Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial

[EN] Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5-4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.This work was supported by a grant for medical research from Spanish Government (FIS-PI12/00799) and by the Spanish Ministerio de Ciencia, Innovacion y Universidades under "Programa Estatal de I+D+i Orientada a los Retos de la Sociedad", Grant RTI2018-094357-B-C21.Radosevic, A.; Quesada, R.; Serlavos, C.; Sánchez, J.; Zugazaga, A.; Sierra, A.; Coll, S.... (2022). Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial. Scientific Reports. 12(1):1-10. https://doi.org/10.1038/s41598-021-03802-xS11012

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Consumption of polyunsaturated fat improves the saturated fatty acid-mediated impairment of HDL antioxidant potential

[Scope] The present study aimed to compare the effects of diets containing high-fat, high-cholesterol and saturated fatty acids (HFHC-SFA) and HFHC-polyunsaturated fatty acids-containing (HFHC-PUFA) diets on two major antiatherogenic functions of HDL, the HDL antioxidant function and the macrophage-to-feces reverse cholesterol transport. [Methods and results] Experiments were carried out in mice fed a low-fat, low-cholesterol (LFLC) diet, an HFHC-SFA diet or an HFHC-PUFA diet in which SFAs were partly replaced with an alternative high-linoleic and α-linolenic fat source. The HFHC-SFA caused a significant increase in serum HDL cholesterol and phospholipids as well as elevated levels of oxidized HDL and oxidized LDL. Replacing SFA with PUFA significantly reduced the levels of these oxidized lipoproteins and enhanced the ability of HDL to protect LDL from oxidation. The SFA-mediated impairment of HDL antioxidant potential was not associated with the cholesterol content of the diet, obesity or insulin resistance. In contrast, the effect of the HFHC diets on fecal macrophage-derived cholesterol excretion was independent of the fatty acid source. [Conclusion] SFA intake impairs the antioxidant potential of HDL and increases serum levels of oxidized lipoprotein species whereas the antioxidant potential of HDL is enhanced after PUFA consumption.Peer Reviewe

Circulating lipoprotein-carried miRNome analysis reveals novel VLDL-enriched microRNAs that strongly correlate with the HDL-microRNA profile

Lipoproteins have been described as microRNAs (miRNAs) carriers. Unfortunately, the bibliography on this topic is scarce and shows a high variability between independent investigations. In addition, the miRNA profiles of the LDL and VLDL fractions have not been completely elucidated. Here, we profiled the human circulating lipoprotein-carried miRNome. Lipoprotein fractions (VLDL, LDL and HDL) were isolated from the serum of healthy subjects by ultracentrifugation and purified by size-exclusion chromatography. A panel of 179 miRNAs commonly expressed in circulation was evaluated in the lipoprotein fractions using quantitative real-time PCR (qPCR) assays. A total of 14, 4 and 24 miRNAs were stably detected in the VLDL, LDL and HDL fractions, respectively. VLDL- and HDL-miRNA signatures were highly correlated (rho 0.814), and miR-16–5p, miR-142–3p, miR-223–3p and miR-451a were among the top 5 expressed miRNAs in both fractions. miR-125a-5p, miR-335–3p and miR-1260a, were detected in all lipoprotein fractions. miR-107 and miR-221–3p were uniquely detected in the VLDL fraction. HDL showed the larger number of specifically detected miRNAs (n = 13). Enrichment in specific miRNA families and genomic clusters was observed for HDL-miRNAs. Two sequence motifs were also detected for this group of miRNAs. Functional enrichment analysis including the miRNA signatures from each lipoprotein fraction suggested a potential role in mechanistic pathways previously associated with cardiovascular disease: fibrosis, senescence, inflammation, immune response, angiogenesis, and cardiomyopathy. Collectively, our results not only support the role of lipoproteins as circulating miRNA carriers but also describe for the first time the role of VLDL as a miRNA transporter.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "Miguel Servet 2020: CP20/00041" and co-funded by the European Union. This work is supported by Instituto de Salud Carlos III (PI16/00471, PI20/00334, PI20/00577 and PI21/01523), co-funded by the European Union, IRBLleida - Fundació Dr. Pifarré, CERCA Programme/Generalitat de Catalunya. NR has received financial support from Ministerio de Ciencia, Innovación y Universidades (PID2019-104367RB-100), and Agencia Estatal de Investigación (AEI/10.13039/501100011033) within the Subprograma Ramón y Cajal (RYC-201722879). CIBERDEM (CB07/08/0016), CIBERES (CB07/06/2008) and CIBERCV (CB16/11/00276) are initiatives of the Instituto de Salud Carlos III

Soluble LRP1 is an independent biomarker of epicardial fat volume in patients with type 1 diabetes mellitus

Epicardial adipose tissue (EAT) is a metabolically active tissue intimately associated with metabolic syndrome and cardiovascular disease. Quantification of EAT volume is an interesting clinical tool for the evaluation of cardiometabolic disease. Nevertheless, current methodology presents serious disadvantages. The soluble form of the receptor LRP1 (sLRP1) is a non-invasive biomarker of EAT in general population. Here, we analysed the potential of circulating sLRP1 as biomarker of EAT volume in patients with type 1 diabetes mellitus (T1DM). The study included a well-characterized cohort of T1DM patients without clinical cardiovascular disease (N = 73). EAT volume was assessed by a multidetector computed tomography (MDCT). sLRP1 and panel of inflammatory and endocrine mediators were measured using commercially available ELISA. EAT volume showed a direct association with circulating sLRP1 (β = 0.398, P = 0.001) in univariate linear regression analysis. This association was higher than that observed for other potential inflammatory and endocrine biomarkers. Using multivariate linear regression analyses, we demonstrated that the association between EAT volume and circulating sLRP1 was independent of potential confounding factors, including age, sex, body mass index, CRP, HbA1c and LDL-C (P < 0.050 for all multivariate linear regression models). In conclusion, sLRP1 is an independent biomarker of EAT in T1DM patients.Tis work was supported by FIS PI14/01729 and FIS PI13/00364 from the Instituto Salud Carlos III, co-fnanced by the European Fund for Regional Development (E.F.R.D), Fundació Marató TV3 (201521 10) and Ayudas Sociedad Española de Diabetes (SED) de Investigación Básica y Clínica en Diabetes 2011. CIBER Cardiovascular (CB16/11/00403) and CIBERDEM (CB07/08/0016) are Instituto de Salud Carlos III Projects. DdG-C was a recipient of a Sara Borrell grant from the Instituto de Salud Carlos III (CD14/00109). AR-U, MP-C and JLS-Q are members of the Quality Research Group 2014-SGR-0246 and VLL-C, DdG-C are members of the Quality Research Group 2014-SGR-00170 from Generalitat de Catalunya.Peer reviewe

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

Antecedents. Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Aim. Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. Methods. 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction  21 ng/L (). Conclusion. Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.This study was supported in part by the Instituto de Salud Carlos III Spanish Network on Cardiovascular Research (RIC, n° RD12/0042/000), CIBERCV, and FEDER (Fondo Europeo de Desarrollo Regional).Peer reviewe

Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study

International audienceBackground: The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV.Methods: This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity.Results: Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 Å (IQR -0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = -0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 μmol/min/mL (IQR -2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR -102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed.Conclusions: Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2

Plasma microRNA profiling reveals novel biomarkers of epicardial adipose tissue: A multidetector computed tomography study

Epicardial adipose tissue (EAT) constitutes a novel parameter for cardiometabolic risk assessment and a target for therapy. Here, we evaluated for the first time the plasma microRNA (miRNA) profile as a source of biomarkers for epicardial fat volume (EFV). miRNAs were profiled in plasma samples from 180 patients whose EFV was quantified using multidetector computed tomography. In the screening study, 54 deregulated miRNAs were identified in patients with high EFV levels (highest tertile) compared with matched patients with low EFV levels (lowest tertile). After filtering, 12 miRNAs were selected for subsequent validation. In the validation study, miR-15b-3p, miR-22-3p, miR-148a-3p miR-148b-3p and miR-590-5p were directly associated with EFV, even after adjustment for confounding factors (p value < 0.05 for all models). The addition of miRNA combinations to a model based on clinical variables improved the discrimination (area under the receiver-operating-characteristic curve (AUC) from 0.721 to 0.787). miRNAs correctly reclassified a significant proportion of patients with an integrated discrimination improvement (IDI) index of 0.101 and a net reclassification improvement (NRI) index of 0.650. Decision tree models used miRNA combinations to improve their classification accuracy. These results were reproduced using two proposed clinical cutoffs for epicardial fat burden. Internal validation corroborated the robustness of the models. In conclusion, plasma miRNAs constitute novel biomarkers of epicardial fat burden.D.d.G.-C. was a recipient of a Juan de la Cierva-Incorporación grant from the Ministerio de Economía y Competitividad (IJCI-2016-29393). O.B. (Project 201521-10) and N.P. (Project 201716) were recipients of Fundació Marató TV3. S.B. and J.L.S.-Q. (2017-SGR-1149) and D.d.G.-C., L.N., À.V., D.V., R.L. and V.L.-C. (2017-SGR-946) are members of Quality Research Groups from Generalitat de Catalunya. S.B., J.L.S.-Q., N.P., V.L.-C. and D.d.G.-C. are members of the Group of Vascular Biology of the Spanish Society of Atherosclerosis (SEA). This work was funded by FIS PI14/01729 (to V.L.-C.), FIS PI16/00471 (to J.L.S.-Q.) & FIS PI18/01584 (to V.L.-C.) grants from Instituto Salud Carlos III, co-financed by the European Fund for Regional Development (EFRD) and by Project 201521-10 from Fundació MARATÓ TV3 (to V.L.-C.). CIBERCV (CB16/11/00403 to V.L.-C. and D.d.G.-C. and CB16/11/00276 to A.F.-G.) and CIBERDEM (CB07/08/0016 to J.L.S.-Q.) are projects from Instituto de Salud Carlos III.Peer reviewe

Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation

Aggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly1127-Cys1140 exclusively recognizes aggregated LDL and it is crucial for aggregated LDL binding. Our aim was to study the effect of the sequence Gly1127-Cys1140 (named peptide LP3 and its retro-enantio version, named peptide DP3) on the structural characteristics of sphingomyelinase- (SMase) and phospholipase 2 (PLA2)-modified LDL particles. Turbidimetry, gel filtration chromatography (GFC) and transmission electronic microscopy (TEM) analysis showed that LP3 and DP3 peptides strongly inhibited SMase- and PLA2-induced LDL aggregation. Nondenaturing polyacrylamide gradient gel electrophoresis (GGE), agarose gel electrophoresis and high-performance thin-layer chromatography (HPTLC) indicated that LP3 and DP3 prevented SMase-induced alterations in LDL particle size, electric charge and phospholipid content, respectively, but not those induced by PLA2. Western blot analysis showed that LP3 and DP3 counteracted changes in ApoB-100 conformation induced by the two enzymes. LDL proteomics (LDL trypsin digestion followed by mass spectroscopy) and computational modeling methods evidenced that peptides preserve ApoB-100 conformation due to their electrostatic interactions with a basic region of ApoB-100. These results demonstrate that LRP1-derived peptides are protective against LDL aggregation, even in conditions of extreme lipolysis, through their capacity to bind to ApoB-100 regions critical for ApoB-100 conformational preservation. These results suggests that these LRP1(CR9) derived peptides could be promising tools to prevent LDL aggregation induced by the main proteolytic enzymes acting in the arterial intima.The Ministry of Science and Innovation of Spain, in the framework of the State Plan of Scientific and Technical Innovation Investigation 2013–2016, awarded funding to the project “DEVELOPMENT OF AN INNOVATIVE THERAPY FOR THE TREATMENT OF THE ATHEROSCLEROSIS THROUGH INHIBITION OF CHOLESTEROL VASCULAR ACCUMULATION”, led by IPROTEOS SL with file number RTC-2016-5078-1. This project was also financed by the Ministry of Economy, Industry and Competitiveness (MINECO) in the framework of the Subprogram RETOS-COLABORACIÓN, 2016 call. The project is also co-financed by the European Union with the objective to promoting the technological development, innovation and quality research. Support was also received from SAF2017-89613R (to SV), co-financed by the European Regional Development Fund (ERDF), the Fundació la Marató de TV3 Project 201521-10 (to VLlC), FIS PI13/00364 and PI16/00471 (to JSQ) and FIS PI18/01584 (to VLlC) from the Instituto de Salud Carlos III (ISCIII) and co-financed with ERDF. Support was also received from Ministerio de Economía y Competitividad to DdG-C (IJCI-2016-29393). CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM; CB07/08/0016 (JSQ) and CIBER de Enfermedades Cardiovasculares (CIBERCV; CB16/1100403 (DdG-C, VLlC) are projects run by the Instituto de Salud Carlos III (ISCIII). The CRG/UPF Proteomics Unit is member of ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We also acknowledge support from the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012-0208, and “Secretaria d'Universitats i Recerca del Departament d'Economia I Coneixement de la Generalitat de Catalunya” (2017SGR595 to ES and 2017SGR946 to VLl-C). SB, JLS-Q, AR-U, DdG-C and VL-C are members of the Group of Vascular Biology of the Spanish Society of Atherosclerosis (SEA)