Risk of venous thromboembolism and arterial events in patients with hypoalbuminemia: a comprehensive meta-analysis of more than 2 million of patients.

BACKGROUND: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values <3.5 g/dl is associated with arterial thrombosis; its impact with venous thromboembolism (VTE) is unclear. The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia. PATIENTS/METHODS: MEDLINE and EMBASE were searched up to January 2024 for observational studies and randomized trials reporting data of interest. Primary outcome was the risk of VTE while secondary outcome was myocardial infarction and stroke risk in patients with versus without hypoalbuminemia. The risk of bias was evaluated using Newcastle-Ottawa scale and Cochrane tool. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. RESULTS: 43 studies for a total of 2,531,091 patients (39,738 medical, 2,491,353 surgical) were included in primary analysis; 79.1% of the studies used 3.5 g/dl cut-off value for hypoalbuminemia definition. Follow-up duration was 30 days in 60.5% of studies. Patients with hypoalbuminemia had a higher risk of VTE (RR, 1.88; 95%CI, 1.66-2.13). RR were similar in both medical (RR, 1.87; 95%CI, 1.53-2.27) and surgical patients (RR, 1.87; 95%CI, 1.61-2.16) and in patients with (RR, 1.86; 95%CI, 1.66-2.10) and without cancer (RR, 1.89; 95%CI, 1.47-2.44). Risk of myocardial infarction (RR, 1.88; 95%CI, 1.54-2.31) and stroke (RR 1.77; 95%CI, 1.26-2.48) was higher in patients with hypoalbuminemia. CONCLUSIONS: Hypoalbuminemia is a risk factor for VTE in both medical and surgical patients irrespective of cancer coexistence. Serum albumin analysis may represent a simple and cheap tool to identify patients at VTE risk.

Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

Risk of adverse events in anticoagulated patients with atrial fibrillation and non-alcoholic fatty liver disease.

BACKGROUND: The clinical impact of Nonalcoholic fatty liver disease(NAFLD) in patients with atrial fibrillation(AF) is still controversial. AIM: To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF-NAFLD patients. METHODS: Retrospective study with a health research network(TriNetX). AF patients on oral anticoagulation(OAC) were categorized according to the presence of NAFLD into two groups. The primary outcomes were the 1-year risks of: i) a composite cardiovascular outcome (all-cause death, myocardial infarction, stroke, cardiac arrest, and pulmonary embolism); and ii) a composite hemorrhagic outcome(intracranial hemorrhage and gastrointestinal bleeding). Cox regression analysis before and after propensity-score-matching(PSM) was used to estimate Hazard Ratio(HR) and 95% confidence intervals(95%CI). Sensitivity analyses investigated the risk associated with cirrhosis, thrombocytopenia, and type of OAC(warfarin vs non-vitamin K antagonist oral anticoagulants(NOAC). RESULTS: We identified 22,636 AF-NAFLD patients (69±12 years, 46.7% females) and 391,014 AF patients without liver disease(72±12 years, 42.7% females). NAFLD was associated with a higher risk of composite cardiovascular (HR 1.54,95%CI 1.47-1.61) and hemorrhagic (HR 1.56,95%CI 1.42-1.72) outcomes. This was consistent also for all the single outcomes. Cirrhotic and thrombocytopenic AF-NAFLD patients showed the highest risks. Compared to AF-NAFLD patients on NOAC, those on warfarin were associated with a higher risk of cardiovascular and hemorrhagic outcomes. CONCLUSION: In AF patients, NAFLD is associated with a higher 1-year risk of adverse events, with the risk of adverse events progressively increasing from non-cirrhotic to cirrhotic and from non-thrombocytopenic to thrombocytopenic patients. NOACs were associated with a better effectiveness and safety profile compared to warfarin.

Prediction of new-onset atrial fibrillation with the C2HEST score in patients admitted with community-acquired pneumonia.

PURPOSE: Patients hospitalized for community-acquired pneumonia (CAP) may have a higher risk of new-onset atrial fibrillation (NOAF). The C2HEST score was developed to evaluate the NOAF risk in the general population. Data on the value of the C2HEST score in acute patients admitted with CAP are lacking. We want to establish the predictive value of C2HEST score for NOAF in patients with CAP. METHODS: Patients with CAP enrolled in the SIXTUS cohort were enrolled. C2HEST score was calculated at baseline. In-hospital NOAF was recorded. Receiver-operating Characteristic (ROC) curve and multivariable Cox proportional hazard regression analysis were performed. RESULTS: We enrolled 473 patients (36% women, mean age 70.6 ± 16.5 years), and 54 NOAF occurred. Patients with NOAF were elderly, more frequently affected by hypertension, heart failure, previous stroke/transient ischemic attack, peripheral artery disease and hyperthyroidism. NOAF patients had also higher CURB-65, PSI class and CHA2DS2-VASc score. The C-index of C2HEST score for NOAF was 0.747 (95% confidence interval [95%CI] 0.705-0.786), higher compared to CURB-65 (0.611, 95%CI 0.566-0.655, p = 0.0016), PSI (0.665, 95%CI 0.621-0.708, p = 0.0199) and CHA2DS2-VASc score (0.696, 95%CI 0.652-0.737, p = 0.0762). The best combination of sensitivity (67%) and specificity (70%) was observed with a C2HEST score ≥ 4. This result was confirmed by the multivariable Cox analysis (Hazard Ratio [HR] for C2HEST score ≥ 4 was 10.7, 95%CI 2.0-57.9; p = 0.006), independently from the severity of pneumonia. CONCLUSION: The C2HEST score was a useful predictive tool to identify patients at higher risk for NOAF during hospitalization for CAP. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT01773863).

Food contamination and cardiovascular disease: a narrative review.

Cardiovascular disease is a significant cause of morbidity and mortality among non-communicable diseases worldwide. Evidence shows that a healthy dietary pattern positively influences many risk factors of cardiometabolic health, stroke, and heart disease, supported by the effectiveness of healthy diet and lifestyles for the prevention of CVD. High quality and safety of foods are prerequisites to ensuring food security and beneficial effects. Contaminants can be present in foods mainly because of contamination from environmental sources (water, air, or soil pollution), or artificially introduced by the human. Moreover, the cross-contamination or formation during food processing, food packaging, presence or contamination by natural toxins, or use of unapproved food additives and adulterants. Numerous studies reported the association between food contaminants and cardiovascular risk by demonstrating that (1) the cross-contamination or artificial sweeteners, additives, and adulterants in food processing can be the cause of the risk for major adverse cardiovascular events and (2) environmental factors, such as heavy metals and chemical products can be also significant contributors to food contamination with a negative impact on cardiovascular systems. Furthermore, oxidative stress can be a common mechanism that mediates food contamination-associated CVDs as substantiated by studies showing impaired oxidative stress biomarkers after exposure to food contaminants.This narrative review summarizes the data suggesting how food contaminants may elicit artery injury and proposing oxidative stress as a mediator of cardiovascular damage.

Prognostic role of serum albumin levels in patients with chronic heart failure.

BACKGROUND: Hypoalbuminemia is common in heart failure (HF) patients; however, there are no data regarding the possible long-term prognostic role of serum albumin (SA) in the younger population with chronic HF without malnutrition. The aim of this study was to examine the long-term prognostic role of SA levels in predicting major adverse cardiac events (MACE) in middle-aged outpatients with chronic HF. METHODS: In the present retrospective analysis, 378 subjects with HF were enrolled. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery, and cardiovascular death), total mortality, and HF hospitalizations (hHF) occurrence were evaluated during a median follow-up of 6.1 years. RESULTS: In all population, 152 patients had a SA value < 3.5 g/dL and 226 had a SA value ≥ 3.5 g/dL. In patients with SA ≥ 3.5 g/dL, the observed MACE were 2.1 events/100 patient-year; while in the group with a worse SA levels, there were 7.0 events/100 patient-year (p < 0.001). The multivariate analysis model confirmed that low levels of SA increase the risk of MACE by a factor of 3.1. In addition, the presence of ischemic heart disease, serum uric acid levels > 6.0 mg/dL, chronic kidney disease, and a 10-year age rise, increased the risk of MACE in study participants. Finally, patients with SA < 3.5 g/dl had a higher incidence of hHF (p < 0.001) and total mortality (p < 0.001) than patients with SA ≥ 3.5 g/dl. CONCLUSIONS: Patients with chronic HF that exhibits low SA levels show a higher risk of MACE, hHF and total mortality.

Endotoxemia and Platelets: 2 Players of Intrahepatic Microthrombosis in NAFLD.

Gut dysbiosis-related intestinal barrier dysfunction with increased translocation of bacterial products such as lipopolysaccharide (LPS) into systemic circulation is emerging as pathogenic factor of nonalcoholic fatty liver disease (NAFLD). Experimental and clinical studies suggested a potential role of LPS as a trigger eliciting in situ liver inflammation upon interaction with its receptor toll-like receptor 4. Also, LPS has been reported to prime platelets to respond to the common agonists indicating that it behaves as a prothrombotic molecule. Of note, recent studies suggested platelet-related intrahepatic thrombosis triggered by LPS as a mechanism implicated in the process of liver inflammation. This review describes: 1) the impact of gut barrier dysfunction and endotoxemia in the process of NAFLD; 2) the relationship between endotoxemia and platelet activation in NAFLD; 3) clinical evidence for the use of antiplatelet drugs in NAFLD/nonalcoholic steatohepatitis patients; and 4) the potential therapeutic approach to modulate endotoxemia and eventually platelet activation.

Hypoalbuminemia as predictor of thrombotic events in patients with community-acquired pneumonia.

BACKGROUND: Hypoalbuminemia complicates acute diseases and infections and is associated with a worst prognosis. The aim is to evaluate whether hypoalbuminemia is associated with higher incidence and risk of thrombotic events in community-acquired pneumonia. METHODS: We retrospectively collected data from a prospective study investigating the incidence of thrombotic events in community-acquired pneumonia hospitalized patients from 2011 to 2016 at University-Hospital Policlinico Umberto I. Baseline characteristics and outcomes were collected. Incidence of outcomes were calculated. Kaplan-Meier curves were created, Cox model used to identify predictors for the outcomes, and competing risk analysis performed. RESULTS: From a total of 231 patients, 130 (56.3%) and 101 (43.7%) had or not hypoalbuminemia. Age, proportion of female, BMI, major comorbidities, and severity of pneumonia were similar between two subgroups. A less proportion of patients with hypoalbuminemia received antithrombotic and statin therapy. Median hospital stay was 11 days in both subgroups. Patients with hypoalbuminemia had higher D-dimer and high- sensitivity C-reactive-protein values with an inverse relation between albumin values and these markers. Incidence of thrombotic events was 26 and 11 per 1000 patient-days in patient with and without hypoalbuminemia. At Cox model, hypoalbuminemia was associated with thrombotic events development in univariable (hazard ratio; 2.67, 95% confidence intervals, 1.30-5.40) and multivariable (hazard ratio 3.19; 95% confidence intervals, 1.48-6.89) analysis. CONCLUSIONS: More than a half of patients with community acquired pneumonia had hypoalbuminemia that is associated with a doubled incidence and a three-fold increased risk of thrombotic events. The inverse relation between baseline albumin and D-dimer values confirms this association.

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

BACKGROUND: With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. METHODS AND RESULTS: The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. CONCLUSION: Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.

In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase.

The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4+T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4+T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells.

Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.

Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

Albumin Levels and Risk of Early Cardiovascular Complications After Ischemic Stroke: A Propensity-Matched Analysis of a Global Federated Health Network.

BACKGROUND: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke. METHODS: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching. RESULTS: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels. CONCLUSIONS: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

COVID-19 and Long-COVID Thrombosis: From Clinical and Basic Science to Therapeutics.

Coronavirus infectious disease-19 (COVID-19) is a pandemic characterized by serious lung disease and thrombotic events in the venous and circulation trees, which represent a harmful clinical sign of poor outcome. Thrombotic events are more frequent in patients with severe disease requiring intensive care units and are associated with platelet and clotting activation. However, after resolution of acute infection, patients may still have clinical sequelae, the so-called long-COVID-19, including thrombotic events again in the venous and arterial circulation. The mechanisms accounting for thrombosis in acute and long COVID-19 have not been fully clarified; interactions of COVID-19 with angiotensin converting enzyme 2 or toll-like receptor family or infection-induced cytokine storm have been suggested to be implicated in endothelial cells, leucocytes, and platelets to elicit clotting activation in acute as well in chronic phase of the disease. In acute COVID-19, prophylactic or full doses of anticoagulants exert beneficial effects even if the dosage choice is still under investigation; however, a residual risk still remains suggesting a need for a more appropriate therapeutic approach. In long COVID-19 preliminary data provided useful information in terms of antiplatelet treatment but definition of candidates for thrombotic prophylaxis is still undefined.

Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia.

OBJECTIVES: Community-acquired pneumonia (CAP) is associated with low-grade endotoxemia but its relationship with cardiovascular events (CVE) has not been investigated. METHODS: We evaluated the incidence of CVE including myocardial infarction, stroke, and cardiovascular death in 523 adult patients hospitalized for CAP. Serum lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, were analyzed in the cohort, that was followed-up during hospitalization and up to 43 months thereafter. RESULTS: During the hospital-stay, 55 patients experienced CVE with a progressive increase from the lowest (0.6%) to highest LPS tertile (23.6%, p < 0.001). Logistic regression analyses showed that higher LPS tertile was independently associated with CVE; LPS significantly correlated with age, hs-CRP and zonulin. In a sub-group of 23 CAP patients, blood E. coli DNA was higher in patients compared to 24 controls and correlated with LPS. During the long-term follow-up, 102 new CVE were registered; the highest tertile of LPS levels was associated with incident CVE; Cox regression analysis showed that LPS tertiles, age, history of CHD, and diabetes independently predicted CVE. CONCLUSIONS: In CAP low-grade endotoxemia is associated to short- and long-term risk of CVE. Further study is necessary to assess if lowering LPS by non-absorbable antibiotics may result in improved outcomes.

Gut dysbiosis-related thrombosis in inflammatory bowel disease: Potential disease mechanisms and emerging therapeutic strategies.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.

Risk of venous thromboembolism in autoimmune diseases: A comprehensive review.

Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE.