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.)

Objective There is no standardized therapy for renal amyloidosis, which shows rapid progression and poor prognosis. Here, we used

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A 63-year-old woman was admitted to the hospital with general malaise and pericardial and thoracoabdominal effusions of unknown cause. After pericardial drainage for drug-resistant right heart failure, she developed right ventricular (RV) dysfunction and cardiogenic shock caused by severe tricuspid regurgitation (TR). Findings during emergency surgery included tricuspid valve (TV) junction failure caused by shortening of the chordae tendineae of the TV, which is an organic abnormality. Additionally, myocardial biopsy results revealed myocarditis. Although acute myocarditis developed with RV dysfunction, pericardial effusion suppressed venous return, which temporarily improved her pathological condition. However, RV dysfunction and severe TR were thought to have manifested after the venous return suppression was alleviated by pericardial drainage. Because venous return changes significantly after pericardial drainage, it is necessary to examine the need for drainage and re-evaluate the post-operative RV system.

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