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.)

No abstract

No abstract

No abstract

No abstract

Pleomorphic adenoma commonly develops in the salivary gland, but rarely in the breast. The dynamic contrast-enhanced MR imaging findings of pleomorphic adenoma of the breast have not been well described. We report a 43-year-old woman with pleomorphic adenoma of the left breast. The imaging findings, including those on dynamic contrast-enhanced MR imaging, included an oval mass with a smooth margin, which consisted of solid and cystic components. The solid component was hypo-intense on T1-weighted imaging, hyper-intense on short tau inversion recovery imaging, with no apparent restricted diffusion, and had heterogeneous enhancement with dark internal septation and a fast/plateau dynamic contrast enhancement pattern. The cystic component was slightly hyper-intense on T1-weighted imaging, slightly hypo-intense on short tau inversion recovery imaging and had no apparent restricted diffusion or contrast enhancement. Together with its rarity, the similarities of imaging findings and the pathologic findings of pleomorphic adenoma of the breast to those of other tumors make accurate preoperative diagnosis difficult. Therefore, through this case report, awareness of pleomorphic adenoma of the breast on dynamic contrast-enhanced MR imaging will facilitate appropriate surgery and postoperative observation based on an accurate diagnosis.

No abstract

No abstract