ObjectiveTo evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.MethodsA total of 800 infants of ≤32‐week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age.ResultsDeath and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk [RR] = 0.40, 95% confidence interval [CI] = 0.27–0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19–0.55, p < 0.001), and no excess adverse events were observed.InterpretationRepeated low‐dose rhEPO treatment reduced the risk of long‐term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24–34
The efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie's disease (PD) has been controversial for a very long time. We aimed to evaluate the efficiency of ESWT for PD and provide possible evidence on the basis of a meta-analysis of existing comparative studies. All controlled studies, including randomized controlled trials (RCTs), cohort studies and case-control studies, that focused on the efficiency of ESWT for PD, were prospectively identified through comprehensive searches of PubMed, the Cochrane Library and Embase databases. We conducted a meta-analysis of these studies. Six studies including 443 patients were selected for the meta-analysis. Pooling data of these studies showed that ESWT could significantly increase the percentage of men with lessening of penile plaques (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.11-3.85, P=0.02), relief of pain (OR 4.46, 95% CI 2.29-8.68, P<0.0001) and complete remission of pain (OR 5.86, 95% CI 2.66-12.92, P<0.0001). However, insignificant differences were found in improvement of penile curvature (OR 1.88, 95% CI 0.97-3.65, P=0.06) and sexual function (OR 2.22, 95% CI 0.69-7.11, P=0.18) between ESWT and placebo groups. Further, similar results were shown for sensitivity and publication bias analysis when only RCTs were included. However, sporadic complications caused by ESWT were reported, but no patient needed additional treatment aside from conservative observation. ESWT may be an effective and safe treatment for lessening of penile plaques and relieving pain for men with PD, but not for improving of penile curvature and sexual function.
In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users.
Early amplitude-integrated electroencephalography (aEEG) has been widely used in term infants with brain injury to predict neurodevelopmental outcomes; however, the prognostic value of early aEEG in preterm infants is unclear. We evaluated how well early aEEG could predict brain damage and long-term neurodevelopmental outcomes in very preterm infants compared with brain imaging assessments. We found that severe aEEG abnormalities (p = 0.000) and aEEG total score < 5 (p = 0.006) within 72 h after birth were positively correlated with white-matter damage, but aEEG abnormalities were not associated with intracranial hemorrhage (p = 0.186). Severe abnormalities in aEEG recordings, head ultrasound, and cranial magnetic resonance imaging (MRI) were all positively correlated with poor outcome at 18 months corrected age. The predictive power of poor outcomes of the aEEG and MRI combination was the same as the aEEG, MRI, and head ultrasound combination with a sensitivity of 52.4%, specificity of 96.2%, positive predictive value of 78.6%, and negative predictive value of 88.4%. These results indicate that severely abnormal aEEG recordings within 72 h after birth can predict white-matter damage and long-term poor outcomes in very preterm infants. Thus aEEG can be used as an early marker to monitor very preterm infants.
The role of statins in preventing prostate cancer is currently a controversial issue. The aim of this review is to investigate the effects of statins use on prostate cancer risk. Electronic databases (the Cochrane Library, PubMed, Medline, Embase, Web of Science, and ClinicalTrials.gov) were searched systematically up to April, 2015. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CIs). Statistic heterogeneity scores were assessed with the standard Cochran’s Q test and I2 statistic. The pooled estimates of randomized controlled trials (RCTs) and retrospective studies suggest that statins have a neutral effect on total prostate cancer (RR = 1·02, 95% CI: 0·90–1·14; and RR = 0·91, 95% CI: 0·79–1·02, respectively). This research provides no evidence to suggest that the use of statins for cholesterol lowering is beneficial for the prevention of low-grade or localized prostate cancer, although a plausible association between statins use and the reduction risk of advanced (RR = 0·87, 95% CI: 0·82–0·91) or high-grade prostate cancer (RR = 0·83, 95% CI: 0·66–0·99) is observed. Furthermore, it shows that prostate cancer risk does not statistically significant benefit from long-term statins use.
Prophylactic antibiotics could be beneficial for the reduction of infective complications after TRPB. Single-dose or short-course oral administration with any type of antibiotic appears to be optimal. One additional type of antibiotic added to the basic antibiotic agent may contribute to the minimization of severe infection and drug resistance.
SummaryEmbryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency. Gene targeting combined with small-molecule screening experiments identified that concomitant inhibition of Wnts, STAT3, and p38 pathways (3i) could largely convert FP to MGE under AD conditions. Thus, differentiation paradigms and signaling regulators can be integrated together to specify distinct neuronal subtypes for studying and treating related neurological diseases, such as epilepsy, Alzheimer's disease, and Parkinson's disease.
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