FH phenotype: monogenic, polygenic and other causes

Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.Cibelle Mariano was supported by a PhD student grant [SFRH/BD/52494/2014]. Marta Futema is supported by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no 14 CVD03). The work of Marilia Antunes is partially funded by UID/MAT/000016/2019. SEH acknowledges funding from the British Heart Foundation grant (BHF PG08/008) and from the NIHR UCLH BRC. MB acknowledges funding from Science and Technology Foundation (PIC/IC/83020/2007) (PIC/IC/83333/2007) for the e_COR and Portuguese FH Study and from Portuguese Cardiology Society for the Portuguese FH Study.info:eu-repo/semantics/publishedVersio

Single-institution experience in clinical trials during the COVID-19 pandemic in Spain: Not so bad after all?

The impact of the COVID-19 outbreak in Spain during March-April 2020 has been unbalanced throughout the different regions of the country. The alarm status defined by the government on March 14, and still in place at the time of this writing, has transformed the country in different perspectives, including care of patients with cancer.1 In many centers, clinical trial activity was suspended, because it was not considered a priority under the health care challenge of the COVID-19 pandemic.2 Nevertheless, experimental therapy is the only and/or best therapeutic option for many patients with cancer

Estudio Integral sobre la Evaluación del Recurso Eólico en Entornos Urbanos. Estación Anemométrica Adaptable

Como consecuencia de un intenso proceso de trabajo, coordinado con Investigadores del CIEMAT (Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas), se pretende comunicar el estado del trabajo de Investigación relacionado con la Evaluación del Potencial Eólico en entornos urbanos, con vistas a la posible generación de energía eléctrica limpia

Immunotherapy moves to the early-stage setting in non-small cell lung cancer: emerging evidence and the role of biomarkers

Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival in advanced non-small cell lung cancer (NSCLC) and both therapies are now well-established in this clinical setting. However, it is time for immunotherapy to be applied in patients with early-stage disease, which would be an important qualitative leap in the treatment of lung cancer patients with curative intent. Preliminary data from a multitude of studies are highly promising, but therapeutic decision-making should be guided by an understanding of the molecular features of the tumour and host. In the present review, we discuss the most recently published studies and ongoing clinical trials, controversies, future challenges and the role of biomarkers in the selection of best therapeutic options

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true