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An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction: X-linked myotubular myopathy (XLMTM), characterized by severe hypotonia, weakness, respiratory distress, and early mortality, is rare and natural history studies are few., Methods: RECENSUS is a multicenter chart review of male XLMTM patients characterizing disease burden and unmet medical needs. Data were collected between September 2014 and June 2016., Results: Analysis included 112 patients at six clinical sites. Most recent patient age recorded was ≤18 months for 40 patients and >18 months for 72 patients. Mean (SD) age at diagnosis was 3.7 (3.7) months and 54.3 (77.1) months, respectively. Mortality was 44% (64% ≤18 months; 32% >18 months). Premature delivery occurred in 34/110 (31%) births. Nearly all patients (90%) required respiratory support at birth. In the first year of life, patients underwent an average of 3.7 surgeries and spent 35% of the year in the hospital., Discussion: XLMTM is associated with high mortality, disease burden, and healthcare utilization. Muscle Nerve 57: 550-560, 2018., (© 2017 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.)

The objective of this study was to determine the effect of augmenting screw fixation with an injectable calcium sulfate cement (CSC) in the osteoporotic bone of ovariectomized rats. The influence of the calcium sulfate (CS) on bone remodeling and screw anchorage in osteoporotic cancellous bone was systematically investigated using histomorphometric and biomechanical analyses. The femoral condyles of 55 Sprague-Dawley ovariectomized rats were implanted with screw augmented with CS, while the contralateral limb received a nonaugmented screw. At time intervals of 2, 4, 8, 12, and 16 weeks, 11 rats were euthanized. Six pair-matched samples were used for histological analysis, while five pair-matched samples were preserved for biomechanical testing. Histomorphometric data showed that CS augmented screws activated cancellous bone formation, evidenced by a statistically higher (p < 0.05) percentage of osteoid surface at 2, 4, and 8 weeks and a higher rate of bone mineral apposition at 12 weeks compared with nonaugmented screws. The amount of the bone-screw contact at 2, 8, and 12 weeks and of bone ingrowth on the threads at 4 and 8 weeks was greater in the CS group than in the nonaugmented group (p < 0.05), although these parameters increased concomitantly with time for both groups. The CS was resorbed completely at 8 weeks without stimulating fibrous encapsulation on the screw surface. Also, the cement significantly increased the screw pull-out force and the energy to failure at 2, 4, 8, and 12 weeks after implantation, when compared with the control group (p < 0.05). These results imply that augmentation of screw fixation with CS may have the potential to decrease the risk of implant failure in osteoporotic bone.