BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Renal multiphase 3D MR angiography is an accurate technique requiring no bolus timing. The performance of early arterial phase imaging leads to improved depiction, particularly of the distal renovascular tree, compared to that with standard single-phase 3D MR angiography.

Purpose Coronal correction errors after medial opening wedge high tibial osteotomy (MOWHTO) occasionally occur even with the assistance of navigation. The purpose of the present study was to determine the navigation accuracy in MOWHTO and to identify factors that affect the coronal correction error after navigation-assisted MOWHTO. Methods A total of 114 knees treated with navigation-assisted MOWHTO were reviewed retrospectively. Mechanical axis (MA) on standing radiograph and medial proximal tibial angle (MPTA) were measured preoperatively and at 6 months postoperatively, and the differences (ΔMA and ΔMPTA) were calculated. Joint line convergence angle (JLCA) on supine and standing radiographs was measured preoperatively, and their difference (ΔJLCA) was calculated. To assess the navigation accuracy, ΔMA and ΔMPTA were compared with the coronal correction by navigation (ΔNMA) using intraclass correlation coefficients (ICCs). Univariable and multivariable regression analyses were used to identify factors that affect coronal correction discrepancy (ΔMA − ΔNMA). ResultsThe reliability of navigation was good in terms of bony correction (ICC between ΔNMA and ΔMPTA, 0.844) and fair in terms of MA correction (ICC between ΔNMA and ΔMA, 0.706). The mean coronal correction discrepancy was 2.0° ± 2.4°. In the multivariable analysis, ΔJLCA was shown to be a predictive factor of coronal correction discrepancy (unstandardized coefficient, 1.026; R 2 , 0.470). Conclusion Navigation in MOWHTO provided reliable information about bony correction; however, MA tended to be overcorrected. The difference in JLCA between the supine and standing radiographs was the most important preoperative factor that predicted the coronal correction discrepancy after MOWHTO. In patients with larger ΔJLCA, each degree of ΔJLCA should be subtracted from the planned amount of correction angle when preoperative planning is performed using standing radiographs. Level of evidence IV.

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