Citations

DNA methylation is an essential epigenetic modification that plays a crucial role in regulating gene expression and maintaining genomic stability. With the advancement in sequencing technology, methylation studies have provided valuable insights into the diagnosis of rare diseases through the various identification of episignatures, epivariation, epioutliers, and allele-specific methylation. However, current methylation studies are not without limitations. This mini-review explores the current understanding of DNA methylation in rare diseases, highlighting the key mechanisms and diagnostic potential, and emphasizing the need for advanced methodologies and integrative approaches to enhance the understanding of disease progression and design more personable treatment for patients, given the nature of rare diseases.

Giant cell arteritis (GCA) is a relapsing large vessel vasculitis with risk of serious ischemic manifestations, including vision loss and vascular damage in the form of large artery stenosis, aneurysms, and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life‐ or organ‐threatening presentations and can be controlled successfully, frequent relapses may lead to increased prescription of GC and consequent treatment‐related morbidity, in addition to risk of further vascular damage. Emerging data suggest that persistent disease activity may lead to increased vascular morbidity. Additionally, although tocilizumab decreases the frequency of relapses, more than 50% of patients relapse after discontinuation of therapy. Therefore, although interleukin‐6 blockade suppresses disease activity, it does not restore tolerance. In this article, we discuss the practical diagnosis and management of GCA relapses from an expert perspective. Current treatment options for GCA relapses, including those recommended by international guidelines, and novel potential therapies are reviewed.

Abstract Background: Tracheobronchomalacia (TBM) presents diagnostic challenges due to its nonspecific symptoms and variability in diagnostic methods. This study evaluates physician concordance in TBM diagnosis and phenotyping using chest computed tomography (CT) scans with dynamic expiratory views. Methods: We conducted a retrospective cross-sectional study at Mayo Clinic Rochester, analyzing 150 patients with dynamic expiratory CT scans. Three specialists—a thoracic radiologist, a bronchoscopist, and a pulmonologist—reviewed identical CT scans, blinded to prior interpretations. Inter-rater agreement was assessed using Fleiss's Kappa for TBM diagnosis and Cohen's Kappa for TBM phenotype classification into six categories: No TBM, Excessive Dynamic Airway Collapse (EDAC), Crescent Type, Circumferential Type, Saber-Sheath Type, and Mixed Type. Results: Among the 150 patients, 54 (36%) were diagnosed with TBM or EDAC. TBM was more prevalent in males, older individuals, and smokers. Agreement among specialists was substantial for TBM diagnosis (Fleiss’s Kappa = 0.61, p < 0.001) but moderate for phenotype classification (Fleiss’s Kappa = 0.52, p < 0.001). The highest concordance was between the thoracic radiologist and the pulmonologist (Cohen's Kappa = 0.68), while the lowest was between the bronchoscopist and other specialists. Conclusion: There is substantial agreement in TBM diagnosis using chest CT scans with dynamic expiratory views, but moderate variability in phenotyping. Standardizing criteria and integrating pulmonary function testing could enhance diagnostic consistency and clinical relevance.

Abstract Aims We aimed to perform a retrospective cohort study using the Centers for Disease Control and Prevention’s (CDC’s) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyse the trends in cardiovascular disease (CVD)–related mortality in patients with myeloproliferative neoplasms (MPNs) from 1999 to 2020. Methods and results We analysed the death certificate data from the CDC WONDER database from 1999 to 2020 for CVD with co-morbid myeloproliferative disorders in the US population. Age-adjusted mortality rates (AAMRs) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual national mortality trends, we employed the Joinpoint regression model, calculating the annual per cent change in AAMR and corresponding 95% CIs. A total of 15 269 deaths related to CVD occurred in patients with co-morbid MPNs from 1999 to 2020. Overall, there was a decreasing trend in CVD-related AAMRs throughout these years. Males contributed to 51% of total deaths, and their AAMR was persistently higher than women throughout the study. Non-Hispanic (NH) Whites had the highest overall AAMR, followed by NH Blacks, NH American Indians or Alaska Natives, Hispanics or Latinos, and NH Asian or Pacific Islanders. Conclusion Our findings indicate a significant decline with notable gender, racial/ethnic, and regional differences in CVD-related mortality among patients with MPN over the past two decades. We emphasize the importance of a collaborative approach between oncologists and cardiologists in managing these patients, highlighting the potential benefits of integrating cardio-oncology services to enhance patient outcomes.