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12/10/23

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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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.

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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.

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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.

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.

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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

High dose melphalan is commonly used as a conditioning regimen for autologous stem cell transplantation in multiple

Abstract

High dose melphalan is commonly used as a conditioning regimen for autologous stem cell transplantation in multiple myeloma. There are reports of adverse cardiac events with melphalan manifested by supraventricular tachycardia and atrial fibrillation. Here, we report a rare case of a 58 year old female with multiple myeloma, who developed sinus arrest after autologous stem cell transplantation using high dose melphalan as a conditioning regimen. It was severe and rare, therefore, monitoring for cardiac toxicity in patients receiving high-dose melphalan is mandatory.

PMID: 32190351 [PubMed]

11:12

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miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway.

Toxicol Res (Camb). 2019 Nov 01;8(6):875-884

Authors: Chen XY, Huang WL, Peng XP, Lv YN, Li JH, Xiong JP

WHAT IS KNOWN AND OBJECTIVES: The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide

Abstract

WHAT IS KNOWN AND OBJECTIVES: The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or refractory non-Hodgkin's lymphoma. However, vincristine and doxorubicin hydrochloride are relatively toxic, leading to neurovirulence and cardiotoxicity, respectively. In this study, we replaced these drugs with vindesine and epirubicin hydrochloride to reduce the cardiotoxicity and evaluated admixtures containing these drugs along with etoposide in a single infusion bag in vitro.

METHODS: The appearance and pH of the admixtures were evaluated, and the number of particles was detected. High-performance liquid chromatography was used to measure the concentration and degradation rates of etoposide, epirubicin hydrochloride and vindesine sulphate in each admixture.

RESULTS AND DISCUSSION: No precipitation occurred when mixing clinically relevant concentrations of etoposide, epirubicin hydrochloride and vindesine sulphate in a 0.9% NaCl injection solution. Furthermore, the delta pH of the admixtures was ≤0.12 throughout the experiment, and the number of particles (≥10 and ≥25 μm) in the solutions over the 24 hours post-preparation period met USP standards. Etoposide, epirubicin hydrochloride and vindesine sulphate were retained at >96% of their initial concentrations in the admixtures at 25°C over the course of the experiment. Etoposide, epirubicin hydrochloride and vindesine sulphate are compatible when mixed in a 0.9% NaCl injection solution, and the admixtures are stable for at least 24 hours when stored in infusion bags.

WHAT IS NEW AND CONCLUSION: This in vitro analysis indicates the suitability of our novel admixtures containing less toxic drug equivalents in a single infusion bag for clinical application.

PMID: 31529525 [PubMed - indexed for MEDLINE]

14:12

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

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Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.

Eur Heart J Acute Cardiovasc Care. 2020 Mar 18;:2048872620907322

Authors: Koch V, Biener M, Müller-Hennessen M, Vafaie M, Staudacher I, Katus HA, Giannitsis E

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity

Abstract

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1-3 µM markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity.

PMID: 32185414 [PubMed - as supplied by publisher]

13:40

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In vitro compatibility and stability of admixtures containing etoposide, epirubicin hydrochloride and vindesine sulphate in a single infusion bag.

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

In vitro compatibility and stability of admixtures containing etoposide, epirubicin hydrochloride and vindesine sulphate in a single infusion bag.

J Clin Pharm Ther. 2019 Dec;44(6):875-882

Authors: Li J, Yao C, Xu Y, Ping P, Yin H, Sun Y

BACKGROUND: Cancer is a risk factor for perioperative deep venous thrombosis and pulmonary embolism (DVT/PE). However

Abstract

BACKGROUND: Cancer is a risk factor for perioperative deep venous thrombosis and pulmonary embolism (DVT/PE). However, there is a paucity of data on non-malignant digestive diseases. In this study, we aimed to investigate the incidence of DVT/PE among patients, following surgery for acute appendicitis and other digestive diseases.

METHODS: We retrospectively reviewed the records of patients who underwent surgical procedures involving the digestive system between April 2018 and March 2019 attended by anesthesiologists (n = 536).

RESULTS: DVT/PE developed in seven patients (7/77, 9.1%, 95% confidence interval [CI] 3.7-17.8%) after surgery for acute appendicitis, and in six patients (6/83, 7.2%, 95%CI 2.7-15.1%) after elective surgery for colorectal cancer. Among the acute appendicitis group, six patients (6/30 20.0%) with complicated appendicitis (gangrenous or perforated appendicitis), and one patient (1/47 2.1%) with simple appendicitis showed postoperative DVT/PE. Patients with complicated appendicitis had a higher risk of DVT/PE than those with simple appendicitis with an odds ratio of 11.5 (95%CI 1.3-101.1).

CONCLUSIONS: Although patients with acute appendicitis lack three of the risk factors for DVT/PE (cancer, long operative time, and older age), their 95% CI for the incidence of DVT/PE was comparable to that of patients undergoing elective surgery for colorectal cancer. Therefore, caution must be exercised during the perioperative period for preventing DVT/PE.

PMID: 32180028 [PubMed]

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Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism.

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Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism.

Acta Haematol. 2019;142(4):233-238

Authors: Patel A, Williams H, Baer MR, Zimrin AB, Law JY

Background: No clear guidelines exist for the management of phlegmasia cerulea dolens. This case report shows how a hybrid

Abstract

Background: No clear guidelines exist for the management of phlegmasia cerulea dolens. This case report shows how a hybrid approach might be successful. It also shows how rare pathologies can combine to create a life- and limb-threatening condition. Case Presentation. A 75-year-old man, known for nephrotic syndrome currently under investigation, presented to the emergency department with a 24-hour history of left leg swelling followed by intense pain. The left lower limb showed a phlegmasia cerulean dolens. Renal function, coagulation profile, and inflammatory parameters were normal; D-Dimers 5,6 mg/L. The CT scan showed juxtarenal thrombosis of the hypoplastic IVC, involving both renal veins, reaching the left iliac-femoral-popliteal axis, with collateralization to the pelvic and mesenteric veins, associated with bilateral segmental pulmonary embolisms. A suspected left breast nodule was also found. Intravenous heparin was immediately administered, and urgent hybrid procedure with surgical thrombectomy and venous angiography and thromboaspiration, liberating the iliolumbar collaterals, was performed. A lateral leg fasciotomy was mandatory due to the phlegmasia cerulea. Postoperative Doppler US showed a good venous compressibility of the left leg. Thrombophilia screening was negative. The breast nodule was biopsied showing an invasive ductal carcinoma. The patient was discharged with oral rivaroxaban and indication for left mastectomy and oncological therapy with aromatase inhibitors.

Conclusion: This case highlights the dramatic consequence of different risk factors for venous thromboembolism as cancer and nephrotic syndrome in a patient with hypoplasia of the inferior cava vein. Venous thromboaspiration has been used in order to timely recanalize important collaterals. Phlegmasia cerulea dolens was resolved after the procedure and lateral calf fasciotomy. Further evidence is needed to clearly define the role of venous thromboaspiration in the treatment of complex proximal deep venous thrombosis of the lower extremity.

PMID: 32181047 [PubMed]

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Incidence of postsurgical pulmonary embolism and deep venous thrombosis: a single-center retrospective observational study.

JA Clin Rep. 2020 Mar 16;6(1):22

Authors: Otsuka H, Izumi M, Ota E, Mochizuki N

After heart transplantation, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting from

Abstract

After heart transplantation, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting from calcineurin inhibitors (CNI) to EVL. The aim of this study was to describe the effects of combining low-dose EVL and CNI in maintenance immunosuppression regimen (quadritherapy) and compare it to standard tritherapy associating standard-dose CNI, MMF and corticosteroids. In 3-years registry cohort of heart transplanted patients, those who received quadritherapy were compared to those who received tritherapy. EVL was added after 3 months post-transplantation. Three analyses were performed to control for confounders: propensity-score matching, multivariable survival and inverse-probability-score weighting (IPSW) analyses. Among 213 patients who were included (75 with quadritherapy), propensity-score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n=128), quadritherapy was associated with fewer deaths (3 (4.7%) vs 17 (21.9%), p-value=0.007) and biopsy-proven acute rejections (15 (23.4%) vs 31 (48.4%), p-value=0.002). These results were confirmed in the overall cohort (n=213), after multivariable and IPSW analyses. Renal function and donor-specific HLA-antibodies remained similar in both groups. Low-dose combination quadritherapy was associated with fewer deaths and rejections, compared to standard immunosuppression tritherapy.

PMID: 32180354 [PubMed - as supplied by publisher]

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Cancer therapy cardiotoxicity detection: understanding the limitations of cardiac imaging.

Heart. 2020 Mar 16;:

Authors: Palaskas N, Lopez-Mattei J

PMID: 32179588 [PubMed - as supplied by publisher]

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Hypertension and incident cardiovascular events following ibrutinib initiation.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--ashpublications.org-images-pubmed-logo.png Related Articles

Hypertension and incident cardiovascular events following ibrutinib initiation.

Blood. 2019 11 28;134(22):1919-1928

Authors: Dickerson T, Wiczer T, Waller A, Philippon J, Porter K, Haddad D, Guha A, Rogers KA, Bhat S, Byrd JC, Woyach JA, Awan F, Addison D

BACKGROUND: Optimal pain control post pancreaticoduodenectomy is a challenge. Epidural analgesia (EDA) is used

Abstract

BACKGROUND: Optimal pain control post pancreaticoduodenectomy is a challenge. Epidural analgesia (EDA) is used increasingly, despite inherent risks and unclear effects on outcomes.

METHODS: All pancreaticoduodenectomies (PDs) performed from January 2013 through December 2017 were included. Clinical parameters were obtained from a retrospective review of a prospective clinical database, the American College of Surgeons NSQIP prospective institutional database, and medical record review. Chi-square, Fisher's exact test, and independent-samples t-tests were used for univariable analyses. Multivariable regression was performed.

RESULTS: Six hundred and seventy-one consecutive PDs from a single institution were included (429 EDA, 242 non-EDA). On univariable analysis, EDA patients experienced significantly less wound disruption (0.2% vs 2.1%), unplanned intubation (3.0% vs 7.9%), pulmonary embolism (0.5% vs 2.5%), mechanical ventilation longer than 48 hours (2.1% vs 7.9%), septic shock (2.6% vs 5.8%), and lower pain scores. On multivariable regression (accounting for baseline group differences (ie sex, hypertension, preoperative transfusion, laboratory results, approach, and pancreatic duct size), EDA was associated with less superficial wound infections (odds ratio [OR] 0.34; 95% CI 0.14 to 0.83; p = 0.017), unplanned intubations (OR 0.36; 95% CI 0.14 to 0.88; p = 0.024), mechanical ventilation longer than 48 hours (OR 0.22; 95% CI 0.08 to 0.62; p = 0.004), and septic shock (OR 0.39; 95% CI 0.15 to 1.00; p = 0.050). Epidural analgesia improved pain scores post-PD days 1 to 3 (p < 0.001). No differences were seen in cardiac or renal complications; pancreatic fistula (B+C) or delayed gastric emptying, 30-/90-day mortality, length of stay, readmission, discharge destination, or unplanned reoperation.

CONCLUSIONS: Based on the largest single-institution series published to date, our data support the use of EDA for optimization of pain control. More importantly, our data document that EDA improved infectious and pulmonary complications significantly.

PMID: 30677524 [PubMed - indexed for MEDLINE]

18 March 2020

11:28

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

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Digoxin Enhances the Anticancer Effect on Non-Small Cell Lung Cancer While Reducing the Cardiotoxicity of Adriamycin.

Front Pharmacol. 2020;11:186

Authors: Wang Y, Ma Q, Zhang S, Liu H, Zhao B, Du B, Wang W, Lin P, Zhang Z, Zhong Y, Kong D

Digoxin is widely used to treat heart failure. Epidemiological studies suggested it might be used as an anticancer drug or sensitizing

Abstract

Digoxin is widely used to treat heart failure. Epidemiological studies suggested it might be used as an anticancer drug or sensitizing agent for cancer therapy. Adriamycin is a well-known anticancer drug, but often causes cardiotoxicity which limits its use. We recently investigated the anticancer effects of digoxin alone or in combination with adriamycin on human non-small cell lung cancer in vitro and in vivo. Digoxin reduced the viability of A549 and H1299 cells in vitro, increased DNA damage by promoting ROS generation and inhibiting both DNA double strand break (DSB) and single strand break (SSB) repair. Combination with adriamycin showed synergistic antiproliferative effects at the ratios of 1/2IC50DIG:IC50ADR and IC50DIG:IC50ADR on A549 and H1299 cells, respectively. In vivo, digoxin potently inhibited A549 growth in both zebraﬁsh and nude mouse xenograft model. Co-treatment with adriamycin not only enhanced the antitumor efficacy, but also reduced the cardiotoxicity. Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting both DNA DSB and SSB repair, and combination with adriamycin for therapy of human non-small cell lung cancer is reasonable.

PMID: 32180730 [PubMed]

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Quadritherapy versus standard tritherapy immunosuppressant regimen after heart transplantation: a propensity-score-matched cohort analysis.

Am J Transplant. 2020 Mar 17;:

Authors: Nguyen LS, Suc G, Kheav VD, Coutance G, Carmagnat M, Rouvier P, Zahr N, Salem JE, Leprince P, Ouldammar S, Varnous S

INTRODUCTION: Little is known about the clinical course and treatment decisions in patients with cancer-associated venous

Abstract

INTRODUCTION: Little is known about the clinical course and treatment decisions in patients with cancer-associated venous thromboembolism (VTE) beyond the initial treatment period of 3 to 6 months. This information is important for clinicians and patients to inform their decisions regarding duration of anticoagulation.

MATERIALS AND METHODS: We reviewed health records from consecutive patients referred to our institution for cancer-associated VTE management between 2013 and 2015 to describe their clinical course and outcomes from 6 to 24 months following their index VTE. Details on patient and cancer characteristics, objectively documented recurrent venous thromboembolism (rVTE), clinically relevant bleeding (CRB) and overall mortality were captured.

RESULTS: 524 patients met eligibility criteria and 322 were alive at 6 months after the index VTE. At 6 months, anticoagulation was continued in 222 patients (68.9%). During follow-up, there were 33 rVTE events in 30 patients (1-year cumulative incidence of 8.2%; 95% CI: 5.5%-11.6%), and 16 CRB events in 15 patients (1-year cumulative incidence of 4.1%; 95% CI: 2.3%-6.7%); 20 (60.6%) rVTE events and 13 (81.3%) CRB events occurred while on anticoagulation. One-year survival beyond 6 months was 73.7% (95% CI: 68.5%-78.2%). A higher proportion of patients with advanced cancer and receiving cancer treatment was found among those who continued anticoagulation beyond 6 months compared to those who stopped anticoagulation.

CONCLUSIONS: Patients with cancer-associated VTE who are alive at 6 months after VTE diagnosis remain at high risk of rVTE, CRB and death.

PMID: 32171947 [PubMed - as supplied by publisher]

14:06

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Post-Pancreaticoduodenectomy Outcomes and Epidural Analgesia: A 5-year Single-Institution Experience.

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

Post-Pancreaticoduodenectomy Outcomes and Epidural Analgesia: A 5-year Single-Institution Experience.

J Am Coll Surg. 2019 04;228(4):453-462

Authors: Simpson RE, Fennerty ML, Colgate CL, Kilbane EM, Ceppa EP, House MG, Zyromski NJ, Nakeeb A, Schmidt CM

OBJECTIVE: Ovarian cancer is a risk factor for venous thromboembolism (VTE), which worsens overall survival. The main

Abstract

OBJECTIVE: Ovarian cancer is a risk factor for venous thromboembolism (VTE), which worsens overall survival. The main objective of our study was to calculate the incidence of VTE in our population. We analyzed VTE impact on diagnosis and management of ovarian cancer.

METHODS: We conducted a retrospective, monocentric study in ovarian, fallopian tube and primary peritoneal cancer patients, divided into 2 groups (« Presence of VTE » and « Absence of VTE »). A univariate and multivariate analysis of factors associated with VTE was performed, and we compared delays of management in both groups.

RESULTS: Among 157 patients included in the study, 22.9% presented a VTE, and 52.8% were asymptomatic. The VTE was diagnosed prior to any treatment in 61.1% of patients and revealed the ovarian cancer in 27.8% of cases. In multivariate analysis, tumor size (OR=1.1, 95%CI:1-2.21, p=0.012), malnutrition (OR=3.79, 95%CI:1.16-12,4, p=0.028) and Ddimer level above 1.5 µg/mL (OR=13.8, 95%CI 1.2-152.8, p=0.02) were significantly associated with VTE. No significant difference was found between the two groups in diagnostic or therapeutic strategy, as well as in delays of management.

CONCLUSION: We report a high incidence of VTE in ovarian cancer, including a lot of asymptomatic events. An early diagnosis with clinical examination and Ddimer level could improve its management and its prognosis.

PMID: 32173596 [PubMed - as supplied by publisher]

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Anticoagulation in thrombocytopenic patients with hematological malignancy: A multinational clinical vignette-based experiment.

Eur J Intern Med. 2020 Mar 12;:

Authors: Leader A, Ten Cate V, Ten Cate-Hoek AJ, Beckers EAM, Spectre G, Giaccherini C, Gurevich-Shapiro A, Krashin E, Raanani P, Schouten HC, Falanga A, Ten Cate H

BACKGROUND: Thrombocytopenia in cancer patients with an indication for anticoagulation poses a unique clinical challenge.

Abstract

BACKGROUND: Thrombocytopenia in cancer patients with an indication for anticoagulation poses a unique clinical challenge. There are guidelines for the setting of venous thromboembolism but not atrial fibrillation (AF). Evidence is lacking and current practice is unclear.

OBJECTIVE: To identify patient and physician characteristics associated with anticoagulation management in hematological malignancy and thrombocytopenia.

METHODS: A clinical vignette-based experiment was designed. Eleven hematologists were interviewed, identifying 5 relevant variable categories with 2-5 options each. Thirty hypothetical vignettes were generated. Each physician received 5 vignettes and selected a management strategy (hold anticoagulation; no change; transfuse platelets; modify type/dose). The survey was distributed to hematologists and thrombosis specialists in 3 countries. Poisson regression models with cluster robust variance estimates were used to calculate relative risks for using one management option over the other, for each variable in comparison to a reference variable.

RESULTS: 168 physicians answered 774 cases and reported continuing anticoagulation for venous thromboembolism or AF in 607 (78%) cases, usually with dose reduction or platelet transfusion support. Overall, management was affected by platelet count, anticoagulation indication, time since indication, type of hematological disease and treatment, and prior major bleeding, as well as physician demographics and practice setting. The CHA2DS2-VASc score and time since AF diagnosis affected anticoagulation management in AF.

CONCLUSION: This study indicates what the widely accepted management strategies are. These strategies, and possibly others, should be assessed prospectively to ascertain effectiveness. The decision process is intricate and compatible with current venous thromboembolism guidelines.

PMID: 32173172 [PubMed - as supplied by publisher]

14:06

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Supportive Care in Multiple Myeloma.

Curr Hematol Malig Rep. 2020 Mar 14;:

Authors: Guzdar A, Costello C

We report here a 70-year-old female patient with a history of breast cancer who presented with dyspnea that had lasted for 2 weeks

Abstract

We report here a 70-year-old female patient with a history of breast cancer who presented with dyspnea that had lasted for 2 weeks following a long-distance trip by bus. She was at first suspected of having a pulmonary embolism given the typical presentation, elevated D-dimer level, and enlargement of the right-side heart. However, her systemic condition deteriorated despite the initiation of anti-coagulation therapy. Given the absence of a major thrombus in the pulmonary major arteries but multiple low perfusion lesions in the periphery of the lungs, refractoriness to conventional therapy, an increase in tumor markers, and anaplastic cells demonstrated by aspiration cytology from the pulmonary artery, we diagnosed her as pulmonary tumor thrombotic microangiopathy (PTTM). She died on day 23 due to respiratory failure despite administration of inotropes and prostaglandin I2. The patient had an obvious history of malignancy, but we should emphasize that PTTM can develop even in patients with early-stage or completely cured malignancies. Although an early and definite diagnosis of PTTM is currently challenging, an optimal diagnostic and therapeutic strategy is warranted.

PMID: 32173712 [PubMed - as supplied by publisher]

14:05

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[Incidence and impact of venous thrombosis in the diagnosis and therapeutic management of ovarian cancer.]

Gynecol Obstet Fertil Senol. 2020 Mar 12;:

Authors: Achen G, Dolivet E, Turck M, Raffaèle F

BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs)

Abstract

BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking.

METHODS: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone.

RESULTS: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05)<0.0001)<0.001)<0.001),

CONCLUSION: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.

PMID: 32171470 [PubMed - as supplied by publisher]

13:30

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Contemporary Trends and Outcomes of Percutaneous and Surgical Mitral Valve Replacement or Repair in Patients With Cancer.

Am J Cardiol. 2020 Feb 08;:

Authors: Guha A, Dey AK, Omer S, Abraham WT, Attizzani G, Jneid H, Addison D

In the era of emerging options for mitral valvular intervention, we sought to characterize the relative utilization, outcomes

Abstract

In the era of emerging options for mitral valvular intervention, we sought to characterize the relative utilization, outcomes, and posthospital dispositions of patients referred for transcatheter mitral valve repair (TMVRepair) and surgical mitral valve procedures (SMVP), by cancer-status. Leveraging the National Inpatient Sample, a representative national dataset, ICD-9 codes for all adults >18 years with co-morbid mitral regurgitation, and cancer without metastatic disease admitted from 2003 to 2015 were queried. TMVRepair was performed in 700 hospitalizations from 2012 to 2015, whereas SMVP was utilized during 12,863 hospitalizations from 2003 to 2015. During follow-up, we observed a proportional increase in TMVRepair utilization among cancer patients (vs noncancer), particularly in 2015 (14.2% vs 8.2%, p <0.0001).<0.0001).<0.0001),<0.0001).

PMID: 32171440 [PubMed - as supplied by publisher]

13:30

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Detection of chemotherapy-induced cardiotoxicity with antimyosin pretargeted imaging.

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

Detection of chemotherapy-induced cardiotoxicity with antimyosin pretargeted imaging.

J Nucl Cardiol. 2019 08;26(4):1345-1347

Authors: Strauss HW, Mariani G

PMID: 29392625 [PubMed - indexed for MEDLINE]

14:05

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

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Direct versus conventional anticoagulants for treatment of cancer associated thrombosis: a pooled and interaction analysis between observational studies and randomized clinical trials.

Ann Transl Med. 2020 Feb;8(4):95

Authors: Gu ZC, Yan YD, Yang SY, Shen L, Kong LC, Zhang C, Wei AH, Li Z, Wang XH, Lin HW

PURPOSE: We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ

Abstract

PURPOSE: We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ specialists that adopts a real-life, case-by-case approach in the management of patients with immune-related adverse events (irAEs).

EXPERIMENTAL DESIGN: The ImmunoTOX assessment board was set up in 2016 at Gustave Roussy in France. It meets every 2 weeks to discuss the case-by-case management of patients presenting with irAEs. Here, we describe the ImmunoTOX board's activities between 2016 and 2019.

RESULTS: Over study period, 398 requests (concerning 356 patients) were submitted to the ImmunoTOX board. Most of the requests concerned the putative causal link between immunotherapy and the irAE (n = 148, 37%), followed by possible retreatment after temporary withdrawal because of an adverse event (n = 109, 27%), the clinical management of complex situations (n = 100, 25%) and the initiation of immunotherapy in patients with pre-existing comorbidities (n = 41, 10%). The ImmunoTOX board discerned 273 irAEs. The five organ systems most frequently involved by irAEs were lung (n = 58, 21%), gastrointestinal tract (n = 36, 13%), liver or biliary tract (n = 33, 12%), musculoskeletal system (n = 27, 10%), and nervous system (n = 23, 8%). The time to occurrence was shorter for severe irAEs (grade III and VI) than for mild irAEs (grades I and II), with medians of 47 and 91 days, respectively (p = 0.0216).

CONCLUSION: The main medical needs in the management of irAEs involved the lung organ. Severe irAEs were expected to occur earlier than mild irAEs. This real-life study can help to better estimate medical needs and therefore help to assess the management of irAEs.

PMID: 32172197 [PubMed - as supplied by publisher]

13:30

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Androgenic effects on ventricular repolarization: A translational study from the international pharmacovigilance database to iPSC-cardiomyocytes.

Ann Endocrinol (Paris). 2020 Feb 29;:

Authors: Salem JE, Yang T, Moslehi JJ, Waintraub X, Gandjbakhch E, Bachelot A, Hidden-Lucet F, Hulot JS, Knollmann BC, Lebrun-Vignes B, Funck-Brentano C, Glazer AM, Roden DM

Open-access gene expression data sets provide a useful resource for identifying novel drug targets and biomarkers. The IGF1-PI3K

Abstract

Open-access gene expression data sets provide a useful resource for identifying novel drug targets and biomarkers. The IGF1-PI3K pathway is a critical mediator of physiological cardiac enlargement/hypertrophy and protection. This study arose after mining a gene microarray data set from a previous study that compared heart tissue from cardiac-specific PI3K transgenic mouse models. The top-ranked candidate identified from the microarray data was clusterin. Clusterin has been proposed as a biomarker for multiple diseases including heart failure, and as a cancer drug target. Here, we show that clusterin gene expression is increased in hearts of transgenic mice with increased PI3K and decreased in mice with depressed cardiac PI3K. In vitro, clusterin secretion was elevated in media from neonatal rat ventricular myocytes treated with IGF1. Furthermore, by mining gene expression data from hearts during normal mouse postnatal growth, we also report an increase in clusterin expression with postnatal heart growth. Given we show that clusterin is regulated by the IGF1-PI3K pathway in the heart, and this pathway mediates physiological cardiac hypertrophy and cardioprotection, caution is required when considering clusterin as a biomarker for heart failure and as a cancer target. Mining pre-existing cardiac profiling data sets may be a useful approach to assess whether regulating new drug targets is likely to lead to cardiac damage/toxicity.

PMID: 32172307 [PubMed - as supplied by publisher]

13:30

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The 2016-2019 ImmunoTOX assessment board report of collaborative management of immune-related adverse events, an observational clinical study.

Eur J Cancer. 2020 Mar 12;130:39-50

Authors: Michot JM, Lappara A, Le Pavec J, Simonaggio A, Collins M, De Martin E, Danlos FX, Ammari S, Cauquil C, Ederhy S, Barreau E, Belkhir R, Berdelou A, Lazarovici J, Chanson P, Izzedine H, Seferian A, Le Pajolec C, Baldini C, Martin-Romano P, Mariette X, Robert C, Besse B, Hollebecque A, Varga A, Laghouati S, Mateus C, Voisin AL, Soria JC, Massard C, Marabelle A, Champiat S, Lambotte O

12/8/23

INTRODUCTION: Respiratory distress is an uncommon clinical event after caesarean section and occurs due to pulmonary

Abstract

INTRODUCTION: Respiratory distress is an uncommon clinical event after caesarean section and occurs due to pulmonary thromboembolism. Various causes of pulmonary thromboembolism are thrombophlebitis, ovarian venous thrombosis and mesenteric vein thrombosis.

PRESENTATION OF CASE: We report a case of 30 year old female who presented with respiratory distress after eight days of uneventful caesarian section. On emergency explorative laparotomy, small gut was found to be gangrenous, so resection of the segment was performed. On histopathological examination, there was ischaemic necrosis of bowel with presence of large thrombus in mesenteric vessel. On correlating radiological findings of pulmonary thromboembolism and mesenteric vessel thrombosis with bad obstetric history, a possibility of Antiphospholipid syndrome (APS) was suggested in this case. Unfortunately, patient died the day following laparotomy so there was insufficient time to evaluate the patient for thrombophilic disorders.

DISCUSSION: Pregnancy and perpeurium are associated with higher risk of thrombosis as these are hypercoagulable states. Operative delivery and history of thrombophilia in previous pregnancies (APS) are other predisposing factors which lead to increased thrombotic state and pulmonary thromboembolism.

CONCLUSION: High index of suspicion for thrombophilic disorders is required in postpartum patients presenting with respiratory distress as prompt diagnosis and urgent intervention can save patient's life.

PMID: 32169825 [PubMed - as supplied by publisher]

13:51

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

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Uses of pharmacovigilance databases: An overview.

Therapie. 2020 Feb 26;:

Authors: Bihan K, Lebrun-Vignes B, Funck-Brentano C, Salem JE

Over the past decades, assessment of drug safety and of their benefits harms balance has been profoundly modified by the availability

Abstract

Over the past decades, assessment of drug safety and of their benefits harms balance has been profoundly modified by the availability of large databases and computerized automated statistical approaches. Improvement of digital data storage capacity has been applied to pharmacovigilance reports. VigiBase, the international pharmacovigilance database, is now aggregating over 21 million individual case safety reports in 2020. Identification and investigation of drug safety signals - concerning notably rare and unknown adverse drug reactions - is one of the major tasks in pharmacovigilance that can be amplified by automated signal detection. Several quantitative statistical methods exist, each with its own strengths and limits. Integrating signal detection, pharmacovigilance databases can be used for a wide variety of retrospective observational studies illustrated here by concrete examples. Confirming these signals by orthogonal validation using pre-clinical platforms and prospective trials is helpful. Pharmacovigilance databases represent a considerable source of information. However, the quality of signal detection and of pharmacoepidemiology studies in the field of adverse drug reaction closely depends on the quality of the individual data recorded.

PMID: 32169289 [PubMed - as supplied by publisher]

17 March 2020

13:30

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

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Clinical factors associated with the development of postoperative atrial fibrillation in esophageal cancer patients receiving multimodality therapy before surgery.

J Gastrointest Oncol. 2020 Feb;11(1):68-75

Authors: Song EY, Venkat P, Fradley M, Frakes JM, Klocksieben F, Fontaine J, Mehta R, Saeed S, Hoffe SE, Pimiento JM

Objective: To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.

Abstract

Objective: To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.

Methods: The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March, 2016, and comprised thirty Wistar Sprague male rats aged 3-4 months and weighing 200-400 g. The rats were divided into three equal groups (n=10); Group І (control): rats were treated with distilled water, Group ІІ (doxorubicin): rats were treated with distilled water and doxorubicin 20 mg/kg, and Group ІІІ (GB): rats were treated with GB and doxorubicin 20mg/kg. Serum malondialdehyde (MDA), glutathione reductase (GSH), lipid peroxidise (LPO), tumour necrosis factor-alpha (TNF-α), cardiac troponin (cTnI), brain natriuretic peptide (BNP) and caspase-3 (Cas-3) were measured using enzyme-linked immunosorbent assay kits. SPSS 20 was used to compare the effect GB with doxorubicin on the biomarkers of doxorubicin induced-cardiotoxicity.

Results: Doxorubicin led to cardiotoxicity through elevation of cTnI, BNP, Cas-3 and LPO compared with controls (p<0.01).also,<0.01)<0.05).0.05) compared with the doxorubicin.

Conclusions: GB has significant cardio-protective effect through attenuation of oxidative stress during doxorubicin induced-cardiotoxicity in rats.

PMID: 31603888 [PubMed - indexed for MEDLINE]

15 March 2020

12:21

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

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A rare case of mesenteric vessel thrombosis post caesarian section-An underdiagnosed entity.

Int J Surg Case Rep. 2020 Feb 19;68:170-173

Authors: Pawar R, Brar K, Malhotra C, Chhabra S, Rana D, Gupta A

AIMS: The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to

Abstract

AIMS: The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to examine the association between CRF and mortality in cancer patients.

METHODS AND RESULTS: This was a single-center cohort analysis of 1,632 patients (58% male; 64±12 years) with adult onset cancer who were clinically referred for exercise treadmill testing a median of 7 (IQR: 3, 12) years after primary diagnosis. CRF was defined as peak metabolic equivalents (METs) achieved during standard Bruce protocol, and categorized by tertiles. The association between CRF and all-cause and cause-specific mortality was assessed using multivariable Cox proportional hazard models adjusting for important covariates.

RESULTS: Median follow-up was 4.6 (IQR: 2.6, 7.0) years; a total of 411 deaths (229, 50, and 132 all-cause, cardiovascular, and cancer related, respectively) occurred during this period. Compared with low CRF (range: 1.9-7.6 METs), the adjusted hazard ratio (HR) for all-cause mortality was 0.38 (95% CI: 0.28-0.52) for intermediate CRF (range: 7.7-10.6 METs) and 0.17 (95% CI: 0.11-0.27) for high CRF (range: 10.7-22.0 METs). The corresponding HRs were 0.40 (95% CI: 0.19-0.86) and 0.41 (95% CI: 0.16-1.05) for cardiovascular mortality and 0.40 (95% CI: 0.26-0.60) and 0.16 (95% CI: 0.09-0.28) for cancer mortality, respectively. The adjusted risk of all-cause, cardiovascular, and cancer mortality decreased by 26%, 14%, and 25% with each 1 MET increment in CRF.

CONCLUSION: CRF is a strong, independent predictor of all-cause, cardiovascular, and cancer mortality, even after adjustment for important clinical covariates in patients with certain cancers.

PMID: 32167560 [PubMed - as supplied by publisher]

13:04

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Gingko Biloba protects cardiomyocytes against acute doxorubicin induced cardiotoxicity by suppressing oxidative stress.

J Pak Med Assoc. 2019 Aug;69(Suppl 3)(8):S103-S107

Authors: Jasim ST, Al-Kuraishy HM, Al-Gareeb AI

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for

Abstract

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab.

METHODS: TRIBE2 was an open-label, phase 3, randomised study of patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatme[...]

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nt given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov, NCT02339116.

FINDINGS: Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1-41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3-21·4) in the experimental group and 16·4 months (15·1-17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63-0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3-4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis).

INTERPRETATION: Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria.

FUNDING: The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann-La Roche.

PMID: 32164906 [PubMed - as supplied by publisher]

13:04

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

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Association of Post-Diagnosis Cardiorespiratory Fitness with Cause-Specific Mortality in Cancer.

Eur Heart J Qual Care Clin Outcomes. 2020 Mar 13;:

Authors: Groarke JD, Payne DL, Claggett B, Mehra MR, Gong J, Caron J, Mahmood SS, Hainer J, Neilan TG, Partridge AH, Di Carli M, Jones LW, Nohria A

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic

Abstract

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

PMID: 32163687 [PubMed - as supplied by publisher]

12:22

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Religious observance and perceptions of end-of-life care.

Nurs Inq. 2020 Mar 12;:e12347

Authors: Tarabeih M, Bokek-Cohen Y, Abu Rakia R, Nir T, Coolidge NE, Azuri P

BACKGROUND: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating

Abstract

BACKGROUND: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome's payload(s) upon its uptake and regulation of the TME.

EVIDENCE: Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.

CONCLUSION: Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.

PMID: 32162012 [PubMed - as supplied by publisher]

15:04

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

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Development and Validation of a Risk Score for Prediction of Venous Thromboembolism in Patients With Lung Cancer.

Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620910793

Authors: Li Z, Zhang G, Zhang M, Mei J, Weng H, Peng Z

This study examines the impact of the level of religious observance on the attitudes toward end-of-life (EOL) decisions and euthanasia

Abstract

This study examines the impact of the level of religious observance on the attitudes toward end-of-life (EOL) decisions and euthanasia of Jews in Israel-where euthanasia is illegal-as compared to Jews living in the USA, in the states where euthanasia is legal. A self-reporting questionnaire on religiosity and personal beliefs and attitudes regarding EOL care and euthanasia was distributed, using a convenience sample of 271 participants from Israel and the USA. Findings show that significant differences were found in attitudes between Jews of different levels of religious observance with respect to patient autonomy, right to die with dignity, and dying in familiar and supportive surroundings. The USA and Israeli Jews have similar knowledge regarding EOL care and expressed similar attitudes and perceptions toward the issues of authority of medical staff and religious figures and patient's autonomy. Findings indicate that the level of religious observance has more potency in shaping their attitudes and perceptions of EOL decisions than the state law. We conclude by discussing the implications of our findings with regard to multicultural health systems and providing practical recommendations.

PMID: 32162408 [PubMed - as supplied by publisher]

12:22

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Tumor-derived exosomes in the regulation of macrophage polarization.

Inflamm Res. 2020 Mar 11;:

Authors: Baig MS, Roy A, Rajpoot S, Liu D, Savai R, Banerjee S, Kawada M, Faisal SM, Saluja R, Saqib U, Ohishi T, Wary KK

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A

Abstract

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A total of 827 patients with lung cancer from February 2013 to February 2018 in our hospital were retrospectively analyzed. Demographic and clinicopathological variables independently correlated to VTE were applied to develop the risk score in the development group while examined in the validation group. The regression coefficients of multivariable logistic regression test were applied to assign a risk score system. The incidence of VTE was 12.3%, 12.7%, and 11.8% in all patients, in the development and validation groups, respectively. The 496 patients in the development group were classified into 3 groups: low risk (scores ≤3), moderate risk (scores 4-5), and high risk (scores ≥6). The risk of VTE was significantly and positively related to the risk scores in both development and validation groups. The risk score system aided proper stratification of patients with either high or low risk of VTE in the development and validation groups (c statistic = 0.819 and 0.827, respectively). This risk score system based on the factors with most significant correlation showed good predictive ability and is potentially useful for predicting VTE in patients with lung cancer. However, it was developed and validated by a retrospective analysis and has significant limitations, and a prospective validation with all the classic variables assessing the thrombotic risk is needed for a solid conclusion.

PMID: 32162530 [PubMed - in process]

14 March 2020

11:45

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

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Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial.

Lancet Oncol. 2020 Mar 09;:

Authors: Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, Bordonaro R, Latiano TP, Tamburini E, Santini D, Passardi A, Marmorino F, Grande R, Aprile G, Zaniboni A, Murgioni S, Granetto C, Buonadonna A, Moretto R, Corallo S, Cordio S, Antonuzzo L, Tomasello G, Masi G, Ronzoni M, Di Donato S, Carlomagno C, Clavarezza M, Ritorto G, Mambrini A, Roselli M, Cupini S, Mammoliti S, Fenocchio E, Corgna E, Zagonel V, Fontanini G, Ugolini C, Boni L, Falcone A, GONO Foundation Investigators

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer.

Abstract

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer. The cardiotoxicity of DOX is related to the accumulation of its main metabolite doxorubicinol (DOXOL) in the cardiac tissue. Although the pharmacokinetics of DOX shows high interindividual variability, there are no significant covariates to improve dose adjustment. The present study reports the pharmacokinetics of both DOX and DOXOL in a homogeneous population of young female patients with breast cancer (n = 12) making use of a standardized drug association, evaluated in the very first chemotherapy cycle, using plasma and urine data that allowed the calculation of the renal clearance of DOX, the formation clearance of DOXOL and the hepatic clearance of DOX. The extensive data availability also made it possible to estimate the hepatic extraction ratio of DOX for the investigated population, as well as to determine DOXOL unbound fraction in plasma for the first time in humans. DOX and DOXOL simultaneous analysis in plasma, plasma ultrafiltrate, and urine were performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The pharmacokinetics profile of both DOX and DOXOL showed high variability (geometric coefficient of variation of area under the plasma concentration versus time curve extrapolated to infinity was approximately 215 %). The geometrics means were 0.26 for DOXOL/DOX AUC ratio, 15 % and 17 % for unbound fractions of DOX and DOXOL, respectively, 30.70 L⋅h-1 for total clearance, 0.66 L⋅h-1 for renal clearance, 29.97 L⋅h-1 for hepatic clearance and 0.39 L⋅h-1 for the formation clearance of the metabolite DOXOL. The 95 % confidence interval of the estimated hepatic extraction ratio of DOX ranged from 0.14 to 0.79, which characterizes DOX as a drug of low, intermediate or high hepatic extraction ratio.

PMID: 32163849 [PubMed - as supplied by publisher]

12:22

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[Сurrent views on predictors and biomarkers of early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer (review of literature).]

Klin Lab Diagn. 2020;65(3):141-148

Authors: Kit OI, Gvaldin DY, Omelchuk EP, Timoshkina NN

An increasingly aged population, early cancer diagnosis and new oncology and surgical therapies that improve survival favor the

Abstract

An increasingly aged population, early cancer diagnosis and new oncology and surgical therapies that improve survival favor the presentation of cancer patients who are simultaneously affected by a cardiac disease requiring surgery. Oncological therapy can lead to cardiovascular injury, impacting surgical strategies and risk. Current opinion in patients affected by concomitant heart disease and cancer is to give priority to the surgical treatment of cardiac disease, thus allowing the treatment of neoplasm in an active or advanced stage, either by surgical resection or by means of radiation and oncology therapies. Therefore, prior to heart surgery, tumor staging, assessment of prognosis, as well as the interaction between tumor and extracorporeal circulation and the possibility of being able to improve survival with appropriate therapies even in advanced stages, are crucial. Then, an adequate preoperative screening of cardiovascular abnormalities related to antitumoral therapy and the assessment of other conditions linked to the type of cancer, are both extremely important to decide the most appropriate surgical approach. Careful evaluation of the association of cardiovascular diseases and the prognosis of the active or remitted malignancy should be established to improve the prediction of short-, medium- and long-term outcomes. This article aims to review the literature on cardiovascular effects of antitumoral therapy in cardiac surgery candidates. Moreover, the authors provide an overview of the factors that should be considered in patients with a prior history of malignancy or with active cancer, who need cardiac surgery.

PMID: 31530950 [PubMed - indexed for MEDLINE]

13 March 2020

12:22

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

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Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio.

J Pharm Biomed Anal. 2020 Mar 04;185:113231

Authors: Pippa LF, Oliveira ML, Rocha A, de Andrade JM, Lanchote VL

Patients with malignant tumors are usually accompanied with hypercoagulability state and high incidence risk of venous thromboembolism (VTE)

Abstract

Patients with malignant tumors are usually accompanied with hypercoagulability state and high incidence risk of venous thromboembolism (VTE), especially in patients with pancreatic ductal adenocarcinoma (PDAC). However, conventional coagulation test is failed to identify this abnormity. We retrospectively reviewed clinical data of 78 PDAC patients and 79 age-matched controls with rapid thromboelastography (r-TEG) and conventional coagulation test. The main index of r-TEG include TEG-ACT (second), R (second), K (second), angleα (°) and MA (mm), and a short TEG-ACT, short R, a short K, a broad angleα and a prolonged MA can identify hypercoagulability. Compared with age-matched controls, the PADC patients were analyzed to have a shorter K value (72. + 24 ± 22.90 vs. 85.63 ± 32.81, P = 0.0014), increased angleα value (76.20 ± 3.68 vs. 74.415 ± 4.73, P = 0.009) and MA value (63.33 ± 7.19 vs. 60.89 ± 5.52, P = 0.18). Both TEG-ACT (101.72 ± 7.57 vs. 103.78 ± 7.33, P = 0.086) and R (32.95 ± 4.72 vs. 34.34 ± 4.61, P = 0.085) value showed no significant difference in two groups. The laboratory values for conventional coagulation test were within normal ranges: PT (11.65 ± 0.95 vs. 11.38 ± 0.79, P = 0.049), INR (1.01 ± 0.09 vs. 0.98 ± 0.08, P = 0.101), aPTT (28.75 ± 3.45 vs. 28.00 ± 2.98, P = 0.149) and TT (19.44 ± 1.12 vs. 19.69 ± 1.35, P = 0.212). Incidence rates of VTE were 3.8% (3 of 78 patients) and 1.3% (1 of 79 patients) respectively (Fisher's exact test: P = 0.367). Several r-TEG indexes can indicate coagulation disorders within PDAC patients, but the incidence rates of VTE for both PDAC patients and normal controls had no significant difference. Compare to the control group, the potential hypercoagulability of PDAC patients did not correlate to thrombotic complications.

PMID: 31250338 [PubMed - indexed for MEDLINE]

12:51

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

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((cardiotoxicity OR cardio-toxicity) AND cancer) OR Cardio-oncology OR Cardioncology OR cardiooncology; +22 new citations

22 new pubmed citations were retrieved for your search.

Click on the search hyperlink below to display the complete search results:

((cardiotoxicity OR cardio-toxicity) AND cancer) OR Cardio-oncology OR Cardioncology OR cardiooncology

These pubmed results were generated on 2020/03/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.

Citations may include links to full-text content from PubMed Central and publisher web sites.

12 March 2020

13:20

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

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Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented.

Cancers (Basel). 2020 Mar 06;12(3):

Authors: Farge D, Bournet B, Conroy T, Vicaut E, Rak J, Zogoulous G, Barkun J, Ouaissi M, Buscail L, Frere C

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