Midregional-proAdrenomedullin as a prognostic tool in sepsis and septic shock: A systematic review and meta-analysis.

BACKGROUND: Midregional-proAdrenomedullin (MR-proADM) has been recently proposed as a tool in patients with sepsis and septic shock. Our aim was to evaluate the prognostic role of MR-proADM in hospitalized patients with sepsis and septic shock. METHODS: PRISMA guideline was followed. MEDLINE and EMBASE were searched up to June 2023. Primary outcome was mean difference in MR-proADM among survivors and nonsurvivors, secondary outcome mean difference in MR-proADM according to infection severity and type. Risk of bias was evaluated using Newcastle-Ottawa scale for observational studies and Cochrane tool for randomized trials. Pooled mean differences (MD) with corresponding 95% confidence intervals (CIs) were calculated in a random-effects model. RESULTS: Twenty-four studies included 6730 adult patients (1208 nonsurvivors and 5522 survivors) and three studies included 195 paediatric patients (30 nonsurvivors and 165 survivors). A total of 10, 4 and 13 studies included, respectively, patients with sepsis (3602 patients), septic shock (386 patients) and a mixed population (2937 patients). Twenty-one studies included patients with different source of infection, three with pneumonia and one with a catheter-related infection. Most studies (n = 12) had a follow-up of 28 days. In adult cohort, pooled mean difference between nonsurvivors and survivors of MR-proADM was 2.55 mmol/L (95% CI: 1.95-3.15) with higher values in patients with septic shock (4.25 mmol/L; 95% CI, 2.23-6.26 mmol/L) than in patients with sepsis (1.77 mmol/L; 95% CI: 1.11-2.44 mmol/L). In paediatric cohort, pooled mean difference was 3.11 mmol/L (95% CI: -0.02-6.24 mmol/L). CONCLUSIONS: Higher values of MR-proADM are detectable in nonsurvivors adult and paediatric-hospitalized patients with sepsis or septic shock.

Anticoagulant therapy for splanchnic vein thrombosis: a systematic review and meta-analysis.

Treatment of splanchnic vein thrombosis (SVT) is challenging, and evidence to guide therapeutic decisions remains scarce. The objective of this systematic review and meta-analysis was to determine the efficacy and safety of anticoagulant therapy for SVT. MEDLINE, EMBASE, and clinicaltrials.gov were searched from inception through December 2019, without language restrictions, to include observational studies and randomized controlled trials reporting radiological or clinical outcomes in patients with SVT. Pooled proportions and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. Of 4312 records identified by the search, 97 studies including 7969 patients were analyzed. In patients receiving anticoagulation, the rates of SVT recanalization, SVT progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were 58% (95% CI, 51-64), 5% (95% CI, 3-7), 11% (95% CI, 8-15), 9% (95% CI, 7-12), and 11% (95% CI, 9-14), respectively. The corresponding values in patients without anticoagulation were 22% (95% CI, 15-31), 15% (95% CI, 8-27), 14% (95% CI, 9-21), 16% (95% CI, 13-20), and 25% (95% CI, 20-31). Compared with no treatment, anticoagulant therapy obtained higher recanalization (RR, 2.39; 95% CI, 1.66-3.44) and lower thrombosis progression (RR, 0.24; 95% CI, 0.13-0.42), major bleeding (RR, 0.73; 95% CI, 0.58-0.92), and overall mortality (RR, 0.45; 95% CI, 0.33-0.60). These results demonstrate that anticoagulant therapy improves SVT recanalization and reduces the risk of thrombosis progression without increasing major bleeding. The incidence of recurrent VTE remained substantial in patients receiving anticoagulation, as well. Effects were consistent across the different subgroups of patients. This trial was registered on the PROPERO database at (https://www.crd.york.ac.uk/prospero//display_record.php?ID=CRD42019127870) as #CRD42019127870.

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology.

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1-2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of mid-regional proadrenomedullin (MR-proADM) as a marker of SARS-CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV-2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.

Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit.

Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer's instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.

Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis.

BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references. SELECTION CRITERIA: Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence. MAIN RESULTS: We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.

Influenza B virus infection complicated by life-threatening pericarditis: a unique case-report and literature review.

BACKGROUND: Acute pericarditis may occur frequently after viral infections. To our knowledge, influenza B virus infection complicated by pericarditis without myocardial involvement has never been reported. We report the first case of life-threatening pericarditis caused by influenza B virus infection. CASE PRESENTATION: A 48-years-old woman with trisomy 21 and ostium primum atrial septal defect was transferred from Cardiology to our Internal Medicine Department for severe pericardial effusion unresponsive to ibuprofen and colchicine. Based on the recent patient history of flu-like syndrome, and presence of pleuro-pericardial effusion, a viral etiology was suspected. Laboratory evaluation and molecular assay of tracheal aspirate identified influenza B virus. Therefore, the ongoing metilprednisolone and colchicine therapy was implemented with oseltamivir with progressive patient improvement and no evidence of pericardial effusion recurrence during follow-up. CONCLUSIONS: Especially in autumn and winter periods, clinicians should include Influenza B virus infection on differential diagnosis of pericarditis with large pericardial effusion.

Long-term performance of risk scores for venous thromboembolism in ambulatory cancer patients.

The long-term performance of prediction scores for venous thromboembolism (VTE) in cancer patients has been poorly investigated. We evaluated the discriminatory performance of the Khorana, PROTECHT, CONKO, and ONKOTEV scores for the first 3-6 months and for 12 months, and re-assessed scores after 3-6 months to determine the influence of variations in patients' risk classification on performance. Retrospective cohort of ambulatory patients with active cancer who were scheduled to receive first or new line of chemotherapy. The primary outcome was symptomatic or incidental VTE. A total of 776 patients were included of whom 540 (70%) had distant metastases. The time-dependent c-statistics of Khorana, PROTECHT, CONKO, and ONKOTEV scores at 6 months were 0.61 (95% CI 0.56 to 0.66), 0.61 (95% CI 0.55 to 0.66), 0.60 (95% CI 0.54 to 0.66), and 0.59 (0.52 to 0.66), respectively, with a tendency to decrease during follow-up. None of the scores discriminated between high and low risk patients at the conventional 3-point positivity threshold. The use of a 2-point positivity threshold improved performance of all scores and captured a higher proportion of VTE. The accuracy of risk scores re-assessed at 3-6 months was modest. The Khorana, PROTECHT, CONKO, and ONKOTEV scores are not sufficiently accurate when used at a conventional threshold of 3 points. Performance improves at positivity threshold of 2 points, as evaluated in recent randomized studies on VTE prophylaxis. Score accuracy tends to decrease over time suggesting the need of periodic re-evaluation to estimate possible variation of risk.

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.

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

BACKGROUND: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values of <3.5 g/dL, is associated with arterial thrombosis; its impact on venous thromboembolism (VTE) is unclear. OBJECTIVES: The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia. 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 outcomes were myocardial infarction and stroke risk in patients with hypoalbuminemia versus those 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: Forty-three studies for a total of 2 531 091 patients (39 738 medical and 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). RRs 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. CONCLUSION: 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.

Aging and Antithrombotic Treatment.

Significance: Several aging-related pathophysiological mechanisms have been described to contribute to increased thrombotic risk in the elderly, including oxidative stress, endothelial dysfunction, and platelet and coagulation cascade activation. Antithrombotic treatment in the elderly should be individualized. Recent Advances: Recent studies have clarified some pathophysiological mechanisms of enhanced oxidative stress and thrombotic alterations in older adults. In the last decade, randomized trials have evaluated different antithrombotic strategies to reduce the risk of cardiovascular events in these patients. Critical Issues: The proportion of elderly patients included in clinical trials is generally low, thus not reflecting the daily clinical practice. There is no consensus on the most appropriate antithrombotic treatment in the elderly, also considering that bleeding risk management may be challenging in this high-risk subgroup of patients. Routine antiplatelet treatment is not a valid strategy for the primary prevention of cardiovascular events given the associated high risk of bleeding. In elderly patients with acute coronary syndrome, low-dose prasugrel or clopidogrel, shorter dual antiplatelet therapy, and no pretreatment before stent placement should be considered. Advanced age should not be the only reason for the underuse of oral anticoagulation in patients with atrial fibrillation, with direct oral anticoagulants preferred over warfarin for stroke prevention. Instead, a case-by-case clinical evaluation is warranted based on patient's bleeding risk also. Future Directions: There is a need for a structured tailored approach to manage thrombotic risk in elderly patients. The choice of the most appropriate antithrombotic treatment should balance efficacy and safety to reduce the risk of bleeding.

Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis.

INTRODUCTION: The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients. MATERIALS AND METHODS: MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated. RESULTS: 377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region. CONCLUSIONS: Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.

How to treat patients with splanchnic vein thrombosis: recent advances.

Splanchnic vein thrombosis (SVT) is an unusual-site venous thromboembolism that includes portal, mesenteric, and splenic vein thrombosis as well as the Budd-Chiari syndrome. SVT is a relatively rare disease (portal vein thrombosis and Budd-Chiari syndrome are, respectively, the most and the least common presentations); roughly one­third of the cases are detected incidentally, and liver cirrhosis and solid cancer represent the main risk factors. Once SVT is diagnosed, careful patient evaluation should be performed to assess the stage, grade, and extension of the thrombosis, as well as the risks and benefits of the anticoagulation regimen. Anticoagulant therapy is effective in SVT treatment and is associated with high rates of vein recanalization, low rates of thrombosis progression or recurrence, and an acceptable rate of bleeding complications. Most available data come from observational studies in patients with liver cirrhosis-related SVT receiving low­molecular­weight heparin or vitamin K antagonists. Data on the use of direct oral anticoagulants are increasing and promising. In selected patients and in specialized centers, interventional procedures may be considered in adjunction to anticoagulation in the cases of mesenteric or extensive SVT, intestinal ischemia, or in the patients whose condition deteriorates despite adequate anticoagulant therapy. In this narrative review, we summarize the available data regarding anticoagulation in patients with SVT, identify specific subgroups of patients who may achieve the greatest benefits from anticoagulant therapy, and provide practical advice for clinicians caring for these patients.

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients.

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1). CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

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.

Antithrombotic treatment for retinal vein occlusion: a systematic review and meta-analysis.

BACKGROUND: Retinal vein occlusion (RVO) represents a common thrombotic disorder. OBJECTIVES: In this meta-analysis, we evaluated the efficacy and safety of anticoagulant and antiplatelet therapy in RVO. METHODS: MEDLINE and EMBASE were searched up to December 2021 for observational studies and randomized controlled trials including patients with RVO. Efficacy outcomes were best-corrected visual acuity improvement, recurrent RVO, fluorescein angiography improvement, cardiovascular events, and safety outcomes were major bleeding and intraocular bleeding. RESULTS: A total of 1422 patients (15 studies) were included. Antiplatelet therapy was administered to 477 patients (13 studies), anticoagulant therapy to 312 patients (12 studies), and 609 (7 studies) patients received no antithrombotic treatment. The treatment duration ranged between 0.5 and 3 months. The median follow-up duration was 12 months. Best-corrected visual acuity improvement was reported in 58% of the patients (95% confidence interval [CI], 45%-69%) overall, 64% (95% CI, 58%-71%) in those on anticoagulant therapy, and 33% (95% CI, 21%-47%) in those on antiplatelet therapy. The rates of recurrent RVO was 11% (95% CI, 7%-17%), 7% (95% CI, 2%-19%), and 15% (95% CI, 8%-28%), respectively. The rate of recurrent RVO in untreated patients was 9% (95% CI, 6%-14%). The rate of major bleeding was 5% (95% CI, 3%-9%) overall, 4% (95% CI, 2%-9%) in those on anticoagulant therapy, and 7% (95% CI, 2%-23%) in those on antiplatelet therapy. CONCLUSION: Anticoagulant therapy was associated with higher visual acuity improvement and fewer recurrent RVO events than antiplatelet therapy, at the cost of an acceptable proportion of bleeding complications.

Outcome of COVID-19 patients with haematological malignancies after the introduction of vaccination and monoclonal antibodies: results from the HM-COV 2.0 study.

Patients with haematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. This is a single-centre retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of intensive care unit (ICU) admission (8.2% vs. 27.7%, p = 0.005), shorter viral shedding [17 (IQR 10-28) vs. 24 days (IQR 15-50), p = 0.011] and shorter hospitalization length [13 (IQR 7-23) vs. 20 (IQR 14-41) days, p = 0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs. 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs. 29.2% PRE-V-mAb, respectively). At the multivariable analysis, an active malignancy (p = 0.042), a critical COVID-19 at admission (p = 0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP (p = 0.022) or mechanical ventilation (p = 0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor (p = 0.033). Despite the new therapeutic and preventive strategies available, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates.

Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis.

BACKGROUND: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. OBJECTIVES: The objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT. METHODS: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate. RESULTS: In total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35). CONCLUSION: Patients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT.