ABSTRACT

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE.

METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding).

FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001).

IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

PMID:37838562 | DOI:10.1016/j.clinthera.2023.09.014

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PubMed articles on: Cancer & VTE/PE

Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study

J Thromb Thrombolysis. 2023 Oct 15. doi: 10.1007/s11239-023-02903-w. Online ahead of print.

ABSTRACT

Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q test, "Leave-one-out," and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998-1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, - 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE. Causal effect of atrial fibrillation on pulmonary embolism: a Mendelian randomization study. AF atrial fibrillation, PE pulmonary embolism, GWAS genome-wide association studies, SNPs single nucleotide polymorphisms, OR odds ratio, CI confidence interval.

PMID:37839022 | DOI:10.1007/s11239-023-02903-w

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PubMed articles on: Cancer & VTE/PE

Concomitant Cerebral Venous Thrombosis and Intracranial Hemorrhages in Presentation of a Patient with Secondary Polycythemia: A Case Report

Am J Case Rep. 2023 Oct 15;24:e941507. doi: 10.12659/AJCR.941507.

 

ABSTRACT

OBJECTIVES: Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity.

MATERIALS AND METHODS: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured.

RESULTS: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB.

CONCLUSION: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.

PMID:37885998 | PMC:PMC10598814 | DOI:10.22038/IJBMS.2023.70997.15422

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PubMed articles on: Cancer & VTE/PE

Clinical Care of Pediatric Patients with or At-Risk of Post-Thrombotic Syndrome: Guidance from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Haemostasis

J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00780-8. doi: 10.1016/j.jtha.2023.10.012. Online ahead of print.

NO ABSTRACT

PMID:37866514 | DOI:10.1016/j.jtha.2023.10.012

19:49

PubMed articles on: Cancer & VTE/PE

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

Thromb Res. 2023 Oct 11;231:128-134. doi: 10.1016/j.thromres.2023.10.004. Online ahead of print.

ABSTRACT

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.

PMID:37857226 | DOI:10.1016/j.thromres.2023.10.004

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PubMed articles on: Cancer & VTE/PE

Intensify Standardized Anticoagulation for Cancer-Associated Pulmonary Embolism: From Single-Center Real-World Data

Clin Ther. 2023 Oct 12:S0149-2918(23)00378-8. doi: 10.1016/j.clinthera.2023.09.014. Online ahead of print.

 

ABSTRACT

This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.

PMID:37844585 | PMC:PMC10586005 | DOI:10.1177/10760296231206799

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PubMed articles on: Cancer & VTE/PE

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism

Res Synth Methods. 2023 Oct 17. doi: 10.1002/jrsm.1676. Online ahead of print.

ABSTRACT

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

PMID:37846195 | DOI:10.1002/jrsm.1676

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PubMed articles on: Cardio-Oncology

Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity

Iran J Basic Med Sci. 2023;26(11):1298-1304. doi: 10.22038/IJBMS.2023.70997.15422.

 

ABSTRACT

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient's cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases.

PMID:37886969 | PMC:PMC10605822 | DOI:10.3390/cimb45100526

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PubMed articles on: Cancer & VTE/PE

Comparison of Direct Oral Anticoagulants versus Low Molecular Weight Heparin in Primary and Metastatic Brain Cancers: A Meta-Analysis and Systematic Review

J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.

ABSTRACT

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.

OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.

METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.

RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants.

DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

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PubMed articles on: Cancer & VTE/PE

Catheter Directed Thrombectomy and Other Deep Venous Interventions in Cancer Patients

Tech Vasc Interv Radiol. 2023 Jun;26(2):100900. doi: 10.1016/j.tvir.2023.100900. Epub 2023 Aug 5.

ABSTRACT

Treating cancer patients with deep venous thrombosis/venous thromboembolism (DVT/VTE) can be challenging as patients are frequently unable to receive the standard therapy of anticoagulation due to the increased risk of bleeding complications seen in this population. Similarly, the hesitation of interventionalists to use thrombolytic agents due to bleeding risks limits percutaneous intervention options as well. Further, outcome data and guidelines do not exist for oncologic patients and often treatment is tailored to patient-specific factors after multidisciplinary discussion. This article reviews specific factors to consider when planning percutaneous treatment of cancer patients with DVT/VTE, focusing on the iliocaval system.

PMID:37865450 | DOI:10.1016/j.tvir.2023.100900

19:49

PubMed articles on: Cancer & VTE/PE

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231206799. doi: 10.1177/10760296231206799.

 

ABSTRACT

Non-bacterial thrombotic endocarditis (NBTE) involves the deposition of fibrin and platelets on heart valves, frequently leading to systemic embolism. The association between NBTE and cancer demands thorough investigation in cases lacking an evident cause. This case report elucidates the clinical course of a nonsmoking woman in her sixties with NBTE linked to pulmonary adenocarcinoma. The patient, who had a history of multiple sclerosis (MS) and was receiving dimethyl fumarate treatment, presented to the emergency department with stroke-like symptoms. Diagnostic challenges arose due to preexisting motor sensory impairment from MS. Initial evaluations revealed hypocapnia and elevated inflammatory markers. Blood cultures were obtained twice, and imaging confirmed pneumonia, left pleural effusion, and chronic pulmonary embolism while excluding acute vascular events or intracranial hemorrhage. The first transthoracic echocardiogram (TTE) indicated no cardiac abnormalities. Treatment encompassed parenteral antibiotics, systemic anticoagulation, and admission to medical floors. Although the initial treatment yielded a positive clinical response, subsequent complications emerged. On the tenth day, the patient required additional interventions, including broad-spectrum antibiotics and supplemental oxygen. A follow-up chest X-ray revealed persistent pneumonia and pleural effusion, and blood cultures upon admission returned negative. A subsequent head MRI confirmed an embolic stroke and displayed evidence of MS progression. Around the twentieth day, empirical treatment for infective endocarditis was initiated, and an 8 mm vegetation on the aortic valve was identified via transesophageal echocardiography (TOE). Acute pulmonary edema prompted a transfer to the intermediate care unit. Further investigations, including left thoracocentesis and CT, unveiled exudate and metastatic lesions in the liver, ilium, and kidney. Unfortunately, on the twenty-fifth day, the patient experienced acute myocardial infarction, right leg ischemia, disseminated intravascular coagulation, and shock. Pleural fluid analysis revealed malignant cells suggestive of lung adenocarcinoma. This case underscores the pivotal role of timely NBTE recognition and the search for malignancy when workup for infective endocarditis and autoimmune panels is negative. Moreover, it emphasizes the significance of vigilant monitoring, particularly in immunocompromised individuals or those with preexisting neurological deficits, especially when new neurological symptoms manifest. These insights significantly contribute to the comprehension of NBTE management and its implications for analogous patient cohorts.

PMID:37846253 | PMC:PMC10576842 | DOI:10.7759/cureus.45271

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PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Front Pharmacol. 2023 Oct 4;14:1263975. doi: 10.3389/fphar.2023.1263975. eCollection 2023.

ABSTRACT

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

PMID:37860116 | PMC:PMC10582335 | DOI:10.3389/fphar.2023.1263975

19:49

PubMed articles on: Cardio-Oncology

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine

Curr Issues Mol Biol. 2023 Oct 15;45(10):8337-8358. doi: 10.3390/cimb45100526.

 

ABSTRACT

Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100 K/μL at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio (SHR) 2.4, P=0.02) and CRNMB (17.9% vs. 9.6%, SHR 2.0, P=0.01). Thrombocytopenia did not impact recurrent VTE (9.8% vs. 7.4%, SHR 1.3, P=0.37) nor overall mortality (21.8% vs. 26.0%, HR 0.9, P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs 0, p.

PMID:37855029 | DOI:10.3324/haematol.2023.284192

19:49

PubMed articles on: Cardio-Oncology

Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy

Curr Oncol. 2023 Oct 6;30(10):9049-9062. doi: 10.3390/curroncol30100654.

ABSTRACT

Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab-pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.

PMID:37887554 | PMC:PMC10605836 | DOI:10.3390/curroncol30100654

19:49

PubMed articles on: Cancer & VTE/PE

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study

Eur J Intern Med. 2023 Oct 16:S0953-6205(23)00369-2. doi: 10.1016/j.ejim.2023.10.014. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking.

OBJECTIVES: We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment.

PATIENTS/METHODS: Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study.

RESULTS: In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]).

CONCLUSIONS: Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.

PMID:37852838 | DOI:10.1016/j.ejim.2023.10.014

19:49

PubMed articles on: Cancer & VTE/PE

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign

Cureus. 2023 Sep 14;15(9):e45271. doi: 10.7759/cureus.45271. eCollection 2023 Sep.

 

ABSTRACT

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

PMID:37887865 | PMC:PMC10607871 | DOI:10.3390/jcdd10100418

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PubMed articles on: Cancer & VTE/PE

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer

Haematologica. 2023 Oct 19:0. doi: 10.3324/haematol.2023.284192. Online ahead of print.

 

ABSTRACT

Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.

PMID:37889357 | DOI:10.1007/s10565-023-09835-4

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PubMed articles on: Cardio-Oncology

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study

J Cardiovasc Dev Dis. 2023 Oct 4;10(10):418. doi: 10.3390/jcdd10100418.

 

ABSTRACT

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.

PMID:37890926 | DOI:10.1016/bs.mcb.2023.02.014

19:49

PubMed articles on: Cardio-Oncology

Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity

Cell Biol Toxicol. 2023 Oct 27. doi: 10.1007/s10565-023-09835-4. Online ahead of print.

 

ABSTRACT

BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE).

METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database.

RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs).

CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.

PMID:37882319 | DOI:10.1002/cam4.6626

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PubMed articles on: Cardio-Oncology

Cardiovascular Impact of Near Complete Estrogen Deprivation in Premenopausal Women with Breast Cancer: The CROWN Study

Am Heart J. 2023 Oct 25:S0002-8703(23)00300-9. doi: 10.1016/j.ahj.2023.10.007. Online ahead of print.

ABSTRACT

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

PMID:37890547 | DOI:10.1016/j.ahj.2023.10.007

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PubMed articles on: Cardio-Oncology

Methods to assess radiation-induced cardiotoxicity in rodent models

Methods Cell Biol. 2023;180:127-146. doi: 10.1016/bs.mcb.2023.02.014. Epub 2023 Apr 24.

 

ABSTRACT

OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.

DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.

SETTING: PICUs within U.S. CHAT Consortium participating centers.

PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.

CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.

PMID:37882641 | DOI:10.1097/PCC.0000000000003383

19:49

PubMed articles on: Cancer & VTE/PE

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study

Cancer Med. 2023 Oct 26. doi: 10.1002/cam4.6626. Online ahead of print.

 

ABSTRACT

BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.

PMID:37872733 | DOI:10.12659/AJCR.941360

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PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium

Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.

 

ABSTRACT

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

PMID:37892201 | PMC:PMC10604821 | DOI:10.3390/biom13101519

19:48

PubMed articles on: Cancer & VTE/PE

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury

Am J Case Rep. 2023 Oct 24;24:e941360. doi: 10.12659/AJCR.941360.

 

ABSTRACT

BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated.

METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions.

RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples.

CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors.

TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

PMID:37891699 | DOI:10.1186/s40959-023-00179-w

19:48

PubMed articles on: Cardio-Oncology

Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases

Biomolecules. 2023 Oct 13;13(10):1519. doi: 10.3390/biom13101519.

 

ABSTRACT

D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), to evaluate the risk of VTE recurrence as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, spanning from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals presenting with increased Ddimer without signs or symptoms of thrombus formation. To the management of these cases by the hematologist is dedicated this narrative review.

PMID:37881856 | DOI:10.3324/haematol.2023.283966

19:48

PubMed articles on: Cardio-Oncology

Simplified rules-based tool to facilitate the application of up-to-date management recommendations in cardio-oncology

Cardiooncology. 2023 Oct 27;9(1):37. doi: 10.1186/s40959-023-00179-w.

 

ABSTRACT

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

PMID:37892623 | PMC:PMC10607346 | DOI:10.3390/jcm12206486

19:48

PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients

Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.

ABSTRACT

OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.

RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.

RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.

CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.

PMID:37883026 | DOI:10.1080/17474086.2023.2276209

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PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism

AORN J. 2023 Nov;118(5):321-328. doi: 10.1002/aorn.14019.

ABSTRACT

Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.

PMID:37882602 | DOI:10.1002/aorn.14019

19:48

PubMed articles on: Cancer & VTE/PE

How we manage a high D-dimer

Haematologica. 2023 Oct 26. doi: 10.3324/haematol.2023.283966. Online ahead of print.

 

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in lung cancer patients undergoing thoracic surgery. We examined the risk and timing of VTE following surgery for primary non-small cell lung cancer (NSCLC).

METHODS: in the Danish Lung Cancer Registry. VTE events in the year after surgery were assessed by stage, patient characteristics, and surgical procedure.

RESULTS: We identified 13,197 patients who underwent surgery for NSCLC in 2003-2021 (mean age 67.6 years, 50% female); 10,524 (79.7%) had stage I-II NSCLS and 2673 (20.3%) had stage III-IV. During one-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I versus 4.1% for stage IV), but varied little by pathological type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%, 95% CI 3.2-6.9), followed by pneumonectomy (3.6%, 95% CI 2.5-5.1). The hazard of VTE was highest during the first three months after surgery, whereafter it declined. For stage IV cancer hazards increased again after six months. At one-year, all-cause death was 12.6% (95% CI: 12.0-13.1 %).

CONCLUSIONS: Among patients undergoing surgery for NSCLC, 3.3% developed VTE, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.

PMID:37890818 | DOI:10.1016/j.athoracsur.2023.10.015

19:48

PubMed articles on: Cancer & VTE/PE

A Novel Model to Prevent Venous Thromboembolism in Patients with Lung Cancer

Altern Ther Health Med. 2023 Oct 27:AT9245. Online ahead of print.

ABSTRACT

OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer patients with carboplatin and gemcitabine chemotherapy after peripheral venipuncture central venous catheterization (PICC).

METHODS: 100 patients with lung cancer admitted to the 2nd Affiliated Hospital of Hainan Medical University from April 2020 to April 2022 were selected. All patients received a combination chemotherapy of carboplatin and gemcitabine and PICC catheterization. The patients were divided into an observation group and a control group by 1:1 simple random method, with 50 cases in each group. Patients in the control group were given routine nursing for lung cancer, and patients in the observation group were treated with nurse-patient co-management mode, and nursing intervention lasted for 2 months. General Comfort Questionnaire, self-management ability, quality of life, Self-care ability Scale, self-rating Anxiety Scale (SAS), and self-rating depression Scale were compared before and after intervention between the two groups. The recovery of immune ability indices (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) in 2 groups were detected. Complications after PICC catheterization were recorded in the two groups.

RESULTS: After nursing, self-rating depression Scale and self-rating Anxiety Scale scores in both groups were significantly decreased, which were lower in the observation group than the control group (P < .001). After nursing, scores of self-concept, self-responsibility, self-care skills, and health knowledge level were significantly increased in both groups, which were higher in the observation group than control group (P < .001). After nursing, scores on the General Comfort Questionnaire, self-management scale, and quality of life were increased in both groups, which were higher in the observation group than control group (P < .0501). After nursing care, the immune competence indices of both patients increased significantly, and the immune indexes of CD3+, CD3+CD4+, and CD3+ CD4+/CD3+CD8+ in the observation group were significantly higher than those in the control group (P < .05). The total incidence of complications in the observation group was significantly lower than that in the control group (8.00% vs. 26.00%, P < .001), and the incidence of venous thromboembolism was significantly lower than that in the control group (2.00% vs. 14.00%, P < .001).

CONCLUSION: The nurse-patient co-management model has shown to be effective in reducing the incidence of venous thromboembolism in patients who have undergone PICC catheterization while receiving carboplatin and gemcitabine chemotherapy. This model also helps patients improve their self-care and self-management abilities, alleviates adverse psychological effects, and contributes to the recovery of their immune system.

PMID:37883756

19:48

PubMed articles on: Cardio-Oncology

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

J Clin Med. 2023 Oct 12;12(20):6486. doi: 10.3390/jcm12206486.

 

ABSTRACT

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

PMID:37893193 | PMC:PMC10604204 | DOI:10.3390/biomedicines11102820

19:48

PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study

Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.

 

ABSTRACT

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.

PMID:37898967 | DOI:10.1007/s11739-023-03426-1

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PubMed articles on: Cardio-Oncology

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Cancers (Basel). 2023 Oct 18;15(20):5036. doi: 10.3390/cancers15205036.

ABSTRACT

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

PMID:37894403 | PMC:PMC10605752 | DOI:10.3390/cancers15205036

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PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.

ABSTRACT

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.

PMID:37893585 | DOI:10.3390/medicina59101867

19:48

PubMed articles on: Cardio-Oncology

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Biomedicines. 2023 Oct 18;11(10):2820. doi: 10.3390/biomedicines11102820.

 

ABSTRACT

We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient's DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma.

PMID:37900811 | PMC:PMC10601721 | DOI:10.1159/000531761

19:48

PubMed articles on: Cardio-Oncology

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs

Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

ABSTRACT

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

PMID:37895146 | PMC:PMC10607179 | DOI:10.3390/ijms242015466

19:48

PubMed articles on: Cancer & VTE/PE

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis

Intern Emerg Med. 2023 Oct 29. doi: 10.1007/s11739-023-03426-1. Online ahead of print.