ABSTRACT

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Surgical valve replacement, transcatheter valve implantation, balloon valvuloplasty, and medical therapy are possible treatments for aortic valve stenosis, but when malignancy is present, the choice between these options must take into account the stage of cancer and associated treatment, expected outcome, and comorbidities. Physical examination and Doppler echocardiography are critical in the diagnosis and evaluation of aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer and the therapeutic options.

PMID:37762745 | PMC:PMC10532214 | DOI:10.3390/jcm12185804

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PubMed articles on: Cardio-Oncology

α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades

Int J Mol Sci. 2023 Sep 13;24(18):14013. doi: 10.3390/ijms241814013.

ABSTRACT

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3β signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested.

PMID:37762315 | PMC:PMC10530367 | DOI:10.3390/ijms241814013

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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

08:39

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: Cancer & VTE/PE

ReLiFiRa (Real Life Filgotinib in Rheumatoid Arthritis): Retrospective Study of Efficacy and Safety in Common Clinical Practice

J Pers Med. 2023 Aug 25;13(9):1303. doi: 10.3390/jpm13091303.

ABSTRACT

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).

RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.

CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

PMID:37763071 | PMC:PMC10532886 | DOI:10.3390/jpm13091303

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PubMed articles on: Cancer & VTE/PE

Estimating Venous Thromboembolism Risk in Metastatic Colorectal Cancer Inpatients: Validation of Existing Risk Scores and Development of New Risk Scores

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231196859. doi: 10.1177/10760296231196859.

ABSTRACT

Metastatic colorectal cancer (mCRC) patients are predisposed to venous thromboembolism (VTE). This study aimed to (1) evaluate the efficacy of 4 existing cancer-specific VTE models in predicting VTE incidence among hospitalized mCRC patients, and (2) examine the influence of incorporating mCRC molecular subtypes into these models. We conducted an evaluation of 4 cancer-specific VTE models, including Khorana, Vienna CATS, Protecht, and CONKO in a dataset involving 1392 mCRC patients. To evaluate the predictive performance, we utilized receiver operating characteristic (ROC) curves for both the original models and the modified models that incorporated microsatellite instability status or KRAS/NRAS/BRAF mutations. Moreover, we computed the net reclassification improvement (NRI) to quantify the enhancements made to the modified VTE risk models. All models demonstrated a moderate area under the ROC curve (ROC-AUC) when predicting the occurrence of VTE: Khorana (0.550), Vienna CATS (0.671), Protecht (0.652), and CONKO (0.578). The incorporation of KRAS and BRAF mutations significantly improved the ROC-AUC of all 4 existing models (modified Khorana: 0.796, modified Vienna CATS: 0.832, modified Protecht: 0.834, and modified CONKO: 0.809). After dichotomizing the risk using a threshold of 3 points and comparing them with the original models, NRI values for the 4 modified models were 0.97, 0.95, 1.11, and 0.98, respectively. All 4 cancer-specific VTE models exhibit moderate performance when identifying mCRC patients at high risk of VTE. Incorporating KRAS and BRAF mutations may enhance the prediction of VTE in hospitalized mCRC patients.

PMID:37691565 | PMC:PMC10498692 | DOI:10.1177/10760296231196859

08:40

PubMed articles on: Cardio-Oncology

Reply to Comment on: Cardiotoxicity in children with cancer treated with anthracyclines: A position statement on dexrazoxane

Pediatr Blood Cancer. 2023 Sep 22:e30690. doi: 10.1002/pbc.30690. Online ahead of print.

NO ABSTRACT

PMID:37737681 | DOI:10.1002/pbc.30690

08:40

PubMed articles on: Cancer & VTE/PE

Thromboembolic disease and cancer: Attitude and practice of general practitioners. A qualitative study

Bull Cancer. 2023 Sep 8:S0007-4551(23)00347-8. doi: 10.1016/j.bulcan.2023.08.001. Online ahead of print.