ABSTRACT

INTRODUCTION: As nearly 50% of cancer patients receive radiation therapy (RT) as treatment, the effects of RT on the outcomes of future total hip arthroplasty (THA) remain unclear. The purpose of this study was to assess the odds of developing medical and surgical adverse events following THA in patients who have a history of RT.

METHODS: A retrospective cohort study was conducted using a national database to identify patients who underwent primary THA (Current Procedural Terminology (CPT) code 27130) from 2002 to 2022. Patients who had a prior RT were identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes Z51.0 (encounter for antineoplastic RT), Z92.3 (personal history of irradiation), or CPT code 101843 (radiation oncology treatment). One-to-one propensity score matching was conducted to generate 3 pairs of cohorts: 1) THA with/without history of RT; 2) THA with/without history of cancer; and 3) THA patients who have a history of cancer treated with/without RT. Surgical and medical complications were assessed at the 30-day, 90-day, and 1-year postoperative periods.

RESULTS: Patients who have a history of RT had higher odds of developing anemia, deep vein thrombosis, pneumonia, pulmonary embolism, and prosthetic joint infection at all intervals. When controlling for a history of cancer, RT was associated with an increased risk of pulmonary embolism, heterotrophic ossification, prosthetic joint infection, and periprosthetic fracture at all post-operative time points. There was additionally an increased risk of aseptic loosening at 1-year (Odds Ratio (OR): 2.0, 95% Confidence Interval (CI): 1.2-3.1).

CONCLUSIONS: These findings suggest that patients who have a history of antineoplastic RT are at an increased risk of developing various surgical and medical complications following THA.

PMID:37301238 | DOI:10.1016/j.arth.2023.05.066

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PubMed articles on: Cancer & VTE/PE

Incidence of recurrent venous thromboembolism and bleeding complications in patients with cancer and isolated distal deep vein thrombosis

Thromb Res. 2023 Jun 4;228:81-84. doi: 10.1016/j.thromres.2023.05.027. Online ahead of print.

ABSTRACT

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is a common clinical presentation of DVT. The efficacy and safety of anticoagulant therapy for the management of IDDVT in patients with cancer are unclear. We sought to assess the incidence of recurrent venous thromboembolism (VTE) and major bleeding in this patient population.

METHODS: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2, 2022 was performed. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding. The secondary outcomes were clinically relevant non-major bleeding (CRNMB) and mortality. The incidence rates of thrombotic, bleeding, and mortality outcomes were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI).

RESULTS: Out of a total of 5234 articles, 10 observational studies including 8160 patients with cancer and IDDVT were included in the analysis. The incidence rate of recurrent VTE was 5.65 (95 % CI: 2.09-15.30) per 100 patient-years regardless of type and duration of anticoagulant therapy. The incidence rate of major bleeding was 4.08 (95 % CI: 2.52-6.61) per 100 patient-years. The incidence rates for CRNMB and mortality per 100 patient-years were 8.11 (95 % CI: 5.56-11.83) and 30.22 (95 % CI: 22.60-40.42.89), respectively.

CONCLUSION: Patients with cancer and IDDVT are at high risk of developing recurrent VTE and bleeding complications (both major bleeding and CRNMB). More studies are needed to define the optimal management for this high-risk population.

PMID:37301116 | DOI:10.1016/j.thromres.2023.05.027

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PubMed articles on: Cancer & VTE/PE

Clonal haematopoiesis of indeterminate potential in patients with venous thromboembolism

J Thromb Thrombolysis. 2023 Jun 10. doi: 10.1007/s11239-023-02836-4. Online ahead of print.

ABSTRACT

Over the last decade, the concept of Clonal haematopoiesis of undetermined potential (CHIP) has emerged. Low frequency somatic mutations in hematopoietic cells can occur with age and might allow formation of clones in individuals with no characterized haematological pathology. These CHIP mutations are associated with an increased risk of cancer or atherothrombosis, and their prevalence are more and more studied in pathologies with an inflammatory component. In our study, we analysed, by next generation sequencing, the prevalence of CHIP mutation in 94 patients with deep venous thrombosis (DVT), distinguishing two clinical phenotypes: provoked distal and non-provoked proximal DVTs. We show that there is no difference in CHIP prevalence between these two groups, nor with a matched-aged control group. The number of mutation per patients and the affected genes remain also the same between the three groups. Consequently and despite the relative small number of patients in each cohort, it seems that CHIP is not a strong concern in venous thromboembolism.

PMID:37300604 | DOI:10.1007/s11239-023-02836-4

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PubMed articles on: Cancer & VTE/PE

Low Molecular Weight Heparin Treatment Patterns and Outcomes in Cancer Patients with Acute Venous Thromboembolism: A Nationwide Cohort Study in France

Cancers (Basel). 2023 May 31;15(11):3011. doi: 10.3390/cancers15113011.

ABSTRACT

Patients with cancer have an increased risk of developing venous thromboembolism (VTE) and an increased risk of death from VTE. Until recently, the standard of care for treatment of VTE in cancer patients was low molecular weight heparins (LMWH). To determine treatment patterns and outcomes, we performed an observational study using a nationwide health database. Treatment patterns, rates of bleeding, and VTE recurrence at 6 and 12 months were assessed in cancer patients with VTE in France prescribed LMWH in 2013-2018. Of 31,771 patients administered LMWH (mean age 66.3 years), 51.0% were male, 58.7% had pulmonary embolism, and 70.9% had metastatic disease. At 6 months LMWH persistence was 81.6%, VTE recurrence had occurred in 1256 patients (4.0%) at a crude rate per 100 person-months (PM) of 0.90, and bleeding had occurred in 1124 patients (3.5%) at a crude rate per 100 PM of 0.81. At 12 months, VTE recurrence had occurred in 1546 patients (4.9%) at a crude rate per 100 PM of 0.71 and bleeding had occurred in 1438 patients (4.5%) at a crude rate per 100 PM of 0.66. Overall, VTE-related clinical event rates were high among patients administered LMWH, suggesting an unmet medical need.

PMID:37296971 | PMC:PMC10251904 | DOI:10.3390/cancers15113011

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PubMed articles on: Cancer & VTE/PE

Covariate-specific ROC curve analysis can accommodate differences between covariate subgroups in the evaluation of diagnostic accuracy

J Clin Epidemiol. 2023 Jun 7:S0895-4356(23)00142-7. doi: 10.1016/j.jclinepi.2023.06.001. Online ahead of print.

ABSTRACT

OBJECTIVE: We present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing for excluding pulmonary embolism.

STUDY DESIGN AND SETTING: Bayesian nonparametric covariate-specific ROC curves were constructed to examine the performance/positivity thresholds in covariate subgroups. Standard ROC curves were constructed. Three scenarios were outlined based on comparison between subgroups and standard ROC curve conclusion: (1) identical distribution/identical performance, (2) different distribution/identical performance, and (3) different distribution/different performance. Scenarios were illustrated using clinical covariates. Covariate-adjusted ROC curves were also constructed.

RESULTS: Age groups had prominent differences in D-dimer concentration, paired with differences in performance (Scenario 3). Different positivity thresholds were required to achieve the same level of sensitivity. D-dimer had identical performance, but different distributions for YEARS algorithm items (Scenario 2), and similar distributions for sex (Scenario 1). For the later covariates, comparable positivity thresholds achieved the same sensitivity. All covariate-adjusted models had AUCs comparable to the standard approach.

CONCLUSION: Subgroup differences in performance and distribution of results can indicate that the conventional ROC curve is not a fair representation of test performance. Estimating conditional ROC curves can improve the ability to select thresholds with greater applicability.

PMID:37295733 | DOI:10.1016/j.jclinepi.2023.06.001

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PubMed articles on: Cardio-Oncology

Cardiac calcified amorphous tumor in a patient with colon cancer

Clin Case Rep. 2023 Jun 7;11(6):e7491. doi: 10.1002/ccr3.7491. eCollection 2023 Jun.

ABSTRACT

Although one of the most important differential diagnoses of cardiac masses in cancer patients is metastasis from the underlying tumor, it may also be caused by benign etiologies. In this article, we describe cardiac calcified amorphous tumor, which is one of the benign causes of cardiac masses, in a patient with colon cancer.

PMID:37305859 | PMC:PMC10248199 | DOI:10.1002/ccr3.7491

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PubMed articles on: Cardio-Oncology

Chemotherapy-induced cardiotoxicity: a new perspective on the role of Digoxin, ATG7 activators, Resveratrol, and herbal drugs

J Med Life. 2023 Apr;16(4):491-500. doi: 10.25122/jml-2022-0322.

ABSTRACT

Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.

PMID:37305823 | PMC:PMC10251384 | DOI:10.25122/jml-2022-0322

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PubMed articles on: Cardio-Oncology

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial

Front Oncol. 2023 May 25;13:1139347. doi: 10.3389/fonc.2023.1139347. eCollection 2023.

ABSTRACT

BACKGROUND: The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity.

METHODS: Using the Agena Bioscience MassARRAY system, we genotyped TRPC6rs77679196, BRINP1rs62568637, LDB2rs55756123, RAB22Ars707557, intergenic rs4305714, LINC01060rs7698718, and CBR3rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates.

RESULTS: Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6rs77679196 and CBR3rs1056892 were significantly associated with congestive heart failure, p< 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab.

CONCLUSIONS: TRPC6rs77679196 and CBR3rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

PMID:37305569 | PMC:PMC10248403 | DOI:10.3389/fonc.2023.1139347

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PubMed articles on: Cardio-Oncology

Drug therapy for myocarditis induced by immune checkpoint inhibitors

Front Pharmacol. 2023 May 25;14:1161243. doi: 10.3389/fphar.2023.1161243. eCollection 2023.

ABSTRACT

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and its ligand 1 (PD-L1), have improved the survival in multiple types of cancers; however, ICIs may cause cardiovascular toxicity. Although rare, ICI-mediated cardiotoxicity is an extremely serious complication with a relatively high mortality. In this review, we discuss the underlying mechanism and clinical manifestations of cardiovascular toxicity induced by ICIs. According to previous studies, multiple signaling pathways are involved in myocarditis induced by ICIs. Further, we summarize the clinical trials of drugs for the treatment of ICI-associated myocarditis. Although these drugs have shown the beneficial effects of alleviating cardiac function and reducing mortality rates, their efficacy is not optimal. Finally, we discuss the therapeutic potential of some novel compounds as well as the underlying mechanisms of their action.

PMID:37305530 | PMC:PMC10248045 | DOI:10.3389/fphar.2023.1161243

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PubMed articles on: Cardio-Oncology

Ambulatory blood pressure monitoring in patients with onco-hematological diseases

Hipertens Riesgo Vasc. 2023 Jun 9:S1889-1837(23)00033-8. doi: 10.1016/j.hipert.2023.05.006. Online ahead of print.

ABSTRACT

Hypertension (HT) is a frequent pathology in patients with active or surviving onco-haematological malignancies. It is estimated that the prevalence of HT in this population ranges between 30 and 70%. The relationship between cancer and HT is multifactorial: common risk factors, neoplasia that cause HT through hormonal secretion, and, especially, chemotherapy drugs that cause HT. Ambulatory blood pressure monitoring (ABPM) is a fundamental tool in the diagnosis and adequate control of blood pressure, avoiding having to suspend or reduce the dose of chemotherapy treatment. In addition, it can help in the diagnosis of autonomic dysfunction related to certain neoplastic pathologies.

PMID:37302940 | DOI:10.1016/j.hipert.2023.05.006

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PubMed articles on: Cardio-Oncology

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease

Transl Oncol. 2023 Jun 2;34:101709. doi: 10.1016/j.tranon.2023.101709. Online ahead of print.

ABSTRACT

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated.

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001).interaction

CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

PMID:37302348 | PMC:PMC10235676 | DOI:10.1016/j.tranon.2023.101709

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PubMed articles on: Cardio-Oncology

Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic Breast Cancer

J Am Heart Assoc. 2023 Jun 10:e029361. doi: 10.1161/JAHA.123.029361. Online ahead of print.

ABSTRACT

Background Cyclin-dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor-positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninthand Tenth Revisions(ICD-9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine-Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all-cause death was studied using Cox proportional hazard models. Propensity-weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person-years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all-cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98-8.05]; and 5.88 [95% CI, 3.56-9.73], respectively). Conclusions CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.

PMID:37301767 | DOI:10.1161/JAHA.123.029361

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PubMed articles on: Cardio-Oncology

Vernonia amygdalina Ethanol Extract Protects against Doxorubicin-Induced Cardiotoxicity via TGFβ, Cytochrome c, and Apoptosis

Molecules. 2023 May 24;28(11):4305. doi: 10.3390/molecules28114305.

ABSTRACT

Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalinaethanol extract (VAEE) was produced by soaking dried Vernonia amygdalinaleaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg/kgbw + 100, 200, 400, 600, and 800 mg/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- (p < 0.001). These findings suggest that Vernonia amygdalinamay protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalinacould be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.

PMID:37298779 | PMC:PMC10254146 | DOI:10.3390/molecules28114305

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PubMed articles on: Cardio-Oncology

Toll-like Receptor 4 Inflammatory Perspective on Doxorubicin-Induced Cardiotoxicity

Molecules. 2023 May 24;28(11):4294. doi: 10.3390/molecules28114294.

ABSTRACT

Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety of cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms of Dox-induced cardiotoxicity are still not fully understood. More significantly, there are no established therapeutic guidelines for Dox-induced cardiotoxicity. To date, Dox-induced cardiac inflammation is widely considered as one of the underlying mechanisms involved in Dox-induced cardiotoxicity. The Toll-like receptor 4 (TLR4) signaling pathway plays a key role in Dox-induced cardiac inflammation, and growing evidence reports that TLR4-induced cardiac inflammation is strongly linked to Dox-induced cardiotoxicity. In this review, we outline and address all the available evidence demonstrating the involvement of the TLR4 signaling pathway in different models of Dox-induced cardiotoxicity. This review also discusses the effect of the TLR4 signaling pathway on Dox-induced cardiotoxicity. Understanding the role of the TLR4 signaling pathway in Dox-induced cardiac inflammation might be beneficial for developing a potential therapeutic strategy for Dox-induced cardiotoxicity.

PMID:37298770 | PMC:PMC10254273 | DOI:10.3390/molecules28114294

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PubMed articles on: Cardio-Oncology

Feasibility of a Virtual Educational Programme for Behaviour Change in Cardiac Patients from a Low-Resource Setting

Int J Environ Res Public Health. 2023 May 24;20(11):5934. doi: 10.3390/ijerph20115934.