ABSTRACT

OBJECTIVE: Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients.

METHODS: A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively.

RESULTS: The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%).

CONCLUSION: Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients.

PMID:37313468 | PMC:PMC10258345 | DOI:10.3389/fonc.2023.1165437

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PubMed articles on: Cancer & VTE/PE

Thromboembolic complications associated to malignant diseases

Magy Onkol. 2023 Jun 13;67(2):139-145. Epub 2023 Apr 18.

ABSTRACT

Cancers are known to increase the tendency for thrombosis, both on the venous and arterial side, which to this day is an important factor in the management of oncology patients. Malignant disease is an independent risk factor for developing venous thromboembolism (VTE). Thromboembolic complications in addition to the disease worsen prognosis and are accompanied by significant morbidity and mortality. VTE is the second most common cause of death in cancer after disease progression. Tumors are characterized by hypercoagulability, in addition to which venous stasis and endothelial damage also occur in cancer patients promoting increased clotting. Treatment of cancer-associated thrombosis is often complex; therefore, it is important to identify patients who benefit from primary thromboprophylaxis. The importance of cancer-associated thrombosis is indisputable in everyday oncology. We briefly summarize the frequency and characteristics of their occurrence, the underlying mechanisms, risk factors, clinical appearance, laboratory diagnostics, and the possibilities of prevention and treatment.

PMID:37314075

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PubMed articles on: Cardio-Oncology

A comparative review and computational assessment of acetochlor toxicity in fish: A novel endocrine disruptor?

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Jun 14:109685. doi: 10.1016/j.cbpc.2023.109685. Online ahead of print.

ABSTRACT

Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.

PMID:37328132 | DOI:10.1016/j.cbpc.2023.109685

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PubMed articles on: Cardio-Oncology

Perspective on AHFTC Specialty by Women in Heart Transplant and MCS (WiTMCS)

J Card Fail. 2023 Jun 14:S1071-9164(23)00203-8. doi: 10.1016/j.cardfail.2023.05.022. Online ahead of print.

ABSTRACT

BACKGROUND: The Advanced Heart Failure & Transplant cardiology specialty has seen a decline in applicants seeking training in the field. Data is needed to identify principal reform areas to generate and maintain interest in the field for sustainability.

METHODS: Women in Transplant and Mechanical Circulatory support (WiTMCS) conducted a survey across their membership group investigating the barriers to attracting new talent and areas that need reform to improve the status of the specialty . A Likert scale was utilized to assess various perceived barriers to attracting new trainees and reform needed to improve the specialty.

RESULTS: A total of 131 women physicians in transplant and MCS responded to the survey. Five principal areas in need of reform were identified. : need for practice model variety 86.9%, inadequate compensation for non-RVU activities and total compensation at 86.4% and 79.1 % respectively, challenging work life balance at 78.5%, need for curriculum reform & specialized pathways at 73.1% and 65.4% respectively, and exposure during general cardiology fellowship at 65.1%.

CONCLUSION: Given the rising number of heart failure patients and the increased demand for more heart failure specialists,reformation is needed to restructure the five elements identified in our survey to increase interest in the field of AHFTC and maintain the current talent.

PMID:37328051 | DOI:10.1016/j.cardfail.2023.05.022

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PubMed articles on: Cardio-Oncology

[Retracted] CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma

Oncol Rep. 2023 Aug;50(2):151. doi: 10.3892/or.2023.8588. Epub 2023 Jun 16.

ABSTRACT

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that, for the western blots showing the CtBP1 and SOX2 bands in Fig. 5C on p. 74, the data were in fact the same, but flipped horizontally; moreover, two pairs of overlapping data panels were identified comparing between the cell invasion and assay data images shown in Figs. 3E and 6C, such that these were likely to have been derived from the same original sources even though they were intended to show the results from differently performed experiments; similarly, the 'shSOX2 / 24 h' and 'shCtBP1 / 24 h' data panels in Fig. 6B showing the results of differently performed scratch‑wound assay experiments appeared to be overlapping, albeit with one of the panels being slightly rotated relative to the other. Finally, there were erroneous calculations included for the CtBP1 expression data shown in Table III. Given the large number of apparent errors that were made during the assembly of various of the figures and Table III in this paper, the Editor of Oncology Reportshas decided that this paper should be retracted from the Journal due to an overall lack of confidence in the presented data. After contacting the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 67‑78, 2019; DOI: 10.3892/or.2019.7142].

PMID:37326128 | DOI:10.3892/or.2023.8588

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PubMed articles on: Cardio-Oncology

Burden and prognostic impact of cardiovascular disease in patients with cancer

Heart. 2023 Jun 15:heartjnl-2022-321324. doi: 10.1136/heartjnl-2022-321324. Online ahead of print.

ABSTRACT

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

PMID:37321830 | DOI:10.1136/heartjnl-2022-321324

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PubMed articles on: Cardio-Oncology

2023 National Heart Center/Saudi Heart Association Focused Update of the 2019 Saudi Heart Association Guidelines for the Management of Heart Failure

J Saudi Heart Assoc. 2023 May 25;35(1):71-134. doi: 10.37616/2212-5043.1334. eCollection 2023.

ABSTRACT

BACKGROUND: The burden of cardiovascular diseases is undeniable in local populations, who have high mortality rates and a young age of disease onset. A systematic review of emerging evidence and update of the Saudi Heart Association (SHA) 2019 heart failure (HF) guidelines was therefore undertaken.

METHODOLOGY: A panel of expert cardiologists reviewed recommendations of the 2019 guidelines following the Saudi Heart Association methodology for guideline recommendations. When needed, the panel provided updated and new recommendations endorsed by the national heart council that are appropriate for clinical practice and local resources in Saudi Arabia.

RECOMMENDATIONS AND CONCLUSION: The focused update describes the appropriate use of clinical assessment as well as invasive and non-invasive modalities for the classification and diagnosis of HF. The prevention of HF was emphasized by expanding on both primary and secondary prevention approaches. Pharmacological treatment of HF was supplemented with recommendations on newer therapies, such as SGLT-2 inhibitors. Recommendations were also provided on the management of patients with cardiovascular and non-cardiovascular co-morbidities, with a focus on cardio-oncology and pregnancy. Updated clinical algorithms were included in support of HF management in both the acute and chronic settings. The implementation of this focused update on HF management in clinical practice is expected to lead to improved patient outcomes by providing evidence-based comprehensive guidance for practitioners in Saudi Arabia.

PMID:37323135 | PMC:PMC10263126 | DOI:10.37616/2212-5043.1334

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PubMed articles on: Cardio-Oncology

Amentoflavone mitigates doxorubicin-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation through inhibition of the STING/NLRP3 signalling pathway

Phytomedicine. 2023 Jun 10;117:154922. doi: 10.1016/j.phymed.2023.154922. Online ahead of print.

ABSTRACT

BACKGROUND: Doxorubicin (DOX) is a potent anticancer chemotherapeutic agent whose clinical application is substantially constrained by its cardiotoxicity. The pathophysiology of DOX-induced cardiotoxicity manifests as cardiomyocyte pyroptosis and inflammation. Amentoflavone (AMF) is a naturally occurring biflavone possessing anti-pyroptotic and anti-inflammatory properties. However, the mechanism through which AMF alleviates DOX-induced cardiotoxicity remains undetermined.

PURPOSE: This study aimed at investigating the role of AMF in alleviating DOX-induced cardiotoxicity.

STUDY DESIGN AND METHODS: To assess the in vivo effect of AMF, DOX was intraperitoneally administered into a mouse model to induce cardiotoxicity. To elucidate the underlying mechanisms, the activities of STING/NLRP3 were quantified using the NLRP3 agonist nigericin and the STING agonist amidobenzimidazole (ABZI). Primary cardiomyocytes isolated from neonatal Sprague-Dawley rats were treated with saline (vehicle) or DOX with or without AMF and/or ABZI. The echocardiogram, haemodynamics, cardiac injury markers, heart/body weight ratio, and pathological alterations were monitored; the STING/NLRP3 pathway-associated proteins were detected by western blot and cardiomyocyte pyroptosis was analysed by immunofluorescence staining of cleaved N-terminal GSDMD and scanning electron microscopy. Furthermore, we evaluated the potential of AMF in compromising the anticancer effects of DOX in human breast cancer cell lines.

RESULTS: AMF substantially alleviated cardiac dysfunction and reduced heart/body weight ratio and myocardial damage in mice models of DOX-induced cardiotoxicity. AMF effectively suppressed DOX-mediated upregulation of IL-1β, IL-18, TNF-α, and pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and cleaved N-terminal GSDMD. The levels of apoptosis-related proteins, namely Bax, cleaved caspase-3, and BCL-2 were not affected. In addition, AMF inhibited STING phosphorylation in DOX-affected hearts. Intriguingly, the administration of nigericin or ABZI dampened the cardioprotective effects of AMF. The in vitro anti-pyroptotic effect of AMF was demonstrated in attenuating the DOX-induced reduction in cardiomyocyte cell viability, upregulation of cleaved N-terminal GSDMD, and pyroptotic morphology alteration at the microstructural level. AMF exhibited a synergistic effect with DOX to reduce the viability of human breast cancer cells.

CONCLUSION: AMF alleviates DOX-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation via inhibition of the STING/NLRP3 signalling pathway, thereby validating its efficacy as a cardioprotective agent.

PMID:37321078 | DOI:10.1016/j.phymed.2023.154922

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PubMed articles on: Cardio-Oncology

When Cancer and Cardiovascular Disease Intersect: The Challenge and the Opportunity of Cardio-Oncology

Heart Lung Circ. 2023 Jun 13:S1443-9506(23)00510-3. doi: 10.1016/j.hlc.2023.04.301. Online ahead of print.

ABSTRACT

Cancer and cardiovascular disease (CVD) commonly coexist, with increasing evidence that long-term cancer survivors are more likely to die from CVD than the general population. Effective management of CVD and its risk factors requires identification of patients at increased risk who may benefit from early intervention and their appropriate monitoring across the disease trajectory. Improving outcomes requires new models of multidisciplinary cancer care supported by care pathways. Such pathways require a clear delineation of the roles and responsibilities of all team members and provision of appropriate enablers for their delivery. These include accessible point-of-care tools/risk calculators, patient resources, and the provision of tailored training opportunities for health care providers.

PMID:37321867 | DOI:10.1016/j.hlc.2023.04.301

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PubMed articles on: Cardio-Oncology

Doxorubicin Interaction with Lipid Monolayers Leads to Decreased Membrane Stiffness when Experiencing Compression-Expansion Dynamics

Langmuir. 2023 Jun 15. doi: 10.1021/acs.langmuir.3c00250. Online ahead of print.

ABSTRACT

Physical membrane models permit to study and quantify the interactions of many external molecules with monitored and simplified systems. In this work, we have constructed artificial Langmuir single-lipid monolayers with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), or sphingomyelin to resemble the main lipid components of the mammalian cell membranes. We determined the collapse pressure, minimum area per molecule, and maximum compression modulus (Cs-1) from surface pressure measurements in a Langmuir trough. Also, from compression/expansion isotherms, we estimated the viscoelastic properties of the monolayers. With this model, we explored the membrane molecular mechanism of toxicity of the well-known anticancer drug doxorubicin, with particular emphasis in cardiotoxicity. The results showed that doxorubicin intercalates mainly between DPPS and sphingomyelin, and less between DPPE, inducing a change in the Cs-1 of up to 34% for DPPS. The isotherm experiments suggested that doxorubicin had little effect on DPPC, partially solubilized DPPS lipids toward the bulk of the subphase, and caused a slight or large expansion in the DPPE and sphingomyelin monolayers, respectively. Furthermore, the dynamic viscoelasticity of the DPPE and DPPS membranes was greatly reduced (by 43 and 23%, respectively), while the reduction amounted only to 12% for sphingomyelin and DPPC models. In conclusion, doxorubicin intercalates into the DPPS, DPPE, and sphingomyelin, but not into the DPPC, membrane lipids, inducing a structural distortion that leads to decreased membrane stiffness and reduced compressibility modulus. These alterations may constitute a novel, early step in explaining the doxorubicin mechanism of action in mammalian cancer cells or its toxicity in non-cancer cells, with relevance to explain its cardiotoxicity.

PMID:37320858 | DOI:10.1021/acs.langmuir.3c00250

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PubMed articles on: Cardio-Oncology

Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis

Circulation. 2023 Jun 15. doi: 10.1161/CIRCULATIONAHA.123.062405. Online ahead of print.