Incidence and risk factors of immune checkpoint inhibitor myocardial and muscle toxicity: a French nationwide study.

Background And Aims: Immune checkpoint inhibitor (ICI)-induced (cardio)-myotoxicities, including myocarditis and myositis, are uncommon but frequently severe adverse drug reactions seen in cancer patients. Real-life ICI myotoxicity incidence estimates span from limited-size cohorts, with risk factors and prognosticators poorly established, as well as their impact on survival.

Methods: This retrospective French National Health Data System cohort study included all adult patients starting ICI between 1 January 2012 and 30 September 2022.

Transgender-Affirming Hormone Therapies, QT Prolongation, and Cardiac Repolarization.

Importance: Transgender women (assigned male at birth) usually take antiandrogens associated with estrogens (or are castrated) to induce feminization, whereas transgender men (assigned female at birth) take testosterone to induce masculinization. However, the cardiovascular outcomes of these gender-affirming hormone therapies (GAHTs) remain poorly studied.

Objective: To examine the association between GAHT intake and cardiac repolarization alterations on electrocardiography in transgender individuals.

Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis.

Background: Pegylated liposomal doxorubicin (PLD) and bevacizumab are commonly used to treat platinum-resistant ovarian cancer. While both agents are associated with cardiovascular toxicities, their combined impact on cardiotoxicity in real-world settings is not well defined. This study investigates whether co-administration of PLD and bevacizumab increases the risk of cardiovascular adverse events compared to PLD alone.

Immune checkpoint inhibitor-associated myocarditis: a novel risk score.

Background And Aims: Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking.

Comedications Associated with Immune-Related Adverse Events from Immune-Checkpoint Inhibitors.

Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment but are responsible for various immune-related adverse events (irAE). The impact of non-anticancer medications (comedications) on irAE occurrence remains largely unexplored. The objective of this study was to assess comedications associated with an increased reporting of irAE with ICIs.

Metabolic dysfunction-associated steatotic liver disease (MASLD) biomarkers and progression of lower limb arterial calcification in patients with type 2 diabetes: a prospective cohort study.

Background: Studies have demonstrated that both lower limb arterial calcification and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to the development of peripheral artery disease. However, the potential relationship between MASLD biomarkers and progression of lower limb arterial calcification in individuals with type 2 diabetes (T2D) remains unclear. This study aimed to investigate whether the biomarkers of MASLD included in the FibroMax® panels are associated with the progression of lower limb arterial calcification in patients with T2D.

Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.

Objectives: The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M.

MAIT Cells Promote Cholesterol Excretion Pathways Mitigating Atherosclerosis.

Background: Previous clinical studies have indicated reduced circulating mucosal-associated invariant T (MAIT) cells in individuals with coronary artery disease. However, the precise role and underlying mechanisms of MAIT cells in this context remain unclear. Immune homeostasis plays a pivotal role in the development of atherosclerosis.

A high-performance extracellular field potential analyzer for iPSC-derived cardiomyocytes.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a pivotal model for research. Specialized devices can generate Extracellular Field Potential (EFP) measurements from these cells, analogous to the ventricular complex of the electrocardiogram. However, electrophysiological analysis can be complex and requires specialized expertise, posing a barrier to broader adoption in non-specialized labs.

Real-life prognosis of neurological complications of botulinum toxin: A nationwide pharmacovigilance study of adverse drug reactions reported in France between 1994 and 2020.

Background: Botulinum toxin is commonly used in the treatment of neurological disorders. Although neurological complications predominate and can lead to respiratory failure or death, no observational studies have specifically described their clinical features or prognoses.

Objectives: To characterise real-life clinical features and prognoses of botulinum toxin-related neurological complications.

Case Report: Immune checkpoint-inhibitor related myotoxicity monitoring using a comprehensive cardiothoracic MRI approach: insights from a clinical case.

Recent advances in immunotherapy have significantly improved outcomes for cancer patients. However, therapies such as immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events, including potentially fatal ICI-myocarditis. The diagnosis of ICI-myocarditis is complex, and cardiac MRI plays a crucial role in identifying this condition.

Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes.

Background: Sphingosine 1-phosphate (S1P) is a key mediator of lipid signaling with strong immunomodulatory and anti-inflammatory effects. Circulating S1P levels including S1P in high-density lipoproteins (HDL) were demonstrated to be inversely associated with cardiovascular diseases (CVD). However, no studies are available regarding a potential implication of S1P on the risk of CVD in type 2 diabetes (T2D).

Successful treatment of immune checkpoint inhibitor-associated fulminant myocarditis with abatacept and ruxolitinib: a case report.

Background: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events.

Diagnosis of cancer therapy-related cardiovascular toxicities: A multimodality integrative approach and future developments.

Diagnosing cancer therapy-related cardiovascular toxicities may be a challenge. The interplay between cancer and cardiovascular diseases, beyond shared cardiovascular and cancer risk factors, and the increasingly convoluted cancer therapy schemes have complicated cardio-oncology. Biomarkers used in cardio-oncology include serum, imaging and rhythm modalities to ensure proper diagnosis and prognostic stratification of cardiovascular toxicities.

Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) may induce overlapping myositis/myasthenia gravis (MG) features, sparking current debate about pathophysiology and management of this emerging disease entity. We aimed to clarify whether ICI-induced (ir-) myositis and ir-MG represent distinct diseases or exist concurrently.

Methods: We performed a retrospective multicenter cohort study.

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.

Abatacept dose-finding phase II triaL for immune checkpoint inhibitors myocarditis (ACHLYS) trial design.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a life-threatening adverse drug reaction. Abatacept (a CTLA-4-immunoglobulin fusion protein) has been proposed as a compassionate-use treatment for ICI myocarditis (in combination with corticosteroids and ruxolitinib) but no clinical trial has yet been performed. The abatacept dose can be adjusted using real-time assessment of its target, the CD86 receptor occupancy on circulating monocytes (CD86RO).

EFP Analyzer: A fast, accurate, and easy-to-teach program for analyzing Extracellular Field Potentials from iPSC-derived cardiomyocytes.

Rationale: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an emerging model for determining drug effects and modeling disease. Specialized devices can generate Extracellular Field Potential (EFP) measurements from these cells, analogous to the ventricular complex of the electrocardiogram.

Objective: The objective of this study was to develop an easy-to-use, easy-to-teach, reproducible software tool to measure EFPs.

Clinical correlates of lifetime and current comorbidity patterns in autoimmune and inflammatory diseases.

Background: Autoimmune and inflammatory diseases (AIDs) are a heterogeneous group of disorders with diverse etiopathogenic mechanisms. This study explores the potential utility of family history, together with present and past comorbidities, in identifying distinct etiopathogenic subgroups. This approach may facilitate more accurate diagnosis, prognosis and personalized therapy.

Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.