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11/1/23

BACKGROUND: The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity

Abstract

BACKGROUND: The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy.

METHODS: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy.

RESULT: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway.

CONCLUSIONS: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

PMID: 32013934 [PubMed - in process]

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Response by Salem et al to Letter Regarding Article, "Androgenic Effects on Ventricular Repolarization: A Translational Study From the International Pharmacovigilance Database to iPSC-Cardiomyocytes".

Circulation. 2020 Feb 04;141(5):e63-e64

Authors: Salem JE, Moslehi JJ, Funck Brentano C, Roden DM

PMID: 32011925 [PubMed - in process]

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A tumor-targeted, intracellular activatable and theranostic nanodiamond drug platform for strongly enhanced in vivo antitumor therapy.

J Mater Chem B. 2020 Feb 03;:

Authors: Du X, Li L, Wei S, Wang S, Li Y

Anthracyclines (Anth) are widely used in the treatment of various types of cancer. Unfortunately, they exhibit serious adverse effects

Abstract

Anthracyclines (Anth) are widely used in the treatment of various types of cancer. Unfortunately, they exhibit serious adverse effects, such as hematopoietic depression and cardiotoxicity, leading to heart failure. In this review, we focus on recently developed conjugates of anthracyclines with a range of nanocarriers, such as polymers, peptides, DNA or inorganic systems. Manipulation of the composition, size and shape of chemical entities at the nanometer scale makes possible the design and development of a range of prodrugs. In this review we concentrate on synthetic chemistry in the long process leading to the introduction of novel therapeutic products.

PMID: 32014639 [PubMed - as supplied by publisher]

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Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity.

BMC Cardiovasc Disord. 2020 Feb 03;20(1):43

Authors: Yadi W, Shurui C, Tong Z, Suxian C, Qing T, Dongning H

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.

Abstract

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.

METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P

CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

PMID: 32016393 [PubMed - as supplied by publisher]

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Synthetic routes to nanoconjugates of anthracyclines.

Bioorg Chem. 2020 Jan 25;96:103617

Authors: Piorecka K, Smith D, Kurjata J, Stanczyk M, Stanczyk WA

PURPOSE OF REVIEW: Chimeric antigen receptor T cell therapy is gaining clinical use in the management of B cell lymphomas.

Abstract

PURPOSE OF REVIEW: Chimeric antigen receptor T cell therapy is gaining clinical use in the management of B cell lymphomas. As the use of this unique treatment option increases, its associated toxicities will require recognition and treatment. In this review, we aim to discuss the cardiovascular toxicities of chimeric antigen receptor T cell therapy and our approach to their clinical management.

RECENT FINDINGS: Cardiotoxicity may be due to direct or indirect effects of infused chimeric antigen receptor T cells. The cytokine release syndrome has been described extensively in the literature. Studies have also reported cardiovascular dysfunction including hypotension, left ventricular dysfunction, heart failure, and cardiogenic shock in the setting of cytokine release syndrome. While there are no standardized guidelines for the treatment of cytokine release syndrome or associated cardiotoxicity, we present our current clinical practices. Further research is indicated into the pathophysiology of therapy-associated cardiac dysfunction and effective management strategies to optimize patient outcomes.

PMID: 32016789 [PubMed - as supplied by publisher]

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Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.

Eur Heart J. 2020 Feb 04;:

Authors: López-Sendón J, Álvarez-Ortega C, Zamora Auñon P, Buño Soto A, Lyon AR, Farmakis D, Cardinale D, Canales Albendea M, Feliu Batlle J, Rodríguez Rodríguez I, Rodríguez Fraga O, Albaladejo A, Mediavilla G, González-Juanatey JR, Martínez Monzonis A, Gómez Prieto P, González-Costello J, Serrano Antolín JM, Cadenas Chamorro R, López Fernández T

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality

Abstract

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure.

METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states).

RESULTS: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001).

CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

PMID: 32017181 [PubMed - as supplied by publisher]

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The Cardiovascular Complications of Chimeric Antigen Receptor T Cell Therapy.

Curr Hematol Malig Rep. 2020 Feb 03;:

Authors: Jamal FA, Khaled SK

BACKGROUND: Transurethral resection of the prostate is the most commonly performed procedure for the management of benign

Abstract

BACKGROUND: Transurethral resection of the prostate is the most commonly performed procedure for the management of benign prostatic obstruction. However, little is known about the effect surgical duration has on complications. We assess the relationship between operative time and TURP complications using a modern national surgical registry.

METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2006 to 2016 for patients undergoing TURP. Patients were separated into five groups based on operative time: 0-30 min, 30.1-60 min, 60.1-90 min, 90.1-120 min, and greater than 120 min. Standard statistical analysis, including multivariate regression, was performed to determine factors associated with complications.

RESULTS: 31,813 patients who underwent TURP were included. The overall complication rate was 9.0% and increased significantly with longer surgical duration (p < 0.001).

CONCLUSIONS: As surgical duration increases, there is a significant increase in the rate of complications after TURP. These data demonstrate that this procedure is safest when performed in under 90 min.

PMID: 30385836 [PubMed - indexed for MEDLINE]

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

J Card Surg. 2020 Feb 03;:

Authors: Guha A, McKinley G, Dey AK, Carter R, Miller PE, Deshmukh AJ, Zaghlol R, Barac A, Desai NR, Addison D

BACKGROUND: A paucity of randomized trials have compared prophylactic dose of unfractionated heparin (UFH) versus low-molecular

Abstract

BACKGROUND: A paucity of randomized trials have compared prophylactic dose of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH) for the prevention of venous thromboembolic events in spinal surgery. Our objective was to determine the most prevalent chemoprophylactic techniques in spine surgery.

METHODS: The Accreditation Council for Graduate Medical Education was queried for all neurosurgical residency programs, which were subsequently sent an electronic survey about prophylactic UFH versus LMWH in spine surgery for (1) degenerative/deformity, (2) traumatic, and (3) neoplastic pathologies.

RESULTS: Of 69 unique responding residencies, the first dose of chemoprophylaxis for degenerative/deformity spinal disease started most commonly on postoperative day (POD) 1 in 75.3% of neurosurgery programs, followed by POD 2 in 10.1% of programs, POD 0 (same day of surgery) in 8.7% of programs, POD 3 in 1.4% of programs, and morning of surgery in 1.4% of programs. Choice of postoperative chemoprophylaxis did not differ statistically significantly between UFH versus LMWH: 56.5% versus 36.2% in degenerative/deformity pathologies (P = 0.080) and 50.7% versus 43.4% in traumatic pathologies (P = 0.535). Three programs (4.3%) in both the degenerative/deformity and trauma groups documented no chemoprophylaxis. Neoplastic pathologies saw a statistically significantly higher proportion of prophylactic UFH (60.8%) compared with prophylactic LMWH (36.2%) (P = 0.037). One program (1.4%) in the neoplastic group did not utilize chemoprophylaxis. Two institutions (2.8%) in the degenerative/deformity cohort and 1 institution (1.4%) in the trauma and cancer cohorts reported "other".

CONCLUSIONS: Prophylactic UFH was statistically more common than LMWH in neoplastic spinal surgery, but not in the degenerative/deformity and trauma groups (cohorts). Further trials are warranted.

PMID: 31525483 [PubMed - indexed for MEDLINE]

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The impact of surgical duration on complications after transurethral resection of the prostate: an analysis of NSQIP data.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_npg.gif Related Articles

The impact of surgical duration on complications after transurethral resection of the prostate: an analysis of NSQIP data.

Prostate Cancer Prostatic Dis. 2019 05;22(2):303-308

Authors: Riedinger CB, Fantus RJ, Matulewicz RS, Werntz RP, Rodriguez JF, Smith ND

Background: The risk of venous thromboembolic events (VTE) during adjuvant chemotherapy for colorectal cancer (CRC) is unknown

Abstract

Background: The risk of venous thromboembolic events (VTE) during adjuvant chemotherapy for colorectal cancer (CRC) is unknown. We aim to evaluate if the Khorana score (KS) can predict this risk, and if it represents a prognostic factor for overall survival (OS) through a post hoc analysis of the phase III TOSCA trial of different durations (3- versus 6-months) of adjuvant chemotherapy.

Methods: A logistic regression model was used to test the associations between the risk of VTE and the KS. The results are expressed as odds ratios (OR) with 95% confidence intervals (95% CI). To assess the effect of the KS on OS, multivariable analyses using Cox regression models were performed. The results are expressed as hazard ratios (HR) with 95% CI.

Results: Among 1380 CRC patients with available data, the VTE risk (n = 72 events: 5.2%) was similar in the two duration arms (5.5% versus 4.9%), with 0.2% of patients belonging to the high-risk KS group. Rates of VTE were similar in the low- and intermediate-risk groups (4.8% versus 6.4%). KS did not represent an independent predictive factor for VTE occurrence. Chemotherapy duration was not associated with VTE risk. In addition, KS was not prognostic for OS in multivariate analysis (HR: 0.92, 95% CI, 0.63-1.36; p = 0.6835).

Conclusions: The use of the KS did not predict VTEs in a low-moderate thromboembolic risk population as CRC. These data did not support the use of KS to predict VTE during adjuvant chemotherapy, and suggest that other risk assessment models should be researched.

PMID: 32010236 [PubMed]

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Factors in the feasibility and safety of outpatient robotic-assisted hysterectomy for endometrial or cervical carcinoma.

Gynecol Oncol. 2020 Jan 30;:

Authors: Matern T, Kang E, Lim PC

Abstract

OBJECTIVE: Identify factors influencing the feasibility and safety of outpatient robotic-assisted hysterectomy for endometrial or cervical carcinoma.

METHODS: A single-institution retrospective chart review of patients who underwent robotic hysterectomy for cervical or endometrial cancer between 2012 and 2016 was performed. Outcomes were measured by length of stay (LOS), which was categorized as an admit-to-discharge time of >12 h or <12 h.12 h. These factors were evaluated using multivariate logistic regression. Readmission rates were compared between the two groups using an independent-samples t-test.

RESULTS: Of the 254 patients, 150 (59.1%) had a LOS >12 h and 104 (40.9%) had a LOS < 12 h.12 h (p < 0.05)180 min, uterine mass > 150 g, start time after 15:00, history of venous thromboembolism (VTE), age > 75 years, body mass index (BMI) 35-40, and post-operative VTE formation. Patients discharged in <12-hours12-hours to be re-admitted (p = 0.92).

CONCLUSIONS: Robotic hysterectomy for the treatment of endometrial and cervical carcinoma is both feasible and safe in the outpatient setting, as >40% of patients were successfully discharged within 12 h with no increase in readmission. Multiple risk factors were identified for extended hospitalization, offering potential for the development of a risk stratification model to improve the efficacy of outpatient robotic hysterectomy.

PMID: 32008793 [PubMed - as supplied by publisher]

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A Survey of Chemoprophylaxis Techniques in Spine Surgery Among American Neurosurgery Training Programs.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

A Survey of Chemoprophylaxis Techniques in Spine Surgery Among American Neurosurgery Training Programs.

World Neurosurg. 2020 Jan;133:e428-e433

Authors: Macki M, Haider SA, Anand SK, Fakih M, Elmenini J, Suryadevara R, Chang V

Background: Safety and short-term efficacy of robot-assisted thoracoscopic surgery (RATS) for early-stage non-small cell lung cancer (NSCLC)

Abstract

Background: Safety and short-term efficacy of robot-assisted thoracoscopic surgery (RATS) for early-stage non-small cell lung cancer (NSCLC) have been previously proven; however, RATS for N2 stage NSCLC was barely evaluated. The aim of this randomized controlled trial (RCT) was to explore the short-term outcome of RATS for cN2 stage NSCLC.

Methods: Total of 113 patients who were diagnosed with clinically single cN2 stage NSCLC were enrolled and randomly assigned to RATS and thoracotomy groups. The patients in RATS group were treated by lobectomy and mediastinal lymph node dissection using the da Vinci Surgical System, while the patients in thoracotomy group underwent lobectomy and mediastinal lymph node dissection from. And, short-term outcomes were analyzed statistically.

Results: The data from 108 subjects (58 in RATS and 55 in thoracotomy groups) were eligible for analyses. Five patients who received robot-assisted lobectomy initially was converted intraoperatively to open operation due to extensive pleural adhesion and equipment issues. And, one subject underwent robot-assisted surgery was died preoperatively due to pulmonary embolism. Compared with thoracotomy, RATS was associated with less intraoperative blood loss (86.3±41.1 vs. 165.7±46.4 mL, P<0.001),<0.01),<0.001),

Conclusions: Present study proves that the feasibility and safety of RATS lobectomy to treat patients with cN2 stage NSCLC, and it should be superior to thoracotomy due to lesser intraoperative blood loss.

PMID: 32010573 [PubMed]

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Khorana score and thromboembolic risk in stage II-III colorectal cancer patients: a post hoc analysis from the adjuvant TOSCA trial.

Ther Adv Med Oncol. 2020;12:1758835919899850

Authors: Barni S, Rosati G, Lonardi S, Pella N, Banzi M, Zampino MG, Dotti KF, Rimassa L, Marchetti P, Maiello E, Artioli F, Ferrari D, Labianca R, Bidoli P, Zaniboni A, Sobrero A, Iaffaioli V, De Placido S, Frassineti GL, Ciarlo A, Buonadonna A, Silvestris N, Piazza E, Pavesi L, Moroni M, Clerico M, Aglietta M, Giordani P, Galli F, Galli F, Petrelli F

INTRODUCTION: There has been a burgeoning interest for implementing bundled payments for hip fractures being treated

Abstract

INTRODUCTION: There has been a burgeoning interest for implementing bundled payments for hip fractures being treated with hemiarthroplasty, percutaneous pinning, and/or open reduction and internal fixation. Concerns exist about how hip fracture bundles may impede access to care for patients who require more resources, such as those with pathologic/neoplastic fractures.

METHODS: The 2011 to 2017 American College of Surgeons-National Surgical Quality Improvement Program database was queried to identify patients undergoing percutaneous pinning, hemiarthroplasty, plate/screw, and intramedullary nail for hip fractures. Multivariate regression analyses were used to identify notable differences in 30-day complications, readmissions, reoperations, mortality, length of stay, and nonhome discharges between native and pathologic/neoplastic hip fractures.

RESULTS: A total of 67,548 patients were included-of which 378 (0.6%) had a pathologic/neoplastic hip fracture. Pathologic fractures (versus native hip fractures) had significantly higher odds of experiencing a prolonged length of stay >5 days (odds ratio [OR] 1.57), pulmonary embolism (OR 3.67), deep vein thrombosis (OR 2.03), 30-day readmissions (OR 1.43), and 30-day mortality (OR 2.66).

DISCUSSION: Patients sustaining a pathologic/neoplastic hip fracture have a worse adverse event profile. Risk adjustment based on facture etiology will be necessary to ensure that providers taking care of pathologic/neoplastic fractures are appropriately reimbursed to minimize barriers to access of care for this vulnerable cohort.

PMID: 32011546 [PubMed - as supplied by publisher]

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Robot-assisted thoracoscopic surgery versus thoracotomy for c-N2 stage NSCLC: short-term outcomes of a randomized trial.

Transl Lung Cancer Res. 2019 Dec;8(6):951-958

Authors: Huang J, Li C, Li H, Lv F, Jiang L, Lin H, Lu P, Luo Q, Xu W

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk

Abstract

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.

PMID: 32012923 [PubMed - in process]

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Where Will Pathologic Hip Fractures Go in a Value-based Hip Fracture Bundle?

J Am Acad Orthop Surg. 2020 Jan 31;:

Authors: Malik AT, Alexander JH, Khan SN, Scharschmidt TJ

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality

Abstract

METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states).

CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

PMID: 32017181 [PubMed - as supplied by publisher]

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MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma.

Int J Mol Sci. 2020 Jan 28;21(3):

Authors: Oto J, Navarro S, Larsen AC, Solmoirago MJ, Plana E, Hervás D, Fernández-Pardo Á, España F, Kristensen SR, Thorlacius-Ussing O, Medina P

BACKGROUND: Current risk assessment models (RAMs) for prediction of venous thromboembolism (VTE) risk in the outpatient cancer population hav

Abstract

BACKGROUND: Current risk assessment models (RAMs) for prediction of venous thromboembolism (VTE) risk in the outpatient cancer population have shown poor predictive value in many of the most common cancers. The Comparison of Methods for Thromboembolic Risk Assessment with Clinical Perceptions and AwareneSS in Real Life Patients-Cancer Associated Thrombosis (COMPASS-CAT) RAM was derived in this patient population and predicted patients at high risk for VTE even after initiation of chemotherapy. We sought to externally validate this RAM.

MATERIALS AND METHODS: Patients aged ≥18 years who presented to a tertiary care center between January 1, 2014, and December 31, 2016, with invasive breast, ovarian, lung, or colorectal cancers were included. The COMPASS-CAT RAM was applied using our health system's tumor registry and variables that were identified by International Statistical Classification of Diseases and Related Health Problems-9 and -10 codes of the electronic health record and independent chart review. The primary endpoint at 6-month study follow-up was documented VTE.

RESULTS: A total of 3,814 patients were included. Documented VTE at 6-month follow-up occurred in 5.85% of patients. Patients stratified into low/intermediate- and high-risk groups had VTE rates of 2.27% and 6.31%, respectively. The sensitivity, specificity, and negative and positive predictive value of the RAM were 95%, 12%, 97.73%, and 6.31%, respectively. Diagnostic accuracy via receiver operating characteristic curve was calculated at 0.62 of the area under the curve.

CONCLUSION: In this large retrospective external validation study of the COMPASS-CAT RAM for VTE in patients with cancer undergoing active treatment, model discrimination was moderate and calibration was poor. The model had good negative predictive value. Further prospective validation studies-especially within 6 months of cancer diagnosis-are needed before the model can be implemented into routine clinical practice for primary thromboprophylaxis of high-VTE-risk patients with cancer with solid tumors.

IMPLICATIONS FOR PRACTICE: This study provides further guidance for researchers and clinicians in determining clinical and laboratory risk factors associated with development of venous thromboembolism among the ambulatory population of patients being treated for lung, breast, colorectal, or ovarian cancer. It validates the COMPASS-CAT risk model that was developed in this cancer population and suggests that further prospective validation of the model, with more focus on patients within 6 months of their index cancer diagnosis, would likely enhance the accuracy and usefulness of this model as a clinical prediction tool.

PMID: 32017293 [PubMed - as supplied by publisher]

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The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

J Card Surg. 2020 Feb 03;:

Authors: Guha A, McKinley G, Dey AK, Carter R, Miller PE, Deshmukh AJ, Zaghlol R, Barac A, Desai NR, Addison D

BACKGROUND: The risk of thromboembolism in myelofibrosis remains incompletely understood. OBJECTIVES: To examine the association between

Abstract

BACKGROUND: The risk of thromboembolism in myelofibrosis remains incompletely understood.

OBJECTIVES: To examine the association between myelofibrosis and each of venous and arterial thromboembolism.

METHODS: A cohort of 1,469,790 adults without a diagnosis of myelofibrosis was identified on 1 January 2007, from the electronic medical records of the largest healthcare provider in Israel. Participants were followed-up until 31 December 2016, for the occurrence of myelofibrosis. Four randomly selected controls (without myelofibrosis) were matched to each case of myelofibrosis on age, sex, religious identification and index date. The two groups were followed from the index date until 31 December 2017 for the occurrence of venous and arterial thromboembolism.

RESULTS: The study included 642 patients with myelofibrosis and 2,568 matched controls. Myelofibrosis was independently associated with increased risk of venous thromboembolism but not with arterial thromboembolism. The propensity score adjusted HRs were 6.88 (95% CI, 2.02-23.45) for venous thromboembolism, and 0.94 (0.49-1.77) for arterial thromboembolism. Atypical sites of venous thromboembolism occurred almost exclusively in patients with myelofibrosis (4 events of Budd Chiari versus none, and 2 mesenteric vein thrombosis events versus 1) and were more likely to occur around the time of myelofibrosis diagnosis. No significant association was found between JAK-2 inhibitor treatment (ruxolitinib) and the risk of venous HR 0.97 (0.30-3.12) or arterial thromboembolism 1.68 (0.78-3.62).

CONCLUSIONS: Myelofibrosis is associated with increased risk of venous thromboembolism but not of arterial thromboembolism. Atypical sites of venous thromboembolism are more frequent in myelofibrosis and are more likely to occur shortly after the diagnosis.

PMID: 32017387 [PubMed - as supplied by publisher]

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External Validation of a Venous Thromboembolic Risk Score for Cancer Outpatients with Solid Tumors: The COMPASS-CAT Venous Thromboembolism Risk Assessment Model.

Oncologist. 2020 Feb 04;:

Authors: Spyropoulos AC, Eldredge JB, Anand LN, Zhang M, Qiu M, Nourabadi S, Rosenberg DJ

BACKGROUND: Venous Thrombo-embolism (VTE) is the major preventable cause of death and disability worldwide. It has the third

Abstract

BACKGROUND: Venous Thrombo-embolism (VTE) is the major preventable cause of death and disability worldwide. It has the third highest incidence rate of hospital death after coronary artery disease (CAD) and stroke. With the establishment of Virchow's triad stating the major factors responsible for VTE including stasis, hypercoagulability and endothelial dysfunction, the last decade reported number of studies regarding its diagnosis and prophylaxis. Till date the most commonly used clinical marker for its diagnosis is the D-dimer test, detecting endogenous fibrinolysis. This test often gives false positive results and has low specificity. Other markers of coagulation are being used in combination with D-dimer; however, a reliable and sensitive biomarker is still needed for early and accurate diagnosis of VTE. Non-coding regulatory RNAs such as MicroRNAs (miRNAs) are small molecules that play a significant role in RNA silencing and post-transcriptional gene expression regulation. They can specifically bind to their target genes forming silencing complex, thereby inducing degradation and altered gene expression. A wide range of miRNAs have extensively been studied in a variety of cardiovascular diseases such as CAD, stroke, myocardial infarction (MI), atherosclerosis, obstructive sleep apnoea (OSA) and other complex diseases such as cancer. It has been demonstrated that circulating miRNAs have enormous potential to function as clinical diagnostic biomarkers for many diseases. This review comprehends recent studies establishing the inevitable role of miRNAs in pathogenesis of complex diseases with special emphasis on venous thrombosis. The differential expression pattern of these miRNAs shows a strong positive correlation with the manifestation of the pathological symptoms of diseases. Systematic consolidation of different miRNAs linked to VTE in various studies could be helpful in finding accurate diagnostic markers for thrombosis and may also find its place in VTE therapeutics. However, more extensive research and confirmatory experiments are needed to establish the role of these miRNAs as biomarkers.

PMID: 32017924 [PubMed - as supplied by publisher]

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Association between Myelofibrosis and Thromboembolism: A Population-Based Retrospective Cohort Study.

J Thromb Haemost. 2020 Feb 03;:

Authors: Saliba W, Mishchenko Y, Cohen S, Rennert G, Preis M

Ambulatory cancer patients receiving systemic cancer therapy are at varying risk for venous thromboembolism (VTE). The VTE risk depends

Abstract

Ambulatory cancer patients receiving systemic cancer therapy are at varying risk for venous thromboembolism (VTE). The VTE risk depends on different cancer types, cancer stage, anti-cancer treatment and individual patient risk factors. Whereas pharmacologic thromboprophylaxis is recommended in most hospitalized cancer patients with an acute medical condition and in patients undergoing major cancer surgery, the role of primary thromboprophylaxis in the ambulatory setting is not clear. A VTE risk stratification using specific scoring systems, e. g. the Khorana score or the recently published CAT-score should be performed. Recently, two large randomized controlled studies using rivaroxaban (CASSINI trial) and apixaban (AVERT trial) versus placebo as primary VTE prevention in high-risk ambulatory cancer patients were published. When considered together, the two trials showed a significant benefit for the prevention of VTE with a low incidence of major bleeding. The DOAC had no effect on mortality. Primary thromboprophylaxis may be offered to high-risk outpatients with cancer, e. g. patients with advanced pancreatic carcinoma, provided there are no risk factors for bleeding and no drug-interactions. The patient's preference should also be respected. Current guidelines differ in their recommendations concerning the choice of anticoagulation. Whereas LMWH is still preferred to DOAC in the current German guideline, the ISTH guidance suggest to use DOAC in high-risk ambulatory cancer patients with no drug-drug interactions and not at high risk for bleeding. Of note, DOAC are currently not approved in this indication.

PMID: 32018283 [PubMed - in process]

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MicroRNAs in Venous Thrombo-Embolism.

Clin Chim Acta. 2020 Feb 01;:

Authors: Angelina Hembrom A, Srivastava S, Garg I, Kumar B

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer

Abstract

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs.

PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed.

RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score.

CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

PMID: 32007440 [PubMed - as supplied by publisher]

5 February 2020

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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[Thromboprophylaxis in ambulatory patients with cancer].

Dtsch Med Wochenschr. 2020 Feb;145(3):130-134

Authors: Hart C, Heudobler D, Linnemann B

10/31/23

Upper-extremity deep vein thrombosis (UEDVT) accounts for about 5-10% of all cases of deep vein thrombosis (DVT). It is often associated with

Abstract

Upper-extremity deep vein thrombosis (UEDVT) accounts for about 5-10% of all cases of deep vein thrombosis (DVT). It is often associated with cancer and/or presence of a central venous catheter (CVC), but it may also occur in the absence of these favoring conditions. The safety and efficacy of using direct oral anticoagulants (DOACs) in subjects with UEDVT has not been systematically evaluated and the only data available in the literature derive from anecdotal evidence, analysis of registries, and small single-centre studies. In addition, a specific analysis of UEDVT not associated with cancer and/or CVC has never been made. In this study, we specifically focused on patients with no cancer and without a CVC who were diagnosed with a first episode of UEDVT and were treated with a DOAC. We studied 61 patients, treated in six Italian centres between January 2014 and December 2018. Treatment lasted at least 3 months in all patients. In terms of efficacy, no recurrence of thrombosis or pulmonary embolism were recorded, while Doppler ultrasonography, performed after at least three months of treatment, documented in all cases either partial or complete recanalization of obstructed veins. In terms of safety, no cases of major bleedings were recorded. This is the only series available in the literature of patients treated with DOACs for UEDVT not associated with cancer and/or CVC. This small multicenter real world experience supports the concept that DOACs might be safe and effective for treating UEDTV. Further studies are required to better understand the role of DOACs in these patients.

PMID: 32008208 [PubMed - as supplied by publisher]

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Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

Clin Genitourin Cancer. 2020 Jan 08;:

Authors: Bamias A, Tzannis K, Dimitriadis I, Tsironis G, Papatheorodidi AM, Tsiara A, Fragkoulis C, Xirokosta A, Barbarousi D, Papadopoulos G, Zakopoulou R, Varkarakis I, Mitsogiannis I, Adamakis I, Alamanis C, Stravodimos K, Papatsoris AG, Dellis AE, Drivalos A, Ntoumas K, Matsouka H, Halvatsiotis P, Raptis A, Gerotziafas GT, Dimopoulos MA

BACKGROUND: Anthracycline anticancer drugs such as epirubicin and doxorubicin may induce myocardial dysfunction, leading to

Abstract

BACKGROUND: Anthracycline anticancer drugs such as epirubicin and doxorubicin may induce myocardial dysfunction, leading to poor prognosis. Early detection of minor left ventricular (LV) myocardial dysfunction is important for the prevention of anthracylcine-induced cardiotoxicity. Using layer-specific speckle tracking echocardiography (STE), we investigated the progressive distribution of myocardial dysfunction in both breast cancer patients and an animal toxicity model.

METHODS: Patients with preserved LV ejection fraction (LVEF) preparing for epirubicin chemotherapy (N = 125) were prospectively enrolled. Layer-specific STE, including LV longitudinal and circumferential strains on subepicardium and subendocardium, were evaluated at baseline and after the first cycle, third cycle and six months of epirubicin therapy. A decline of LVEF above 10% to <55%

RESULTS: In patients developing cardiotoxicity, LV longitudinal strain on subendocardium (LVLSendo) was significantly reduced after three cycles of therapy despite no significant changes in conventional LV systolic, diastolic parameters as well as LV circumferential strains at that moment. Compared to conventional echocardiographic parameters, LVLSendo was significantly predictive of cardiotoxicity. Declines in LVLSendo were also observed in doxorubicin-treated rats at an early stage. These reductions also predicted significant fibrosis in the subendocardial layer.

CONCLUSION: LVLSendo is useful for the early detection of minor cardiac dysfunction during chemotherapy, thereby implicating endocardial involvement in the development of cardiotoxicity.

PMID: 32005451 [PubMed - as supplied by publisher]

3 February 2020

12:42

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Upper extremity deep vein thrombosis treated with direct oral anticoagulants: a multi-center real world experience.

J Thromb Thrombolysis. 2020 Feb 01;:

Authors: Porfidia A, Agostini F, Giarretta I, Tonello D, Pastori D, Pignatelli P, Santoliquido A, Sartori M, Lessiani G, Visonà A, Donadini MP, Pola R

According to international clinical practice guidelines, low-molecular-weight heparins are advocate for the treatment and the prevention of cancer

Abstract

According to international clinical practice guidelines, low-molecular-weight heparins are advocate for the treatment and the prevention of cancer associated thrombosis. Direct oral anticoagulants recently introduced represent an alternative to vitamin K antagonists and low-molecular-weight heparins since their use doesn't require coagulation monitoring or daily subcutaneous injections. Recent studies comparing direct oral anticoagulants and low-molecular-weight heparins have shown a trend towards a reduction of venous thromboembolism events of direct oral anticoagulants but an increased risk of major bleeding. Recent French inter-group recommendations on the treatment of venous thromboembolism in cancer patients, favor low molecular weight heparins over direct oral anticoagulants as curative agents. In the light of recent studies, the objective of this review is to re-evaluate the place of low-molecular-weight heparins in the management of patents with cancer-associated thrombosis and to focus on the recent updates of international guidelines.

PMID: 32005356 [PubMed - as supplied by publisher]

13:26

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Layer-specific distribution of myocardial deformation from anthracycline-induced cardiotoxicity in patients with breast cancer-From bedside to bench.

Int J Cardiol. 2020 Jan 16;:

Authors: Chang WT, Feng YH, Kuo YH, Chen WY, Wu HC, Huang CT, Huang TL, Chen ZC

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Abstract

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures: A panel of several established cardiovascular risk factors.

Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated [...]

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with higher VTE risk.

PMID: 30649175 [PubMed - indexed for MEDLINE]

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Venous thromboembolism prevention in lower limb trauma - Can we do better?

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png Related Articles

Venous thromboembolism prevention in lower limb trauma - Can we do better?

Phlebology. 2019 06;34(5):291-293

Authors: Langridge BJ, Goodall RJ, Onida S, Shalhoub J, Davies AH

PMID: 30354874 [PubMed - indexed for MEDLINE]

2 February 2020

12:06

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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[Low-molecular-weight heparins for cancer-associated thromboembolism: What place in 2019?]

Bull Cancer. 2020 Jan 28;:

Authors: Debourdeau P, Cossou-Gbeto C, Takam-Sohwe T, Laroche JP

BACKGROUND: Patients with cancer are of a high level risk of venous thromboembolism (VTE). Low molecular weight heparin (LMWH)

Abstract

BACKGROUND: Patients with cancer are of a high level risk of venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is recommended as the normal treatment for cancer-associated venous thrombosis. Recently, some studies suggest that patients with cancer-associated venous thrombosis can get a good efficacy and safety profile from treating with direct oral anticoagulants (DOACs) compared with other anticoagulants. However, when it comes to the efficacy of DAOCs in preventing VTE in patient with cancer, the data are limited. Thus, we performed such a meta-analysis to determine the efficacy and safety of DOACs in preventing VTE in patient with cancer compared with LMWHs.

METHODS: Medline/PubMed and CENTRAL (The Cochrane Central Register of Controlled Trials) were systematically searched for relevant studies. For each trial, data on VTE, major bleeding, or bleeding were extracted by 2 reviewers independently. Pooled risk ratios (RRs) were calculated by using Review Manager 5.3 software and the significance was determined by the Z test.

RESULTS: A total of 6 studies with 7185 patients were included in our meta-analysis. DOACs (RR = 0.55, 95% confidence interval [95%CI]: 0.34-0.90, I = 31%) had a similar prevention effect of VTE to LMWH (RR = 0.59, 95% CI: 0.37-0.95, I = 59%). DOACs (RR = 1.52, 95% CI: 0.99-2.33, I = 0%) yielded a similar bleeding occurrence rate compared with LMWH (RR = 1.35, 95% CI: 1.07-1.70, I = 35%). DOACs (RR = 1.95, 95% CI: 0.88-4.30, I = 0%) showed a sight higher major bleeding occurrence rate than LMWH (RR = 1.38, 95% CI: 0.88-2.14, I = 0%).

CONCLUSION: DOACs show comparable efficacy to LMWH in cancer patients without VTE with a slightly higher major bleeding occurrence rate. DOACs are inclined to be an alternative thromboprophylaxis strategy in cancer patients as they have superiorities compared to traditional anticoagulation agents. Further studies are still demanded as exiting relevant researches are limited.

PMID: 32000440 [PubMed - in process]

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Cardiovascular Risk Factors Associated With Venous Thromboembolism.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--jamanetwork.com-images-JAMA_cardio_linkout.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

JAMA Cardiol. 2019 02 01;4(2):163-173

Authors: Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among

Abstract

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

PMID: 32000631 [PubMed - as supplied by publisher]

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Prevention of venous thromboembolism in patients with cancer with direct oral anticoagulants: A systematic review and meta-analysis.

Medicine (Baltimore). 2020 Jan;99(5):e19000

Authors: Chen H, Tao R, Zhao H, Jiang J, Yang J

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC)

Abstract

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period.

METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE.

RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 μg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001< 0.001)50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 μg/ml) and tuberculosis had statistical significance.

CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 μg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.

PMID: 32001042 [PubMed - as supplied by publisher]

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Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Vasc Med. 2020 Jan 30;:1358863X19893432

Authors: Majmudar K, Golemi I, Tafur AJ, Toro JD, Visonà A, Falgá C, Sahuquillo JC, Lorente MA, Tufano A, Weinberg I, Monreal M, RIETE Investigators

BACKGROUND: The influence of morbid obesity on mortality in patients receiving anticoagulant therapy for venous thromboembolism (VTE)

Abstract

BACKGROUND: The influence of morbid obesity on mortality in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated.

METHODS: We used the data from RIETE registry to compare the mortality risk during anticoagulation in VTE patients with morbid obesity (body mass index [BMI] ≥40) versus those with normal weight (BMI: 18.5-24.9). Patients with or without active cancer were analyzed separately.

RESULTS: By September 2018, there were 4,443 VTE patients with morbid obesity and 12,047 with normal weight in RIETE. Of these, 245 (5.5%) and 1,397 (11.6%) respectively had cancer. Median duration of anticoagulant therapy was longer in the morbidly obese, with- (185 vs. 114 days) or without cancer (203 vs. 177 days). Among cancer patients, 44 (18.0%) morbidly obese and 1,377 (32.8%) patients with normal weight died during anticoagulation. Among those without cancer, 44 (3.1%) and 601 (5.6%) respectively died. On bivariate analysis, morbid obesity was associated with a lower mortality rate, both in patients with cancer (hazard ratio [HR]: 0.34; 95%CI: 0.25-0.45) and in those without cancer (HR: 0.43; 95%CI: 0.32-0.58). Multivariable analysis confirmed a lower hazard of death in morbidly obese patients with- (HR: 0.68; 95%CI: 0.50-0.94) or without cancer (HR: 0.67; 95%CI: 0.49-0.96). The risk for VTE recurrences or major bleeding did not differ in patients with or without morbid obesity.

CONCLUSIONS: In patients with VTE, the risk for death during anticoagulation was about one third lower in morbidly obese patients than in those with normal weight, independently of the presence of cancer.

PMID: 32004553 [PubMed - as supplied by publisher]

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Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period.

Eur J Surg Oncol. 2020 Jan 20;:

Authors: Zhou Q, Zhu C, Shen Z, Zhang T, Li M, Zhu J, Qin J, Xie Y, Zhang W, Chen R, Wang G, Qian L, Wu D, Nashan B, Zhou Y

BACKGROUND: Use of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy

Abstract

BACKGROUND: Use of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy, immune-related adverse events are still a major concern. Immune-related cardiotoxicity, which is rare but fatal, has recently become a focus of attention. Cardiotoxicities including myocarditis, cardiomyopathy, cardiac fibrosis, heart block and cardiac arrest have been reported. Of these toxicities, myocarditis is often accompanied by dysrhythmia. The presentation of sick sinus syndrome as an immune-related adverse event has not yet been reported. Here, we reported the first case of sick sinus syndrome, a rare toxicity induced by anti-PD-1.

CASE PRESENTATION: A 42-year-old male patient who had metastatic hepatocellular carcinoma failed treatment with sorafenib. Pembrolizumab at a fixed dose of 100 mg every three weeks was given. His heart rate gradually slowed down and he presented sick sinus syndrome with a lowest heart rate of 38 bpm after six cycles of pembrolizumab. He denied chest tightness, cold sweating, palpitation and dyspnea. Lab data including cardiac enzyme, electrolytes and thyroid function were all within a normal range. Simultaneously, he complained of fatigue, dizziness and anorexia with hypotension. Lab data revealed low cortisol and ACTH levels. Anti-PD-1 induced adrenal insufficiency was suspected. Low-dose cortisone (12.5 mg) was prescribed, and the patient's symptoms, hypotension and sick sinus syndrome showed rapid improvement. Cortisone was gradually titrated and discontinued three weeks later. His sick sinus syndrome did not relapse and the cortisol and ACTH level returned to normal.

CONCLUSIONS: Sick sinus syndrome caused by anti-PD-1 treatment is a rare adverse event. With the development of sick sinus syndrome, myocarditis should be the first differential diagnosis because of its lethality. From this case, we learned that sick sinus syndrome may be a presentation of immune- or adrenal insufficiency-mediated sinus node dysfunction, both could be reversed with a glucocorticoid supplement.

PMID: 30012209 [PubMed - indexed for MEDLINE]

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Morbid obesity and mortality in patients with venous thromboembolism. Findings from real life clinical practice.

Chest. 2020 Jan 28;:

Authors: Giorgi-Pierfranceschi M, Núñez JJL, Monreal M, Cattabiani C, Lodigiani C, Di Micco P, Bikdeli B, Braester A, Soler S, Dentali F

RATIONALE: Pyothorax-associated lymphoma (PAL) is a rare type of malignant pleural lymphoma. Most lymphomas are normally

Abstract

RATIONALE: Pyothorax-associated lymphoma (PAL) is a rare type of malignant pleural lymphoma. Most lymphomas are normally discovered around 20 to 50 years after tuberculosis infection. In China, there have been few reports about PAL cases so far. We report a case of a patient, whose tuberculosis and lymphoma were diagnosed concurrently.

PATIENT CONCERNS: The patient, a 76-year-old male, was reported to our hospital on March 13, 2015. He had recurrent shortness of breath during the previous 2 years of routine activities solely. His symptoms became more serious which was manifested by edema of lower limbs 1 day before his admission to our hospital.

DIAGNOSES: Doctors reached the diagnosis of PAL based on the patient's pathologic cell morphology and immunohistochemistry. The chest computed tomography examination revealed that there were pleural effusions on both sides, and some extent of compressive atelectasis in the lower parts of the inflamed lungs yet without space-occupying lesions. There were multiple small nodules which may be benign in the right upper lung.

INTERVENTIONS: The current first-line treatment for diffuse large B-cell lymphoma is the cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) protocol. Given that the patient had cardiac diseases and cardiotoxicity of anthracyclines, doctors decided to adopt rituximab with cyclophosphamide, vincristine, and prednisone chemotherapy without anthracyclines.

OUTCOMES: The treatment effect was obvious after one cycle of chemotherapy. The patient's pleural and pericardial effusions were significantly reduced. With the chemotherapy protocol above continuously adopted, pleural and pericardial effusions did not increase in multiple reexaminations on October 25, 2015, February 15, 2016, and August 10, 2016.

LESSONS: Analytical research revealed that chemotherapy with rituximab can increase the complete remission rate of non-Hodgkin lymphoma, reduce the possibility of failure and relapse, and prolong disease-free and overall survival. Moreover, there is no significant increase in adverse drug reactions compared with the effect of chemotherapy with CHOP alone. In the case of this patient, chemotherapy with rituximab was safe and efficacious.

PMID: 31852157 [PubMed - indexed for MEDLINE]

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Sick sinus syndrome associated with anti-programmed cell death-1.

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Sick sinus syndrome associated with anti-programmed cell death-1.

J Immunother Cancer. 2018 07 16;6(1):72

Authors: Hsu CY, Su YW, Chen SC

Bleeding is the most concerning complication associated with anticoagulant therapy but poorly characterized and important for risk

Abstract

Bleeding is the most concerning complication associated with anticoagulant therapy but poorly characterized and important for risk/benefit assessment. We developed a risk stratification score to predict vitamin K antagonist (VKA)-associated bleeding in venous thromboembolism (VTE) using the UK Clinical Practice Research Datalink. Significant bleeding events in outpatients consisted of major bleeding and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H) within 90 days of VKA initiation. A scoring scheme for predicting bleeding was developed from subhazard ratios, validated using cross-validation and expressed by the C-statistic. The study cohort consisted of 10,010 patients with first VTE receiving initial VKA treatment, mean age 62·2 years. Between 2008 and 2016, 167 significant bleeding events were recorded (1·7%), i.e. incidence rate was 7·4/100 person-years. Independent predictors for community-acquired significant bleeding included active cancer, trauma/surgical procedure, male gender, dementia, liver disease, anaemia, history of bleeding, cerebrovascular, renal and chronic pulmonary disease, VTE presenting as pulmonary embolism and age over 75. The overall C-statistic was 0·68 (95% CI, 0·60-0·76), 0·75 (0·60-0·88) for major bleeding and 0·65 (0·55-0·75) for CRNMB-H, and higher than in other risk schemes applied to our study population. The developed risk score may identify patients having a significant bleeding risk, in particular major bleeding events, in outpatients.

PMID: 31997309 [PubMed - as supplied by publisher]

14:38

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Preventive Cardio-Oncology: The Time Has Come.

Front Cardiovasc Med. 2019;6:187

Authors: Brown SA

PMID: 31998754 [PubMed]

1 February 2020

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cardiac PET/CT-Determined Amyloid Light Chain Depositions: A New Risk Biomarker?

J Am Coll Cardiol. 2020 Feb 04;75(4):391-394

Authors: Schindler TH, Gropler RJ, Lenihan DJ

PMID: 32000950 [PubMed - in process]

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A case report on the effect of rituximab on pyothorax-associated lymphoma.

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A case report on the effect of rituximab on pyothorax-associated lymphoma.

Medicine (Baltimore). 2019 Dec;98(50):e18393

Authors: Wang F, Lan H

Venous thromboembolism is a common complication of asparaginase-based chemotherapy regimens for the treatment of acute lymphoblastic

Abstract

Venous thromboembolism is a common complication of asparaginase-based chemotherapy regimens for the treatment of acute lymphoblastic leukemia. Thrombosis associated with asparaginase administration poses a number of specific and often clinically challenging management decisions. This review provides guidance on the prevention and treatment of thrombosis associated with asparaginase in adults including discussions on antithrombin repletion, pharmacologic thromboprophylaxis, cerebral venous thrombosis, and therapeutic anticoagulation.

PMID: 31999063 [PubMed - in process]

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Prediction of significant bleeding during vitamin K antagonist treatment for venous thromboembolism in outpatients.

Br J Haematol. 2020 Jan 29;:

Authors: Martinez C, Katholing A, Wallenhorst C, Cohen AT

BACKGROUND: Randomized controlled trials (RCTs

Abstract

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that low-dose direct oral anticoagulants (DOACs), including rivaroxaban and apixaban, may help reduce the incidence of cancer-associated venous thromboembolism (VTE).

METHODS: A cost-utility analysis was performed from the health sector perspective using a Markov state-transition model in patients with cancer who are at intermediate-to-high risk for VTE. Transition probability, relative risk, cost, and utility inputs were obtained from a meta-analysis of the RCTs and relevant epidemiology studies. Differences in cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) per patient were calculated over a lifetime horizon. One-way, probabilistic, and scenario sensitivity analyses were conducted.

RESULTS: In patients with cancer at intermediate-to-high risk for VTE, treatment with low-dose DOAC thromboprophylaxis for 6 months, compared with placebo, was associated with 32 per 1000 fewer VTE and 11 per 1000 more major bleeding episodes over a lifetime. The incremental cost and QALY increases were $1445 and 0.12, respectively, with an ICER of $11,947 per QALY gained. Key drivers of ICER variations included the relative risks of VTE and bleeding as well as drug cost. This strategy was 94% cost effective at the threshold of $50,000 per QALY. The selection of patients with Khorana scores ≥3 yielded the greatest value, with an ICER of $5794 per QALY gained.

CONCLUSIONS: Low-dose DOAC thromboprophylaxis for 6 months appears to be cost-effective in patients with cancer who are at intermediate-to-high risk for VTE. The implementation of this strategy in patients with Khorana scores ≥3 may lead to the highest cost-benefit ratio.

PMID: 31999844 [PubMed - as supplied by publisher]

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Prevention of venous thromboembolism in medical cancer patients: Guidance or guideline?

J Thromb Haemost. 2020 Feb;18(2):520-521

Authors: Douketis JD

PMID: 31999064 [PubMed - in process]

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The prevention and management of asparaginase-related venous thromboembolism in adults: Guidance from the SSC on Hemostasis and Malignancy of the ISTH.

J Thromb Haemost. 2020 Feb;18(2):278-284

Authors: Zwicker JI, Wang TF, DeAngelo DJ, Lauw MN, Connors JM, Falanga A, McMasters M, Carrier M

BACKGROUND: The SELECT-D trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban

Abstract

BACKGROUND: The SELECT-D trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared to dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation.

OBJECTIVES: To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months PATIENTS/METHODS: In SELECT-D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomisation to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomisation closed prematurely due to low recruitment when 92 of the planned 300 patients were recruited.

RESULTS: 92 of 136 eligible patients were randomised to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomisation, was 14% with placebo and 4% with rivaroxaban (Hazard Ratio 0.32; 95% CI 0.06-1.58). The major and clinically-relevant non-major bleeding rates were 0% and 0% with placebo; and 5% (95% CI 1-18%) and 4% (95% CI 1-17%) with rivaroxaban. In an exploratory analysis, 7 (15.2 %) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT-negative cohort (P=0.03).

CONCLUSION: The SELECT-D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

PMID: 31995662 [PubMed - as supplied by publisher]

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Enhanced recovery after surgery: implementing a new standard of surgical care.

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Enhanced recovery after surgery: implementing a new standard of surgical care.

CMAJ. 2019 04 29;191(17):E469-E475

Authors: Altman AD, Helpman L, McGee J, Samouëlian V, Auclair MH, Brar H, Nelson GS, Society of Gynecologic Oncology of Canada’s Communities of Practice in ERAS and Venous Thromboembolism

PMID: 31036609 [PubMed - indexed for MEDLINE]

31 January 2020

13:22

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cost-effectiveness analysis of low-dose direct oral anticoagulant (DOAC) for the prevention of cancer-associated thrombosis in the United States.

Cancer. 2020 Jan 30;:

Authors: Li A, Carlson JJ, Kuderer NM, Schaefer JK, Li S, Garcia DA, Khorana AA, Carrier M, Lyman GH

OBJECTIVE: To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treat

Abstract

OBJECTIVE: To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer.

DESIGN: Retrospective cohort study.

SETTING: 27 institutions participating in the Childhood Cancer Survivor Study.

PARTICIPANTS: 23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included.

MAIN OUTCOME MEASURES: Cumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments.

RESULTS: The 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01),

CONCLUSIONS: Historical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01120353.

PMID: 31941657 [PubMed - indexed for MEDLINE]

15:13

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Treatment of Cancer-Associated Venous Thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomisation of the SELECT-D Trial. (SELECT-D: 12m).

J Thromb Haemost. 2020 Jan 29;:

Authors: Marshall A, Levine M, Hill C, Hale D, Thirlwall J, Wilkie V, French K, Kakkar A, Lokare A, Maraveyas A, Chapman O, Arif A, Petrou S, Maredza M, Hobbs FR, Dunn JA, Young AM

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC) remains the main long-term and irreversible side effect in malignancy

Abstract

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC) remains the main long-term and irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of most reasonable attitudes.

AIM: To verify whether ramipril is able to protect from early-onset AIC in prospective randomized open-label study.

METHODS: Women with breast cancer (BC) were randomized to ramipril (RA) or control arm (CA). Data from 96 women, median age 47 years, without significant cardiovascular diseases, post-breast surgery and eligible for adjuvant anthracyclines, was analyzed. Cardiotoxicity was estimated with repeated echocardiography, troponin I and NT-proBNP levels over one-year follow-up. AIC was defined as a decrease in left ventricular ejection fraction (LVEF) and/or biomarkers elevation and/or occurrence of heart failure (HF) or cardiac death.

RESULTS: LVEF decrease ˃10 percent points occurred in 6.3% in RA vs 18.5% in controls (P = 0.15). No cases of HF, cardiac death or LVEF decline below ˂50% were reported. Percentage of patients with NT-proBNP elevation increased with time in CA (P = 0.003), whereas it remained unchanged in RA. At the end of observation, more patients in CA showed NTproBNP increase and fewer NT-proBNP decline (P = 0.01). No significant difference in troponin levels was found between the study arms. Ramipril was well tolerated in normotensive women.

CONCLUSIONS: In relatively young BC women without serious co-morbidities, who underwent anthracycline therapy, one year treatment with ramipril exerts potentially protective effect on the cardiotoxicty assessed with NT-proBNP, however its efficacy in long-term follow-up needs further investigations.

PMID: 31995035 [PubMed - as supplied by publisher]

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LncRNA OIP5-AS1 promotes the development of esophageal squamous cell carcinoma by binding to miR-1297.

Panminerva Med. 2020 Jan 24;:

Authors: Wang L, Ren X, Ma X, Yin L, Niu X, Xing S

PMID: 31992030 [PubMed - as supplied by publisher]

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Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort.

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Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort.

BMJ. 2020 01 15;368:l6794

Authors: Mulrooney DA, Hyun G, Ness KK, Ehrhardt MJ, Yasui Y, Duprez D, Howell RM, Leisenring WM, Constine LS, Tonorezos E, Gibson TM, Robison LL, Oeffinger KC, Hudson MM, Armstrong GT

AIMS: Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from the

Abstract

AIMS: Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from the anthracyclines such as doxorubicin. Doxorubicin enhances oxidative stress and stimulates matrix metalloproteinase-2 (MMP-2) in cardiomyocytes. We investigated whether MMP inhibitors protect against doxorubicin cardiotoxicity given the role of MMP-2 in proteolyzing sarcomeric proteins in the heart and remodeling the extracellular matrix.

METHODS AND RESULTS: 8-week old male C57BL/6J mice were treated with doxorubicin weekly with or without MMP inhibitors doxycycline or ONO-4817 by daily oral gavage for 4 weeks. Echocardiography was used to determine cardiac function and left ventricular remodeling before and after treatment. MMP inhibitors ameliorated doxorubicin-induced systolic and diastolic dysfunction by reducing the loss in left ventricular ejection fraction, fractional shortening, and E'/A'. MMP inhibitors attenuated adverse left ventricular remodeling, reduced cardiomyocyte dropout, and prevented myocardial fibrosis. Doxorubicin increased myocardial MMP-2 activity in part also by upregulating N-terminal truncated MMP-2. Immunogold transmission electron microscopy showed that doxorubicin elevated MMP-2 levels within the sarcomere and mitochondria which were associated with myofilament lysis, mitochondrial degeneration, and T-tubule distention. Doxorubicin-induced myofilament lysis was associated with increased titin proteolysis in the heart which was prevented by ONO-4817. Doxorubicin also increased the level and activity of MMP-2 in human embryonic stem cell-derived cardiomyocytes, which was reduced by ONO-4817.

CONCLUSIONS: MMP-2 activation is an early event in doxorubicin cardiotoxicity and contributes to myofilament lysis by proteolyzing cardiac titin. Two orally available MMP inhibitors ameliorated doxorubicin cardiotoxicity by attenuating intracellular and extracellular matrix remodeling, suggesting their use may be a potential prophylactic strategy to prevent heart injury during chemotherapy.

TRANSLATIONAL PERSPECTIVE: Heart failure is the primary chronic toxicity of anthracycline chemotherapy. Anthracyclines such as doxorubicin cause left ventricular remodeling and loss of myofilament proteins. We determined in mice whether matrix metalloproteinase-2, an intracellular and extracellular protease in the heart, contributes to doxorubicin cardiotoxicity. Doxorubicin activated myocardial MMP-2 in mouse hearts and human cardiomyocytes, including de novo expression of an N-terminal truncated MMP-2 isoform which is exclusively expressed by increased oxidative stress. Increased MMP-2 levels and activity in the heart contributed to left ventricular remodeling, interstitial fibrosis, and titin proteolysis in doxorubicin cardiotoxicity. These adverse effects on the heart were prevented by two orally available MMP inhibitors, demonstrating the potential benefits of MMP inhibition in the prophylaxis of doxorubicin cardiotoxicity.

PMID: 31995179 [PubMed - as supplied by publisher]

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Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in low-risk breast cancer women: results of a prospective randomized study.

Kardiol Pol. 2020 Jan 29;:

Authors: Słowik A, Jagielski P, Potocki P, Streb J, Ochenduszko S, Wysocki P, Gajos G, Konduracka E

Doxorubicin (DOX) is a classic anti-tumor chemotherapeutic used to treat a wide range of tumors. One major downfall of DOX treatment is it can in

Abstract

Doxorubicin (DOX) is a classic anti-tumor chemotherapeutic used to treat a wide range of tumors. One major downfall of DOX treatment is it can induce fatal cardiotoxicity. Astragaloside IV (AS-IV) is one of the primary active ingredients that can be isolated from the traditional Chinese herbal medicine, Astragalus membranaceus. This study uses both in vitro and in vivo tools to investigate whether AS-IV alleviates DOX induced cardiomyopathy. We found that AS-IV supplementation alleviates body weight loss, myocardial injury, apoptosis of cardiomyocytes, cardiac fibrosis and cardiac dysfunction in DOX-treated mice. Also, DOX-induced cardiomyocyte injury and apoptosis were effectively improved by AS-IV treatment in vitro. NADPH oxidase (NOX) plays an important role in the progress of the oxidative signal transduction and DOX-induced cardiomyopathy. In this study, we found that AS-IV treatment relieves DOX-induced NOX2 and NOX4 expression and oxidative stress in cardiomyocytes. In conclusion, AS-IV, an antioxidant, attenuates DOX-induced cardiomyopathy through the suppression of NOX2 and NOX4.

PMID: 31229536 [PubMed - indexed for MEDLINE]

30 January 2020

12:31

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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MMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodeling.

Cardiovasc Res. 2020 Jan 29;:

Authors: Chan BYH, Roczkowsky A, Cho WJ, Poirier M, Sergi C, Keschrumrus V, Churko JM, Granzier H, Schulz R

Abstract

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described.

METHODS: First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90

RESULTS: In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively).

CONCLUSIONS: Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD.

TRIAL REGISTRATION NUMBERS: NCT03678337, NCT03882580, and NCT03492528.

PMID: 31988143 [PubMed - in process]

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Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress.

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Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress.

Eur J Pharmacol. 2019 Sep 15;859:172490

Authors: Lin J, Fang L, Li H, Li Z, Lyu L, Wang H, Xiao J

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2

Abstract

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, these therapies have also been associated with significant left ventricular dysfunction. The incidence of trastuzumab-induced heart failure has decreased significantly since the initial reports, in large part due to improved screening, closer monitoring for early changes in left ventricular function, and a significant decrease in the concurrent administration of anthracyclines. The mechanism of trastuzumab cardiotoxicity is still not well understood, but current knowledge suggests that ErbB2 inhibition in cardiac myocytes plays a key role. In addition to trastuzumab and other HER2-targeted agents, vascular endothelial growth factor inhibitors, proteasome inhibitors, and immune checkpoint inhibitors are all additional classes of drugs used with great success in the treatment of solid tumors and hematologic malignancies. Yet these, too, have been associated with cardiac toxicity that ranges from a mild asymptomatic decrease in ejection fraction to fulminant myocarditis. In this review, we summarize the cardiotoxic effects of tumor-targeted and immunotherapies with a focus on HER2 antagonists.

PMID: 31988685 [PubMed - in process]

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The Burgeoning Field of Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):241-242

Authors: Trachtenberg BH

PMID: 31988683 [PubMed - in process]

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Barry H. Trachtenberg Leads Issue on Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):240

Authors:

PMID: 31988682 [PubMed - in process]

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Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors.

J Immunother Cancer. 2020 Jan;8(1):

Authors: Dolladille C, Ederhy S, Allouche S, Dupas Q, Gervais R, Madelaine J, Sassier M, Plane AF, Comoz F, Cohen AA, Thuny FR, Cautela J, Alexandre J

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