Evolución e impacto bibliométrico de las becas de la Sociedad Española de Cardiología/Fundación Española del Corazón en el periodo 2007-2012

Introduction and objectivesThe Spanish Society of Cardiology/Spanish Heart Foundation (SEC/FEC) annually awards grants for cardiovascular research projects. Our objective was to analyze the trend in these investments and their resulting scientific production from 2007 to 2012.MethodsA search of the publications funded by the SEC/FEC was carried out, according to the following inclusion criteria: publication in a journal indexed in MEDLINE or EMBASE, publication date after the grant, authorship by the principal investigator of the grant, and acknowledgment of SEC/FEC funding. The impact factor and subsequent citations of the articles were analyzed (Web of Science).ResultsA total of 235 grants were awarded (39/y) with an allocation of €3 854 300 (€642 383/y), 37% of them to women. In all, 122 publications resulted from 88 research projects (37%) funded by the SEC/FEC. Up to October 2017, these publications had received 2258 citations in subsequent studies in the Web of Science, with a mean of 18.5 and a median of 8 citations/study.ConclusionsDespite the economic crisis, the mean number and size of the grants awarded by the SEC/FEC increased in the period analyzed. Grants were awarded on an equal opportunity basis to men and women. The bibliometric impact of the funded projects is acceptable, although efforts should be made to improve it.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (～76014 cases and ～264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.     

Same-Day Repeat Hepatopulmonary Shunt Measurement during Planning Angiography for Hepatic Radioembolization

This report describes a technique for measuring lung shunt fraction (LSF) twice in a single session during planning arteriography for radioembolization using low and standard dose technetium-99m macroaggregated albumin (^99mTc-MAA). A patient with a 16.0 cm hepatocellular carcinoma and LSF of 70% was treated with lenvatinib for 4 weeks. Planning arteriography with administration of 0.5 millicuries of ^99mTc-MAA was then performed. Arterial access was maintained while the LSF was calculated, which was persistently elevated at 54%. Embolization of arteriovenous shunts was performed during the same session and 5.0 millicuries of ^99mTc-MAA were administered. The repeat LSF was 29%. Successful radioembolization was subsequently performed.     

Long-term health and socioeconomic outcome of obstructive sleep apnea in children and adolescents

BackgroundThere is limited information about the long-term outcome of obstructive sleep apnea (OSA) diagnosed in children and adolescents for educational and social factors. Here, we estimate the long-term socioeconomic outcome and health care costs of OSA.MethodsThe historical case-control cohort study included Danish individuals with OSA diagnosed in childhood or adolescence between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. A total of 5419 were diagnosed during this period; of these we traced 1004 patients who we compared with 4085 controls (mean index age, 10.2 years; Standard Deviation (SD), 5.6 years) until the age of 20 years. Controls were matched for age, gender, and residency.ResultsComparing the OSA patient and control groups at age 20 years we found: 1) lower parental educational level; 2) significantly lower educational level also after adjustment for parental educational level; 3) lower school grade-point averages; 4) lower employment rate and lower income, which was not fully compensated when transfer payments were considered; and 5) patients' initial health care costs were higher due to higher morbidity. Patients showed higher mortality rates than controls (Hazard Ratio (HR) = 7.63, 95% CI = 4.87–11.95, P < 0.001).ConclusionsOSA in children and adolescent is associated with a significant influence on morbidity, mortality, educational level, grading, social outcome, and welfare consequences.     

术前减轻黄疸对壶腹部癌行Whipple手术治疗效果的影响

目的:探讨术前减轻黄疸对壶腹部癌患者行Whipple手术治疗效果的影响。方法:回顾性分析2012年1月—2018年7月45例在Whipple手术术前行减轻黄疸治疗的壶腹部癌患者(减轻黄疸组)的临床资料,与同期34例行Whipple手术术前未行减轻黄疸治疗的壶腹部癌患者(未减轻黄疸组)的临床资料进行比较。比较两组患者术前、术中情况(手术时间、出血量、输血量)和术后并发症的差异。结果:减轻黄疸组患者治疗后总胆红素(TBil)、结合胆红素(DBil)、谷丙转氨酶(ALT)与治疗前比较差异有统计学意义(P<0.05)。两组R 0切除率比较差异无统计学意义(P>0.05)。减轻黄疸组手术时间、术中出血量、术中输血量优于未减轻黄疸组,差异均有统计学意义(P<0.05)。减轻黄疸组术后并发症发生率、胰漏发生率和胆漏发生率少于未减轻黄疸组,差异均有统计学意义(P<0.05)。结论:壶腹部癌患者行Whipple手术术前彻底减轻黄疸,可以缩短手术时间,减少术中出血量和术后并发症的发生。     

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).