Desarrollo de indicaciones de uso apropiado del implante transcateter de protesis valvular aortica en el tratamiento de la estenosis aortica grave sintomatica

En cubierta aparecen logos del Ministerio de Sanidad, Servicios Sociales e Igualdad y de la Red Espanola de Agencias de Evaluacion de Tecnologias y Prestaciones del SN

Dp71, utrophin and beta-dystroglycan expression and distribution in PC12/L6 cell cocultures.

International audienceFunction of dystrophin Dp71 isoforms is unknown but seems related to neurite outgrowth and synapse formation. To evaluate Dp71 role in myoneural synapses, we established a coculture model using PC12 cells and L6 myotubes and analyzed expression and localization of Dp71 and related proteins, utrophin and beta-dystroglycan, in PC12 cells. Confocal microscopy showed Dp71d isoform in PC12 nuclei, golgi-complex-like and endoplasmic reticulum-like structures, whereas Dp71ab concentrates at neurite tips and cytoplasm, colocalizing with beta-dystroglycan, utrophin, synaptophysin and acetylcholine receptors. Evidences suggest that Dp71ab isoform, unlike Dp71d, may take part in neurite-related processes. This is the first work on Dp and members of Dp-associated protein complex roles in a cell-line based coculturing system, which may be useful in determining Dp71 isoforms associations

Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial.

PurposeTo determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).Patients and methodsPatients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks.ResultsA total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ≥3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1-11.1] months. The response rate was higher in human papillomavirus-positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFNγ-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1-31.7) and 64.7% (95% CI: 45.3-78.7), respectively.ConclusionsSD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity

The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes

Cardiorespiratory fitness cutoff points for early detection of present and future cardiovascular risk in children: A 2-year follow-up study

On behalf of the UP&DOWN Study Group.[Objective]: To examine the association between cardiorespiratory fitness (CRF) at baseline and cardiovascular disease (CVD) risk in 6- to 10-year-olds (cross-sectional) and 2 years later (8- to 12-year-olds [longitudinal]) and whether changes with age in CRF are associated with CVD risk in children aged 8 to 12 years. [Patients and Methods]: Spanish primary schoolchildren (n=236) aged 6 to 10 years participated at baseline. Of the 23 participating primary schools, 22% (n=5) were private schools and 78% (n=18) were public schools. The dropout rate at 2-year follow-up was 9.7% (n=23). The 20-m shuttle run test was used to estimate CRF. The CVD risk score was computed as the mean of 5 CVD risk factor standardized scores: sum of 2 skinfolds, systolic blood pressure, insulin/glucose, triglycerides, and total cholesterol/high-density lipoprotein cholesterol. [Results]: At baseline, CRF was inversely associated with single CVD risk factors (all P0.85; P<.001) and to predict CVD risk 2 years later (P=.004). Persistent low CRF or the decline of CRF from 6-10 to 8-12 years of age is associated with increased CVD risk at age 8 to 12 years (P<.001). [Conclusion]: During childhood, CRF is a strong predictor of CVD risk and should be monitored to identify children with potential CVD risk.This work was supported by grant DEP 2010-21662-C04-00 (DEP 2010-21662-C04-01: DEP 2010-21662-C04-02: DEP 2010-21662-C04-03: DEP 2010-21662-C04-04) from the National Plan for Research: Development and Innovation (R+D+i) MICINN and by grant FPU15/05337 from the Spanish Ministry of Education.Peer Reviewe

A randomized trial of planned cesarean or vaginal delivery for twin pregnancy

Background: Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy.\ud \ud Methods: We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison.\ud \ud Results: A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P = 0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P = 0.49).\ud \ud Conclusion: In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery