Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis. Although regulatory T cells (Tregs) have previously been studied in AD, their role remains controversial, likely owing to patient heterogeneity. Thus, we recruited adult AD patients and age-matched healthy controls, and assessed their filaggrin (FLG) genotype, serum IgE level, and eczema area and severity index (EASI). We found increased proportions of all circulating Treg subpopulations in AD patients. Moreover, we show positive correlations between circulating Tregs and serum IgE FLG null mutations limited the expansion of both memory and effector Tregs and enhanced that of recently thymus-emigrated Tregs. Furthermore, proportions of circulating Th2- or Th17-Tregs but not Th1-Tregs were increased in AD patients, and accentuated by FLG null mutations, thereby mimicking the immune deviation observed in Th cell populations. Moreover, ICOS+ Tregs showed reduced production of interleukin-10, suggesting impaired immunosuppression in AD. The level of demethylation of FOXP3i1, which reflects the stability of FOXP3 expression, was similar in the blood and skin of AD patients and healthy controls. Overall, these results show that Tregs may participate into AD pathogenesis and that FLG null mutations exert further modifications on specific subpopulations of circulating Tregs.

Impact of personal protective equipment on neonatal resuscitation procedures: a randomised, cross-over, simulation study.

BACKGROUND AND OBJECTIVE: Healthcare providers should use personal protective equipment (PPE) when performing aerosol-generating medical procedures during highly infectious respiratory pandemics. We aimed to compare the timing of neonatal resuscitation procedures in a manikin model with or without PPE for prevention of SARS-COVID-19 transmission. METHODS: A randomised controlled cross-over (AB/BA) trial of resuscitation with or without PPE in a neonatal resuscitation scenario. Forty-eight participants were divided in 12 consultant-nurse teams and 12 resident-nurse teams. The primary outcome measure was the time of positive pressure ventilation (PPV) initiation. The secondary outcome measures were duration of tracheal intubation procedure, time of initiation of chest compressions, correct use of PPE and discomfort/limitations using PPE. RESULTS: There were significant differences in timing of PPV initiation (consultant-nurse teams: mean difference (MD) 6.0 s, 95% CI 1.1 to 10.9 s; resident-nurse teams: MD 11.0 s, 95% CI 1.9 to 20.0 s), duration of tracheal intubation (consultant-nurse teams: MD 22.0 s, 95% CI 7.0 to 36.9 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s) and chest compressions (consultant-nurse teams: MD 32.3 s, 95% CI 14.4 to 50.1 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s). Twelve participants completed the dressing after entering the delivery room. PPE was associated with visual limitations (43/48 participants), discomfort in movements (42/48), limitations in communication (32/48) and thermal discomfort (29/48). CONCLUSIONS: In a manikin model, using PPE delayed neonatal resuscitation procedures with potential clinical impact. Healthcare workers reported limitations and discomfort when wearing PPE. TRIAL REGISTRATION NUMBER: NCT04666233.