ABSTRACT

Hormone therapies (HTs) with anti-androgenic properties are a cornerstone for the treatment of prostate cancer (PC) and have significantly improved the survival of patients, though exposing them to a higher risk of cardiovascular diseases (CVDs), which represent a major cause of morbidity and mortality. This occurs due to the high average age of patients undergoing HT for PC, an age group in which CVDs have a high prevalence and incidence, and due to the type and duration of HTs that are increasingly effective but at the same time more aggressive towards cardiovascular health. Recent evidence from the real world suggests, however, that the cardiometabolic risk is widely underestimated and undertreated with significant impact also on the oncological prognosis. In the light of the results of the PRONOUNCE study, in this review it is emphasized the need for a multidisciplinary management of patients with PC who are candidate for or treated with HT by implementing a personalized treatment program in accordance with the current European guidelines on CVD prevention.

PMID:37767830 | DOI:10.1714/4100.40978

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis for hospitalized adult patients: a survey of US health care providers on attitudes and practices

Res Pract Thromb Haemost. 2023 Aug 7;7(6):102168. doi: 10.1016/j.rpth.2023.102168. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of preventable mortality among hospitalized patients, but appropriate risk assessment and thromboprophylaxis remain underutilized or misapplied.

OBJECTIVES: We conducted an electronic survey of US health care providers to explore attitudes, practices, and barriers related to thromboprophylaxis in adult hospitalized patients and at discharge.

RESULTS: A total of 607 US respondents completed the survey: 63.1% reported working in an academic hospital, 70.7% identified as physicians, and hospital medicine was the most frequent specialty (52.1%). The majority of respondents agreed that VTE prophylaxis is important (98.8%; 95% CI: 97.6%-99.5%) and that current measures are safe (92.6%; 95% CI: 90.2%-94.5%) and effective (93.8%; 95% CI: 91.6%-95.6%), but only half (52.0%; 95% CI: 47.9%-56.0%) believed that hospitalized patients at their institution are on appropriate VTE prophylaxis almost all the time. One-third (35.4%) reported using a risk assessment model (RAM) to determine VTE prophylaxis need; 44.9% reported unfamiliarity with RAMs. The most common recommendation for improving rates of appropriate thromboprophylaxis was to leverage technology. A majority of respondents (84.5%) do not reassess a patient's need for VTE prophylaxis at discharge, and a minority educates patients about the risk (16.2%) or symptoms (18.9%) of VTE at discharge.

CONCLUSION: Despite guideline recommendations to use RAMs, the majority of providers in our survey do not use them. A majority of respondents believed that technology could help improve VTE prophylaxis rates. A majority of respondents do not reassess the risk of VTE at discharge or educate patients about this risk of VTE at discharge.

PMID:37767063 | PMC:PMC10520566 | DOI:10.1016/j.rpth.2023.102168

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PubMed articles on: Cancer & VTE/PE

Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy

Life (Basel). 2023 Sep 10;13(9):1888. doi: 10.3390/life13091888.

ABSTRACT

Optimizing the anticoagulation therapy is of pivotal importance in patients with a malignant tumor, as venous thromboembolism (VTE) has become the second-leading cause of death in this population. Cancer can highly increase the risk of thrombosis and bleeding. Consequently, the management of cancer-associated VTE is complex. In recent years, translational research has intensified, and several studies have highlighted the role of inflammatory cytokines in cancer growth and progression. Simultaneously, the pleiotropic effects of anticoagulants currently recommended for VTE have emerged. In this review, we describe the anti-inflammatory and anticancer effects of both direct oral anticoagulants (DOACs) and low-molecular-weight heparins (LWMHs).

PMID:37763292 | PMC:PMC10532829 | DOI:10.3390/life13091888

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PubMed articles on: Cardio-Oncology

Cardiac safety assessment of a novel recombinant bispecific antibody targeting the ether-à-go-go related gene 1 (hERG1)-β1 integrin macromolecular complex

Front Pharmacol. 2023 Sep 12;14:1237431. doi: 10.3389/fphar.2023.1237431. eCollection 2023.

ABSTRACT

Introduction: In the last decades, mounting evidence has pointed out the human ether-á-go-go-related gene (hERG1) potassium channel as a novel biomarker in human cancers. However, hERG1 sustains the cardiac repolarizing current IKr and its blockade can induce a prolonged QT interval at the ECG, which increases the risk of life-threatening arrhythmias. This represents a major hindrance for targeting hERG1 for antineoplastic therapeutic purposes. Based on our discovery that hERG1 resides in a macromolecular complex with the β1 subunit of integrin adhesion receptors only in tumors, and not in the heart, we generated (and patented WO2019/015936) a novel engineered, single chain, bispecific antibody in the format of a diabody (scDb-hERG1-β1). This antibody has been proven to target with high affinity the hERG1/β1 integrin complex and to exert a good antineoplastic activity in preclinical mouse models. Methods: In the present study, we evaluated the cardiac safety of the scDb-hERG1-β1, determining the action potential duration (APD) of human cardiomyocytes, either atrial (from valve-disease patients) or ventricular (from aortic stenosis patients). Cardiac cells were incubated in vitro with i) the scDb-hERG1-β1, ii) the full length anti-hERG1 monoclonal antibody (mAb-hERG1) and iii) its single chain Fragment variable derivative (scFv-hERG1), from which the scDb-hERG1-β1 was assembled. All the tests were performed before and after treatment with the specific hERG1 blocker E4031. In addition, we have performed preliminary experiments, analyzing the effects of the scDb-hERG1/β1 in vivo measuring the QT interval length of the surface ECG after its injection intravenously in farm-pigs. Results: The scDb-hERG1-β1 did not produce any lengthening of APD compared to control (vehicle) conditions, either in atrial or ventricular cardiomyocytes, whereas both the hERG1-mAb and the scFv-hERG1 produced a significant APD prolongation. The addition of E4031 further prolonged APD. The scDb-hERG1-β1 did not produce any alterations of the QT (and QTc) interval values, once injected intravenously in farm pigs. Discussion: Overall, the above evidences plead for the cardiac safety of the scDb-hERG1-β1, suggesting that an application of this antibody for anti-cancer therapy will be untainted by cardiotoxicity.

PMID:37767396 | PMC:PMC10520717 | DOI:10.3389/fphar.2023.1237431

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PubMed articles on: Cardio-Oncology

Usefulness of Longitudinal Strain to Assess Cancer Therapy-Related Cardiac Dysfunction and Immune Checkpoint Inhibitor-Induced Myocarditis

Pharmaceuticals (Basel). 2023 Sep 14;16(9):1297. doi: 10.3390/ph16091297.

ABSTRACT

Longitudinal strain (LS) measured by echocardiography has been reported to be useful not only for the diagnosis and risk stratification of various cardiac diseases, but also in cardio-oncology. Most previous studies have been conducted on patients undergoing treatment with anthracyclines and human epidermal growth factor receptor 2-targeted therapies. Existing guidelines recommend that global LS (GLS) should be measured before and after the administration of cancer drugs. This recommendation is based on many reports showing that a decline in GLS is indicative of early or mild cancer therapy-related cardiac dysfunction. The main purpose of this article is to provide insight into the importance of LS in patients undergoing cancer treatment and highlight the role of LS evaluation in patients undergoing immune checkpoint inhibitor (ICI) treatment, which is being used with increasing frequency. Among cancer drug therapies, immune checkpoint inhibitors (ICIs) have an important place in cancer treatment and are used for the treatment of many types of cancer. Although the efficacy of ICIs in cancer treatment has been reported, immune-related adverse events (irAEs) have also been reported. Among these irAEs, cardiovascular complications, although rare, are recognized as important adverse events that may result in ICI treatment discontinuation. Myocarditis is one severe adverse event associated with ICIs, and it is important to standardize diagnostic and therapeutic approaches to it. Several studies have reported a relationship between LS and cardiac complications associated with ICIs which may contribute to the early diagnosis of ICI-induced cardiac complications.

PMID:37765105 | PMC:PMC10535915 | DOI:10.3390/ph16091297

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PubMed articles on: Cancer & VTE/PE

The Risk of Thromboembolism in Patients with Muscle Invasive Bladder Cancer before and after Cystectomy Depending on Blood Group and Neoadjuvant Chemotherapy-A Multicentre Retrospective Cohort Study

J Pers Med. 2023 Sep 4;13(9):1355. doi: 10.3390/jpm13091355.

ABSTRACT

PURPOSE: Previous studies have indicated that patients with muscle-invasive bladder cancer with non-O blood types have an increased risk of experiencing thromboembolic events (TEEs). This is finding is in relation to neoadjuvant-chemotherapy (NAC)-naïve patients.

AIM: to establish the risk of TEEs and any association with blood types among NAC patients as well as NAC-naïve patients.

METHODS: Cystectomized patients at four centres treated from 2009 to 2018 (n = 244) were analysed. The quantities of patients corresponding to each blood group were as follows: A-108 (44%); O-99 (41%); B-30 (12%); and AB-7 (3%). NAC patients (n = 167) and NAC-naïve NAC-eligible patients (n = 77) were assessed. In total, 54 women (22%) and 190 men (78%), with a median age of 69 years, were included in the study. The occurrence of any type of TEE from six months pre-cystectomy to 12-24 months after was analysed using logistic regression adjusted for NAC and confounders.

RESULTS: Sixty-six TEEs were detected in 21% of the patients (n = 52). Pulmonary embolus (n = 33) and deep venous thrombosis (n = 11) were the most common forms. No significant differences between blood types were found in the analysis, although B blood type had a nearly significant increased crude risk compared with O blood type, for which there was an OR of 2.48 (95% CI 0.98-6.36). Adjustment for NAC and covariates weakened the OR, which plummeted to 1.98 (95% CI 0.71-5.51).

CONCLUSIONS: No significant associations were found between blood types and TEE occurrences in this cohort including both NAC and NAC-naïve NAC-eligible patients.

PMID:37763123 | PMC:PMC10533159 | DOI:10.3390/jpm13091355

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PubMed articles on: Cardio-Oncology

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice

Pharmaceuticals (Basel). 2023 Aug 28;16(9):1212. doi: 10.3390/ph16091212.