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n post-infarction. Strategies that control bile acid metabolism and TGR5 signaling to ameliorate the inflammatory responses may provide beneficial effects in patients with myocardial infarction.Atrial fibrillation (AF) occurrence and maintenance is associated with progressive remodeling of electrophysiological (repolarization and conduction) and 3D structural (fibrosis, fiber orientations, and wall thickness) features of the human atria. Significant diversity in AF etiology leads to heterogeneous arrhythmogenic electrophysiological and structural substrates within the 3D structure of the human atria. Since current clinical methods have yet to fully resolve the patient-specific arrhythmogenic substrates, mechanism-based AF treatments remain underdeveloped. Here, we review current knowledge from in-vivo, ex-vivo, and in-vitro human heart studies, and discuss how these studies may provide new insights on the synergy of atrial electrophysiological and 3D structural features in AF maintenance. In-vitro studies on surgically acquired human atrial samples provide a great opportunity to study a wide spectrum of AF pathology, including functional changes in single-cell action potentials, ion channels, and gey to identify patient-specific arrhythmogenic substrates and develop novel AF treatments.
Blood eosinophil (EOS) counts are critical to the accurate identification of asthma phenotypes. However, there are few long-term data on intraindividual EOS count variability among patients with eosinophilic asthma.
This post hoc analysis of 2 phase III clinical trials from the reslizumab BREATH program explored the variability of blood EOS counts in patients with eosinophilic asthma receiving placebo.
Pooled data from study participants receiving placebo (previously randomized 11 to receive reslizumab or placebo) were analyzed for blood EOS count variability over 52 weeks. EOS counts were measured up to twice during screening, every 4 weeks from randomization to the end of treatment and at the 90-day follow-up visit.
Of 476 included patients, 31 (6.5%), 38 (8.0%), 55 (11.6%), and 352 (73.9%) patients had baseline blood EOS counts of <150, ≥150 to <300, ≥300 to <400, and ≥400 cells/μL, respectively. Selleck MCC950 Patients frequently shifted between EOS count categories during the 52-week treatment period, most often moving to the highest EOS category. Among patients in each of the lower 3 EOS categories, 27% to 56% of patients shifted to the ≥400 cells/μL category at some point during the treatment period.
Intraindividual variability in blood EOS count was high among patients with eosinophilic asthma receiving placebo, with shifts to ≥400 cells/μL from lower categories frequently observed. Repeat determinations of blood EOS count may be important to ensure appropriate selection of therapy in patients with severe asthma.
Intraindividual variability in blood EOS count was high among patients with eosinophilic asthma receiving placebo, with shifts to ≥400 cells/μL from lower categories frequently observed. Repeat determinations of blood EOS count may be important to ensure appropriate selection of therapy in patients with severe asthma.Asthma treatments have evolved from bronchodilators to interventions directed toward the regulation of airway inflammation. From these advances has come greater disease control and reduced morbidity. The addition of biologics directed toward specific pathways of inflammation has advanced the efficacy of asthma control. With these treatment advances, a renewed interest in achieving a remission in asthma has arisen. Although asthma remission has been considered to reflect a "cure," new evaluations of this concept have proposed criteria for remission while on treatment. These criteria reflect a high level of disease control including absence of symptoms, optimization and stabilization of lung function, and absence of the use of systemic corticosteroids and have been proposed to indicate a remission of disease activity. Given the added efficacy found with biologics in asthma treatment for patients with moderate to severe disease, the question has arisen as to whether the use of biologics meets criteria for remission and may this change a component of underlying disease and risks. Biologics are highly effective in reducing exacerbations, diminishing symptoms, and improving lung function in well-defined asthma populations. At present, however, biologics achieve some, but in most cases not all criteria for a remission on treatment. However, the concept of promoting treatment efforts to achieve disease remission in asthma is important, potentially achievable, and merits consideration for future guideline-directed care approaches.The emergence of a worldwide pandemic due to coronavirus disease 2019 (COVID-19) and frequent reports of smell loss in COVID-19-infected patients have brought new attention to this very important sense. Data are emerging that smell impairment is a prominent symptom in COVID-19 and that this coronavirus behaves differently in causing olfactory dysfunction compared with other respiratory viruses. Anosmia and hyposmia, the complete and partial loss of smell, respectively, can result from many causes, most commonly from viral infections, sinonasal disease, and head trauma. Olfactory dysfunction negatively impacts quality of life, because sense of smell is important for flavor perception and the enjoyment of food. Olfaction is also important for the detection of warning smells, such as smoke, natural gas leaks, and spoiled food. Allergists and immunologists frequently encounter anosmia and hyposmia in patients with severe chronic rhinosinusitis with nasal polyps, and will likely see more infection-induced olfactory dysfunction in the era of COVID-19. Therefore, now more than ever, it is crucial that we understand this impairment, how to evaluate and how to measure it. In this review, we offer a clinically relevant primer for the allergist and immunologist on olfactory dysfunction subtypes, exploring the pathophysiology, appropriate clinical assessment, objective smell testing, and management of this condition. We will also focus on the emerging literature on COVID-19 olfactory dysfunction, its unique features, and its important implications for this pandemic.
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