ABSTRACT

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

PMID:37489755 | DOI:10.1161/JAHA.123.029618

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PubMed articles on: Cancer & VTE/PE

Role of Intravascular Ultrasound in Pulmonary Embolism Patients Undergoing Mechanical Thrombectomy: A Systematic Review

Tomography. 2023 Jul 14;9(4):1393-1407. doi: 10.3390/tomography9040111.

ABSTRACT

BACKGROUND: Traditionally, mechanical thrombectomy performed for pulmonary embolism (PE) necessitates the utilization of iodinated contrast. Intravascular ultrasound (IVUS) has been used as a diagnostic and therapeutic modality in the management of acute high and intermediate-risk PE. Recently, with the shortage of contrast supplies and the considerable incidence of contrast-induced acute kidney injury (CI-AKI), other safer and more feasible IVUS methods have become desirable. The purpose of this systematic review was to evaluate the importance of IVUS in patients with PE undergoing thrombectomy.

METHODS: Medline/PubMed, Embase, Scopus, and Google Scholar were searched for review studies, case reports, and case series. Clinical characteristics, outcomes and the usage of IVUS-guided mechanical thrombectomy during the treatment of acute high and intermediate-risk PE were examined in a descriptive analysis.

RESULTS: In this systematic review, we included one prospective study, two case series, and two case reports from July 2019 to May 2023. A total of 39 patients were evaluated; most were female (53.8%). The main presenting symptoms were dyspnea and chest pain (79.5%); three patients (7.9%) presented with syncope, one with shock and one with cardiac arrest. Biomarkers (troponin and BNP) were elevated in 94.6% of patients. Most patients (87.2%) had intermediate-risk PE, and 12.8% had high-risk PE. All patients presented with right-heart strain (RV/LV ratio ≥ 0.9, n= 39). Most patients (56.4%) had bilateral PE. Mechanical thrombectomy was performed using IVUS without contrast utilization in 39.4% of the patients. After the initial learning curve, contrast usage decreased gradually over time. There was a significant decrease in the composite mean arterial pressure immediately following IVUS-guided thrombectomy from 35.1 ± 7.2 to 25.2 ± 8.3 mmHg (p < 0.001). Post-procedure, there was no reported (0%) CI-AKI, no all-cause mortality, no major bleeding, or other adverse events. There was a significant improvement in symptoms and RV function at the mean follow-up.

CONCLUSIONS: New evidence suggests that IVUS-guided mechanical thrombectomy is safe, with visualization of the thrombus for optimal intervention, and reduces contrast exposure.

PMID:37489479 | PMC:PMC10366920 | DOI:10.3390/tomography9040111

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PubMed articles on: Cancer & VTE/PE

Incidence and Risk Factors of Venous Thromboembolism in Patients with Lung Adenocarcinoma Receiving Anti-tumor Therapy

Zhongguo Fei Ai Za Zhi. 2023 Jun 20;26(6):439-448. doi: 10.3779/j.issn.1009-3419.2023.102.22.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE.

METHODS: The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test.

RESULTS: The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05).

CONCLUSIONS: History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence. .

PMID:37488081 | PMC:PMC10365962 | DOI:10.3779/j.issn.1009-3419.2023.102.22

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PubMed articles on: Cancer & VTE/PE

Recommendations for thromboembolic disease in oncological processes. A view from primary care

Semergen. 2023 Jul 22;49(7):102030. doi: 10.1016/j.semerg.2023.102030. Online ahead of print.

ABSTRACT

Venous thromboembolic disease (VTE) is a frequent complication in patients diagnosed with cancer and a cause of morbidity and mortality. Approximately 20% of thromboembolic episodes develop in association with active cancer. On the other hand, it is estimated that about 2-12% of cases, the thromboembolic episode is the first manifestation of an occult cancer, diagnosed at that time or subsequently, which offers an opportunity for early diagnosis and treatment. There are multiple factors that contribute to increase the risk of VTE in oncological patients in relation to specific characteristics of the patient, the tumor and the treatments. Knowledge of these risk factors will contribute to early diagnosis when signs of VTE appear, as well as the assessment of thromboprophylaxis if indicated. The diagnosis of VTE in patients with cancer does not differ of those who do not suffer from it. Regarding the treatment of VTE in these patients, low molecular weight heparin (LMWH), direct acting anticoagulants (DACs) and antivitamin K (VKA) are the most commonly used, although the dosing regimen and length are not clear yet. The management of these patients should be interdisciplinary and early, so the primary care physician plays a key role in this process as he/she is liaise with his/her patients. It is also necessary to update knowledge in order to improve the care of these patients. For these reasons, this document has been prepared by the Working Group on Vasculopathies of the Spanish Society of Primary Care Physicians (SEMERGEN) whose objective is to present the available information regarding the management of VTE that may appear in oncological patients, as well as the assessment of thromboprophylaxis and treatment, if appropriate, from an approach focused on a primary care field.

PMID:37487423 | DOI:10.1016/j.semerg.2023.102030

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PubMed articles on: Cancer & VTE/PE

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis

JAMA Netw Open. 2023 Jul 3;6(7):e2325283. doi: 10.1001/jamanetworkopen.2023.25283.

ABSTRACT

IMPORTANCE: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored.

OBJECTIVES: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021.

EXPOSURES: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin.

MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs.

RESULTS: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

PMID:37486628 | PMC:PMC10366701 | DOI:10.1001/jamanetworkopen.2023.25283

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PubMed articles on: Cancer & VTE/PE

Clinical outcome of open ankle fractures in patients above 70 years of age

World J Orthop. 2023 Jul 18;14(7):554-561. doi: 10.5312/wjo.v14.i7.554. eCollection 2023 Jul 18.

ABSTRACT

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal.

AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes.

METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed.

RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n= 30 females median age: 84 years, range: 70-97); n= 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P= 0.008, stroke P= 0.001, length of stay > 33 d P= 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P= 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P< 0.001, number of operations P< 0.001, diabetes P= 0.041).

CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

PMID:37485433 | PMC:PMC10359747 | DOI:10.5312/wjo.v14.i7.554

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PubMed articles on: Cancer & VTE/PE

Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery

Clin Spine Surg. 2023 Jul 24. doi: 10.1097/BSD.0000000000001498. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort study.

OBJECTIVES: Venous thromboembolism (VTE) is a potentially high-risk complication for patients undergoing spine surgery. Although guidelines for assessing VTE risk in this population have been established, development of new techniques that target different aspects of the medical history may prove to be of further utility. The goal of this study was to develop a predictive machine learning (ML) model to identify nontraditional risk factors for predicting VTE in spine surgery patients.

SUMMARY OF BACKGROUND DATA: A cohort of 63 patients was identified who had undergone spine surgery at a single center from 2015 to 2021. Thirty-one patients had a confirmed VTE, while 32 had no VTE. A total of 113 attributes were defined and collected via chart review. Attribute categories included demographics, medications, labs, past medical history, operative history, and VTE diagnosis.

METHODS: The Waikato Environment for Knowledge Analysis (WEKA) software was used in creating and evaluating the ML models. Six classifier models were tested with 10-fold cross-validation and statistically evaluated using t tests.

RESULTS: Comparing the predictive ML models to the control model (ZeroR), all predictive models were significantly better than the control model at predicting VTE risk, based on the 113 attributes (P<0.001).

CONCLUSION: Further development of these tools may provide high diagnostic value and may guide chemoprophylaxis treatment in this setting of high-risk patients.

PMID:37482644 | DOI:10.1097/BSD.0000000000001498

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PubMed articles on: Cancer & VTE/PE

Automated detection and segmentation of pulmonary embolisms on computed tomography pulmonary angiography (CTPA) using deep learning but without manual outlining

Med Image Anal. 2023 Jul 14;89:102882. doi: 10.1016/j.media.2023.102882. Online ahead of print.

ABSTRACT

We present a novel computer algorithm to automatically detect and segment pulmonary embolisms (PEs) on computed tomography pulmonary angiography (CTPA). This algorithm is based on deep learning but does not require manual outlines of the PE regions. Given a CTPA scan, both intra- and extra-pulmonary arteries were firstly segmented. The arteries were then partitioned into several parts based on size (radius). Adaptive thresholding and constrained morphological operations were used to identify suspicious PE regions within each part. The confidence of a suspicious region to be PE was scored based on its contrast in the arteries. This approach was applied to the publicly available RSNA Pulmonary Embolism CT Dataset (RSNA-PE) to identify three-dimensional (3-D) PE negative and positive image patches, which were used to train a 3-D Recurrent Residual U-Net (R2-Unet) to automatically segment PE. The feasibility of this computer algorithm was validated on an independent test set consisting of 91 CTPA scans acquired from a different medical institute, where the PE regions were manually located and outlined by a thoracic radiologist (>18 years' experience). An R2-Unet model was also trained and validated on the manual outlines using a 5-fold cross-validation method. The CNN model trained on the high-confident PE regions showed a Dice coefficient of 0.676±0.168 and a false positive rate of 1.86 per CT scan, while the CNN model trained on the manual outlines demonstrated a Dice coefficient of 0.647±0.192 and a false positive rate of 4.20 per CT scan. The former model performed significantly better than the latter model (p<0.01).

PMID:37482032 | DOI:10.1016/j.media.2023.102882

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PubMed articles on: Cancer & VTE/PE

Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study

J Thromb Haemost. 2023 Jul 20:S1538-7836(23)00571-8. doi: 10.1016/j.jtha.2023.07.009. Online ahead of print.

ABSTRACT

BACKGROUND: Guidelines recommend thromboprophylaxis for cancer patients at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction, but have not yet been evaluated in cancer patients.

METHODS: We assessed the performance of the 5-SNP, 37-SNP, 297-SNP, extended 297-SNP (additionally including factor V Leiden and prothrombin G20210A), and 100-SNP scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios (SHR) in the upper vs three lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification.

FINDINGS: Of 36,150 cancer patients (median age, 66 years; 48.7% females), 1,018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95%CI, 0.54-0.58) for the 5-SNP to 0.60 (95%CI, 0.58-0.62) for the extended 297-SNP scores. SHRs ranged from 1.36 (95%CI, 1.19-1.56) for the 5-SNP to 1.90 (95%CI, 1.68-2.16) for the extended 297-SNP scores, and were consistent after adjusting for cancer type. For the Khorana cancer type classification the c-index was 0.60 (95%CI, 0.58-0.61), which increased to 0.65 (95%CI, 0.63-0.67; +0.05, 95%CI, 0.04-0.07) when combined with the extended 297-SNP score.

INTERPRETATION: These findings demonstrate that polygenic VTE risk scores can identify cancer patients with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.

PMID:37481074 | DOI:10.1016/j.jtha.2023.07.009

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PubMed articles on: Cancer & VTE/PE

Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients

Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.

ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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PubMed articles on: Cancer & VTE/PE

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Curr Res Transl Med. 2023 Jul 13;71(3):103405. doi: 10.1016/j.retram.2023.103405. Online ahead of print.