Occupational Risks of Radiation Exposure to Cardiologists.

PURPOSE OF REVIEW: Invasive cardiologists are exposed to large amounts of ionizing radiation. This review aims to summarize the main occupational risks in a radiation-exposed cardiology practice. RECENT FINDINGS: We carried out a literature review on the subject. The studies reviewed allowed us to list six main health risk categories possibly associated with radiation exposure among cardiologists: deoxyribonucleic acid (DNA) and biochemical damages; cancers; ocular manifestations; olfaction, vascular, and neuropsychological alterations; musculoskeletal problems; and reproductive risks. Our descriptive analysis demonstrates higher risks of DNA damage and lens opacities among radiation-exposed cardiology staff. Surveys and questionnaires have demonstrated a higher risk of musculoskeletal disease in exposed workers. Studies reported no difference in cancer frequency between radiation-exposed workers and controls. Changes in olfactory performance, neuropsychological aspects, and vascular changes have also been reported. Limited literature supports the security of continuing radiation-exposed work during pregnancy. Therefore, there is an urgent need to increase knowledge of the occupational risks of radiation exposure and to adopt technologies to reduce them.

Primary prevention of venous thromboembolism in ambulatory cancer patients: recent advances and practical implications.

Venous thromboembolism (VTE) is a common complication in ambulatory cancer patients receiving anticancer therapies. Many patient-, cancer- and treatment-related factors along with specific biomarkers can be associated with an increased risk of VTE in patients with cancer. Risk assessment models such as the Khorana score serve as valuable tools to aid in the identification of patients with cancer who are at high risk of VTE. Two randomized controlled trials have evaluated the efficacy of primary thromboprophylaxis with low-dose direct oral anticoagulants, apixaban and rivaroxaban, to reduce the risk of VTE in ambulatory patients with cancer who are at intermediate to high risk of VTE identified by the Khorana score. This narrative review summarizes the literature on the risk factors and risk assessment process for VTE and the use of primary thromboprophylaxis in ambulatory cancer patients. We also outline important practical considerations for initiating primary thromboprophylaxis in this population.

Prognostic Factors Associated with Venous Thromboembolism Following Traumatic Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Trauma patients are at increased risk of venous thromboembolism (VTE), including deep venous thrombosis (DVT) and/or pulmonary embolism (PE). We conducted a systematic review and meta-analysis summarizing the association between prognostic factors and the occurrence of VTE following traumatic injury. METHODS: We searched the EMBASE and MEDLINE databases from inception to August 2023. We identified studies reporting confounding adjusted associations between patient, injury or post-injury care factors and risk of VTE. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS tool. RESULTS: We included 31 studies involving 1,981,946 patients. Studies were predominantly observational cohorts from North America. Factors with moderate or higher certainty of association with increased risk of VTE include older age, obesity, male sex, higher injury severity score, pelvic injury, lower extremity injury, spinal injury, delayed VTE prophylaxis, need for surgery and tranexamic acid use. After accounting for other important contributing prognostic variables, a delay in the delivery of appropriate pharmacologic prophylaxis for as little as 24 to 48 hours independently confers a clinically meaningful two-fold increase in incidence of VTE. CONCLUSION: These findings highlight the contribution of patient predisposition, the importance of injury pattern, and the impact of potentially modifiable post-injury care on risk of VTE after traumatic injury. These factors should be incorporated into a risk stratification framework to individualize VTE risk assessment and support clinical and academic efforts reduce thromboembolic events among trauma patients.Study TypeSystematic Review & Meta-Analysis. LEVEL OF EVIDENCE: Level II.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

BACKGROUND: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. OBJECTIVES: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. PATIENTS/METHODS: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. RESULTS: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). CONCLUSION: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer.

BACKGROUND: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. OBJECTIVES: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. METHODS: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. RESULTS: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. CONCLUSIONS: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.

Incidence and predictors of post-thrombotic syndrome in patients with proximal DVT in a real-world setting: findings from the GARFIELD-VTE registry.

Although substantial progress has been made in the pathophysiology and management of the post-thrombotic syndrome (PTS), several aspects still need clarification. Among them, the incidence and severity of PTS in the real world, the risk factors for its development, the value of patient's self-evaluation, and the ability to identify patients at risk for severe PTS. Eligible participants (n = 1107) with proximal deep-vein thrombosis (DVT) from the global GARFIELD-VTE registry underwent conventional physician's evaluation for PTS 36 months after diagnosis of their DVT using the Villalta score. In addition, 856 patients completed a Villalta questionnaire at 24 months. Variable selection was performed using stepwise algorithm, and predictors of severe PTS were incorporated into a multivariable risk model. The optimistic adjusted c-index was calculated using bootstrapping techniques. Over 36-months, 27.8% of patients developed incident PTS (mild in 18.7%, moderate in 5.7%, severe in 3.4%). Patients with incident PTS were older, had a lower prevalence of transient risk factors of DVT and a higher prevalence of persistent risk factors of DVT. Self-assessment of overall PTS at 24 months showed an agreement of 63.4% with respect to physician's evaluations at 36 months. The severe PTS multivariable model provided an optimistic adjusted c-index of 0.68 (95% CI 0.59-0.77). Approximately a quarter of DVT patients experienced PTS over 36 months after VTE diagnosis. Patient's self-assessment after 24 months provided added value for estimating incident PTS over 36 months. Multivariable risk analysis allowed good discrimination for severe PTS.

Management of catheter-related upper extremity deep vein thrombosis in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer commonly require a central venous catheter, which is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding in patients with cancer and catheter-related upper extremity DVT. METHODS: We searched MEDLINE, Embase, Scopus, and CENTRAL from inception to June 2, 2023. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates (with 95% CI) of outcomes were pooled using random effects model. RESULTS: We included 29 studies (N = 2,836), among which 5 were prospective. The duration of follow-up and anticoagulation varied considerably. The main long-term anticoagulant used was low molecular weight heparin, followed by direct oral anticoagulants. The pooled 3-month recurrent VTE rate from 14 studies (N = 1,128) was 0.56% (95% CI, 0.10%-3.01%; I2 = 0%). The pooled 3-month major bleeding rate from 10 studies (N = 834) was 2.34% (95% CI, 1.14%-4.76%; I2 = 0%). We were unable to pool event rates beyond 3 months, given high heterogeneity. All studies had serious risk of bias. CONCLUSIONS: Our study demonstrated a relatively low rate of recurrent VTE and moderate rate of major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

INTRODUCTION: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes. METHODS AND ANALYSIS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques. ETHICS AND DISSEMINATION: This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting. TRAIL REGULATIONS: Registration ID with Open Science Framework: osf.io/zp4ge.

Comparing U.S. and Canadian treatment patterns on venous thromboembolism outcomes in the GARFIELD-VTE registry.

BACKGROUND: Economically developed countries continue to find that venous thromboembolism (VTE) is a major cause of morbidity and mortality. OBJECTIVE: To compare baseline risk profiles and patient workflow patterns between the United States (U.S.) and Canadian management of VTE patients from 2014 to 2017. METHODS: The Global Anticoagulant Registry in the FIELD (GARFIELD-VTE) is a prospective, observational study of 10,679 patients with objectively confirmed VTE, followed for 3 years. In total 1101 patients enrolled in the U.S. and Canada were included in this analysis. RESULTS: Median age and body mass index were comparable between the U.S. (60.5; 30.2) and Canadian (59.7; 29) patients. A higher percentage of U.S. patients were black (n = 128, 24.1 %; n = 22, 3.9 %) and had a higher VTE-associated risk profile, including immobilization, hospitalization, and recent surgery. U.S. patients had a higher combined DVT and PE primary diagnoses (20.3 %) and were more likely to be treated in hospitals (77.2 %) than Canadians (13.3 %; 48.1 %). Direct oral anticoagulant therapy (DOAC) was nearly two-fold more frequent in Canadian patients (n = 218, 39.2 %) at the end of 3 years in comparison to the U.S. (n = 118, 23.0 %). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, the risk of all-cause mortality was 51.9 % higher in patients from the U.S. compared to those in Canada after 3 years. Patients from the U.S. also had a higher likelihood of hospitalization, major bleeding, and recurrent VTE after controlling for prior history and comorbid conditions. CONCLUSION: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies. TYPE OF RESEARCH: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). KEY FINDINGS: 531 U.S. and 557 Canadians patients included in study. DOAC use more frequent in Canadian patients after 3 years than U.S. (39.2 % vs. 23.0 %, respectively). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, all-cause mortality risk remained higher in U.S. patients vs. Canadian patients after 3 years. U.S. patients had higher likelihood of hospitalization, major bleeding, and recurrent VTE. TAKE-HOME MESSAGE: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and composition of specialists and their subsequent treatment strategies. TABLE OF CONTENTS SUMMARY: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). Higher rates of adverse VTE-associated outcomes were observed in U.S. patients vs Canadian patients, which may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies.

Previous Ischemic Stroke Significantly Alters Stroke Risk in Newly Diagnosed Cancer Patients.

BACKGROUND: Previous ischemic stroke (IS) is a risk factor for subsequent IS in the general population; it is unclear if this relationship remains true in patients with cancer. Our objective was to examine the association between previous IS and risk for future IS in individuals newly diagnosed with cancer. METHODS: We conducted a retrospective population-based matched cohort study of newly diagnosed adult cancer patients (excluding nonmelanoma skin cancers and primary central nervous system tumors) in Ontario, Canada from 2010 to 2020; those with prior IS were matched (1:4) by age, sex, year of cancer diagnosis, cancer stage, and cancer site to those without a history of stroke. Cumulative incidence function curves were created to estimate the incidence of IS. Subdistribution adjusted hazard ratios (aHRs) and 95% CIs were calculated, where death was treated as a competing event. Multivariable analysis was adjusted for imbalanced baseline characteristics. RESULTS: We examined 65 525 individuals with cancer, including 13 070 with a history of IS. The median follow-up duration was 743 days (interquartile range, 177-1729 days). The incidence of IS following cancer diagnosis was 261.3/10 000 person-years in the cohort with prior IS and 75.3/10 000 person-years in those without prior IS. Individuals with prior IS had an increased risk for IS after cancer diagnosis compared with those without a history (aHR, 2.68 [95% CI, 2.41-2.98]); they also had more prevalent cardiovascular risk factors. The highest risk for stroke compared with those without a history of IS was observed in the gynecologic cancer (aHR, 3.84 [95% CI, 2.15-6.85]) and lung cancer (aHR, 3.18 [95% CI, 2.52-4.02]) subgroups. The risk of IS was inversely correlated with lag time of previous stroke; those with IS 1 year before their cancer diagnosis had the highest risk (aHR, 3.68 [95% CI, 3.22-4.22]). CONCLUSIONS: Among individuals with newly diagnosed cancer, those with IS history were almost 3× more likely to experience a stroke after cancer diagnosis, especially if the prediagnosis stroke occurred within 1 year preceding cancer diagnosis.

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies.

BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

Inflammasome Signaling, Thromboinflammation, and Venous Thromboembolism.

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-1ß 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.

Serial D-dimers after anticoagulant cessation in unprovoked venous thromboembolism: Data from the REVERSE cohort study.

INTRODUCTION: While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation. METHODS: Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles. RESULTS: Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9-2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1-2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4-5.6) among patients in the lowest ∆D-dimer quartile. CONCLUSION: Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.

Anticoagulation for the Prevention of Arterial Thrombosis in Ambulatory Cancer Patients: Systematic Review and Meta-Analysis.

Background: The risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs. Objectives: This study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients. Methods: We performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality. Results: Fourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P = 0.08; I2 = 0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P = 0.38; I2 = 0%). Conclusions: Anticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.