Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-ß, in dogs with atopic dermatitis.

BACKGROUND: Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction. HYPOTHESIS/OBJECTIVES: We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-ß)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months. ANIMALS: We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT. MATERIALS AND METHODS: Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-ß1 were measured by enzyme-linked immunosorbent assay. RESULTS: The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-ß1 serum concentrations between the five groups. CONCLUSIONS AND CLINICAL RELEVANCE: Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.

Out-of-hospital cardiac arrest due to hanging: a retrospective analysis.

BACKGROUND: There has been little research into the prehospital management of cardiac arrest following hanging despite it being among the most prevalent methods of suicide worldwide. The aim of this study was to report the characteristics, resuscitative treatment and outcomes of patients managed in the prehospital environment for cardiac arrest secondary to hanging and compare these with all-cause out-of-hospital cardiac arrest (OHCA). METHODS: Data from a UK ambulance service cardiac arrest registry were extracted for all cases in which treatment was provided for OHCA due to hanging between 1 January 2013 and 30 June 2018. Cases were linked to outcome data obtained from the Trauma Audit and Research Network. Comparison of the cohort was made to previously published data from a UK study of all-cause OHCA with 95% CIs calculated for the proportional difference between the studies in selected presentation and outcome variables. RESULTS: 189 cases were identified. 95 patients were conveyed to hospital and four of these survived to discharge. 40 patients were conveyed despite absence of a spontaneous circulation and none of these patients survived. While only three patients were initially in a shockable rhythm, DC shocks were administered in 20 cases. There was one case of failed ventilation prompting front-of-neck access for oxygenation. By comparison with all-cause OHCA the proportion of patients with a spontaneous circulation at hospital handover was similar (27.0% vs 27.5%; 0.5% difference, 95% CI -5.9% to 6.8%, p=0.882) but survival to hospital discharge was significantly lower (2.2% vs 8.4%; 6.2% difference, 95% CI 4.1% to 8.3%, p=0.002). CONCLUSION: Clinical outcomes following OHCA due to hanging are poor, particularly when patients are transported while in cardiac arrest. Failure to ventilate was uncommon, and clinicians should be alert to the possibility of shockable rhythms developing during resuscitation.