Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

Prognostic Value of D-dimer to Lymphocyte Ratio (DLR) in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients: A Validation Study in a National Cohort.

BACKGROUND: This study aimed to validate the role of the D-dimer to lymphocyte ratio (DLR) for mortality prediction in a large national cohort of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective, multicenter, observational study that included hospitalized patients due to SARS-CoV-2 infection in Spain was conducted from March 2020 to March 2022. All biomarkers and laboratory indices analyzed were measured once at admission. RESULTS: A total of 10,575 COVID-19 patients were included in this study. The mean age of participants was 66.9 (±16) years, and 58.6% (6202 patients) of them were male. The overall mortality rate was 16.3% (n = 1726 patients). Intensive care unit admission was needed in 10.5% (n = 1106 patients), non-invasive mechanical ventilation was required in 8.8% (n = 923 patients), and orotracheal intubation was required in 7.5% (789 patients). DLR presented a c-statistic of 0.69 (95% CI, 0.68-0.71) for in-hospital mortality with an optimal cut-off above 1. Multivariate analysis showed an independent association for in-hospital mortality for DLR > 1 (adjusted OR 2.09, 95% CI 1.09-4.04; p = 0.03); in the same way, survival analysis showed a higher mortality risk for DLR > 1 (HR 2.24; 95% CI 2.03-2.47; p < 0.01). Further, no other laboratory indices showed an independent association for mortality in multivariate analysis. CONCLUSIONS: This study confirmed the usefulness of DLR as a prognostic biomarker for mortality associated with SARS-CoV-2 infection, being an accessible, cost-effective, and easy-to-use biomarker in daily clinical practice.

Atrial Fibrillation and Diabetes Mellitus: Dangerous Liaisons or Innocent Bystanders?

Atrial fibrillation (AF) is the most common arrhythmia in adults and diabetes mellitus (DM) is a major risk factor for cardiovascular diseases. However, the relationship between both pathologies has not been fully documented and new evidence supports the existence of direct and independent links. In the myocardium, a combination of structural, electrical, and autonomic remodeling may lead to AF. Importantly, patients with AF and DM showed more dramatic alterations than those with AF or DM alone, particularly in mitochondrial respiration and atrial remodeling, which alters conductivity, thrombogenesis, and contractile function. In AF and DM, elevations of cytosolic Ca2⁺ and accumulation of extra cellular matrix (ECM) proteins at the interstitium can promote delayed afterdepolarizations. The DM-associated low-grade inflammation and deposition/infiltration of epicardial adipose tissue (EAT) enforce abnormalities in Ca2+ handling and in excitation-contraction coupling, leading to atrial myopathy. This atrial enlargement and the reduction in passive emptying volume and fraction can be key for AF maintenance and re-entry. Moreover, the stored EAT can prolong action of potential durations and progression from paroxysmal to persistent AF. In this way, DM may increase the risk of thrombogenesis as a consequence of increased glycation and oxidation of fibrinogen and plasminogen, impairing plasmin conversion and resistance to fibrinolysis. Additionally, the DM-associated autonomic remodeling may also initiate AF and its re-entry. Finally, further evidence of DM influence on AF development and maintenance are based on the anti-arrhythmogenic effects of certain anti-diabetic drugs like SGLT2 inhibitors. Therefore, AF and DM may share molecular alterations related to Ca2+ mobility, mitochondrial function and ECM composition that induce atrial remodeling and defects in autonomic stimulation and conductivity. Likely, some specific therapies could work against the associated cardiac damage to AF and/or DM.

Arterial and venous involvement in Behçet's syndrome: a narrative review.

Behçet syndrome (BS) is a unique type of vasculitis that affects veins and arteries of all sizes, leading to recurrent vascular events, mostly venous thrombosis. The prevalence of venous thromboembolism in BS patients ranges between 15 and 40%. Thrombosis is usually an early manifestation leading to diagnosis of BS in up to 40% of patients. BS is per se a model of inflammation-induced thrombosis. The primary autoimmune response activates lymphocytes that in turn produce a cytokine cascade that activates neutrophils, which modify the secondary structure of fibrinogen making it less susceptible to plasmin-induced lysis. This leads to endothelial dysfunction, platelet activation and overexpression of tissue factor leading to inflammatory thrombi, usually attached to the wall. The pathogenesis of thrombosis is especially relevant to direct the specific treatment, that is based on immunosuppression rather than anticoagulation. Superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) are the most common form of thrombosis in BS, but thrombosis in atypical sites (cava vein, suprahepatic veins, intracardiac thrombus) and arterial involvement can also occur. We assessed the latest update of the European League Against Rheumatism recommendations for the management of BS. Vascular Behçet treatment is usually based of immunosuppressants, and the role of anticoagulation remains controversial. The use of interventional and surgical procedures should be carefully evaluated, due to the risk of triggering a vascular pathergy phenomenon.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study.

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for mortality were 2.40 and 0.46, respectively. The LR+ and LR- for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62-0.81) and 0.72 (95% CI, 0.62-0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

MR-Proadrenomedullin as biomarker of renal damage in urinary tract infection in children.

BACKGROUND: Midregional-proadrenomedullin (MR-proADM) is a useful prognostic peptide in severe infectious pathologies in the adult population. However, there are no studies that analyze its utility in febrile urinary tract infection (fUTI) in children. An accurate biomarker would provide an early detection of patients with kidney damage, avoiding other invasive tests like renal scintigraphy scans. Our objective is to study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchymal damage in fUTI within the pediatric population. METHODS: A prospective cohort study was conducted in pediatric patients with fUTI between January 2015 and December 2018. Plasma and urine MR-proADM levels were measured at admission in addition to other laboratory parameters. After confirmation of fUTI, renal scintigraphy scans were performed during the acute and follow-up stages. A descriptive study has been carried out and sensitivity, specificity and ROC curves for MR-proADM, C-reactive protein, and procalcitonin were calculated. RESULTS: 62 pediatric patients (34 female) were enrolled. Scintigraphy showed acute pyelonephritis in 35 patients (56.5%). Of those patients, the median of plasmatic MR-proADM (P-MR-proADM) showed no differences compared to patients without pyelonephritis. 7 patients (11.3%) developed renal scars (RS). Their median P-MR-proADM levels were 1.07 nmol/L (IQR 0.66-1.59), while in patients without RS were 0.48 nmol/L (0.43-0.63) (p < 0.01). The AUC in this case was 0.92 (95% CI 0.77-0.99). We established an optimal cut-off point at 0.66 nmol/L with sensitivity 83.3% and specificity 81.8%. CONCLUSION: MR-ProADM has demonstrated a poor ability to diagnose pyelonephritis in pediatric patients with fUTI. However, P-MR-proADM proved to be a very reliable biomarker for RS prediction.

C-reactive protein level predicts 30-day mortality and bleeding in patients with venous thromboembolism: A prospective single-center study / Proteína C reactiva como predictor de mortalidad y hemorragia a 30 días en pacientes con enfermedad tromboembólica venosa: estudio prospectivo, monocéntrico

AIMS: The association of on-admission CRP and early adverse outcomes in acute venous thromboembolism (VTE) has not been investigated. We hypothesized that increased on-admission CRP levels would correlate with adverse outcomes in patients with acute VTE. METHOD: In this prospective observational study, consecutive patients with acute VTE were enrolled and CRP levels were measured within the first 24h after diagnosis. Mortality, bleeding and recurrence were recorded during a 30-day follow-up. RESULTS: 586 patients were included. Higher CRP levels were found in patients with mortality (7.5 vs 4.0mg/dL; p = 0.01) and bleeding (7.8 vs 3.9mg/dL; p = 0.03). Multivariable logistic regression showed that CRP levels >5mg/dL were associated with higher mortality (OR 6.25; 95% CI, 2.1-18.6) and bleeding (OR 2.7; CI 95% 1.3-5.7). These results were independent to ESC risk score and simplified PESI score for mortality prediction. The predictive capacity of CRP showed an area under the ROC curve - AUC - of .7 (CI 95% .56-.85) for mortality and .65 (CI 95% .54-.75) for bleeding. The prognostic capacity of the ESC risk score and simplified PESI score was improved after adding the CRP cutoff of 5mg/dL (AUC of .87 CI 95% .79-.95). CONCLUSION: Our findings suggest that on-admission CRP level may be a simple, widely available and valuable biomarker to identify high-risk VTE patients for early mortality and bleeding. CRP ≥5mg/dL was independently associated with 30-day VTE related death and bleeding

OBJETIVOS: La asociación de la medición de PCR al ingreso y las complicaciones precoces en la enfermedad tromboembólica venosa (ETV) aguda no ha sido evaluado. Nuestra hipótesis es que los niveles elevados de PCR al ingreso podrían estar correlacionados con complicaciones precoces en pacientes con ETV aguda. MÉTODOS: Estudio observacional prospectivo, en el que se incluyeron pacientes consecutivos con ETV aguda en los que se midió la PCR en las primeras 24h del diagnóstico. La mortalidad, el sangrado y la recurrencia fueron registrados durante el seguimiento a 30 días. RESULTADOS: Se incluyeron 586 pacientes. Se encontraron niveles más elevados de PCR en pacientes que fallecieron (7,5 vs. 4mg/dl; p = 0,01) y que sangraron (7,8 vs. 3,9mg/dl; p = 0,03). Una regresión logística multivariante mostró que niveles de PCR>5mg/dl se asociaron significativamente con mayor mortalidad (OR: 6,25; IC 95%: 2,1-18,6) y sangrado (OR: 2,7; IC 95%: 1,3-5,7). Estos resultados fueron independientes de las escalas pronósticas de mortalidad ESC y PESI simplificada. La capacidad predictiva de la PCR mostró un área bajo la curva (ABC) ROC de 0,7 (IC 95%: 0,56-0,85) para mortalidad y 0,65 (IC 95%: 0,54-0,75) para sangrado. La capacidad pronóstica de las escalas pronósticas ESC y PESI simplificada mejoró de forma significativa al añadir el punto de corte de PCR>5mg/dl (ABC de 0,87; IC 95%: 0,79-0,95). CONCLUSIÓN: La medición de PCR al ingreso puede ser un marcador sencillo y ampliamente disponible para identificar a pacientes con ETV aguda y alto riesgo de mortalidad y sangrado precoces. Niveles de PCR≥5mg/dl se asociaron de forma independiente con mayor mortalidad y sangrado a 30 días en pacientes con ETV aguda

C-reactive protein level predicts 30-day mortality and bleeding in patients with venous thromboembolism: A prospective single-center study.

AIMS: The association of on-admission CRP and early adverse outcomes in acute venous thromboembolism (VTE) has not been investigated. We hypothesized that increased on-admission CRP levels would correlate with adverse outcomes in patients with acute VTE. METHOD: In this prospective observational study, consecutive patients with acute VTE were enrolled and CRP levels were measured within the first 24h after diagnosis. Mortality, bleeding and recurrence were recorded during a 30-day follow-up. RESULTS: 586 patients were included. Higher CRP levels were found in patients with mortality (7.5 vs 4.0mg/dL; p=0.01) and bleeding (7.8 vs 3.9mg/dL; p=0.03). Multivariable logistic regression showed that CRP levels >5mg/dL were associated with higher mortality (OR 6.25; 95% CI, 2.1-18.6) and bleeding (OR 2.7; CI 95% 1.3-5.7). These results were independent to ESC risk score and simplified PESI score for mortality prediction. The predictive capacity of CRP showed an area under the ROC curve - AUC - of .7 (CI 95% .56-.85) for mortality and .65 (CI 95% .54-.75) for bleeding. The prognostic capacity of the ESC risk score and simplified PESI score was improved after adding the CRP cutoff of 5mg/dL (AUC of .87 CI 95% .79-.95). CONCLUSION: Our findings suggest that on-admission CRP level may be a simple, widely available and valuable biomarker to identify high-risk VTE patients for early mortality and bleeding. CRP ≥5mg/dL was independently associated with 30-day VTE related death and bleeding.

Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an "FCS score".

Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice. Features included in this FCS score comprise: severe elevation of plasma TGs (fasting TG levels >10 mmol/L [885 mg/dL] on multiple occasions), refractory to standard TG-lowering therapies, a young age at onset, the lack of secondary factors (except for pregnancy and oral oestrogens) and a history of episodes of acute pancreatitis. Considering 53 FCS patients from three cohorts and 52 MCS patients from three cohorts, the overall sensitivity of the FCS score (≥10) was 88% (95% confidence interval [CI]: 0.76, 0.97) with an overall specificity of 85% (95% CI: 0.75, 0.94). Receiver operating characteristic curve area was 0.91. Pragmatic clinical scoring, by standardising diagnosis, may help differentiate FCS from MCS, may alleviate the need for systematic genotyping in patients with severe HTG and may help identify high-priority candidates for genotyping.

Cholesterol control according to the presence of metabolic syndrome in coronary and diabetic patients. Relationship with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Metabolic syndrome (MS) is an association of cardiovascular risk factors that increases the risk of coronary disease or type 2 diabetes mellitus (DM2), and has also been associated with the presence of liver steatosis (LS). In this study the relation of MS and LS with cholesterol control was analyzed in very high cardiovascular risk patients (coronary patients and/or DM2). METHODS: A cross-sectional epidemiological study including 6988 patients, from whom information was obtained on their characteristics, lipid profile and treatments. RESULTS: 4455 patients (65%) of the total study population had MS. Of MS criteria, high BP was the criterion most represented in the total population, while high TGs was the least. Within the total population, coronary patients showed a greater proportion of high BP, high TG and low HDL-c than those without coronary disease. Although no influence of MS was seen on the achievement of LDL-c targets (<70 mg/dL), the presence of high BP, high blood glucose and low HDL-c was related to poorer control of LDL-c. Finally, patients with MS showed a greater proportion of liver steatosis and this was associated in turn with poorer control of LDL-c. CONCLUSIONS: The criteria for MS are closely related to cholesterol control. LS is more prevalent in patients with MS, and it is associated with poorer control of LDL-c. We should focus on the presence of MS in high and very high CV risk patients in order to improve their lipid control.

Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis.

Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.

Hierro y riesgo vascular residual dependiente del perfil lipídico: una relación olvidada / Iron and residual vascular risk lipid profile dependent: a forgotten relationship

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Hierro y riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana / Iron and cardiovascular risk in HIV-infected patients

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Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.

The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes.