ABSTRACT
PURPOSE OF REVIEW: Myeloproliferative neoplasm (MPN) burdens the lives of those affected. MPN patients endure significant impacts on their physical, psychological, and social well-being. While pharmacological interventions offer some disease and symptom control, they often have unfavorable side effects. This review explores the potential of Integrative Oncology (IO) therapies in managing MPNs and their associated symptoms. RECENT FINDINGS: IO is dedicated to augmenting conventional treatments through integrating interventions targeting the mind, body, nutrition, supplements, and other supportive care therapies. Several small studies suggest the benefit of an IO approach in MPN patients. These benefits are postulated to be modulated through enhanced physical capacity, reduced disease-related inflammation, subconscious mind training, and gut microbiome modulation. By combining IO with evidence-based pharmacological treatments, the potential exists to enhance the quality of life and clinical outcomes for individuals with MPNs. Future research should prioritize well-powered studies, including diverse demographics and symptom profiles, with appropriate study duration, to draw definite conclusions regarding the observed effects.
ABSTRACT
Type A aortic dissection (AD) is a devastating cardiovascular emergency requiring emergent surgical intervention. Most patients with AD have several risk factors for the disease including longstanding hypertension, smoking history, atherosclerosis, and old age. Younger patients may also present with AD if a genetic disorder affecting the integrity of the aorta is present. This case presents an otherwise healthy 36-year-old male with no known significant family history who presented with an atypical presentation of aortic dissection. He described a five-day history of chest pressure made worse with exertion followed by progressive dyspnea which prompted him to seek medical attention. His initial laboratory workup revealed an elevated troponin I level which prompted a cardiology consultation in the emergency department. Transthoracic echocardiography revealed dilatation of the aortic root and aortic regurgitation. CT angiography of the chest was performed revealing a type A dissection beginning at the aortic root and terminating proximal to the right brachiocephalic artery. Involvement of the coronary arteries was suspected due to the elevated troponin I. He was taken to the operating room and underwent aortic grafting, right coronary artery bypass, and repair of the left main artery. Unfortunately, at the end of the operation, the patient went into refractory ventricular fibrillation, which progressed to asystole. He was unable to be revived.
ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by pathogenic variants in sarcomeric genes, leading to left ventricular hypertrophy and complex phenotypic heterogeneity. While HCM is the most common inherited cardiomyopathy, pharmacological treatment options have previously been limited and were predominantly directed towards symptom control owing to left ventricular outflow obstruction. These therapies, including beta blockers, calcium channel blockers, and disopyramide, have not been shown to affect the natural history of the disease, which is of particular concern for younger patients who have an increased lifetime risk of experiencing arrhythmias, heart failure, and sudden cardiac death. Increased knowledge of the genetic mechanisms underlying this disease in recent years has led to the development of targeted, potentially disease-modifying therapies for both obstructive and nonobstructive phenotypes that may help to prevent or ameliorate left ventricular hypertrophy. In this review article, we will define the etiology and clinical phenotypes of HCM, summarize the conventional therapies for obstructive HCM, discuss the emerging targeted therapies as well as novel invasive approaches for obstructive HCM, describe the therapeutic advances for nonobstructive HCM, and outline the future directions for the treatment of HCM.
ABSTRACT
Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy has produced dramatic responses in hematologic malignancies. One of the challenges in the field is the lack of a simple assay for the detection of CARs on the surface of immune effector cells. In this study, we describe a novel luciferase-based assay, termed Topanga Assay, for the detection of CAR expression. The assay utilizes a recombinant fusion protein, called Topanga reagent, generated by joining the extra-cellular domain of a CAR-target in frame with one of the marine luciferases or their engineered derivatives. The assay involves incubation of CAR expressing cells with the Topanga reagent, a few washes and measurement of luminescence. The assay can detect CARs comprising either immunoglobulin- or non-immunoglobulin-based antigen binding domains. We further demonstrate that addition of epitope tags to the Topanga reagent not only allows its convenient one step purification but also extends its use for detection of CAR cells using flow cytometry. However, crude supernatant containing the secreted Topanga reagent can be directly used in both luminescence and flow-cytometry based assays without prior protein purification. Our results demonstrate that the Topanga assay is a highly sensitive, specific, convenient, economical and versatile assay for the detection of CARs.
