Retrospective cohort analysis of Spanish national trends of coronary artery bypass grafting and percutaneous coronary intervention from 1998 to 2017

Introduction Spain is one of the countries with the lowest rates of revascularisation and highest ratio of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG). Objectives To investigate the changes and trends in the two revascularisation procedures between 1998 and 2017 in Spain. Design Retrospective cohort study. Analysis of in-hospital outcomes. Setting Minimum basic data set from the Spanish National Department of Health: mandatory database collecting information of patients who are attended in the Spanish public National Health System. Participants 603 976 patients who underwent isolated CABG or PCI in the Spanish National Health System. The study period was divided in four 5-year intervals. Patients with acute myocardial infarction on admission were excluded. Primary and secondary outcomes We investigated the volume of procedures nationwide, the changes of the risk profile of patients and in-hospital mortality of both techniques. Results We observed a 2.2-fold increase in the rate of any type of myocardial revascularisation per million inhabitants-year: 357 (1998) to 776 (2017). 93 682 (15.5%) had a coronary surgery. PCI to CABG ratio rose from 2.2 (1998-2002) to 8.1 (2013-2017). Charlson's index increased by 0.8 for CABG and 1 for PCI. The median annual volume of PCI/hospital augmented from 136 to 232, while the volume of CABG was reduced from 137 to 74. In the two decades, we detected a significant reduction of CABG in-hospital mortality (6.5% vs 2.6%, p<0.001) and a small increase in PCI (1.2% vs 1.5%, p<0.001). Risk adjusted mortality rate was reduced for both CABG (1.51 vs 0.48, p<0.001), and PCI (1.42 vs 1.05, p<0.001). Conclusion We detected a significant increase in the volume of revascularisations (particularly PCI) in Spain. Risk-adjusted in-hospital mortality was significantly reduce

Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab : the BEYOND study (GEMCAD 17-01)

Altres ajuts: Fundació la Marató de TV3 (201330.10); Fundacion Olga Torres (Modalitat A. 2019/2020); Spanish Association Against Cancer (AECC, PROYE19040POST_001).Purpose: Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods: In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results: Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions: The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation

High rate of uncovered struts in latest generation drug-eluting stents with durable, biodegradable polymer or lack of it 1 month after implantation

Introduction and objectives: Delayed vascular healing may induce late stent thrombosis. Optical coherence tomography (OCT) is useful to evaluate endothelial coverage. The objective of this study was to compare stent coverage and apposition in non-complex coronary artery lesions treated with durable polymer-coated everolimus-eluting stents (durable-polymer EES) vs biodegradable polymer-coated everolimus-eluting stents ( biodegradable-polymer EES) vs polymer-free biolimus-eluting stents (BES) 1 and 6 months after stent implantation. Methods: Prospective, multicenter, non-randomized study that compared the 3 types of DES. Follow-up angiography and OCT were performed 1 and 6 months later. The primary endpoint was the rate of uncovered struts as assessed by the OCT at 1 month. Results: A total of 104 patients with de novo non-complex coronary artery lesions were enrolled. A total of 44 patients were treated with polymer-free BES, 35 with biodegradable-polymer EES, and 25 with durable-polymer EES. A high rate of uncovered struts was found at 1 month with no significant differences reported among the stents (80.2%, polymer-free BES; 88.1%, biodegradable-polymer EES; 82.5%, durable-polymer EES; P =.209). Coverage improved after 6 months in the 3 groups without significant differences being reported (97%, 95%, and 93.7%, respectively; P =.172). Conclusions: In patients with de novo non-complex coronary artery lesions treated with durable vs biodegradable vs polymer-free DES, strut coverage and apposition were suboptimal at 1 month with significant improvement at 6 months

Hyperkalemia in Heart Failure Patients in Spain and Its Impact on Guidelines and Recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry

[Abstract] Introduction and objectives: Hyperkalemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction because it limits the use of effective drugs. We report estimates of the magnitude of this problem in routine clinical practice in Spain, as well as changes in potassium levels during follow-up and associated factors. Methods: This study included patients with acute (n=881) or chronic (n=3587) heart failure recruited in 28 Spanish hospitals of the European heart failure registry of the European Society of Cardiology and followed up for 1 year. Various outcomes were analyzed, including changes in serum potassium levels and their impact on treatment. Results: Hyperkalemia (K+> 5.4 mEq/L) was identified in 4.3% (95%CI, 3.7%-5.0%) and 8.2% (6.5%-10.2%) of patients with chronic and acute heart failure, respectively, and was responsible for 28.9% of all cases of contraindication to mineralocorticoid receptor antagonist use and for 10.8% of all cases of failure to reach the target dose. Serum potassium levels were not recorded in 291 (10.8%) of the 2693 chronic heart failure patients with reduced ejection fraction. During follow-up, potassium levels increased in 179 of 1431 patients (12.5%, 95%CI, 10.8%-14.3%). This increase was directly related to age, diabetes, and history of stroke and was inversely related to history of hyperkalemia. Conclusions: This study highlights the magnitude of the problem of hyperkalemia in patients with heart failure in everyday clinical practice and the need to improve monitoring of this factor in these patients due to its interference with the possibility of receiving optimal treatment.[Resumen] Introducción y objetivos. La hiperpotasemia es una preocupación creciente en el tratamiento de los pacientes con insuficiencia cardiaca y fracción de eyección reducida, pues limita el uso de fármacos eficaces. Este trabajo ofrece estimaciones de la magnitud de este problema en la práctica clínica habitual en España, los cambios en las concentraciones de potasio en el seguimiento y los factores asociados. Métodos. Pacientes con insuficiencia cardiaca aguda (n = 881) y crónica (n = 3.587) seleccionados en 28 hospitales españoles del registro europeo de insuficiencia cardiaca de la European Society of Cardiology y seguidos 1 año para diferentes desenlaces, incluidos cambios en las cifras de potasio y su impacto en el tratamiento. Resultados. La hiperpotasemia (K+ > 5,4 mEq/l) está presente en el 4,3% (IC95%, 3,7-5,0%) y el 8,2% (6,5-10,2%) de los pacientes con insuficiencia cardiaca crónica y aguda; causa el 28,9% de todos los casos en que se contraindica el uso de antagonistas del receptor de mineralocorticoides y el 10,8% de los que no alcanzan la dosis objetivo. Del total de 2.693 pacientes ambulatorios con fracción de eyección reducida, 291 (10,8%) no tenían registrada medición de potasio. Durante el seguimiento, 179 de 1.431 (12,5%, IC95%, 10,8-14,3%) aumentaron su concentración de potasio, aumento relacionado directamente con la edad, la diabetes mellitus y los antecedentes de ictus e inversamente con los antecedentes de hiperpotasemia. Conclusiones. Este trabajo destaca el problema de la hiperpotasemia en pacientes con insuficiencia cardiaca de la práctica clínica habitual y la necesidad de continuar y mejorar la vigilancia de este factor en estos pacientes por su interferencia en el tratamiento óptimo

Carbapenem-resistant and carbapenem-susceptible isogenic isolates of Klebsiella pneumoniae ST101 causing infection in a tertiary hospital

Background: In this study we describe the clinical and molecular characteristics of an outbreak due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) producing CTX-M-15 and OXA-48 carbapenemase. Isogenic strains, carbapenem-susceptible K. pneumoniae (CS-KP) producing CTX-M-15, were also involved in the outbreak. Results: From October 2010 to December 2012 a total of 62 CR-KP and 23 CS-KP were isolated from clinical samples of 42 patients (22 had resistant isolates, 14 had susceptible isolates, and 6 had both CR and CS isolates). All patients had underlying diseases and 17 of them (14 patients with CR-KP and 3 with CS-KP) had received carbapenems previously. The range of carbapenem MICs for total isolates were: imipenem: 2 to >32 mu g/ml vs. <2 mu g/ml; meropenem: 4 to >32 mu g/ml vs. <2 mu g/ml; and ertapenem: 8 to >32 mu g/ml vs. <2 mu g/ml. All the isolates were also resistant to gentamicin, ciprofloxacin, and cotrimoxazole. Both types of isolates shared a common PFGE pattern associated with the multilocus sequence type 101 (ST101). The bla(CTX-M-15) gene was detected in all the isolates, whereas the bla(OXA-48) gene was only detected in CR-KP isolates on a 70 kb plasmid. Conclusions: The clonal spread of K. pneumoniae ST101 expressing the OXA-48 and CTX-M-15 beta-lactamases was the cause of an outbreak of CR-KP infections. CTX-M-15-producing isolates lacking the blaOXA-48 gene coexisted during the outbreak.This study was supported by CIBER de Enfermedades Respiratorias (CIBERES - CB06/06/0037), ISCIII - Instituto de Salud Carlos III, Madrid, Spain

Ribavirin Can Be Mutagenic for Arenaviruses ▿

Arenaviruses include several important human pathogens, and there are very limited options of preventive or therapeutic interventions to combat these viruses. An off-label use of the purine nucleoside analogue ribavirin (1-β-d-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is the only antiviral treatment currently available for arenavirus infections. However, the ribavirin antiviral mechanism action against arenaviruses remains unknown. Here we document that ribavirin is mutagenic for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) in cell culture. The mutagenic activity of ribavirin on LCMV was observed under single- and multiple-passage regimes and could not be accounted for by a decrease of the intracellular GTP pool promoted by ribavirin-mediated inhibition of inosine monophosphate dehydrogenase (IMPDH). Our findings suggest that the antiviral activity of ribavirin on arenaviruses might be exerted, at least partially, by lethal mutagenesis. Implications for antiarenavirus therapy are discussed

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.This work was subsidized by grants from the Instituto de Salud Carlos III (Ministerio de. Economía y Competitividad from Spain), ID: PI12/01867 and PI13/00412; and Instituto Canario de Investigación del Cáncer (ICIC-GR-F-14/11). Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC)

Simulations of Nucleic Acids and Their Complexes

International audienceRecent years have seen considerable progress in simulations of nucleic acids. Improvements in force fields, simulation techniques and protocols, and increasing computer power have all contributed to making nanosecond-scale simulations of both DNA and RNA commonplace. The results are already helping to explain how nucleic acids respond to their environment and to their base sequence and to reveal the factors underlying recognition processes by probing biologically important nucleic acid-protein interactions and medically important nucleic acid-drug complexation. This Account summarizes methodological progress and applications of molecular dynamics to nucleic acids over the past few years and tries to identify remaining challenges.Recent years have seen considerable progress in simulations of nucleic acids. Improvements in force fields, simulation techniques and protocols, and increasing computer power have all contributed to making nanosecond-scale simulations of both DNA and RNA commonplace. The results are already helping to explain how nucleic acids respond to their environment and to their base sequence and to reveal the factors underlying recognition processes by probing biologically important nucleic acid-protein interactions and medically important nucleic acid-drug complexation. This Account summarizes methodological progress and applications of molecular dynamics to nucleic acids over the past few years and tries to identify remaining challenges