Venous thromboembolism (VTE) developing after ankle sprain. Comparison with VTE after knee arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) is a critical complication after non-major trauma or surgery. While the risk and severity of VTE following major orthopedic surgery is well-documented, there is significant knowledge gap regarding, non-major trauma such as ankle sprains. METHODS: We analyzed data from the RIETE registry to assess the clinical characteristics, VTE prophylaxis usage, and outcomes in patients with VTE following ankle sprain versus those post elective knee arthroplasty. We aimed to assess the risk and severity of VTE in a population traditionally considered at lower risk. Risk stratification was performed using the TRiP(cast) score. RESULTS: Among 1,250 patients with VTE, those with ankle sprain (n = 459) were much younger than those post knee arthroplasty (n = 791), less often female, had fewer comorbidities, and received VTE prophylaxis less often (27% vs. 93 %). During anticoagulation, 26 patients developed recurrent VTE, 31 had major bleeding, and 12 died (fatal PE 3, fatal bleeding 2). There were no differences between the two groups in the rates of VTE recurrences (rate ratio (RR): 1.65; 95%CI: 0.69-3.88) or death (RR: 1.12; 95%CI: 0.33-3.46), but patients with VTE after ankle sprain had a lower rate of major bleeding (RR: 0.39; 95%CI: 0.13-0.99). CONCLUSIONS: Ankle sprain patients are often undertreated for VTE prophylaxis and have similar severity of VTE than those undergoing elective knee surgery, indicating the need for a more customized approach to VTE management.

COVID-19-associated venous thromboembolism: risk of recurrence and major bleeding.

Background: Complications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported. Objectives: This study aimed to compare the 90-day rates of VTE recurrences and major bleeding in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Methods: We used the RIETE registry to compare the 3-month outcomes in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Results: The study included 1,747 patients with COVID-19-associated VTE and 8,711 with VTE without COVID-19. Patients with COVID-19-associated VTE were more likely to be hospitalized at baseline and to present with pulmonary embolism. During the first 90 days, 123 patients (1.17%) developed VTE recurrences, and 266 (2.54%) experienced major bleeding. Patients with COVID-19-associated VTE had a similar rate of VTE recurrences (0.9% vs 1.2%) but a higher rate of major bleeding (4.6% vs 2.1%; P < .001) than those without COVID-19. Multivariable analysis adjusted for competing risks showed that patients with COVID-19-associated VTE had an increased risk of major bleeding (subhazard ratio, 1.395; 95% confidence interval, 1.037-1.877). The 30-day mortality after major bleeding was 26.3% in patients with COVID-19-associated VTE and 17.7% in those without COVID-19. Conclusion: Patients with COVID-19-associated VTE had a 5-fold higher rate of major bleeding than VTE recurrences during the first 90 days of anticoagulation. In VTE patients without COVID-19, both rates were similar. These findings highlight the importance of carefully monitoring and optimizing anticoagulation in these patients.

Clinical Characteristics and Risk Factors for Mortality in Very Old Patients Hospitalized With COVID-19 in Spain.

BACKGROUND: Advanced age is a well-known risk factor for poor prognosis in COVID-19. However, few studies have specifically focused on very old inpatients with COVID-19. This study aims to describe the clinical characteristics of very old inpatients with COVID-19 and identify risk factors for in-hospital mortality at admission. METHODS: We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years hospitalized with COVID-19 in 150 Spanish hospitals (SEMI-COVID-19) Registry (March 1-May 29, 2020). The primary outcome was in-hospital mortality. A uni- and multivariate logistic regression was performed to assess predictors of mortality at admission. RESULTS: A total of 2772 consecutive patients (49.4% men, median age 86.3 years) were analyzed. Rates of atherosclerotic cardiovascular disease, diabetes mellitus, dementia, and Barthel Index < 60 were 30.8%, 25.6%, 30.5%, and 21.0%, respectively. The overall case-fatality rate was 46.9% (n: 1301) and increased with age (80-84 years: 41.6%; 85-90 years: 47.3%; 90-94 years: 52.7%; ≥95 years: 54.2%). After analysis, male sex and moderate-to-severe dependence were independently associated with in-hospital mortality; comorbidities were not predictive. At admission, independent risk factors for death were: oxygen saturation < 90%; temperature ≥ 37.8°C; quick sequential organ failure assessment (qSOFA) score ≥ 2; and unilateral-bilateral infiltrates on chest x-rays. Some analytical findings were independent risk factors for death, including estimated glomerular filtration rate < 45 mL/min/1.73 m2; lactate dehydrogenase ≥ 500 U/L; C-reactive protein ≥ 80 mg/L; neutrophils ≥ 7.5 × 103/µL; lymphocytes < 0.8 × 103/µL; and monocytes < 0.5 × 103/µL. CONCLUSIONS: This first large, multicenter cohort of very old inpatients with COVID-19 shows that age, male sex, and poor preadmission functional status-not comorbidities-are independently associated with in-hospital mortality. Severe COVID-19 at admission is related to poor prognosis.

Metabolic disorders and inflammation are associated with familial combined hyperlipemia.

BACKGROUND: Familial Combined Hyperlipidemia (FCH) is related to different metabolic disorders. The objective of this study was to evaluate the presence of alterations of hydrocarbonated metabolism and lipid profile together with inflammatory and adhesion molecules in subjects with FCH compared to controls. METHODS: 75 HFC patients and 75 healthy individuals were studied. Glucose, insulin, HOMA-IR index and lipid parameters, in addition to anti-oxidized LDL antibodies (Anti ox-LDL), small and dense LDL (sdLDL) and HDL subfractions, proinflammatory cytokines and adhesion molecules were measured. RESULTS: FCH patients showed higher levels of hydrocarbonated metabolism parameters, total cholesterol, triglycerides, LDLc, Apolipoprotein B and non-HDLc (p < .001), and lower levels of HDLc (p < .001) and Apolipoprotein AI (p < .05) than controls. In addition, the inflammatory markers hsCRP, IL-6, IL-8, P-selectin, E-selectin and ICAM were all higher with (p < .05) respect to controls. The increase of sdLDL was correlated with the presence of IR and IL-6 levels. Significant differences in diameter and percentage of phenotype B LDL, small HDL subfractions and Anti ox-LDL were also detected between patients and controls. CONCLUSIONS: The lipid characteristics of FCH are confirmed by IR and a low grade inflammatory state in patients, and are associated with the predominance of sdLDL and Anti ox-LDL.

Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols.

A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects. This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of beta-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.

Small and dense LDL in familial combined hyperlipidemia and N291S polymorphism of the lipoprotein lipase gene.

There is a predominance of small and dense LDL cholesterol particles in familial combined hyperlipidemia (FCH). The lipoprotein lipase gene could exert an influence in these circumstances.To study the relationship of pattern B LDL and lipids with N291S polymorphism of lipoprotein lipase (LPL) in FCH patients.Lipid profile, apolipoproteins, diameter of LDL and N291S polymorphism were determined in 93 patients with FCH and 286 individuals from the general population.FCH patients with N291S polymorphism showed a lower mean diameter of LDL. FCH patients with pattern B LDL showed higher concentrations of triglycerides, VLDLc, non-HDLc and apo B100 and lower levels of HDLc than those with pattern A. Of FCH patients with polymorphism 87.5% presented pattern B and 12.5% pattern A, while patients without polymorphism presented pattern A in 69.2% cases and pattern B in 30.8% cases, with differences being statistically significant (p < 0.004). The prevalence of this mutation in our FCH patients was 9.7%.The prevalence of N291S mutation in our FCH patients was similar to the 9.3% described in Dutch FCHL patients but clearly higher than the 2-5% described for other Caucasian populations. No polymorphism was found in our general population sample. FCH patients with phenotype B of LDL possessed an atherogenic lipid profile. The relationship between small and dense LDL and the presence of the N291S mutation may identify patients with high cardiovascular risk.

Parameters of inflammation in morbid obesity: lack of effect of moderate weight loss.

BACKGROUND: Obesity has been associated with a chronic activation of the acute-phase response. The aims of our study were to investigate whether levels of inflammatory cytokines are higher in obese patients, to evaluate their relationship with metabolic syndrome, and to analyze the effect of moderate weight loss upon their levels. METHODS: Sixty-seven severe or morbid obese patients were compared with 67 controls. Patients were submitted to a 4-week very low calorie diet followed by a low calorie diet for 2 months. Exclusion criteria were organic disease, ischemic heart disease or stroke, diabetes mellitus, hyperlipidemia, and hypertension. An evaluation was performed before and after the diet, in which fibrinogen, blood count, high-sensitive C-reactive protein (CRP), interleukin 6 (IL-6), and tumoral necrosis factor alpha (TNF-alpha) were measured. The Student t test was employed to compare differences between the groups and Pearson correlation coefficients were calculated. RESULTS: Obese patients showed higher levels of CRP (P < 0.001), IL-6 (P < 0.001), TNF-alpha (P < 0.001), leukocyte (P = 0.001), and neutrophil count (P < 0.001) than controls. In obese patients, inflammatory parameters were significantly correlated with anthropometric parameters and did not differ between obese subjects with or without metabolic syndrome. Moderate weight loss (excess weight loss 19.6%) was achieved through dieting, but no change was observed in any inflammatory parameter. CONCLUSIONS: Obesity is associated to a chronic inflammatory state that seems to be due to an increased secretion of cytokines, and this state is not related to the presence of metabolic syndrome. Moderate weight loss does not ameliorate this inflammatory state in the short term.