Pancreatitis severity in mice with impaired CFTR function but pancreatic sufficiency is mediated via ductal and inflammatory cells-Not acinar cells.

Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, pancreatitis patients with CFTR mutations have mostly preserved exocrine pancreatic function. We therefore used a strain of transgenic mice with significant residual CFTR function (CFTRtm1HGU ) to induce pancreatitis experimentally by serial caerulein injections. Protease activation and necrosis were investigated in isolated acini, disease severity over 24h, pancreatic function by MRI, isolated duct stimulation and faecal chymotrypsin, and leucocyte function by ex vivo lipopolysaccharide (LPS) stimulation. Pancreatic and lung injury were more severe in CFTRtm1HGU but intrapancreatic trypsin and serum enzyme activities higher than in wild-type controls only at 8h, a time interval previously attributed to leucocyte infiltration. CCK-induced trypsin activation and necrosis in acini from CFTRtm1HGU did not differ from controls. Fluid and bicarbonate secretion were greatly impaired, whereas faecal chymotrypsin remained unchanged. LPS stimulation of splenocytes from CFTRtm1HGU resulted in increased INF-γ and IL-6, but decreased IL-10 secretion. CFTR mutations that preserve residual pancreatic function significantly increase the severity of experimental pancreatitis-mostly via impairing duct cell function and a shift towards a pro-inflammatory phenotype, not by rendering acinar cells more susceptible to pathological stimuli.

Impact of COVID-19-adapted guidelines on resuscitation quality in out-of-hospital-cardiac-arrest: a manikin study.

BACKGROUND: The aim of this study is to evaluate the effects of European Resuscitation Council (ERC) COVID-19-guidelines on resuscitation quality emphasizing advanced airway management in out-of-hospital-cardiac-arrest. METHODS: In a manikin study paramedics and emergency physicians performed advanced cardiac life support in three settings: ERC guidelines 2015 (control), COVID-19-guidelines as suggested with minimum staff (COVID-19-minimal-personnel); COVID-19-guidelines with paramedics and an emergency physician (COVID-19-advanced-airway-manager). Main outcome measures were no-flow-time, quality metrics as defined by ERC and time intervals to first chest compression, oxygen supply, intubation and first rhythm analysis. Data were presented as mean±standard deviation. RESULTS: Thirty resuscitation scenarios were completed. No-flow-time was markedly prolonged in COVID-19-minimal-personnel (113±37 s) compared to control (55±9 s) and COVID-19-advanced-airway-manager (76±38s; P<0.001 each). In both COVID-19-groups chest compressions started later (COVID-19-minimal-personnel: 32±6 s; COVID-19-advanced-airway-manager: 37±7 s; each P<0.001 vs. control [21±5 s]), but oxygen supply (COVID-19-minimal-personnel: 29±5 s; COVID-19-advanced-airway-manager: 34±7 s; each P<0.001 vs. control [77±19 s]) and first intubation attempt (COVID-19-minimal-personnel: 111±14 s; COVID-19-advanced-airway-manager: 131±20 s; each P<0.001 vs. control [178±44 s]) were performed earlier. However, time interval to successful intubation was similar (control: 198±48 s; COVID-19-minimal-personnel: 181±42 s; COVID-19-advanced-airway-manager: 130±25 s) due to a longer intubation time in COVID-19-minimal-personnel (61±35 s) compared to COVID-19-advanced-airway-manager (P=0.002) and control (19±6 s; P<0.001). Time to first rhythm analysis was more than doubled in COVID-19-minimal-personnel (138±96 s) compared to control (50±12 s; P<0.001). CONCLUSIONS: Delayed chest compressions and prolonged no-flow-time markedly reduced the quality of resuscitation. These negative effects were attenuated by increasing the number of staff and by adding an experienced airway manager. The use of endotracheal intubation for reducing aerosol release during resuscitation should be discussed critically as its priorization is associated with an increase in no-flow-time.