VEXAS syndrome as a cause for multifocal, relapsing head and neck inflammation.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a novel autoinflammatory syndrome. We describe a case of VEXAS syndrome with upper airway and oral cavity involvement which are not well described in the literature.

Eosinophil recruitment to nasal nerves after allergen challenge in allergic rhinitis.

In allergen challenged animal models, eosinophils localize to airway nerves leading to vagally-mediated hyperreactivity. We hypothesized that in allergic rhinitis eosinophils recruited to nasal nerves resulted in neural hyperreactivity. Patients with persistent allergic rhinitis (n=12), seasonal allergic rhinitis (n=7) and controls (n=10) were studied. Inferior nasal turbinate biopsies were obtained before, 8 and 48h after allergen challenge. Eight hours after allergen challenge eosinophils localized to nerves in both rhinitis groups; this was sustained through 48h. Bradykinin challenge, with secretion collection on the contralateral side, was performed to demonstrate nasal nerve reflexes. Twenty fourhours after allergen challenge, bradykinin induced a significant increase in secretions, indicating nasal hyperreactivity. Histological studies showed that nasal nerves expressed both vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 26 (CCL-26). Hence, after allergen challenge eosinophils are recruited and retained at nerves and so may be a mechanism for neural hyperreactivity.

Emergency medical admissions and COVID-19: impact on 30-day mortality and hospital length of stay.

BACKGROUND: The COVID-19 pandemic has put considerable strain on healthcare systems. AIM: To investigate the effect of the COVID-19 pandemic on 30-day in-hospital mortality, length of stay (LOS) and resource utilization in acute medical care. METHODS: We compared emergency medical admissions to a single secondary care centre during 2020 to the preceding 18 years (2002-2019). We investigated 30-day in-hospital mortality with a multiple variable logistic regression model. Utilization of procedures/services was related to LOS with zero truncated Poisson regression. RESULTS: There were 132,715 admissions in 67,185 patients over the 19-year study. There was a linear reduction in 30-day in-hospital mortality over time; over the most recent 5 years (2016-2020), there was a relative risk reduction of 36%, from 7.9 to 4.3% with a number needed to treat of 27.7. Emergency medical admissions increased 18.8% to 10,452 in 2020 with COVID-19 admissions representing 3.5%. 18.6% of COVID-19 cases required ICU admission with a median stay of 10.1 days (IQR 3.8, 16.0). COVID-19 was a significant univariate predictor of 30-day in-hospital mortality, 18.5% (95%CI: 13.9, 23.1) vs. 3.0% (95%CI: 2.7, 3.4)-OR 7.3 (95%CI: 5.3, 10.1). ICU admission was the dominant outcome predictor-OR 12.4 (95%CI: 7.7, 20.1). COVID-19 mortality in the last third of 2020 improved-OR 0.64 (95%CI: 0.47, 0.86). Hospital LOS and resource utilization were increased. CONCLUSION: A diagnosis of COVID-19 was associated with significantly increased mortality and LOS but represented only 3.5% of admissions and did not attenuate the established temporal decline in overall in-hospital mortality.

Lung function and outcomes in emergency medical admissions.

BACKGROUND: We examine the ability of pre-existing measures of Forced Expiratory Volume in 1 s (FEV1), and Diffusion Capacity for Carbon Monoxide (DLCO) to determine the subsequent 30-day mortality outcome following unselected acute medical admission. METHODS: Between 2002 and 2017, we studied all emergency medical admissions (106,586 episodes in 54,928 patients) of whom 8071 were classified as respiratory. We employed logisitic multiple variable regression models to evaluate the ability of FEV1 or DLCO to predict the 30-day hospital mortality outcome. RESULTS: The 30-day hospital episode mortality outcome demonstrated curvilinear relationships to the underlying FEV1 or DLCO values; adjusted for major outcome predictors, a higher FEV1 - OR 0.85 (95% CI: 0.82, 0.89) or DLCO OR 0.76 (95% CI: 0.73, 0.79) values predicted survival. The range of predicted mortalities was from 3.3% (95% CI: 2.5, 4.0) to 23.5% (95% CI: 20.8, 26.2); the FEV1 (Model1) and DLCO (Model2) outcome prediction was essentially equivalent (Chi2 = 2.9: p = 0.08). CONCLUSION: The 30-day mortality outcome was clearly related to the pre-admission FEV1 and DLCO value. The outcome relationship was curvilinear. Either parameter appears a useful tool to explore hospital outcomes. Previously suggested cut-points are likely an artefact and not supported by these data.

Eosinophil peroxidase induces expression of cholinergic genes via cell surface neural interactions.

Eosinophils localize to and release their granule proteins in close association with nerves in patients with asthma and rhinitis. These conditions are associated with increased neural function. In this study the effect of the individual granule proteins on cholinergic neurotransmitter expression was investigated. Eosinophil peroxidase (EPO) upregulated choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) gene expression. Fluorescently labeled EPO was seen to bind to the IMR-32 cell surface. Both Poly-L-Glutamate (PLG) and Heparinase-1 reversed the up-regulatory effect of EPO on ChAT and VAChT expression and prevented EPO adhesion to the cell surface. Poly-L-arginine (PLA) had no effect on expression of either gene, suggesting that charge is necessary but insufficient to alter gene expression. EPO induced its effects via the activation of NF-κB. MEK inhibition led to reversal of all up-regulatory effects of EPO. These data indicate a preferential role of EPO signaling via a specific surface receptor that leads to neural plasticity.

Activated eosinophils in association with enteric nerves in inflammatory bowel disease.

Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n = 4), (p = 0.03), and 10-fold in CD (n = 3), (p = 0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p = 0.04) and 15-fold in CD (p = 0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor ß-1 (TGFß-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD.