Navigating Post-Traumatic Osteoporosis: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis, Treatment, and Future Directions.

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies' efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes.

Ninerafaxstat in the Treatment of Cardiometabolic Disease: Shifting Metabolic Paradigms.

Cardiovascular disease (CVD) refers to a wide array of conditions that damage the heart muscle and impede its ability to effectively circulate blood throughout the body. In damaged or pathological states, the heart muscle might not function as effectively as it would have had there been no insult to it. Understanding this, certain CVDs can put the heart in a "metabolic disadvantage"-a state in which it cannot synthesize energy stores, in the form of adenosine triphosphate (ATP), as efficiently as it was once able to do. While the heart typically uses fatty acids for its ATP synthesis, the metabolic processes required to do so consume more oxygen per mole than the processes required to convert glucose (or carbohydrates) to ATP. In conditions when oxygen demand outweighs supply-such as angina, heart failure, and certain inherited CVDs-the myocardium can more efficiently run via glucose oxidation. Despite this knowledge, there are no currently approved therapeutics or interventions that encourage this "metabolic shift" in the myocardial cells. Currently in phase II clinical trials, however, is a novel medication called ninerafaxstat. This novel drug is a partial inhibitor of fatty acid oxidation and thus pushes the heart to convert glucose (instead of fatty acids) to ATP-ultimately cutting down on oxygen supply. While still completing clinical trials, ninerafaxstat must undergo further safety and efficacy evaluation before it can be used as a standard of care. If, however, the drug makes it to market, it might offer a unique way to improve both the symptoms and quality of life of the millions of Americans who suffer from CVDs.

Percutaneous Tricuspid Valve Repair: The Triclip.

Tricuspid regurgitation is an often overlooked, but severe cardiac valvular disease associated with significant morbidity and poor quality of life. Tricuspid valve surgery is the only treatment that prevents progression of the disease but is often complicated or made impossible by perioperative risk factors. Due to the high-risk nature, tricuspid valve surgery is typically only done for severe tricuspid regurgitation at the time of left heart surgery, leaving many patients untreated. Medical therapy is limited primarily to diuretic agents, which are often unsuccessful in alleviating symptoms. Treatment of tricuspid regurgitation with transcatheter edge-to-edge repair has emerged after the success of this technique in mitral valve pathologies. This percutaneous procedure parallels surgical principles previously used for valve repair but eliminates the need for cardiac surgery, thus having the potential to serve as an alternative treatment in high-risk patients. The TriClip (Abbott Labs) device is an example of this therapy and the subject of this review.

Cardiopulmonary Resuscitation Education in United States Schools: Shortcomings and Future Directions.

Cardiopulmonary resuscitation (CPR) is a lifesaving procedure that is performed during a cardiac arrest. CPR consists of chest compressions, rescue breaths, and the usage of an automated external defibrillator (AED) based on availability. Performance of CPR can greatly increase the chances of survival by enabling the manual perfusion of vital organs in lieu of the heart's normal function. Despite extensive studies demonstrating the efficacy and necessity of CPR in an emergency, most of the public across the United States is ill-equipped and/or educated on how to perform it. While there may be other contributing factors, the lack of CPR education across schools in the United States almost certainly furthers the CPR illiteracy of the general population. Although states require some degree of CPR training, the level of education that students receive varies widely across communities and school districts, largely dictated by the available funding for training courses. Despite the lack of CPR education in the United States, studies conducted abroad have shown the efficacy of a CPR course in preparing students to respond in emergencies-lending hope to mending the current situation in the United States. In this article, we analyze legislation dictating CPR instruction and hypothesize ways in which states' Department of Education might be able to promote education and hands-on experience for students across all ages of schooling. Ultimately, we hope to highlight the importance and feasibility of preparing the next generation of citizens across the United States to respond when their name is called upon in an emergency.

Pitavastatin in the Prevention of Cardiovascular Disease in People Living with HIV: A Review.

HIV is associated with a wide array of pathophysiologic mechanisms that ultimately contribute to mortality. While HIV is traditionally known as a disease that attacks the immune system, it is now established that infection with HIV can cause cardiovascular disease (CVD). Through inflammation, atherogenesis, interactions with antiretroviral therapy/highly-active antiretroviral therapy (ART/HAART), and other mechanisms, HIV is an independent risk factor for the development of CVD. The treatment of the CVD risks associated with HIV is complicated, especially due to interactions with hyperlipidemic drugs and ART/HAART. There is a prompt need for a drug (or drug class) that is known to reduce the risk of CVD, specifically in people living with HIV. Recently, the randomized trial to prevent vascular events in HIV trial evaluated the usage of pitavastatin in preventing major cardiac events in people with HIV, showing a significant reduction in cardiac events among those taking the therapeutic. In this review, we evaluate the mechanisms by which HIV contributes to CVD, and the randomized trial to prevent vascular events in HIV trial, and postulate about future directions of the drug in treating people living with HIV.

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

IMPORTANCE: The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

The vascular complications of diabetes: a review of their management, pathogenesis, and prevention.

INTRODUCTION: This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED: We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION: Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.

Factor XI/XIa Inhibitors: A New Approach to Anticoagulation.

For more than 60 years, anticoagulation drugs have served as a mainstay in preserving and improving the cardiovascular health of patients across the globe. Functioning to reduce a patient's ability to produce blood clots, prescription rates for anticoagulants have been steadily rising year-over-year both in the United States and abroad. Despite decades of clinical usage, modern-day anticoagulants have been shown to predispose an individual to pathological bleeding. Even in seemingly benign instances of bleeding, patients on anticoagulation therapy might require intensive and expensive medical procedures or monitoring. Understanding the clinical implications of pathological bleeding, research and development of future anticoagulants seeking to minimize these effects. One emerging category of anticoagulant drugs are Factor XI/XIa (FXI) inhibitors. Targeting the coagulation cascade, clinical trials of Factor XIa inhibitors have shown promising results in preventing blood clot formation without increasing the instances of spontaneous and/or pathological bleeding events. While still in phase II and III clinical trials, and potentially years away from being implemented as standard of care, these novel drugs might have the potential to improve the safety and quality of life of patients taking anticoagulants. In this review, we discuss a brief history of anticoagulation therapy, followed by an analysis of the potential risks, benefits, and implications of Factor XI/XIa inhibitors across elements of patient care.

Artificial Intelligence in the Prevention and Detection of Cardiovascular Disease.

For more than 60 years, artificial intelligence (AI) has served as a mainstay in augmenting and assisting the lives of individuals across a wide array of interests and professional fields. Functioning to create deep computer simulations, analyze data, solve problems, and synthesize human behavior/emotion, AI has recently become a topic of popular interest in many fields of medicine. Despite decades of usage, modern AI-and its newer branch of machine learning (ML)-have yet to find a fully established and regulated niche in medicine. Understanding the clinical implications that AI and ML might be able to play in cardiovascular medicine, studies have sought to understand and compare how this technology compares with human rationality and diagnostics. Utilizing AI and ML in an array of cardiovascular medical techniques, analyses, and predictive measurements seems to have produced accurate results while also saving healthcare providers time and enabling them to expand their reach to further populations. Although current research and literature might hypothesize AI's potential clinical applications, it is nearly impossible to fully understand the breadth and scope that this new technology can play in the future. In this article, we attempt to analyze a few of the potential applications of AI and ML for the detection, prevention, and treatment of cardiovascular disease. Additionally, we discuss how AI might make cardiovascular care more equitable and highlight a few precautions for utilizing this technology.

Immune response, phenotyping and molecular graft surveillance in kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 vaccination.

BACKGROUND: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS: We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS: Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS: SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

Cardiac Xenotransplantation: Barriers, Future Directions, and Ethical Considerations.

Since data collection began in 1995, 12,713 people have died while waiting for a heart transplant. Combined with a significant number of individuals with end-stage organ disease-eligible and waiting to receive a transplant offer-is a critical shortage of registered organ donors and acceptable organs. Strategies to overcome this organ shortage include efforts to increase the number of individuals registered as donors as well as new therapeutic approaches to managing organs that would have been otherwise deemed unacceptable for donation. One emerging technology that has the potential to further alleviate the demand for organs is xenotransplantation, where genetically engineered animal tissue or organ is transplanted into a human patient. While still in its elementary phases, this method shows great promise in reducing transplant wait-time and ultimately improving the quality of life and survival rate of transplant recipient patients. In 2021-2022, researchers at the University of Maryland Medical Center performed the first pig-to-human cardiac xenotransplantation on a live recipient. This review analyzes the case and discusses barriers, future directions, and ethical considerations to implementing cardiac xenotransplantation as a standard of care.