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: Intravenous immunoglobulin and plasma exchange are proven treatments for Guillain-Barré syndrome. Despite these treatments, the prognosis for severe Guillain-Barré syndrome is still not satisfactory. This article seeks for a logical timing for plasma exchange-intravenous immunoglobulin synergy, which may improve outcome in severe Guillain-Barré syndrome requiring mechanical ventilation. Study Design: This study is an open-label study. Nine pediatric severe Guillain-Barré syndrome patients requiring mechanical ventilation were treated with novel treatment strategy named as "zipper method." In this method, following diagnosis of Guillain-Barré syndrome, plasma exchange was started immediately. In the first session of plasma exchange, one and a half volume of patients' plasma was removed by using 5% albumin as replacement solution. At the end of the plasma exchange session, 0.4 g/kg intravenous immunoglobulin infusion was started immediately. Second plasma exchange session was applied with one volume change after 24 hours from the end of the intravenous immunoglobulin infusion. Each plasma exchange session was followed by intravenous immunoglobulin infusions. This plasma exchange-intravenous immunoglobulin cycle was repeated for 5 times. Results: Among the 9 patients, the mean mechanical ventilation duration was 7 (5-14) days and the mean hospital stay was 18 (10-30) days. Medical Research Council sum score was increased in all patients, especially after the third session. All patients survived and all patients were able to walk unaided on the 28th day of admission. Conclusion: The zipper method as a novel treatment modality seems to reduce mortality, speed up weaning from mechanical ventilation, and shorten hospital stay, with excellent outcome in severe Guillain-Barré syndrome patients, who require intensive care. This technique stands as a promising immunomodulation strategy for various scenarios.

pRIFLE identified AKI more frequently than the AKIN criteria. pRIFLE identified patients at risk for AKI earlier, and was more sensitive in pediatric patients. Any degree of AKI in both classifications was associated with increased mortality. Both sets of criteria had the same association with mortality.

The CRRT in critically ill patients is successful in achieving fluid removal and correction of metabolic imbalances caused by organ failures or attacks of inborn errors of metabolism. It has a positive effect on expected mortality in high-risk PICU patients. To affect the outcome, follow-up should be focused on starting therapy in early stages of fluid overload. Prospective studies defining relative importance of risk factors causing mortality can assist in building up guidelines to affect the outcome.

There is a substantial variability among clinicians' perceptions regarding indications for delay to initiate enteral feeding in critically ill children, especially after the first 6 h of PICU admission. ERTEN, but not EIF, is associated with a significantly lower mortality rate in critically ill children.