ABSTRACT
OBJECTIVES: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE.
METHODS: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 μg/ml.
RESULTS: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001
CONCLUSIONS: LLVU in patients with a preoperative D-dimer>1.0 μg/ml is a useful method to prevent postoperative symptomatic VTE.
PMID:37496573 | PMC:PMC10368439 | DOI:10.23922/jarc.2022-071
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PubMed articles on: Cancer & VTE/PE
Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study
J Am Heart Assoc. 2023 Aug;12(15):e029618. doi: 10.1161/JAHA.123.029618. Epub 2023 Jul 25.
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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90 days is probably higher with combined endovenous ablation and compression compared with compression therapy alone or compression with deferred endovenous treatment (risk ratio (RR) 1.14, 95% CI 1.00 to 1.30; I2 = 0%; 2 studies, 466 participants). There is low-certainty evidence showing an unclear effect on ulcer recurrence at one year in people with healed ulcers with combined endovenous treatment and compression when compared with compression alone or compression with deferred endovenous treatment (RR 0.29, 95% CI 0.03 to 2.48; I2 = 78%; 2 studies, 460 participants). There is also low-certainty evidence that the median number of ulcer-free days at one year may not differ (306 (interquartile range (IQR) 240 to 328) days versus 278 (IQR 175 to 324) days) following combined endovenous treatment and compression when compared with compression and deferred endovenous treatment; (1 study, 450 participants). There is low-certainty evidence of an unclear effect in rates of thromboembolism between groups (RR 2.02, 95% CI 0.51 to 7.97; I2 = 78%, 2 studies, 506 participants). The addition of endovenous ablation to compression is probably cost-effective at one year (99% probability at GBP 20,000/QALY; 1 study; moderate-certainty evidence).
AUTHORS' CONCLUSIONS: Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.
PMID:37497816 | PMC:PMC10373122 | DOI:10.1002/14651858.CD009494.pub3
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PubMed articles on: Cardio-Oncology
Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study
Cancer Med. 2023 Aug 16. doi: 10.1002/cam4.6455. Online ahead of print.
ABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions.
OBJECTIVES: We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs).
METHODS: A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow-up duration. Logistic regression analysis identified ATE risk factors in ICI-treated patients.
RESULTS: Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non-ICI group (RR, 2.01 [95% CI (1.61-2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI-treated patients within 1 year (Limited to a max 9-month follow-up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI-treated patients.
CONCLUSION: ICI-treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.
PMID:37584246 | DOI:10.1002/cam4.6455
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PubMed articles on: Cardio-Oncology
BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice
Cell Death Dis. 2023 Aug 15;14(8):523. doi: 10.1038/s41419-023-06011-8.
ABSTRACT
Long-living individuals (LLIs) escape age-related cardiovascular complications until the very last stage of life. Previous studies have shown that a Longevity-Associated Variant (LAV) of the BPI Fold Containing Family B Member 4 (BPIFB4) gene correlates with an extraordinarily prolonged life span. Moreover, delivery of the LAV-BPIFB4 gene exerted therapeutic action in murine models of atherosclerosis, limb ischemia, diabetic cardiomyopathy, and aging. We hypothesize that downregulation of BPIFB4 expression marks the severity of coronary artery disease (CAD) in human subjects, and supplementation of the LAV-BPIFB4 protects the heart from ischemia. In an elderly cohort with acute myocardial infarction (MI), patients with three-vessel CAD were characterized by lower levels of the natural logarithm (Ln) of peripheral blood BPIFB4 (p = 0.0077). The inverse association between Ln BPIFB4 and three-vessel CAD was confirmed by logistic regression adjusting for confounders (Odds Ratio = 0.81, p = 0.0054). Moreover, in infarcted mice, a single administration of LAV-BPIFB4 rescued cardiac function and vascularization. In vitro studies showed that LAV-BPIFB4 protein supplementation exerted chronotropic and inotropic actions on induced pluripotent stem cell (iPSC)-derived cardiomyocytes. In addition, LAV-BPIFB4 inhibited the pro-fibrotic phenotype in human cardiac fibroblasts. These findings provide a strong rationale and proof of concept evidence for treating CAD with the longevity BPIFB4 gene/protein.
PMID:37582912 | DOI:10.1038/s41419-023-06011-8
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PubMed articles on: Cardio-Oncology
Pretreatment with tadalafil attenuates cardiotoxicity induced by combretastatin A4 disodium phosphate in rats
J Toxicol Pathol. 2023 Jul;36(3):151-158. doi: 10.1293/tox.2022-0143. Epub 2023 Feb 15.
ABSTRACT
Combretastatin A4 disodium phosphate (CA4DP) is a prodrug of combretastatin A4 (CA4), a microtubule-disassembling agent that exhibits antitumor effects by inhibiting tumor cell proliferation and inducing morphological changes and apoptosis in vascular endothelial cells in tumors. However, cardiotoxicity induced by ischemia and hypertension is a severe adverse event. In this study, we focused on the fact that phosphodiesterase (PDE) 5 inhibitors dilate the heart and peripheral blood vessels and aimed to investigate whether co-administration of tadalafil, a PDE5 inhibitor, can attenuate cardiotoxicity without altering the antitumor effect of CA4DP. To investigate cardiotoxicity, CA4DP and/or tadalafil were administered to rats, and blood pressure, echocardiography, histopathology, and cGMP concentration in the myocardium were examined. Administration of CA4DP increased systolic blood pressure, decreased cardiac function, lowered cGMP levels in the myocardium, and led to necrosis of myocardial cells. Co-administration of tadalafil attenuated these CA4DP-induced changes. To investigate the antitumor effect, canine mammary carcinoma cell lines (CHMp-13a) and human umbilical vein endothelial cells were cultured with CA4 and/or tadalafil, and cell proliferation and endothelial vascular tube disruption were examined. CHMp-13a cells were transplanted into nude mice and treated with CA4DP and/or tadalafil. CA4-induced inhibition of cell proliferation and disruption of the endothelial vascular tube were not affected by co-treatment with tadalafil, and the antitumor effects of CA4DP in xenograft mice were not reduced by co-administration of tadalafil. These results revealed that myocardial damage induced by CA4DP was attenuated by co-administration of tadalafil while maintaining antitumor efficacy.
PMID:37577366 | PMC:PMC10412959 | DOI:10.1293/tox.2022-0143
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PubMed articles on: Cardio-Oncology
Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review
Int Cancer Conf J. 2023 Jun 26;12(4):299-304. doi: 10.1007/s13691-023-00620-y. eCollection 2023 Oct.
ABSTRACT
Entrectinib, a multikinase inhibitor of ROS1and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.
PMID:37577345 | PMC:PMC10421830 | DOI:10.1007/s13691-023-00620-y
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PubMed articles on: Cardio-Oncology
KMU-191 Induces Apoptosis in Human Clear Cell Renal Cell Carcinoma Caki Cells Through Modulation of Bcl-xL, Mcl-1 (L), c-FLIP (L), and p53 Proteins
J Cancer. 2023 Jul 16;14(12):2224-2235. doi: 10.7150/jca.85650. eCollection 2023.
ABSTRACT
The anti-proliferative effects of a newly developed N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191, have been previously evaluated in various cancer cells. However, the detailed anti-cancer molecular mechanisms of KMU-191 remain unknown. In this study, we investigated anti-cancer mechanisms by which KMU-191 regulates apoptosis-related genes in human clear cell renal cell carcinoma Caki cells. KMU-191 induced poly ADP-ribose polymerase cleavage and caspase-dependent apoptosis. In addition, KMU-191 induced down-regulation of the long form of cellular FADD-like IL-1β-converting enzyme inhibitory protein (c-FLIP (L)) at the transcriptional level as well as that of long form of myeloid cell leukemia (Mcl-1 (L)) and B-cell lymphoma-extra large at the post-transcriptional level. Furthermore, KMU-191-induced apoptosis was closely associated with the Mcl-1 (L) down-regulation, but also partially associated with c-FLIP (L) down-regulation. In contrast, KMU-191 up-regulated p53, which is closely related to KMU-191-induced apoptosis. Although KMU-191 showed cytotoxicity of normal cells, it unusually did not induce cardiotoxicity. Taken together, these results suggest that a multi-target small molecule, N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191 is a potential anti-cancer agent that does not induce cardiotoxicity.
PMID:37576393 | PMC:PMC10414049 | DOI:10.7150/jca.85650
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PubMed articles on: Cardio-Oncology
5-fluorouracil-induced coronary vasospasm: A cardiovascular magnetic resonance imaging case report
Glob Cardiol Sci Pract. 2023 Aug 1;2023(3):e202316. doi: 10.21542/gcsp.2023.16. eCollection 2023 Aug 1.
ABSTRACT
Certain agents frequently used in patients with active neoplasms, such as anthracyclines or HER-2 inhibitors, are commonly recognized for their cardiotoxicity. Fluoropyrimidines have also frequently been associated with cardiotoxic effects. These antimetabolites, including capecitabine, floxuridine, and 5-fluorouracil (5-FU), are commonly used chemotherapeutic agents, particularly for gastrointestinal malignancies. Numerous studies have described variability in the incidence of 5-FU associated cardiotoxicity (0-35%)1. The clinical presentation may vary, from myocardial ischemia, arrhythmias, cardiogenic shock, to sudden cardiac arrest1,2. We describe a case of 5-FU induced coronary vasospasm, confirmed on CMR, in a patient with stage IV colon cancer presenting as myocardial ischemia and new-onset LV systolic dysfunction.
PMID:37575292 | PMC:PMC10422872 | DOI:10.21542/gcsp.2023.16
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PubMed articles on: Cardio-Oncology
Cardiovascular Disease in Patients With Breast Cancer Treated in the Modern Era
Heart Lung Circ. 2023 Aug 11:S1443-9506(23)04223-3. doi: 10.1016/j.hlc.2023.05.021. Online ahead of print.
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