Mogensenbech8984

T2-low patients with severe asthma had significantly lower 24-hour cough frequency compared to T2-intermediate and T2-high patients.

In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2-eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies.

In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2-eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies.We read with great interest the study investigating the association between immunosuppressant and the outcome of patients withs SARS-CoV-2 infection [1]. They found that the prior use of immunosuppressant would be associated with a significantly increased risk of death (adjusted relative risk [RR], 1.56; 95% CI, 1.10–2.22) which was mainly driven by exposure to systemic glucocorticoids (aRR, 2.38; 95% CI 1.72–3.30). Overall, it is a well-designed study; however, we have three concerns about the findings of this study.Relievers account for the majority of inhaler use and associated GHG emissions. Implementing treatment guidelines can reduce the unmet need in respiratory care by improving disease control and reducing reliever overuse and the overall carbon footprint. https//bit.ly/3zh3c2B

COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase-1 (hCMA1) and it's ortholog mCMA1/mouse mast cell (MC) protease-5 (mMCP5) are exocytosed from activated MCs and have adverse roles in numerous disorders, but their role in COPD is unknown.

We evaluated hCMA1 levels in lung tissues of COPD patients. We used

-deficient (

) mice to evaluate this proteases' role and potential for therapeutic targeting in CS-induced experimental COPD. We also used

studies to define mechanisms.

The levels of hCMA1 mRNA and CMA1

MCs were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated MC numbers and mMCP5 protein were increased in lung tissues of wild-type (WT) mice with experimental COPD.



mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of MCs from WT but not



mice with WT lung macrophages increased in TNF-α release. It also caused the release of CMA1 from human MCs, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.

CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.

CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.

Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma. Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO) and nuclear/extranuclear antigens (antinuclear antibodies (ANAs)) have been reported. Our objective was to describe the prevalence and clinical characteristics of asthmatic patients with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity.

We analysed anti-EPX, anti-MARCO and ANAs in 218 sputum samples collected prospectively from 148 asthmatic patients, and evaluated their association with lung function parameters, blood/airway inflammation, severity indices and exacerbations. Additionally, 107 of these patients consented to fill out an autoimmune checklist to determine personal/family history of systemic autoimmune disease and symptoms.

Out of the 148 patients, 59 (40%) were anti-EPsts despite anti-inflammatory treatment and is associated with exacerbations.

We report 55% of moderate-severe asthmatic patients to have airway autoreactivity that persists despite anti-inflammatory treatment and is associated with exacerbations.Corticosteroids were the first drugs proven to reduce mortality in Covid-19. In June 2020, the RECOVERY group announced the results of their seminal trial showing dexamethasone 6 mg per day was able to reduce 28-day mortality in hospitalized patients with Covid needing supplemental oxygen or mechanical ventilation [1]. Meta-analysis from randomized controlled trials (RCT) in Covid-19 patients confirmed RECOVERY results [2]. In those RCTs, corticosteroid doses were low (dexamethasone 6 mg per day) or intermediate (dexamethasone up to 20mg per day).Global access to rifapentine is essential to implement the latest WHO recommendations on treatment of TB infection and disease. Measures to increase access to rifapentine include strengthening regulatory reliance practices. https//bit.ly/3xNDwID

Accumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development; however, the role of BMP4 in modulating lung fibrosis remains unknown.

The aim of this study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts and lung samples from patients with IPF.

BMP4 expression was downregulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with transforming growth factor (TGF)-β1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblbrosis.Cardiac hypertrophy (CH) is a pathological phenotype of cardiomyopathy. Epigenetic modification is a mechanism associated with CH. Our study here investigated the histone demethylase KDM3C in relation to epigenetic regulation in CH. Eltanexor inhibitor We found that KDM3C mRNA silencing alleviated CH, as evidenced by reduced ANP, BNP, and β-MHC mRNAs, increased α-MHC mRNA, decreased cell surface area, and reduced cellular protein/DNA ratios. Specifically, KDM3C upregulated miR-200c-3p expression through demethylation of H3K9me2, leading to enhanced binding of miR-200c-3p to GAS5 and suppression of GAS5 expression; these effects then led to reduced binding of GAS5 to miR-495-3p, increased miR-495-3p expression, and repression of PHF8 transcription. Through these mechanisms, our data indicate that KDM3C-dependent epigenetic modification promotes CH.A 70-year-old man with mCRPC (metastatic castration-resistant prostate cancer) was referred for 68 Ga-PSMA PET/CT for restaging and the possibility of targeted molecular radioligand therapy with 177 Lu-PSMA. Numerous 68 Ga-PSMA-avid skeletal metastases with low SUVs were noted. Because of low PSMA expression, a 68 Ga-FAPI-46 PET/CT was performed to evaluate the eligibility for FAPI-based radioligand therapy. There were some discordant findings between 68 Ga-PSMA and 68 Ga-FAPI PET/CT scans regarding the detectability of lesions and SUVs. Our case signifies that 68 Ga-FAPI theragnostic may have a potential role in the treatment of mCRPC patients with insignificant PSMA expression or in cases after the failure of 177 Lu-PSMA therapy.[This corrects the article DOI 10.14423/SMJ.0000000000001104.].

Patients who develop cytokine storm while they have coronavirus disease 2019 (COVID-19) experience more severe symptoms. This article aims to evaluate the effect of biochemical parameters on the clinical course of the disease in patients treated with tocilizumab (TCZ) due to cytokine storm.

Medical documents of patients with COVID-19 were searched retrospectively. Patients who entered cytokine storm were classified as group 1 and divided into two subgroups as patients who were followed up in the ward and in the intensive care unit (ICU). Less severe COVID-19 patients who did not enter cytokine storm were included in the control group as group 2.

A total of 522 patients with COVID-19 infection were included in the study. The mean age was 62.0 ± 15.6 years, and the majority were male (64.4%). Hypertension and diabetes mellitus were the two most common diseases, seen in 50.8% and 29.9%, respectively. There were 392 patients with TCZ application (group 1) and 130 patients without TCZ (group 2). Significantly higher serum glucose, magnesium, and sodium and lower calcium levels were present in group 1 than in group 2 (<0.001). Hypocalcemia, hypernatremia, hypermagnesemia, and hyperkalemia were more frequently detected in the ICU compared with the patients treated in the wards (

0.001,

0.001,

0.039, and

0.001, respectively).

Following up closely electrolyte disturbances may support patient survival and decrease the probability of ICU necessity. This approach should be taken before the development of important disorders to be effective in the treatment process of the main disease.

Following up closely electrolyte disturbances may support patient survival and decrease the probability of ICU necessity. This approach should be taken before the development of important disorders to be effective in the treatment process of the main disease.

People with human immunodeficiency virus (HIV) are at an increased risk of developing cardiovascular diseases. Hypertensive emergency (HTNE), a complication of hypertension with potentially serious health implications, has high healthcare utilization. We attempted to determine the association between HIV status and risk for 30-day readmission after index hospitalization for HTNE.

We used the Nationwide Readmissions Database to identify all of the admissions during 2010-2017 with a primary discharge diagnosis of HTNE. Admissions were stratified by HIV status and comparisons were made with the χ

test. We investigated predictors of all-cause 30-day readmission via multivariable logistic regression.

A total of 612,854 hospitalizations with a primary discharge diagnosis of HTNE were identified, and 4115 (0.7%) were HIV positive. There was a total of 43,937 (7.16%) 30-day readmissions, and the rate was higher in regard to positive HIV status (29.8% vs 15.0%;

< 0.001). Renal failure was the most frequent reason for HIV readmissions and the second most frequent reason for non-HIV readmissions (15.6% vs 10.3%;

< 0.001). In contrast, heart failure was the most frequent reason for non-HIV readmissions and the second most frequent reason for HIV readmissions (10.3% vs 11.9%;

= 0.234). There was a higher median cost for HIV readmissions in comparison to non-HIV readmissions ($7660 vs $7490;

< 0.001). Finally, HIV was attributed to 40.6% increased odds of readmission after adjusting for pertinent clinical and demographic factors (

< 0.001).

HIV-positive status is associated with an increased risk for 30-day readmission after index hospitalization for HTNE.

HIV-positive status is associated with an increased risk for 30-day readmission after index hospitalization for HTNE.