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.)
Background: Reliable prediction models of subarachnoid hemorrhage (SAH) outcomes are needed for decision-making of the treatment. SAFIRE score using only four variables is a good prediction scoring system. However, making such prediction models needs a large number of samples and time-consuming statistical analysis. Deep learning (DL), one of the artificial intelligence, is attractive, but there were no reports on prediction models for SAH outcomes using DL. We herein made a prediction model using DL software, Prediction One (Sony Network Communications Inc., Tokyo, Japan) and compared it to SAFIRE score. Methods: We used 153 consecutive aneurysmal SAH patients data in our hospital between 2012 and 2019. Modified Rankin Scale (mRS) 0–3 at 6 months was defined as a favorable outcome. We randomly divided them into 102 patients training dataset and 51 patients external validation dataset. Prediction one made the prediction model using the training dataset with internal cross-validation. We used both the created model and SAFIRE score to predict the outcomes using the external validation set. The areas under the curve (AUCs) were compared. Results: The model made by Prediction One using 28 variables had AUC of 0.848, and its AUC for the validation dataset was 0.953 (95%CI 0.900–1.000). AUCs calculated using SAFIRE score were 0.875 for the training dataset and 0.960 for the validation dataset, respectively. Conclusion: We easily and quickly made prediction models using Prediction One, even with a small single-center dataset. The accuracy of the model was not so inferior to those of previous statistically calculated prediction models.
The surgical efficacy for supratentorial intracerebral hemorrhage (ICH) remains unknown. We compared the advantages of the widely practiced endoscopic hematoma removal under local anesthesia with that of craniotomy under general anesthesia for ICH. We also focused on our novel operative concept of intentional hematoma leaving technique to avoid further damage to the brain. We retrospectively analyzed 134 consecutive patients (66 endoscopies and 68 craniotomies) who were surgically treated for supratentorial ICH. The characteristics of the 134 patients were as follows: The median (interquartile range) age was 73 (61-82) years. The median Glasgow Coma Scale scores at admission, on day 7, and the median modified Rankin Scale (mRS) score at 6 months were 10 (7-13), 13 (10-14), and 4 (3-5) respectively. The statistical comparison revealed there were no differences in GCS score on day seven between the endoscopy 13 (12-14) and craniotomy group 12 (9-14). No differences were observed in mRS scores at 6 months between the endoscopy 4 (2-5) and craniotomy group 4 (3-5). However, the patients treated with our technique tended to have favorable outcomes. Multivariate analysis revealed the operative time was significantly decreased in the endoscopy group compared to the craniotomy group (p < 0.001). Spontaneous intracerebral hemorrhages (ICHs) are responsible for 10%-30% of all strokes and they remain a significant cause of all stroke-related mortality and morbidity 1,2. ICH is a medical emergency with high fatality and disability rates. The median 30-day mortality rate after ICH is approximately 15-50% 3,4 and only 20% of patients regain functional independence within three months after the ictus 5. Surgical hematoma removal and conservative therapy are the main treatments for ICH; however, the role of surgery for most patients with ICH remains controversial. Theoretically, surgical hematoma removal prevents herniation by reducing the intracranial pressure and decreasing the pathophysiological impact of the hematoma on surrounding tissue 2. However, the effectiveness of surgery has been repeatedly evaluated 6,7 and its benefits are still under discussion. The Surgical Trial in Intracerebral Haemorrhage (STICH) indicated that patients with spontaneous supratentorial ICH showed no overall benefit from the early surgery when compared to the initial conservative therapy. However, operative intervention occurred in 24% of patients in the initial conservative treatment group 6. Therefore, the interpretation of these results is complicated. The STICH II trial confirmed that early surgery did not increase the rate of death or disability, 6 months postoperatively, and may have a small but clinically relevant survival advantage for patients with spontaneous superficial ICH without an intraventricular hemorrhage 7. A recent report based primarily on the STICH II trial reported that only patients with a GCS 10-13 or a large ICH were likely to benefit from surgery 8. However, the STICH and STICH II trials did not exhibit an overall comp...
Background: Skeletal muscle mass is an important factor for various diseases’ outcomes. As for its indicators, temporal muscle thickness (TMT) and temporal muscle area (TMA) on the head computed tomography are useful, and TMT and TMA were reported as potential prognostic factors for aneurysmal subarachnoid hemorrhage (SAH). We examined the clinical characteristics, including TMT and TMA, of SAH patients aged 75 or younger. Methods: We retrospectively investigated 127 SAH patients with all World Federation of Neurosurgical Societies (WFNS) grades and treated by clipping between 2009 and 2019. Clinical outcome was measured with the modified Rankin Scale (mRS) at 6 months, with favorable outcome defined as mRS 0–2. The associations between the clinical variables and the outcomes were analyzed. Results: The mean age was 60.6 (32–74) years, and 65% were women. The mean ± standard deviation of WFNS grade was 2.8 ± 1.4. TMT and TMA were larger in the favorable outcome group than the poor one. Multivariate analysis revealed that age, smoking, WFNS grade, and TMT or TMA were associated with favorable outcome. Receiver operating characteristic analysis found that the threshold of TMT was 4.9 mm in female and 6.7 mm in male, and that of TMA was 193 mm2 in female and 333 mm2 in male. Conclusion: The odds ratios for TMT and TMA related to clinical outcome were lower than for smoking and WFNS grade; however, on multivariate analysis they remained independent prognostic factors in SAH patients aged 75 or younger treated by clipping. Further studies are needed to confirm these findings.
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