topics / مواضيع: 11/01/23

BACKGROUND: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment

Abstract

BACKGROUND: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls.

METHODS AND RESULTS: In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05

CONCLUSION: Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors.

PMID: 32078215 [PubMed - as supplied by publisher]

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Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1.

J Biol Chem. 2020 Feb 19;:

Authors: Xia P, Chen J, Liu Y, Fletcher M, Jensen BC, Cheng Z

Chemotherapy-induced cardiovascular toxicity (CICT) is a well-established risk for cancer survivors and causes diseases such as heart failure

Abstract

Chemotherapy-induced cardiovascular toxicity (CICT) is a well-established risk for cancer survivors and causes diseases such as heart failure, arrhythmia, vascular dysfunction, and atherosclerosis. As our knowledge of the precise cardiovascular risks of each chemotherapy agent has improved, it has become clear that genomics is one of the most influential predictors of which patients will experience cardiovascular toxicity. Most recently, GWAS-led, top-down approaches have identified novel genetic variants and their related genes that are statistically related to CICT. Importantly, the advent of human-induced pluripotent stem cell (hiPSC) models provides a system to experimentally test the effect of these genomic findings in vitro, query the underlying mechanisms, and develop novel strategies to mitigate the cardiovascular toxicity liabilities due to these mechanisms. Here we review the cardiovascular toxicities of chemotherapy drugs, discuss how these can be modeled in vitro, and suggest how these models can be used to validate genetic variants that predispose patients to these effects.

PMID: 32078739 [PubMed - as supplied by publisher]

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Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls.

Eur J Heart Fail. 2020 Feb 20;:

Authors: Tromp J, Boerman LM, Sama IE, Maass SWMC, Maduro JH, Hummel YM, Berger MY, de Bock GH, Gietema JA, Berendsen AJ, van der Meer P

INTRODUCTION: Despite the growing spotlight on value-based care and patient safety, little is known about the influence of patient

Abstract

INTRODUCTION: Despite the growing spotlight on value-based care and patient safety, little is known about the influence of patient-, reconstruction-, and facility-level factors on safety events following breast reconstruction. The purpose of this study is to characterize postoperative complications in light of hospital-level risk factors.

METHODS: Using the National Inpatient Sample, all patients who underwent free flap and prosthetic breast reconstruction from 2012 to 2014 were identified. Predictor variables included patient demographic and clinical characteristics, type and timing of reconstruction, annual hospital reconstructive volume, hospital bed size, hospital setting (rural vs. urban), and length of stay. Patient safety indicators (PSIs) were based on the Agency for Healthcare Research and Quality's designation of preventable hospital complications: venous thromboembolism, bleeding, wound complications, pneumonia, and sepsis. Logistic models were used to analyze outcomes.

RESULTS: The sample included 103,301 women, of which 27,695 (26.8%) underwent free flap reconstruction. 3.6% of patients experienced ≥ 1 PSI, most commonly wound PSI (4.9% and 2.5% for free flap and prosthetic reconstruction, respectively). Significant predictors of PSIs included rural setting (p < 0.01)< 0.01)< 0.01)0.05).

CONCLUSION: PSIs were associated with rural hospitals and greater comorbidities for patients undergoing reconstruction with free flaps. Annual reconstructive facility volume was not associated with adverse inpatient outcomes with either method of reconstruction.

PMID: 31338643 [PubMed - indexed for MEDLINE]

21 February 2020

19:33

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

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Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity.

J Cardiovasc Transl Res. 2020 Feb 20;:

Authors: Pinheiro EA, Magdy T, Burridge PW

Myocardial steatosis, also known as lipomatosis cordis, is characterized by adipose tissue within the myocardium without significant fibrosis

Abstract

Myocardial steatosis, also known as lipomatosis cordis, is characterized by adipose tissue within the myocardium without significant fibrosis. Evidence suggests that accumulation of fat can disturb the normal electromechanical physiology of the myocardium. Herein, we discuss the case of a 60-year-old woman with a history of chronic obstructive pulmonary disease who died because of anoxic encephalopathy after a sudden cardiac arrest (SCA). An electrocardiogram showed QRS fragmentation noted as notched R in inferior leads. The autopsy revealed a very small thromboembolus in a distal subsegmental branch of the pulmonary artery, which could not explain the SCA. There was an extensive intramyocardial accumulation of adipose tissue involving the right ventricle and interventricular septum, which split the myocardium into discrete bundles. Arrhythmogenic right ventricular cardiomyopathy was ruled out based on the absence of typical fibrofatty changes. The mechanism of fat replacement was likely secondary to redistribution of visceral fat in the setting of Cushing syndrome. We propose that severe myocardial steatosis can create an anatomic substrate to facilitate the development of SCA. Myocardial steatosis should be reported to identify patients who are at risk for developing cardiovascular events secondary to extreme cardiac adiposity.

PMID: 32000221 [PubMed - indexed for MEDLINE]

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The impact of hospital volume on patient safety indicators following post-mastectomy breast reconstruction in the US.

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The impact of hospital volume on patient safety indicators following post-mastectomy breast reconstruction in the US.

Breast Cancer Res Treat. 2019 Nov;178(1):177-183

Authors: Sheckter CC, Rochlin D, Kiwanuka H, Curtin C, Momeni A

PURPOSE: Verify whether there is a difference in likelihood of developing pulmonary embolism (PE) between pregnant women,

Abstract

PURPOSE: Verify whether there is a difference in likelihood of developing pulmonary embolism (PE) between pregnant women, nonpregnant women of reproductive age, and postpartum (up to 6 weeks) women, by comparing their outcomes on computed tomography pulmonary angiography (CTPA) done for suspicion of PE.

MATERIALS AND METHODS: Retrospective cohort study of 1463 CTPA done for suspicion of PE in females of reproductive age (18-40 years), nonpregnant, pregnant (antepartum), and postpartum, from 2 tertiary-care academic hospitals between October 2006 and September 2015. Primary outcome was diagnosis of PE on imaging. Additional assessment was made of technical adequacy of the studies and method of delivery for the postpartum cohort (vaginal vs caesarean birth). Twenty-nine technically nondiagnostic studies were excluded. The effect of any potential variable on PE status was tested using univariate logistic regression. Subgroup analysis was performed after excluding patients with independent risk factors for PE.

RESULTS: The rate of CTPA positive for PE was less among pregnant patients compared to early postpartum and nonpregnant women of similar age, 2.9% vs 11.5% and 10.3%, respectively. Pregnancy was associated with statistically significant decreased odds ratio of developing a PE on CTPA, 0.23 (0.09-0.89), P value = .004. After excluding patients with additional independent risk factors for PE, there was no statistically significant odds ratio association between presence of PE on CTPA and pregnancy 0.41 (0.13-1.34), P value = .14.

CONCLUSION: Rate of CTPA positive for PE in pregnant women was lower than in nonpregnant and early postpartum women. Pregnancy was statistically significantly less likely to be associated with positive PE on a CTPA study. The common perception that pregnancy (antepartum state) is associated with an increased risk of PE may require a thorough critical reappraisal.

PMID: 32070114 [PubMed - as supplied by publisher]

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Severe Myocardial Steatosis: Incidental Finding or a Significant Anatomic Substrate for Sudden Cardiac Arrest?

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Severe Myocardial Steatosis: Incidental Finding or a Significant Anatomic Substrate for Sudden Cardiac Arrest?

Am J Forensic Med Pathol. 2020 Mar;41(1):42-47

Authors: Tuzzolo A, Febres-Aldana CA, Poppiti R

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-Dimer is associated with an increased risk of

Abstract

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-Dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-Dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear.

OBJECTIVES: To explore the potential role of longitudinal D-Dimer trajectories for personalized prediction of cancer-associated VTE.

PATIENTS/METHODS: 167 patients with active malignancy were prospectively enrolled (gastrointestinal: n=59 (35%), lung: n=56 (34%), brain: n=50 (30%), others: n=2 (1%); metastatic disease: n=74 (44%)). D-Dimer (median=0.8µg/mL [25th -75th percentile: 0.4-2.0]) was measured at baseline and during 602 monthly follow-up visits. Joint models of longitudinal and time-to-event data were implemented to quantify the association between D-Dimer trajectories and prospective risk of VTE.

RESULTS: VTE occurred in 20 patients (250-day VTE risk=12.1%, 95%CI: 7.8-18.5). D-Dimer increased by 34%/month (0.47µg/mL/month, 95%CI: 0.22-0.72, p<0.0001)<0.0001).

CONCLUSIONS: D-Dimer increases before the onset of cancer-associated VTE, but remains constant over time in patients without VTE. This study represents proof-of-concept that longitudinal trajectories of D-Dimer may advance the personalized assessment of VTE risk in the oncologic setting.

PMID: 32073229 [PubMed - as supplied by publisher]

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Outcomes of Multidetector Computed Tomography Pulmonary Angiography in Pregnant and Postpartum Women With Suspected Pulmonary Embolism.

Can Assoc Radiol J. 2020 Feb 19;:846537119899552

Authors: Sun S, Diaconescu M, Zhe T, Mesurolle B, Semionov A

CASE DESCRIPTION: A 55-year-old patient with locally advanced pancreatic carcinoma will start Folfirinox. Should he get thromboprophylaxis

Abstract

CASE DESCRIPTION: A 55-year-old patient with locally advanced pancreatic carcinoma will start Folfirinox. Should he get thromboprophylaxis?

CONSIDERATION: Patients with malignant disease have increased risk of venous thromboembolism (VTE). Several types of malignancy, surgery, chemotherapy and metastasis lead to increased risk. VTE is an underdiagnosed phenomenon and the second cause of death in patients treated with chemotherapy. Therapeutic doses increase the risk of bleeding compared to prophylactic anticoagulant treatment. Even though they are less than perfect, several risk scores are able to identify patients with high risk of VTE. The AVERT and CASSINI trials showed that prophylactic doses of DOACs in cancer patients with high risk of VTE are able to significantly reduce this risk.

CONCLUSION: Even though there are many unresolved questions, it seems rational to start thromboprophylaxis in patients with aggressive types of cancer, preferably using DOACs, but low molecular weight heparins are possible as well. Risk scores may be helpful when selecting patients.

PMID: 32073785 [PubMed - as supplied by publisher]

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Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

J Thromb Haemost. 2020 Feb 19;:

Authors: Posch F, Riedl J, Reitter EM, Crowther MJ, Grilz E, Quehenberger P, Jilma B, Pabinger I, Ay C

Cardiac dysfunction is a major side effect of trastuzumab therapy for patients with HER2-positive breast cancer. Beta blockers

Abstract

Cardiac dysfunction is a major side effect of trastuzumab therapy for patients with HER2-positive breast cancer. Beta blockers, such as carvedilol, have been used for protection of trastuzumab cardiotoxicity but there is no definitive conclusive clinical report on their efficacy. In the present study, the preservability effects of carvedilol on trastuzumab-induced left ventricular (LV) dysfunction and the reversibility of trastuzumab-induced cardiotoxicity were evaluated in Wistar rats by echocardiography method. We showed that trastuzumab treatment of rats could induce the LV dysfunction through increasing the LV internal systolic diameter (LVIDs), increasing the end-systolic volume (ESV), decreasing the ejection fraction (EF), and decreasing the fractional shortening (FS). These parameters were not reversed after 14 days of stopping trastuzumab administration. Interestingly, carvedilol improved LVIDs, ESV, EF, and FS. Collectively, the results of this study have verified clinical observations which simultaneously administration of carvedilol may be considered as a possible therapeutic strategy to prevent trastuzumab-mediated LV dysfunction.

PMID: 32074649 [PubMed - as supplied by publisher]

15:44

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

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[Whether or not to use thromboprophylaxis in patients treated with chemotherapy for malignant disease].

Ned Tijdschr Geneeskd. 2019 Nov 28;163:

Authors: Otten JMMB, Fijnheer R

INTRODUCTION: Urothelial carcinoma of the urinary bladder is a tumour of advanced age. The demographic change increases the number of very

Abstract

INTRODUCTION: Urothelial carcinoma of the urinary bladder is a tumour of advanced age. The demographic change increases the number of very old patients ( > 80 years) subjected to TUR-B.

MATERIAL AND METHODS: In a retrospective analysis, perioperative complications in 89 patients (> 80 years), who underwent a transurethral resection of the bladder between 2013 and 2016 in our department, were recorded and evaluated using the Clavien-Dindo grading system.

RESULTS: Mean patient age was 87 years (82 - 94). 81 patients (91 %) were treated with oral anticoagulants (32 × ASA, 24 × NOACs, 25 × Marcumar). A histological examination revealed no tumour in 25/89 (28 %) patients, pTa in 28/89 (31 %), pT1 in 22/89 (25 %) and pT2 or higher in 14/89 patients (16 %), respectively. A total of 36/89 (40 %) patients experienced complications according to the Clavien-Dindo classification. 21/89 (23 %) of patients had a prolonged bladder irrigation due to macrohaematuria, 5/89 (6 %) needed surgical reintervention. 14 (12.4 %) patients needed a blood transfusion, 6 (5.3 %) of them preoperatively. According to the Clavien-Dindo classification, 4/89 (4 %) patients were graded as I, 21/89 (24 %) as II, 5/89 (6 %) as IIb and 3/89 (3 %) as IVa, respectively. Three patients (3 %) died postoperatively (Clavien-Dindo V). One of them died as a result of aspiration pneumonia (86 y, ASA IV), one as a result of pulmonary embolism (90 y, ASA IV) and one as a result of multiorgan failure (84 y, ASA III). In multivariate analyses, a tumour stage > T2 was confirmed as a significant predictor of the occurrence of postoperative complications (odds ratio of 9.541 (95 % CI 1.14 - 84.67 p = 0.032). For oral anticoagulants the odds ratio was 4.10 (95 % CI, 41.00 - 1.23, p = 0.050).

CONCLUSION: Overall, the data show that a TUR-B is feasible in patients > 80 years with an increased complication rate in comparison to younger patients. Prolonged macrohaematuria and a high transfusion rate are attributable to the high percentage of orally anticoagulated patients.

PMID: 29518819 [PubMed - indexed for MEDLINE]

20 February 2020

12:51

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

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In Vivo Evaluation of Carvedilol Cardiac Protection Against Trastuzumab Cardiotoxicity.

Drug Res (Stuttg). 2020 Feb 19;:

Authors: Beiranvand E, Ostad SN, Ardakani EM, Torkashvand F, Sardari S, Vaziri B

Vascular air embolism (VAE) is a known complication of contrast-enhanced CT (CECT) scan occurring in venous or arterial circulation with a

Abstract

Vascular air embolism (VAE) is a known complication of contrast-enhanced CT (CECT) scan occurring in venous or arterial circulation with a wide spectrum of presentations. We report a case of a 44-year-old woman with endometrial adenocarcinoma stage IVB complicated with liver abscess and pulmonary embolism who developed VAE following a routine CECT scan after the sixth cycle of chemotherapy. This was an incidental finding and the patient remained asymptomatic throughout. As such, she was treated conservatively and gradually recovered. This case report serves as a reminder that VAE should be considered in patients presenting with unexplained symptoms following this procedure.

PMID: 31466969 [PubMed - indexed for MEDLINE]

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[Intra- and postoperative complications classified according to the Clavien-Dindo classification in patients > 80 years after transurethral resection of the urinary bladder].

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[Intra- and postoperative complications classified according to the Clavien-Dindo classification in patients > 80 years after transurethral resection of the urinary bladder].

Aktuelle Urol. 2019 Jul;50(3):274-279

Authors: Barakat B, Dawood Y, Horstmann M

INTRODUCTION: Patients with cancer have higher risk of thrombosis compared to the general population and particularly lung

Abstract

INTRODUCTION: Patients with cancer have higher risk of thrombosis compared to the general population and particularly lung adenocarcinoma is considered at high risk for venous thromboembolism. Some targetable oncogenic drivers are supposed to further increase this risk.

CASE DESCRIPTION: A 35-year-old man who had developed a recurrent venous thromboembolism and pulmonary embolism (PE) was diagnosed with ROS1 rearranged non-small cell lung cancer (NSCLC). While molecular examinations were ongoing, he developed progressive respiratory failure. For PE and thrombosis worsening with detection of right heart thrombus, he underwent therapy with unfractionated heparin. Despite initial good radiologic results, only with the start of crizotinib did the patient's clinical condition significantly improve to configure a Lazarus response.

CONCLUSIONS: Cancer diagnosis should always be considered in patients with unprovoked thrombosis and, if NSCLC is diagnosed, genetic alterations should be always sought after. A possible relation between venous thromboembolism and oncogenic drivers, particularly for ALK translocations, has been hypothesized. Similarly to ALK-positive NSCLC, ROS1 rearranged disease has been associated with an increased thromboembolic risk. Further studies are needed to better evaluate this relation and to evaluate the potential benefit of a prophylactic anticoagulating treatment in this subset of patients.

PMID: 32066344 [PubMed - as supplied by publisher]

18:40

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Multiple asymptomatic vascular air embolisms following contrast-enhanced CT scan.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-bmjjournals_full.gif Related Articles

Multiple asymptomatic vascular air embolisms following contrast-enhanced CT scan.

BMJ Case Rep. 2019 Aug 28;12(8):

Authors: Zulkifle AM, Faisal M

Background Coexistence of cancer and cardiovascular disease is increasingly frequent, but nationwide data covering cancer patients with

Abstract

Background Coexistence of cancer and cardiovascular disease is increasingly frequent, but nationwide data covering cancer patients with myocardial infarction (MI) are scarce. We sought to investigate the prevalence of cancer in patients with first MI, and its impact on cardiovascular and bleeding outcome. Methods and Results Using nationwide Swedish quality registries, all patients admitted for first MI between 2001 and 2014 were identified. Data on comorbidity, cancer, and outcome were obtained from the national cancer and patient registries. Stratification was performed according to cancer during the 5 years before MI. Multivariable Cox proportional hazards analyses adjusting for cardiovascular risk factors and invasive treatment assessed the association of cancer with outcome. In total, 175 146 patients with first MI were registered, of whom 9.3% (16 237) had received care for cancer in the 5 years before admission. The cancer rate increased from 6.7% in the years 2001-2002 to 10.7% in 2013-2014, independent of sex and cancer type. The presence of a new cancer diagnosis within 5 years increased from 4.9% to 6.2%. During a median follow-up of 4.3 years, cancer was associated with all-cause mortality (hazard ratio, 1.44; 95% CI, 1.40-1.47), recurrent MI (hazard ratio, 1.08; 95% CI, 1.04-1.12), heart failure (hazard ratio, 1.10; 95% CI, 1.06-1.13), and major bleeding (hazard ratio, 1.45; 95% CI, 1.34-1.57). Risk for adverse events varied strongly according to cancer extent, timing, and type. Conclusions Cancer as a comorbid disorder is increasing and is strongly associated with mortality, severe bleeding, and adverse cardiovascular outcome after first MI.

PMID: 32067596 [PubMed - in process]

18:40

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

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Recurrent thrombosis followed by Lazarus response in ROS1 rearranged NSCLC treated with crizotinib: a case report.

Tumori. 2020 Feb 17;:300891620905665

Authors: Beninato T, Lo Russo G, Garassino MC, De Braud F, Platania M

PURPOSE: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

Abstract

PURPOSE: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

PATIENTS AND METHODS: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities.

RESULTS: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040).

CONCLUSION: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.

PMID: 32067901 [PubMed - as supplied by publisher]

15:27

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Temporal Trends in the Prevalence of Cancer and Its Impact on Outcome in Patients With First Myocardial Infarction: A Nationwide Study.

J Am Heart Assoc. 2020 Feb 18;9(4):e014383

Authors: Velders MA, Hagström E, James SK

INTRODUCTION: The number of hematopoietic stem cell transplants (HSCTs) performed in the United States and worldwide is increasing

Abstract

INTRODUCTION: The number of hematopoietic stem cell transplants (HSCTs) performed in the United States and worldwide is increasing. Cardiac events have been well described in HSCT, and the incidence and type of cardiac events have not changed over recent decades.

PATIENTS AND METHODS: This study adds to the body of evidence in describing the incidence and type of cardiac events experienced by an allogeneic and autologous HSCT population at a single institution from 2012 to 2017.

RESULTS: Sixty-five (9.8%) patients experienced cardiac events, including atrial arrhythmia (N = 39), acute heart failure (N = 9), acute coronary syndrome (N = 7), and new onset hypertension (N = 9), with a few instances of bradycardia, ventricular arrhythmia, pericardial effusion, and pericarditis. Our multivariable regression analysis identified age (older), creatinine (higher), and history of coronary artery disease to significantly correlate with risk of cardiac event (P = .005, P = .039, and P = .038, respectively). A subgroup analysis of those patients experiencing a cardiac event found pre-transplant atrial dilation by trans-thoracic echocardiogram to correlate with increased risk of atrial arrhythmia (33.8% vs. 9.7%; P = .03). Patients developing a CE had an increased risk of death within 1 year (11% vs. 32%; P < .001).

CONCLUSION: We review our results in context of other important HSCT cardiac studies to illuminate the most relevant factors of medical history, laboratory data, and cardiac measurements that will identify patients at higher risk, allowing for intervention to improve HSCT outcomes.

PMID: 32067953 [PubMed - as supplied by publisher]

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New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

Clin Breast Cancer. 2019 Dec 19;:

Authors: Nack E, Koffer PP, Blumberg CS, Leonard KL, Huber KE, Fenton MA, Dizon DS, Wazer DE, Hepel JT

AIMS: Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac

Abstract

AIMS: Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients.

METHODS AND RESULTS: PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001].

CONCLUSIONS: BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

PMID: 32069386 [PubMed - as supplied by publisher]

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Inflammation begets inflammation: cancer and acute MI.

Eur Heart J. 2020 Feb 18;:

Authors: Kondapalli L, Moslehi J, Bonaca MP

PMID: 32068786 [PubMed - as supplied by publisher]

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Cardiotoxicity in Hematopoietic Stem Cell Transplant: Keeping the Beat.

Clin Lymphoma Myeloma Leuk. 2020 Jan 18;:

Authors: Baker JK, Shank-Coviello J, Zhou B, Dixon J, McCorkle R, Sarpong D, Medoff E, Cooper D, Seropian S, Dai F

BACKGROUND: Mechanisms underlying impaired exercise capacity and increased cardiovascular mortality observed in breast cancer (BC)

Abstract

BACKGROUND: Mechanisms underlying impaired exercise capacity and increased cardiovascular mortality observed in breast cancer (BC) patients remain unclear. The prevalence, functional, and prognostic significance of elevated resting heart rate (HR) and abnormal heart rate recovery (HRR) in breast cancer (BC) requires evaluation.

METHODS: In a single-center, retrospective, case-control study of women referred for exercise treadmill testing (ETT), 448 BC patients (62.6 ± 10.0 years) were compared to 448 cancer-free, age-matched controls. Elevated resting HR was defined as HR ≥80 bpm at rest. Abnormal HRR at 1-minute following exercise was defined as ≤12 bpm if active recovery or ≤18 bpm if passive recovery. Association of these parameters with exercise capacity and all-cause mortality was evaluated.

RESULTS: Elevated resting HR (23.7% vs 17.0%, P = 0.013) and abnormal HRR (25.9% vs 20.3%, P = 0.048) were more prevalent in BC cohort than controls. In adjusted analyses, BC patients with elevated resting HR (-0.9 METs (SE 0.3); P = 0.0003) or abnormal HRR (-1.3 METs (SE 0.3); P < 0.0001)

CONCLUSIONS: Women across the BC survivorship continuum, referred for ETT, have an increased prevalence of elevated resting HR and abnormal HRR relative to cancer-free, age-matched female controls. These parameters were associated with decreased exercise capacity. Strategies to modulate these abnormalities may help improve functional capacity in this cohort.

PMID: 30578624 [PubMed - indexed for MEDLINE]

15:27

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

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Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

ESC Heart Fail. 2020 Feb 18;:

Authors: Michel L, Mincu RI, Mrotzek SM, Korste S, Neudorf U, Rassaf T, Totzeck M

Anthracyclines have proved to be one of the most effective chemotherapeutic agents in the treatment of numerous solid tumors and hematologic

Abstract

Anthracyclines have proved to be one of the most effective chemotherapeutic agents in the treatment of numerous solid tumors and hematologic malignancies in both adult and pediatric patients. Their clinical benefit, however, is sometimes hampered by the development of cardiotoxicity, a process that still remains elusive despite decades of investigation. It has been postulated that anthracycline-induced cardiotoxicity is mediated in part by reactive oxygen species and redox cycling. This article reviews anthracycline cardiotoxicity in terms of historical significance, epidemiology, current detection strategies, prevention strategies, and patient care after anthracycline-based chemotherapy.

PMID: 31587778 [PubMed - indexed for MEDLINE]

00:40

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Case-control study of heart rate abnormalities across the breast cancer survivorship continuum.

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Case-control study of heart rate abnormalities across the breast cancer survivorship continuum.

Cancer Med. 2019 01;8(1):447-454

Authors: Groarke JD, Mahmood SS, Payne D, Ganatra S, Hainer J, Neilan TG, Partridge AH, Di Carli MF, Jones LW, Mehra MR, Nohria A

The introduction of targeted agents into modern cancer therapy pursued the goal of molecularly more specific, and thereby more effective

Abstract

The introduction of targeted agents into modern cancer therapy pursued the goal of molecularly more specific, and thereby more effective and safer, therapies. Paradoxically, however, several toxicities were brought to greater attention, among these not only cardiac but also vascular toxicities. The latter reach far beyond venous thromboembolism and include a broad spectrum of presentations based on the vascular territories and pathomechanisms involved, including abnormal vascular reactivity, acute thrombosis, or accelerated atherosclerosis. This article provides an overview of the most common presentations and their management strategies.

PMID: 31587779 [PubMed - indexed for MEDLINE]

00:40

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Anthracycline Cardiotoxicity: It Is Possible to Teach an Old Dog Some New Tricks.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.us.elsevierhealth.com-extractor-graphics-pubmed-clinicslogo.gif Related Articles

Anthracycline Cardiotoxicity: It Is Possible to Teach an Old Dog Some New Tricks.

Cardiol Clin. 2019 Nov;37(4):355-363

Authors: Alvarez-Cardona J, Lenihan DJ

The advent of immunotherapy, particularly immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy, has ushered in a promising

Abstract

The advent of immunotherapy, particularly immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy, has ushered in a promising new era of treatment of patients with a variety of malignancies who historically had a poor prognosis. However, these therapies are associated with potentially life-threatening cardiovascular adverse effects. As immunotherapy evolves to include a wider variety of malignancies, risk stratification, prompt recognition, and treatment of cardiotoxicity will become increasingly important and hence cardiologists will need to play a fundamental role in the comprehensive care of these patients. This article reviews cardiotoxicity associated with contemporary immunotherapy and discusses potential management strategies.

PMID: 31587780 [PubMed - indexed for MEDLINE]

00:39

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Common Vascular Toxicities of Cancer Therapies.

Cardiol Clin. 2019 Nov;37(4):365-384

Authors: Herrmann J

Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by

Abstract

Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by cardiotoxicity. The incidence and precise mechanisms of cardiotoxicity remain uncertain. Clinical presentations of fluoropyrimidine toxicity are varied and include chest pain, myocardial infarction, acute cardiomyopathy, arrhythmia, cardiogenic shock, and sudden cardiac death. Proposed mechanisms include coronary vasospasm, coronary endothelial dysfunction, direct myocardial toxicity, myocarditis, and Takotsubo cardiomyopathy. Therapeutic and prophylactic interventions primarily target coronary vasospasm as the underlying cause. Prospective studies are needed to develop evidence-based approaches to cardioprotection in patients receiving fluoropyrimidines.

PMID: 31587781 [PubMed - indexed for MEDLINE]

00:39

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Cardiotoxicity of Immune Therapy.

Cardiol Clin. 2019 Nov;37(4):385-397

Authors: Ganatra S, Parikh R, Neilan TG

Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of

Abstract

Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands, with an emphasis on their mechanism of action and therapeutic potential. We also describe how these ligands have been used to explore PHB signaling in different physiological and pathological settings.

PMID: 32062751 [PubMed - as supplied by publisher]

00:38

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Solid organ transplant rejection associated with immune-checkpoint inhibitors.

Ann Oncol. 2020 Jan 24;:

Authors: Saberianfar S, Nguyen LS, Manouchehri A, Lebrun-Vignes B, Moslehi JJ, Johnson DB, Hertig A, Salem JE

PMID: 32061451 [PubMed - as supplied by publisher]

00:39

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Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.

Lancet. 2020 Feb 15;395(10223):492-493

Authors: Earl HM, Hiller L, Plummer C, Miles D, Wardley AM, Cameron DA, Dunn JA

PMID: 32061290 [PubMed - in process]

00:39

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Fluoropyrimidine-Associated Cardiotoxicity.

Cardiol Clin. 2019 Nov;37(4):399-405

Authors: Kanduri J, More LA, Godishala A, Asnani A

Background: Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses receive

Abstract

Background: Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established.

Methods: A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain.

Results: Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany.

Conclusions: Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model.

PMID: 32063753 [PubMed]

00:38

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Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases.

Cell Mol Life Sci. 2020 Feb 15;:

Authors: Wang D, Tabti R, Elderwish S, Abou-Hamdan H, Djehal A, Yu P, Yurugi H, Rajalingam K, Nebigil CG, Désaubry L

To uncover the genetic basis of anthracycline-induced cardiotoxicity (AIC), we recently established a genetic suppressor screening strategy in zebrafish

Abstract

To uncover the genetic basis of anthracycline-induced cardiotoxicity (AIC), we recently established a genetic suppressor screening strategy in zebrafish. Here, we report the molecular and cellular nature of GBT0419, a salutary modifier mutant that affects retinoid x receptor alpha a (rxraa). We showed that endothelial, but not myocardial or epicardial, RXRA activation confers AIC protection. We then identified isotretinoin and bexarotene, two FDA-approved RXRA agonists, which exert cardioprotective effects. The therapeutic effects of these drugs only occur when administered during early, but not late, phase of AIC or as pretreatment. Mechanistically, these spatially- and temporally-predominant benefits of RXRA activation can be ascribed to repair of damaged endothelial cell-barrier via regulating tight-junction protein Zonula occludens-1. Together, our study provides the first in vivo genetic evidence supporting RXRA as the therapeutic target for AIC, and uncovers a previously unrecognized spatiotemporally-predominant mechanism that shall inform future translational efforts.

PMID: 32064346 [PubMed - in process]

00:38

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Capsule Networks Showed Excellent Performance in the Classification of hERG Blockers/Nonblockers.

Front Pharmacol. 2019;10:1631

Authors: Wang Y, Huang L, Jiang S, Wang Y, Zou J, Fu H, Yang S

Abstract

Capsule networks (CapsNets), a new class of deep neural network architectures proposed recently by Hinton et al., have shown a great performance in many fields, particularly in image recognition and natural language processing. However, CapsNets have not yet been applied to drug discovery-related studies. As the first attempt, we in this investigation adopted CapsNets to develop classification models of hERG blockers/nonblockers; drugs with hERG blockade activity are thought to have a potential risk of cardiotoxicity. Two capsule network architectures were established: convolution-capsule network (Conv-CapsNet) and restricted Boltzmann machine-capsule networks (RBM-CapsNet), in which convolution and a restricted Boltzmann machine (RBM) were used as feature extractors, respectively. Two prediction models of hERG blockers/nonblockers were then developed by Conv-CapsNet and RBM-CapsNet with the Doddareddy's training set composed of 2,389 compounds. The established models showed excellent performance in an independent test set comprising 255 compounds, with prediction accuracies of 91.8 and 92.2% for Conv-CapsNet and RBM-CapsNet models, respectively. Various comparisons were also made between our models and those developed by other machine learning methods including deep belief network (DBN), convolutional neural network (CNN), multilayer perceptron (MLP), support vector machine (SVM), k-nearest neighbors (kNN), logistic regression (LR), and LightGBM, and with different training sets. All the results showed that the models by Conv-CapsNet and RBM-CapsNet are among the best classification models. Overall, the excellent performance of capsule networks achieved in this investigation highlights their potential in drug discovery-related studies.

PMID: 32063849 [PubMed]

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Evaluation of the cost-effectiveness of dexrazoxane for the prevention of anthracycline-related cardiotoxicity in children with sarcoma and haematologic malignancies: a European perspective.

Cost Eff Resour Alloc. 2020;18:7

Authors: Dewilde S, Carroll K, Nivelle E, Sawyer J

INTRODUCTION: Within the first year of diagnosis, up to 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE).

Abstract

INTRODUCTION: Within the first year of diagnosis, up to 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE). The International Myeloma Working Group (IMWG) has thromboprophylaxis guidelines that stratify patients into low or high risk for thrombosis and subsequently recommend thromboprophylaxis, but it is unknown if these recommendations are being followed or if they are effective. The purpose of this study was to assess efficacy of the IMWG guidelines and investigate other potential VTE risk factors.

METHODS: Study participants were treated at the University of Kansas Medical Center between 2007 and 2013, and charts were reviewed to extract data. Cases (MM and VTE) were matched to controls (MM and no VTE) at approximately 1:3 ratio based on gender, age (±5 years), and time of MM diagnosis (±5 years).

RESULTS: A total of 80 cases and 211 controls were matched. Most patients (82%) were considered high risk for experiencing a VTE at the time of their MM diagnosis and 18% were considered low risk. Neither risk category (P = 0.16) nor thromboprophylaxis at baseline (P = 0.37) predicted VTE, though cases were more likely than controls to have an increased risk of thrombosis at the time of clot compared to their baseline risk (P = 0.09).

CONCLUSION: Our results suggest that IMWG guidelines are not being consistently followed and therefore could not be validated. Additional risk factors were not identified, but risk for VTE may change over time suggesting patients may require ongoing assessment of VTE risk and thromboprophylaxis throughout the disease course.

PMID: 30585435 [PubMed - indexed for MEDLINE]

19 February 2020

00:38

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

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Retinoid X receptor alpha is a spatiotemporally predominant therapeutic target for anthracycline-induced cardiotoxicity.

Sci Adv. 2020 Jan;6(5):eaay2939

Authors: Ma X, Zhu P, Ding Y, Zhang H, Qiu Q, Dvornikov AV, Wang Z, Kim M, Wang Y, Lowerison M, Yu Y, Norton N, Herrmann J, Ekker SC, Hsiai TK, Lin X, Xu X

OBJECTIVE: The objective of this study was to evaluate complications of Greenfield (Boston Scientific, Marlborough, Mass) stainless steel

Abstract

OBJECTIVE: The objective of this study was to evaluate complications of Greenfield (Boston Scientific, Marlborough, Mass) stainless steel inferior vena cava (IVC) filters on follow-up computed tomography (CT) imaging and to elucidate associated risk factors.

METHODS: Ninety-three patients with CT studies obtained for other reasons after Greenfield IVC filter placement (2007-2014) were retrospectively studied. Greenfield filters were placed permanently in those with venous thromboembolism and an expected lifelong contraindication to anticoagulation or life expectancy <6 months.

RESULTS: A total of 190 follow-up CT imaging studies were available for review. In total, filter-associated IVC thrombus (n = 10 [10.7%]) and pulmonary embolism breakthrough (n = 4 [4.3%)] were documented by contrast-enhanced CT. Perforation was evident in 18 patients (19.4%) with an average indwelling time of 256 days. No symptomatic perforation and no strut fracture were documented. There was no significant difference in perforation rate with respect to age of the patient (P = .61), sex (P = 1.00), or history of malignant disease (P = .40). The filter perforation rate and number of perforating struts were significantly higher in patients with longer indwelling time (>90 days) than in patients with shorter indwelling time (<90 days;90 days were significantly smaller than those of nonperforated patients (284 vs 358 mm2; P < .01).

CONCLUSIONS: Stainless steel Greenfield filters remain a relatively safe option for patients requiring permanent mechanical filtration.

PMID: 32063523 [PubMed - as supplied by publisher]

23:24

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Evaluation of the efficacy and safety of apixaban and rivaroxaban in cancer patients receiving concomitant active anti-neoplastic therapy at an outpatient cancer setting.

J Oncol Pharm Pract. 2020 Feb 16;:1078155220901777

Authors: Yassine D, Brown EN, Putney D, Fasoranti O

PMID: 32063102 [PubMed - as supplied by publisher]

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Cancer related venous thromboembolism: both a complication and negative prognostic indicator.

Gastroenterology. 2020 Feb 13;:

Authors: Ghukasyan R, Donahue TR

PMID: 32061863 [PubMed - as supplied by publisher]

23:25

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Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real-world evaluation.

Cancer Med. 2019 01;8(1):455-462

Authors: Baker HA, Brown AR, Mahnken JD, Shireman TI, Webb CE, Lipe BC

OBJECTIVE: Lower extremity deep venous thrombosis (LEDVT) is common and can lead to pulmonary embolism (PE). Currently

Abstract

OBJECTIVE: Lower extremity deep venous thrombosis (LEDVT) is common and can lead to pulmonary embolism (PE). Currently, the mechanism of how LEDVT causes PE is unclear. The aim of this study was to explore the relationship between the thrombus sites and PE in LEDVT patients.

METHODS: A retrospective study that included the medical data of 3101 patients aged >18 years who were diagnosed with LEDVT by duplex ultrasound was performed at The First Affiliated Hospital of Wenzhou Medical University from 2008 to 2017. The clinical information of the patients was collected. According to the thrombosis sites, the patients were divided into three groups. We determined the cumulative prevalence and prevalence rate of PE between the groups and used Cox proportional hazard regression models, which were stratified on matched sets, to calculate the hazard ratios (HRs) for all of the outcomes of interest. We focused on the relationship of proximal or isolated distal LEDVT with PE and also analyzed the relationship of the left side or right side of LEDVT with PE.

RESULTS: A total of 1629 (52.5%) patients had left LEDVT (group 1), 912 (29.4%) patients had right LEDVT (group 2), and 560 (18.1%) patients had bilateral LEDVT (group 3). The rate of PE was higher in group 2 than in group 1, although there were more patients suffering from LEDVT in group 1 than in group 2 (P < .001). The patients with proximal LEDVT in group 3 exhibited a greater risk of PE compared with those with isolated distal LEDVT (adjusted HR, 2.79; 95% confidence interval, 1.42-5.49). We also observed that the proportion of patients with proximal LEDVT who were receiving treatment was much higher than that of patients with distal LEDVT (P < .05). The patients with right LEDVT had a higher risk of PE than the patients with left LEDVT (adjusted HR, 1.60; 95% confidence interval, 1.15-2.21), and the patients with right LEDVT had more comorbidities, such as malignant neoplasms, hypertension, and diabetes (P < .001).

CONCLUSIONS: Patients with proximal bilateral LEDVT had a higher likelihood for development of PE than did patients with distal LEDVT, which may be associated with inadequate therapy for proximal bilateral LEDVT. PE was more likely to develop with right-sided LEDVT because these patients had more comorbidities in our study.

PMID: 32063525 [PubMed - as supplied by publisher]

23:24

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Greenfield stainless steel vena cava filters on computed tomography follow-up.

J Vasc Surg Venous Lymphat Disord. 2020 Feb 13;:

Authors: Chen J, Castle JC, Makary MS, Yang X, Dowell JD

BACKGROUND: Anatomical lung resection for curative treatment of a tumour disease is the most common selective procedure in oncological thoracic surgery.

Abstract

BACKGROUND: Anatomical lung resection for curative treatment of a tumour disease is the most common selective procedure in oncological thoracic surgery. The goal of the working group of the German Thoracic Surgery Society (DGT) was to achieve a consensus on the perioperative management of selective oncological lung resection procedures.

METHODS: The assigned group of the DGT designed and conducted two electronic rounds of questions in all major thoracic and lung centres. Consensus was considered as a rate of ≥ 75%. After statistical analysis of the results, an expert meeting took place and a final Delphi process poll was used in order to reach consensus for controversial topics.

RESULTS: Fourteen questions on the perioperative management of anatomical oncological lung resections were proposed and voted on. A consensus was reached for the following topics: preoperative infectiological screening, extended respiratory diagnostics for impaired lung function, use of a cardiac risk assessment score, postoperative monitoring, prophylaxis for venous thromboembolism, control bronchoscopy after sleeve resections or pneumonectomy, blood gas test before discharge from the hospital. No consensus was reached for the following topics: preoperative endobronchial microbiological diagnostics, pleural rinsing, standardised clinical chemistry blood test postoperatively.

CONCLUSION: Our manuscript depicts the results of a Delphi process in 2018/2019 involving experts of the German Thoracic Surgery Society from high volume departments certified for thoracic surgery and/or lung cancer surgery. In general, a very high rate of consensus was documented for the majority of the topics concerning the perioperative management of oncological anatomical selective lung resection procedures. The most important topic for which no consensus could be reached was preoperative endobronchial microbiological diagnostic testing.

PMID: 32066185 [PubMed - as supplied by publisher]

23:24

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Relationship between the site of thrombosis and the prevalence of pulmonary embolism in acute lower extremity deep venous thrombosis.

J Vasc Surg Venous Lymphat Disord. 2020 Feb 14;:

Authors: Zhang C, Li Q, Yu H, Wang F, Lin Z, Yin W, Pan Y, Wu M, Xie W, Chen X, Liu N

OBJECTIVES: Neoadjuvant chemotherapy may be considered for women with epithelial ovarian cancer who have poor

Abstract

OBJECTIVES: Neoadjuvant chemotherapy may be considered

for women with epithelial ovarian cancer who have poor

performance status or a disease burden not amenable to

primary cytoreductive surgery. Overlap exists between

indications for neoadjuvant chemotherapy and known risk

factors for venous thromboembolism, including impaired

mobility, increasing age, and advanced malignancy. The

objective of this study was to determine the rate of

venous thromboembolism among women receiving

neoadjuvant chemotherapy for epithelial ovarian cancer.

METHODS: A multi-institutional, observational study of

patients receiving neoadjuvant chemotherapy for primary

epithelial ovarian, fallopian tube, or peritoneal

cancer was conducted. Primary outcome was rate of

venous thromboembolism during neoadjuvant chemotherapy.

Secondary outcomes included rates of venous

thromboembolism at other stages of treatment

(diagnosis, following interval debulking surgery,

during adjuvant chemotherapy, or during treatment for

recurrence) and associations between occurrence of

venous thromboembolism during neoadjuvant chemotherapy,

subject characteristics, and interval debulking

outcomes. Venous thromboembolism was defined as deep

vein thrombosis in the upper or lower extremities or in

association with peripherally inserted central

catheters or ports, pulmonary embolism, or concurrent

deep vein thrombosis and pulmonary embolism. Both

symptomatic and asymptomatic venous thromboembolism

were reported.

RESULTS: A total of 230 patients receiving neoadjuvant

chemotherapy were included; 63 (27%) patients overall

experienced a venous thromboembolism. The primary

outcome of venous thromboembolism during neoadjuvant

chemotherapy occurred in 16 (7.7%) patients. Of the

remaining venous thromboembolism events, 22 were at

diagnosis (9.6%), six post-operatively (3%), five

during adjuvant chemotherapy (3%), and 14 during

treatment for recurrence (12%). Patients experiencing a

venous thromboembolism during neoadjuvant chemotherapy

had a longer mean time to interval debulking and were

less likely to undergo optimal cytoreduction (50% vs

80.2%, p=0.02).

CONCLUSIONS: Patients with advanced ovarian cancer are

at high risk for venous thromboembolism while receiving

neoadjuvant chemotherapy. Consideration of

thromboprophylaxis may be warranted.

PMID: 32054646 [PubMed - as supplied by publisher]

18 February 2020

23:24

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

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[Delphi Expert Consensus of the German Thoracic Surgery

Society on Perioperative Management of Oncological

Anatomical Lung Resections].

[Delphi Expert Consensus of the German Thoracic Surgery

Society on Perioperative Management of Oncological

Anatomical Lung Resections].

Zentralbl Chir. 2020 Feb 17;:

Authors: Koryllos A, Ludwig C, Hecker E, Leschber G

BACKGROUND: Our knowledge on the burden of symptomatic and asymptomatic venous thromboembolism (VTE) in

Abstract

BACKGROUND: Our knowledge on the burden of symptomatic

and asymptomatic venous thromboembolism (VTE) in

patients with cancer undergoing chemotherapy is

limited. The aim of our study was to prospectively

investigate the frequency of symptomatic VTE and

asymptomatic deep vein thrombosis of the lower limbs

among cancer patients undergoing chemotherapy.

METHODS: We studied 231 patients (164 men) with

pancreatic (n=36), lung (n=136), ovarian (n=32) or

prostate (n=27) cancer receiving first line (n=192,

83.1%) or adjuvant chemotherapy, followed-up for 3-6

months.

RESULTS: Some 17 patients were diagnosed with VTE,

either asymptomatic detected on leg ultrasound (n=7) or

symptomatic (n=10). The total frequency of VTE was

10.3% (17/165 with follow-up). Pancreatic cancer had

the highest frequency of VTE (4/25, 16%) followed by

ovarian (3/26, 11.5%) and lung cancer (10/94, 10.6%).

There was no statistically significant difference in

VTE rates among cancer types (p=0.36). VTE occurred

more frequently in the presence of metastases (13/85,

15.3% vs. 4/80, 5.0%, for the remainder, p=0.03, OR

3.4). In the subgroup of patients receiving first line

treatment, VTE occurred more frequently in patients

with metastases (13/84, 15.5% vs 2/53, 3.8%, for the

remainder, p=0.033). In patients with pancreatic, lung

or ovarian cancer receiving first line treatment, VTE

occurred more frequently in patients with metastatic

disease (19.1% vs. 4.0%, for the remainder, p=0.015).

CONCLUSIONS: VTE occurrence in this real-world patient

cohort was high, reaching almost 20% in certain groups,

like those with disseminated pancreatic, lung or

ovarian cancer receiving first-line chemotherapy.

Furthermore, VTE occurs mostly as a symptomatic event,

being likely a result of the prothrombotic state of

malignancy.

PMID: 32057213 [PubMed - as supplied by publisher]

14:59

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Incidence of venous thromboembolism among patients

receiving neoadjuvant chemotherapy for advanced

epithelial ovarian cancer.

Incidence of venous thromboembolism among patients

receiving neoadjuvant chemotherapy for advanced

epithelial ovarian cancer.

Int J Gynecol Cancer. 2020 Feb 12;:

Authors: Salinaro JR, McQuillen K, Stemple M, Boccaccio

R, Ehrisman J, Lorenzo AM, Havrilesky L, Secord AA,

Galvan Turner V, Moore KN, Davidson B

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of

Abstract

Venous thromboembolism (VTE) is a common disease

complication in cancer patients and the second cause of

death after cancer progression. VTE management and

prophylaxis are critical in cancer patients, but

effective therapy can be challenging because these

patients are at higher risk of VTE recurrence and

bleeding under anticoagulant treatment. Numerous

published studies report inconsistent implementation of

existing evidence-based clinical practice guidelines

(CPG), including underutilization of

thromboprophylaxis, and wide variability in clinical

practice patterns across different countries and

various practitioners. This review aims to summarize

the 2019 ITAC-CME evidence-based CPGs for treatment and

prophylaxis of cancer-related VTE, which include

recommendations on the use of direct oral

anticoagulants specifically in cancer patients. The

guidelines underscore the gravity of developing VTE in

cancer and recommend the best approaches for treating

and preventing cancer-associated VTE, while minimizing

unnecessary or over-treatment. Greater adherence to the

2019 ITAC guidelines could substantially decrease the

burden of VTE and improve survival of cancer patients.

PMID: 32057323 [PubMed - in process]

14:59

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Frequency and predictors of chemotherapy-associated

venous thromboembolism: the prospective PREVENT study.

Frequency and predictors of chemotherapy-associated

venous thromboembolism: the prospective PREVENT study.

Int Angiol. 2020 Feb 13;:

Authors: Kakkos SK, Arnaoutoglou E, Tsolakis IA,

Giannoukas A, Papadimitriou CA, Kentepozidis N,

Boukovinas I, Kalofonos HP, Labropoulos N, Matsagkas M

Radiofrequency ablation (RFA) can be a therapeutic option in medically inoperable lung cancer patients. In

Abstract

Radiofrequency ablation (RFA) can be a therapeutic

option in medically inoperable lung cancer patients. In

this study, we evaluated a prototype bipolar RFA device

applicator that can be deployed from a standard

endobronchial ultrasound (EBUS) bronchoscope to

determine feasibility and histopathological analysis in

animal models. Rabbit lung cancers were created by

transbronchial injection of VX2 rabbit cancer cells.

Once the tumors were developed, they were ablated

transpleurally, under EBUS guidance using the prototype

RFA device. The animals were then sacrificed for

specimen resection. Pig inflammatory lung pseudo-tumors

and lymphadenopathy were created by transbronchial

injection of a talc paste and ablated transbronchially

under EBUS guidance. Pigs were evaluated at five days,

two weeks, and four weeks following ablation by

bronchoscopy and cone-beam computed tomography before

necropsy. Nicotinamide adenine dinucleotide hydrogen

diaphorase staining was employed to measure the

ablation area. Twenty-four VX2 rabbit tumors were

ablated. The total ablated area ranged from 0.6 to 3.0

cm2 (mean: 1.8 cm2), corresponding to a total energy

range of 1 to 6 kJ. Six pig lung pseudo-tumors and five

mediastinal lymph nodes (LNs) were ablated. Adjacent

airway ulceration was observed in three ablations of

LNs. These airway complications resolved within four

weeks of RFA without any treatment. There was no

hemoptysis, air embolism, respiratory distress, or

other serious complication noted. In these two animal

models, we provide evidence that EBUS-guided bipolar

RFA is feasible and histopathology shows that can

ablate lung tumors and mediastinal lymph nodes under

real-time ultrasound guidance.

PMID: 32057971 [PubMed - as supplied by publisher]

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Management of cancer-related thrombosis in the era of

direct oral anticoagulants: A comprehensive review of

the 2019 ITAC-CME clinical practice guidelines. On

behalf of the Groupe Francophone Thrombose et Cancer

(GFTC).

Management of cancer-related thrombosis in the era of

direct oral anticoagulants: A comprehensive review of

the 2019 ITAC-CME clinical practice guidelines. On

behalf of the Groupe Francophone Thrombose et Cancer

(GFTC).

J Med Vasc. 2020 Feb;45(1):28-40

Authors: Rafii H, Frère C, Benzidia I, Crichi B, Andre

T, Assenat E, Bournet B, Carpentier A, Connault J,

Doucet L, Durant C, Emmerich J, Gris JC, Hij A, Le

Hello C, Madelaine I, Messas E, Ndour A, Villiers S,

Marjanovic Z, Ait Abdallah N, Yannoutsos A, Farge D

Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving

Abstract

Radiation therapy (RT) is an important component of

cancer therapy, with >50% of cancer patients receiving

RT. As the number of cancer survivors increases, the

short- and long-term side effects of cancer therapy are

of growing concern. Side effects of RT for thoracic

tumors, notably cardiac and pulmonary toxicities, can

cause morbidity and mortality in long-term cancer

survivors. An understanding of the biological pathways

and mechanisms involved in normal tissue toxicity from

RT will improve future cancer treatments by reducing

the risk of long-term side effects. Many of these

mechanistic studies are performed in animal models of

radiation exposure. In this area of research, the use

of small animal image-guided RT with treatment planning

systems that allow more accurate dose determination has

the potential to revolutionize knowledge of clinically

relevant tumor and normal tissue radiobiology. However,

there are still a number of challenges to overcome to

optimize such radiation delivery, including dose

verification and calibration, determination of doses

received by adjacent normal tissues that can affect

outcomes, and motion management and identifying

variation in doses due to animal heterogeneity. In

addition, recent studies have begun to determine how

animal strain and sex affect normal tissue radiation

injuries. This review article discusses the known and

potential benefits and caveats of newer technologies

and methods used for small animal radiation delivery,

as well as how the choice of animal models, including

variables such as species, strain, and age, can alter

the severity of cardiac radiation toxicities and impact

their clinical relevance.

PMID: 32053873 [PubMed]

14:58

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Endobronchial ultrasound-guided radiofrequency ablation

of lung tumors and mediastinal lymph nodes: a

preclinical study in animal lung tumor and mediastinal

adenopathy models.

Endobronchial ultrasound-guided radiofrequency ablation

of lung tumors and mediastinal lymph nodes: a

preclinical study in animal lung tumor and mediastinal

adenopathy models.

Semin Thorac Cardiovasc Surg. 2020 Feb 10;:

Authors: Motooka Y, Fujino K, Gregor A, Bernards N,

Chan H, Inage T, Ujiie H, Kato T, Kinoshita T, Ishiwata

T, Suzuki M, Yasufuku K

Owing to early diagnosis and rapid development of treatments for cancers, the five-year survival rate of

Abstract

Owing to early diagnosis and rapid development of

treatments for cancers, the five-year survival rate of

all cancer types has markedly improved worldwide. Over

time, however, there has been an increase in the number

of cancer patients who develop coronary artery disease

(CAD) due to different causes. First, many risk factors

are shared between cancer and CAD. Second, inflammation

and oxidative stress are common underlying pathogeneses

in both disorders. Lastly, cancer therapy can result in

endothelial injury, coronary artery spasm, and

coagulation, thereby increasing the risk of CAD. As

more cancer patients are being diagnosed with CAD,

specialized cardiac care should be established to

minimize the cardiovascular mortality of cancer

survivors.

PMID: 32055781 [PubMed]

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Advances in Preclinical Research Models of Radiation-

Induced Cardiac Toxicity.

Advances in Preclinical Research Models of Radiation-

Induced Cardiac Toxicity.

Cancers (Basel). 2020 Feb 11;12(2):

Authors: Schlaak RA, SenthilKumar G, Boerma M, Bergom C

BACKGROUND: Cardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer

Abstract

BACKGROUND: Cardiovascular disease (CVD) has become an

increasingly common limitation to effective anticancer

therapy. Yet, whether CVD events were consistently

reported in pivotal trials supporting contemporary

anticancer drugs is unknown.

OBJECTIVES: The authors sought to evaluate the

incidence, consistency, and nature of CVD event

reporting in cancer drug trials.

METHODS: From the Drugs@FDA, clinicaltrials.gov,

MEDLINE, and publicly available U.S. Food and Drug

Administration (FDA) drug reviews, all reported CVD

events across latter-phase (II and III) trials

supporting FDA approval of anticancer drugs from 1998

to 2018 were evaluated. The primary outcome was the

report of major adverse cardiovascular events (MACE),

defined as incident myocardial infarction, stroke,

heart failure, coronary revascularization, atrial

fibrillation, or CVD death, irrespective of treatment

arm. The secondary outcome was report of any CVD event.

Pooled reported annualized incidence rates of MACE in

those without baseline CVD were compared with reported

large contemporary population rates using relative

risks. Population risk differences for MACE were

estimated. Differences in drug efficacy using pooled

binary endpoint hazard ratios on the basis of the

presence or absence of reported CVD were also assessed.

RESULTS: Overall, there were 189 trials, evaluating 123

drugs, enrolling 97,365 participants (58.5 ± 5 years,

46.0% female, 72.5% on biologic, targeted, or immune-

based therapies) with 148,138 person-years of follow-

up. Over a median follow-up of 30 months, 1,148

incidents of MACE (375 heart failure, 253 myocardial

infarction, 180 strokes, 65 atrial fibrillation, 29

revascularizations, and 246 CVD deaths; 792 in the

intervention vs. 356 in the control arm; p < 0.01)<

0.01),

CONCLUSIONS: Among pivotal clinical trials linked to

contemporary FDA-approved cancer drugs, reported CVD

event rates trail expected population rates.

PMID: 32057377 [PubMed - in process]

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Optimal management of coronary artery disease in cancer

patients.

Optimal management of coronary artery disease in cancer

patients.

Chronic Dis Transl Med. 2019 Dec;5(4):221-233

Authors: Han XJ, Li JQ, Khannanova Z, Li Y

INTRODUCTION: Unprovoked venous thromboembolism (uVTE) may be the first manifestation of cancer. The main objectives of this study

Abstract

INTRODUCTION: Unprovoked venous thromboembolism (uVTE) may be the first manifestation of cancer. The main objectives of this study were to compare limited screening (LS) and extended screening (ES) and to make a protocol to approach these patients.

METHODS: This is a retrospective, unicentric observational study that included 245 patients with venous thromboembolism (VTE) admitted to an Internal Medicine Service for five years. The incidence of cancer and mortality during hospitalization, and at one and three years after admission were calculated in both LS and ES groups and compared.

RESULTS: Of the 245 patients with VTE, 59 (24.1%) had uVTE: 35 (59.3%) were submitted to LS and 24 (40.7%) to ES, with 10 (4.1%) diagnosis of cancer. In the following three years, 10 more patients were diagnosed. There were no statistically significant differences in inpatient diagnosis rates (8.6% vs. 4.2%; p=0.51) or in-hospital mortality (2.9% vs. 4.2%; p=0.79) or mortality at one year (8.6% vs. 8.3%; p=0.97) and three years (20.0% vs. 20.8%; p = 0.94) between LS and ES groups respectively. The Computerized Registry of Patients with Venous Thromboembolism (RIETE) score was equal or superior to 3 in 69.5% (N=41) of the population with uVTE.

DISCUSSION: The results of our study are consistent with the literature; there are no differences between screenings, as the difference in the number of diagnoses does not reflect on mortality.

CONCLUSION: There were no statistically significant differences between the two types of screening in this population. We suggest a protocol that includes the RIETE score to better select the patients who might benefit the most from an ES.

PMID: 32051805 [PubMed]

15 February 2020

12:06

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Adverse Cardiovascular Events in Cancer Trials: Missing in Action?

J Am Coll Cardiol. 2020 Feb 18;75(6):629-631

Authors: Bishopric NH, Lippman ME

PMID: 32057378 [PubMed - in process]

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Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

J Am Coll Cardiol. 2020 Feb 18;75(6):620-628

Authors: Bonsu JM, Guha A, Charles L, Yildiz VO, Wei L, Baker B, Brammer JE, Awan F, Lustberg M, Reinbolt R, Miller ED, Jneid H, Ruz P, Carter RR, Milks MW, Paskett ED, Addison D

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE)

Abstract

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

PMID: 32052314 [PubMed - as supplied by publisher]

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Cancer Screening in Patients with Unprovoked Thromboembolism: How to do it and Who Benefits?

Cureus. 2020 Feb 10;12(2):e6934

Authors: Ferreira F, Pereira J, Lynce A, Nunes Marques J, Martins A

PURPOSE OF REVIEW: Current standard for HER2+ early breast cancer patients includes chemotherapy and trastuzumab for 1 year

Abstract

PURPOSE OF REVIEW: Current standard for HER2+ early breast cancer patients includes chemotherapy and trastuzumab for 1 year. The purpose of this article is to review available evidence on escalated treatment strategies for high-risk patients and de-escalated treatments for patients at low risk of relapse or high risk of cardiac toxicity.

RECENT FINDINGS: Recent results have led to the approval of two adjuvant escalated treatment strategies: pertuzumab and trastuzumab combined with chemotherapy for up to 1 year for high-risk patients; extension of adjuvant anti-HER2 treatment with 1 year of neratinib. However, these treatments are associated with increased costs and toxicity, therefore careful patients' selection is highly required. With regard to de-escalated treatments, the anthracycline-free regimen of adjuvant paclitaxel and 1 year trastuzumab has entered clinical practice for early-stage patients. One year of trastuzumab remains the standard; however, shorter trastuzumab could be an option for low-risk patients and in case of increased risk of cardiotoxocity. Chemotherapy-free regimens are attractive but deserve further evaluation.

SUMMARY: There have been advances in treatment individualization for HER2+ early breast cancer patients. Integration of promising biomarkers into risk classification will further help progressing in the field.

PMID: 30325338 [PubMed - indexed for MEDLINE]

14 February 2020

13:08

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DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis.

J Thromb Thrombolysis. 2020 Feb 12;:

Authors: Mai V, Tanguay VF, Guay CA, Bertoletti L, Magnan S, Turgeon AF, Lacasse Y, Lega JC, Provencher S

Patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis,

Abstract

Patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are at increased risk for arterial and venous thrombosis/thromboembolism. In particular, the risk of splanchnic venous thrombosis, such as portal vein thrombosis or Budd-Chiari syndrome, is significantly higher in patients with MPN than in the normal population. At the same time, MPN patients are at increased risk for severe bleeding. Therefore, the treatment of patients with MPN must be based on their suspected probability of thrombosis/thromboembolism and bleeding. For this purpose, patient and MPN-specific risk factors are used. Patients at expected high risk of thrombosis should receive adequate primary or secondary thromboprophylaxis in addition to cytoreductive therapy. This may consist of antiplatelet agents and/or anticoagulant agents and must be balanced with the individual bleeding risk. The goal is to increase the quality of life and life span of patients with MPNs by preventing (re-)thrombosis and severe bleeding.

PMID: 32050290 [PubMed - in process]

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Prospective evaluation of drug-drug interactions in ambulatory cancer patients initiated on prophylactic anticoagulation.

J Oncol Pharm Pract. 2020 Feb 11;:1078155220901569

Authors: Ng HK, Rogala BG, Ades S, Schwartz JR, Ashikaga T, Vacek P, Holmes CE

PMID: 32046579 [PubMed - as supplied by publisher]

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Escalation and de-escalation in HER2 positive early breast cancer.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles

Escalation and de-escalation in HER2 positive early breast cancer.

Curr Opin Oncol. 2019 01;31(1):35-42

Authors: Dieci MV, Vernaci G, Guarneri V

OBJECTIVE: To determine the cause of a markedly raised D-dimer among patients in whom a diagnosis of pulmonary embolism (PE)

Abstract

OBJECTIVE: To determine the cause of a markedly raised D-dimer among patients in whom a diagnosis of pulmonary embolism (PE) has been excluded by CT pulmonary angiogram (CTPA) with particular reference to new cases of cancer and aortic dissection.

METHODS: One thousand consecutive patients, suspected of PE, who had undergone CTPA and for whom a D-dimer had been requested, were seen between 2012 and 2016. Retrospectively we examined the case records of all those in the top quintile of the D-dimer distribution whose CTPA was negative for PE. D-dimer in the top quintile ranged from 7.5 to 260 times upper limit normal.

RESULTS: Eighty-five patients fulfilled our inclusion criteria. The likely causes of their very high D-dimer were infection (n=35, 41.2%), cardiovascular disease (n=12, 14.1% including two patients with previously undiagnosed aortic dissection), surgery or trauma (n=12, 14.1%), new or active cancer (n=9, 10.6% comprising six new cancers and three patients with cancers diagnosed previously that were considered to be active) and miscellaneous causes (n=17, 20.0%). Thirty-five patients (43.5%) died over a 2-year follow-up. Kaplan-Meier survival analysis showed poorer outcomes for patients with new or active cancer, when compared with those with no known cancer (p

CONCLUSIONS: We have shown that a small proportion of patients suspected of PE whose D-dimers are markedly elevated have diagnoses we would not want to miss including previously unsuspected cancer and aortic dissection. Further studies will be required to define the optimal workup of patients with extremely high D-dimer who do not have venous thromboembolism.

PMID: 32041827 [PubMed - as supplied by publisher]

13 February 2020

12:38

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How I Manage Thrombotic/Thromboembolic Complications in Myeloproliferative Neoplasms.

Hamostaseologie. 2020 Feb;40(1):47-53

Authors: Koschmieder S

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