant can improve management recommendations and predictions of crop economic value

Die Fremdkörperingestion – eine seltene Ursache persistierender, unklarer abdomineller Schmerzen

Anamnese und klinischer befund: Ein 50-jähriger Patient stellt sich mit rechtsseitigen Unterbauchschmerzen in der Notaufnahme vor. Er gibt an, dass jene Beschwerden seit ca. 5 Monaten bestünden und bei der Miktion an Intensität zunähmen.Untersuchungen: Nach einer Vielzahl frustraner diagnostischer Maßnahmen (CT Abdomen, MR-Sellink, Ileokoloskopie) gelingt es letztlich mittels Darmsonografie, einen ingestierten Zahnstocher im terminalen Ileum als Ursache für die Beschwerden zu identifizieren. Jener perforiert die Darmwand lokal und affektiert die angrenzende Blasenwand bei jeder Erhöhung des intraabdominellen Druckes schmerzhaft.Therapie und verlauf: Explorative Laparotomie mit Nachweis eines entzündlichen Konglomerattumors mit ileosigmoidaler Fistel im rechten Unterbauch. Die Entzündungsreaktion wird durch einen das terminale Ileum zweifach perforierenden Zahnstocher verursacht. Die operative Versorgung erfolgt mittels Ileumsegmentresektion und Sigmaresektion mit End-zu-End-Anastomosierung. Im postoperativen Verlauf kommt es zu einer subkutanen Wundheilungsstörung, die mittels VAC-Therapie versorgt wird. Am 16. postoperativen Tag kann der Patient in einem guten Allgemeinzustand nach Hause entlassen werden.Folgerung: Eine Fremdkörperingestion stellt eine seltene, aber relevante Differenzialdiagnose unklarer abdomineller Schmerzen, insbesondere im Kindesalter, dar. Neben einer ausführlichen Anamnese sollte als primäre apparative Maßnahme stets zunächst eine qualifizierte und sorgfältig durchgeführte Abdomensonografie erfolgen, mithilfe derer auch strahlentransparente ingestierte Fremdkörper detektiert werden können.</p

Fecal microbiota transfer for refractory intestinal graft-versus-host disease - Experience from two German tertiary centers

Rationale Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD. Objectives We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing. Results Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P < .05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT. Conclusions In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action

Proceedings of the Tenth Annual Beef Cattle Short Course.

91 p