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1/12/26

ABSTRACT

Anthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents; however, their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline-induced cardiotoxicity (AIC) remains incomplete. Insulin-like growth factor binding protein (IGFBP) 3 (Igfbp-3), the most abundant IGFBP family member in the circulation, is associated with effects on the metabolism, proliferation, and survival of various cells. Whereas Igfbp-3 is induced by Dox in the heart, its role in AIC is ill-defined. We investigated molecular mechanisms as well as systems-level transcriptomic consequences of manipulating Igfbp-3 in AIC using neonatal rat ventricular myocytes and human-induced pluripotent stem cell-derived cardiomyocytes. Our findings reveal that Dox induces the nuclear enrichment of Igfbp-3 in cardiomyocytes. Furthermore, Igfbp-3 reduces DNA damage, impedes topoisomerase IIβ expression (Top2β) which forms Top2β-Dox-DNA cleavage complex leading to DNA double-strand breaks (DSB), alleviates detyrosinated microtubule accumulation-a hallmark of increased cardiomyocyte stiffness and heart failure-and favorably affects contractility following Dox treatment. These results indicate that Igfbp-3 is induced by cardiomyocytes in an effort to mitigate AIC.

PMID:37219486 | DOI:10.1096/fj.202201885RR

16:52

PubMed articles on: Cardio-Oncology

Correlation between high-resolution computed tomography appearance and histopathological features in the diagnosis of interstitial lung diseases. A real-life study

Minerva Surg. 2023 May 23. doi: 10.23736/S2724-5691.23.09948-3. Online ahead of print.

ABSTRACT

BACKGROUND: According to current guidelines, a surgical biopsy is rarely required when a high-confidence radiologic interstitial lung disease (ILD) diagnosis is made on thin-section high-resolution computed tomography (HRCT). Nevertheless, disowning HRCT scans diagnosed by biopsy are more common than presumed. Our study aimed to describe the concordance rate between HRCT scans and pathological diagnoses of ILDs obtained by surgical biopsy. The current guideline suggests the use of surgical lung biopsy (SLB) in patients with newly detected ILD of unknown cause.

METHODS: Patients who underwent mini-invasive surgical biopsies for interstitial lung diseases from January 2018 to August 2022 were analyzed. The HRCT scans were reviewed by an observer blinded to the patient's clinical information. The concordance between histological and HRCT-scan were assessed.

RESULTS: Data from 104 patients with uncertain low confidence diagnosis of interstitial lung diseases at HRCT were analyzed. Most of the patients are male (65; 62.5%). The more frequent HRCT pattern were: alternative diagnoses (46; 44.23%), UIP probable (42; 40.38%), UIP indeterminate (7; 6.73%), and non-specific interstitial pneumonia (NSIP) (9, 8.65%). The more common histological diagnosis was UIP definite (30; 28.84%), hypersensitivity pneumonia [HP](19; 18.44%), NSIP (15; 14.42%), sarcoidosis (10; 9.60%). In 7 (20%) cases, the final pathological finding denies HRCT-scans diagnoses; indeed, a moderate agreement was observed between HRCT-scan findings and the definitive histological diagnosis (kappa index: 0.428).

CONCLUSIONS: HRCT-scan has limitations if the objective is to define interstitial lung diseases accurately. Consequently, pathological assessment should be taken into account in order to provide more accurate tailored treatment strategies because the risk is to wait from 12 to 24 months to ascertain if the ILD will be treatable as progressive pulmonary fibrosis (PPF). Undeniably true, video-assisted surgical lung biopsy (VASLB) with endotracheal intubation and mechanical ventilation is associated with a risk of mortality and morbidity that is far from nil. Nevertheless, in recent years a VASLB approach performed in awake subjects under loco-regional anesthesia (awake-VASLB) has been suggested as an effective method to obtain a highly confident diagnosis in patients with diffuse pathologies of the lung parenchyma.

PMID:37218142 | DOI:10.23736/S2724-5691.23.09948-3

16:52

PubMed articles on: Cardio-Oncology

Diastolic function assessment with left atrial strain in long-term survivors of childhood acute lymphoblastic leukemia

Rev Esp Cardiol (Engl Ed). 2023 May 20:S1885-5857(23)00138-X. doi: 10.1016/j.rec.2023.05.001. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to exposure to cardiotoxic treatment. Although assessment of diastolic function is challenging in this relatively young population, left atrial strain might provide a novel insight in this evaluation. Our aim was to examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia by using left atrial strain and conventional echocardiographic parameters.

METHODS: Long-term survivors who were diagnosed at a single center between 1985 and 2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and atrial strain were compared, and the latter was measured during the 3 atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups.

RESULTS: We analyzed 90 survivors (age, 24.6 ± 9.7 years, time since diagnosis 18 [11-26] years) and 58 controls. PALS and LACS were significantly reduced compared with the control group: 46.4 ± 11.2 vs 52.1 ± 11.7; P = .003 and 32.5 ± 8.8 vs 38.2 ± 9.3; P = .003, respectively. Conventional diastolic parameters and PACS were similar between the groups. The reductions in PALS and LACS were associated with exposure to cardiotoxic treatment in age- and sex-adjusted analysis (≥ moderate risk, low risk, controls): 45.4 ± 10.5, 49.5 ± 12.9, 52.1 ± 11.7; Padj = .003, and 31.7 ± 9.0, 35.2 ± 7.5, 38.2 ± 9.3; Padj = .001, respectively.

CONCLUSIONS: Long-term childhood leukemia survivors showed a subtle impairment of diastolic function that was detected with atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher exposure to cardiotoxic treatment.

PMID:37217136 | DOI:10.1016/j.rec.2023.05.001

16:52

PubMed articles on: Cardio-Oncology

Severe sotorasib-related hepatotoxicity and non-liver adverse events associated with sequential anti-PD(L)1 and sotorasib therapy in KRASG12C-mutant lung cancer

J Thorac Oncol. 2023 May 20:S1556-0864(23)00572-5. doi: 10.1016/j.jtho.2023.05.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Sequential anti-PD-(L)1 followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in non-small cell lung cancer (NSCLC). KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs.

METHODS: This is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (NCI-CTCAE v5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation.

RESULTS: We identified 102 patients who received sotorasib, including 48 (47%) in sequence group and 54 (53%) in control group. Patients in control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in sequence group compared to control group (50% vs 13%, p<0.001).<0.001).

CONCLUSIONS: Sequential anti-PD-(L)1 and sotorasib therapy is associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.

PMID:37217096 | DOI:10.1016/j.jtho.2023.05.013

16:52

PubMed articles on: Cardio-Oncology

Clinical Outcomes and Prognostic Factors of Patients With Early Malignant Melanoma in One Latin American Country: Results of the Epidemiological Registry of Malignant Melanoma in Colombia Study

JCO Glob Oncol. 2023 May;9:e2200377. doi: 10.1200/GO.22.00377.

ABSTRACT

To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).

PMID:37216624 | DOI:10.1200/GO.22.00377

16:52

PubMed articles on: Cardio-Oncology

Assessment of left heart dysfunction to predict doxorubicin cardiotoxicity in children with lymphoma

Front Pediatr. 2023 May 5;11:1163664. doi: 10.3389/fped.2023.1163664. eCollection 2023.

ABSTRACT

OBJECTIVES: The objectives of this study were to assess the changes in the left myocardial function after chemotherapy for childhood lymphoma and observe the predictive or monitor value for cancer treatment-related cardiac dysfunction (CTRCD) by speckle-tracking echocardiography.

METHODS: A total of 23 children with histopathological diagnoses of lymphoma were included, with age-matched normal controls. Comparative analysis of clinical serological tests and left heart strain parameters in children with lymphoma, including left ventricular global longitudinal strain (LVGLS); global myocardial work (GMW) indices, which include global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency; and the LS of subendocardial, middle, and subepicardial layer myocardium during left ventricular systole were measured: left atrial strain of reservoir phase (LASr), left atrial strain of conduit phase (LAScd), and left atrial strain of contraction phase (LASct).

RESULTS: One-way ANOVA showed that GLS, GWI, GCW, LASr, and LAScd were closely associated with CTRCD and multivariate logistic regression analysis showed that GLS was the most sensitive predictor for detecting patients at lofty risk of anthracycline-related cardiotoxicity. Both before and after chemotherapy, GLS in the left ventricle showed a pattern of basal segment < middle segment < apical segment and subepicardial < middle < subendocardial layer (p < 0.05), and the degree of decrease also showed a regular pattern of epicardial layer < middle layer < subendocardial layer while the difference was not significant (p > 0.05). After chemotherapy, maximum flow rate in early mitral relaxation/left atrial systolic maximum flow rate (E/A) and left atrial volume index of each group were in the normal range, and the values of LASr, LAScd, and LASct slightly increased in the second cycle and decreased significantly in the fourth cycle after chemotherapy, reaching the lowest level; LASr and LAScd were positively correlated with GLS.

CONCLUSION: LVGLS is a more sensitive and earlier indicator to predict CTRCD compared with conventional echocardiography-related parameters and serological markers, and GLS of each myocardial layer showed a certain regularity. Left atrial strain can be used for early monitoring of cardiotoxicity in children with lymphoma after chemotherapy.

PMID:37215605 | PMC:PMC10196234 | DOI:10.3389/fped.2023.1163664

16:52

PubMed articles on: Cardio-Oncology

Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations

Arch Clin Cases. 2023 May 18;10(2):55-60. doi: 10.22551/2023.39.1002.10241. eCollection 2023.

ABSTRACT

Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.

PMID:37215066 | PMC:PMC10194170 | DOI:10.22551/2023.39.1002.10241

16:52

PubMed articles on: Cardio-Oncology

Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?

Front Pharmacol. 2023 May 4;14:1143361. doi: 10.3389/fphar.2023.1143361. eCollection 2023.

ABSTRACT

Cancer is one of the leading causes of death worldwide, and with the continuous development of life sciences and pharmaceutical technology, more and more antitumor drugs are being used in clinics to benefit cancer patients. However, the incidence of chemotherapy-induced cardiotoxicity has been continuously increasing, threatening patients' long-term survival. Cardio-oncology has become a research hot spot, and the combination of nanotechnology and biomedicine has brought about an unprecedented technological revolution. Nanomaterials have the potential to maximize the efficacy and reduce the side effects of chemotherapeutic drugs when used as their carriers, and several nano-formulations of frequently used chemotherapeutic drugs have already been approved for marketing. In this review, we summarize chemotherapeutic drugs that are highly associated with cardiotoxicity and evaluate the role of nano-delivery systems in reducing cardiotoxicity based on studies of their marketed or R&D nano-formulations. Some of the marketed chemotherapy drugs are combined with nano-delivery systems that can effectively deliver chemotherapy drugs to tumors and cannot easily penetrate the endothelial barrier of the heart, thus decreasing their distribution in the heart and reducing the cardiotoxicity to some extent. However, many chemotherapy nanomedicines that are marketed or in R&D have not received enough attention in determining their cardiotoxicity. In general, nanomedicine is an effective method to reduce the cardiotoxicity of traditional chemotherapy drugs. However, cardiovascular complications in cancer treatment are very complex diseases, requiring the application of multiple measures to achieve effective management and prevention.

PMID:37214453 | PMC:PMC10194942 | DOI:10.3389/fphar.2023.1143361

16:52

PubMed articles on: Cardio-Oncology

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2022: positron emission tomography, computed tomography, and magnetic resonance

J Nucl Cardiol. 2023 May 19. doi: 10.1007/s12350-023-03283-7. Online ahead of print.

ABSTRACT

In 2022, the Journal of Nuclear Cardiology® published many excellent original research articles and editorials focusing on imaging in patients with cardiovascular disease. In this review of 2022, we summarize a selection of articles to provide a concise recap of major advancements in the field. In the first part of this 2-part series, we addressed publications pertaining to single-photon emission computed tomography. In this second part, we focus on positron emission tomography, cardiac computed tomography, and cardiac magnetic resonance. We specifically review advances in imaging of non-ischemic cardiomyopathy, cardio-oncology, infectious disease cardiac manifestations, atrial fibrillation, detection and prognostication of atherosclerosis, and technical improvements in the field. We hope that this review will be useful to readers as a reminder to articles they have seen during the year as well as ones they have missed.

PMID:37204688 | DOI:10.1007/s12350-023-03283-7