Mónica Ballesteros

Serum Activin A and Follistatin Levels in Gestational Diabetes and the Association of the Activin A-Follistatin System with Anthropometric Parameters in Offspring

Context The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth. Objective To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity. Design and methods A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity. Results Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = −0.199, P = 0.008) and the diagnosis of gestational diabetes (β = −0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively). Conclusions Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy.

Gender determines the actions of adiponectin multimers on fetal growth and adiposity

OBJECTIVE We sought to analyze the role of cord blood adiponectin and its multimeric forms in neonatal adiposity and fetal growth velocity (FGV) during the third trimester of pregnancy according to fetal gender. STUDY DESIGN This was a prospective analytical observational study conducted at the Diabetes and Pregnancy Unit, University Hospital Joan XXIII, Tarragona, Spain. In all, 96 healthy pregnant women were included in the early third trimester and were followed up until delivery. Maternal blood was obtained upon recruitment, and cord blood was obtained at delivery. Serial fetal ultrasounds were performed during the third trimester to assess FGV. Skinfolds were measured after birth to assess neonatal adiposity. Adiponectin multimers were determined in maternal and cord blood. RESULTS In female neonates, adiposity and FGV in the late third trimester were correlated positively with cord blood insulin (r = 0.343, P = .015 and r = 0.430, P = .002, respectively) and maternal pregravid body mass index (r = 597, P < .001 and r = 0.428, P = .002, respectively), and negatively with maternal high-molecular-weight (HMW)/total adiponectin ratio (r = -0.269, P = .035 and r = -0.387, P = .005, respectively), but in the stepwise multiple regression model, the main determinants were cord blood insulin, pregravid body mass index, and cord blood HMW adiponectin. Otherwise, in male neonates, adiposity and fetal growth were correlated with cord blood low-molecular-weight adiponectin (r = 0.486, P = .003 and r = 0.394, P = .020, respectively), and it was this multimeric form that emerged as an independent determinant in the stepwise regression model. CONCLUSION Adiponectin seems to determine fetal growth and adipose tissue accretion, and low molecular weight is more specifically implicated in males, whereas the HMW isoform may be more important in females.

Zinc-α2-Glycoprotein Is Unrelated to Gestational Diabetes: Anthropometric and Metabolic Determinants in Pregnant Women and Their Offspring

Context Zinc-α2-Glycoprotein (ZAG) is an adipokine with lipolytic action and is positively associated with adiponectin in adipose tissue. We hypothesize that ZAG may be related with hydrocarbonate metabolism disturbances observed in gestational diabetes mellitus (GDM). Objective The aim of this study was to analyze serum ZAG concentration and its relationship with carbohydrate metabolism in pregnant women and its influence on fetal growth. Design 207 pregnant women (130 with normal glucose tolerance (NGT) and 77 with GDM) recruited in the early third trimester and their offspring were studied. Cord blood was obtained at delivery and neonatal anthropometry was assessed in the first 48 hours. ZAG was determined in maternal serum and cord blood. Results ZAG concentration was lower in cord blood than in maternal serum, but similar concentration was observed in NGT and GDM pregnant women. Also similar levels were found between offspring of NGT and GDM women. In the bivariate analysis, maternal ZAG (mZAG) was positively correlated with adiponectin and HDL cholesterol, and negatively correlated with insulin and triglyceride concentrations, and HOMA index. On the other hand, cord blood ZAG (cbZAG) was positively correlated with fat-free mass, birth weight and gestational age at delivery. After adjusting for confounding variables, gestational age at delivery and HDL cholesterol emerged as the sole determinants of cord blood ZAG and maternal ZAG concentrations, respectively. Conclusion mZAG was not associated with glucose metabolism during pregnancy. ZAG concentration was lower in cord blood compared with maternal serum. cbZAG was independently correlated with gestational age at delivery, suggesting a role during the accelerated fetal growth during latter pregnancy.

Description of the protocols for randomized controlled trials on cancer drugs conducted in Spain (1999-2003).

Objective To describe the characteristics of randomized controlled clinical trials (RCT) on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. Methods We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Española del Medicamento y Productos Sanitarios (AEMPS) (Spanish Agency for Medicines and Medical Devices) during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. Results We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%), overall survival (20.7%), and progression-free survival (14.5%). Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724). Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001) and were more likely to implement centralized randomization (p<0.001), blinding of the intervention (p<0.001), and survival as primary outcome (p<0.001). Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01). In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7%) was lower. Conclusion RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non-profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide on-going initiatives that aim to increase the transparency and quality of future research.

Development of a prioritisation tool for the updating of clinical guideline questions: the UpPriority Tool protocol

Introduction Due to a continuous emergence of new evidence, clinical guidelines (CGs) require regular surveillance of evidence to maintain their trustworthiness. The updating of CGs is resource intensive and time consuming; therefore, updating may include a prioritisation process to efficiently ensure recommendations remain up to date. The objective of our project is to develop a pragmatic tool to prioritise clinical questions for updating within a CG. Methods and analysis To develop the tool, we will use the results and conclusions of a systematic review of methodological research on prioritisation processes for updating and will adopt a methodological approach we have successfully implemented in a previous experience. We will perform a multistep process including (1) generation of an initial version of the tool, (2) optimisation of the tool (feasibility test of the tool, semistructured interviews, Delphi consensus survey, external review by CG methodologists and users and pilot test of the tool) and (3) approval of the final version of the tool. At each step of the process, we will (1) calculate absolute frequencies and proportions (quantitative data), (2) use content analysis to summarise and draw conclusions (qualitative data) and (3) draft a final report, discuss results and refine the previous versions of the tool. Finally, we will calculate intraclass coefficients with 95% CIs for each item and overall as indicators of agreement among reviewers. Ethics and dissemination We have obtained a waiver of approval from the Clinical Research Ethics Committee at the Hospital de la Santa Creu i Sant Pau (Barcelona). The results of the study will be published in peer-reviewed journal and communicated to interested stakeholders. The tool could support the standardisation of prioritisation processes for updating CGs and therefore have important implications for a more efficient use of resources in the CG field.

Síndrome de transfusión feto-fetal

Resumen El sindrome de transfusion feto-fetal (STFF) es una complicacion que se presenta en un 10-15% de las gestaciones gemelares monocoriales biamnioticas. Es una afeccion exclusiva de este tipo de gemelaridad y se caracteriza por la presencia de anastomosis arteriovenosas cuyo flujo unidireccional no esta equilibrado por otras conexiones vasculares y, por consiguiente, se produce la secuencia oligoamnios-hidramnios. La afeccion fetal es debida a una hipovolemia del gemelo donante y a una hipervolemia del gemelo receptor Presentamos nuestra experiencia en este tipo de enfermedad. En los casos presentados, diagnosticados al final del segundo trimestre, se llevaron a cabo como medida terapeutica amniodrenajes seriados, los cuales permitieron prolongar la gestacion para la maduracion pulmonar fetal, aunque no solucionaron el STFF Realizamos, asimismo, una revision en cuanto a las diferentes opciones de tratamiento actual que van desde la conducta expectante, con una mortalidad cercana al 100%, hasta los tratamientos etiologicos basados en la ablacion selectiva con laser de los vasos comunicantes con una supervivencia de al menos un gemelo del 70%, con una tasa de handicap neurologico menor al 5%

Evidence mapping based on systematic reviews of therapeutic interventions for gastrointestinal stromal tumors (GIST)

BackgroundGastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach.MethodsWe followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot.ResultsA total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm.ConclusionsThe most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.