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12/10/23

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]

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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?

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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.

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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]

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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

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]

12:02

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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.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--misc.karger.com-LinkOuticons-sk_nlm_ft.jpg Related Articles

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]

12:02

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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]

11:28

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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]

14:06

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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

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