Risk Of Recurrence After Withdrawal Of Anticoagulation In Patients With Unprovoked Venous Thromboembolism: External Validation Of The Vienna Nomogram And The Dash Prediction Score

[ES] Introducción: Las escalas predictivas de recurrencias de ETV son útiles para decidir la duración del tratamiento anticoagulante. Aunque hay varias escalas, desconocemos la aplicabilidad de las mismas en nuestro medio. Por ello nos planteamos validar el modelo predictivo DASH y el nomograma de Viena a 12 meses.-- Métodos: Estudio retrospectivo de pacientes consecutivos no seleccionados con ETV no provocada desde 2006 hasta 2014. Comparamos la capacidad de predecir recurrencias de ETV de la escala DASH y el nomograma de Viena. La validación se realizó estratificando a los pacientes como de bajo o alto riesgo, según cada escala (discriminación) y comparando las recurrencias observadas frente a las esperadas (calibración).-- Resultados: De 353 pacientes evaluados, se analizaron 195, con una edad media de 53,5+/-19 años. Hubo 21 recurrencias a 1 año (10,8%, IC95%: 6,8-16%). Según la escala DASH, fueron catalogados de bajo riesgo el 42%, observando ETV recurrente en el grupo de bajo fue del 4,9% (IC95%: 1,3-12%) vs. el grupo de alto riesgo en que fue del 15% (IC95%: 9-23%) (p<0,05). Según el nomograma de Viena, fueron catalogados de bajo riesgo el 30%, observando ETV recurrente en el grupo de bajo vs. alto riesgo en el 4,2% (IC95%: 0,5-14%) vs. 16,2% (IC95%: 9,9-24,4%) (p<0,05).-- Conclusiones: Nuestro estudio valida la escala DASH y el nomograma de Viena en nuestra población. El modelo predictivo DASH sería el más aconsejable, tanto por su sencillez como por la capacidad de identificar a más pacientes de bajo riesgo frente al nomograma de Viena (42% vs. 30%).[EN ] Introduction: Scales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.-- Methods: This was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration).-- Results: Of 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05).-- Conclusions: Our study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).Peer reviewe

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil

14 Páginas.-- 6 Figuras.-- 2 TablasEvidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.This research is part of the R+D+i project PID2019-107837RB-I00, funded by the Spanish Ministry of Science and Innovation/Spanish National Research Agency, grant number MCIN/AEI/10.13039/501100011033/. A. G.-G. is grateful for funding received from the “Next Generation EU” funds, the European Union through the Recovery, Transformation and Resilience Plan and by the Ministry of Universities, in the framework of the Margarita Salas, Maria Zambrano grants for the Requalification of the Spanish University System 2021–2023, organized by the Pablo de Olavide University, Seville. J. J. R.-M. obtained an Erasmus+ scholarship (No. 2021-1-IT02-KA131-HED-000008483) from the University of Sassari (ITALY), for a stay at the Department of Food and Health of the Instituto de la Grasa-CSIC. The authors especially thank the ACESUR Group (Dos Hermanas, Seville, Spain), which donated the commercial olive oil for the trial. This collaborator had no role in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication.Peer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men

Postprandial triglyceride-rich lipoproteins (TRLs) are recognized as atherogenic particles whose lipid composition and function can be modified by the composition of dietary oils. This study was designed to test the hypothesis that minor components of pomace olive oil (POMACE) can not only change the composition of postprandial TRL but also affect the clearance of triglyceride (TG) molecular species of postprandial TRL. Meals enriched in either POMACE or refined olive oil (OLIVE) were administered to 10 healthy young men. TRL were isolated from serum at 2, 4, and 6 hours postprandially, and their fatty acid and TG molecular species compositions were analyzed by gas chromatography. The apolipoprotein B concentration was determined by immunoturbidimetry. POMACE and OLIVE, differing mainly in their unsaponifiable fraction, led to similar fatty acid and TG molecular species profiles in postprandial TRL. However, POMACE-TRL presented a higher particle size, estimated as TG to apolipoprotein B ratio, which was also found for the main TG molecular species (trioleoyl-glycerol, palmitoyl-dioleoyl-glycerol, palmitoyl-oeloyl-linoleoyl-glycerol, and dioleoyl-linoleoyl-glycerol). TG from POMACE-TRL also showed higher clearance rates. In this regard, apolar TG (with a higher equivalent carbon number) disappeared more rapidly from TRL particles obtained after the ingestion of either POMACE or OLIVE. In conclusion, minor components of POMACE facilitated TG clearance from TRL by modifying their particle size and the hydrolysis of the most apolar species. © 2014 Elsevier Inc.This work was supported by funds from Comisión Interministerial de Ciencia y Tecnología (AGL2011-23810). The authors declare no conflicts of interest.Peer Reviewe

Plasma lipid modifications in elderly people after administration of two virgin olive oils of the same variety (Olea europaea var. hojiblanca) with different triacylglycerol composition

In the present study we examined whether two virgin olive oils (VOO1 and VOO2), of the same variety (Olea europaea var. hojiblanca) and with a similar composition of minor components but differing in the content of triacylglycerol molecular species, had different effects on blood pressure and plasma lipid levels in a healthy elderly population. Thirty-one participants, aged 84.9 (SD 6.4) years, were asked to participate in the study. No differences were found with regard to blood pressure after both experimental periods (VOO1 and VOO2). However, plasma total cholesterol and LDL-cholesterol were reduced only after VOO1 (P0.418, P<0.07), except for phospholipids in VOO1 (P=0.130 for total cholesterol and P=0.360 for LDL-cholesterol). These results have demonstrated that blood pressure and plasma lipids can be modified by the consumption of VOO in elderly people, but that the extent of such modification depends on the composition and amount of active minor components and triacylglycerol molecular species.This work was supported in part by grants FEDER 1FD97-2288 (European Community) and CAO001-002 (Junta de Andalucía).Peer Reviewe

Determination of fatty acid and triacylglycerol composition of human adipose tissue

The fatty acid composition of adipose tissue was studied in a population in western Andalusia with a diet in which the fat contribution is mainly from olive oil. The lipid composition of adipose tissue, including the fatty acid composition of triacylglycerols, was examined by capillary gas chromatography. Thirty-five peaks wer resolved, ranging in chain length from 12 to 24 carbon atoms, including geometric and positional isomers. The major triacylglycerol was POO, followed by PLO and OOO