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Transplantation ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31403557


BACKGROUND: Data on the prevention of fractures after heart transplant (HTx) are controversial in the literature. Understanding the effects of HTx on bone may guide appropriate treatments in this high-risk population. METHODS: Seventy adult HTx patients were followed for 12 months. Clinical and laboratory parameters, bone mineral density (BMD), microarchitecture and vertebral fractures were assessed at baseline (after intensive care unit discharge) and at 6 and 12 months. Patients received recommendations regarding calcium intake and vitamin D supplementation after HTx. RESULTS: At baseline, 27% of patients had osteoporosis, associated with the length of hospitalization before HTx (p=0.001). BMD decreased in the first 6 months, with partial recovery later. Bone microarchitecture deteriorated, mainly in the trabecular bone in the first 6 months and cortical bone in the subsequent 6 months. At baseline, 92.9% of patients had vitamin D levels <30 ng/mL and 20.0% <10 ng/mL. Patients also had calcium at the lower limit of normal, high alkaline phosphatase, and high bone resorption biomarker. These abnormalities were suggestive of impaired bone mineralization and normalized at 6 months with correction of vitamin D deficiency. The majority of vertebral fractures were identified at baseline (23% of patients). After multivariate analyses, only a lower fat mass persisted as a risk factor for vertebral fractures (OR 1.23, 95% CI 1.04-1.47, p=0.012). CONCLUSIONS: High frequencies of densitometric osteoporosis, vitamin D deficiency, bone markers abnormalities and vertebral fractures were observed shortly after HTx. Calcium and vitamin D supplementation should be the first step in correcting bone mineralization impairment before specific osteoporosis treatment.

Oncotarget ; 8(4): 6994-7002, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28052002


Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from "Carvedilol Effect on Chemotherapy-induced Cardiotoxicity" (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.

Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/genética , Doxorrubicina/efeitos adversos , MicroRNAs/sangue , Biomarcadores , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Carbazóis , Cardiotoxicidade/sangue , Cardiotoxicidade/fisiopatologia , Carvedilol , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Propanolaminas , Curva ROC , Volume Sistólico/efeitos dos fármacos , Troponina C/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos