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1/6/26

 


ABSTRACT


BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy.


MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive.


RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak.


CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.


PMID:37286435 | DOI:10.1016/j.clbc.2023.04.010

21:52

PubMed articles on: Cardio-Oncology

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design


J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.


ABSTRACT


AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme.


METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up.


CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines.


CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).


PMID:37285278 | DOI:10.2459/JCM.0000000000001491

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PubMed articles on: Cancer & VTE/PE

Adult breast, lung, pancreatic, upper and lower gastrointestinal cancer patients with hospitalized venous thromboembolism in the national French hospital discharge database


BMC Cancer. 2023 Jun 10;23(1):531. doi: 10.1186/s12885-023-10877-4.


ABSTRACT


BACKGROUND: Venous thromboembolism (VTE) and cancer are strongly associated. In France, evidence on patients with pancreatic, upper GI [gastrointestinal], lower GI, lung, or breast cancer-associated VTE and their hospital management is limited. The aims of this study were to provide data on the number of hospitalized VTE events among cancer patients, the patients' characteristics, and their hospital management to estimate the burden of disease and the hospital burden of cancer-related VTE and to provide guidance on research.


METHODS: This longitudinal, observational, and retrospective study was based on the comprehensive hospital discharge database (PMSI). Adult patients (≥ 18 years old) hospitalized with a cancer of interest in 2016 and hospitalized (within 2 years with VTE (captured a as a principal, related, or significant associated diagnosis) were included in the study.


RESULTS: We identified 340,946 cancer patients, of which 7.2% (24,433 patients) were hospitalized with VTE. The proportions of hospitalized VTE were 14.6% (3,237) for patients with pancreatic cancer, 11.2% (8,339) for lung cancer, 9.9% (2,232) for upper GI cancer, 6.7% (7,011) for lower GI cancer, and 3.1% (3,614) for breast cancer. Around two thirds of cancer patients with a hospitalized VTE had active cancer (with metastases and/or receiving chemotherapy during the six months prior to the index date): from 62% of patients with pancreatic cancer to 72% with breast cancer. Around a third of patients were admitted to the hospital through the emergency room, up to 3% of patients stayed in an intensive care unit. The average length of stay ranged from 10 (breast cancer) to 15 days (upper GI cancer). Nine (lower GI cancer) to 18% (pancreatic cancer) of patients died during the VTE hospital stay.


CONCLUSIONS: The burden of cancer-associated VTE is substantial, both in terms of the number of patients affected and in the hospital use. These findings offer guidance on future research on VTE prophylaxis in a very high-risk population, particularly in patients with active cancer.


PMID:37301828 | DOI:10.1186/s12885-023-10877-4

23:31

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PubMed articles on: Cancer & VTE/PE

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group


Clin Transl Oncol. 2023 Jun 10. doi: 10.1007/s12094-023-03233-2. Online ahead of print.


ABSTRACT


PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation.


METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification.


RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375).


CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.


PMID:37301805 | DOI:10.1007/s12094-023-03233-2

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PubMed articles on: Cancer & VTE/PE

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


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


ABSTRACT


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


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


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


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


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

23:31

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PubMed articles on: Cancer & VTE/PE

Clonal haematopoiesis of indeterminate potential in patients with venous thromboembolism


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


ABSTRACT


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


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

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PubMed articles on: Cancer & VTE/PE

Diagnostic Approach for Venous Thromboembolism in Cancer Patients


Cancers (Basel). 2023 Jun 2;15(11):3031. doi: 10.3390/cancers15113031.


ABSTRACT


Venous thromboembolic disease (VTE) is a common complication in cancer patients. The currently recommended VTE diagnostic approach involves a step-by-step algorithm, which is based on the assessment of clinical probability, D-dimer measurement, and/or diagnostic imaging. While this diagnostic strategy is well validated and efficient in the noncancer population, its use in cancer patients is less satisfactory. Cancer patients often present nonspecific VTE symptoms resulting in less discriminatory power of the proposed clinical prediction rules. Furthermore, D-dimer levels are often increased because of a hypercoagulable state associated with the tumor process. Consequently, the vast majority of patients require imaging tests. In order to improve VTE exclusion in cancer patients, several approaches have been developed. The first approach consists of ordering imaging tests to all patients, despite overexposing a population known to have mostly multiple comorbidities to radiations and contrast products. The second approach consists of new diagnostic algorithms based on clinical probability assessment with different D-dimer thresholds, e.g., the YEARS algorithm, which shows promise in improving the diagnosis of PE in cancer patients. The third approach uses an adjusted D-dimer threshold, to age, pretest probability, clinical criteria, or other criteria. These different diagnostic strategies have not been compared head-to-head. In conclusion, despite having several proposed diagnostic approaches to diagnose VTE in cancer patients, we still lack a dedicated diagnostic algorithm specific for this population.


PMID:37296993 | DOI:10.3390/cancers15113031

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PubMed articles on: Cancer & VTE/PE

Congenital hepatic hemangioma: an unusual case report of pulmonary hypertension

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12 June 2023

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PubMed articles on: Cardio-Oncology

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


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


ABSTRACT


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


PMID:37301767 | DOI:10.1161/JAHA.123.029361

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PubMed articles on: Cardio-Oncology

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


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


ABSTRACT


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


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

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PubMed articles on: Cardio-Oncology

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


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


ABSTRACT


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


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

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PubMed articles on: Cardio-Oncology

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


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


ABSTRACT


Patient education is an integral part of recovery from a critical cardiac life event and a core component of cardiac rehabilitation (CR) programmes. This study addressed the feasibility of a virtual educational programme for behaviour change in CR patients from a low-resource setting in Brazil. Cardiac patients from a CR programme closed due to the pandemic received a 12-week virtual educational intervention (WhatsApp messages and bi-weekly calls from healthcare providers). Acceptability, demand, implementation, practicality, and limited efficacy were tested. Overall, 34 patients and 8 healthcare providers agreed to participate. The intervention was considered practical and acceptable by the participants, who reported a satisfaction median of 9.0 (7.4-10.0)/10 (patients) and 9.8 (9.6-10.0)/10 (providers). The main difficulties in carrying out the intervention activities were related to technology, motivation to self-learning, and a lack of in-person orientation. All the patients reported that the information included in the intervention was aligned with their information needs. The intervention was associated with changes in exercise self-efficacy, sleep quality, depressive symptoms, and performance of high-intensity physical activity. In conclusion, the intervention was considered feasible to educate cardiac patients from a low-resource setting. It should be replicated and expanded to support patients that face barriers to onsite CR participation. Challenges related to technology and self-learning should be addressed.


PMID:37297538 | PMC:PMC10252834 | DOI:10.3390/ijerph20115934

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PubMed articles on: Cardio-Oncology

Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology


Cancers (Basel). 2023 Jun 5;15(11):3055. doi: 10.3390/cancers15113055.


ABSTRACT


It is more likely that a long-term survivor will have both cardiovascular disease and cancer on account of the progress in cancer therapy. Cardiotoxicity is a well-recognized and highly concerning adverse effect of cancer therapies. This side effect can manifest in a proportion of cancer patients and may lead to the discontinuation of potentially life-saving anticancer treatment regimens. Consequently, this discontinuation may adversely affect the patient's survival prognosis. There are various underlying mechanisms by which each anticancer treatment affects the cardiovascular system. Similarly, the incidence of cardiovascular events varies with different protocols for malignant tumors. In the future, comprehensive cardiovascular risk assessment and clinical monitoring should be considered for cancer treatments. Baseline cardiovascular evaluation risk should be emphasized prior to initiating clinical therapy in patients. Additionally, we highlight that there is a need for cardio-oncology to avoid or prevent cardiovascular side effects. Cardio-oncology service is based on identifying cardiotoxicity, developing strategies to reduce these toxicities, and minimizing long-term cardiotoxic effects.


PMID:37297017 | PMC:PMC10252624 | DOI:10.3390/cancers15113055

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PubMed articles on: Cardio-Oncology

The Role of the Cardiac Biomarkers in the Renal Cell Carcinoma Multidisciplinary Management


Diagnostics (Basel). 2023 May 30;13(11):1912. doi: 10.3390/diagnostics13111912.


ABSTRACT


Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients.


PMID:37296764 | PMC:PMC10253077 | DOI:10.3390/diagnostics13111912

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PubMed articles on: Cardio-Oncology

Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies


Diagnostics (Basel). 2023 May 26;13(11):1864. doi: 10.3390/diagnostics13111864.


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  ABSTRACT Doxorubicin (Dox) is a highly potent chemotherapy drug. Despite its efficacy, Dox's clinical application is limited due to it...