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Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders a Review
No full textPegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21’s associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100
Pharmacological Update and Emerging Treatments of Pulmonary Hypertension
No full textPulmonary hypertension (PH) is defined as elevated pressures in the pulmonary artery and is associated with significant morbidity and mortality. The World Health Organization classifies PH into 5 distinct groups based on underlying etiology, pathology, and modality of treatment. Therapeutic approach may be challenging due to the extensive spectrum of causes and underlying mechanisms mediating PH. The 5 groups include pulmonary arterial hypertension (group 1), PH secondary to left heart disease (group 2), PH secondary to chronic lung disease (group 3), chronic thromboembolic pulmonary hypertension (group 4), and PH due to miscellaneous causes (group 5). Although significant progress has been made in the treatment of group 1 PH, there is a continued need to develop new therapies for all types of PH. Additionally, most treatments currently available improve functional capacity and symptoms but without a significant benefit in mortality. In this review, we aim to describe the various etiologies of PH and their established pharmacotherapies, as well as expand on emerging therapeutic options for each group
Cardiopulmonary Resuscitation Education in United States Schools: Shortcomings and Future Directions
No full textCardiopulmonary 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\u27s 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\u27 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
No full textHIV 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
Echocardiographic Parameters and Risk Prediction in Pulmonary Arterial Hypertension: Insights From the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Network
No full textBackground: Echocardiographic metrics of right ventricular (RV) chamber size and function enhance prognostication, risk stratification, and measurement of therapeutic response in patients with pulmonary arterial hypertension (PAH), though the most effective metrics remain unclear. Research Question: In a well-phenotyped cohort of patients with incident and prevalent PAH, can qualitative grades of RV echocardiographic function be established based on their association with functional outcomes, and do they demonstrate prognostic value beyond traditional risk scores? Study Design and Methods: In the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) program, 405 (prevalent, n = 336; incident, n = 69) participants were investigated. Multivariable linear regression examined associations with 6-minute walk distance and the Comparative Prospective Registry for Newly Initiated Therapies (COMPERA) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 PAH risk scores. Penalized Cox regression was used to develop new models combining prior risk score variables with echo parameters. Cluster analysis combined with survival analysis adjusting for potential confounders was used to demonstrate prognostic significance. Results: In both incident and prevalent PAH, reduced RV function was associated with increased N-terminal pro-B-type natriuretic peptide levels, reduced 6-minute walk distance, and increased COMPERA and REVEAL Lite 2.0 risk scores after adjusting for duration of PAH and relevant confounders. The addition of echocardiographic variables to models incorporating the COMPERA and REVEAL 2.0 scores yielded a 10% increase in the C-statistic. The severe RV dysfunction group was associated with increased all-cause mortality, with up to a threefold increase in mortality in multivariable models adjusted for relevant confounders, PAH duration, and invasive pulmonary vascular resistance. Interpretation: Our results show that reduced RV function on echocardiography in PAH is associated with worsened outcomes in incident and prevalent PAH. Echocardiographic assessment of RV function provided additional value to existing PH risk prediction scores and invasive hemodynamics. Furthermore, defining severity of RV function through cluster analysis has important implications for risk prognostication, with potential application to monitor response to therapy
Early Outcomes After Initiation of Faricimab in Patients With Diabetic Macular Edema
No full textBACKGROUND AND OBJECTIVE: This study evaluated treatment patterns and outcomes among patients with diabetic macular edema (DME) treated with the bispecific antibody faricimab in routine clinical practice in the United States. PATIENTS AND METHODS: FARETINA-DME was a retrospective study among patients with DME initiating faricimab from February 2022 to June 2023 identified from the United States IRIS® Registry. RESULTS: Four thousand five hundred fourteen (4,514) patients (6,204 eyes) previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy and 691 treatment-naïve patients (851 eyes) were included. In previously treated eyes, mean ± SD visual acuity was 64.0 ± 18.3 letters at index and 65.3 ± 19.0 at faricimab injection 4. In treatment-naïve eyes, visual acuity improved from 60.3 ± 19.8 to 63.9 ± 18.5 letters (P \u3c 0.01). Mean ± SD central subfield thickness improved from 364.3 ± 132.2 to 330.1 ± 121.2 μm in previously treated eyes and 359.6 ± 115.0 to 307.4 ± 114.6 μm in treatment-naïve eyes (both P \u3c 0.01). CONCLUSIONS: In patients with DME receiving far-icimab, visual acuity was maintained in previously treated and improved in treatment-naïve eyes. Both groups had anatomical improvement
Pediatric Cancer Rehabilitation: An Overview With Special Considerations in Transitional Care for Adolescents and Young Adults and Palliative Rehabilitation
No full textTraditional Chinese Medicine for Pediatric Allergic Diseases
No full textPurpose of Review: There is a clinically important and unmet need for long-term safe and effective preventative and therapeutic options for pediatric allergic diseases. This communication reviewed the use of Traditional Chinese Medicine (TCM) in pediatric allergic disease, including eczema, urticaria, eosinophilic esophagitis (EoE), food allergy (FA), asthma, and allergic rhinitis. Recent Findings: Through evaluation of case studies, series, or clinical trials of pediatric allergy patients, or in vitro studies involving samples collected from pediatric allergy patients and in vivo model systems, naturally occurring small molecule compounds’ mechanism of action by evidence-based scientific outcomes were elucidated. Notable clinical outcomes include reduction in severity score, reduction across various allergic diseases that demonstrated no toxicity, no severe adverse effects, and are well-tolerated. Immunological outcomes that attribute to this include a switch from Th2-mediated allergic response to a Th1/Treg response, characterized by reduced total and specific IgE, total eosinophil counts, and levels of exotoxin, TNF-a, IL-6, IL-8, IL-5, and IL-4, with elevated levels of IFN-γ and IL-10. For eczema, both multiple and single herbal formulations are common treatment modalities, including internal administration and external herbal baths and creams, whereby both provide substantial beneficial outcomes. For EoE, internally administrated formulations and use of acupuncture have been reported and shown mitigation of allergic responses. In FA, formulations have been studied in clinical trials showing consistent safety, with protection remaining to be established. More advanced development of single herbal compounds may provide an advantage for use in FA treatment. For allergic rhinitis, several multiple herbal formulations and acupuncture have demonstrated improved symptom scores. Similarly, in asthma herbal formulas and acupuncture were highly clinically effective. Summary: TCM has demonstrated high safety and efficacy in both preclinical and clinical models of various allergic diseases, including eczema, food allergy, eosinophilic esophagitis, allergic rhinitis, and asthma. Therefore, this scientific evidence suggests that naturally occurring small molecule compounds are promising preventives and therapeutics for pediatric allergic diseases. Disclosure: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and national/institutional guidelines)
A Review of Alpha-Gal Syndrome for the Infectious Diseases Practitioner
No full textAlpha-gal syndrome (AGS) is an emerging allergic disease caused by an immunoglobulin E (IgE) response to galactose-α-1,3-galactose (alpha-gal), a sugar found in mammalian meat. The initial IgE sensitization follows a bite from the Amblyomma americanum (lone star) tick in the United States, although other tick species can also cause the disease. AGS presents with delayed symptoms, primarily gastrointestinal or allergic reactions like urticaria or anaphylaxis, hours after mammalian meat consumption. The nonspecificity of the symptoms can delay the diagnosis of AGS for years. Diagnosis relies on clinical evaluation and detection of alpha-gal-specific IgE in blood. As the lone star tick\u27s range is expanding beyond the southern United States, AGS is gaining recognition in other regions. However, many healthcare providers remain unaware of the condition, leading to misdiagnosis. Infectious diseases physicians who frequently evaluate patients with tick exposure must be familiar with AGS, including tick identification, bite prevention, and knowledge of the alpha-gal-containing vaccines
Brexpiprazole in the Management of Schizophrenia: A Consensus Report of Best Practices From Acute to Maintenance Treatment
No full textBrexpiprazole is a second-generation antipsychotic with multiple indications, including the treatment of schizophrenia. As a partial dopamine agonist, brexpiprazole differs from most other antipsychotics, yet uncertainties about its full mechanism of action have led to some ambiguity among prescribers. To address this gap, an international panel of psychiatric experts was organized and convened with funding from Otsuka Pharmaceutical Europe Ltd and H. Lundbeck A/S to discuss the safe and effective use of brexpiprazole across different stages of schizophrenia treatment. Brexpiprazole’s pharmacological profile—characterized by balanced binding affinities across norepinephrine, dopamine, and serotonin receptors—contributes to its efficacy in multiple symptom domains, including agitation and negative symptoms. Its tolerable safety profile, marked by minimal activation and minimal sedation and a relatively low risk of long-term cardiometabolic concerns, further supports its clinical utility. Brexpiprazole is a viable first-line therapy in both inpatient and outpatient settings when properly titrated and monitored. Brexpiprazole also serves as an option for different symptom domains in schizophrenia and for patients needing to switch antipsychotics due to inadequate symptom control or intolerable adverse events. Long-term maintenance therapy is essential for relapse prevention in schizophrenia, and when prescribed at appropriate doses for psychotic symptom control, brexpiprazole can provide sustained benefits with minimal long-term safety concerns. This report outlines the consensus panel’s recommendations on the optimal initiation and administration of brexpiprazole in management of schizophrenia treatment, including a treatment algorithm, which is supported by a literature review