Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.

Subacute cutaneous lupus erythematosus: A facultative paraneoplastic dermatosis.

Subacute cutaneous lupus erythematosus (SCLE) is a photosensitive dermatosis characterized by a nonscarring papulosquamous eruption and specific antibodies in the patient's serum. Genetic and environmental factors represent the leading causes of SCLE; however, several case reports in the literature link SCLE to various types of cancer. This review assesses the association between SCLE and neoplastic disorders. A PubMed search was performed for all relevant publications on cancer-associated SCLE from 1982 to 2022. This review supports the hypothesis that SCLE should be considered a facultative paraneoplastic phenomenon. It also emphasizes the importance of cancer screening in patients presenting SCLE manifestations.

Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia-Reperfusion Injury.

Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia-reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis.

Metabolic syndrome (MetS) represents a cluster of disorders that increase the risk of a plethora of conditions, in particular type two diabetes, cardiovascular diseases, and certain types of cancers. MetS is a complex entity characterized by a chronic inflammatory state that implies dysregulations of adipokins and proinflammatory cytokins together with hormonal and growth factors imbalances. Of great interest is the implication of microRNA (miRNA, miR), non-coding RNA, in cancer genesis, progression, and metastasis. The adipose tissue serves as an important source of miRs, which represent a novel class of adipokines, that play a crucial role in carcinogenesis. Altered miRs secretion in the adipose tissue, in the context of MetS, might explain their implication in the oncogenesis. The interplay between miRs expressed in adipose tissue, their dysregulation and cancer pathogenesis are still intriguing, taking into consideration the fact that miRNAs show both carcinogenic and tumor suppressor effects. The aim of our review was to discuss the latest publications concerning the implication of miRs dysregulation in MetS and their significance in tumoral signaling pathways. Furthermore, we emphasized the role of miRNAs as potential target therapies and their implication in cancer progression and metastasis.

The Impact of Obesity on Left Ventricular Hypertrophy and Diastolic Function in Caucasian Children.

Background: Left ventricular hypertrophy (LVH) and diastolic dysfunction are correlated with obesity and hypertension in adult patients, but few studies have investigated the association between obesity itself and left ventricular function in children. The aim of this study was to evaluate the effect of obesity and LVH on left ventricular diastolic function in pediatric subjects compared with children without obesity. Methods: A number of 454 patients from an outpatient cardiology service were enrolled in a prospective study, 33 children with obesity, 20 overweight children, and 401 children without obesity. The subjects were assigned to three groups according to age and school grade. A standardized two-dimensional echocardiography analysis was performed in all children. The evaluated echocardiographic parameters included thickness of the interventricular septum (IVS), thickness of the posterior wall of the left ventricle, and left atrium size. The left ventricular diastolic function was analyzed by the classic pulsed-wave Doppler technique, tissue Doppler technique, and continuous Doppler technique. Results: The number of children with obesity was higher in the school and adolescent groups. The median age of children with obesity was 9 years. The subjects were classified according to blood pressure values in hypertensive, with high-normal blood pressure/prehypertension and with normal blood pressure values. Standard echocardiography showed that children with obesity had significantly increased thickness of the IVS and of the posterior wall compared with nonobesity subjects (P < 0.001). Left ventricular systolic function was preserved in both groups. Diastolic function was normal in the obesity group and in the non-obesity group, respectively. Conclusions: The results of this study demonstrate that childhood obesity is associated with significant changes in the myocardial structure consisting of LVH, but we did not find an early alteration in the left ventricular diastolic function of the subjects with obesity compared with patients with a normal weight.

Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging.

BACKGROUND: Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then overt heart failure. However, in the last few years, several studies suggested that systolic subclinical dysfunction measured by speckle-tracking echocardiography (STE) may appear ahead of diastolic dysfunction. In this review, the main endpoint is to show whether subclinical myocardial systolic dysfunction appears ahead of diastolic dysfunction and the implication this may have on the evolution and management of DCM. MATERIALS AND METHODS: We performed a search in PubMed for all relevant publications on the assessment of DCM by STE from 1 June 2015 to 1 June 2020. RESULTS AND CONCLUSIONS: The results illustrate that subclinical systolic dysfunction assessed by STE is present in early DCM stages, with or without the association of diastolic dysfunction. This could be a promising perspective for the early management of patients with DCM leading to the prevention of the overt form of disease.