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4/12/26

ABSTRACT

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

PMID:37489755 | DOI:10.1161/JAHA.123.029618

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PubMed articles on: Cardio-Oncology

Radiation-Induced Pericardial Disease: Mechanisms, Diagnosis, and Treatment

Curr Cardiol Rep. 2023 Aug 16. doi: 10.1007/s11886-023-01933-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: We aim to give a concise overview of the different clinical manifestations of both acute and long-term radiotherapy-related pericardial diseases, the underlying pathophysiology as well as the diagnosis and treatment options.

RECENT FINDINGS: Radiotherapy-related pericardial disease is common, but despite radiotherapy being a cornerstone of many cancer treatments, this disease entity is relatively underrepresented in clinical trials, resulting in a paucity of research data on pathophysiology and management. Since the development of innovative cancer treatments, survival has significantly improved. Therefore, the importance of long-term treatment-related side effects increases, most notably cancer treatment-related cardiovascular toxicity. In patients undergoing radiotherapy as a part of their cancer treatment, radiotherapy-related pericardial disease can manifest early (during or shortly after radiotherapy administration) or very late (several years to decades after treatment). This exceptionally long latency period confronts physicians with treatment-related side effects of radiotherapy regimens that may have been abandoned already.

PMID:37584875 | DOI:10.1007/s11886-023-01933-3

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PubMed articles on: Cardio-Oncology

Discovery of 2-Aminopyrimidine Derivatives as Potent Dual FLT3/CHK1 Inhibitors with Significantly Reduced hERG Inhibitory Activities

J Med Chem. 2023 Aug 16. doi: 10.1021/acs.jmedchem.3c00245. Online ahead of print.

ABSTRACT

FLT3 inhibitors as single agents have limited effects because of acquired and adaptive resistance and the cardiotoxicity related to human ether-a-go-go-related gene (hERG) channel blockade further impedes safe drugs to the market. Inhibitors having potential to overcome resistance and reduce hERG affinity are highly demanded. Here, we reported a dual FLT3/CHK1 inhibitor 18, which displayed potencies to overcome varying acquired resistance in BaF3 cells with FLT3-TKD and FLT3-ITD-TKD mutations. Moreover, 18displayed high selectivity over c-KIT more than 1700-fold and greatly reduced hERG affinity, with an IC50 value of 58.4 μM. Further mechanistic studies demonstrated 18can upregulate p53 and abolish the outgrowth of adaptive resistant cells. In the in vivo studies, 18demonstrated favorable PK profiles and good safety, suppressed the tumor growth in the MV-4-11 cell inoculated mouse xenograft model, and prolonged the survival in the Molm-13 transplantation model, supporting its further development.

PMID:37584545 | DOI:10.1021/acs.jmedchem.3c00245