OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary

 

Abstract

OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary objective of this systematic review was to examine the comparative safety of the Food and Drug Administration-approved vaginal estrogen preparations among postmenopausal women.

METHODS: We performed a PubMed search of the primary literature from January 1, 1966 to July 16, 2019 for English-language clinical trials. Manual review of retrieved citations identified additional citations.

RESULTS: Of 882 retrieved citations, 75 clinical trials met inclusion criteria. Maximum trial duration was 52 weeks. None of the trials predesignated breast or endometrial cancer, cardiovascular events, or venous thromboembolism as primary outcomes. Studies were not designed to rule out an increase in endometrial carcinoma risk with long-term use of vaginal estrogen. There were few head-to-head comparisons. Fifty trials examined serum sex steroid and gonadotrophin levels; assay methodologies varied. Serum estradiol levels were 11 pg/mL at baseline or during placebo use and increased to a mean of 30 pg/mL after treatment. Estradiol levels were usually highest during the first 12 weeks of treatment, and were higher for estrogen creams than for inserts or rings. The 22 trials of endometrial thickness and the 15 trials of endometrial biopsy did not clearly demonstrate endometrial proliferation after vaginal estrogen treatment, but data were limited, and studies did not always perform systematic endometrial biopsy.

CONCLUSIONS: Newer low-dose estradiol rings, tablets, and inserts appear to induce the least increases in serum hormones, possibly indicating greater safety. Limited evidence in trials lasting up to 52 weeks suggest endometrial safety of vaginal estrogen use. Long-term trials are needed. : Video Summary:http://links.lww.com/MENO/A513.

PMID: 31913230 [PubMed - as supplied by publisher]

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Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

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

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

Dis Colon Rectum. 2019 11;62(11):1381-1389

Authors: Trepanier M, Alhassan N, Sabapathy CA, Liberman AS, Charlebois P, Stein BL, S Feldman L, Lee L

Background Little is known about how practicing Internal Medicine (IM) clinicians perceive diagnostic error, and whether p

 

Abstract

Background Little is known about how practicing Internal Medicine (IM) clinicians perceive diagnostic error, and whether perceptions are in agreement with the published literature. Methods A 16-question survey was administered across two IM practices: one a referral practice providing care for patients traveling for a second opinion and the other a traditional community-based primary care practice. Our aim was to identify individual- and system-level factors contributing to diagnostic error (primary outcome) and conditions at greatest risk of diagnostic error (secondary outcome). Results Sixty-five of 125 clinicians surveyed (51%) responded. The most commonly perceived individual factors contributing to diagnostic error included atypical patient presentations (83%), failure to consider other diagnoses (63%) and inadequate follow-up of test results (53%). The most commonly cited system-level factors included cognitive burden created by the volume of data in the electronic health record (EHR) (68%), lack of time to think (64%) and systems that do not support collaboration (40%). Conditions felt to be at greatest risk of diagnostic error included cancer (46%), pulmonary embolism (43%) and infection (37%). Conclusions Inadequate clinician time and sub-optimal patient and test follow-up are perceived by IM clinicians to be persistent contributors to diagnostic error. Clinician perceptions of conditions at greatest risk of diagnostic error may differ from the published literature.

PMID: 31913847 [PubMed - as supplied by publisher]

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Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis.

Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis.

Cancer. 2020 Jan 08;:

Authors: Chakraborty R, Bin Riaz I, Malik SU, Marneni N, Mejia Garcia A, Anwer F, Khorana AA, Rajkumar SV, Kumar S, Murad MH, Wang Z, Khan SU, Majhail NS

Cancer therapeutics-related cardiac dysfunction(CTRCD)is receiving more attention.Risk factors assessment before cancer therapy,cardia

Abstract

Cancer therapeutics-related cardiac dysfunction(CTRCD)is receiving more attention.Risk factors assessment before cancer therapy,cardiac function monitoring during and after cancer therapy,and early detection and treatment of myocardial injury are key to preventing clinical heart failure.The incidence and severity of cardiotoxicity can be reduced by measures such as reducing drug dose,adjusting administration route,and using low toxic drugs.Cardioprotective agents including anti-heart failure drugs and dexrazoxane are important for the prevention and treatment of CTRCD.Patients with advanced heart failure may also benefit from mechanical treatments including cardiac resynchronization therapy and mechanically-assisted ventricular devices.This article reviews the recent advances in the prevention and treatment of CTRCD.

PMID: 31907138 [PubMed - in process]

9 January 2020

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

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A survey of outpatient Internal Medicine clinician perceptions of diagnostic error.

A survey of outpatient Internal Medicine clinician perceptions of diagnostic error.

Diagnosis (Berl). 2020 Jan 09;:

Authors: Matulis JC, Kok SN, Dankbar EC, Majka AJ

A growing number of effective cancer therapies is associated with cardiovascular (CV) toxicities including myocardial injury or dysfunction,

 

Abstract

A growing number of effective cancer therapies is associated with cardiovascular (CV) toxicities including myocardial injury or dysfunction, leading to reduced ventricular function, and increased risk of heart failure. As the timing of administration of cancer treatment is known, the potential for risk stratification pre-treatment, and appropriate surveillance and monitoring during treatment, and intervention with cardio-protective treatment strategies in patients exhibiting early evidence of CV toxicity is an appealing clinical strategy. The field of cardio-oncology has developed, and the application of monitoring strategies using CV biomarkers and CV imaging has been to focus of many studies and is now implemented in dedicated cardio-oncology services supporting oncology centres. In this article, we review the background and rationale for monitoring, the different options and their strengths, weaknesses and where they are helpful in specific cardiotoxic cancer therapies, and the impact in cardio-oncology care.

PMID: 31908616 [PubMed]

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[Prevention and Treatment of Cancer Therapeutics-related Cardiac Dysfunction].

[Prevention and Treatment of Cancer Therapeutics-related Cardiac Dysfunction].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2019 Dec 30;41(6):842-850

Authors: Chen WG, Zhao L

BACKGROUND: Extensive multi-visceral resection, including components of the urinary tract, is often required to achieve clea

 

Abstract

BACKGROUND: Extensive multi-visceral resection, including components of the urinary tract, is often required to achieve clear resection margins, which is now well established as a key predictor of long-term survival for locally advanced pelvic tumours. The aims of this study were to analyse major morbidity and factors predicting complications and long-term outcomes following a urological procedure within extended radical resections.

METHODS: Data were collected from prospective databases at two high-volume institutions specialising in extended radical resections for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary endpoints were general major complications (Clavien-Dindo ≥ 3) and factors influencing complications and overall survival after urological resection.

RESULTS: A total of 646 consecutive patients requiring an extended radical resection for locally advanced or recurrent pelvic malignancies were identified. The median age was 63 years (range 19-89 years) and the majority were female (371; 57.4%). A urological resection was performed as part of the resection in 226 patients (35.0%). The overall 30-day major complication rate was significantly higher in the urological intervention group (23%; n = 52) compared to the non-urological group (12.9%; n = 54 patients; p = 0.001). Intestinal anastomotic leak (p = 0.001) and intra-abdominal collections (p = 0.001) were more common in the urological cohort. Ileal conduit formation was an independent predictor of major morbidity (OR 1.95; 95% CI 1.24-3.07; p = 0.004). Independent prognostic markers for poor 5-year survival following urological procedures were recurrent tumour, cardiovascular disease, previous thromboembolic event and postoperative pulmonary embolism.

CONCLUSIONS: Extended radical resections which include a urological resection are associated with significantly more major morbidity than those without urological resection. Ileal conduit formation is independently associated with the development of major morbidity. Five-year overall survival is no different for patients who had or did not have urological resection as part of extended radical surgery for locally advanced or recurrent pelvic malignancy.

PMID: 31907722 [PubMed - as supplied by publisher]

14:34

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

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Cardiology care delivered to cancer patients.

Cardiology care delivered to cancer patients.

Eur Heart J. 2020 Jan 07;41(2):205-206

Authors: Asteggiano R, Aboyans V, Lee G, Salinger S, Richter D

PMID: 31909424 [PubMed - in process]

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Monitoring the heart during cancer therapy.

Monitoring the heart during cancer therapy.

Eur Heart J Suppl. 2019 Dec;21(Suppl M):M44-M49

Authors: Habibian M, Lyon AR

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality

Abstract

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.

PMID: 31908214 [PubMed - in process]

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Complications and 5-year survival after radical resections which include urological organs for locally advanced and recurrent pelvic malignancies: analysis of 646 consecutive cases.

Complications and 5-year survival after radical resections which include urological organs for locally advanced and recurrent pelvic malignancies: analysis of 646 consecutive cases.

Tech Coloproctol. 2020 Jan 06;:

Authors: Peacock O, Waters PS, Kong JC, Warrier SK, Wakeman C, Eglinton T, Murphy DG, Heriot AG, Frizelle FA, McCormick JJ

To facitinib and baricitinib are two of the currently available Janus kinase (JAK) inhibitors for the treatment of patients

 

Abstract

To facitinib and baricitinib are two of the currently available Janus kinase (JAK) inhibitors for the treatment of patients with RA. Randomized controlled trials have shown that these JAK inhibitors are as efficacious as biological DMARDs. Safety profiles of these JAK inhibitors in randomized controlled trials and their long-term extension studies have been demonstrated; however, real world evidence remains to be established to bridge the gap between randomized controlled trials and rheumatology clinics. Fundamentally, no difference in the screening, prevention, and monitoring of infections between JAK inhibitors and biological DMARDs exists. However, increased risk of herpes zoster is probably common to all JAK inhibitors. No indication of increased risk for malignancy in patients with RA treated with JAK inhibitors has been reported. To evaluate risks of relatively rare serious adverse events such as thromboembolic events, gastrointestinal perforation, and interstitial lung disease in clinical settings, accumulation of cases with these events are needed. Continuous pharmacovigilance activity is absolutely warranted to establish the safety of JAK inhibitors in patients with RA and other rheumatic diseases.

PMID: 30806708 [PubMed - indexed for MEDLINE]

8 January 2020

13:02

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

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Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group.

Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group.

Am Surg. 2019 Dec 01;85(12):1334-1340

Authors: Armstrong EA, Beal EW, Lopez-Aguiar AG, Poultsides G, Cannon JG, Rocha F, Crown A, Barrett J, Ronnkleiv-Kelly S, Fields RC, Krasnick BA, Idrees K, Smith PM, Nathan H, Beems MV, Maithel SK, Schmidt CR, Pawlik TM, Dillhoff M

Complex aortic atheroma is a high-risk factor for recurrent embolic stroke. An accurate identification of stroke etiology

 

Abstract

Complex aortic atheroma is a high-risk factor for recurrent embolic stroke. An accurate identification of stroke etiology is clinically important; however, it can be challenging. A 91-year-old man with atrial fibrillation was diagnosed with cardioembolic stroke and treated with mechanical thrombectomy. The removed thrombus microscopically contained foamy cells, suggesting an atheroembolism. An autopsy revealed an atherosclerotic lesion with ulceration, located in the aortic arch. At the lesion, the plaque had microscopically ruptured into the lumen. We therefore concluded that the aortic atherosclerotic lesion was the embolic source. Removed thrombi should be pathologically examined even if a cardioembolic stroke is clinically suspected.

PMID: 31178514 [PubMed - indexed for MEDLINE]

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Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--academic.oup.com-images-oup_pubmed.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis.

Rheumatology (Oxford). 2019 02 01;58(Suppl 1):i34-i42

Authors: Harigai M

PURPOSE: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak).

 

Abstract

PURPOSE: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk.

METHODS: Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise.

RESULTS: Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, -16%; ET, -7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R = 0.47, P < 0.01).

CONCLUSION: Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function.

CLINICAL TRIAL REGISTRATION: ACTRN12616001602415.

PMID: 30829962 [PubMed - indexed for MEDLINE]

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Aortogenic Embolic Stroke Diagnosed by a Pathological Examination of Endovascularly Removed Thrombus: An Autopsy Report.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkout.jstage.jst.go.jp-logo.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Aortogenic Embolic Stroke Diagnosed by a Pathological Examination of Endovascularly Removed Thrombus: An Autopsy Report.

Intern Med. 2019 Oct 01;58(19):2851-2855

Authors: Usui G, Hashimoto H, Sugiura Y, Nishi Y, Kusakabe M, Horiuchi H, Okubo S, Morikawa T

Rationale: Exosomes are emerging as a promising drug delivery carrier. However, rapid uptake of exosomes by the

 Abstract

Rationale: Exosomes are emerging as a promising drug delivery carrier. However, rapid uptake of exosomes by the mononuclear phagocyte system (MPS) remains an obstacle for drug delivery into other targeted organs, including the heart. We hypothesized that prior blocking of uptake of exosomes by the MPS would improve their delivery to the targeted organs. Methods: Exosomes were isolated from the cell culture medium. Fluorescence-labeled exosomes were tracked in vitro and in vivo by fluorescence imaging. The expression of clathrin heavy chain (Cltc), cavolin1, Pak1 and Rhoa, known genes for endocytosis, were profiled in various cell lines and organs by qPCR. The knockdown efficiency of siRNA against Cltc was analyzed by Western blotting. Exosomecontrol and exosomeblocking were constructed by encapsulating isolated exosomes with siControl or siClathrin via electroporation, while exosometherapeutic was constructed by encapsulating isolated exosomes with miR-21a. Doxorubicin-induced cardiotoxicity model was used to verify the therapeutic efficiency of the exosome-based miR-21a delivery by echocardiography. Results: Exosomes were preferentially accumulated in the liver and spleen, mainly due to the presence of abundant macrophages. Besides the well-known phagocytic effect, efficient endocytosis also contributes to the uptake of exosomes by macrophages. Cltc was found to be highly expressed in the macrophages compared with other endocytosis-associated genes. Accordingly, knockdown of Cltc significantly decreased the uptake of exosomes by macrophages in vitro and in vivo. Moreover, prior injection of exosomeblocking strikingly improved the delivery efficiency of exosomes to organs other than spleen and liver. Consistently, compared with the direct injection of exosometherapeutic, prior injection of exosomeblocking produced a much better therapeutic effect on cardiac function in the doxorubicin-induced cardiotoxicity mouse model. Conclusions: Prior blocking of endocytosis of exosomes by macrophages with exosomeblocking successfully and efficiently improves the distribution of following exosometherapeutic in targeted organs, like the heart. The established two-step exosome delivery strategy (blocking the uptake of exosomes first followed by delivery of therapeutic exosomes) would be a promising method for gene therapy.

PMID: 31903116 [PubMed - in process]

12:22

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Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy.

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

Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy.

Med Sci Sports Exerc. 2019 08;51(8):1573-1581

Authors: Foulkes SJ, Howden EJ, Bigaran A, Janssens K, Antill Y, Loi S, Claus P, Haykowsky MJ, Daly RM, Fraser SF, LA Gerche A

OBJECTIVES: To investigate the association of extremes in body weight EBW and outcomes in patients with acute veno

 

ABSTRACT

OBJECTIVES: To investigate the association of extremes in body weight EBW and outcomes in patients with acute venous thromboembolism (VTE), recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with body weight <60120 kg.

METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.

RESULTS: Amongst 2577 patients with the weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 - 120 kg, 223 (8.7%) bodyweight <60120 kg. Patients with bodyweight <60kg120kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (p=0.01).

CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60kg.120kg on rivaroxaban.

PMID:32557773 | DOI:10.1111/ejh.13471

The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectomy and left

 

ABSTRACT

The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectomy and left cystectomy were performed for bilateral ovarian endometriomas, which were both pathologically diagnosed as benign. Six months later, she presented with left lower abdominal pain and expressive aphasia. Examination revealed multiple cerebral infarctions and pulmonary embolism. The patient was diagnosed with Trousseau's syndrome secondary to ovarian cancer, and anticoagulant therapy was initiated. Despite treatment, she developed visual field loss due to occlusion of the left retinal artery; dizziness due to cerebellar infarction and myocardial infarction; and right hemiplegia due to new cerebral infarction. She received chemotherapy (two courses of paclitaxel and carboplatin), which did not improve her condition, and died two months after onset. An autopsy revealed that her left ovary was enlarged to a size of 12 cm and an endometrioid carcinoma G2 was identified. Ovarian cancer had spread throughout the abdominal cavity, and a large amount of pleural and ascites fluid was present. Multiple thrombi were found in bilateral pulmonary arteries and bilateral common iliac veins. There was a 2.5 cm thrombus in the left ventricle apex, and the anterior descending branch was obstructed by thrombus with recanalization.

PMID:32566336 | PMC:PMC7293738 | DOI:10.1155/2020/3738618

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PubMed articles on: Cancer & VTE/PE

Effectiveness and Safety of Apixaban and Rivaroxaban for Acute Venous Thromboembolism Therapy in Patients with Extremes in Body Weight (ClinicalTrials.gov: NCT03504007)

Wysokinski WE, et al. Eur J Haematol 2020.

Backgrounds:The last 30 years have witnessed major improvements in understanding of all aspects of infective endocarditis (IE)

 

ABSTRACT

Backgrounds:The last 30 years have witnessed major improvements in understanding of all aspects of infective endocarditis (IE). The Iranian Registry of Infective Endocarditis (IRIE) was formed to address epidemiological aspects of IE vis-à-vis its main pathogens and underlying heart diseases over a 12-year period. Indeed, a multidisciplinary team (MDT) for IE was developed alongside.Methods: In a longitudinal observational study, data of adult patients with definite or possible IE based on modified Duke criteria were collected from 2007 to 2016 in our tertiary centre, Iran. From 2016 until 2019, we run a prospective observational study using formation of an IE MDT to provide better patient management and compared data before and after this.Results: Totally, 645 patients with mean age of 48 ± 17 years were enrolled. Data of 445 and 200 patients were compared before and after IRIE and MDT formation, respectively. We found significantly reduced type and number of applied antibiotics (p = 0.04) and higher rate of positive blood culture (p = 0.001). Hospital length of stay increased significantly after formation of the IRIE and IE MDT (p = 0.02). The rate of heart failure, new abscess formation and cerebral emboli were significantly decreased after IRIE and IE MDT (p < 0.001) and consequently in-hospital mortality reduced significantly (p = 0.05).Conclusion: Developing national registries and MDTs has potential to enhance patient management and reduce IE burden. Our results demonstrated that establishment of the Iranian IRIE and IE MDT conferred better diagnoses, standardised treatments and significantly reduced cardiac and extra cardiac morbidity.

PMID:32589112 | DOI:10.1080/00015385.2020.1781423

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PubMed articles on: Cancer & VTE/PE

A Case of Trousseau's Syndrome Accompanying Ovarian Cancer with Widespread Thromboembolisms

Kobayashi H, et al. Case Rep Obstet Gynecol 2020.

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the VTE

 

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the VTE incidence after major thoracic surgery is high. However, there have been no exclusive data after thymectomy thus far. To investigate the incidence of postoperative VTE, we conducted a single-center, prospective cohort study.

METHODS: Patients who underwent thymectomy between December 2017 and January 2020 were enrolled. None of the patients received any prophylaxis perioperatively. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥9). Occurrence of VTE events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), were identified by imaging.

RESULTS: There were 192 patients who underwent thymectomy enrolled into the study. The overall VTE incidence was 8.9%. All the patients were diagnosed with DVT, and none were diagnosed with PE. The VTE incidence was 4.6% in patients with benign thymic diseases and 14.5% with malignant diseases. The VTE incidence was 4.7% in patients undergoing thoracoscopic surgery and 22.7% undergoing median sternotomy. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 10.3% and 37.5%, respectively. In patients with thymic malignancy, the VTE incidence in the moderate and high risk groups were 8.8% and 31.8%, respectively.

CONCLUSIONS: VTE occurred frequently in patients after thymectomy without VTE prophylaxis. The median sternotomy procedure and malignant tumor may be the major risk factors for the development of VTE. Aggressive VTE screening/treatment protocols should be implemented in patents after thymectomy.

PMID:32558357 | DOI:10.1111/1759-7714.13543

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PubMed articles on: Cardio-Oncology

Impact of the Iranian Registry of Infective Endocarditis (IRIE) and multidisciplinary team approach on patient management

Sadeghpour A, et al. Acta Cardiol 2020.

Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because man

 

ABSTRACT

Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer are treated with agents that exert significant vascular toxicity. Coronary heart disease in patients with cancer presents particular challenges, which directly impact the management of both the coronary disease and malignancy. Several chemotherapeutic agents have been shown to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be dedicated to improving early recognition and prevention of cardiac vascular toxicity. Cardiac imaging could facilitate early detection of vascular toxicity, but a thorough risk stratification should always be performed to identify patients at higher risk of vascular impairment.

PMID:32566461 | PMC:PMC7293870 | DOI:10.4103/jcecho.jcecho_3_19

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism after adult thymus or thymic tumor resection: A single-center experience

Yang X, et al. Thorac Cancer 2020.

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity

 

ABSTRACT

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it.

METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam.

RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression.

CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.

PMID:32583016 | DOI:10.1007/s00394-020-02301-5

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PubMed articles on: Cardio-Oncology

Vascular Damage - Coronary Artery Disease

Cadeddu Dessalvi C, et al. J Cardiovasc Echogr 2020 - Review.

Deep vein thrombosis and pulmonary artery embolism are common and serious concomitant diseases in patients with cancer

 

ABSTRACT

Deep vein thrombosis and pulmonary artery embolism are common and serious concomitant diseases in patients with cancer. The prophylaxis and therapy of such venous thromboembolic events (VTE) in oncology have so far been achieved with low-molecular-weight heparins. An increasing number of studies show evidence of the use of direct oral anticoagulants. However, since none of the possible options were shown to have a clear advantage in all patients, the individual decision to use a drug should be made depending on its effectiveness in preventing VTE, the risk of bleeding, the nature of the cancer, the interactions with other medications, the route of administration, and finally the cost of treatment.

PMID:32564097 | DOI:10.1007/s00059-020-04961-9

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PubMed articles on: Cardio-Oncology

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis

Ghosh S, et al. Eur J Nutr 2020.

Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been p

 

ABSTRACT

Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been proposed as a new approach to coordinate preventive strategies in oncologic patients. Cardiac imaging plays a critical role in this process. This article summarizes current practices and future needs in cardiac imaging to improve the cardiovascular surveillance of cancer patients.

PMID:32583314 | PMC:PMC7314619 | DOI:10.1007/s12265-020-10028-1

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PubMed articles on: Cancer & VTE/PE

Prevention and treatment of venous thromboembolism in cancer patients

Spehlmann ME, et al. Herz 2020 - Review.

External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically

 

ABSTRACT

External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically intact external validation studies are a scarce finding. Utilization of big datasets can help overcome several causes of methodological failure. However, transparent reporting is needed to standardize the methods, assess the risk of bias and synthesize multiple validation studies in order to infer model generalizability. We describe the methodological challenges faced when using multiple big datasets to perform the first retrospective external validation study of the Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis (COMPASS-CAT) Risk Assessment Model for predicting venous thromboembolism in patients with cancer. The challenges included choosing the starting point, defining time sensitive variables that serve both as risk factors and outcome variables and using non-research oriented databases to form validated definitions from administrative codes. We also present the structured plan we used so as to overcome those obstacles and reduce bias with the target of producing an external validation study that successfully complies with prediction model reporting guidelines.

PMID:32564180 | DOI:10.1007/s11239-020-02191-8

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PubMed articles on: Cardio-Oncology

Cardiac Imaging in Oncology Patients in Europe: a Model for Advancement of CV Safety and Development of Comprehensive CV Care

López-Fernández T. J Cardiovasc Transl Res 2020 - Review.

Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing prote

 

ABSTRACT

Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing protection against pulmonary embolism (PE) for patients contraindicated for anticoagulant therapy. However, because absorbable filters are not radiopaque, monitoring of the filter using conventional X-ray imaging modalities (e.g. plain film radiographs, computed tomography [CT] and fluoroscopy) during deployment and follow-up is not possible and represents a potential obstacle to widespread clinical integration of the device. Here, we demonstrate that gold nanoparticles (AuNPs) infused into biodegradable filters made up of poly-p-dioxanone (PPDO) may improve device radiopacity without untoward effects on device efficacy and safety, as assessed in swine models for 12 weeks. The absorbable AuNP-infused filters demonstrated significantly improved visualization using CT without affecting tensile strength, in vitro degradation, in vivo resorption, or thrombus-capturing efficacy, as compared to similar non-AuNPs infused resorbable IVCFs. This study presents a significant advancement to the development of imaging enhancers for absorbable IVCFs.

PMID:32558854 | DOI:10.1039/d0bm00414f

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PubMed articles on: Cancer & VTE/PE

Using big data to retrospectively validate the COMPASS-CAT risk assessment model: considerations on methodology

Nikolakopoulos I, et al. J Thromb Thrombolysis 2020.

BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity

 

ABSTRACT

BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity.

PURPOSE: The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity.

METHODS: A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks.

RESULTS: Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity.

CONCLUSIONS: In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.

PMID:32567177 | DOI:10.1002/nbm.4327

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PubMed articles on: Cancer & VTE/PE

In vivo performance of gold nanoparticle-loaded absorbable inferior vena cava filters in a swine model

Huang SY, et al. Biomater Sci 2020.

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with in

 

ABSTRACT

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.

PMID:32545233 | DOI:10.3390/cancers12061536

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PubMed articles on: Cardio-Oncology

Cardiac MRI Myocardial Functional and Tissue Characterization Detects Early Cardiac Dysfunction in a Mouse Model of Chemotherapy-Induced Cardiotoxicity

Naresh NK, et al. NMR Biomed 2020.

As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increas

 

ABSTRACT

As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increasingly come into focus in recent years. The new cardiological subspecialty of oncocardiology is developing strategies to prevent and/or detect those effects early in order to treat them in a timely and adequate manner. The diagnosis of cardiotoxic effects is based mainly on imaging and specific biomarkers. Echocardiography has become the main imaging technique due to its wide availability. In addition to quantitative determination of left ventricular function using two-dimensional methods, three-dimensional methods offer better precision and less variability in the detection of cardiac dysfunction. Furthermore, the analysis of the global longitudinal strain (GLS) reveals even subtle changes in left ventricular function and thus detects very early damage before left ventricular ejection fraction drops. Various biomarkers have been tested recently for their potential to detect cardiotoxicity. Cardiac troponins are currently the best investigated biomarkers and certainly have the highest impact. Due to contradicting results, the importance of natriuretic peptides has not yet been conclusively clarified. Results for myeloperoxidase are promising, as are the results for circulating microRNAs, which still mainly derive from experimental data. In this context, further studies still need to show the value of these in everyday clinical practice.

PMID:32564096 | DOI:10.1007/s00059-020-04957-5

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PubMed articles on: Cancer & VTE/PE

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors

Oto J, et al. Cancers (Basel) 2020.

Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management

 

ABSTRACT

Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa-inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low-molecular-weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo-controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis-expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real-world evidence studies, including investigator-initiated research.

PMID:32548552 | PMC:PMC7292665 | DOI:10.1002/rth2.12327

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PubMed articles on: Cardio-Oncology

Echocardiography and biomarkers for the diagnosis of cardiotoxicity

Berliner D, et al. Herz 2020 - Review.

PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular

 

ABSTRACT

PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies.

RECENT FINDINGS: Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.

PMID:32564220 | DOI:10.1007/s11912-020-00923-w

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PubMed articles on: Cancer & VTE/PE

Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban

Bauersachs R, et al. Res Pract Thromb Haemost 2020 - Review.

BACKGROUND: Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venou

 

ABSTRACT

BACKGROUND: Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta-analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer.

METHODS: Biomedical databases were screened for RCTs evaluating DOACs for cancer-associated VTE. Primary efficacy and safety outcomes of this meta-analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model.

RESULTS: We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43-0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83-2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19-2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83-1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81-0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08-4.88]).

CONCLUSION: In patients with cancer-associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.

PMID:32548553 | PMC:PMC7292654 | DOI:10.1002/rth2.12359

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PubMed articles on: Cardio-Oncology

Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review

Upshaw JN. Curr Oncol Rep 2020 - Review.

PURPOSE OF REVIEW: In this article, we review the different model systems based on human-induced pluripotent stem

 

ABSTRACT

PURPOSE OF REVIEW: In this article, we review the different model systems based on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and how they have been applied to identify the cardiotoxic effects of anticancer therapies.

RECENT FINDINGS: Developments on 2D and 3D culture systems enabled the use of hiPSC-CMs as screening platforms for cardiotoxic effects of anticancer therapies such as anthracyclines, monoclonal antibodies, and tyrosine kinase inhibitors. Combined with computational approaches and higher throughput screening technologies, they have also enabled mechanistic studies and the search for cardioprotective strategies. As the population ages and cancer treatments become more effective, the cardiotoxic effects of anticancer drugs become a bigger problem leading to an increased role of cardio-oncology. In the past decade, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become an important platform for preclinical drug tests, elucidating mechanisms of action for drugs, and identifying cardioprotective pathways that could be further explored in the development of combined treatments. In this article, we highlight 2D and 3D model systems based on hiPSC-CMs that have been used to study the cardiotoxic effects of anticancer drugs, investigating their mechanisms of action and the potential for patient-specific prediction. We also present some of the important challenges and opportunities in the field, indicating possible future developments and how they could impact the landscape of cardio-oncology.

PMID:32562096 | DOI:10.1007/s11886-020-01325-x

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PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants compared to low-molecular-weight heparin for the treatment of cancer-associated thrombosis: Updated systematic review and meta-analysis of randomized controlled trials

Moik F, et al. Res Pract Thromb Haemost 2020.

INTRODUCTION: We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of

 

ABSTRACT

INTRODUCTION: We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival.

MATERIAL AND METHODS: We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85-day study period. Patients were followed for 3 months after the study period. We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy.

RESULTS AND CONCLUSIONS: In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D-dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.

PMID:32548563 | PMC:PMC7292676 | DOI:10.1002/rth2.12317

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PubMed articles on: Cardio-Oncology

Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity

Lyra-Leite DM and Burridge PW. Curr Cardiol Rep 2020 - Review.

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing

 

ABSTRACT

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.

PMID:32552629 | DOI:10.6002/ect.2020.0062

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PubMed articles on: Cancer & VTE/PE

Effect of chemotherapy and longitudinal analysis of circulating extracellular vesicle tissue factor activity in patients with pancreatic and colorectal cancer

Kasthuri RS, et al. Res Pract Thromb Haemost 2020.

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all

ABSTRACT

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.

PMID:32540780 | DOI:10.1016/j.critrevonc.2020.103005

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PubMed articles on: Cardio-Oncology

Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy

Sipahi NF, et al. Exp Clin Transplant 2020.

 

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been

 

ABSTRACT

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.

PMID:32554494 | DOI:10.1073/pnas.1922072117

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PubMed articles on: Cancer & VTE/PE

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis

Sidahmed S, et al. Crit Rev Oncol Hematol 2020 - Review.

In comparison to male patients with coronary artery disease, female patients suffer from more comorbidities, experience symptoms of coronary

 

ABSTRACT

In comparison to male patients with coronary artery disease, female patients suffer from more comorbidities, experience symptoms of coronary artery disease differently and report poorer health-related quality of life (HRQoL) after coronary revascularization. However, there is limited data on the impact of comorbidity burden on the recovery in HRQoL in female and male patients. We investigated the impact of comorbidity burden on the change in HRQoL following coronary revascularization in female patients versus male patients. 230 patients (60 female) with coronary artery disease were assessed before, and two weeks, three months and six months after coronary revascularization. Disease-specific HRQoL was measured with the Short-Form Seattle Angina Questionnaire. Physical and mental health was measured with the Short-Form Health Survey. Comorbidity burden was assessed by the total number of identified comorbidity conditions and by the Charlson comorbidity score. Linear mixed models were used to estimate the effects of time, gender and comorbidity burden on HRQoL. Whereas HRQoL improved after coronary revascularization in all patients, female patients reported poorer physical health and disease-specific HRQoL and their physical health improved more slowly than male patients. A higher comorbidity burden was related with poorer physical health and disease-specific HRQoL in male patients, but not in female patients. A higher comorbidity burden was associated with slower improvement in HRQoL for both female and male patients. Female patients reported poorer HRQoL and their physical health improved more slowly after coronary revascularization, irrespective of comorbidity burden. Higher comorbidity burden was associated with poorer physical health and disease-specific HRQoL in male patients only. Our results indicate that female and male patients recover differently after coronary revascularization. These findings highlight the importance of comorbidity- and gender-specific approaches for evaluating coronary artery disease and coronary revascularization procedures.

PMID:32555617 | PMC:PMC7299316 | DOI:10.1371/journal.pone.0234543

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PubMed articles on: Cardio-Oncology

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin

Qiao X, et al. Proc Natl Acad Sci U S A 2020.

PURPOSE OF REVIEW: Patients with cancer are at high risk for thrombotic events, mainly deep vein thrombosis and pulmonary

 

ABSTRACT

PURPOSE OF REVIEW: Patients with cancer are at high risk for thrombotic events, mainly deep vein thrombosis and pulmonary embolism. Low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the current treatment options for cancer-associated thrombosis (CAT). We assessed real world data (RWD) regarding treatment patterns of CAT from 1 September 2018 to 31 January 2020.

RECENT FINDINGS: RWD showed that LMWHs were the most common initial anticoagulation treatment for CAT. Based on these data DOACs had a lower risk of recurrent venous thromboembolism compared with LMWHs and warfarin. However, the selection bias and the small number of patients in these studies might explain this difference and these limitations should be taken into consideration. Moreover, there was no statistical difference regarding adverse events during anticoagulant treatment between LMWHs and DOACs with the limitations of RWD. As far as the duration of the treatment is concerned, the adherence ranged from 100% to 67.3% at 6 months.

SUMMARY: The current review of RWD illustrates that LMWHs and DOACs are used for the treatment of CAT. LMWHs are most commonly used for the initial management of CAT. Data regarding recurrence of CAT, adverse events, compliance and duration of anticoagulant treatment should be analyzed with caution as RWD are observational studies with many limitations. Further research is needed to elucidate the best algorithm for the management of CAT.

PMID:32541315 | DOI:10.1097/CCO.0000000000000646

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PubMed articles on: Cardio-Oncology

Gender differences in quality of life in coronary artery disease patients with comorbidities undergoing coronary revascularization

Oreel TH, et al. PLoS One 2020.

INTRODUCTION: Infantile hepatic hemangioendothelioma is a type of benign hepatic tumor that occurs in infancy. Many

 

ABSTRACT

INTRODUCTION: Infantile hepatic hemangioendothelioma is a type of benign hepatic tumor that occurs in infancy. Many hepatic tumors are diagnosed when screening is done for multiple cutaneous hemangiomas. Hepatic tumors are small multifocal lesions and are mostly asymptomatic. There have been many case reports of asymptomatic infantile hepatic hemangioendothelioma, but few of these have pointed out that hepatic hemangiomas can sometimes be life-threatening due to fatal hepatomegaly complications such as pulmonary artery hypertension or even congestive heart failure. At present, there are no standard protocols for treating infantile hepatic hemangioendothelioma, though most clinicians agree that treatment is unnecessary for multiple small hepatic hemangiomas in asymptomatic patients. Little is known about treatment for cases with life-threatening complications induced by infantile hepatic hemangioendothelioma as there are so few reported cases. Here, we report a special case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency induced by infantile hepatic hemangioendothelioma.

PATIENT CONCERNS: We present a case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency caused by infantile hepatic hemangioendothelioma.

DIAGNOSIS: Infantile hepatic hemangioendothelioma was diagnosed.

INTERVENTIONS: The patient underwent transcatheter arterial embolization and was given propranolol.

OUTCOMES: The patient responded well to treatment with transcatheter arterial embolization and propranolol. The patient gained weight steadily, liver volume, and mass size have decreased considerably, echocardiography showed normal pulmonary artery pressure and ejection fraction, and we discovered no serious complications after 1 year of follow-up.

CONCLUSION: Transcatheter arterial embolization combined with propranolol is an effective treatment for life-threatening infantile hepatic hemangioendothelioma.

PMID:32541524 | PMC:PMC7302649 | DOI:10.1097/MD.0000000000020728

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PubMed articles on: Cancer & VTE/PE

Real world data regarding the management of cancer-associated thrombosis

Tsoukalas N, et al. Curr Opin Oncol 2020.

PURPOSE: With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians

 

ABSTRACT

PURPOSE: With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians to understand the steps in developing and interpreting such models.

METHODS: A retrospective registry of 20 Dutch hospitals with data on patients treated for castration-resistant prostate cancer was used to guide clinicians through the steps of developing a prediction model. The model of choice was the Cox proportional hazard model.

RESULTS: Using the exemplary dataset several essential steps in prediction modelling are discussed including: coding of predictors, missing values, interaction, model specification and performance. An advanced method for appropriate selection of main effects, e.g. Least Absolute Shrinkage and Selection Operator (LASSO) regression, is described. Furthermore, the assumptions of Cox proportional hazard model are discussed, and how to handle violations of the proportional hazard assumption using time-varying coefficients.

CONCLUSION: This study provides a comprehensive detailed guide to bridge the gap between the statistician and clinician, based on a large dataset of real-world patients treated for castration-resistant prostate cancer.

PMID:32556680 | DOI:10.1007/s00432-020-03286-8

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PubMed articles on: Cancer & VTE/PE

Infantile hepatic hemangioendothelioma associated with pulmonary artery hypertension and cardiac insufficiency successfully treated with transcatheter arterial embolization and propranolol: A case report

Wang L, et al. Medicine (Baltimore) 2020.

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right v

 

ABSTRACT

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome.

METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories.

RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category.

CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

PMID:32542216 | PMC:PMC7283932 | DOI:10.1016/j.mayocpiqo.2020.02.002

05:35

PubMed articles on: Cardio-Oncology

A clinician's guide for developing a prediction model: a case study using real-world data of patients with castration-resistant prostate cancer

Veen KM, et al. J Cancer Res Clin Oncol 2020 - Review.

There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated hear

ABSTRACT

There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.

PMID:32557158 | DOI:10.1007/s12265-020-10041-4

05:35

PubMed articles on: Cancer & VTE/PE

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism

Cambron JC, et al. Mayo Clin Proc Innov Qual Outcomes 2020.

It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.

 

ABSTRACT

BACKGROUND: It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.

OBJECTIVES: To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.

METHODS: At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods.

RESULTS: Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty-eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio-oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety-two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta-blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi-institutional collaboration to standardize cardiovascular care for CCS.

CONCLUSIONS: While there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi-institutional, standardized approaches to cardiovascular management in CCS.

PMID:32558321 | DOI:10.1002/cam4.3190

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PubMed articles on: Cardio-Oncology

Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure

Mirić D, et al. J Cardiovasc Transl Res 2020.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immatur

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs).

METHODS: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy. Baseline RAMs included the Khorana-, Vienna Cancer, Thrombosis-, Protecht-, ONKOTEV-, and Catscore. IPF, MPV, P-selectin, D-dimer, and TG were analysed at baseline and 3-month follow-up.

RESULTS: We enrolled 100 patients, of whom 89 completed the follow-up. Frequent tumour types were breast (30%), gastric (14%), gynaecological (14%), and colorectal (14%) cancer. Ten of the 89 patients (11.2%) developed VTE. The highest VTE rate was observed in patients with cholangiocarcinoma (3/5; 60%). Baseline D-dimer levels but not IPF, MPV, or P-selectin were associated with the risk of developing VTE (HR 6.9; p = 0.021). None of the RAMs showed statistical significance in predicting VTE. Peak thrombin and endogenous thrombin potential were lower in patients who developed VTE. Biomarker changes between baseline and follow-up were not associated with VTE risk.

CONCLUSIONS: VTE risk was well predicted by baseline D-dimer levels. Adding D-dimer could improve existing RAMs to better identify patients who may benefit from primary VTE prophylaxis. The VTE risk among patients with cholangiocarcinoma should be further evaluated.

PMID:32580190 | DOI:10.1159/000508271

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Cardiotoxicity News

PubMed articles on: Cardio-Oncology

Cardiovascular disease and asymptomatic childhood cancer survivors: Current clinical practice

Bottinor WJ, et al. Cancer Med 2020.

 

Trastuzumab, the humanized monoclonal antibody specific for HER2 receptor, is the gold standard in the treatment of HER2+ breast cancer

 

ABSTRACT

Trastuzumab, the humanized monoclonal antibody specific for HER2 receptor, is the gold standard in the treatment of HER2+ breast cancer. Despite its high therapeutic efficacy, cardiotoxicity has emerged as a significant side effect. The molecular mechanisms involved are not well understood, but all converge on mitochondria. Mitochondrial Cx43 can confer cardioprotection by regulating mitochondrial calcium homeostasis, ROS production and propagation of apoptotic signals, and studies report that it is overexpressed both in ischemic preconditioning and in Doxorubicin-induced cardiotoxicity. This study was designed to evaluate whether mitochondrial Cx43 (mCx43) is also involved in Trastuzumab-induced cardiotoxicity. Here we demonstrated that mCx43 is overexpressed in Trastuzumab-treated H9c2 cells. Our data showed that inhibition of Cx43 translocation to mitochondria, obtained by radicicol pre-treatment, significantly increases cytosolic and mitochondrial superoxide formation, mitochondrial membrane depolarization and the consequent apoptosis induced by Trastuzumab. Our results support the hypothesis that disruption of mitochondrial function is the principal mechanism by which Trastuzumab elicits its cardiotoxicity and mCx43 appears to counteract the Trastuzumab-induced mitochondrial damage.

PMID:32599261 | DOI:10.1016/j.tiv.2020.104926

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PubMed articles on: Cancer & VTE/PE

Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients

Schorling RM, et al. Oncol Res Treat 2020.

BACKGROUND: Prognosis for patients with advanced hepatocellular carcinoma with a tumor thrombus in the inferior vena cava or

 

ABSTRACT

BACKGROUND: Prognosis for patients with advanced hepatocellular carcinoma with a tumor thrombus in the inferior vena cava or right atrium is extremely poor due to cancer progression, pulmonary embolism, and congestion of the circulatory system caused by right heart failure. Surgical resection of the tumor thrombi may potentially yield better results than non-surgical treatments through prevention of sudden death. However, the benefits of surgical resection in patients with hepatocellular carcinoma and a tumor thrombus extending to the inferior vena cava, right atrium, and potentially in the phrenic vein are unclear. Here, we report three such cases.

CASE PRESENTATION: Of the total 136 patients who underwent hepatectomies for hepatocellular carcinoma in our institution, three patients with prior hepatectomies and recurrent hepatocellular carcinoma had tumor thrombi in the inferior vena cava, right atrium, and phrenic vein. Surgical resections were performed, as there was a possibility of sudden death, despite the risk of leaving residual tumor. For all patients, we performed resection of the tumor thrombi in the inferior vena cava and right atrium and combined diaphragm resection. Surgical resection was performed using the total hepatic vascular exclusion technique in all cases. Additional passive veno-venous bypass was also performed in two cases, in which complete tumor resections could not be achieved. The microscopic surgical margins of the combined resected diaphragms were positive in all cases. Progression-free survival was 20.2, 3.8, and 9.5 months for case 1, 2, and 3, respectively. The respective overall postoperative survival was 98.0, 38.9, and 30.9 months. The patients died due to liver cirrhosis, acute heart failure, and hepatocellular carcinoma, respectively. Sudden death did not occur for any of the patients.

CONCLUSION: Surgical resections may extend prognosis for patients with recurrent hepatocellular carcinoma with tumor thrombi in the inferior vena cava, right atrium, and phrenic vein, although the indications should be considered carefully.

PMID:32571339 | PMC:PMC7310451 | DOI:10.1186/s12957-020-01914-8

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PubMed articles on: Cardio-Oncology

Trastuzumab-induced cardiotoxicity and role of mitochondrial connexin43 in the adaptive response

Pecoraro M, et al. Toxicol In Vitro 2020 - Review.

A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were

 

ABSTRACT

A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temperature afforded isocoumarins. Two compounds e.g. 3n and 4d showed promising cytotoxic effects when tested against HCT 116, HepG2 and PA-1 cell lines at 10 μM. Indeed, 4d was found to be a potent cytotoxic agent (IC50 ∼ 0.76-4.51 μM). Both 3n and 4d were tested for their effects on PANC-1 cells. Considerable decrease in p-Akt substrates shown by 4d and 3n at 50 μM (western blot analysis) indicated their ability to inhibit p-Akt signal transduction pathway and arresting growth of PANC-1 cells in vitro. This was further supported by the cytotoxic effect of 4d on PANC-1 cells (MTT assay) that was better than rosuvastatin. While none of 3n and 4d showed any significant effect on non-cancerous HEK cell line (indicating their potential selectivity towards cancer cells) these compounds were further evaluated for their toxicities in Zebrafish embryo. The NOAEL (No Observed Adverse Effect Level) for teratogenicity, hepatotoxicity and cardiotoxicity was found to be 100 μM for both compound. Thus, 4d as a novel and potent but safer cytotoxic agent with potential to treat colorectal/ovarian and pancreatic cancer is of further medicinal interest.

PMID:32599323 | DOI:10.1016/j.ejmech.2020.112335

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PubMed articles on: Cancer & VTE/PE

Resection of recurrent hepatocellular carcinoma with thrombi in the inferior vena cava, right atrium, and phrenic vein: a report of three cases

Tomita K, et al. World J Surg Oncol 2020.

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal

 

ABSTRACT

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.

PMID:32593707 | DOI:10.1016/j.lfs.2020.117984

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PubMed articles on: Cardio-Oncology

Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents

Kumar JS, et al. Eur J Med Chem 2020.

PURPOSE: Late cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin lymphoma has been well reported.

 

ABSTRACT

PURPOSE: Late cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin lymphoma has been well reported. However, the relatively higher cardiac dose exposure for esophageal cancer (EC) may result in earlier onset of cardiac diseases. In this report, we examined the incidence, onset, and long-term survival outcomes of high-grade cardiac events after RT in a large cohort of EC patients.

PATIENTS AND METHODS: Between March 2005 and August 2017, 479 patients with EC from a prospectively maintained institutional database at The University of Texas MD Anderson Cancer Center were analyzed. All patients were treated with either intensity modulated RT (IMRT) or proton beam therapy (PBT), either pre-operatively or definitively. We focused on any grade 3 or higher (G3+) cardiac events according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

RESULTS: G3+ cardiac events occurred in 18% of patients at a median of 7 months with a median follow-up time of 76 months. Pre-existing cardiac disease (P=0.001) and radiation modality (IMRT vs PBT) (P=0.027) were significantly associated with G3+ cardiac events. Under multivariable analysis, mean heart dose, particularly < 15 Gy, was associated with reduced G3+ events. Furthermore, G3+ cardiac events were associated with worse overall survival (P=0.041).

CONCLUSION: Severe cardiac events were relatively common with early onset in EC patients after radiotherapy, especially those with pre-existing cardiac disease and higher radiation doses to the heart. Optimal treatment approaches should be taken to reduce cumulative doses to the heart, especially for patients with pre-existing cardiac disease.

PMID:32599073 | DOI:10.1016/j.jtho.2020.06.014

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PubMed articles on: Cardio-Oncology

Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects

Ashrafizadeh M, et al. Life Sci 2020 - Review.

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE)

 

ABSTRACT

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients.

MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017.

RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.).

CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

PMID:32571559 | DOI:10.1016/j.jdmv.2020.04.011

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PubMed articles on: Cardio-Oncology

Incidence and Onset of Severe Cardiac Events After Radiotherapy for Esophageal Cancer

Wang X, et al. J Thorac Oncol 2020.

Cardiovascular diseases are possible complications of antineoplastic treatment and may lead to premature morbidity and mortality

 

ABSTRACT

Cardiovascular diseases are possible complications of antineoplastic treatment and may lead to premature morbidity and mortality among cancer survivors. A symptom-based follow-up is ineffective, and there are growing evidences that early detection of myocardial damage in patients treated with antineoplastic drugs is the key point to prevent the occurrence of damage and improve the prognosis of these patients. Different techniques have been proposed to monitor cardiac function in oncologic patients such as cardiac imaging (echocardiography, nuclear imaging, and cardiac magnetic resonance) and biomarkers (troponin and natriuretic peptides). The European Association of Cardiovascular Imaging/American Society of Echocardiography consensus document encourages an integrated approach to early detect cardiotoxicity.

PMID:32566460 | PMC:PMC7293866 | DOI:10.4103/jcecho.jcecho_2_19

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PubMed articles on: Cancer & VTE/PE

Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases

Mauger C, et al. J Med Vasc 2020.

Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer

 

ABSTRACT

Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer are treated with agents that exert significant vascular toxicity. Coronary heart disease in patients with cancer presents particular challenges, which directly impact the management of both the coronary disease and malignancy. Several chemotherapeutic agents have been shown to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be dedicated to improving early recognition and prevention of cardiac vascular toxicity. Cardiac imaging could facilitate early detection of vascular toxicity, but a thorough risk stratification should always be performed to identify patients at higher risk of vascular impairment.

PMID:32566461 | PMC:PMC7293870 | DOI:10.4103/jcecho.jcecho_3_19

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PubMed articles on: Cardio-Oncology

Early Detection of Myocardial Damage: A Multimodality Approach

Novo G, et al. J Cardiovasc Echogr 2020 - Review.

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most

 

ABSTRACT

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

PMID:32565232 | PMC:PMC7293502 | DOI:10.1016/j.htct.2020.06.001

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PubMed articles on: Cardio-Oncology

Vascular Damage - Coronary Artery Disease

Cadeddu Dessalvi C, et al. J Cardiovasc Echogr 2020 - Review.

A primary cardiac angiosarcoma is a rare type of soft-tissue sarcoma with a high mortality rate. This report describes a young woman

 

ABSTRACT

A primary cardiac angiosarcoma is a rare type of soft-tissue sarcoma with a high mortality rate. This report describes a young woman who presented with chest pain and worsening shortness of breath over the course of a year. She was diagnosed with and treated for latent tuberculosis and autoimmune pericarditis over the last year, however, her condition kept worsening. Further workup revealed a large pericardial and right atrial mass associated with multiple lung nodules. The biopsy from the lung mass showed angiosarcoma, and she was diagnosed with primary metastatic angiosarcoma of the pericardium. She was treated with doxorubicin and Ifosfamide (AIM-75 regimen), which led to a partial response. However, soon after completion of six cycles, the tumour progressed rapidly, leading to cardio-respiratory failure. In this report, we will discuss the clinical challenges and treatment options (surgical and medical) that are available for treating patients with angiosarcoma of the heart.

PMID:32582371 | PMC:PMC7302885 | DOI:10.3332/ecancer.2020.1056

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PubMed articles on: Cancer & VTE/PE

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

Orsi FA, et al. Hematol Transfus Cell Ther 2020 - Review.

Venous thromboembolism (VTE) represents a major health problem, especially in cancer patients, who experience a significantly

 

ABSTRACT

Venous thromboembolism (VTE) represents a major health problem, especially in cancer patients, who experience a significantly higher incidence of both deep vein thrombosis and pulmonary embolism compared to the general population. Indeed, patients with cancer have a prothrombotic state resulting in both increased expression of procoagulants and suppression of fibrinolytic activity. In addition, VTE increases the morbidity and mortality of these patients. For all these reasons, the prevention and treatment of VTE in cancer setting represent major challenges in daily practice. In general, low-molecular-weight heparin monotherapy is the standard of care for the management of cancer-associated VTE, as Vitamin K antagonists are less effective in this setting. Direct oral anticoagulants offer a potentially promising treatment option for cancer patients with VTE, since recent studies demonstrated their efficacy and safety also in this peculiar setting.

PMID:32566465 | PMC:PMC7293865 | DOI:10.4103/jcecho.jcecho_63_19

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PubMed articles on: Cardio-Oncology

Primary pericardial angiosarcoma: case report and review of treatment options

Yadav U and Mangla A. Ecancermedicalscience 2020.

The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectom

 

ABSTRACT

The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectomy and left cystectomy were performed for bilateral ovarian endometriomas, which were both pathologically diagnosed as benign. Six months later, she presented with left lower abdominal pain and expressive aphasia. Examination revealed multiple cerebral infarctions and pulmonary embolism. The patient was diagnosed with Trousseau's syndrome secondary to ovarian cancer, and anticoagulant therapy was initiated. Despite treatment, she developed visual field loss due to occlusion of the left retinal artery; dizziness due to cerebellar infarction and myocardial infarction; and right hemiplegia due to new cerebral infarction. She received chemotherapy (two courses of paclitaxel and carboplatin), which did not improve her condition, and died two months after onset. An autopsy revealed that her left ovary was enlarged to a size of 12 cm and an endometrioid carcinoma G2 was identified. Ovarian cancer had spread throughout the abdominal cavity, and a large amount of pleural and ascites fluid was present. Multiple thrombi were found in bilateral pulmonary arteries and bilateral common iliac veins. There was a 2.5 cm thrombus in the left ventricle apex, and the anterior descending branch was obstructed by thrombus with recanalization.

PMID:32566336 | PMC:PMC7293738 | DOI:10.1155/2020/3738618

01:32

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PubMed articles on: Cancer & VTE/PE

Thrombotic Risk in Cancer Patients: Diagnosis and Management of Venous Thromboembolism

Citro R, et al. J Cardiovasc Echogr 2020 - Review.

Even if cancer and cardiovascular diseases are considered two distinct diseases, an intricate interconnection between these co

 

ABSTRACT

Even if cancer and cardiovascular diseases are considered two distinct diseases, an intricate interconnection between these conditions has been established. Increased risk of malignancy has been identified in patients with cardiovascular disease, as well as a greater propensity to the development of cardiovascular diseases has been observed in patients with cancer. The development of cardiotoxicity following exposure to certain anticancer drugs only partially explains this relationship. Shared risk factors and common pathogenic mechanisms suggest the existence of a common biology and a complex interplay between these two conditions. Due to improving longevity and therapeutic advances, the number of patients affected or potentially at risk of developing these two diseases is constantly increasing and currently, several drugs against cancer from anthracyclines to checkpoint inhibitors, can also cause a wide range of unexpected cardiovascular side effects. Management of these issues in clinical practice is an emerging challenge for cardiologists and oncologists, and led to the development of a new dedicated discipline called cardio-oncology. Surveillance and prevention strategies as well as interventions to reduce cardiovascular risk and prevent cardiotoxicities are the primary objectives of cardio-oncology. In this review, we explore the etiopathogenesis common to cardiovascular disease and cancer and the complex interplay between them. We also report the main characteristics of the drugs responsible for cardiotoxicity, highlighting the available strategies for optimal patient management based on a multidisciplinary approach in the cardio-oncology setting.

PMID:32571000 | DOI:10.4081/monaldi.2020.1348

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PubMed articles on: Cancer & VTE/PE

A Case of Trousseau's Syndrome Accompanying Ovarian Cancer with Widespread Thromboembolisms

Kobayashi H, et al. Case Rep Obstet Gynecol 2020.