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Background: Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE)., Objectives: We aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting., Methods: We used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline-recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy. Patients were followed for 6 months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using C statistics., Results: We included 12 471 patients from 2012 to 2020. Of these, 416 (3.3%) developed VTE. The C statistic was 0.71 (95% CI, 0.68-0.74) for the new CAT score and 0.66 (95% CI, 0.63-0.70) for the Khorana score. The 6-month cumulative VTE incidence was 5.0% in 6175 patients classified as high risk by the new CAT score compared with 1.7% in 6296 patients classified as low risk. The 6-month cumulative VTE incidence was 5.2% in 4263 patients classified as high risk by the Khorana score compared with 2.4% in 8208 patients classified as low risk., Conclusion: The new CAT score had a discriminatory ability similar to that reported in the derivation study. The C statistic was numerically higher than that of the Khorana score. Our findings support the implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE., Competing Interests: Declaration of competing interests M.D.N. received personal fees as an invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from Leo Pharma, Janssen, and Pfizer, and institutional funding from Leo Pharma, all outside the submitted work. P.W.K. received research funding from Daiichi Sankyo and Roche Diagnostics. N.v.E. received advisory board honoraria from Daiichi Sankyo, LEO Pharma, and Bayer, which were transferred to his institute. The other authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions., Aim:  To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT., Methods:  For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot., Results:  After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies., Conclusion:  The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging., Competing Interests: M.G. is an employee of Daiichi Sankyo. A.Y.Y.L. reports consulting fees and honoraria from Bayer AG, consulting fees and honoraria from LEO Pharma, consulting fees and honoraria from Pfizer, consulting fees from Servier, and honoraria from Bristol Myers Squibb. M.D.N. reports personal fees as an invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from Leo Pharma, Janssen, and Pfizer, and institutional funding from Leo Pharma, all outside the submitted work. G.E.R. reports consultancy fees or honoraria from AMAG Pharma, Alnylam, Anthos Therapeutics, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb, Daiichi Sankyo Inc., Ionis, Janssen Global Services LLC, Pfizer, Regeneron, Sirius Pharmaceutical; honoraria from BMS, Pfizer, Daiichi Sankyo; DSMB or advisory board membership from Anthos Therapeutics, Janssen, Bristol-Myers Squibb, and Pfizer, leadership or fiduciary role in other board, society, committee or advocacy group of OU Health, and the National Blood Clot Alliance. P.W.K. reports research funding from Daiichi Sankyo and Roche diagnostics. H.R.B. reports research support from Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis. Consultant from Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis. Scientific advisory board from Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis. N.v.E. reports advisory board honoraria from Daiichi Sankyo, LEO Pharma, and Bayer, which were transferred to his institute. The other authors have nothing to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses., Aims: This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs., Methods: No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies., Content: The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context., Conclusions: The management of CRT is still challenging with constant need for updated evidence to support tailored approaches., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Deep vein thrombosis (DVT) is a cause of considerable morbidity worldwide. It is a common clinical disease in the daily practice of several medical disciplines including general medicine, angiology, and internal medicine, as well as of interest to public health because of its preventability and its sensitivity to secular changes in the distribution of population risk factors. In this review we present a comprehensive overview of the epidemiological features of DVT, including incidence and risk factors. Additionally, we give an overview of the burden that DVT poses on modern health care systems.

Background: Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk., Objectives: This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding)., Methods: PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs)., Results: Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results., Conclusion: In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE., Competing Interests: Declaration of competing interests N.A.M.G., A.-M.L.B., S.S.W., N.K., F.I.M., M.J.L.P., M.t.W, J.M.M.B.O., E.P., V.S.-L., and P.M.M.B. have no competing interests to disclose. M.C. has received research funding from BMS, Pfizer, and LEO Pharma. He has also received Honoria from Bayer, BMS, Pfizer, Servier, and LEO Pharma. A.D. has received research funding from BMS-Pfizer and Honoria from Bayer, BMS-Pfizer, Servier, and LEO Pharma. L.J.-P. has received research funding from LEO Pharma and MSD. He has also received honoraria from Bayer Hispania, Actelion, Pfizer, Rovi, LEO Pharma, Menarini, and MSD. M.D. has received research funding from LEO Pharma and honoraria and consultancy fees from Daiichi Sankyo, Bayer, BMS-Pfizer, Sanofi, and LEO Pharma outside the submitted work. W.A. has received research funding from Bayer and honoraria from Bayer, BMS-Pfizer, Aspen, Sanofi, Janssen, Werfen, LEO Pharma, and Portola. J.B.-W. has received research funding from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. He has also received honoraria from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. T.V. has served as a speaker and/or advisor for Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Bayer, Sanofi, and LEO Pharma. F.A.K. reports research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch Thrombosis Association, and the Dutch Heart foundation. B.C. reports speakers’ fees from Daiichi Sankyo and Sanofi. V.E.A.G. reports lecture fees from Novo Nordisk, and funding of studies by Dutch Thrombosis Foundation, AstraZeneca, and Zambon. H.B. reports consulting fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. N.v.E. has received advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma, which were transferred to his institute. P.W.K. received research grants from Daiichi Sankyo and Roche Diagnostics., (Copyright © 2024. Published by Elsevier Inc.)

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is linked to deep vein thrombosis (DVT) or pulmonary embolism (PE) in up to one fourth of cases. Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban, however, these require further evidence. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

Background: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available., Objectives: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach., Methods: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored., Results: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history., Conclusion: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management., Competing Interests: Declaration of competing interests N.P. reports a training fellowship from the International Society on Thrombosis and Haemostasis and research funding from International Network of VENous Thromboembolism Clinical Research Networks (INVENT) outside of the submitted work. I.M. reports research funding from Leo Pharma and BMS-Pfizer outside of the submitted work, and advisory board/honoraria from Bayer, BMS-Pfizer, Leo, and Sanofi. P.A. reports research funding from Novo Nordisk, Sanofi, and Spark Therapeutics outside of the submitted work. G.C.M. reports personal fees from Bayer and BMS-Pfizer outside the submitted work. N.V.E. received, outside of the submitted work, advisory board honoraria from Daiichi-Sankyo, Bayer, and Leo Pharma paid to his institution. A.L. reports lecture fees from Leo Pharma outside the submitted work. E.O. reports funding from Novo Nordisk outside the submitted work and Pfizer advisory board/honoraria. F.N.A. reports grant funding (IIS paid to university) from Daiichi-Sankyo, Leo Pharma, Sanofi, and Actelion, and consultancy for Boston Scientific, outside of the submitted work. H.C.O. received a training fellowship from the International Society on Thrombosis and Haemostasis. D.M. reports speaker fees from Leo Pharma, BMS, and Pfizer. C.A. reports personal fees from Bayer, BMS/Pfizer, Daiichi-Sankyo, and Sanofi outside the submitted work. L.A.C. reports that her research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, Leo Pharma, Sanofi, Valeo Pharma, and Servier. S.B. received consultancy and speaker fees from Bayer, Concept Medical, Boston Scientific, and Inari outside of the submitted work. M.D.N. reports personal fees from Bayer, Daiichi-Sankyo, BMS-Pfizer, Leo Pharma, and Viatris outside the submitted work. The remaining authors report no relevant conflicts of interest to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is a frequent cardiovascular (CV) comorbidity in cancer., Objectives: The purpose of this study was to examine clinical characteristics and contemporary management of patients with AF and cancer with a specific focus on antithrombotic treatments., Methods: This was a prospective, multicenter, observational study of patients with a recent cancer diagnosis and electrocardiographically confirmed AF (the BLITZ-AF Cancer Registry). CHA 2 DS 2 VASc scores were calculated for study participants., Results: Overall, 1,514 individuals were enrolled from June 2019 to September 2021 (mean age 74 ± 9 years, 47.5% of participants >75 years of age; 63.5% males). CV diseases were common: 20.9% had heart failure, 18.1% had coronary artery disease, 38.5% had valvular heart disease, and 9.8% had peripheral artery disease. Previous thromboembolic and hemorrhagic events occurred in 13.9% and 10.4% of subjects, respectively. The most common cancer types were lung (14.9%), colorectal (14.1%), prostate (8.8%), and non-Hodgkin lymphoma (8.1%). In total, 41.5% of the patients had a CHA 2 DS 2 VASc score ≥4. Before admission or prior to cardiologist consultation, 16.6% of subjects were not taking any antithrombotic therapy and 22.7% were receiving antiplatelet agents and/or low-molecular-weight heparin. At discharge or after cardiologic assessment, these percentages dropped to 7.7% and 16.6%, respectively. This trend was paralleled by an increase in the use of direct-acting oral anticoagulant, while the proportion of vitamin K antagonist declined., Conclusions: This study demonstrates that there is underuse of appropriate antithrombotic therapy for AF in cancer patients highlighting the need to integrate early CV assessment in the management of these patients. (Non-interventional Study on Patients With Atrial Fibrillation and Cancer [BLITZ-AF Cancer]; NCT03909386)., Competing Interests: The study was realized by Heart Care Foundation with own research funds, partially supported by a not conditional grant by Daiichi Sankyo Italia. Dr Ameri received speaker and/or advisor fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Daiichi Sankyo, Janssen, and MSD, all outside the scope of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Cancer is an important condition associated with the development of atrial fibrillation (AF). The objectives of the BLITZ-AF Cancer study were to collect real-life information on the clinical profile and use of antithrombotic drugs in patients with AF and cancer to improve clinical management, as well as the evaluation of the association between different antithrombotic treatments (or their absence) and the main clinical events., Methods: European multinational, multicenter, prospective, non-interventional study conducted in patients with AF (electrocardiographically confirmed) and cancer occurring within 3 years. The CHA2DS2-VASc and the HAS-BLED scores were calculated in all enrolled patients., Results: From June 2019 to July 2021, 1514 patients were enrolled, 36.5% women, from 112 cardiology departments in 6 European countries (Italy, Belgium, the Netherlands, Spain, Portugal and Ireland). Italy enrolled 971 patients in 77 centers. Average age of patients was 74 ± 9 years, of which 20.9% affected by heart failure, 18.1% by ischemic heart disease, 9.8% by peripheral arterial disease and 38.5% by valvular diseases; 41.5% of patients had a CHA2DS2-VASc score ≥4. The most represented cancer sites were lung (14.9%), colorectal tract (14.1%), prostate (8.8%), or non-Hodgkin's lymphoma (8.1%). Before enrollment, 16.6% of patients were not taking antithrombotic therapy, while 22.7% were on therapy with antiplatelet agents and/or low molecular weight heparin. After enrollment these percentages decreased to 7.7% and 16.6%, respectively and, at the same time, the percentage of patients on direct oral anticoagulant (DOAC) therapy increased from 48.4% to 68.4%, also to the detriment of those on vitamin K antagonist therapy., Conclusions: The BLITZ-AF Cancer study, which enrolled patients diagnosed with AF and cancer, highlights that the use of DOACs by cardiologists in this clinical context has increased, even though the guidelines on AF do not give accurate indications about oral anticoagulant therapy in patients with cancer.

Immunothrombosis-immune-mediated activation of coagulation-is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1β and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy and is approved for the treatment of hypoxaemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps, and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19., Competing Interests: Conflict of interest: N.P. has received a training fellowship from the International Society on Thrombosis and Haemostasis and research funding from the International Network of VENous Thromboembolism Clinical Research Networks (INVENT), outside of the present work. Y.K. is an inventor on a patent application (US20180369278A1) by the University of Michigan on the use of biogases in vascular disease. M.D.N. reports personal fees as an invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from LEO Pharma and Pfizer, and institutional funding from LEO Pharma. G.K. has received honorary fees from Swedish Orphan Biovitrum, Chugai-Roche, and Amgen. A.B. received a travel grant from Kiniksa Pharmaceuticals Ltd to attend the 2019 AHA Scientific Sessions and honoraria from Effetti s.r.l. (Milan, Italy) to collaborate on the medical website http://www.inflammology.org, outside the present work. J.M.C. has received personal fees for scientific advisory boards and consulting from Abbott, Anthos, Alnylam, Bristol Myers Squibb, Five Prime Therapeutics, Pfizer, Takeda, and research funding from CSL Behring, outside of the submitted work. R.D.C. has received personal fees from Boehringer-Ingelheim, Bayer, BMS-Pfizer, Daiichi Sankyo, Novartis, Roche, Sanofi, Amgen, Milestone, Menarini, AstraZeneca, and Guidotti, outside the submitted work. A.A. has received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum, outside of the submitted work. E.G. has nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Venous thromboembolism (VTE) remains a major health burden despite anticoagulation advances, suggesting incomplete management of pathogenic mechanisms. The NLRP3 (NACHT-, LRR- and pyrin domain-containing protein 3) inflammasome, interleukin (IL)-1, and pyroptosis are emerging contributors to the inflammatory pathogenesis of VTE. Inflammasome pathway activation occurs in patients with VTE. In preclinical models, inflammasome signaling blockade reduces venous thrombogenesis and vascular injury, suggesting that this therapeutic approach may potentially maximize anticoagulation benefits, protecting from VTE occurrence, recurrence, and ensuing post-thrombotic syndrome. The nonselective NLRP3 inhibitor colchicine and the anti-IL-1β agent canakinumab reduce atherothrombosis without increasing bleeding. Rosuvastatin reduces primary venous thrombotic events at least in part through lipid-lowering independent mechanisms, paving the way to targeted anti-inflammatory strategies in VTE. This review outlines recent preclinical and clinical evidence supporting a role for inflammasome pathway activation in venous thrombosis, and discusses the, yet unexplored, therapeutic potential of modulating inflammasome signaling to prevent and manage VTE., Competing Interests: Dr Potere has received a training fellowship from the International Society on Thrombosis and Haemostasis, and research grant funding from the International Network of VENous Thromboembolism Clinical Research Networks (INVENT). Dr Abbate has received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum. Dr Kanthi has received research grant funding from the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health, and the Lasker Foundation, and is an inventor on a patent application by the University of Michigan on the use of biogases in vascular disease (US20180369278A1). Dr Carrier has received research funding from Leo Pharma, Bristol Myers Squibb, and Pfizer, and honoraria from Bayer, Bristol Myers Squibb, Sanofi, Servier, Pfizer, and Leo Pharma. Dr Toldo and Dr Abbate are supported by a National Institutes of Health grant (R01HL150115). Dr Toldo has served as a paid scientific advisor to Cardiol Therapeutics and Novo Nordisk, and received research grant funding from Kiniksa, Olatec, Serpin Pharma, and Cardiol Therapeutics. Dr Di Nisio has received personal fees from Bayer, Daiichi Sankyo, Sanofi, Bristol Myers Squibb, Pfizer, Leo Pharma, and Viatris. Dr Porreca has reported that he has no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

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., Competing Interests: Declaration of competing interests E.V., M.C., N.R., S.M.B., M.M., J.A.D.P., J.M., A.M.D.B., V.P.C., M.S., and A.D.G. have nothing to disclose. M.D.N. received honoraria for participation at the advisory boards from Bayer, Daiichi Sankyo, Pfizer, Leo Pharma, Sanofi, and Viatris outside the submitted work. W.A. has received a research grant from Bayer to support a clinical study in patients with splanchnic vein thrombosis, received honoraria for participation at advisory boards from Bayer, BMS/Pfizer, Sanofi, Leo Pharma, and Portola, and reports grants and personal fees from Bayer, and personal fees from BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, Portola, and Werfen, outside the submitted work; M. Monreal received honoraria for participation at advisory boards from Bristol and Sanofi, outside the submitted work; S.S. has received research funding from Boehringer Ingelheim and Octapharma and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, and Sanofi; J.C.G.P. is a consulting for Cook Medical, Shionogi, WL Gore y Asociados, Vifor Pharma, and Boehringer Ingelheim and has received a research frant from Mallinckrodt and Noorik., (Copyright © 2023 International Society on Thrombosis and Haemostasis. All rights reserved.)

Background and Objectives : Prophylactic doses of low-molecular-weight heparins or fondaparinux showed their efficacy and safety for treatment of all superficial vein thrombosis (SVT) of the lower limbs, yet not for those extended to the last 3 cm of the great saphenous vein, close to the sapheno-femoral junction, or considered as a deep-vein thrombosis. Some experts suggest that these patients should be managed with full anticoagulant doses but evidence to support this recommendation is lacking, suggesting the need for a properly designed trial. Materials and Methods : Before starting a new trial, the Italian Society of Angiology and Vascular Medicine (SIAPAV) decided to verify the common therapeutic approaches for patients with an SVT in Italian vascular centers based on a hypothetical significant variation in each daily clinical practice. A standardized questionnaire of 10 questions was administered to all SIAPAV affiliates by means of the official Society website. Results : From 1 December 2022 to 20 January 2023 a total of 191 members (31.8%) answered the questionnaire, showing a detailed and a substantial heterogeneity in the therapeutic approach to SVT patients among experienced vascular physicians and angiologists. Detailed results are reported in the relative section. Conclusions : The therapeutic approach of SVT extended to the iuxta-femoral segment of the great saphenous vein is still a matter of debate, and data to support therapeutic strategies are lacking. The wide heterogeneity in the management of SVT patients, including those with more extended thrombosis, confirmed that a randomized controlled clinical trial investigating the efficacy and the safety of a tailored therapeutic regimen in this particular subgroup of patients is strongly warranted.

Background: In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain., Aim: To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule., Patients and Methods: Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism., Results: Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate., Conclusions: In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MDN received personal fees as invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from Leo Pharma and Pfizer, and institutional funding from Leo Pharma. NP received a training fellowship from the International Society on Thrombosis and Haemostasis, and research funding from International Network of VENous Thromboembolism Clinical Research Networks, outside of the present work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosure AF reports personal fees as an invited speaker from LEO Pharma, Pfizer, Rovi, Sanofi, Stago and Werfen. CA reports personal fees as an invited speaker from Bayer, Bristol-Myers Squibb (BMS)/Pfizer, Daiichi Sankyo and Sanofi; and personal fees for advisory board membership from Bayer, BMS/Pfizer and Sanofi. MDN reports personal fees as an invited speaker from Bayer, Daiichi Sankyo and Viatris; personal fees for advisory board membership from LEO Pharma and Pfizer; and institutional funding from LEO Pharma. GG reports no conflicts of interest. LJP reports personal fees as an invited speaker from Actelion, Daiichi Sankyo, LEO Pharma, MSD, Pfizer and Rovi; and institutional funding from LEO Pharma and MSD. FL reports personal fees as an invited speaker from Bayer, BMS, Janssen-Cilag, LEO Pharma, Mitsubishi Tanabe Pharma and Pfizer; personal fees for advisory board membership from Alexion, Aspen, BioMarin, Chugai, CSL Behring, Daiichi Sankyo, GSK, Mylan (Viatris), Roche, SOBI, Takeda and Werfen; and institutional funding from Bayer, CSL Behring, Intersero, Novo Nordisk and SOBI. RL reports personal fees as an invited speaker from BMS, Daiichi Sankyo, Janssen, Laboratorios Rovi, LEO Pharma and Sanofi; personal fees for advisory board membership from Janssen, LEO Pharma and Sanofi; institutional funding from Laboratorios Rovi; and complimentary product samples from Laboratorios Rovi. MM reports personal fees as an invited speaker from Sun Pharma; and personal fees for advisory board membership from BMS, Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre and Sanofi. AM reports personal fees as an invited speaker from Bayer, BMS, LEO Pharma, Pfizer and Sanofi; personal fees for advisory board membership from Bayer, BMS, LEO Pharma and Pfizer; and personal fees for a writing engagement from BMS and LEO Pharma. IP reports personal fees as an invited speaker from Bayer, BMS, Pfizer and Sanofi; and personal fees for advisory board membership from Bayer, BMS, Daiichi Sankyo and Pfizer. MS reports personal fees as an invited speaker for art tempi at ASCO Direct, BMS, Esanum, MSD, Pfizer and Pierre Faber; personal fees for advisory board membership from Amgen, AstraZeneca, Sanofi and Servier; expert testimony for Incyte and institutional funding as local principal investigator (PI) from Amgen, AstraZeneca, BeiGene, BMS and GSK; non-remunerated membership to Association of Scientific Medical Societies in Germany Guidelines Pancreatic and Liver Cancer; and a non-remunerated leadership role at Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.V (AIO) Leitgruppe Pancreatic Cancer. KS reports personal fees for advisory board membership from Amgen and BMS; and institutional funding from MSD. AY reports personal fees as an invited speaker from LEO Pharma; and personal fees for advisory board membership from BMS/Pfizer Alliance. KJ reports personal fees as an invited speaker from Amgen, art tempi, Helsinn, Hexal, med update GmbH, MSD, Mundipharma, onkowissen, Riemser, Roche, Shire (Takeda) and Vifor; personal fees for advisory board membership from Amgen, AstraZeneca, BD Solutions, Hexal, Karyopharm and Voluntis; royalties from Elsevier and Wolters Kluwer; institutional funding as a coordinating PI from Helsinn; non-remunerated membership to the American Society for Clinical Oncology, Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie and Multinational Association of Supportive Care in Cancer; a non-remunerated leadership role at Arbeitsgemeinschaft Supportive Massnahmen in der Onkologie, AIO and ESMO; and a non-remunerated advisory role at Deutsche Krebshilfe, the Federal Ministry of Education and Research, the Hamburg Cancer Society and Leopoldina.

Aims: The anamnestic frailty phenotype (AFP) is a quick, instrument-free tool derived from frailty phenotype (FP). We prospectively evaluated the discriminative capacity and prognostic value of AFP in ambulatory patients receiving DOACs for atrial fibrillation (AF) or venous thromboembolism (VTE), and compared AFP performance with that of FP., Methods and Results: Sensitivity, specificity, positive and negative predictive value (PPV, NPV) with corresponding 95% confidence intervals (95%CI), were estimated for bleeding, thromboembolism, and all-cause mortality. Risk ratios (RRs) were calculated in frail versus non-frail patients. Of 236 patients (median age 78 years), 98 (42%) and 89 (38%) were classified as frail according to FP and AFP, respectively (Kappa= 0.76). Frailty, as assessed by AFP, was associated with higher risk of bleeding (RR 2.3; 95%CI, 1.2 to 4.6), and mortality (RR 4.4; 95%CI, 1.3 to 19.7). Similarly, to FP, AFP exhibited modest sensitivity and specificity, but high NPV that was 91% (95%CI, 85 to 95) for bleeding, 98% (95%CI, 94 to 100) for thromboembolism, and 98% (95%CI, 94 to 100) for mortality., Conclusion: Among patients receiving DOACs for AF or VTE, AFP was associated with an increased risk of adverse outcomes. AFP exhibited modest sensitivity and specificity, but excellent NPV. If confirmed, these findings suggest that AFP may represent a rapid, easy-to-use and unexpensive tool that may potentially help identify patients at lower risk for adverse outcomes and tailor anticoagulation management., Competing Interests: Declaration of Competing Interest Matteo Candeloro, Nicola Potere, Camilla Federici, Raffaella Auciello, and Ettore Porreca have no conflict of interest to declare; Marcello Di Nisio received honoraria for participation at advisory boards from Bayer, Daiichi Sankyo, Pfizer, Leo Pharma, Sanofi, and Viatris, outside the submitted work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies., Objectives: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE)., Methods: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity., Results: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47)., Conclusion: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm., Competing Interests: Declaration of competing interests N.K., F.I.M., N.A.G., M.t.W., H.-M.B.O., S.G.J.G.I.t.V., E.P., V.S.-L., K.Z., J.R., P.M.M.B., and E.P. report no conflicts of interest. M.C. has received research funding from BMS, Pfizer, and LEO Pharma. He has also received Honoria from Bayer, BMS, Pfizer, Servier, and LEO Pharma. A.D. has received research funding from BMS-Pfizer and Honoria from Bayer, BMS-Pfizer, Servier, and LEO Pharma. T.W. is an inventor on relevant patent applications, received funding from Illumina Inc, and is a shareholder of GRAIL, Inc. L.J.-P. has received research funding from LEO Pharma and MSD. He has also received honoraria from Bayer Hispania, Actelion, Pfizer, Rovi, LEO Pharma, Menarini, and MSD. P.W.K. has received research grants from Daiichi Sankyo and Roche Diagnostics M.D.N. has received research funding from LEO Pharma and honoraria and consultancy fees from Daiichi Sankyo, Bayer, BMS-Pfizer, Sanofi, and LEO Pharma outside the submitted work. M.G.B. is an inventor on relevant patent applications. W.A. has received research funding from Bayer and honoraria from Bayer, BMS-Pfizer, Aspen, Sanofi, Janssen, Werfen, LEO Pharma, and Portola. J.B.-W. has received research funding from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. He has also received Honoria from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. T.V. has served as a speaker and/or advisor for Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Bayer, Sanofi, and LEO Pharma. F.A.K. has received research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch thrombosis association, and the Dutch Heart foundation. B.C. has received speakers’ fees from Daiichi Sankyo and Sanofi. H.B. reports personal fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. N.v.E. has received advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma which were transferred to his institute., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricle dysfunction (RVD) at echocardiography predicts mortality in patients with acute pulmonary embolism (PE), but heterogeneous definitions of RVD have been used. We performed a meta-analysis to assess the role of different definitions of RVD and of individual parameters of RVD as predictors of death., Methods: A systematic search for studies including patients with confirmed PE reporting on right ventricle (RV) assessment at echocardiography and death in the acute phase was performed. The primary study outcome was death in-hospital or at 30 days., Results: RVD at echocardiography, regardless of its definition, was associated with increased risk of death (risk ratio 1.49, 95% CI 1.24-1.79, I 2 =64%) and PE-related death (risk ratio 3.77, 95% CI 1.61-8.80, I 2 =0%) in all-comers with PE, and with death in haemodynamically stable patients (risk ratio 1.52, 95% CI 1.15-2.00, I 2 =73%). The association with death was confirmed for RVD defined as the presence of at least one criterion or at least two criteria for RV overload. In all-comers with PE, increased RV/left ventricle (LV) ratio (risk ratio 1.61, 95% CI 1.90-2.39) and abnormal tricuspid annular plane systolic excursion (TAPSE) (risk ratio 2.29 CI 1.45-3.59) but not increased RV diameter were associated with death; in haemodynamically stable patients, neither RV/LV ratio (risk ratio 1.11, 95% CI 0.91-1.35) nor TAPSE (risk ratio 2.29, 95% CI 0.97-5.44) were significantly associated with death., Conclusion: Echocardiography showing RVD is a useful tool for risk stratification in all-comers with acute PE and in haemodynamically stable patients. The prognostic value of individual parameters of RVD in haemodynamically stable patients remains controversial., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)

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., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC-treated patients at higher risk of adverse clinical outcomes., Methods: Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre-frail, or non-frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non-major bleeding, arterial and venous thromboembolism, and all-cause mortality., Results: 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety-eight (41%) patients were frail, 115 (49%) pre-frail, and 23 (10%) non-frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non-frail or pre-frail patients. Over a median follow-up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre-frail, respectively, while no study outcome occurred among non-frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre-frail and non-frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6)., Conclusion: In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all-cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis., (© 2022 The American Geriatrics Society.)

Background: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty., Methods: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media., Results: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received., Conclusions: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Competing Interests: Declaration of Competing Interest MDN received honoraria for participation at advisory boards from Bayer, Daiichi Sankyo, Pfizer, Leo Pharma, Sanofi, and Viatris, outside the submitted work. NP and EP have no conflict of interest to declare.

Background: Hospitalized COVID-19 patients are at high risk of venous thromboembolism (VTE). Standard doses of anticoagulant prophylaxis may not be sufficiently effective for the prevention of VTE. The objective of this systematic-review and meta-analysis was to compare the efficacy and safety of high-dose versus low-dose thromboprophylaxis in hospitalized patients with COVID-19., Material and Methods: MEDLINE and EMBASE were searched up to October 2021 for randomized clinical trials (RCTs) comparing high-dose with low-dose thromboprophylaxis in hospitalized adult patients with COVID-19. The primary efficacy outcome was the occurrence of VTE and the primary safety outcome was major bleeding., Results: A total of 5470 patients from 9 RCTs were included. Four trials included critically ill patients, four non-critically ill patients, and one included both. VTE occurred in 2.9% of patients on high-dose and in 5.7% of patients on low-dose thromboprophylaxis (relative risk [RR] 0.53; 95% confidence intervals [CIs], 0.41-0.69; I 2  = 0%; number needed to treat for an additional beneficial outcome, 22). Major bleeding occurred in 2.5% and 1.4% of patients, respectively (RR 1.78; 95% CI, 1.20-2.66; I 2  = 0%; number needed to treat for an additional harmful outcome, 100). All-cause mortality did not differ between groups (RR 0.97; 95% CI, 0.75-1.26; I 2  = 47%). The risk of VTE was significantly reduced by high-dose thromboprophylaxis in non-critically ill (RR 0.54; 95% CI, 0.35-0.86; I 2  = 0%), but not in critically ill patients (RR 0.69; 95% CI, 0.39-1.21; I 2  = 36%)., Discussion: In hospitalized patients with COVID-19, high-dose thromboprophylaxis is more effective than low-dose for the prevention of VTE but increases the risk of major bleeding., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. Treatment of cancer-associated VTE comes with a heightened risk of anticoagulant-related bleeding that differs by choice of anticoagulant as well as by patient- and disease-specific risk factors. Available data from randomized controlled trials and observational studies in cancer-associated VTE suggest that direct oral anticoagulants are effective, continuing anticoagulation beyond six months is indicated in those with active cancer and that patients who develop 'breakthrough' thrombotic events can be effectively treated. We review the evidence that addresses these key clinical questions and offer pragmatic approaches in individualizing care. While significant investigative efforts over the past decade have made impactful advances, future research is needed to better define the factors that contribute to anticoagulant-related bleeding and VTE recurrence, in order to aid clinical decision-making that improves the care of patients with cancer-associated VTE., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that plays a major role in innate immunity. Following tissue injury, activation of the NLRP3 inflammasome results in cytokine production, primarily interleukin(IL)-1β and IL-18, and, eventually, inflammatory cell death - pyroptosis. While a balanced inflammatory response favors damage resolution and tissue healing, excessive NLRP3 activation causes detrimental effects. A key involvement of the NLRP3 inflammasome has been reported across a wide range of cardiovascular diseases (CVDs). Several pharmacological agents selectively targeting the NLRP3 inflammasome system have been developed and tested in animals and early phase human studies with overall promising results. While the NLRP3 inhibitors are in clinical development, multiple randomized trials have demonstrated the safety and efficacy of IL-1 blockade in atherothrombosis, heart failure and recurrent pericarditis. Furthermore, the non-selective NLRP3 inhibitor colchicine has been recently shown to significantly reduce cardiovascular events in patients with chronic coronary disease. In this review, we will outline the mechanisms driving NLRP3 assembly and activation, and discuss the pathogenetic role of the NLRP3 inflammasome in CVDs, providing an overview of the current and future therapeutic approaches targeting the NLRP3 inflammasome., Competing Interests: Declaration of Competing Interest ST has received research grant funding from Kiniksa, Olatec and Serpin Pharma. AA has received research grant funding and has served as a paid scientific advisor to Cromos Pharma, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, Serpin Pharma, and Swedish Orphan Biovitrum. LFB has served as a consultant to Kiniksa Pharmaceuticals. GBZ has served as a consultant to Cardionovum, CrannMedical, Meditrial, Optisense Medical, and Replycare. All other authors declare no conflict of interest related to the content of the present work to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Retinal vein occlusion (RVO) represents a common cause of visual impairment and blindness. RVO may be associated with both local (e.g., hyperopia, glaucoma) and systemic (e.g., hypertension, diabetes, smoking, obesity, and dyslipidaemia) risk factors. The association with thrombophilia remains controversial. Data on the use of antithrombotic therapy for RVO are poor and inconsistent with most of the information being derived from observational studies. Here we provide a position statement from the Italian Society on Thrombosis and Haemostasis (SISET) to guide the clinical and therapeutic management of patients with RVO based on the available evidence and expert opinion.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Data on anticoagulant treatment for upper extremity deep vein thrombosis (UEDVT) are largely derived from studies on usual site venous thromboembolism (VTE)., Objectives: The objective of this meta-analysis was to evaluate the efficacy and safety of anticoagulant therapy for UEDVT., Patients/methods: A systematic search of MEDLINE and EMBASE was conducted for studies including patients with UEDVT. Primary outcomes were recurrent VTE and major bleeding. Secondary outcomes included clinically-relevant non-major bleeding and all-cause mortality. Summary estimates with 95% confidence intervals (CIs) were calculated by random-effect meta-analysis., Results: A total of 1473 patients from 11 prospective and nine retrospective studies were included. Sixty percent of patients had an indwelling catheter and 56.1% had cancer. Anticoagulant treatment consisted of direct oral anticoagulants, low molecular weight heparin followed by vitamin K antagonists, and low molecular weight heparin alone in 45.1%, 35.0%, and 19.9% of patients, respectively. During a median follow-up of 13 months, recurrent VTE occurred in 3% of patients (95% CI: 2-4; 21/1334 patients), major bleeding in 3% (95% CI: 2%-5%; 29/1235 patients), clinically-relevant non-major bleeding in 4% (95% CI: 3-6; 40/1075 patients), and all-cause mortality in 9% (95% CI: 5-15; 108/1084 patients). Rates of these outcomes were not significantly different between patients with or without cancer, patients with or without an indwelling catheter, and among those receiving different anticoagulant treatments., Conclusions: In patients with UEDVT, anticoagulant treatment is associated with a low risk of recurrent VTE and a nonnegligible risk of major bleeding., (© 2021 International Society on Thrombosis and Haemostasis.)

Direct oral anticoagulants (DOACs) are not recommended in COVID-19 patients receiving dexamethasone because of potential drug-drug and drug-disease interactions affecting anticoagulant concentration and activity. To evaluate short- and long-term pharmacokinetic interactions, serial through and peak DOAC plasma levels were prospectively measured during and after dexamethasone therapy, as well as during the acute phase and after recovery from COVID-19 in hospitalized, non-critically ill patients undergoing treatment with DOACs. Thirty-three (18 males, mean age 79 years) consecutive patients received DOACs (17 apixaban, 12 rivaroxaban, 4 edoxaban) for atrial fibrillation (n = 22), venous thromboembolism (n = 10), and acute myocardial infarction (n = 1). Twenty-six patients also received dexamethasone at a dose of 6 mg once daily for a median of 14 days. Trough DOAC levels on dexamethasone were within and below expected reference ranges respectively in 87.5 and 8.3% of patients, with no statistically significant differences at 48-72 h and 14-21 days after dexamethasone discontinuation. Peak DOAC levels on dexamethasone were within expected reference ranges in 58.3% of patients, and below ranges in 33.3%, of whom over two thirds had low values also off dexamethasone. No significant differences in DOAC levels were found during hospitalization and after resolution of COVID-19. Overall, 28 patients were discharged alive, and none experienced thrombotic or bleeding events. In this study, dexamethasone administration or acute COVID-19 seemed not to affect DOAC levels in hospitalized, non-critically ill COVID-19 patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Patients hospitalized for acute ischemic stroke have an increased risk of venous thromboembolism (VTE) that may persist beyond the currently recommended period of 6 to 14 days of thromboprophylaxis. This systematic review evaluated the efficacy and safety of extended venous thromboprophylaxis in patients hospitalized for acute ischemic stroke., Materials and Methods: MEDLINE, EMBASE and Clinicaltrials.gov were searched up to December 2020 for randomized controlled trials comparing extended versus standard venous thromboprophylaxis in patients hospitalized for acute ischemic stroke. The efficacy outcome was a composite of asymptomatic or symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and VTE-related death. The safety outcome was major bleeding. Summary risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects models., Results: Four randomized controlled trials enrolling 33718 patients were included. Of 4330 (12.8%) patients hospitalized for acute ischemic stroke, 2152 (49.7%) received extended thromboprophylaxis for four to five weeks with betrixaban (n = 405, 18.8%), enoxaparin (n = 198, 9.2%), or rivaroxaban (n = 1549, 72.0%), and 2178 (50.3%) received standard venous thromboprophylaxis with enoxaparin. VTE risk was lower in acute ischemic stroke patients receiving extended thromboprophylaxis (RR 0.67; 95% CI, 0.43 to 1.04; 13 fewer per 1000), whereas the increase in major bleeding seemed trivial when compared with standard prophylaxis (RR 1.10; 95% CI, 0.31 to 3.95; 1 more per 1000)., Conclusion: In patients hospitalized for acute ischemic stroke, the net clinical benefit may favor extended venous thromboprophylaxis for four to five weeks over standard thromboprophylaxis., (Copyright © 2021. Published by Elsevier B.V.)

Upper extremity deep vein thrombosis (UEDVT) represents about 5-10% of all cases of deep vein thrombosis (DVT) with a steadily increasing incidence mostly due to the high prevalence of cancer and frequent use of intravascular devices such as central venous catheters and pacemaker. In primary UEDVT, the venous outflow obstruction and subsequent thrombosis are related to congenital or acquired anatomical abnormalities, whereas secondary UEDVT is often associated with malignancy or indwelling lines. A considerable proportion of patients with UEDVT develops serious complications such as recurrent thrombosis, post-thrombotic syndrome, and pulmonary embolism, therefore timely diagnosis and adequate treatment are of crucial importance. Despite sharing many similarities with lower extremity DVT, UEDVT has distinctive features requiring specific diagnostic and therapeutic approaches. The present review discusses the latest evidence on the epidemiology, diagnosis, and treatment of UEDVT, and provides management indications which may help guide clinical decision making.

Background: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients., Objectives: To evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban., Patients/methods: In this nested case-control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4-week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type., Results: Twenty-four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01-12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5-16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1-1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5-3.5)., Conclusion: Advanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power., (© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR., Objectives: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort., Methods: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule., Results: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively)., Conclusion: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort., (© 2021 International Society on Thrombosis and Haemostasis.)

Cancer patients have a high risk of developing venous thromboembolism and arterial thrombosis, along with an increased risk of anticoagulant-related bleeding with primary and secondary prophylaxis of cancer-associated thrombosis. Decisions on initiation, dosing, and duration of anticoagulant therapy for prevention and treatment of cancer-associated thrombosis are challenging, as clinicians have to balance patients' individual risk of (recurrent) thrombosis against the risk of bleeding complications. For this purpose, several dedicated risk assessment models for venous thromboembolism in cancer patients have been suggested. However, most of these scores perform poorly and have received limited to no validation. For bleeding and arterial thrombosis, no risk scores have been developed specifically for cancer patients, and treatment decisions remain based on clinical gestalt and rough and unstructured estimation of the risks. The aims of this review are to summarize the characteristics and performance of risk assessment scores for (recurrent) venous thromboembolism and discuss available data on risk assessment for bleeding and arterial thrombosis in the cancer population. This summary can help clinicians in daily practice to make a balanced decision when considering the use of risk assessment models for cancer-associated venous thromboembolism. Future research attempts should aim at improving risk assessment for arterial thrombosis and anticoagulant-related bleeding in cancer patients., Competing Interests: D.N.M. reports personal fees from Daiichi Sankyo, personal fees from Bayer, personal fees from Bristol Myers Squibb, personal fees from Aspen, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Pfizer, outside the submitted work., (Thieme. All rights reserved.)

Objective: To compare the effectiveness of single, multiple, and multifactorial interventions to prevent falls and fall-related fractures in community-dwelling older persons., Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) evaluating the effectiveness of fall prevention interventions in community-dwelling adults aged ≥65 years, from inception until February 27, 2019. Two large RCTs (published in 2020 after the search closed) were included in post hoc analyses. Pairwise meta-analysis and network meta-analysis (NMA) were conducted., Results: NMA including 192 studies revealed that the following single interventions, compared with usual care, were associated with reductions in number of fallers: exercise (risk ratio [RR] 0.83; 95% confidence interval [CI] 0.77-0.89) and quality improvement strategies (e.g., patient education) (RR 0.90; 95% CI 0.83-0.98). Exercise as a single intervention was associated with a reduction in falls rate (RR 0.79; 95% CI 0.73-0.86). Common components of multiple interventions significantly associated with a reduction in number of fallers and falls rate were exercise, assistive technology, environmental assessment and modifications, quality improvement strategies, and basic falls risk assessment (e.g., medication review). Multifactorial interventions were associated with a reduction in falls rate (RR 0.87; 95% CI 0.80-0.95), but not with a reduction in number of fallers (RR 0.95; 95% CI 0.89-1.01). The following single interventions, compared with usual care, were associated with reductions in number of fall-related fractures: basic falls risk assessment (RR 0.60; 95% CI 0.39-0.94) and exercise (RR 0.62; 95% CI 0.42-0.90)., Conclusions: In keeping with Tricco et al. (2017), several single and multiple fall prevention interventions are associated with fewer falls. In addition to Tricco, we observe a benefit at the NMA-level of some single interventions on preventing fall-related fractures., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Gastrointestinal bleeding frequently complicates anticoagulant therapy causing treatment discontinuation. Data to guide the decision regarding whether and when to resume anticoagulation based on the risks of thromboembolism and recurrent bleeding are scarce., Objectives: We aimed to retrospectively evaluate the incidence of these events after anticoagulant-related gastrointestinal bleeding and assess their relationship with timing of anticoagulation resumption., Methods: Patients hospitalized because of gastrointestinal bleeding during oral anticoagulation for any indication were eligible. All patients were followed up to 2 years after the index bleeding for recurrent major or clinically relevant non-major bleeding, venous or arterial thromboembolism, and mortality., Results: We included 948 patients hospitalized for gastrointestinal bleeding occurring during treatment with vitamin K antagonists (n = 531) or direct oral anticoagulants (n = 417). In time-dependent analysis, anticoagulant treatment was associated with a higher risk of recurrent clinically relevant bleeding (hazard ratio [HR] 1.55; 95% confidence interval [CI] 1.08-2.22), but lower risk of thromboembolism (HR 0.34; 95% CI 0.21-0.55), and death (HR 0.50; 95% CI 0.36-0.68). Previous bleeding, index major bleeding, and lower glomerular filtration rate were associated with a higher risk of recurrent bleeding. The incidence of recurrent bleeding increased after anticoagulation restart independently of timing of resumption., Conclusions: Anticoagulant treatment after gastrointestinal bleeding is associated with a lower risk of thromboembolism and death, but higher risk of recurrent bleeding. The latter seemed to be influenced by patient characteristics and less impacted by time of anticoagulation resumption., (© 2021 International Society on Thrombosis and Haemostasis.)

Background:  Splanchnic vein thrombosis (SVT) is a common complication in patients with liver cirrhosis. The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy for SVT in cirrhotic patients., Methods:  In this systematic review and meta-analysis, studies reporting on SVT recanalization and progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were searched in MEDLINE, EMBASE, and ClinicalTrial.gov up to December 2019. Pooled proportions and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated., Results:  A total of 1,475 patients were included in 26 studies (23 observational and 3 randomized controlled trials). In patients receiving anticoagulant therapy, SVT recanalization occurred in 68% (95% CI, 62-74; 571/842 patients; 22 studies), SVT progression in 6% (95% CI, 4-9; 25/748 patients; 22 studies), recurrent VTE in 10% (95% CI, 4-22; 48/399 patients; 7 studies), major bleeding in 6% (95% CI, 4-10; 58/785 patients; 18 studies), and overall mortality in 9% (95% CI, 6-14; 68/787 patients; 17 studies). Anticoagulant treatment was associated with higher SVT recanalization (RR 3.19; 95% CI, 1.42-7.17), lower thrombosis progression (RR 0.28; 95% CI, 0.15-0.52), major bleeding (RR 0.52; 95% CI, 0.28-0.97), and overall mortality (RR 0.42; 95% CI, 0.24-0.73) compared with no treatment., Conclusion:  Anticoagulant therapy seems to improve vein recanalization and to reduce SVT progression, major bleeding, and overall mortality in cirrhotic patients with SVT. The incidence of recurrent VTE during anticoagulation remains substantial., Competing Interests: E.V., N.R., O.C., E.P., M.S., A.D.G., and M.M. have nothing to disclose. M.D.N. reports personal fees from Bayer, Daiichi Sankyo, BMS-Pfizer, Leo Pharma, Sanofi, and Aspen, outside the submitted work; J.-C. G.-P. reports other (consulting) from W.L. Gore and Associates, Cook Medical, Shionogi, Vifor Pharma, grants from Conatus Pharmaceuticals, Theravance Biopharma, Novartis, Exalenz Bioscience, outside the submitted work; W.A. has received a research grant from Bayer to support a clinical study in patients with splanchnic vein thrombosis, received personal fees from Bayer, Boehringer Inghelheim, BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, and Portola, outside the submitted work., (Thieme. All rights reserved.)

Objective: To assess the efficacy of medication review as an isolated intervention and with several co-interventions for preventing hospital readmissions in older adults., Methods: Ovid MEDLINE, Embase, The Cochrane Central Register of Controlled Trials and CINAHL were searched for randomized controlled trials evaluating the effectiveness of medication review interventions with or without co-interventions to prevent hospital readmissions in hospitalized or recently discharged adults aged ≥65, until September 13, 2019. Included outcomes were "at least one all-cause hospital readmission within 30 days and at any time after discharge from the index admission.", Results: Twenty-five studies met the inclusion criteria. Of these, 11 studies (7,318 participants) contributed to the network meta-analysis (NMA) on all-cause hospital readmission within 30 days. Medication review in combination with (a) medication reconciliation and patient education (risk ratio (RR) 0.45; 95% confidence interval (CI) 0.26-0.80) and (b) medication reconciliation, patient education, professional education and transitional care (RR 0.64; 95% CI 0.49-0.84) were associated with a lower risk of all-cause hospital readmission compared to usual care. Medication review in isolation did not significantly influence hospital readmissions (RR 1.06; 95% CI 0.45-2.51). The NMA on all-cause hospital readmission at any time included 24 studies (11,677 participants). Medication review combined with medication reconciliation, patient education, professional education and transitional care resulted in a reduction of hospital readmissions (RR 0.82; 95% CI 0.74-0.91) compared to usual care. The quality of the studies included in this systematic review raised some concerns, mainly regarding allocation concealment, blinding and contamination., Conclusion: Medication review in combination with medication reconciliation, patient education, professional education and transitional care, was associated with a lower risk of hospital readmissions compared to usual care. An effect of medication review without co-interventions was not demonstrated. Trials of higher quality are needed in this field., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)