Percutaneous image-guided thermal ablation has gained wide acceptance among physicians for the treatment of benign and malignant tumors of the musculoskeletal system. Increasing evidence to support the efficacy of thermal ablation techniques in primary and adjuvant treatment of soft-tissue sarcomas, treatment of oligometastatic disease to bone and soft tissue, and metastatic pain palliation has positioned interventional oncology alongside surgery, systemic therapies, and radiation therapy as the fourth pillar of modern comprehensive cancer care. Despite the expanding indications and increasing use in clinical practice, thermal ablation carries a significant risk of injury to the adjacent vulnerable structures, predominantly the skin, bowel, and neural structures.
View Article and Find Full Text PDFHypertrophic cardiomyopathy (HCM) affects approximately 600,000 people in the United States. Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of HCM, with the majority of mutations resulting in haploinsufficiency. To restore cardiac MYBPC3, we use an adeno-associated virus (AAV9) vector and engineer an optimized expression cassette with a minimal promoter and cis-regulatory elements (TN-201) to enhance packaging efficiency and cardiomyocyte expression.
View Article and Find Full Text PDFHematopoietic stem cell transplantation (HSCT) is the only definitive cure for pediatric acute myeloid leukemia (AML). Despite adjustments in HSCT protocols and improvements in supportive care, 30% of high-risk patients who receive HSCT as part of their therapy still experience disease relapse with high transplant-related mortality. Relapsed AML has a dismal prognosis, and novel therapies are needed.
View Article and Find Full Text PDFThe urgency for climate action is recognized by international government and healthcare organizations, including the United Nations (UN) and World Health Organization (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at the highest risk, an inequity further exacerbated by differences in access to healthcare globally.
View Article and Find Full Text PDFThe urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally.
View Article and Find Full Text PDFSARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed.
View Article and Find Full Text PDFBackground: Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes.
Methods: Among 51 859 UK Biobank participants (mean age, 56.
Cerebrovascular injuries leading to edema and hemorrhage after ischemic stroke are common. The mechanisms underlying these events and how they are connected to known risk factors for poor outcome, like obesity and diabetes, is relatively unknown. Herein we demonstrate that increased adipose tissue lipolysis is a dominating risk factor for the development of a compromised cerebrovasculature in ischemic stroke.
View Article and Find Full Text PDFHeart failure is a leading cause of morbidity and mortality. Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides, which act through their receptor (NPR1) to affect vasodilation, diuresis and natriuresis, lowering venous pressures and relieving venous congestion. Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect.
View Article and Find Full Text PDFBackground: False-positive results on screening mammography may affect women's willingness to return for future screening.
Objective: To evaluate the association between screening mammography results and the probability of subsequent screening.
Design: Cohort study.
Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.
Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.
Background: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a pan-scan (head/cervical spine [C-spine]/torso) or a selective scan (head/C-spine ± torso). We hypothesized that a patient's initial history and examination could be used to guide imaging.
View Article and Find Full Text PDFBackground: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community.
View Article and Find Full Text PDFBackground: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood.
View Article and Find Full Text PDFObjective: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries.
Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology.
Transl Lung Cancer Res
February 2024
Arterioscler Thromb Vasc Biol
April 2024
Background: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.
Methods: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology.
Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell.
View Article and Find Full Text PDFOncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA). Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation.
View Article and Find Full Text PDFBackground: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown.
Objectives: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls.
Chemosphere
January 2024
Current study had made a significant progress in microalgal wastewater treatment through the implementation of an economically viable polyethylene terephthalate (PET) membrane derived from plastic bottle waste. The membrane exhibited an exceptional pure water flux of 156.5 ± 0.
View Article and Find Full Text PDFHealth Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress.
View Article and Find Full Text PDFBackground: Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era.
Methods: We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support.