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d values. Although default values are generally deemed acceptable by regulatory agencies, use of risk/hazard estimates based on these default values may compel insufficiently justified remedial action in some instances. BCKGROUND &amp; AIMS Volixibat is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT), hypothesized to treat non-alcoholic steatohepatitis (NASH) by blocking bile acid reuptake and stimulating hepaticbile acid production. METHODS Adults with ≥5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive double-blind volixibat 5, 10 or 20 mg or placebo once daily for 48 weeks. A predefined interim analysis (n = 80) at week 24 had endpoints of ≥5% reduction in magnetic resonance imaging-proton density fat fraction and ≥20% reduction in serum alanine aminotransferase levels. The primary endpoint was ≥2-point reduction in non-alcoholic fatty liver disease activity score without worsening fibrosis at week 48. RESULTS Volixibat did not meet either interim endpoint; the study was terminated owing to lack of efficacy. In participants receiving any volixibat dose, mean serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile acid synthesis) increased from baseline to week 24 (+38.5 ng/mL [standard deviation (SD) 53.18]), with concomitant decreases in serum total cholesterol (-14.5 mg/dL [SD 28.32]) and low-density lipoprotein cholesterol (-16.1 mg/dL [SD 25.31]). These changes were generally dose-dependent. In the liver histology analysis, a greater proportion of participants receiving placebo (38.5%, n = 5/13) than volixibat (30.0%, n = 9/30) met the primary endpoint. Treatment-emergent adverse events (TEAEs) were mainly mild or moderate. No serious TEAEs were related to volixibat. Diarrhoea was the most common TEAE overall and the most common TEAE leading to discontinuation. CONCLUSIONS Increased serum C4 and decreased serum cholesterol levels provide evidence of target engagement. [https://www.selleckchem.com/products/uc2288.html this website] However, there was no therapeutic benefit of ASBT inhibition with volixibat on the liver in adults with NASH (ClinicalTrials.gov identifier NCT02787304). V.BACKGROUND Outcomes following 1-surgeon single-anesthetic sequential bilateral total knee arthroplasty (seq-BTKA) compared to 2-surgeon single-anesthetic simultaneous bilateral total knee arthroplasty (sim-BTKA) are largely unknown. The current study compared revision rates and all-cause mortality following seq-BTKA vs sim-BTKA using data from the Australian Orthopedic Association National Joint Replacement Registry. METHODS Seq-BTKA and sim-BTKA procedures recorded within the registry between September 1, 1999 and December 31, 2018 were analyzed for subsequent revision and patient mortality. Cumulative percent revision and cumulative percent survival were determined using the Kaplan-Meier method. Revision and mortality rates for sim-BTKA and seq-BTKA were compared using Cox proportional hazards models, adjusting for age and gender. RESULTS Included in the analysis were 27,480 seq-BTKAs and 471 sim-BTKAs. There was no difference in the cumulative percent revision between the 2 groups (hazard ratio 1.23, 95% confidence interval 0.82-1.85). Cumulative percent patient survival was not significantly different between the 2 groups (hazard ratio 1.20, 95% confidence interval 0.93-1.54). CONCLUSION Revision rates and mortality were similar for seq-BTKA and sim-BTKA. Investigation of additional outcomes such as complications not requiring revision, pain, function, and cost is required to comprehensively understand the relative merits of each procedure. BACKGROUND Pre-existing patellofemoral disease has traditionally been a contraindication to unicompartmental knee arthroplasty (UKA), as proposed by Kozinn and Scott. More recently, some propose that patellofemoral disease can be ignored in UKA; however, the supporting research is predominantly in mobile-bearing designs. The study purpose was to evaluate the effect of patellofemoral disease osteoarthritis severity on latest outcomes after fixed-bearing medial UKA. METHODS A retrospective review of 147 consecutive medial fixed-bearing UKAs with minimum 1-year follow-up was performed. The medial and lateral patellofemoral compartments were graded according to the Kellgren &amp; Lawrence grading system, Osteoarthritis Research Society International atlas, and intraoperative assessment performed using the Outerbridge classification. Prospectively collected University of California Los Angeles Activity Level, modern Knee Society pain and function scores, and Likert scale satisfaction were correlated with presence and g patellofemoral disease as a contraindication for UKA. BACKGROUND The aim of this systematic review is to determine if robotic-assisted total knee arthroplasty (RATKA) results in improved clinical and radiological outcomes, and to elucidate the breadth and depth of studies conducted on this topic. METHODS A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review was conducted using 4 databases (MEDLINE, EMBASE, Cochrane, and Web of Science) to identify all clinical studies that investigate clinical or radiological outcomes using RATKA. The Critical Appraisal Skills Program checklist for cohort studies was employed for critical appraisal and evaluation of all 22 studies that met the inclusion criteria. RESULTS All studies reviewed determined that knee arthroplasty improved clinical outcomes. Twelve studies found statistically better clinical outcomes with RATKA compared with conventional TKA, whereas 9 studies found no difference. One study did not assess clinical outcomes. When assessing radiological outcomes, 14 studies reported that RATKA resulted in more consistent and accurate postoperative mechanical alignment, whereas 2 studies reported no difference. Six studies did not assess radiological outcomes. CONCLUSION Although knee arthroplasty is one of the most commonly performed orthopedic operations, the level of patient satisfaction varies. The meta-analyses conducted in our systematic review shows that RATKA results in greater improvements in postoperative Hospital for Special Surgery score and Western Ontario and McMaster Universities scores compared to conventional TKA. Furthermore, it shows that RATKA results in more accurate postoperative alignment of prostheses. These together can explain the improved postoperative outcomes. More randomized controlled trials must be conducted before this technique is integrated into routine clinical practice.