RESUMEN
Micro-LiNiCoMnO2 (MNCM), a cathode material with highest market share, has increasing demand with the growth of lithium battery industry. However, whether MNCM exposure brings adverse effects to workers remains unclear. This study aimed to explore the association between MNCM exposure with systemic inflammation and cardiac function. A cross-sectional study of 347 workers was undertaken from the MNCM production industry in Guangdong province, China in 2020. Metals in urine were measured using ICP-MS. The associations between metals, systemic inflammation, and cardiac function were appraised using a linear or logistic regression model. Bayesian kernel machine regression (BKMR) and generalized weighted quantile sum (gWQS) models were used to explore mixed metal exposures. The analysis of interaction and mediation was adopted to assess the role of inflammation in the relation between urinary metals and cardiac function. We observed that the levels of lithium (Li) and cobalt (Co) were positively associated with systemic inflammation and heart rate. The amount of Co contributed the highest weight on the increased systemic immune-inflammation index (SII) (59.8%), the system inflammation response index (SIRI) (44.3%), and heart rate (65.0%). Based on the mediation analysis, we estimated that SII mediated 32.3% and 20.9% of the associations between Li and Co with heart rate, and SIRI mediated 44.6% and 22.2% of the associations between Li and Co with heart rate, respectively. This study demonstrated for the first time that MNCM exposure increased the risk of workers' systemic inflammation and elevated heart rate, which were contributed by the excessive Li and Co exposure. Additionally, it indicates that systemic inflammation was a major mediator of the associations of Li and Co with cardiac function in MNCM production workers.
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Cobalto , Inflamación , Litio , Exposición Profesional , Exposición Profesional/estadística & datos numéricos , Humanos , Adulto , Masculino , China , Estudios Transversales , Persona de Mediana Edad , Electrodos , Suministros de Energía Eléctrica , Femenino , Cardiopatías/inducido químicamenteRESUMEN
This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.
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Suplementos Dietéticos , Inositol , Ratones Endogámicos C57BL , Animales , Masculino , Ratones , Administración Oral , Inositol/farmacología , Inositol/administración & dosificación , Litio/administración & dosificación , Litio/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/prevención & control , Arritmias Cardíacas/tratamiento farmacológico , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Cardiopatías/patología , Cardiopatías/tratamiento farmacológicoRESUMEN
Chemotherapy has markedly improved cancer outcomes, yet cancer therapy-related cardiac dysfunction (CTRCD) poses a significant challenge, affecting around 10% of patients. CTRCD can be asymptomatic or present with heart failure symptoms. Multimodality imaging, particularly echocardiography, remains pivotal for monitoring cardiac function. Potential biomarkers for CTRCD assessment include troponin and B-type natriuretic peptide. Pharmacological interventions, such as dexrazoxane, angiotensin-converting enzyme inhibitors, and statins, play a crucial role in primary prevention and mitigating cardiotoxicity alongside cardiac rehabilitation programs. Thus, a comprehensive approach is essential for optimal cardiac recovery and improved patient outcomes.
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Antineoplásicos , Cardiotoxicidad , Cardiopatías , Neoplasias , Recuperación de la Función , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Cardiopatías/fisiopatología , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico , Cardiopatías/diagnóstico por imagen , Cardiopatías/terapia , Cardiopatías/prevención & control , Resultado del Tratamiento , Factores de Riesgo , Rehabilitación Cardiaca , Biomarcadores/sangreRESUMEN
There is a known genetic susceptibility to anthracycline-induced cardiac dysfunction in childhood cancer survivors, but this has not been adequately shown in adolescent and young adult (AYA) patients. Our aim was to determine if the previously identified variants associated with cardiac dysfunction in childhood cancer patients affect AYA cancer patients similarly. Forty-five variants were selected for analysis in 253 AYAs previously treated with anthracyclines. We identified four variants that were associated with cardiac dysfunction: SLC10A2:rs7319981 (p = 0.017), SLC22A17:rs4982753 (p = 0.019), HAS3:rs2232228 (p = 0.023), and RARG:rs2229774 (p = 0.050). HAS3:rs2232228 and SLC10A2:rs7319981 displayed significant effects in our AYA cancer survivor population that were in the opposite direction than that reported in childhood cancer survivors. Genetic variants in the host genes were further analyzed for additional associations with cardiotoxicity in AYA cancer survivors. The host genes were then evaluated in a panel of induced pluripotent stem cell-derived cardiomyocytes to assess changes in levels of expression when treated with doxorubicin. Significant upregulation of HAS3 and SLC22A17 expression was observed (p < 0.05), with non-significant anthracycline-responsivity observed for RARG. Our study demonstrates that there is a genetic influence on cardiac dysfunction in AYA cancer patients, but there may be a difference in the role of genetics between childhood and AYA cancer survivors.
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Antraciclinas , Supervivientes de Cáncer , Cardiotoxicidad , Predisposición Genética a la Enfermedad , Humanos , Adolescente , Antraciclinas/efectos adversos , Adulto Joven , Masculino , Femenino , Cardiotoxicidad/genética , Adulto , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Polimorfismo de Nucleótido Simple/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Cardiopatías/inducido químicamente , Cardiopatías/genética , Antibióticos Antineoplásicos/efectos adversos , Factores de RiesgoRESUMEN
Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.
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Antineoplásicos , Cardiotoxicidad , Nanomedicina , Nanomedicina Teranóstica , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/química , Cardiotoxicidad/etiología , Nanomedicina/métodos , Nanomedicina Teranóstica/métodos , Animales , Cardiopatías/inducido químicamente , Neoplasias/tratamiento farmacológico , Nanopartículas/químicaRESUMEN
OBJECTIVES: To identify subgroups of patients with distinct cough occurrence profiles and evaluate for differences among these subgroups. SAMPLE & SETTING: Outpatients receiving chemotherapy (N = 1,338) completed questionnaires six times over two chemotherapy cycles. METHODS & VARIABLES: Occurrence of cough was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups with distinct cough occurrence profiles. Parametric and nonparametric tests were used to evaluate for differences. RESULTS: Four distinct cough profiles were identified (None, Decreasing, Increasing, and High). Risk factors associated with membership in the High class included lower annual household income; history of smoking; self-reported diagnoses of lung disease, heart disease, and back pain; and having lung cancer. IMPLICATIONS FOR NURSING: Clinicians need to assess all patients with cancer for cough and provide targeted interventions.
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Comorbilidad , Tos , Neoplasias , Fumar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fumar/epidemiología , Adulto , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Factores de Riesgo , Renta/estadística & datos numéricos , Cardiopatías/inducido químicamente , Cardiopatías/epidemiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Costo de Enfermedad , Carga SintomáticaRESUMEN
Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose clinical use is hindered by the onset of cardiotoxic effects, resulting in reduced ejection fraction within the first year from treatment initiation. Recently it has been demonstrated that DOX accumulates within mitochondria, leading to disruption of metabolic processes and energetic imbalance. We previously described that phosphoinositide 3-kinase γ (PI3Kγ) contributes to DOX-induced cardiotoxicity, causing autophagy inhibition and accumulation of damaged mitochondria. Here we intend to describe the maladaptive metabolic rewiring occurring in DOX-treated hearts and the contribution of PI3Kγ signalling to this process. Metabolomic analysis of DOX-treated WT hearts revealed an accumulation of TCA cycle metabolites due to a cycle slowdown, with reduced levels of pyruvate, unchanged abundance of lactate and increased Acetyl-CoA production. Moreover, the activity of glycolytic enzymes was upregulated, and fatty acid oxidation downregulated, after DOX, indicative of increased glucose oxidation. In agreement, oxygen consumption was increased in after pyruvate supplementation, with the formation of cytotoxic ROS rather than energy production. These metabolic changes were fully prevented in KD hearts. Interestingly, they failed to increase glucose oxidation in response to DOX even with autophagy inhibition, indicating that PI3Kγ likely controls the fuel preference after DOX through an autophagy-independent mechanism. In vitro experiments showed that inhibition of PI3Kγ inhibits pyruvate dehydrogenase (PDH), the key enzyme of Randle cycle regulating the switch from fatty acids to glucose usage, while decreasing DOX-induced mobilization of GLUT-4-carrying vesicles to the plasma membrane and limiting the ensuing glucose uptake. These results demonstrate that PI3Kγ promotes a maladaptive metabolic rewiring in DOX-treated hearts, through a two-pronged mechanism controlling PDH activation and GLUT-4-mediated glucose uptake.
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Cardiotoxicidad , Doxorrubicina , Metabolismo Energético , Ácidos Grasos , Glucosa , Oxidación-Reducción , Animales , Doxorrubicina/toxicidad , Glucosa/metabolismo , Ácidos Grasos/metabolismo , Metabolismo Energético/efectos de los fármacos , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Glucólisis/efectos de los fármacos , Autofagia/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Ciclo del Ácido Cítrico/efectos de los fármacos , Ratones Endogámicos C57BL , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/patología , Cardiopatías/prevención & control , Cardiopatías/fisiopatología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/patología , Mitocondrias Cardíacas/enzimología , Ratones Noqueados , Modelos Animales de Enfermedad , Especies Reactivas de Oxígeno/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Antibióticos Antineoplásicos/toxicidad , Antibióticos Antineoplásicos/efectos adversosRESUMEN
Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-ß1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-ß1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.
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Berberina , Curcumina , Ciclofosfamida , Fibrosis , Miocardio , Canales Catiónicos TRPM , Animales , Canales Catiónicos TRPM/metabolismo , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Masculino , Ratas , Curcumina/farmacología , Berberina/farmacología , Miocardio/metabolismo , Miocardio/patología , Biomarcadores/metabolismo , Biomarcadores/sangre , Lípidos/sangre , Ratas Wistar , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/patología , Cardiopatías/prevención & control , Cardiopatías/tratamiento farmacológicoAsunto(s)
Foramen Oval Permeable , Heparina , Trombocitopenia , Trombosis , Humanos , Trombocitopenia/inducido químicamente , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Heparina/efectos adversos , Trombosis/inducido químicamente , Trombosis/diagnóstico por imagen , Femenino , Anticoagulantes/efectos adversos , Masculino , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico por imagen , Cardiopatías/etiología , Persona de Mediana EdadRESUMEN
Doxorubicin (DOX) is an effective anticancer agent, yet its clinical utility is hampered by dose-dependent cardiotoxicity. This study explores the cardioprotective potential of Marein (Mar) against DOX-induced cardiac injury and elucidates underlying molecular mechanisms. Neonatal rat cardiomyocytes (NRCMs) and murine models were employed to assess the impact of Mar on DOX-induced cardiotoxicity (DIC). In vitro, cell viability, oxidative stress were evaluated. In vivo, a chronic injection method was employed to induce a DIC mouse model, followed by eight weeks of Mar treatment. Cardiac function, histopathology, and markers of cardiotoxicity were assessed. In vitro, Mar treatment demonstrated significant cardioprotective effects in vivo, as evidenced by improved cardiac function and reduced indicators of cardiac damage. Mechanistically, Mar reduced inflammation, oxidative stress, and apoptosis in cardiomyocytes, potentially via activation of the Focal Adhesion Kinase (FAK)/AKT pathway. Mar also exhibited an anti-ferroptosis effect. Interestingly, Mar did not compromise DOX's efficacy in cancer cells, suggesting a dual benefit in onco-cardiology. Molecular docking studies suggested a potential interaction between Mar and FAK. This study demonstrates Mar's potential as a mitigator of DOX-induced cardiotoxicity, offering a translational perspective on its clinical application. By activating the FAK/AKT pathway, Mar exerts protective effects against DOX-induced cardiomyocyte damage, highlighting its promise in onco-cardiology. Further research is warranted to validate these findings and advance Mar as a potential adjunctive therapy in cancer treatment.
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Apoptosis , Cardiotoxicidad , Modelos Animales de Enfermedad , Doxorrubicina , Quinasa 1 de Adhesión Focal , Cardiopatías , Miocitos Cardíacos , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Doxorrubicina/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/metabolismo , Transducción de Señal/efectos de los fármacos , Quinasa 1 de Adhesión Focal/metabolismo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/prevención & control , Cardiopatías/enzimología , Cardiopatías/patología , Masculino , Antraquinonas/farmacología , Ratones Endogámicos C57BL , Ratas Sprague-Dawley , Ratas , Línea Celular Tumoral , Citoprotección , Células Cultivadas , Antibióticos Antineoplásicos/toxicidad , RatonesRESUMEN
The development and use of HER2-targeted drugs has improved the prognosis of HER2-positive cancer patients. However, in addition to improved survival rates, treatment-induced adverse events and nontumor-related deaths have increased. We sought to assess the incidence of cardiovascular adverse events when HER2-targeted drugs are combined with other drugs. We systematically searched the literature on the cardiotoxicity of anti-HER2 drugs in electronic databases, including PubMed, Web of Science, Cochrane Library, OVID and CNKI, from their inception to April 2022. The Cochrane Collaboration's tool for assessing risk of bias and the Jadad scale were used to evaluate the risk of bias and quality of the studies, respectively. For each included trial, we calculated the incidence of cardiovascular adverse effects (CAEs) and 95% confidence intervals (95% CIs) and performed a meta-analysis using a random effects model (REM). The meta-analysis was performed using R 4.2.1. We included 41 randomized clinical trials (RCTs) in the meta-analysis, consisting of 56 groups and 31,934 patients. The meta-analysis revealed the following: (1) The incidence of cardiotoxicity in groups given monoclonal antibody treatment was 14% for single therapy (95% CI: 2-34%) and 10%, 11%, and 12% for adjuvant therapy combined with combined therapy (95% CI: 6-13%), chemotherapy (95% CI: 8-13%) and endocrine therapy (95% CI: 7-18%), respectively. However, in the groups treated with the antibodyâdrug conjugates (ADCs), the percentage of patients treated with the combination therapy was 1% (95% CI: 0-2%) and 5% (95% CI: 4-7%), respectively, with a significant difference (P < 0.01). The heterogeneity among the included studies was significant (I2 = 94%, p < 0.01). (2) When monoclonal antibodies were combined with chemotherapy, the incidence of cardiotoxicity under anthracycline-containing therapy (10.3%) was significantly greater than that under nonanthracycline-containing therapy (8.8%). (3) Significant differences were found between subgroups, except for the endocrine group versus some others, although this difference might result from the different inclusion criteria of the original trials. (1) When anti-HER2 drugs are administered in combination with anthracycline-containing chemotherapy, the incidence of cardiotoxicity is greater than with other drugs. (2) Safety benefits can be achieved by replacing traditional monoclonal antibodies with ADCs. The comprehensive use of these drugs necessitates collaboration between oncologists and cardiologists.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cardiotoxicidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2 , Humanos , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Medición de Riesgo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores de Riesgo , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Terapia Molecular Dirigida , Anciano , Incidencia , Inhibidores de Proteínas Quinasas/efectos adversos , Masculino , Adulto , Cardiopatías/inducido químicamente , Cardiopatías/epidemiología , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias/tratamiento farmacológicoRESUMEN
The survival of pediatric cancer patients has significantly increased thanks to the improvement of oncological treatments. Therefore, it is of utmost importance to manage short- and long-term cardiovascular complications. In pediatric cardio-oncology, there are no recognized guidelines as in adults. Several recommendations and many indications have been derived from the data obtained in the adult cancer population, resulting in greater discrepancies in the clinical management of patients. The aim of this position paper of the Italian Society of Pediatric Cardiology (SICP) is to collect the main evidence regarding the diagnosis, prevention, treatment and follow-up of cardiotoxicity in children, to provide useful indications for clinical practice, and to promote a network between pediatric centers.
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Antineoplásicos , Cardiotoxicidad , Neoplasias , Humanos , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Niño , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Italia , Enfermedades Cardiovasculares/prevención & control , Cardiología , Estudios de Seguimiento , Cardiopatías/prevención & control , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico , Sociedades MédicasRESUMEN
INTRODUCTION: Use of doxorubicin, an anthracycline chemotherapeutic agent has been associated with late-occurring cardiac toxicities. Detection of early-occurring cardiac effects of cancer chemotherapy is essential to prevent occurrence of adverse events including toxicity, myocardial dysfunction, and death. OBJECTIVE: To investigate the prevalence of elevated cardiac troponin T (cTnT) and associated factors of myocardial injury in children on doxorubicin cancer chemotherapy. METHODS: Design: A cross-sectional study. SETTING AND SUBJECTS: A hospital-based study conducted on children aged 1-month to 12.4-years who had a diagnosis of cancer and were admitted at Kenyatta National Hospital (KNH). INTERVENTIONS AND OUTCOMES: The patients underwent Echocardiography (ECHO) before their scheduled chemotherapy infusion. Twenty-four (24) hours after the chemotherapy infusion the patients had an evaluation of the serum cardiac troponin T (cTnT) and a repeat ECHO. Myocardial injury was defined as cTnT level > 0.014 ng/ml or a Fractional Shortening (FS) of < 29% on ECHO. RESULTS: One hundred (100) children were included in the final analysis. Thirty-two percent (32%) of the study population had an elevated cTnT. A cumulative doxorubicin dose of > 175 mg/m2 was significantly associated with and elevated cTnT (OR, 10.76; 95% CI, 1.18-97.92; p = 0.035). Diagnosis of nephroblastoma was also associated with an elevated cTnT (OR, 3.0; 95% CI, 1.23-7.26) but not statistically significant (p = 0.105). Nine percent (9%) of the participants had echocardiographic evidence of myocardial injury. CONCLUSION: When compared to echocardiography, elevated levels of cTnT showed a higher association with early-occurring chemotherapy-induced myocardial injury among children on cancer treatment at a tertiary teaching and referral hospital in Kenya.
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Antibióticos Antineoplásicos , Biomarcadores , Cardiotoxicidad , Doxorrubicina , Neoplasias , Centros de Atención Terciaria , Troponina T , Humanos , Estudios Transversales , Masculino , Femenino , Doxorrubicina/efectos adversos , Niño , Kenia/epidemiología , Troponina T/sangre , Preescolar , Antibióticos Antineoplásicos/efectos adversos , Lactante , Neoplasias/tratamiento farmacológico , Neoplasias/sangre , Factores de Riesgo , Biomarcadores/sangre , Prevalencia , Factores de Tiempo , Regulación hacia Arriba , Cardiopatías/inducido químicamente , Cardiopatías/epidemiología , Cardiopatías/diagnóstico por imagen , Cardiopatías/diagnóstico , Cardiopatías/sangre , Factores de Edad , Medición de Riesgo , EcocardiografíaRESUMEN
NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.
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Antiinflamatorios , Antioxidantes , Arsenitos , Betaína , Cardiotoxicidad , Modelos Animales de Enfermedad , Cardiopatías , Mediadores de Inflamación , Estrés Oxidativo , Transducción de Señal , Compuestos de Sodio , Animales , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Masculino , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/farmacología , Ratones , Betaína/farmacología , Cardiopatías/prevención & control , Cardiopatías/inducido químicamente , Cardiopatías/patología , Cardiopatías/metabolismo , Mediadores de Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Biomarcadores/metabolismo , Biomarcadores/sangre , Citoprotección , Miocardio/patología , Miocardio/metabolismoRESUMEN
Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.
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Antineoplásicos Inmunológicos , Función del Atrio Izquierdo , Neoplasias de la Mama , Cardiotoxicidad , Receptor ErbB-2 , Trastuzumab , Función Ventricular Izquierda , Humanos , Trastuzumab/efectos adversos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Estudios Prospectivos , Antineoplásicos Inmunológicos/efectos adversos , Función Ventricular Izquierda/efectos de los fármacos , Función del Atrio Izquierdo/efectos de los fármacos , Adulto , Factores de Tiempo , Factores de Riesgo , Resultado del Tratamiento , Anciano , Valor Predictivo de las Pruebas , Medición de Riesgo , Remodelación Atrial/efectos de los fármacos , Cardiopatías/inducido químicamente , Cardiopatías/fisiopatología , Cardiopatías/diagnóstico por imagen , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/diagnóstico por imagen , Volumen Sistólico/efectos de los fármacosRESUMEN
Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.
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Antraciclinas , Antibióticos Antineoplásicos , Cardiotoxicidad , Cardiopatías , Neoplasias , Valor Predictivo de las Pruebas , Humanos , Antraciclinas/efectos adversos , Neoplasias/tratamiento farmacológico , Antibióticos Antineoplásicos/efectos adversos , Femenino , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico por imagen , Cardiopatías/fisiopatología , Cardiopatías/diagnóstico , Masculino , Persona de Mediana Edad , Diagnóstico Precoz , Factores de Riesgo , Adulto , Anciano , Medición de Riesgo , Imagen por Resonancia Magnética , Función Ventricular Izquierda/efectos de los fármacos , Adulto JovenRESUMEN
The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1ß), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1ß, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1ß, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.
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Cardiotoxicidad , Suplementos Dietéticos , Modelos Animales de Enfermedad , Cardiopatías , Interleucina-18 , Metanfetamina , Condicionamiento Físico Animal , Piroptosis , Ratas Wistar , Animales , Metanfetamina/toxicidad , Metanfetamina/administración & dosificación , Masculino , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Piroptosis/efectos de los fármacos , Interleucina-18/metabolismo , Interleucina-18/genética , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Cardiopatías/patología , Cardiopatías/fisiopatología , Cardiopatías/metabolismo , Síndrome de Abstinencia a Sustancias/fisiopatología , Síndrome de Abstinencia a Sustancias/metabolismo , Síndrome de Abstinencia a Sustancias/prevención & control , Caspasa 1/metabolismo , Caspasa 1/genética , Estimulantes del Sistema Nervioso Central/toxicidad , Estimulantes del Sistema Nervioso Central/administración & dosificación , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Miocardio/metabolismo , Miocardio/patología , Ratas , Trastornos Relacionados con Anfetaminas/fisiopatología , Trastornos Relacionados con Anfetaminas/metabolismo , Trastornos Relacionados con Anfetaminas/terapia , Factores de TiempoRESUMEN
BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.