Hospital Universitario La Paz

About: Hospital Universitario La Paz is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Medicine. The organization has 8960 authors who have published 11499 publications receiving 191509 citations.

Antepartum and Intrapartum Factors Preceding Neonatal Hypoxic-Ischemic Encephalopathy

Abstract: OBJECTIVE: To determine whether antepartum factors alone, intrapartum factors alone, or both in combination, are associated with term neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 405 infants ≥35 weeks’ gestation with early encephalopathy, born between 1992 and 2007, were compared with 239 neurologically normal infants born between 1996 and 1997. All cases met criteria for perinatal asphyxia, had neuroimaging findings consistent with acute hypoxia-ischemia, and had no evidence for a non–hypoxic-ischemic cause of their encephalopathy. RESULTS: Both antepartum and intrapartum factors were associated with the development of HIE on univariate analysis. Case infants were more often delivered by emergency cesarean delivery (CD; 50% vs 11%, P < .001) and none was delivered by elective CD (vs 10% of controls). On logistic regression analysis only 1 antepartum factor (gestation ≥41 weeks) and 7 intrapartum factors (prolonged membrane rupture, abnormal cardiotocography, thick meconium, sentinel event, shoulder dystocia, tight nuchal cord, failed vacuum) remained independently associated with HIE (area under the curve 0.88; confidence interval 0.85–0.91; P < .001). Overall, 6.7% of cases and 43.5% of controls had only antepartum factors; 20% of cases and 5.8% of controls had only intrapartum factors; 69.5% of cases and 31% of controls had antepartum and intrapartum factors; and 3.7% of cases and 19.7% of controls had no identifiable risk factors ( P < .001). CONCLUSIONS: Our results do not support the hypothesis that HIE is attributable to antepartum factors alone, but they strongly point to the intrapartum period as the necessary factor in the development of this condition. * Abbreviations: BW — : birth weight CD — : cesarean delivery CI — : confidence interval CTG — : cardiotocography GA — : gestational age HIE — : hypoxic-ischemic encephalopathy NE — : neonatal encephalopathy OR — : odds ratio PROM — : prolonged rupture of membranes TOBY — : Total Body Hypothermia for Neonatal Encephalopathy

IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer

Abstract: Cisplatin-based chemotherapy is the paradigm of non-small-cell lung cancer (NSCLC) treatment; however, it also induces de novo DNA-hypermethylation, a process that may be involved in the development of drug-resistant phenotypes by inactivating genes required for drug-cytotoxicity. By using an expression microarray analysis, we aimed to identify those genes reactivated in a set of two cisplatin (CDDP) resistant and sensitive NSCLC cell lines after epigenetic treatment. Gene expression, promoter methylation and CDDP-chemoresponse were further analyzed in three matched sets of sensitive/resistant cell lines, 23 human cancer cell lines and 36 NSCLC specimens. Results revealed specific silencing by promoter hypermethylation of IGFBP-3 in CDDP resistant cells, whereas IGFBP-3 siRNA interference, induced resistance to CDDP in sensitive cells (P<0.001). In addition, we found a strong correlation between methylation status and CDDP response in tumor specimens (P<0.001). Thus, stage I patients, whose tumors harbor an unmethylated promoter, had a trend towards increased disease-free survival (DFS). We report that a loss of IGFBP-3 expression, mediated by promoter-hypermethylation, results in a reduction of tumor cell sensitivity to cisplatin in NSCLC. Basal methylation status of IGFBP-3 before treatment may be a clinical biomarker and a predictor of the chemotherapy outcome, helping to identify patients who are most likely to benefit from CDDP therapy alone or in combination with epigenetic treatment.

The Biological Variation Data Critical Appraisal Checklist: A Standard for Evaluating Studies on Biological Variation

Abstract: BACKGROUND: Concern has been raised about the quality of available biological variation (BV) estimates and the effect of their application in clinical practice. A European Federation of Clinical Chemistry and Laboratory Medicine Task and Finish Group has addressed this issue. The aim of this report is to ( a ) describe the Biological Variation Data Critical Appraisal Checklist (BIVAC), which verifies whether publications have included all essential elements that may impact the veracity of associated BV estimates, ( b ) use the BIVAC to critically appraise existing BV publications on enzymes, lipids, kidney, and diabetes-related measurands, and ( c ) apply metaanalysis to deliver a global within-subject BV (CV I ) estimate for alanine aminotransferase (ALT). METHODS: In the BIVAC, publications were rated as A, B, C, or D, indicating descending compliance for 14 BIVAC quality items, focusing on study design, methodology, and statistical handling. A D grade indicated that associated BV estimates should not be applied in clinical practice. Systematic searches were applied to identify BV studies for 28 different measurands. RESULTS: In total, 128 publications were identified, providing 935 different BV estimates. Nine percent achieved D scores. Outlier analysis and variance homogeneity testing were scored as C in >60% of 847 cases. Metaanalysis delivered a CV I estimate for ALT of 15.4%. CONCLUSIONS: Application of BIVAC to BV publications identified deficiencies in required study detail and delivery, especially for statistical analysis. Those deficiencies impact the veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to deliver robust global estimates for safe clinical application.