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Pubblicazioni recenti - cardio-oncology
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The potential use of ABO blood group system for risk stratification of COVID-19.
Med Hypotheses2020 Oct;145():110343. doi: S0306-9877(20)32627-X.
AbdelMassih Antoine Fakhry, Mahrous Reham, Taha AbdelFattah, Saud Alaa, Osman Aliaa, Kamel Bishoy, Yacoub Elaria, Menshawey Esraa, Ismail Habiba-Allah, Aita Lina, Dous Maria, Saad Marina, AbdelAziz Mariam, Zaghar Mario, Shebl Noura, El-Husseiny Nadine, Fahmy Nourhan, Hegazy Nouran, Khalid Omar, Saad Osama, Afdal Peter, Menshawey Rahma, Husseiny Reem, Sherien Sandra, Salama Sara, Gad Salma, Ali Sajjad, Maalim Sayid, Ismail Sarah, ElHefnawi Yara, Aziz Youstina, Fouda Raghda,
Abstract
ABO blood groups is a cheap and affordable test that can be immediately retrieved from COVID-19 patients at the diagnosis. There is increasing evidence that non-O blood groups have both higher susceptibility and higher severity of COVID-19 infections. The reason behind such relationship seems elusive. Regarding susceptibility, Non-O individuals have Anti-A antibodies which can prevent viral entry across ACE-2 receptors, moreover, Non-O individuals are at higher risk of autoimmunity, hypercoagulable state, and dysbiosis resulting in an augmented tendency for vascular inflammatory sequelae of COVID-19. We can conclude, on the diagnostic level, that ABO blood groups can be potentially used for risk stratification of affected COVID-19 patients, to anticipate the deterioration of patients at higher risk for complications. On a therapeutic level, plasma from normal O blood group individuals might potentially replace the use of convalescent serum for the treatment of COVID-19.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Efficacy of Neurohormonal Therapies in Preventing Cardiotoxicity in Patients with Cancer Undergoing Chemotherapy.
JACC CardioOncol2019 Sep;1(1):54-65. doi: 10.1016/j.jaccao.2019.08.006.
Vaduganathan Muthiah, Hirji Sameer A, Qamar Arman, Bajaj Navkaranbir, Gupta Ankur, Zaha Vlad, Chandra Alvin, Haykowsky Mark, Ky Bonnie, Moslehi Javid, Nohria Anju, Butler Javed, Pandey Ambarish,
Abstract
Background:
Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain.
Objectives:
To assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy.
Methods:
This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (beta-blockers, mineralocorticoid receptor antagonists, or ACE inhibitors/ARBs) vs. placebo with follow-up ?4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference (SMD) and weighted mean difference (WMD) between the neurohormonal therapy and placebo groups using random effects models.
Results:
We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up [SMD(95% CI): +1.04(0.57 to 1.50)] but with significant heterogeneity in the pooled estimate (I = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95%CI: 2.9% to 5.0%) less decline in LVEF estimated by WMD, but with significant heterogeneity (I = 98%). There was a trend towards lower adverse clinical events with neurohormonal therapy (vs. placebo) without statistical significance [risk ratio(95%CI): 0.80(0.53-1.20) I = 71%].
Conclusions:
Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies.
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Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology.
J Clin Med2020 Oct;9(10):. doi: E3346.
Chung Robin, Tyebally Sara, Chen Daniel, Kapil Vikas, Walker J Malcolm, Addison Daniel, Ismail-Khan Roohi, Guha Avirup, Ghosh Arjun K,
Abstract
Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized-natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33-68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.
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Inflow Cannula Obstruction of the HeartWare Left Ventricular Assist Device: What Do We Really Know?
Cardiovasc Pathol2020 Oct;():107299. doi: S1054-8807(20)30103-4.
Pappalardo Federico, Bertoldi Letizia F, Sanvito Francesca, Marini Claudia, Consolo Filippo,
Abstract
In the setting of HeartWare left ventricular assist device (HVAD, Medtronic) implantation, pre-pump blood flow obstruction has been described due to intraventricular thrombus formation occluding the inflow cannula. This phenomenon often evolves in suboptimal pump performance, and requires prompt management to prevent its progression. However, to date, effective strategies and tools for the diagnosis and management of this complication are poorly described. We report a case of HVAD inflow cannula obstruction that drove later in-pump thrombosis and, eventually, complete cannula occlusion, and discuss gap of knowledge and limitations of currently available diagnostic and therapeutic tools in this scenario. Furthermore, we reinforce the value of time-frequency analysis of the HVAD log files to early identify abnormal pump operation associated with inflow cannula obstruction despite unremarkable trends of pump parameters.
Copyright © 2020. Published by Elsevier Inc.
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Primer on Biomarker Discovery in Cardio-Oncology: Application of Omics Technologies.
JACC CardioOncol2020 Sep;2(3):379-384. doi: 10.1016/j.jaccao.2020.07.006.
Rhee June-Wha, Ky Bonnie, Armenian Saro H, Yancy Clyde W, Wu Joseph C,
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Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy.
Cardiooncology2020 ;6():23. doi: 10.1186/s40959-020-00079-3.
Kamphuis Janine A M, Linschoten Marijke, Cramer Maarten J, Doevendans Pieter A, Asselbergs Folkert W, Teske Arco J,
Abstract
Background:
Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment.
Methods and results:
From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6?±?16.2?years, median cumulative anthracycline dose 329 [200-329] mg/m), and a median follow-up of 25.0 [9.6-37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early (?1?year) was 4.0 vs. 47.7?months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6?±?4.9% vs. 43.0?±?6.2% and iEDV 63.6 vs. 62.9?mL/m). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (?=?0.015).
Conclusions:
In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment.
© The Author(s) 2020.
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SARS-CoV-2 in pleural fluid in a kidney transplant patient.
Postgrad Med2020 Oct;():. doi: 10.1080/00325481.2020.1838817.
Bennett David, Franchi Federico, De Vita Elda, Mazzei Maria Antonietta, Volterrani Luca, Disanto Maria Giulia, Garosi Guido, Guarnieri Andrea, Cusi Maria Grazia, Bargagli Elena, Scolletta Sabino, Valente Serafina, Gusinu Roberto, Frediani Bruno,
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread all over the globe from China. Pleural involvement is not common; around 5-10% of patients can develop pleural effusion and little is known about the involvement of pleural structures in this new infection. A 61-year-old male kidney transplant patient with a history of multiple biopsy-confirmed acute rejections and chronic allograft rejection was admitted to our COVID-19 Unit with dry cough, exertional dyspnea, oliguria and abdominal distension. Lung ultrasound imaging, chest X-ray and CT scan showed left pleural effusion and atelectasis of the neighboring lung parenchyma. RT-PCR was positive for SARS-CoV-2 in the pleural fluid and cytology showed mesothelial cells with large and multiple nuclei, consistent with a cytopathic effect of the virus. This is one of few reports describing detection of SARS-CoV-2 in the pleural fluid and to the best of our knowledge, is the first to document the simultaneous presence of a direct cytopathic effect of the virus on mesothelial cells in a kidney transplant patient with COVID-19 pneumonia. The pleura proved to be a site of viral replication where signs of a direct pathological effect of the virus on cells can be observed, as we report here. RT-PCR for SARS-CoV-2 should be part of routine examination of pleural effusion even in patients with mild respiratory symptoms or with comorbidities that seem to explain the cause of effusion.
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Cardiovascular toxicity of PI3K? inhibitors.
Clin Sci (Lond)2020 Oct;134(19):2595-2622. doi: 10.1042/CS20200302.
Sadasivan Chandu, Zhabyeyev Pavel, Labib Dina, White James A, Paterson D Ian, Oudit Gavin Y,
Abstract
The phosphoinositide 3-kinases (PI3Ks) are a family of intracellular lipid kinases that phosphorylate the 3'-hydroxyl group of inositol membrane lipids, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. This results in downstream effects, including cell growth, proliferation, and migration. The heart expresses three PI3K class I enzyme isoforms (?, ?, and ?), and these enzymes play a role in cardiac cellular survival, myocardial hypertrophy, myocardial contractility, excitation, and mechanotransduction. The PI3K pathway is associated with various disease processes but is particularly important to human cancers since many gain-of-function mutations in this pathway occur in various cancers. Despite the development, testing, and regulatory approval of PI3K inhibitors in recent years, there are still significant challenges when creating and utilizing these drugs, including concerns of adverse effects on the heart. There is a growing body of evidence from preclinical studies revealing that PI3Ks play a crucial cardioprotective role, and thus inhibition of this pathway could lead to cardiac dysfunction, electrical remodeling, vascular damage, and ultimately, cardiovascular disease. This review will focus on PI3K?, including the mechanisms underlying the adverse cardiovascular effects resulting from PI3K? inhibition and the potential clinical implications of treating patients with these drugs, such as increased arrhythmia burden, biventricular cardiac dysfunction, and impaired recovery from cardiotoxicity. Recommendations for future directions for preclinical and clinical work are made, highlighting the possible role of PI3K? inhibition in the progression of cancer-related cachexia and female sex and pre-existing comorbidities as independent risk factors for cardiac abnormalities after cancer treatment.
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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A case of irreversible bradycardia after rituximab therapy for diffuse large B-cell lymphoma.
Cardiooncology2020 ;6():22. doi: 10.1186/s40959-020-00077-5.
Ko Ko Nway Le, Minaskeian Nareg, El Masry Hicham Z,
Abstract
This is a case of a middle-aged woman with underlying cardiac conduction system with episodes of AV Wenckebach, who subsequently developed significant AV conduction system abnormalities after receiving one standard dose of Rituximab infusion for diffuse large B-cell lymphoma. Rituximab, being a monoclonal antibody against CD-20 antigen, is effective in treatment of B-cell lymphoma but may also cause bradyarrythmias likely due to the calcium ion channel property of CD-20 antigen.
© The Author(s) 2020.
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Impact of pre-existing cardiovascular disease on treatment patterns and survival outcomes in patients with lung cancer.
BMC Cancer2020 Oct;20(1):1004. doi: 10.1186/s12885-020-07487-9.
Batra Atul, Sheka Dropen, Kong Shiying, Cheung Winson Y,
Abstract
BACKGROUND:
Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer.
METHODS:
We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD.
RESULTS:
A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70?years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48-0.58; P?
CONCLUSIONS:
Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.
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[Tumor effects on the heart and circulation].
Internist (Berl)2020 Nov;61(11):1120-1124. doi: 10.1007/s00108-020-00887-w.
Anker M S, Hadzibegovic S, von Haehling S,
Abstract
As a result of the continuous development of modern cancer treatment, more cancer patients can be cured every year. However, since many patients experience cardiovascular problems before, during and after their cancer treatment, cardio-oncology is becoming increasingly important. Numerous therapies can cause cardiotoxicity, such as chemotherapy, immunotherapy, antibody therapy and radiotherapy. If these remain undetected, the patient may develop, e.g. heart failure or severe heart valve damage. The broad spectrum of cardiovascular comorbidities has become an immense challenge for cardiologists and oncologists. Cardio-oncology also deals with the effects that cancer has on the cardiovascular system. New research indicates that the tumor itself also has direct negative effects on the heart, mediated by messenger substances. Therefore, it is important to understand which cancer patients are at increased cardiovascular risk, thereby enabling the development of new therapeutic approaches in the long term to maintain mobility and improve patient prognosis.
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Cellular model systems to study cardiovascular injury from chemotherapy.
J Thromb Thrombolysis2020 Oct;():. doi: 10.1007/s11239-020-02299-x.
Fonoudi Hananeh, Burridge Paul W,
Abstract
In spite of all the efforts for generating efficient pharmacological treatment options for cancer patients, the unwanted side effect of these substances on the cardiovascular system is becoming a major issue for cancer survivors. The fast pacing oncology field necessitate the quest for more accurate and reliable preclinical screenings. hiPSCs derived cardiomyocytes, endothelial and vascular smooth muscle cells provide unlimited source of physiologically relevant cells that could be used in the screening platforms. Cells derived from hiPSCs can measure drug induced alterations to different aspect of the heart including electrophysiology, contractility and structure. In this review, we will give an overview of the different in vivo and in vitro preclinical drug safety screenings. In following sections, we will focus on hiPSCs derived cardiomyocytes, endothelial and vascular smooth muscle cells and present the current knowledge of the application of these cells in unicellular cardiotoxicity assays. In the final part, we will focus on cardiac organoids as multi cell type platform and their role in cardiotoxicity screening of the chemotherapeutic drugs.
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Cardiovascular Toxicity and Mortality Associated With Adoptive Cell Therapy and Tumor-infiltrating Lymphocytes for Advanced Stage Melanoma.
J Immunother2020 Oct;():. doi: 10.1097/CJI.0000000000000341.
Fradley Michael G, Damrongwatanasuk Rongras, Chandrasekhar Sanjay, Alomar Mohammed, Kip Kevin E, Sarnaik Amod A,
Abstract
Adoptive cellular therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has emerged as an effective treatment option for unresectable stage III/IV metastatic melanoma. Acute toxicities, particularly cardiovascular (CV), can have a significant effect on the completion of therapy. We abstracted information on 43 patients who received ACT-TIL treatment for melanoma at the Moffitt Cancer Center between 2010 and 2016. The Student t tests and ? tests were used to compare patient characteristics by presence versus absence of specific CV complications. In this cohort, 32.6% developed hypotension requiring treatment with intravenous fluids and pressors, 14% atrial fibrillation, and 2.3% troponin elevations suggestive of myocardial damage. No patients developed clinical heart failure, and among the patients that underwent echocardiography, there was no significant difference in mean left ventricular ejection fraction before or after therapy (62.9% vs. 63.5%, respectively, P=0.79). There was also no statistically significant difference in survival between those with and without CV complications (overall survival=61.9%, mean: 26.0?mo and progression-free survival=45.2%, mean: 18.1?mo). CV toxicities are common in ACT-TIL protocols; however, survival does not appear to be significantly affected. Further research is needed to define mechanisms and potential prevention strategies to help clinicians manage these complications and mitigate risk.
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Radiation-Associated Valvular Disease.
Curr Cardiol Rep2020 Oct;22(12):167. doi: 10.1007/s11886-020-01411-0.
Xu Samantha, Donnellan Eoin, Desai Milind Y,
Abstract
PURPOSE OF REVIEW:
Radiation-associated valvular disease (RAVD) is characterized by late valvular manifestations following radiation exposure to the mediastinum. Review of current guidelines was performed to examine best practices to reduce risk and optimize outcomes in this patient population.
RECENT FINDINGS:
Early and consistent screening and comprehensive and careful planning are critical in managing RAVD. Due to long latency periods, serial screening and targeted evaluation of risk factors are essential to early detection. Varying and complex presentations of RAVD require an integrated team of experienced specialists equipped with multimodality imaging-based screening protocols to stratify risk, plan intervention, and evaluate treatment response. Patients with valvular manifestations associated with radiation therapy call for an individualized plan of care involving longitudinal multimodality imaging-based screening and experienced decision-making regarding timing and strategy of intervention to improve patient outcomes.
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Cardiac Tumors: Diagnosis, Prognosis, and Treatment.
Curr Cardiol Rep2020 Oct;22(12):169. doi: 10.1007/s11886-020-01420-z.
Bussani Rossana, Castrichini Matteo, Restivo Luca, Fabris Enrico, Porcari Aldostefano, Ferro Federico, Pivetta Alberto, Korcova Renata, Cappelletto Chiara, Manca Paolo, Nuzzi Vincenzo, Bessi Riccardo, Pagura Linda, Massa Laura, Sinagra Gianfranco,
Abstract
PURPOSE OF REVIEW:
Cardiac masses frequently present significant diagnostic and therapeutic clinical challenges and encompass a broad set of lesions that can be either neoplastic or non-neoplastic. We sought to provide an overview of cardiac tumors using a cardiac chamber prevalence approach and providing epidemiology, imaging, histopathology, diagnostic workup, treatment, and prognoses of cardiac tumors.
RECENT FINDINGS:
Cardiac tumors are rare but remain an important component of cardio-oncology practice. Over the past decade, the advances in imaging techniques have enabled a noninvasive diagnosis in many cases. Indeed, imaging modalities such as cardiac magnetic resonance, computed tomography, and positron emission tomography are important tools for diagnosing and characterizing the lesions. Although an epidemiological and multimodality imaging approach is useful, the definite diagnosis requires histologic examination in challenging scenarios, and histopathological characterization remains the diagnostic gold standard. A comprehensive clinical and multimodality imaging evaluation of cardiac tumors is fundamental to obtain a proper differential diagnosis, but histopathology is necessary to reach the final diagnosis and subsequent clinical management.
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[Mechanisms of cardiotoxicity of oncological therapies].
Internist (Berl)2020 Nov;61(11):1132-1139. doi: 10.1007/s00108-020-00881-2.
Lehmann L H, Fröhling S,
Abstract
BACKGROUND:
Oncological therapies show a number of undesired adverse effects on the cardiovascular system. In particular, the side effects of recently established oncological therapies are incompletely understood and clinical data are lacking in the interpretation of novel cardiac complications.
OBJECTIVE:
This article provides a short overview of the mechanisms of cardiac side effects of certain oncological therapies.
MATERIAL AND METHODS:
The review is mainly based on data from preclinical studies.
RESULTS:
Numerous toxic side effects have already been described and investigated in preclinical models. For certain groups of drugs (e.g. anthracyclines, tyrosine kinase inhibitors and immune checkpoint inhibitors) the underlying molecular mechanisms are still not fully understood.
CONCLUSION:
An improved understanding of the molecular mechanism involved in cardiotoxicity might help improve the quality of clinical decisions. Additionally, it will provide new insights into the pathophysiology of cardiac diseases. The aim is to use the results of translational research and to clinically implement them in suitable cardio-oncology units.
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Metastatic Right Ventricular Liposarcoma.
Heart Lung Circ2020 Oct;():. doi: S1443-9506(20)30471-6.
Brennan Anthony P, Newcomb Andrew, Creati Louise, Mariani Justin,
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Clinical significance of transcription factor RUNX2 in lung adenocarcinoma and its latent transcriptional regulating mechanism.
Comput Biol Chem2020 Oct;89():107383. doi: S1476-9271(20)30857-4.
Yang Da-Ping, Huang Wan-Ying, Chen Gang, Chen Shang-Wei, Yang Jie, He Rong-Quan, Huang Su-Ning, Gan Ting-Qing, Ma Jie, Yang Lin-Jie, Song Jian-Hua, Mo Jun-Xian, Tang Zhong-Qing, Li Chang-Bo, Zhou Hua-Fu, Kong Jin-Liang,
Abstract
RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Cancer and Cardiovascular Diseases during the COVID-19 Pandemic.
Arq Bras Cardiol2020 09;115(3):547-557. doi: S0066-782X2020001100547.
Kawahara Lucas Tokio, Costa Isabela Bispo Santos da Silva, Barros Cecília Chie Sakaguchi, Almeida Gabriel Coelho de, Bittar Cristina Salvadori, Rizk Stephanie Itala, Testa Laura, Moniz Camila Motta Venchiarutti, Pereira Juliana, Oliveira Gláucia Maria Moraes de, Diz Maria Del Pilar Estevez, Guimarães Patricia Oliveira, Pinto Ibraim Masciarelli, Kalil Filho Roberto, Hajjar Ludhmila Abrahão, Hoff Paulo M,
Abstract
The challenges that the COVID-19 pandemic cretead to the healthcare system have made it necessary to adapt routines and services, with the objectives of controlling the spread of the virus and preserving health. Safe and correct management of patients in risks groups, such as elderly patients, patients with cardiovascular diseases, and patients with cancer, has become even more important. Thus, cardio-oncology has gained a new dimension, with the aim of adapting to patients' needs during the pandemic by restructuring the system of care in a manner that offers quality and safety in healthcare.
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The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia.
Curr Heart Fail Rep2020 Oct;():. doi: 10.1007/s11897-020-00485-9.
Gatti Milo, Raschi Emanuel, Poluzzi Elisabetta, Martignani Cristian, Salvagni Stefania, Ardizzoni Andrea, Diemberger Igor,
Abstract
PURPOSE OF REVIEW:
Cardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation.
RECENT FINDINGS:
AF in cardio-oncology poses diagnostic and management challenges, also due to the number of anticancer drugs recently associated with AF onset/worsening. Oral targeted drugs can potentially interact with DOACs, with increased bleeding risk mainly due to pharmacokinetic DDIs. Moreover, the vast majority of oral anticancer agents cause QT prolongation with direct and indirect mechanisms, potentially resulting in the occurrence of torsade de pointes, especially in susceptible patients with COVID-19 receiving additional drugs with QT liability. Oncologists and cardiologists must be aware of the increased bleeding risk and arrhythmic susceptibility of patients with AF and cancer due to DDIs. High-risk individuals with COVID-19 should be prioritized to target preventive strategies, including optimal antithrombotic management, medication review, and stringent monitoring.
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