Cellular and molecular mechanisms driving cardiac tissue fibrosis: On the precipice of personalized and precision medicine.

Cardiac fibrosis is a significant contributor to heart failure, a condition that continues to affect a growing number of patients worldwide. Various cardiovascular comorbidities can exacerbate cardiac fibrosis. While fibroblasts are believed to be the primary cell type underlying fibrosis, recent and emerging data suggest that other cell types can also potentiate or expedite fibrotic processes. Over the past few decades, clinicians have developed therapeutics that can blunt the development and progression of cardiac fibrosis. While these strategies have yielded positive results, overall clinical outcomes for patients suffering from heart failure continue to be dire. Herein, we overview the molecular and cellular mechanisms underlying cardiac tissue fibrosis. To do so, we establish the known mechanisms that drive fibrosis in the heart, outline the diagnostic tools available, and summarize the treatment options used in contemporary clinical practice. Finally, we underscore the critical role the immune microenvironment plays in the pathogenesis of cardiac fibrosis.

Simulating mitral repair: lessons learned.

PURPOSE OF REVIEW: With the growing complexity of cardiac surgical cases, increased focus on patient safety, and minimally invasive techniques, simulation-based training has experienced a renaissance. This review highlights important elements of simulation-based training, focusing specifically on available simulators for mitral valve repair and the uses for simulation. RECENT FINDINGS: Referring to simulators as being high or low fidelity is oversimplified. Fidelity is a multifactorial concept, and for surgical task trainers, structural and functional fidelity should be discussed. For mitral valve repair, there are a spectrum of simulators, including tissue-based models, bench-top models, and hybrid models. All these simulator modalities serve a role in training if they align with predetermined objectives. There have been advancements in mitral valve repair simulation, notably patient-specific 3D printed silicone replicas of disease. SUMMARY: There is evidence to support that simulation improves performance in the simulated environment, but future investigation should look to determine whether simulation improves performance in the clinical setting and ultimately patient outcomes.

Ischemic heart disease: Cellular and molecular immune contributions of the pericardium.

Ischemic heart disease promotes complex inflammatory and remodeling pathways which contribute to the development of chronic heart failure. Although blood-derived and local cardiac mediators have traditionally been linked with these processes, the pericardial space has more recently been noted as alternative contributor to the injury response in the heart. The pericardial space contains fluid rich in physiologically active mediators, and immunologically active adipose tissue, which are altered during myocardial infarction. Key immune cells in the pericardial fluid and adipose tissue have been identified which act as mediators for cell recruitment and function after myocardial infarction have been identified in experimental models. Here, we provide an overview of the current understanding of the inflammatory mechanisms of the pericardial space and their role in post-myocardial infarction remodeling and the potential for the use of the pericardial space as a delivery vehicle for treatments to modulate heart healing.

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies.

Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.

Post-Operative Adhesions: A Comprehensive Review of Mechanisms.

Post-surgical adhesions are common in almost all surgical areas and are associated with significant rates of morbidity, mortality, and increased healthcare costs, especially when a patient requires repeat operative interventions. Many groups have studied the mechanisms driving post-surgical adhesion formation. Despite continued advancements, we are yet to identify a prevailing mechanism. It is highly likely that post-operative adhesions have a multifactorial etiology. This complex pathophysiology, coupled with our incomplete understanding of the underlying pathways, has resulted in therapeutic options that have failed to demonstrate safety and efficacy on a consistent basis. The translation of findings from basic and preclinical research into robust clinical trials has also remained elusive. Herein, we present and contextualize the latest findings surrounding mechanisms that have been implicated in post-surgical adhesion formation.

An overview of human pericardial space and pericardial fluid.

The pericardium is a double-layered fibro-serous sac that envelops the majority of the surface of the heart as well as the great vessels. Pericardial fluid is also contained within the pericardial space. Together, the pericardium and pericardial fluid contribute to a homeostatic environment that facilitates normal cardiac function. Different diseases and procedural interventions may disrupt this homeostatic space causing an imbalance in the composition of immune mediators or by mechanical stress. Inflammatory cells, cytokines, and chemokines are present in the pericardial space. How these specific mediators contribute to different diseases is the subject of debate and research. With the advent of highly specialized assays that can identify and quantify various mediators we can potentially establish specific and sensitive biomarkers that can be used to differentiate pathologies, and aid clinicians in improving clinical outcomes for patients.