topics / مواضيع: 12/10/23

Introduction: Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients. Nonetheless,

Abstract

Introduction: Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients. Nonetheless, patients with hematological cancers receive less attention as compared with their solid tumor counterparts regarding this potentially fatal complication.Areas covered: Risk factors that are associated with the development of VTE in hematological cancers are discussed, based on a PubMed literature search. Since different hematological malignancies carry different risk of VTE, risk assessment in individual types of hematological cancers, including acute leukemias, lymphomas, myeloma and myeloproliferative neoplasms, are examined separately. Clinical relevance of VTE assessment and current guidelines on thromboprophylaxis in patients with hematological malignancies are also briefly reviewed.Expert opinion: When assessing VTE risk in patients with hematological cancers, in addition to the non-cancer specific risk factors, individual cancer-type specific and the therapy-related factors must be taken into consideration. Primary thromboprophylaxis should be considered in high risk patients.

PMID: 32249620 [PubMed - as supplied by publisher]

13:27

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

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Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Oncologist. 2020 Apr 06;:

Authors: Reding KW, Aragaki AK, Cheng RK, Barac A, Wassertheil-Smoller S, Chubak J, Limacher MC, Hundley WG, D'Agostino R, Vitolins MZ, Brasky TM, Habel LA, Chow EJ, Jackson RD, Chen C, Morgenroth A, Barrington WE, Banegas M, Barnhart M, Chlebowski RT

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically harmful diseases in modern pig production worldwide. Receptor of activated protein C kinase 1 (RACK1) was previously shown to be indispensable for the PRRSV replication and NF-κB activation in Marc-145 cells. Here we identified a membrane protein, integrin β3 (ITGB3), as a RACK1-interacting protein. PRRSV infection in Marc-145 cells upregulated the ITGB3 expression. Abrogation of ITGB3 by siRNA knockdown or antibody blocking inhibited PRRSV infection and NF-κB activation, while on the other hand, overexpression of ITGB3 enhanced PRRSV infection and NF-κB activation. Furthermore, inhibition of ITGB3 alleviated the cytopathic effects and reduced the TCID50 titer in Marc-145 cells. We also showed that RACK1 and ITGB3 were NF-κB target genes during PRRSV infection, and that they regulate each other. Our data indicated that ITGB3, presumably as a co-receptor, played an imperative role during PRRSV infection and NF-κB activation in Marc-145 cells. PRRSV infection activates a positive feedback loop involving the activation of NF-κB and upregulation of ITGB3 and RACK1 in Marc-145 cells. The findings would advance our elaborated understanding of the molecular host-pathogen interaction mechanisms underlying PRRSV infection in swine and suggest ITGB3 and NF-κB signaling pathway as potential therapeutic targets for PRRS control.

PMID: 32247758 [PubMed - as supplied by publisher]

14:01

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

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Venous thromboembolism in patients hospitalized for hip joint replacement surgery.

Thromb Res. 2020 Mar 27;190:1-7

Authors: Keller K, Hobohm L, Barco S, Schmidtmann I, Münzel T, Engelhardt M, Goldhofer M, Konstantinides SV, Drees P

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms

Abstract

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms of the disease. The use of cardiac magnetic resonance (CMR) imaging and nuclear magnetic resonance (NMR) imaging in preclinical models allows the non-invasive study of subclinical pathophysiological processes that influence cardiac function and establish imaging parameters that can be adopted into clinical practice to predict cardiovascular outcomes. Given the rising population of cancer survivors and the current lack of effective therapies for the management of cardiotoxicity, research combining clinically relevant animal models and non-invasive cardiac imaging remains essential to improve methods to monitor, predict, and treat cardiovascular adverse events. This comprehensive review summarizes the lessons learned from animal models of cardiotoxicity employing CMR and tissue characterization techniques and discusses the ongoing challenges and hopes for the future.

PMID: 32248349 [PubMed - as supplied by publisher]

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Integrin β3, a RACK1 interacting protein, is critical for porcine reproductive and respiratory syndrome virus infection and NF-κB activation in Marc-145 cells.

Virus Res. 2020 Apr 02;:197956

Authors: Yang C, Lan R, Wang X, Zhao Q, Li X, Bi J, Wang J, Yang G, Lin Y, Liu J, Yin G

INTRODUCTION: Cancer patients receiving chemotherapy are a high risk of VTE, yet the importance of thromboprophylaxis for

Abstract

INTRODUCTION: Cancer patients receiving chemotherapy are a high risk of VTE, yet the importance of thromboprophylaxis for cancer patients that are at high risk of developing VTE is still controversial.

AIM: To calculate the benefits and harms of thromboprophylaxis, compared to placebo, in ambulatory high-risk cancer patients that are receiving chemotherapy.

METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WANFANG Data, Chinese National Knowledge Infrastructure and Chinese Scientific Journal Database for randomized controlled trials (RCTs) describing benefits and harms of thromboprophylaxis. Statistical analysis was performed using Stata software (version 15.1).

RESULTS: We included six studies, which contained a total of 3240 cancer patients with thromboprophylaxis and 2874 cancer patients without thromboprophylaxis. Thromboprophylaxis was effective in high-risk patients with two points or higher (RR 0.51, 95% CI 0.36-0.71, I2 = 0.0%, P = 0.526). It was associated with an increase in bleeding events (RR 1.65, 95% CI 1.14-2.40, I2 = 0.0%, P = 0.498) and was mainly efficient in reducing the risk of pulmonary embolism (RR 0.56, 95% CI 0.33-0.96, I2 = 0.0%, P = 0.263). The risk of major (RR 1.85, 95% CI 0.87-3.94, I2 = 0.0%, P = 0.888) and non-major (RR 1.59, 95% CI 0.96-2.62, I2 = 16.3%, P = 0.303) bleeding showed no significant difference with or without thromboprophylaxis. There was no reduction in all-cause mortality with thromboprophylaxis (RR 0.95, 95% CI 0.78-1.18, I2 = 22.0%, P = 0.277).

CONCLUSION: Thromoboprophylaxis is effective and safe in cancer patients that are at high risk for developing VTE with chemotherapy.

PMID: 32246324 [PubMed - as supplied by publisher]

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Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial.

Cancers (Basel). 2020 Apr 01;12(4):

Authors: Pizzuti L, Krasniqi E, Mandoj C, Marinelli D, Sergi D, Capomolla E, Paoletti G, Botti C, Kayal R, Ferranti FR, Sperduti I, Perracchio L, Sanguineti G, Marchetti P, Ciliberto G, Barchiesi G, Mazzotta M, Barba M, Conti L, Vici P

BACKGROUND: Recently, the randomized EINSTEIN-Jr. study showed similar efficacy and safety for rivaroxaban and standard

Abstract

BACKGROUND: Recently, the randomized EINSTEIN-Jr. study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling.

METHODS: Rivaroxaban treatment with tablets or the newly-developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily or thrice-daily for children with bodyweights of ≥30, ≥12-<30,<12kg,<20kg.

RESULTS: Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable.

DISCUSSION: Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.

PMID: 32246743 [PubMed - as supplied by publisher]

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The effectiveness and safety of thromboprophylaxis in cancer patients based on Khorana score: a meta-analysis and systematic review of randomized controlled trials.

Clin Transl Oncol. 2020 Apr 03;:

Authors: Bao Y, Gao B, Yan P, Tian L, Yang K

AIM: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous

Abstract

AIM: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous T cells to kill the cancer cell. Myocarditis cases have been reported in cancer patients after immunological therapy; for example, nivolumab treatment is a monoclonal antibody that blocks programmed cell death-1/programmed cell death ligand-1 ligand interaction. This project provided insight into the inflammatory response as a benchmark to investigate the potential cardiotoxic effect of T cell response to the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis in regulating cardiomyocyte injury in vitro.

METHODS AND RESULTS: We investigated cardiomyopathy resulted from the PD-1/PD-L1 axis blockade using the anti-PD-1 antibody in Rockefeller University embryonic stem cells-derived cardiomyocytes (RUES2-CMs) and a melanoma tumor-bearing murine model. We found that nivolumab alone did not induce inflammatory-related proteins, including PD-L1 expression, and did not induce apoptosis, which was contrary to doxorubicin, a cardiotoxic chemotherapy drug. However, nivolumab was able to exacerbate the immune response by increasing cytokine and inflammatory gene expression in RUES2-CMs when co-cultured with CD4+ T lymphocytes and induced apoptosis. This effect was not observed when RUES2-CMs were co-cultured with CD8+ T lymphocytes. The in vivo model showed that the heart function of tumor-bearing mice was decreased after treatment with anti-PD-1 antibody and demonstrated a dilated left ventricle histological examination. The dilated left ventricle was associated with an infiltration of CD4+ and CD8+ T lymphocytes into the myocardium. PD-L1 and inflammatory-associated gene expression were significantly increased in anti-PD-1-treated tumor-bearing mice. Cleaved caspase-3 and mouse plasma cardiac troponin I expressions were increased significantly.

CONCLUSION: PD-L1 expression on cardiomyocytes suppressed T-cell function. Blockade of PD-1 by nivolumab enhanced cardiomyocyte inflammation and apoptosis through the enhancement of T-cell response towards cardiomyocytes.

PMID: 32244307 [PubMed - as supplied by publisher]

13:08

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

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Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr Phase 3 dose-exposure-response evaluation.

J Thromb Haemost. 2020 Apr 04;:

Authors: Young G, Lensing AWA, Monagle P, Male C, Thelen K, Willmann S, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bajolle F, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Beyer-Westendorf J, Martinelli I, Patricia Massicotte M, Smith WT, Berkowitz SD, Schmidt S, Price V, Prins MH, Kubitza D, EINSTEIN-Jr. Phase 3 Investigators

Heart and blood vessels disorders comprise one of the main causes of death worldwide. Pharmacologically active

Abstract

Heart and blood vessels disorders comprise one of the main causes of death worldwide. Pharmacologically active natural compounds have been used as a complementary therapy in cardiovascular disease around the world in a traditional way. Dietary, natural bioactive compounds, as well as healthy lifestyles, are considered to prevent coronary artery diseases. Pre-clinical and clinical studies reported that consumption of plant-food bioactive derivatives including polyphenolic compounds, peptides, oligosaccharides, vitamins, unsaturated fatty acids possess protective effects on cardiovascular diseases. This review aims to summarize the cardiovascular risk factors, pre-clinical studies and clinical trials related to cardioprotective properties of the plant-food-derived bioactive compounds. Molecular mechanisms by the natural bioactive compounds exert their cardiovascular protective properties have also been highlighted.

PMID: 32235611 [PubMed - in process]

4 April 2020

12:39

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

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Quantifying the impact of surgical decompression on quality of life and identification of factors associated with outcomes in patients with symptomatic metastatic spinal cord compression.

J Neurosurg Spine. 2020 Apr 03;:1-8

Authors: Lak AM, Rahimi A, Abunimer AM, Tafel I, Devi S, Premkumar A, Ida F, Lu Y, Chi JH, Tanguturi S, Groff MW, Zaidi HA

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians

Abstract

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients.

METHOD: We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool.

RESULTS: We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT.

CONCLUSION: Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

PMID: 32243404 [PubMed - as supplied by publisher]

5 April 2020

12:17

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

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Preoperative Peak Oxygen Consumption: A Predictor of Survival in Resected Lung Cancer.

Cancers (Basel). 2020 Mar 31;12(4):

Authors: Lindenmann J, Fink-Neuboeck N, Fediuk M, Maier A, Kovacs G, Balic M, Smolle J, Smolle-Juettner FM

OBJECTIVE: Metastatic spinal cord compression (MSCC) imposes significant impairment on patient quality of life and often

Abstract

OBJECTIVE: Metastatic spinal cord compression (MSCC) imposes significant impairment on patient quality of life and often requires immediate surgical intervention. In this study the authors sought to estimate the impact of surgical intervention on patient quality of life in the form of mean quality-adjusted life years (QALY) gained and identify factors associated with positive outcomes.

METHODS: The authors performed a retrospective chart review and collected data for patients who had neurological symptoms resulting from radiologically and histologically confirmed MSCC and were treated with surgical decompression during the last 12 years.

RESULTS: A total of 151 patients were included in this study (mean age 60.4 years, 57.6% males). The 5 most common metastatic tumor types were lung, multiple myeloma, renal, breast, and prostate cancer. The majority of patients had radioresistant tumors (82.7%) and had an active primary site at presentation (67.5%). The median time from tumor diagnosis to cord compression was 12 months and the median time from identification of cord compression to death was 4 months. Preoperative presenting symptoms included motor weakness (70.8%), pain (70.1%), sensory disturbances (47.6%), and bowel or bladder disturbance (31.1%). The median estimated blood loss was 500 mL and the average length of hospital stay was 10.3 days. About 18% of patients had postoperative complications and the mean follow-up was 7 months. The mean pre- and postoperative ECOG (Eastern Cooperative Oncology Group) performance status grades were 3.2 and 2.4, respectively. At follow-up, 58.3% of patients had improved status, 31.5% had no improvement, and 10.0% had worsening of functional status. The mean QALY gained per year in the entire cohort was 0.55. The mean QALY gained in the first 6 months was 0.1 and in the first year was 0.4. For patients who lived 1-2, 2-3, 3-4, or 4-5 years, the mean QALY gained were 0.8, 1.4, 1.7, and 2.3, respectively. Preoperative motor weakness, bowel dysfunction, bladder dysfunction, and ASA (American Society of Anesthesiologists) class were identified as independent predictors inversely associated with good outcome.

CONCLUSIONS: The mean QALY gained from surgical decompression in the first 6 months and first year equals 1.2 months and 5 months of life in perfect health, respectively. These findings suggest that surgery might also be beneficial to patients with life expectancy < 6 months.

PMID: 32244218 [PubMed - as supplied by publisher]

12:39

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Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

Medicine (Baltimore). 2020 Apr;99(14):e19679

Authors: Danjuma MI, Mohamed MFH, ElShafei MN, Fatima H, Shokri SA, Mohamed S, Abubeker IY, Kartha A, Elzouki AN, Mohamedali MGH, Mahgboub Y, Bidmos M

PURPOSE: Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab

Abstract

PURPOSE: Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab or ado-T emtansine (TDM1) in metastatic breast cancer (MBC) patients enrolled in randomized clinical trial (RCT) vs the real-world.

METHODS: This was a retrospective population-based cohort of all patients with MBC treated with trastuzumab/pertuzumab or TDM1 (2012-2017) in Ontario, Canada. Outcomes were incident heart failure (HF) and overall survival (OS). RCT data were obtained from digitizing survival curves and compared with cohort data using Kaplan-Meier analysis. Age-based comparison of outcomes was conducted for patients ≥ 65 years old vs younger than 65.

RESULTS: The two cohorts composed of 833 and 397 patients treated with trastuzumab/pertuzumab and TDM1, of whom 5.5% and 7.6% had baseline HF, respectively. Incident HF following trastuzumab/pertuzumab or TDM1 was low (trastuzumab/pertuzumab 1.8 events/100 person years; TDM1 0.02 events/100 person years). The median OS was 39.2 and 56.4 months in the trastuzumab/pertuzumab population-based cohort and CLEOPATRA, respectively. The median OS was 15.4 and 30.9 months in the TDM1 population-based cohort and EMILIA, respectively. Cohort OS was significantly worse than RCT OS (trastuzumab/pertuzumab HR 1.67, 95% CI 1.37-2.03, p < 0.0001;< 0.0001).

CONCLUSION: HF incidence during trastuzumab/pertuzumab or TDM1 therapy in this real-world cohort was low. Survival in this cohort was worse compared to RCT, suggesting that recruitment of patients similar to the real-world population is required.

PMID: 32236828 [PubMed - as supplied by publisher]

14:47

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Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds.

Int J Environ Res Public Health. 2020 Mar 30;17(7):

Authors: Sharifi-Rad J, Rodrigues CF, Sharopov F, Docea AO, Can Karaca A, Sharifi-Rad M, Kahveci Karıncaoglu D, Gülseren G, Şenol E, Demircan E, Taheri Y, Suleria HAR, Özçelik B, Nur Kasapoğlu K, Gültekin-Özgüven M, Daşkaya-Dikmen C, C Cho W, Martins N, Calina D

Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer

Abstract

Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer whilst also being implicated in a diverse group of developmental disorders named the "RASopathies"; including Neurofibromatosis 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), and capillary malformation-arteriovenous syndrome (CM-AVM). It remains unclear why i) there is little overlap in mutational subtype between Ras-driven malignancies associated with sporadic disease and those associated with the RASopathy syndromes, and ii) RASopathy-associated cancers are usually of different histological origin to those seen with sporadic mutations of the same genes. For instance, germline variants in KRAS and NRAS are rarely found at codons 12, 13 or 61, the most common sites for somatic mutations in sporadic cancers. An exception is Costello's syndrome, where germline variants in codons 12 and 13 of HRAS occur relatively frequently. Given recent renewed drug interest following early clinical success of RAS G12C and farnesyl transferase inhibitors, an improved understanding of this relationship could help guide targeted therapies for both sporadic and germline cancers associated with the Ras pathway.

PMID: 32240795 [PubMed - as supplied by publisher]

14:46

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sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.

Acta Pharmacol Sin. 2020 Apr 01;:

Authors: Hu YH, Liu J, Lu J, Wang PX, Chen JX, Guo Y, Han FH, Wang JJ, Li W, Liu PQ

INTRODUCTION: D-dimer is widely used in clinical pretests for venous thromboembolism exclusion, and its elevation suggests the

Abstract

INTRODUCTION: D-dimer is widely used in clinical pretests for venous thromboembolism exclusion, and its elevation suggests the presence of thrombus. The extent of hypercoagulability after colorectal surgery has not been systematically compared between patients who have undergone laparoscopic surgery and open surgery. The present study measured D-dimer levels sequentially in patients undergoing colorectal surgery and compared the extent of hypercoagulability between laparoscopic surgery and open surgery.

METHODS: A prospective cohort study involving 169 patients who underwent resection of colorectal cancer at Saitama Medical Center, Dokkyo Medical University, was conducted between January 2013 and September 2014. To measure D-dimer level, peripheral blood was obtained on postoperative day (POD) 1, POD4, and POD7. Enoxaparin sodium was administered twice daily as the routine prophylactic anticoagulant therapy on POD2 to 7.

RESULTS: D-dimer levels on POD1, POD4, and POD7 were significantly higher after open surgery than after laparoscopic surgery. Older age, pathologically advanced stage cancer, greater intraoperative blood loss and higher preoperative D-dimer levels were significantly associated with higher D-dimer levels on POD1, POD4, and POD7. Patients who completed the course of postoperative enoxaparin injections had significantly lower D-dimer levels on POD7 than those who did not receive postoperative enoxaparin injections. Multiple regression analyses of postoperative D-dimer level showed that laparoscopic surgery was a significant and independent factor affecting D-dimer level on POD4 and POD7.

CONCLUSION: This study showed that postoperative D-dimer levels were lower after laparoscopic surgery than after open surgery. The limited invasiveness of laparoscopic surgery may be beneficial to reduce the risk of postoperative deep vein thrombosis.

PMID: 32237071 [PubMed - as supplied by publisher]

11:24

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Urothelial carcinoma of the bladder induces endothelial cell activation and hypercoagulation.

Mol Cancer Res. 2020 Mar 31;:

Authors: John A, Robador JR, Vidal-Y-Sy S, Houdek P, Wladykowski E, Guenes C, Bolenz C, Schneider SW, Bauer AT, Gorzelanny C

Cardiac sarcoma is the commonest histology among primary cardiac tumors but it is a rare clinical entity and it is characterized

Abstract

Cardiac sarcoma is the commonest histology among primary cardiac tumors but it is a rare clinical entity and it is characterized by late stage presentation, poor prognosis from the time of detection and a variety of clinical presentations depending on the size and extent of the mass. We report the case of a high-grade right atrial angiosarcoma presenting with pulmonary embolism and cardiac tamponade. The patient underwent surgical resection and reconstruction of the atrial wall with bovine pericardial patch. This case report underscores the great heterogeneity of the clinical presentation, often non-specific, and the fatal prognosis of angiosarcoma, mostly related to the lack of evidence supporting a standardized therapeutic approach.

PMID: 31697274 [PubMed - indexed for MEDLINE]

11:24

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Venous thromboembolism risk assessment tools: Do we need a consensus?

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

Venous thromboembolism risk assessment tools: Do we need a consensus?

Phlebology. 2019 10;34(9):579-581

Authors: Machin M, Salim S, Onida S, Davies AH

PMID: 30739582 [PubMed - indexed for MEDLINE]

14:46

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

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Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts.

Ann Oncol. 2020 Mar 30;:

Authors: Dunnett-Kane V, Burkitt-Wright E, Blackhall FH, Malliri A, Evans G, Lindsay CR

INTRODUCTION: Venous Thromboembolism (VTE) is an important cause of morbidity and mortality. The risk of recur

Abstract

INTRODUCTION: Venous Thromboembolism (VTE) is an important cause of morbidity and mortality. The risk of recur- rence could be very high without thromboprophylaxis. New oral anticoagulants (NOACs or DOACs) represent a new step in anticoagulation.

MATERIAL AND METHODS: We searched for papers with trials, systematic reviews and meta-analysis involving NOACs in the treatment and secondary prevention of VTE. We also searched for guidelines of two medical societies (American College of Chest Physicians and International Society of Thrombosis and Haemostasis - ISTH).

RESULTS: Six RCT (randomized controlled trial) comparing NOACs with Warfarin shew a non-inferiority in relation with recurrent VTE and major bleeding. Two RCT (SELECT-D and Hokusay cancer) and one meta-analysis shew low recurrence rate of VTE in cancer patients and higher rate of bleeding, mainly in gastrointestinal and genitourinary cancers. There are two RCTs involving NOACs in treatment of patients with Antiphospholipid Syndrome (APS).

DISCUSSION: NOACs shew non-inferiority over AVK. Guidelines of CHEST 2016 recommend NOACs for VTE treatment in no cancer patients, and Low Molecular Weight Heparin (LMWH) for cancer patients. ISTH suggest NOACs as the first option in VTE cancer patients with low risk of bleeding. A recent RCT shews no benefit and increased risk of vascular events in APS patients treated with NOACs. NOACs are the gold standard for VTE treatment and secondary prevention in no cancer patients. They could be the first option in cancer patients with low risk of bleeding.

PMID: 32239823 [PubMed - as supplied by publisher]

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Can I use direct oral anticoagulants to treat cancer-associated venous thromboembolism?

Cleve Clin J Med. 2020 Apr;87(4):201-203

Authors: Emiloju O, Gupta S, Dourado C

PMID: 32238374 [PubMed - as supplied by publisher]

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Comparison of postoperative plasma D-dimer levels between patients undergoing laparoscopic resection and conventional open resection for colorectal cancer.

Asian J Endosc Surg. 2020 Mar 31;:

Authors: Kubota Y, Okuyama T, Oi H, Takeshita E, Mitsui T, Noro T, Sameshima S, Noie T, Oya M

Doxorubicin (DOX) is a chemotherapeutic agent broadly used in the treatment of a range of solid tumors. In spite of its high potency,

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent broadly used in the treatment of a range of solid tumors. In spite of its high potency, as is the case for many other chemotherapeutic drugs, there are many challenges associated with the use of DOX in clinical oncology. This is particularly true for DOX in the treatment of lung cancer where in vitro potency is shown to be very high, but low lung distribution and off-target toxicity (particularly cardiotoxicity) restricts its use. Nanocarrier-based drug delivery systems (nanoDDS) have been shown to help alter biodistribution and alleviate off-target toxicity associated with DOX. While significant understanding exists regarding the design parameters to achieve those clinical benefits, much less is known regarding the design of nanoDDS capable of enhancing tumor penetration of DOX (and other drugs), which is another major factor leading to DOX's reduced efficacy. The purpose of this study was to design a dendrimer-based nanoDDS capable of enhancing the penetration of DOX as measured in an in vitro 3D lung tumor model and to correlate those results with its efficacy. Spheroids formed with A549 human lung adenocarcinoma cells/murine fibroblasts cell line (NIH/3T3 cell line) are shown to produce the essential components of the extracellular matrix (ECM), which is known as a physical barrier that hinder the transport of DOX. DOX was conjugated to generation 4, succinamic acid-terminated poly (amido-amine) (PAMAM) dendrimers (G4SA) through an enzyme-liable tetrapeptide (G4SA-GFLG-DOX) resulting in a nanoDDS with ~5.5 DOX, -17 mV surface (zeta) potential, and 10 nm in hydrodynamic diameter (HD). Penetration of DOX to the core of the spheroid in term of DOX fluorescence's was determined to be 3.1-fold greater compared to free DOX, which positively correlated with enhanced efficacy as measured by Caspase 3/7 assay. This improved penetration happens as the interactions between the G4SA-GFLG-DOX and the highly negatively charged ECM are minimized by shielding the protonatable amine of DOX upon conjugation, and the HD of the conjugate is kept smaller than the estimated mesh size of the ECM. Interestingly, the conjugate provide has more specificity for DOX to tumor cells compared to fibroblasts, while free DOX is equally distributed in both tumor and fibroblasts as assessed in the co-culture spheroids. Growth inhibition studies show that the released DOX maintains its activity, and leads to tumor reduction to the same extent as free DOX. The results obtained here are of relevance for the design of dendrimer-based nanoDDS for the treatment of solid tumors as they provide critical information regarding desirable surface characteristics and sizes for efficient tumor penetration.

PMID: 32227969 [PubMed - as supplied by publisher]

13:49

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

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Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study.

Ther Adv Med Oncol. 2020;12:1758835920909660

Authors: Pineda-Moncusí M, Garcia-Giralt N, Diez-Perez A, Tusquets I, Servitja S, Albanell J, Prieto-Alhambra D, Nogués X

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape

Abstract

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.

PMID: 32231332 [PubMed - as supplied by publisher]

12:49

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Dendrimer Conjugation Enhances Tumor Penetration and Efficacy of Doxorubicin in Extracellular Matrix-Expressing 3D Lung Cancer Models.

Mol Pharm. 2020 Mar 31;:

Authors: Almuqbil RM, Heyder RS, Bielski ER, Durymanov M, Reineke JJ, da Rocha SRP

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration

Abstract

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs.

METHODS: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death.

RESULTS: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002).

CONCLUSION: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

PMID: 30795818 [PubMed - indexed for MEDLINE]

14:54

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Delirium in adult cancer patients: ESMO Clinical Practice Guidelines.

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Delirium in adult cancer patients: ESMO Clinical Practice Guidelines.

Ann Oncol. 2018 Oct;29 Suppl 4:iv143-iv165

Authors: Bush SH, Lawlor PG, Ryan K, Centeno C, Lucchesi M, Kanji S, Siddiqi N, Morandi A, Davis DHJ, Laurent M, Schofield N, Barallat E, Ripamonti CI, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

PMID: 32169223 [PubMed - indexed for MEDLINE]

2 April 2020

12:49

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

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Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia.

Nat Rev Cardiol. 2020 Mar 30;:

Authors: Herrmann J

Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even

Abstract

Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even discontinuation of the drug. Among all the drugs known to cause severe cardiotoxicity are anthracyclines that, though being the oldest chemotherapeutic drugs, are still a mainstay in the treatment of solid and hematological tumors. The recent expansion of the field of Cardio-Oncology, a branch of cardiology dealing with prevention or treatment of heart complications due to cancer treatment, has greatly improved our knowledge of the molecular mechanisms behind anthracycline-induced cardiotoxicity (AIC). Despite excessive generation of reactive oxygen species was originally believed to be the main cause of AIC, recent evidence points to the involvement of a plethora of different mechanisms that, interestingly, mainly converge on deregulation of mitochondrial function. In this review, we will describe how anthracyclines affect cardiac mitochondria and how these organelles contribute to AIC. Furthermore, we will discuss how drugs specifically targeting mitochondrial dysfunction and/or mitochondria-targeted drugs could be therapeutically exploited to treat AIC.

PMID: 32226791 [PubMed]

14:54

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Cell Type-Dependent Specificity and Anti-Inflammatory Effects of Charge-Reversible MSNs-COS-CMC for Targeted Drug Delivery in Cervical Carcinoma.

Mol Pharm. 2020 Mar 30;:

Authors: Cui L, Feng X, Liu W, Liu H, Qin Q, Wu S, He S, Pang X, Men D, Zhu C

Most physicians understand venous thromboembolism (VTE) to be an acute and time-limited disease. However, pathophysiological

Abstract

Most physicians understand venous thromboembolism (VTE) to be an acute and time-limited disease. However, pathophysiological and epidemiological data suggest that in most patients VTE recurrence risk is not resolved after the first 6 months of anticoagulation. Recurrence rates are high and potentially life-threatening. In these cases, it would make sense to prolong anticoagulation for an undetermined length of time. However, what about the bleeding rates, induced by prolonged anticoagulation? Would they not outweigh the benefit of reducing the VTE recurrent risk? How long should anticoagulation be continued, and should all patients suffering from VTE be provided with extended anticoagulation? This review will address the most recent data concerning extended anticoagulation in VTE secondary prophylaxis. The reviews of this paper are available via the supplementary material section.

PMID: 31558116 [PubMed - indexed for MEDLINE]

14:54

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

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Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer?

Front Cardiovasc Med. 2020;7:35

Authors: Murabito A, Hirsch E, Ghigo A

Cavernous sinuses are paired interconnected venous plexuses situated in the floor of the middle cranial fossa on either side of the sella

Abstract

Cavernous sinuses are paired interconnected venous plexuses situated in the floor of the middle cranial fossa on either side of the sella turcica and sphenoid sinus. They are lined by dura mater and consist of multiple venous channels within. The cavernous sinuses are intimately related to the internal carotid artery and its associated sympathetic plexus, the oculomotor nerve, the trochlear nerve, the abducens nerve, and the ophthalmic nerve. Cavernous sinuses are connected to the orbit, the pterygopalatine fossa, the infratemporal fossa, the nasopharynx, and the posterior cranial fossa by various foramina, fissures, and canals in the skull base. A multitude of structures in close relation to the cavernous sinus give rise to a myriad of possible pathologic conditions that can be broadly classified into (a) neoplastic, (b) vascular, (c) infective or inflammatory, or (d) miscellaneous lesions. These pathologic conditions can have overlapping clinical manifestations. Hence, imaging plays a crucial role in identifying the disease, assessing its extent, providing a pertinent differential diagnosis to guide further management, and suggesting a site or route for biopsy. MRI is the modality of choice to depict the cavernous sinuses, with CT and digital subtraction angiography playing supplementary roles in certain situations. In this article, the cavernous sinus lesions encountered in our institution during a 10-year period are reviewed. The purpose of the article is to (a) describe the anatomy of the cavernous sinus; (b) demonstrate the multimodality imaging spectrum of a wide variety of pathologic conditions involving the cavernous sinus, correlating with the histopathologic findings; (c) highlight important imaging clues for differential diagnosis; and (d) help the reader overcome potential pitfalls in interpretation. Online supplemental material is available for this article. ©RSNA, 2019.

PMID: 30978149 [PubMed - indexed for MEDLINE]

1 April 2020

11:16

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

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Extended anticoagulation after venous thromboembolism: should it be done?

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

Extended anticoagulation after venous thromboembolism: should it be done?

Ther Adv Respir Dis. 2019 Jan-Dec;13:1753466619878556

Authors: Fernandes CJ, Calderaro D, Piloto B, Hoette S, Jardim CVP, Souza R

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment

Abstract

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use.

METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding.

RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001

CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).

PMID: 32223112 [PubMed - as supplied by publisher]

13:14

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Application of contrast-enhanced ultrasonography in the diagnosis of post-kidney transplant lymphoproliferative disorder in native kidney- a case report.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--s3-service-broker-live-ddda94b7-dbb0-4917-917d-776dae91ebba.s3.amazonaws.com-bmc-linkout-fulltext.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Application of contrast-enhanced ultrasonography in the diagnosis of post-kidney transplant lymphoproliferative disorder in native kidney- a case report.

BMC Cancer. 2019 Nov 21;19(1):1135

Authors: Zhang JC, Lan HX, Zhao HJ, Lei YY, Ma L, Xie XY, Lu MD, Wang W

Background: Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could

Abstract

Background: Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could benefit patients with cancer is unclear. The aim of this systematic review was to determine the efficacy and safety of thromboprophylaxis in patients with cancer undergoing surgery or chemotherapy.

Methods: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2018 to investigate whether thromboprophylaxis measures were more effective than a placebo in patients with cancer.

Results: In total, 33 trials with 11,942 patients with cancer were identified. In patients with cancer undergoing surgery, the administration of thromboprophylaxis was associated with decreasing trends in venous thromboembolism (VTE) [relative risk (RR) 0.51, 95% confidence interval (CI) 0.32-0.81] and DVT (RR 0.53, 95% CI 0.33-0.87). In patients with cancer undergoing chemotherapy, the administration of thromboprophylaxis reduced the incidences of VTE, DVT, and pulmonary embolism compared with no thromboprophylaxis (RR 0.54, 95% CI 0.40-0.73; RR 0.47, 95% CI 0.31-0.73; RR 0.51, 95% CI 0.32-0.81, respectively). The pooled results regarding major bleeding showed no significant difference between prophylaxis and no prophylaxis in either the surgical or the chemotherapy groups (RR 2.35, 95% CI 0.74-7.52, p = 0.1482, I2 = 0%; RR 1.30, 95% CI 0.93-1.83, p = 0.1274, I2 = 0%, respectively).

Conclusion: Thromboprophylaxis did not increase major bleeding events or the incidence of thrombocytopenia. All-cause mortality was not significantly different between those who received thromboprophylaxis and those who did not. This meta-analysis provides evidence that thromboprophylaxis can reduce the number of VTE and DVT events, with no apparent increase in the incidence of major bleeding in patients with cancer.

PMID: 32215058 [PubMed]

13:55

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Is it time for a specific score for venous thromboembolism risk assessment for non-solid tumors?

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Is it time for a specific score for venous thromboembolism risk assessment for non-solid tumors?

Chin Clin Oncol. 2019 Oct;8(S1):S26

Authors: Macedo AVS, Ramacciotti E

PMID: 31684735 [PubMed - indexed for MEDLINE]

29 March 2020

11:21

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

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Strategies to Prevent Cardiovascular Toxicity in Breast Cancer: Is It Ready for Primetime?

J Clin Med. 2020 Mar 25;9(4):

Authors: Kikuchi R, Shah NP, Dent SF

Abstract

Cardio-oncology is an emerging field tasked with identifying and treating cancer therapy related cardiac dysfunction (e.g., cytotoxic agents, immunotherapies, radiation, and hormone therapies) and optimizing the cardiovascular health of cancer patients exposed to these agents. Novel cancer therapies have led to significant improvements in clinical outcomes for breast cancer patients. In this article, we review the current literature on assessing cardiovascular risk of breast cancer therapies and discuss strategies (including pharmacological and lifestyle interventions) to prevent cardiovascular toxicity.

PMID: 32218132 [PubMed - as supplied by publisher]

14:18

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

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[Janus kinase inhibitors : State of the art in clinical use and future perspectives].

Z Rheumatol. 2020 Mar 26;:

Authors: Alten R, Mischkewitz M, Stefanski AL, Dörner T

Cancer therapies can lead to a broad spectrum of cardiovascular complications. Among these, cardiotoxicities remain of prime

Abstract

Cancer therapies can lead to a broad spectrum of cardiovascular complications. Among these, cardiotoxicities remain of prime concern, but vascular toxicities have emerged as the second most common group. The range of cancer therapies with a vascular toxicity profile and the clinical spectrum of vascular toxic effects are quite broad. Historically, venous thromboembolism has received the greatest attention but, over the past decade, the arterial toxic effects, which can present as acute vasospasm, acute thrombosis and accelerated atherosclerosis, of cancer therapies have gained greater recognition. This Review focuses on these types of cancer therapy-related arterial toxicity, including their mechanisms, and provides an update on venous thromboembolism and pulmonary hypertension associated with cancer therapies. Recommendations for the screening, treatment and prevention of vascular toxic effects of cancer therapies are outlined in the context of available evidence and society guidelines and consensus statements. The shift towards greater awareness of the vascular toxic effects of cancer therapies has further unveiled the urgent needs in this area in terms of defining best clinical practices. Well-designed and well-conducted clinical studies and registries are needed to more precisely define the incidence rates, risk factors, primary and secondary modes of prevention, and best treatment modalities for vascular toxicities related to cancer therapies. These efforts should be complemented by preclinical studies to outline the pathophysiological concepts that can be translated into the clinic and to identify drugs with vascular toxicity potential even before their widespread clinical use.

PMID: 32218531 [PubMed - as supplied by publisher]

31 March 2020

12:10

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

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Efficacy and tolerability of mitoxantrone for neuromyelitis optica spectrum disorder: A systematic review.

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Efficacy and tolerability of mitoxantrone for neuromyelitis optica spectrum disorder: A systematic review.

J Neuroimmunol. 2019 07 15;332:126-134

Authors: Enriquez CAG, Espiritu AI, Pasco PMD

Abstract

The review assessed the efficacy and tolerability of mitoxantrone in patients with neuromyelitis optica spectrum disorder (NMOSD). Eight articles were reviewed with a total of 117 patients. Annualized relapse rate and progression of disability dramatically decreased post-treatment in most studies. Mitoxantrone was generally tolerated. Only one patient developed acute myeloid leukemia, which lead to septicemia and death. No serious cardiotoxicity was reported. Mitoxantrone may be effective in reducing the frequency of relapse and slowing down the progression of disability in patients with NMOSD. The risk of cardiotoxicity and leukemia detains it as a second-line agent for NMOSD.

PMID: 31005713 [PubMed - indexed for MEDLINE]

13:14

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

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Anticoagulant Therapy for Venous Thromboembolism in Cancer.

N Engl J Med. 2020 Mar 29;:

Authors: Lee AYY

PMID: 32223115 [PubMed - as supplied by publisher]

13:14

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Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.

N Engl J Med. 2020 Mar 29;:

Authors: Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro MR, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators

PURPOSE OF REVIEW: This review highlights the literature related to pericardial injury following radiation for oncologic diseases.

Abstract

PURPOSE OF REVIEW: This review highlights the literature related to pericardial injury following radiation for oncologic diseases.

RECENT FINDINGS: Radiation-associated pericardial disease can have devastating consequences. Unfortunately, there is considerably less evidence regarding pericardial syndromes following thoracic radiation as compared to other cardiovascular outcomes. Pericardial complications of radiation may arise acutely or have an insidious onset several decades after treatment. Transthoracic echocardiography is the screening imaging modality of choice, while cardiac magnetic resonance imaging further characterizes the pericardium and guides treatment decision-making. Cardiac CT can be useful for assessing pericardial calcification. Ongoing efforts to lessen inadvertent cardiac injury are directed towards the revision of radiation techniques and protocols. As survival of mediastinal and thoracic malignancies continues to improve, radiation-associated pericardial disease is increasingly relevant. Though advances in radiation oncology demonstrate promise in curtailing cardiotoxicity, the long-term effects pertaining to pericardial complications remain to be seen.

PMID: 31352541 [PubMed - indexed for MEDLINE]

13:55

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

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Efficacy and safety of thromboprophylaxis in cancer patients: a systematic review and meta-analysis.

Ther Adv Med Oncol. 2020;12:1758835920907540

Authors: Liu M, Wang G, Li Y, Wang H, Liu H, Guo N, Han C, Peng Y, Yang M, Liu Y, Ma X, Yu K, Wang C

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently

Abstract

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment-related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment-related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

PMID: 32213102 [PubMed - in process]

11:12

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Radiation-Associated Pericardial Disease.

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Radiation-Associated Pericardial Disease.

Curr Cardiol Rep. 2019 07 27;21(9):97

Authors: Szpakowski N, Desai MY

BACKGROUND: As an inhibitor of programmed death-1 (PD-1) protein, nivolumab has been shown to be effective in various cancers

bstract

BACKGROUND: As an inhibitor of programmed death-1 (PD-1) protein, nivolumab has been shown to be effective in various cancers. We thus conducted this meta-analysis to compare the relative efficacy of nivolumab vs docetaxel-based chemotherapy as a second-line treatment for previously treated advanced non-small cell lung cancer (NSCLC).

METHODS: Relevant studies were identified through searches of databases and conference proceedings. Progression-free survival (PFS), overall survival (OS), drug responses, and adverse effects (AEs) were assessed as the primary endpoints.

RESULTS: After screening, we included six studies (949 patients) in the final analysis. Nivolumab showed better efficacy in terms of the PFS (hazard ratios [HR]: 0.70, P = 0.03), OS (HR: 0.70, P < 0.00001),< 0.00001)

CONCLUSIONS: For advanced NSCLC, nivolumab is a better therapy in terms of both anti-tumor efficacy and safety than docetaxel-based chemotherapy. More high-quality randomized controlled trials are needed to confirm these results.

PMID: 30628185 [PubMed - indexed for MEDLINE]

28 March 2020

11:12

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

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Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy.

Circ Res. 2020 Mar 27;126(7):926-941

Authors: Wallace KB, Sardão VA, Oliveira PJ

Interventional radiologists have the unique ability to apply their imaging knowledge, wide scope of technical skills, and use

Abstract

Interventional radiologists have the unique ability to apply their imaging knowledge, wide scope of technical skills, and use of innovative technologies to comprehensively address the percutaneous management of the thromboembolic disease processes. This report illustrates successful management of a thrombosed IVC, while protecting against possible pulmonary embolism. Here, we present a 49-year-old female with stage IIIB ovarian cancer who presented with severe bilateral lower extremity edema and anasarca in setting of occlusive thrombus of IVC. The thrombus was the result of compressionfrom a large hepatic hematoma which gradually developed after radical hysterectomy. A new mechanical thrombectomy device approved for use in pulmonary embolism, Inari FlowTriever catheter, was used off-label to remove the clot. The self-expanding mesh discs in the Inari FlowTriever catheter were utilized to protect against pulmonary embolism while percutaneously draining the hepatic hematoma and alleviating the IVC compression. The IVC was largely patent at the end of the procedure, and the patient experienced complete resolution of her symptoms. This case report demonstrates the successful and safe off-label use of a new mechanical thrombectomy device approved for pulmonary embolism thrombectomy in the IVC and illustrates a novel application of the nitinol mesh discs in the device as proximal embolic protection.

PMID: 32209508 [PubMed - as supplied by publisher]

22:57

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

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The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview.

Front Cardiovasc Med. 2020;7:32

Authors: Foulkes S, Claessen G, Howden EJ, Daly RM, Fraser SF, La Gerche A

Introduction: Mitral valve prolapse (MVP) is the most common anomaly of the mitral valve. Several studies have shown prevalence

Abstract

Introduction: Mitral valve prolapse (MVP) is the most common anomaly of the mitral valve. Several studies have shown prevalence of MVP in atrial septal defect (ASD) especially secundum types (II). The aims of this study is to show the potential role of 3D echocardiography in improving the diagnosis of MVP and to depict the relationship between reverse remodeling of the right and left ventricles (RV, LV) and MVP after transcatheter closure of ASD II. Methods: Sixty patients underwent transcatheter closure of ASD II and completed follow up by 2D and 3D echocardiography in Cairo University Children Hospital before the procedure and at 24 hours, 1 and 6 months after the procedure. Results: 3D echocardiography was more accurate than 2D echocardiography in detecting MVP frequency in ASD II patients (75% vs. 50%). Maximum statistically significant remodeling was detected by 3D echocardiography 1 month after the procedure (RV: LV ratio by 3D echocardiography 1.9±0.03 24 hours after the procedure vs. 1.6±0.03 1 months after the procedure, P <0.01)

PMID: 32211133 [PubMed]

22:57

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Correlation of HER2 codon 655 polymorphism with cardiotoxicity risk in Chinese HER2-positive breast cancer patients undergoing epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab adjuvant chemotherapy.

Int J Clin Exp Pathol. 2020;13(2):286-294

Authors: Tan L, Su X, Li X, Li H, Hu B

OBJECTIVE: Peripherally inserted central venous catheter (PICC)-related thrombosis (PRT) is a serious complication that

Abstract

OBJECTIVE: Peripherally inserted central venous catheter (PICC)-related thrombosis (PRT) is a serious complication that can lead to interruptions in chemotherapy and other supportive care, as well as increased hospital stay and costs. We conducted a retrospective study to evaluate the patterns of symptomatic PRT in patients with cancer undergoing chemotherapy and their risk factors.

METHODS: A retrospective study of 938 PICC patients from our institution between November 2014 and July 2017 was performed. Symptomatic PRT events were confirmed by color Doppler ultrasonography or computed tomography pulmonary angiography in the presence of clinical symptoms. The variables of interest were extracted from the electronic medical record system. Logistic regression analysis was used to determine the risk factors for PRT.

RESULTS: Of the 938 patients who were followed up for more than 120,000 patient-days, 63 patients (6.7%; 0.51 per 1000 catheter-days) had symptomatic PRT. Sixty-one patients were diagnosed with upper extremity venous thrombosis (UEVT), of which 18 were isolated superficial vein thrombosis (SVT), 19 were isolated deep vein thrombosis (DVT), and 24 were extensive venous thrombosis (EVT). Two patients were diagnosed with pulmonary embolism, and two patients were diagnosed with UEVT with pulmonary embolism. The symptomatic SVT occurred in 42 of 938 patients with cancer (4.5%), which accounted for 68.9% of all UEVT events. The median time to PRT was 21 days, and the median time to catheter removal in the PRT group was 66 days as compared with 117 days in the no PRT group. Predictors associated with increased risk of PRT were age >60 years (odds ratio [OR], 2.142; 95% confidence interval [CI], 1.118-4.103) and a chemotherapy regimen containing fluorouracil (OR, 2.429; 95% CI, 1.013-5.825). Hypertension with medication was a protective factor for PRT (OR, 0.306; 95% CI, 0.113-0.828). Among the 28 patients who did not remove their PICCs immediately after PRT was diagnosed, patients with SVT, DVT, and EVT had similar success rates of retaining catheters in situ after anticoagulant therapy (SVT, 83.3%; DVT, 62.5%; EVT, 75.0%; P = .667).

CONCLUSIONS: Age >60 years and chemotherapy regimens containing fluorouracil were independent risk factors for PRT and hypertension with medication was associated with a lower risk of PRT in patients with cancer with PICCs receiving chemotherapy. PICCs-related SVT was a frequent type of PRT, which might need a better understanding and anticoagulant therapy in patients with cancer with PICCs.

PMID: 32205131 [PubMed - as supplied by publisher]

27 March 2020

21:36

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

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pubmed: caandvteortroorpul

Simultaneous proximal embolic protection and inferior vena cava mechanical thrombectomy using the FlowTriever system.

Diagn Interv Radiol. 2020 Mar 25;:

Authors: Murali N, Nezami N, Latich I, Brown J, Mojibian H

TRIB3 roles in tumor progression have been revealed with similar or opposite results. Here, we found that TRIB3 expression was

Abstract

TRIB3 roles in tumor progression have been revealed with similar or opposite results. Here, we found that TRIB3 expression was highly expressed in lung cancer tissues and correlated with tumor grades and metastasis. Functional experiments showed that TRIB3 knockdown (KD) inhibited lung cancer cell migration, invasion, EMT (epithelial-mesenchymal transition) process and stemness. Mechanistic studies demonstrated that TRIB3 physically interacted with β-catenin and increased the recruitment of β-catenin to the promoter region of genes regulated by Wnt. Re-activation of β-catenin attenuated the inhibition of TRIB3 KD on lung cancer progression. These results suggest that TRIB3 interacts with β-catenin and thus activates β-catenin signaling, which is responsible for lung cancer progression, and blocking TRIB3 activity might be developed to treat lung cancer.

PMID: 31562867 [PubMed - indexed for MEDLINE]

12:02

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

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Emergent Reversal of Direct Oral Anticoagulants Permitting Neurosurgical Intervention for Nonhemorrhagic Pathology.

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

Emergent Reversal of Direct Oral Anticoagulants Permitting Neurosurgical Intervention for Nonhemorrhagic Pathology.

World Neurosurg. 2020 Mar;135:38-41

Authors: Sherrod BA, Condie CK, Brock AA, Ledyard H, Menacho ST, Mazur MD

BACKGROUND: Direct oral anticoagulants (DOACs) are becoming the medication of choice for the management of venous

Abstract

BACKGROUND: Direct oral anticoagulants (DOACs) are becoming the medication of choice for the management of venous thromboembolism and stroke prevention in atrial fibrillation because of simplified dosing, a more predictive pharmacokinetic profile, and better clinical outcomes when compared with traditional vitamin K antagonists. Recently, reversal agents for DOACs have been approved by the U.S. Food and Drug Administration for use in managing life-threatening or uncontrolled bleeding; however, for acute nonhemorrhagic conditions requiring surgical intervention, such as acute hydrocephalus requiring ventriculostomy, there is little evidence to help guide appropriate management for patients on DOACs.

CASE DESCRIPTION: We report the use of andexanet alfa to counteract rivaroxaban treatment in a 28-year-old woman who developed herniation syndrome and acute hydrocephalus from a cerebellar tumor.

CONCLUSIONS: We describe how appropriate timing of administration of the DOAC reversal agent may permit urgent neurosurgical intervention.

PMID: 31809896 [PubMed - indexed for MEDLINE]

25 March 2020

11:42

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

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The Emerging Discipline of Cardio-Oncology; What, why and how?

J Pak Med Assoc. 2020 Mar;70(3):567-568

Authors: Ahmed Naqvi SA, Hasan Zaidi SD, Haider MZ

PMID: 32207454 [PubMed - in process]

11:42

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A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias.

Cancer Chemother Pharmacol. 2019 07;84(1):163-173

Authors: Lin TL, Newell LF, Stuart RK, Michaelis LC, Rubenstein E, Pentikis HS, Callahan T, Alvarez D, Liboiron BD, Mayer LD, Wang Q, Banerjee K, Louie AC

Abstract

PURPOSE: Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization.

METHODS: Twenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and ≤ 4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline.

RESULTS: Mean QTcF changes were < 10 ms30 h. Thirteen (50%) patients achieved remission. The most common adverse events were febrile neutropenia, fatigue, and nausea.

CONCLUSIONS: The cytarabine and daunorubicin in CPX-351 liposomes were metabolized and excreted similarly to conventional formulation; however, plasma pharmacokinetics were altered. CPX-351 did not prolong the QT interval, suggesting that CPX-351 may induce less cardiotoxicity than previously reported for conventional daunorubicin.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02238925.

PMID: 31098682 [PubMed - indexed for MEDLINE]

12:11

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

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Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany.

BJS Open. 2020 Apr;4(2):310-319

Authors: Diers J, Wagner J, Baum P, Lichthardt S, Kastner C, Matthes N, Matthes H, Germer CT, Löb S, Wiegering A

The gut microbiome plays a critical role in various inflammatory conditions, and its modulation is a potential treatment option for these

Abstract

The gut microbiome plays a critical role in various inflammatory conditions, and its modulation is a potential treatment option for these conditions. The role of the gut microbiome in the pathogenesis of thromboembolism has not been fully elucidated. In this review, we summarize the evidence linking the gut microbiome to the pathogenesis of arterial and venous thrombosis. In a human host, potentially pathogenic bacteria are normal residents of the human gut microbiome, but significantly outnumbered by commensal anaerobic bacteria. Several disease states with an increased risk of venous thromboembolism (VTE) are associated with an imbalance in the gut microbiome characterized by a decrease in commensal anaerobic bacteria and an increase in the abundance of pathogenic bacteria of which the most common is the gram-negative Enterobacteriaceae (ENTERO) family. Bacterial lipopolysaccharides (LPS), the glycolipids found on the outer membrane of gram-negative bacteria, is one of the links between the microbiome and hypercoagulability. LPS binds to toll-like receptors to activate endothelial cells and platelets, leading to activation of the coagulation cascade. Bacteria in the microbiome can also metabolite compounds in the diet to produce important metabolites like trimethylamine-N-oxide (TMAO). TMAO causes platelet hyperreactivity, promotes thrombus formation and is associated with cardiovascular disease. Modulating the gut microbiome to target LPS and TMAO levels may be an innovative approach for decreasing the risk of thrombosis.

PMID: 32192995 [PubMed - as supplied by publisher]

13:17

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Thrombophilia screening and thromboprophylaxis may benefit specific ethnic subgroups with paediatric acute lymphoblastic leukaemia.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Thrombophilia screening and thromboprophylaxis may benefit specific ethnic subgroups with paediatric acute lymphoblastic leukaemia.

Br J Haematol. 2019 03;184(6):994-998

Authors: Barzilai-Birenboim S, Arad-Cohen N, Nirel R, Avrahami G, Harlev D, Gilad G, Elhasid R, Izraeli S, Litichever N, Elitzur S

Abstract

This study investigated the prevalence of inherited thrombophilia, risk of venous thromboembolism (VTE) and benefit of low molecular weight heparin prophylaxis in 476 Israeli children with acute lymphoblastic leukaemia (ALL) treated between 2004 and 2016. Thrombophilia was found in 15·5%. Arab children had a higher prevalence of F5 R506Q (factor V Leiden) than Jewish children (19·4% vs. 2·9%, P < 0·01).< 0·001).

PMID: 30632137 [PubMed - indexed for MEDLINE]

23 March 2020

14:07

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

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T2 Mapping Identifies Early Anthracycline-Induced Cardiotoxicity in Elderly Patients With Cancer.

JACC Cardiovasc Imaging. 2020 Mar 13;:

Authors: Martin-Garcia A, Diaz-Pelaez E, Lopez-Corral L, Sanchez-Pablo C, Macias de Plasencia G, Galan-Arriola C, Sanchez-Gonzalez J, Cruz JJ, Ibanez B, Sanchez PL

PMID: 32199840 [PubMed - as supplied by publisher]

24 March 2020

11:30

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

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Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial.

Br J Cancer. 2020 Mar 16;:

Authors: Eiger D, Pondé NF, Agbor-Tarh D, Moreno-Aspitia A, Piccart M, Hilbers FS, Werner O, Chumsri S, Dueck A, Kroep JR, Gomez H, Láng I, Rodeheffer RJ, Ewer MS, Suter T, de Azambuja E

Abstract

BACKGROUND: Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting.

METHODS: This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm.

RESULTS: With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55%64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m2 (vs < 25 mg

CONCLUSIONS: Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006-000562-36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2-06 /EGF106708/N063D.

PMID: 32203207 [PubMed - as supplied by publisher]

11:30

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Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.

J Cancer. 2020;11(9):2602-2609

Authors: Fang Y, Wang Z, Wu J, Huang O, He J, Zhu L, Chen W, Li Y, Chen X, Shen K

Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted

Abstract

Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.

PMID: 32192047 [PubMed]

13:16

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

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Structural alteration in hypochlorous acid modified antithrombin indicates generation of neo-epitopes.

Arch Biochem Biophys. 2020 Mar 17;:108332

Authors: Ahmad P, Tantry IQ, Ali A, Siddiqui SA, Rehman SU, Waris S, Jairajpuri MA

Increased tendency of cancer patient to develop venous thromboembolism (VTE) is associated with high rates of mortality. Elevation of

Abstract

Increased tendency of cancer patient to develop venous thromboembolism (VTE) is associated with high rates of mortality. Elevation of procoagulant proteins and down regulation of naturally occurring coagulation inhibitors appears to form the basis of high risk of VTE in malignancy. A reduced level of anticoagulant protein like antithrombin (AT) will influence both coagulation and angiogenesis, as its cleaved and latent conformations show potent antiangiogenic activity. We show a concentration dependent perturbation in the secondary and tertiary structures of AT conformers exposed to hypochlorous acid (HOCl). Modulated under a very narrow concentration range of HOCl, native AT undergoes oligomerization, aggregation and fragmentation based on spectroscopic, SDS and native-PAGE studies. Factor Xa inhibition assay demonstrated a progressive decrease in inhibition activity of AT on modification by HOCl. Bis-ANS result showed that hydrophobic patches were more exposed in the case of HOCl-modified AT when assessed fluorometrically. Dosage of HOCl-modified AT in experimental animals induced high titer antibodies showing more specificity towards modified forms in comparison to unmodified forms. Auto-antibodies isolated from cancer patients also showed enhanced binding with HOCl-modified AT in comparison to native AT. Compared to normal AT, structurally and functionally altered conformation of HOCl modified AT showed increased immunogenic sensitivity. HOCl modified AT can contribute to prothrombotic and angiogenic environment during cancer progression/development.

PMID: 32194043 [PubMed - as supplied by publisher]

13:17

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The gut microbiome and thromboembolism.

Thromb Res. 2020 Mar 06;189:77-87

Authors: Hasan RA, Koh AY, Zia A

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving

Abstract

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data.

PMID: 32194352 [PubMed]

12:46

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MicroRNAs in Cancer Treatment-Induced Cardiotoxicity.

Cancers (Basel). 2020 Mar 17;12(3):

Authors: Pellegrini L, Sileno S, D'Agostino M, Foglio E, Florio MC, Guzzanti V, Russo MA, Limana F, Magenta A

Radiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue

Abstract

Radiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue side effects. In thoracic cancers, including breast and lung cancers, cardiac radiation is a major concern in treatment planning. There are currently no biomarkers of radiation-induced cardiotoxicity. Complex genetic modifiers can contribute to the risk of radiation-induced cardiotoxicities, yet these modifiers are largely unknown and poorly understood. We have previously reported the SS (Dahl salt-sensitive/Mcwi) rat strain is a highly sensitized model of radiation-induced cardiotoxicity compared to the more resistant Brown Norway (BN) rat strain. When rat chromosome 3 from the resistant BN rat strain is substituted into the SS background (SS.BN3 consomic), it significantly attenuates radiation-induced cardiotoxicity, demonstrating inherited genetic variants on rat chromosome 3 modify radiation sensitivity. Genes involved with mitochondrial function were differentially expressed in the hearts of SS and SS.BN3 rats 1 week after radiation. Here we further assessed differences in mitochondria-related genes between the sensitive SS and resistant SS.BN3 rats. We found mitochondrial-related gene expression differed in untreated hearts, while no differences in mitochondrial morphology were seen 1 week after localized heart radiation. At 12 weeks after localized cardiac radiation, differences in mitochondrial complex protein expression in the left ventricles were seen between the SS and SS.BN3 rats. These studies suggest that differences in mitochondrial gene expression caused by inherited genetic variants may contribute to differences in sensitivity to cardiac radiation.

PMID: 32195269 [PubMed]

12:45

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Administration of trastuzumab with heart irradiation induced acute cardiotoxicity in mice.

Am J Cancer Res. 2020;10(2):536-544

Authors: Yi P, Li H, Fang Y, Su J, Xu C, Cao L, Li M, Chen J

Lung cancer (LC) is the leading cause of cancer mortality. PATP was provided in experimental trials to decrease the venous

Abstract

Lung cancer (LC) is the leading cause of cancer mortality. PATP was provided in experimental trials to decrease the venous thromboembolism (VTE), with ultimate aim to improve overall survival (OS). We undertook an updated systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of PATP with LMWHs on OS and VTE in patients with LC. 5443 patients with LC from nine RCTs were included. The pooled hazard ratio (HR) for OS was 1.02 (95% CI 0.83 to 1.26; P = 0.83) and for progression or metastasis-free survival was 1.03 (95% CI 0.86 to 1.24; P = 0.74). The pooled risk ratio (RR) for VTE was 0.54 (95% CI 0.43 to 0.69; P < 0.00001)< 0.00001).

PMID: 32189065 [PubMed - as supplied by publisher]

21 March 2020

12:45

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

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Exercise Interventions in Cardio-oncology Populations: A Scoping Review of the Literature.

J Cardiovasc Nurs. 2020 Mar 19;:

Authors: Wang HL, Cousin L, Fradley MG, Donovan KA, Smith B, Szalacha L, Lavoie Smith EM, Buck HG

Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA)

Abstract

Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA) approved by the FDA for the treatment of different kinds of cancers, especially colorectal cancer. Although the anti-tumor effects have been verified, the side effects of BVZ are also noteworthy, among which, cardiotoxicity may be the most serious side effect of BVZ. However, the exact mechanisms of cardiotoxicity induced by BVZ have been little explored. This study was conducted in vitro in a human cardiac myocyte (HCM) model. MTT assay was conducted to determine BVZ-stimulated cell viability. For testing the function and mechanism, the cells were transfected with miR-140-5p mimics, miR-140-5p inhibitor and/or VEGFA small interfering RNA (si-VEGFA). Then, apoptosis of the cells was detected via annexin V/propidium iodide (AV-PI) staining followed by flow cytometry. qRT-PCR and western blot assays were applied to measure gene expression (i.e. mRNA) and protein levels, respectively. The CK, LDH, SOD, CAT and GSH-Px activities and MDA level were determined using commercial kits. ROS levels were determined by DCFH-DA assay. Mitochondrial membrane potential was measured by JC-1 assay. Dual-luciferase reporter assay was used to detect the interaction between miR-140-5p and VEGFA. BVZ could inhibit HCM proliferation and induce apoptosis. miR-140-5p was upregulated in response to BVZ treatment and miR-140-5p restraint could alleviate HCM damage caused by BVZ treatment. In contrast, VEGFA and 14-3-3γ expressions were down-regulated by BVZ, and miR-140-5p could inhibit the expression of 14-3-3γ by directly targeting VEGFA. Moreover, VEGFA suppression enhanced HCM injury stimulated by BVZ and partially reversed the functional role of the miR-140-5p inhibitor in BVZ-treated cells. Taken together, miR-140-5p promoted BVZ-treated cardiomyocyte toxicity by targeting the VEGFA/14-3-3γ signal pathway. Collectively, miR-140-5p mediated the BVZ-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway, indicating that miR-140-5p may be a novel target for treating BVZ-induced cardiotoxicity.

PMID: 32190292 [PubMed]

11:12

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Oxidative Stress in Radiation-Induced Cardiotoxicity.

Oxid Med Cell Longev. 2020;2020:3579143

Authors: Ping Z, Peng Y, Lang H, Xinyong C, Zhiyi Z, Xiaocheng W, Hong Z, Liang S

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