ABSTRACT

INTRODUCTION: Cancer is a major public health problem in France. Idiopathic venous thromboembolic disease may be one of the modes of discovery. Few studies have been performed on this subject in primary care. The general practitioner plays a key role in the diagnosis for which a more codified approach seems desirable. The aim was to study how general practitioners conceive the search for cancer in patients with idiopathic venous thromboembolic disease in primary care.

METHOD: A qualitative study, inspired by the grounded theory approach, was carried out using semi-structured interviews with 12 established general practitioners. It was conducted from May to July 2022. The interview guide was developed based on data from the literature.

RESULTS: Idiopathic venous thromboembolic disease as a mode of cancer discovery in primary care was a well-known topic among general practitioners but remained a difficult exercise in practice. Our study revealed similarities in their practices: a complete anamnesis, clinical examination, verification of screening tests, and finally a TAP scan. They emphasized the importance of collaboration with angiologists and asked for a more codified management.

DISCUSSION: The question of etiology of cancer remains unanswered. General practioners would like to be made aware of a common, codified attitude. This raises the question of the applicability of the recommendations. The aim is to avoid misdiagnosing a cancer or delaying a diagnosis, while at the same time, not unnecessarily exposing certain patients to excessive investigations when these are not needed. So, it is time to think about better dissemination of recommendations, tools to help GPs easily finding what they need among the multitude of existing recommendations and tools, to establish better collaboration between general practice and hospital medicine, and between general practice and specialist medicine in order to improve cancer diagnosis as early as possible.

PMID:37690878 | DOI:10.1016/j.bulcan.2023.08.001

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism and risk factors for deep vein thrombosis in patients with pancreatic cancer undergoing chemotherapy

Nihon Shokakibyo Gakkai Zasshi. 2023;120(9):755-763. doi: 10.11405/nisshoshi.120.755.

ABSTRACT

Among various types of cancers, pancreatic cancer is known to be prone to venous thromboembolism (VTE). We investigated the complication rate of VTE and risk factors for deep vein thrombosis (DVT) in patients with pancreatic cancer undergoing chemotherapy. We retrospectively analyzed the data of 51 patients with pancreatic cancer who had undergone chemotherapy at our hospital from January 2016 to March 2021, had their D-dimer levels measured at the initial visit, and had undergone venous ultrasonography if D-dimer levels were elevated. At the initial visit, the complication rate of VTE was 35.3% (18/51 patients). Multivariate analysis revealed that the risk factors for DVT were primary tumors in the pancreas's body and tail and elevated D-dimer levels. Patients with DVT tended to have shorter overall survival than those without (218 vs 523 days). Patients with pancreatic cancer frequently develop VTE and should be aggressively screened for thrombosis, particularly in those with primary tumors in the pancreas's body and tail and elevated D-dimer levels.

PMID:37690831 | DOI:10.11405/nisshoshi.120.755

08:40

PubMed articles on: Cardio-Oncology

A Versatile PDA(DOX) Nanoplatform for Chemo-Photothermal Synergistic Therapy against Breast Cancer and Attenuated Doxorubicin-Induced Cardiotoxicity

J Nanobiotechnology. 2023 Sep 21;21(1):338. doi: 10.1186/s12951-023-02072-1.

ABSTRACT

Photothermal therapy (PTT) is a highly clinical application promising cancer treatment strategy with safe, convenient surgical procedures and excellent therapeutic efficacy on superficial tumors. However, a single PTT is difficult to eliminate tumor cells completely, and tumor recurrence and metastasis are prone to occur in the later stage. Chemo-photothermal synergistic therapy can conquer the shortcomings by further killing residual tumor cells after PTT through systemic chemotherapy. Nevertheless, chemotherapy drugs' extreme toxicity is also a problematic issue to be solved, such as anthracycline-induced cardiotoxicity. Herein, we selected polydopamine nanoparticles (PDA) as the carrier of the chemotherapeutic drug doxorubicin (DOX) to construct a versatile PDA(DOX) nanoplatform for chemo-photothermal synergistic therapy against breast cancer and simultaneously attenuated DOX-induced cardiotoxicity (DIC). The excellent photothermal properties of PDA were used to achieve the thermal ablation of tumors. DOX carried out chemotherapy to kill residual and occult distant tumors. Furthermore, the PDA(DOX) nanoparticles significantly alleviate DIC, which benefits from PDA's excellent antioxidant enzyme activity. The experimental data of the chemotherapy groups showed that the results of the PDA(DOX) group were much better than the DOX group. This study not only effectively inhibits cancer but tactfully attenuates DIC, bringing a new perspective into synergistic therapy against breast cancer.

PMID:37735669 | PMC:PMC10512561 | DOI:10.1186/s12951-023-02072-1

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PubMed articles on: Cardio-Oncology

Complete heart block is a significant predictor of mortality in immune checkpoint inhibitor myocarditis

08:40

PubMed articles on: Cardio-Oncology

One-Lung Ventilation and Postoperative Pulmonary Complications After Major Lung Resection Surgery. A Multicenter Randomized Controlled Trial

J Cardiothorac Vasc Anesth. 2023 Apr 27:S1053-0770(23)00262-8. doi: 10.1053/j.jvca.2023.04.029. Online ahead of print.

ABSTRACT

OBJECTIVES: The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established.

DESIGN: Multicenter, randomized, single-blind, controlled trial.

SETTING: Sixteen Italian hospitals.

PARTICIPANTS: A total of 880 patients undergoing elective major lung resection.

INTERVENTIONS: Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay.

MEASUREMENTS AND MAIN RESULTS: ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p = 0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p = 0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups.

CONCLUSIONS: In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

PMID:37730455 | PMC:PMC10133024 | DOI:10.1053/j.jvca.2023.04.029

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PubMed articles on: Cardio-Oncology

Disparities in cardio-oncology: Implication of angiogenesis, inflammation, and chemotherapy

Life Sci. 2023 Sep 18;332:122106. doi: 10.1016/j.lfs.2023.122106. Online ahead of print.

ABSTRACT

Cancers and cardiovascular diseases are the top two causes of death in the United States. Over the past decades, novel therapies have slowed the cancer mortality rate, yet cardiac failures have risen due to the toxicity of cancer treatments. The mechanisms behind this relationship are poorly understood and it is crucial that we properly treat patients at risk of developing cardiac failure in response to cancer treatments. Currently, we rely on early-stage biomarkers of inflammation and angiogenesis to detect cardiotoxicity before it becomes irreversible. Identification of such biomarkers allows healthcare professionals to decrease the adverse effects of cancer therapies. Angiogenesis and inflammation have a systemic influence on the heart and vasculature following cancer therapy. In the field of cardio-oncology, there has been a recent emphasis on gender and racial disparities in cardiotoxicity and the impact of these disparities on disease outcomes, but there is a scarcity of data on how cardiotoxicity varies across diverse populations. Here, we will discuss how current markers of angiogenesis and inflammation induced by cancer therapy are related to disparities in cardiovascular health.

PMID:37730108 | DOI:10.1016/j.lfs.2023.122106

08:40

PubMed articles on: Cardio-Oncology

Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response

Hepatology. 2023 Sep 20. doi: 10.1097/HEP.0000000000000601. Online ahead of print.

 

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

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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: 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

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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

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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.

 

ABSTRACT

BACKGROUND: Arterial or venous thrombosis can complicate cancer, and 20% of cancer patients may develop venous thromboembolic disorders. Venous thromboembolism (VTE) is common in some haematologic malignancies and may coexist with thrombocytopenia in those haematologic malignancies. We carried out this survey to assess the knowledge and practice of haematologists and resident doctors in haematology in Nigeria regarding the management of thrombocytopenia and cancer-associated thrombosis.

METHODS: This was a survey that was shared electronically with participants who were consultant haematologists and resident doctors in haematology in Nigeria..

RESULTS: There were 106 respondents, 70 (66%) of which were consultant haematologists. About a third (30.2%) of the respondents saw 6-10 patients with blood malignancies monthly. Fifty-seven (53.8%) of the respondents carried out risk assessment in their patients for cancer-associated thrombosis (CAT); 63 (59.4%) of the respondents saw 1-2 cancer patients with thrombosis in 3 months. The most common mode of treatment was pharmacological - 94 (88%) respondents used low molecular weight heparin. The most common haematologic malignancies associated with thrombocytopenia were acute leukaemias (69; 67%). The most common decision taken by respondents was to stop anticoagulants and transfuse platelets because the most frequent concern was the risk of bleeding in this group of patients.

CONCLUSION: Many haematologists and haematology residents had a high level of awareness, knowledge and good practice regarding thrombocytopenia with CAT in haematooncology patients; however, there is a need for improved knowledge and unified protocols for treatment in line with newer management guidelines.

PMID:37767996

08:39

PubMed articles on: Cardio-Oncology

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice

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

ABSTRACT

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

PMID:37765020 | PMC:PMC10534320 | DOI:10.3390/ph16091212

08:39

PubMed articles on: Cardio-Oncology

Creatine and Resistance Training: A Combined Approach to Attenuate Doxorubicin-Induced Cardiotoxicity

Nutrients. 2023 Sep 19;15(18):4048. doi: 10.3390/nu15184048.

ABSTRACT

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (p < 0.05). Additionally, cardiac mass was significantly greater in RT + CR + DOX SED + DOX animals (p < 0.05). These results suggest RT and CR supplementation, separately and in combination, could attenuate some measures of DOX-induced cardiotoxicity and may offer a cost-effective way to complement cancer treatments and enhance patient outcomes. More investigations are essential to better understand CR's prolonged effects during DOX therapy and its clinical implications.

PMID:37764831 | PMC:PMC10536171 | DOI:10.3390/nu15184048

08:39

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

08:39

PubMed articles on: Cardio-Oncology

Aortic Valve Stenosis and Cancer: Problems of Management

J Clin Med. 2023 Sep 6;12(18):5804. doi: 10.3390/jcm12185804.

 

ABSTRACT

RATIONALE: Cardiac arrest (CA) caused by trigeminocardiac reflex (TCR) after endoscopic nasal surgery is rare. Hence, when a patient suffers from TCR induced CA in the recovery room, most doctors may not be able to find the cause in a short time, and standard cardiopulmonary resuscitation and resuscitation measures may not be effective. Providing circulatory assistance through venous-arterial extracorporeal membrane oxygenation (VA-ECMO) can help healthcare providers gain time to identify the etiology and initiate symptom-specific treatment.

PATIENT CONCERNS: We report a rare case of CA after endoscopic nasal surgery treated with VA-ECMO.

DIAGNOSES: We excluded myocardial infarction, pulmonary embolism, allergies, hypoxia, and electrolyte abnormalities based on the relevant examination results. Following a multidisciplinary consultation, clinical manifestation and a review of previous literature, we reasoned that the CA was due to TCR.

INTERVENTIONS: VA-ECMO was established to resuscitate the patient successfully during effective cardiopulmonary resuscitation.

OUTCOMES: ECMO was successfully evacuated a period of 190 minutes of therapy. The patient was discharged home on day 8.

LESSONS: TCR is notable during endoscopic nasal surgery. Our case indicates that CA in operating room is worth prolonged CCPR. The ideal time for ECPR implementation should not be limited within 20 minutes after CCPR.

PMID:37773828 | DOI:10.1097/MD.0000000000035226

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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

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery

JAMA Netw Open. 2023 Sep 5;6(9):e2335311. doi: 10.1001/jamanetworkopen.2023.35311.

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA).

OBJECTIVE: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023.

EXPOSURES: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology.

MAIN OUTCOMES AND MEASURES: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty.

RESULTS: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty.

CONCLUSIONS AND RELEVANCE: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

PMID:37768664 | PMC:PMC10539988 | DOI:10.1001/jamanetworkopen.2023.35311

08:39

PubMed articles on: Cancer & VTE/PE

Survey on the Knowledge and Management of Cancer-Associated Thrombosis (CAT) in Haemato-Oncology Patients with Thrombocytopenia among Haematologists and Haematology Residents in Nigeria

West Afr J Med. 2023 Sep 28;40(9):956-961.

 

ABSTRACT

Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthol (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, and markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.

PMID:37769856 | DOI:10.1016/j.tiv.2023.105704

08:39

PubMed articles on: Cardio-Oncology

Hormone therapy, cardio-metabolic profile, and cardiotoxicity. Still a dark side of cardio-oncology - Part 2: Prostate cancer

G Ital Cardiol (Rome). 2023 Oct;24(10):781-791. doi: 10.1714/4100.40978.

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

08:39

PubMed articles on: Cancer & VTE/PE

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism

BMC Med. 2023 Sep 29;21(1):375. doi: 10.1186/s12916-023-03069-1.

ABSTRACT

BACKGROUND: Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).

METHODS: Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.

RESULTS: Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.

CONCLUSIONS: This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

PMID:37775786 | DOI:10.1186/s12916-023-03069-1

08:39

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

08:39

PubMed articles on: Cancer & VTE/PE

A case report: A patient rescued by VA-ECMO after cardiac arrest triggered by trigeminocardiac reflex after nasal surgery

Medicine (Baltimore). 2023 Sep 29;102(39):e35226. doi: 10.1097/MD.0000000000035226.

 

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis compares the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCS) versus pharmacological thromboprophylaxis alone.

SUMMARY BACKGROUND DATA: Surgical inpatients have elevated VTE risk; recent studies cast doubt whether GCS confer additional protection against VTE, compared to pharmacological thromboprophylaxis alone.

METHODS: The review followed PRISMA guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched to November 2022. Randomised trials reporting VTE rate after surgical procedures, utilising pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism (PE), VTE-related mortality were pooled via fixed and random effects.

RESULTS: In head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of PE for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants).

CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

PMID:37753655 | DOI:10.1097/SLA.0000000000006096

04:39

PubMed articles on: Cardio-Oncology

Tumor Progression Reverses Cardiac Hypertrophy and Fibrosis in a Tetracycline-Regulated ATF3 Transgenic Mouse Model

Cells. 2023 Sep 15;12(18):2289. doi: 10.3390/cells12182289.

ABSTRACT

Cardiovascular diseases (CVD) and cancer are the top deadly diseases in the world. Both CVD and cancer have common risk factors; therefore, with the advances in treatment and life span, both diseases may occur simultaneously in patients. It is becoming evident that CVD and cancer are highly connected, establishing a novel discipline known as cardio-oncology. This includes the cardiomyocyte death following any anti-tumor therapy known as cardiotoxicity as well the intricate interplay between heart failure and cancer. Recent studies, using various mouse models, showed that heart failure promotes tumor growth and metastasis spread. Indeed, patients with heart failure were found to be at higher risk of developing malignant diseases. While the effect of heart failure on cancer is well established, little is known regarding the effect of tumors on heart failure. A recent study from our lab has demonstrated that tumor growth and metastasis ameliorate cardiac remodeling in a pressure-overload mouse model. Nevertheless, this study was inconclusive regarding whether tumor growth solely suppresses cardiac remodeling or is able to reverse existing heart failure outcomes as well. Here, we used a regulable transgenic mouse model for cardiac hypertrophy and fibrosis. Cancer cell implantation suppressed cardiac dysfunction and fibrosis as shown using echocardiography, qRT-PCR and fibrosis staining. In addition, tumor growth resulted in an M1 to M2 macrophage switch, which is correlated with cardiac repair. Macrophage depletion using clodronate liposomes completely abrogated the tumors' beneficial effect. This study highly suggests that harnessing tumor paradigms may lead to the development of novel therapeutic strategies for CVDs and fibrosis.

PMID:37759510 | PMC:PMC10528851 | DOI:10.3390/cells12182289

C

08:39

Cardiotoxicity News

PubMed articles on: Cardio-Oncology

The Effects of Drug Exposure and SNPs on Aaptinib-induced Severe Toxicities in Solid Tumors

Drug Metab Dispos. 2023 Sep 29:DMD-AR-2023-001428. doi: 10.1124/dmd.123.001428. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities.

METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed.

RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P＜0.01; M1-1: P＜0.01) and high-grade anti-angiogenetic toxicities (APA: P = 0.034; P＜0.05), including hypertension, proteinuria and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P＜0.001) and M1-1 (P＜0.01) while CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P＜0.01).

CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need considering in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. Significance Statement Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

PMID:37775332 | DOI:10.1124/dmd.123.001428

08:39

PubMed articles on: Cardio-Oncology

Reverse cardio-oncology: A budding concept

Indian Heart J. 2023 Sep 27:S0019-4832(23)00163-3. doi: 10.1016/j.ihj.2023.09.004. Online ahead of print.

ABSTRACT

Having established the significance of cardiovascular side-effects of anti-neoplastic drugs, present day cardio-oncology has forayed into newer territories buoyed by research into the multiple connections that exist between cardiovascular disease and cancer. An emerging concept of reverse cardio-oncology focuses on the heightened risk of cancer in patients with cardiovascular disease. Common mechanistics of cancer and heart failure (HF) like chronic inflammation and clonal haematopoesis as well as common predisposing factors like obesity and diabetes underline the relation between both cardiovascular disease and various cancers.This review discusses the potential magnitude of the problem, the underlying pathophysiological mechanisms and classification of this novel subject.

PMID:37774949 | DOI:10.1016/j.ihj.2023.09.004

08:39

PubMed articles on: Cardio-Oncology

Early Echocardiography and ECG Changes Following Radiotherapy in Patients with Stage II-III HER2-Positive Breast Cancer Treated with Anthracycline-Based Chemotherapy with or without Trastuzumab-Based Therapy

Med Sci Monit. 2023 Sep 20;29:e941754. doi: 10.12659/MSM.941754.

ABSTRACT

BACKGROUND Cardiotoxicity from radiotherapy and anti-cancer therapies have been reported in patients with breast cancer. This study aimed to investigate the early echocardiography and ECG changes following radiotherapy in 68 patients ages 30-78 years with stages II-III HER2-positive breast cancer treated with anthracycline-based chemotherapy with or without trastuzumab-based therapy from 2015 to 2021. MATERIAL AND METHODS We analyzed data of 68 breast cancer patients aged 30-78 years, predominantly in AJCC stages II-III (61) and HER2-positive (58), treated and monitored from 2015 to 2021. Cardiac function was assessed using echo- and electrocardiography. We employed univariate logistic models to gauge associations between pre-existing cardiac conditions, treatment modalities, and changes in cardiac function. RESULTS A decrease in the left ventricle ejection fraction (EF) by >5% was associated with heart doses >49.3 Gy and with maximum and average doses to the left anterior descending artery (LAD) exceeding 46.9 Gy and 32.7 Gy, respectively. An EF drop of ≥10% was correlated with anti-HER2 therapy, pre-existing ECG changes, and the onset of conditions in the left ventricle, major vessels, and valves. Conditions were exacerbated in patients with prior echocardiographic abnormalities, while some emerged concurrent with the EF decline. CONCLUSIONS This research emphasizes the importance of personalized heart monitoring and care for breast cancer patients undergoing multimodal therapies. Significant and potentially irreversible EF declines can result from radiation and anti-HER2 treatments.

PMID:37772333 | DOI:10.12659/MSM.941754

08:39

PubMed articles on: Cardio-Oncology

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Aging (Albany NY). 2023 Sep 28;15. doi: 10.18632/aging.205062. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.

PMID:37770231 | DOI:10.18632/aging.205062

08:39

PubMed articles on: Cardio-Oncology

Osthole protects H9c2 cardiomyocytes against trastuzumab-induced damage by enhancing autophagy through the p38MAPK/mTOR signaling pathway

Toxicol In Vitro. 2023 Sep 26:105704. doi: 10.1016/j.tiv.2023.105704. Online ahead of print.

 

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

04:39

PubMed articles on: Cardio-Oncology

Hormone therapy, cardio-metabolic profile, and cardiotoxicity. Still a dark side of cardio-oncology - Part 2: Prostate cancer

G Ital Cardiol (Rome). 2023 Oct;24(10):781-791. doi: 10.1714/4100.40978.

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

04:39

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

04:39

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

04:39

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

04:39

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis practices for patients with sickle cell disease prior to and during the COVID-19 pandemic

Blood Coagul Fibrinolysis. 2023 Sep 21. doi: 10.1097/MBC.0000000000001250. Online ahead of print.

ABSTRACT

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% (N = 13) reported they only treat patients more than 21 years old; 38.7% (N = 36) only treat patients 0-21 years old and 47.3% (N = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children (P < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE.

PMID:37756203 | DOI:10.1097/MBC.0000000000001250

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PubMed articles on: Cancer & VTE/PE

A case of metastatic breast cancer complicated by pulmonary tumor thrombotic microangiopathy

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Oct 12;46(10):1014-1018. doi: 10.3760/cma.j.cn112147-20230521-00253.

ABSTRACT

Pulmonary tumor thrombotic microangiopathy is a malignancy-related complication with rapid progression and high mortality. To improve the understanding of the disease, early diagnosis and treatment are key to successful treatment. A 39-year-old patient with pulmonary hypertension transferred from another hospital was admitted to the First Affiliated Hospital of Guangzhou Medical University on September 26, 2021. The patient developed shortness of breath and progressive exacerbation over the past month. No pulmonary artery embolism was seen on computed tomography pulmonary angiography (CTPA) at the outside hospital where the breast cancer was diagnosed. Pulmonary tumor thrombotic microangiopathy was immediately considered on admission and oncological endocrine therapy was started. After treatment, the patient's dyspnoea improved, PET-CT showed significant tumor regression, and cardiac ultrasound showed a significant decrease in pulmonary artery pressure. The successful treatment experience of this case was summarized for reference.

PMID:37752045 | DOI:10.3760/cma.j.cn112147-20230521-00253

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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

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PubMed articles on: Cancer & VTE/PE

An Updated Systematic Review and Meta-Analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients

Ann Surg. 2023 Sep 27. doi: 10.1097/SLA.0000000000006096. Online ahead of print.

 

ABSTRACT

BACKGROUND: Arterial or venous thrombosis can complicate cancer, and 20% of cancer patients may develop venous thromboembolic disorders. Venous thromboembolism (VTE) is common in some haematologic malignancies and may coexist with thrombocytopenia in those haematologic malignancies. We carried out this survey to assess the knowledge and practice of haematologists and resident doctors in haematology in Nigeria regarding the management of thrombocytopenia and cancer-associated thrombosis.

METHODS: This was a survey that was shared electronically with participants who were consultant haematologists and resident doctors in haematology in Nigeria..

RESULTS: There were 106 respondents, 70 (66%) of which were consultant haematologists. About a third (30.2%) of the respondents saw 6-10 patients with blood malignancies monthly. Fifty-seven (53.8%) of the respondents carried out risk assessment in their patients for cancer-associated thrombosis (CAT); 63 (59.4%) of the respondents saw 1-2 cancer patients with thrombosis in 3 months. The most common mode of treatment was pharmacological - 94 (88%) respondents used low molecular weight heparin. The most common haematologic malignancies associated with thrombocytopenia were acute leukaemias (69; 67%). The most common decision taken by respondents was to stop anticoagulants and transfuse platelets because the most frequent concern was the risk of bleeding in this group of patients.

CONCLUSION: Many haematologists and haematology residents had a high level of awareness, knowledge and good practice regarding thrombocytopenia with CAT in haematooncology patients; however, there is a need for improved knowledge and unified protocols for treatment in line with newer management guidelines.

PMID:37767996

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PubMed articles on: Cardio-Oncology

Early Echocardiography and ECG Changes Following Radiotherapy in Patients with Stage II-III HER2-Positive Breast Cancer Treated with Anthracycline-Based Chemotherapy with or without Trastuzumab-Based Therapy

Med Sci Monit. 2023 Sep 20;29:e941754. doi: 10.12659/MSM.941754.

ABSTRACT

BACKGROUND Cardiotoxicity from radiotherapy and anti-cancer therapies have been reported in patients with breast cancer. This study aimed to investigate the early echocardiography and ECG changes following radiotherapy in 68 patients ages 30-78 years with stages II-III HER2-positive breast cancer treated with anthracycline-based chemotherapy with or without trastuzumab-based therapy from 2015 to 2021. MATERIAL AND METHODS We analyzed data of 68 breast cancer patients aged 30-78 years, predominantly in AJCC stages II-III (61) and HER2-positive (58), treated and monitored from 2015 to 2021. Cardiac function was assessed using echo- and electrocardiography. We employed univariate logistic models to gauge associations between pre-existing cardiac conditions, treatment modalities, and changes in cardiac function. RESULTS A decrease in the left ventricle ejection fraction (EF) by >5% was associated with heart doses >49.3 Gy and with maximum and average doses to the left anterior descending artery (LAD) exceeding 46.9 Gy and 32.7 Gy, respectively. An EF drop of ≥10% was correlated with anti-HER2 therapy, pre-existing ECG changes, and the onset of conditions in the left ventricle, major vessels, and valves. Conditions were exacerbated in patients with prior echocardiographic abnormalities, while some emerged concurrent with the EF decline. CONCLUSIONS This research emphasizes the importance of personalized heart monitoring and care for breast cancer patients undergoing multimodal therapies. Significant and potentially irreversible EF declines can result from radiation and anti-HER2 treatments.

PMID:37772333 | DOI:10.12659/MSM.941754

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PubMed articles on: Cardio-Oncology

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Aging (Albany NY). 2023 Sep 28;15. doi: 10.18632/aging.205062. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.

PMID:37770231 | DOI:10.18632/aging.205062

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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: Cardio-Oncology

Osthole protects H9c2 cardiomyocytes against trastuzumab-induced damage by enhancing autophagy through the p38MAPK/mTOR signaling pathway

Toxicol In Vitro. 2023 Sep 26:105704. doi: 10.1016/j.tiv.2023.105704. Online ahead of print.

ABSTRACT

Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthol (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, and markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.

PMID:37769856 | DOI:10.1016/j.tiv.2023.105704

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PubMed articles on: Cancer & VTE/PE

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

 

ABSTRACT

RATIONALE: Cardiac arrest (CA) caused by trigeminocardiac reflex (TCR) after endoscopic nasal surgery is rare. Hence, when a patient suffers from TCR induced CA in the recovery room, most doctors may not be able to find the cause in a short time, and standard cardiopulmonary resuscitation and resuscitation measures may not be effective. Providing circulatory assistance through venous-arterial extracorporeal membrane oxygenation (VA-ECMO) can help healthcare providers gain time to identify the etiology and initiate symptom-specific treatment.

PATIENT CONCERNS: We report a rare case of CA after endoscopic nasal surgery treated with VA-ECMO.

DIAGNOSES: We excluded myocardial infarction, pulmonary embolism, allergies, hypoxia, and electrolyte abnormalities based on the relevant examination results. Following a multidisciplinary consultation, clinical manifestation and a review of previous literature, we reasoned that the CA was due to TCR.

INTERVENTIONS: VA-ECMO was established to resuscitate the patient successfully during effective cardiopulmonary resuscitation.

OUTCOMES: ECMO was successfully evacuated a period of 190 minutes of therapy. The patient was discharged home on day 8.

LESSONS: TCR is notable during endoscopic nasal surgery. Our case indicates that CA in operating room is worth prolonged CCPR. The ideal time for ECPR implementation should not be limited within 20 minutes after CCPR.

PMID:37773828 | DOI:10.1097/MD.0000000000035226

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PubMed articles on: Cardio-Oncology

The Effects of Drug Exposure and SNPs on Aaptinib-induced Severe Toxicities in Solid Tumors

Drug Metab Dispos. 2023 Sep 29:DMD-AR-2023-001428. doi: 10.1124/dmd.123.001428. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities.

METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed.

RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P＜0.01; M1-1: P＜0.01) and high-grade anti-angiogenetic toxicities (APA: P = 0.034; P＜0.05), including hypertension, proteinuria and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P＜0.001) and M1-1 (P＜0.01) while CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P＜0.01).

CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need considering in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. Significance Statement Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

PMID:37775332 | DOI:10.1124/dmd.123.001428

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PubMed articles on: Cancer & VTE/PE

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery

JAMA Netw Open. 2023 Sep 5;6(9):e2335311. doi: 10.1001/jamanetworkopen.2023.35311.

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA).

OBJECTIVE: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023.

EXPOSURES: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology.

MAIN OUTCOMES AND MEASURES: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty.

RESULTS: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty.

CONCLUSIONS AND RELEVANCE: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

PMID:37768664 | PMC:PMC10539988 | DOI:10.1001/jamanetworkopen.2023.35311

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PubMed articles on: Cardio-Oncology

Reverse cardio-oncology: A budding concept

Indian Heart J. 2023 Sep 27:S0019-4832(23)00163-3. doi: 10.1016/j.ihj.2023.09.004. Online ahead of print.

ABSTRACT

Having established the significance of cardiovascular side-effects of anti-neoplastic drugs, present day cardio-oncology has forayed into newer territories buoyed by research into the multiple connections that exist between cardiovascular disease and cancer. An emerging concept of reverse cardio-oncology focuses on the heightened risk of cancer in patients with cardiovascular disease. Common mechanistics of cancer and heart failure (HF) like chronic inflammation and clonal haematopoesis as well as common predisposing factors like obesity and diabetes underline the relation between both cardiovascular disease and various cancers.This review discusses the potential magnitude of the problem, the underlying pathophysiological mechanisms and classification of this novel subject.

PMID:37774949 | DOI:10.1016/j.ihj.2023.09.004

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PubMed articles on: Cancer & VTE/PE

Survey on the Knowledge and Management of Cancer-Associated Thrombosis (CAT) in Haemato-Oncology Patients with Thrombocytopenia among Haematologists and Haematology Residents in Nigeria

West Afr J Med. 2023 Sep 28;40(9):956-961.

 

ABSTRACT

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

PMID:37762897 | PMC:PMC10531873 | DOI:10.3390/jcm12185955

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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.

ABSTRACT

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

PMID:37765020 | PMC:PMC10534320 | DOI:10.3390/ph16091212

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PubMed articles on: Cancer & VTE/PE

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis

Cancers (Basel). 2023 Sep 20;15(18):4640. doi: 10.3390/cancers15184640.

ABSTRACT

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.

PMID:37760609 | PMC:PMC10526875 | DOI:10.3390/cancers15184640

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PubMed articles on: Cancer & VTE/PE

A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients

Cancers (Basel). 2023 Sep 15;15(18):4588. doi: 10.3390/cancers15184588.

ABSTRACT

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

PMID:37760562 | PMC:PMC10527104 | DOI:10.3390/cancers15184588

C

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Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism

BMC Med. 2023 Sep 29;21(1):375. doi: 10.1186/s12916-023-03069-1.

ABSTRACT

BACKGROUND: Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).

METHODS: Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.

RESULTS: Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.

CONCLUSIONS: This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

PMID:37775786 | DOI:10.1186/s12916-023-03069-1

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PubMed articles on: Cancer & VTE/PE

A case report: A patient rescued by VA-ECMO after cardiac arrest triggered by trigeminocardiac reflex after nasal surgery

Medicine (Baltimore). 2023 Sep 29;102(39):e35226. doi: 10.1097/MD.0000000000035226.