ABSTRACT
We present a novel computer algorithm to automatically detect and segment pulmonary embolisms (PEs) on computed tomography pulmonary angiography (CTPA). This algorithm is based on deep learning but does not require manual outlines of the PE regions. Given a CTPA scan, both intra- and extra-pulmonary arteries were firstly segmented. The arteries were then partitioned into several parts based on size (radius). Adaptive thresholding and constrained morphological operations were used to identify suspicious PE regions within each part. The confidence of a suspicious region to be PE was scored based on its contrast in the arteries. This approach was applied to the publicly available RSNA Pulmonary Embolism CT Dataset (RSNA-PE) to identify three-dimensional (3-D) PE negative and positive image patches, which were used to train a 3-D Recurrent Residual U-Net (R2-Unet) to automatically segment PE. The feasibility of this computer algorithm was validated on an independent test set consisting of 91 CTPA scans acquired from a different medical institute, where the PE regions were manually located and outlined by a thoracic radiologist (>18 years' experience). An R2-Unet model was also trained and validated on the manual outlines using a 5-fold cross-validation method. The CNN model trained on the high-confident PE regions showed a Dice coefficient of 0.676±0.168 and a false positive rate of 1.86 per CT scan, while the CNN model trained on the manual outlines demonstrated a Dice coefficient of 0.647±0.192 and a false positive rate of 4.20 per CT scan. The former model performed significantly better than the latter model (p<0.01).
PMID:37482032 | DOI:10.1016/j.media.2023.102882
02:55
PubMed articles on: Cancer & VTE/PE
Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE
J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.
ABSTRACT
BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.
OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.
RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.
PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007
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PubMed articles on: Cancer & VTE/PE
Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study
J Thromb Haemost. 2023 Jul 20:S1538-7836(23)00571-8. doi: 10.1016/j.jtha.2023.07.009. Online ahead of print.
ABSTRACT
BACKGROUND: Guidelines recommend thromboprophylaxis for cancer patients at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction, but have not yet been evaluated in cancer patients.
METHODS: We assessed the performance of the 5-SNP, 37-SNP, 297-SNP, extended 297-SNP (additionally including factor V Leiden and prothrombin G20210A), and 100-SNP scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios (SHR) in the upper vs three lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification.
FINDINGS: Of 36,150 cancer patients (median age, 66 years; 48.7% females), 1,018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95%CI, 0.54-0.58) for the 5-SNP to 0.60 (95%CI, 0.58-0.62) for the extended 297-SNP scores. SHRs ranged from 1.36 (95%CI, 1.19-1.56) for the 5-SNP to 1.90 (95%CI, 1.68-2.16) for the extended 297-SNP scores, and were consistent after adjusting for cancer type. For the Khorana cancer type classification the c-index was 0.60 (95%CI, 0.58-0.61), which increased to 0.65 (95%CI, 0.63-0.67; +0.05, 95%CI, 0.04-0.07) when combined with the extended 297-SNP score.
INTERPRETATION: These findings demonstrate that polygenic VTE risk scores can identify cancer patients with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.
PMID:37481074 | DOI:10.1016/j.jtha.2023.07.009
02:55
PubMed articles on: Cancer & VTE/PE
Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients
Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.
ABSTRACT
Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.
PMID:37479891 | DOI:10.1007/s00277-023-05369-1
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PubMed articles on: Cardio-Oncology
Multimodality imaging in cardio-oncology: the added value of CMR and CCTA
Br J Radiol. 2023 Jul 26:20220999. doi: 10.1259/bjr.20220999. Online ahead of print.
ABSTRACT
During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management.Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies.Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation.Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines.
PMID:37493228 | DOI:10.1259/bjr.20220999
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PubMed articles on: Cardio-Oncology
Penpulimab-induced complete atrioventricular block in a patient with metastatic renal cancer
HeartRhythm Case Rep. 2023 Apr 23;9(7):451-455. doi: 10.1016/j.hrcr.2023.04.007. eCollection 2023 Jul.
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PMID:37492041 | PMC:PMC10363469 | DOI:10.1016/j.hrcr.2023.04.007
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PubMed articles on: Cardio-Oncology
Cardio-oncology: Shared Genetic, Metabolic, and Pharmacologic Mechanism
Curr Cardiol Rep. 2023 Jul 26. doi: 10.1007/s11886-023-01906-6. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: The article aims to investigate the complex relationship between cancer and cardiovascular disease (CVD), with a focus on the effects of cancer treatment on cardiac health.
RECENT FINDINGS: Advances in cancer treatment have improved long-term survival rates, but CVD has emerged as a leading cause of morbidity and mortality in cancer patients. The interplay between cancer itself, treatment methods, homeostatic changes, and lifestyle modifications contributes to this comorbidity. Recent research in the field of cardio-oncology has revealed common genetic mutations, risk factors, and metabolic features associated with the co-occurrence of cancer and CVD. This article provides a comprehensive review of the latest research in cardio-oncology, including common genetic mutations, risk factors, and metabolic features, and explores the interactions between cancer treatment and CVD drugs, proposing novel approaches for the management of cancer and CVD.
PMID:37493874 | DOI:10.1007/s11886-023-01906-6
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PubMed articles on: Cardio-Oncology
Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer
Curr Cardiol Rep. 2023 Jul 25. doi: 10.1007/s11886-023-01909-3. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.
RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.
PMID:37490155 | DOI:10.1007/s11886-023-01909-3
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PubMed articles on: Cardio-Oncology
Identification and protection of early cardiotoxicity in acute myeloid leukemia patients undergoing transplantation
Hematology. 2023 Dec;28(1):2239569. doi: 10.1080/16078454.2023.2239569.
ABSTRACT
Cardiotoxicity of antitumor therapy results in declining survival rates. More specifically, cardiotoxicity is positively correlated with cumulative dose of anthracyclines and eventually develops from reversible to irreversible. In this context, early monitoring methods should be explored for the timely detection of cardiotoxicity and cardioprotective therapy should be performed in patients under consideration for potentially cardiotoxic therapy. This paper reports a 22-year-old male patient with acute myeloid leukemia who underwent whole-course cardiac monitoring after receiving antileukemia therapy. After the early detection of an asymptomatic decrease in left ventricular ejection fraction (LVEF), along with a significant decrease in global longitudinal strain (GLS), the patient was treated with sacubitril/valsartan (Sac/Val). Finally, the patient completed four courses of chemotherapy and subsequent hematopoietic stem cell transplantation as planned. The measurements of LVEF and GLS also recovered after 2 months treatment of Sac/Val. Therefore, the early identification and protection of patients with cardiotoxicity are of paramount importance and future prospective studies are expected to develop the management and treatment of cancer treatment-related cardiac dysfunction.
PMID:37489927 | DOI:10.1080/16078454.2023.2239569
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PubMed articles on: Cardio-Oncology
Acetylcholine receptor agonists effectively attenuated multiple program cell death pathways and improved left ventricular function in trastuzumab-induced cardiotoxicity in rats
Life Sci. 2023 Jul 22;329:121971. doi: 10.1016/j.lfs.2023.121971. Online ahead of print.
ABSTRACT
AIMS: Cardiotoxicity is a seriously debilitating complication of trastuzumab (TRZ) therapy in patients with cancer as a consequence of overexpression of the human epidermal growth factor receptor 2. Although most TRZ-induced cardiotoxicity (TIC) cases are reversible, some patients experience chronic cardiac dysfunction, and these irreversible concepts may be associated with cardiomyocyte death. Acetylcholine receptor (AChR) activation has been shown to exert cardioprotection in several heart diseases, but the effects of AChR agonists against TIC have not been investigated.
MAIN METHOD: Forty adult male Wistar rats were randomized into 5 groups: (i) CON (0.9 % normal saline), (ii) TRZ (4 mg/kg/day), (iii) TRZ + α7nAChR agonist (PNU-282987: 3 mg/kg/day), (iv) TRZ + mAChR agonists (bethanechol: 12 mg/kg/day), and (v) TRZ + combined treatment (Combined PNU-282987 and bethanechol).
KEY FINDINGS: The progression of TIC was driven by mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including by pyroptosis, ferroptosis, and apoptosis, which were significantly alleviated by α7nAChR and mAChR agonists. Interestingly, necroptosis was not associated with development of TIC. More importantly, the in vitro study validated the cytoprotective effects of AChR activation in TRZ-treated H9c2 cells, while not interfering with the anticancer properties of TRZ. All of these findings indicated that TRZ induced mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including pyroptosis, ferroptosis, and apoptosis, leading to impaired cardiac function. These pathological alterations were attenuated by α7nAChR and mAChR agonists.
SIGNIFICANCE: α7nAChR and mAChR agonists might be used as a future therapeutic target in the mitigation of TIC.
PMID:37482212 | DOI:10.1016/j.lfs.2023.121971
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PubMed articles on: Cardio-Oncology
DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes
Noncoding RNA. 2023 Jul 13;9(4):39. doi: 10.3390/ncrna9040039.
ABSTRACT
Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB.
PMID:37489459 | PMC:PMC10366827 | DOI:10.3390/ncrna9040039
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PubMed articles on: Cardio-Oncology
New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review
Cancers (Basel). 2023 Jun 22;15(13):3290. doi: 10.3390/cancers15133290.
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