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12/8/23

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with increased risk for venous

Abstract

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with increased risk for venous and arterial thromboembolism. The aim of this study was to evaluate outcomes following elective posterior lumbar fusion (PLF) and/or posterior interbody fusion (PLIF) among patients with PV.

METHODS: Using PearlDiver retrospective national database, Medicare patients <85

RESULTS: Selected study participants included 1491 patients with PV and 29,056 patients in the matched control group. Patients with PV had a significantly increased rate of 90-day acute pulmonary embolism (1.9% vs. 1.2%, odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.38, P = 0.010), 90-day lower extremity deep vein thrombosis (3.4% vs. 1.9%, OR 1.81, 95% CI 1.33-2.40, P < 0.001), and 1-year diagnosis of surgical site infection (5.4% vs. 4.2%, OR 1.30, 95% CI 1.02-1.63, P = 0.027) compared with patients without PV. Nonetheless, PV was not associated with other major medical complications, including stroke, myocardial infarction, and mortality, following PLF and/or PLIF.

CONCLUSIONS: Patients with PV undergoing elective PLF and/or PLIF have a significantly increased risk for pulmonary embolism, lower extremity deep vein thrombosis, and surgical site infection.

PMID: 31639499 [PubMed - indexed for MEDLINE]

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7 March 2020

13:10

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

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Chemotherapy-associated nonbacterial thrombotic endocarditis: A radiological mimicker of cardiac amyloidosis requiring histopathologic examination for definitive diagnosis.

Cardiovasc Pathol. 2020 Feb 11;47:107210

Authors: Sekulic M, Gupta A, Patterson A, Oliveira G, Rajagopalan S

BACKGROUND: Venous thromboembolism is a well-known complication of Cushing syndrome. Deep vein thrombosis and pulmonary

Abstract

BACKGROUND: Venous thromboembolism is a well-known complication of Cushing syndrome. Deep vein thrombosis and pulmonary embolic events have been widely reported in patients with Cushing syndrome, but cerebral venous sinus thrombosis remains a much less common finding in these patients.

CASE DESCRIPTION: We report one of the first cases of cerebral venous sinus thrombosis in a patient with Cushing disease. An 18-year-old man presented to our clinic with accelerated weight gain despite an active lifestyle and unchanged diet. Workup revealed adrenocorticotrophic hormone-dependent hypercortisolism, and magnetic resonance imaging demonstrated a 6-mm pituitary microadenoma, consistent with Cushing disease. He underwent endoscopic transsphenoidal resection and achieved the desired postoperative adrenal insufficiency. The patient was discharged home, but presented again in a delayed fashion with profound cerebral venous sinus thrombosis requiring a prolonged hospitalization.

CONCLUSIONS: Previous studies have suggested that the coagulation profile of patients with Cushing syndrome normalizes when measured 12 months after correction of hypercortisolism, but these patients may remain hypercoagulable for an undefined period postoperatively, despite becoming adrenally insufficient. Although there have been scarce reports of cerebral venous sinus thrombosis in non-adrenocorticotrophic hormone-dependent Cushing syndrome, we report the first case of cerebral venous sinus thrombosis postoperatively in a patient with Cushing disease in remission.

PMID: 31639504 [PubMed - indexed for MEDLINE]

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23:26

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Outcomes Following Posterior Lumbar Fusion in Patients with Polycythemia Vera.

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Outcomes Following Posterior Lumbar Fusion in Patients with Polycythemia Vera.

World Neurosurg. 2020 Feb;134:e372-e378

Authors: Labaran LA, Vatani J, Bell J, Puvanesarajah V, Sequeira S, Raad M, Jain A, Hassanzadeh H

Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential

Abstract

Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential for cardiotoxicity. The primary objective of this study was to compare cardiac magnetic resonance imaging (CMRI) versus echocardiography (ECHO) to detect a reduction in left ventricular ejection function, suggestive of doxorubicin cardiotoxicity. We studied eligible patients who were 18 years or older, who had breast cancer or lymphoma, and who were offered treatment with doxorubicin with curative intent dosing of 240 to 300 mg/m 2 body surface area between March 1, 2009 and October 31, 2013. Patients underwent baseline CMRI and ECHO. Both imaging studies were repeated after four cycles of treatment. Ejection fraction (EF) calculated by both methods was compared and analyzed with the inferential statistical Student's t test. Twenty-eight eligible patients were enrolled. Two patients stopped participating in the study before undergoing baseline CMRI; 26 patients underwent baseline ECHO and CMRI. Eight of those 26 patients declined posttreatment studies, so the final study population was 18 patients. There was a significant difference in EF pre- and posttreatment in the CMRI group ( p = 0.009) versus the ECHO group that showed no significant differences in EF ( p = NS). It appears that CMRI is superior to ECHO for detecting doxorubicin-induced reductions in cardiac systolic function. However, ECHO is less expensive and more convenient for patients because of its noninvasive character and bedside practicality. A larger study is needed to confirm these findings.

PMID: 32132816 [PubMed]

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

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

Lancet. 2020 02 15;395(10223):492-493

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

PMID: 32061290 [PubMed - indexed for MEDLINE]

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Protective strategies to prevent trastuzumab-induced cardiotoxicity.

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Protective strategies to prevent trastuzumab-induced cardiotoxicity.

Lancet. 2020 02 15;395(10223):491-492

Authors: Guo S, Tse G, Liu T

PMID: 32061289 [PubMed - indexed for MEDLINE]

23:26

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

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The Women's Health Initiative Estrogen-alone Trial had differential disease and medical expenditure consequences across age groups.

Menopause. 2020 Mar 02;:

Authors: Donneyong MM, Chang TJ, Roth JA, Guilds M, Ankrah D, Najafzadeh M, Xu WY, Chlebowski RT, Margolis K, Manson JE

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use

Abstract

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials.

METHODS: Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures.

RESULTS: Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively.

CONCLUSION: The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

PMID: 32132440 [PubMed - as supplied by publisher]

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23:26

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Cerebral Venous Sinus Thrombosis After Transsphenoidal Resection: A Rare Complication of Cushing Disease-Associated Hypercoagulability.

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Cerebral Venous Sinus Thrombosis After Transsphenoidal Resection: A Rare Complication of Cushing Disease-Associated Hypercoagulability.

World Neurosurg. 2020 Feb;134:86-89

Authors: Soni P, Koech H, Silva D, Das P, Sindwani R, Dobri G, Recinos PF

BACKGROUND AND PURPOSE: Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage

Abstract

BACKGROUND AND PURPOSE: Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage response (DDR). Hepatocyte growth factor (HGF) protects cardiomyocytes from injury, but its administration is hampered by low biodistribution. In this study we investigated whether the activation of the HGF receptor - encoded by the Met gene - by an agonist monoclonal antibody (mAb) protects from doxorubicin-induced cardiotoxicity.

EXPERIMENTAL APPROACH: MAb (5 mg/kg) was injected in vivo into C57BL/6J mice prior to doxorubicin (three doses of 7 mg/kg). The cardiac functions were evaluated through magnetic resonance imaging (MRI) after treatment termination. Heart histological staining and mRNA levels of genes associated with heart failure (Acta1, Nppa), inflammation (IL-6) and fibrosis (Ctgf, Col1a2, Timp1, and Mmp9) were assessed. MAb (100 nM) was administered in vitro to H9c2 cardiomyoblasts before addition of doxorubicin (25 μM). DDR and apoptosis markers were evaluated by quantitative western blotting, flow cytometry and immunofluorescence. Stattic was used for pharmacological inactivation of signal transducer and activation of transcription 3 (Stat3).

KEY RESULTS: In vivo, administration of mAb alleviated doxorubicin-induced cardiac dysfunction and fibrosis. In vitro, mAb mimicked the response to HGF by (i) inhibiting histone H2AX phosphorylation at S139, (ii) quenching the expression of the DNA repair enzyme poly (ADP-ribose) polymerase 1, and (iii) reducing the proteolytic activation of caspase 3. The Met-driven cardioprotection involved, at least in vitro, the phosphorylation of Stat3.

CONCLUSION AND IMPLICATIONS: This paper shows that Met agonist mAb provides a new tool for cardioprotection against anthracycline cardiotoxicity.

PMID: 32133617 [PubMed - as supplied by publisher]

20:50

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Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?

Cond Med. 2019 Oct;2(5):204-212

Authors: Chong J, Ho AF, Yap J, Bulluck H, Hausenloy DJ

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology

Abstract

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction.

PMID: 32133437 [PubMed]

20:50

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Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.

Int J Angiol. 2020 Mar;29(1):45-51

Authors: Tak T, Jaekel CM, Gharacholou SM, Dworak MW, Marshall SA

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly

Abstract

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.

PMID: 32135169 [PubMed - as supplied by publisher]

20:49

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Cardio-oncology for better lymphoma therapy outcomes.

Lancet Haematol. 2020 Mar 02;:

Authors: Jurczak W, Długosz-Danecka M, Szmit S

PMID: 32135129 [PubMed - as supplied by publisher]

20:49

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Activation of the Met receptor attenuates doxorubicin-induced cardiotoxicity in vivo and in vitro.

Br J Pharmacol. 2020 Mar 04;:

Authors: Gallo S, Spilinga M, Albano R, Ferrauto G, Di Gregorio E, Casanova E, Balmativola D, Bonzano A, Boccaccio C, Sapino A, Comoglio PM, Crepaldi T

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology

Abstract

PMID: 32133437 [PubMed]

20:50

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Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.

Int J Angiol. 2020 Mar;29(1):45-51

Authors: Tak T, Jaekel CM, Gharacholou SM, Dworak MW, Marshall SA

BACKGROUND: Long QT syndrome (LQTS) can cause the potentially fatal ventricular tachycardia torsades de pointes (TdP).

Abstract

BACKGROUND: Long QT syndrome (LQTS) can cause the potentially fatal ventricular tachycardia torsades de pointes (TdP). QT interval corrected for heart rate (QTc) is shorter in men than in women, with testosterone contributing to shorten QTc. We recently described male hypogonadism as a reversible risk factor for acquired LQTS and TdP, but the clinical characteristics of such patients have not been characterized.

AIMS: To describe the clinical characteristics of men with acquired LQTS or TdP associated with hypogonadism caused by endocrine conditions or androgen deprivation therapy (ADT), and to evaluate the relationship between testosterone concentrations and electrocardiographic changes.

METHODS: We searched MEDLINE (to 04 January 2019) and the French pharmacovigilance database (to 09 August 2018) to identify male cases of acquired LQTS and TdP associated with endocrine hypogonadism or ADT; their narratives were gathered from reporting collaborators.

RESULTS: We identified seven cases of TdP (one fatal) with endocrine hypogonadism, abnormally long QTc and morphologically abnormal T-wave notches. After reversion of low testosterone concentrations in the surviving patients (N=6), QTc shortened, T-wave morphology normalized and there was no TdP recurrence. Among these cases, none had mutation in the LQTS genes, three men required testosterone and three had reversible hypogonadism after resolution of a concurrent acute severe illness. We found an additional 27 reports of men with LQTS (N=6), TdP (N=9; 2/9 fatal) or sudden death (N=12; 10/12 fatal) suspected to be induced or favoured by ADT (24/27 for prostate cancer). Generally, after ADT withdrawal, QTc shortened and no TdP recurred.

CONCLUSION: We propose seeking for hypogonadism caused by endocrine conditions or ADT in men presenting with TdP. Caution is warranted when ADT is used in situations at risk of TdP. Testosterone may be useful to treat or prevent TdP.

PMID: 31477476 [PubMed - indexed for MEDLINE]

6 March 2020

20:49

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

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HERG channel and cancer: A mechanistic review of carcinogenic processes and therapeutic potential.

Biochim Biophys Acta Rev Cancer. 2020 Mar 02;:188355

Authors: He S, Moutaoufik MT, Islam S, Persad A, Wu A, Aly KA, Fonge H, Babu M, Cayabyab FS

BACKGROUND: Cancer and acute myocardial infarction (AMI) have important prognostic consequences. Treatment of some

Abstract

BACKGROUND: Cancer and acute myocardial infarction (AMI) have important prognostic consequences. Treatment of some cancers may affect coronary artery disease, myocardial function and/or AMI management. Whether the early and long-term mortality of patients with AMI differ according to their history of cancer remains questionable.

AIMS: To determine in-hospital outcomes and 5-year mortality following AMI according to patient history of cancer.

METHODS: The FAST-MI registry is a nationwide French survey collecting data on characteristics, management and outcomes of 3670 consecutive patients admitted for AMI during October 2005.

RESULTS: Overall, 246/3664 patients (6.7%) admitted for an AMI (47.6% with ST-segment elevation myocardial infarction [STEMI]; 52.4% with non-STEMI [NSTEMI]) had a history of cancer. In-hospital mortality was not significantly different for patients with versus without a history of cancer, overall (adjusted odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0.68-1.94; P=0.61) and in patients with STEMI (adjusted OR: 1.37, 95% CI: 0.69-2.71; P=0.37) or NSTEMI (adjusted OR: 0.97, 95% CI: 0.41-2.28; P=0.95). All-cause mortality at 5 years was higher among patients with a history of cancer (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.08-1.69; P=0.008), whereas 5-year cardiovascular mortality did not differ (adjusted HR: 1.17, 95% CI: 0.89-1.53; P=0.25), regardless of whether the patients had STEMI or NSTEMI. Similar results were found in populations matched on a propensity score including baseline characteristics and early management.

CONCLUSION: A history of cancer, per se, does not appear to be a risk factor for increased in-hospital mortality or long-term cardiovascular mortality in patients admitted for AMI.

PMID: 31761740 [PubMed - indexed for MEDLINE]

15:16

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Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study.

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Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study.

Arch Cardiovasc Dis. 2019 Nov;112(11):699-712

Authors: Salem JE, Bretagne M, Lebrun-Vignes B, Waintraub X, Gandjbakhch E, Hidden-Lucet F, Gougis P, Bachelot A, Funck-Brentano C, French Network of Regional Pharmacovigilance Centres

Background: Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic BRCA mutations in chemotherapy-resistant malignancies.

Abstract

Background: Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic BRCA mutations in chemotherapy-resistant malignancies. PARP inhibitors cause modest dose-dependent QT prolongation in the setting of a normal baseline QT interval.

Case summary: We describe a case of PARP inhibitor-induced torsades de pointes (TdP) in an 86-year-old gentleman prescribed rucaparib due to chemotherapy-resistant, metastatic prostate cancer with pre-existing long QT, with an apparent dose-dependent increase in QT interval. The patient presented with syncope and recurrent TdP requiring direct cardioversion reversion (200 J biphasic) and an isoprenaline infusion (2 μg/min). There were no other QT prolonging agents and no electrolyte or metabolic disturbance to account for this arrhythmia. Improvement in QT interval was observed within 72 h of rucaparib cessation.

Discussion: PARP inhibitors cause a modest, dose-dependent increase in QT interval in patients with a normal baseline. The safety of PARP inhibitors in patients with pre-existing long QT has not been evaluated. This is the first reported case of rucaparib-associated TdP in a patient with pre-existing long QT, highlighting the amplified effect of this agent in individuals with pre-existing QT prolongation and the risk of fatal arrhythmias.

PMID: 32128485 [PubMed]

15:16

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In-hospital outcomes and 5-year mortality following an acute myocardial infarction in patients with a history of cancer: Results from the French registry on Acute ST-elevation or non-ST-elevation myocardial infarction (FAST-MI) 2005 cohort.

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Arch Cardiovasc Dis. 2019 Nov;112(11):657-669

Authors: Ederhy S, Cohen A, Boccara F, Puymirat E, Aissaoui N, Elbaz M, Bonnefoy-Cudraz E, Druelles P, Andrieu S, Angoulvant D, Furber A, Ferrières J, Schiele F, Cottin Y, Simon T, Danchin N, FAST-MI investigators

Background: Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic BRCA mutations in chemotherapy-resistant malignancies.

Abstract

PMID: 32128485 [PubMed]

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Arch Cardiovasc Dis. 2019 Nov;112(11):657-669

OBJECTIVES: The objective of our work is to identify the risk factors for hospital mortality during pulmonary embolism in a pneumology department.

Abstract

OBJECTIVES: The objective of our work is to identify the risk factors for hospital mortality during pulmonary embolism in a pneumology department.

MATERIAL AND METHOD: All patients admitted to the pneumology department of Habib-Bourguiba hospital between 2014 and 2019, with a final diagnosis of PE are analyzed.

RESULTS: One hundred patients were included, 62% of whom were female, with an average age of 63±16 years. Pulmonary fibrosis was noted in eight patients. On admission, the mean Simplified Pulmonary Embolism Severity Index score was 1.46±1.05. The mean duration of hospitalization was 10.6±7 days. The hospital mortality rate was 12%. The independent risk factors for intra-hospital mortality were arterial hypotension (OR: 6.13; 95%CI: 2.88-14.35; p=0.001), cancer (OR: 2.66; 95%CI: 1.22-9.54; p=0.026), a VD/LV ratio at echocardiography>0.9 (OR: 1.84; 95%CI: 1.06-7.69; p=0.039) and severe hypoxemia (OR: 4.86; 95%CI: 2.19-11,34; p=0.006).

CONCLUSION: Pulmonary embolism mortality remains high despite improvements in diagnostic and therapeutic management. It is important for our country to take these results into consideration for a better management of patients admitted for pulmonary embolism, and to improve survival.

PMID: 32127194 [PubMed - as supplied by publisher]

15:15

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

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Figures of the Heart Failure Association (HFA): Dr. Rudolf de Boer, HFA Board Member (2014-2020), Chair of the Basic Science Section (2016-2018), coordinator of the Study Group on Heart Failure with Preserved Ejection Fraction, and member of the HFA study groups of Translational Research and Cardio-oncology.

Eur J Heart Fail. 2020 Mar 04;:

Authors: Coats AJS

PMID: 32128968 [PubMed - as supplied by publisher]

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Right ventricular involvement in cancer therapy-related cardiotoxicity: the emerging role of strain echocardiography.

Heart Fail Rev. 2020 Mar 03;:

Authors: Keramida K, Farmakis D

The involvement of the right ventricle (RV) in various cardiovascular pathologies is usually explored and demonstrated after thorough research of the

Abstract

The involvement of the right ventricle (RV) in various cardiovascular pathologies is usually explored and demonstrated after thorough research of the left ventricle (LV). This is also true in cardio-oncology, where multimodality imaging with cardiac magnetic resonance and nuclear imaging is essential, but echocardiography plays pivotal role in everyday clinical practice. Chemotherapy and radiotherapy effect on RV has been studied mainly in breast cancer patients and survivors from childhood cancer. Right ventricular geometry and shape limit the ability of classical echocardiographic indices like RV ejection fraction (RVEF), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) to identify reliably subtle changes in RV systolic function in cancer patients. The assessment of diastolic function of the RV in various timepoints during or after chemotherapy leads to conflicting results too. However, longitudinal strain of the RV (RV LS) seems to detect myocardial injury with consistent results. Remarkably, cardiotoxicity of the RV is identified by RV LS almost simultaneously with LV cardiotoxicity and with similar cutoff percent change suggesting the uniform effect of cancer and its treatments on myocardium. The prognostic value of cardiotoxic effects on the RV needs to be investigated by large prospective studies.

PMID: 32128669 [PubMed - as supplied by publisher]

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PARP inhibitor-induced torsades de pointes in long QT syndrome: a case report.

Eur Heart J Case Rep. 2020 Feb;4(1):1-5

Authors: Segan L, Beekman A, Parfrey S, Perrin M

Background: Hospital-acquired venous thromboembolisms (HA-VTE) are a significant source of morbidity and mortality in spine

Abstract

Background: Hospital-acquired venous thromboembolisms (HA-VTE) are a significant source of morbidity and mortality in spine surgery patients. The purpose of this study was to review HA-VTE rates at our institution and evaluate the prevalence of known risk factors in patients who developed HA-VTE among both neurosurgical and orthopedic spine surgeries.

Methods: Retrospective chart reviews were conducted of all spine surgery patients from January 1, 2013, to July 31, 2017, to evaluate rates of HA-VTE and prevalence of known HA-VTE risk factors among these patients. Univariate and multivariate logistic regression analysis for categorical variables and independent Student t test for continuous variables were utilized with significance set at P

Results: The overall HA-VTE rate was 0.94% (0.61% orthopedic, 1.87% neurosurgery). Patients with VTEs had higher rates of thoracic procedure (P = .002), posterior approach (P = .001), diagnosis of fracture (P = .013) or flatback syndrome (P = .028), neurosurgery division (P < .001),< .001),< .001).60 (80% vs 50%, P < .001),

Conclusions: The overall HA-VTE rate at our institution was 0.94% (0.61% orthopedic, 1.87% neurosurgery). In patients who sustained VTE, neurosurgical patients had higher rates of active cancer and age >60 years, and orthopedic patients had higher EBL and rates of anterior-posterior surgery. This highlights the different patient populations between the 2 departments and the need for individualized thromboprophylaxis regimens.

Level of Evidence: 4.

PMID: 32128307 [PubMed]

13:47

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[Risk factors for hospital mortality during pulmonary embolism].

Ann Cardiol Angeiol (Paris). 2020 Feb 29;:

Authors: El Ghoul J, Bendayekh A, Fki W, Yengui I, Ferjani S, Milouchi S, Ayadi H

Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently, there is neither a vaccine nor a consistently effective

Abstract

Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently, there is neither a vaccine nor a consistently effective drug available for this disease. Selective 5-aminopyrazole-4-carboxamide-based bumped-kinase inhibitors (BKIs) are effective in both in vitro and in vivo models of Cryptosporidium parvum. Potential cardiotoxicity in some BKIs led to the continued exploration of the 5-aminopyrazole-4-carboxamide scaffold to find safe and effective drug candidates for Cryptosporidium. A series of newly designed BKIs were tested for efficacy against C. parvum using in vitro and in vivo (mouse infection model) assays and safety issues. Compound 6 (BKI 1708) was found to be efficacious at 8 mg/kg dosed once daily (QD) for 5 days with no observable signs of toxicity up to 200 mg/kg dosed QD for 7 days. Compound 15 (BKI 1770) was found to be efficacious at 30 mg/kg dosed twice daily (BID) for 5 days with no observable signs of toxicity up to 300 mg/kg dosed QD for 7 days. Compounds 6 and 15 are promising preclinical leads for cryptosporidiosis therapy with acceptable safety parameters and efficacy in the mouse model of cryptosporidiosis.

PMID: 30830766 [PubMed - indexed for MEDLINE]

5 March 2020

13:46

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

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pubmed: caandvteortroorpul

Apelin/APJ system: an emerging therapeutic target for respiratory diseases.

Cell Mol Life Sci. 2020 Mar 03;:

Authors: Yan J, Wang A, Cao J, Chen L

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney,

Abstract

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells' proliferation and migration via triggering ERK1/2-cyclin D1 and PAK1-cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.

PMID: 32128601 [PubMed - as supplied by publisher]

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Prevalence of Risk Factors for Hospital-Acquired Venous Thromboembolism in Neurosurgery and Orthopedic Spine Surgery Patients.

Int J Spine Surg. 2020 Feb;14(1):79-86

Authors: Fischer CR, Wang E, Steinmetz L, Vasquez-Montes D, Buckland A, Bendo J, Frempong-Boadu A, Errico T

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney,

Abstract

PMID: 32128601 [PubMed - as supplied by publisher]

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Prevalence of Risk Factors for Hospital-Acquired Venous Thromboembolism in Neurosurgery and Orthopedic Spine Surgery Patients.

Int J Spine Surg. 2020 Feb;14(1):79-86

Authors: Fischer CR, Wang E, Steinmetz L, Vasquez-Montes D, Buckland A, Bendo J, Frempong-Boadu A, Errico T

AIMS: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF)

Abstract

AIMS: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice.

METHODS: This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality and bleeding events.

RESULTS: No differences between the DOACs were observed with regard to the risk of stroke, systemic embolism or cardiovascular death. In contrast, the risk of myocardial infarction was higher among patients prescribed apixaban in comparison to those on rivaroxaban (HR 1.67, 95% CI 1.02-2.71), and all-cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01-1.47]) and dabigatran (1.55 [1.16-2.05]) patients; rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79-15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10-2.03]) and dabigatran (1.58 [1.01-2.48]) patients; the risks of gastrointestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01-2.16] and 1.52 [1.21-1.92], respectively).

CONCLUSIONS: All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all-cause mortality, myocardial infarction and pulmonary embolism warrant further research.

PMID: 30423191 [PubMed - indexed for MEDLINE]

13:31

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

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pubmed: ctoall&ca or conall

Personalized Approach to Cancer Treatment-Related Cardiomyopathy.

Curr Heart Fail Rep. 2020 Mar 03;:

Authors: Slivnick J, Vallakati A, Addison D, Wallner A, Tong MS

We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against KRAS mutant lung adenocarcinoma. Nevertheless

Abstract

We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against KRAS mutant lung adenocarcinoma. Nevertheless, the evident toxicity restricts the use of wild-type (WT)-CVB3 for cancer therapy. The current study aims to engineer the CVB3 to decrease its toxicity and to extend our previous research to determine its safety and efficacy in treating TP53/RB1 mutant small-cell lung cancer (SCLC). A microRNA-modified CVB3 (miR-CVB3) was generated via inserting multiple copies of tumor-suppressive miR-145/miR-143 target sequences into the viral genome. In vitro experiments revealed that miR-CVB3 retained the ability to infect and lyse KRAS mutant lung adenocarcinoma and TP53/RB1-mutant SCLC cells, but with a markedly reduced cytotoxicity toward cardiomyocytes. In vivo study using a TP53/RB1-mutant SCLC xenograft model demonstrated that a single dose of miR-CVB3 via systemic administration resulted in a significant tumor regression. Most strikingly, mice treated with miR-CVB3 exhibited greatly attenuated cardiotoxicities and decreased viral titers compared to WT-CVB3-treated mice. Collectively, we generated a recombinant CVB3 that is powerful in destroying both KRAS mutant lung adenocarcinoma and TP53/RB1-mutant SCLC, with a negligible toxicity toward normal tissues. Future investigation is needed to address the issue of genome instability of miR-CVB3, which was observed in ~40% of mice after a prolonged treatment.

PMID: 32123721 [PubMed]

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[Immune checkpoint inhibitor-related cardiotoxicities].

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--medjournals.cn-CMAPH-Linkout-logo.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journal.yiigle.com-r-cms-jiansuo-CMAPH-Linkout-logo.png Related Articles

[Immune checkpoint inhibitor-related cardiotoxicities].

Zhonghua Nei Ke Za Zhi. 2020 01 01;59(1):75-77

Authors: Zhou L, Li HW, Chen H

PMID: 31887842 [PubMed - indexed for MEDLINE]

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Development of 5-Aminopyrazole-4-carboxamide-based Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles

Development of 5-Aminopyrazole-4-carboxamide-based Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy.

J Med Chem. 2019 03 28;62(6):3135-3146

Authors: Huang W, Hulverson MA, Choi R, Arnold SLM, Zhang Z, McCloskey MC, Whitman GR, Hackman RC, Rivas KL, Barrett LK, Ojo KK, Van Voorhis WC, Fan E

topics

12/8/23

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OBJECTIVES: The objective of our work is to identify the risk factors for hospital mortality during pulmonary embolism in a pneumology department.

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Background: Hospital-acquired venous thromboembolisms (HA-VTE) are a significant source of morbidity and mortality in spine

Cryptosporidium is a leading cause of pediatric diarrhea worldwide. Currently, there is neither a vaccine nor a consistently effective

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney,

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney,

AIMS: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF)

We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against KRAS mutant lung adenocarcinoma. Nevertheless

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