Peritoneal fibrosis remains a problem in kidney failure patients treated with peritoneal dialysis. Severe peritoneal fibrosis with encapsulation or encapsulating peritoneal sclerosis is devastating and life-threatening. Although submesothelial fibroblasts as the major precursor of scar-producing myofibroblasts in animal models and M2 macrophage (M)-derived chemokines in peritoneal effluents of patients before diagnosis of encapsulating peritoneal sclerosis have been identified, attenuation of peritoneal fibrosis is an unmet medical need partly because the mechanism for cross talk between Ms and fibroblasts remains unclear. We use a sodium hypochlorite-induced mouse model akin to clinical encapsulated peritoneal sclerosis to study how the peritoneal Ms activate fibroblasts and fibrosis. Sodium hypochlorite induces the disappearance of CD11b high F4/80 high resident Ms but accumulation of CD11b int F4/80 int inflammatory Ms (InfMs) through recruiting blood monocytes and activating local cell proliferation. InfMs switch to express chemokine (C-C motif) ligand 17 (CCL17), CCL22, and arginase-1 from day 2 after hypochlorite injury. More than 75% of InfMs undergo genetic recombination by Csf1r-driven Cre recombinase, providing the possibility to reduce myofibroblasts and fibrosis by diphtheria toxin-induced M ablation from day 2 after injury. Furthermore, administration of antibody against CCL17 can reduce Ms, myofibroblasts, fibrosis, and improve peritoneal function after injury. Mechanistically, CCL17 stimulates migration and collagen production of submesothelial fibroblasts in culture. By breeding mice that are induced to express red fluorescent protein in Ms and green fluorescence protein (GFP) in Col1a1-expressing cells, we confirmed that Ms do not produce collagen in peritoneum before and after injury. However, small numbers of fibrocytes are found in fibrotic peritoneum of chimeric mice with bone marrow from Col1a1-GFP reporter mice, but they do not contribute to myofibroblasts. These data demonstrate that InfMs switch to pro-fibrotic phenotype and activate peritoneal fibroblasts through CCL17 after injury. CCL17 blockade in patients with peritoneal fibrosis may provide a novel therapy. Diphtheria toxin (DT; Sigma-Aldrich, St Louis, MO, USA) or vehicle (PBS) was given intravenously in Csf1r-CreEsr1 Tg ;Rs26 fstdTomato/+ ;Rs26 iDTR/+ mice at 0,
Background Should all out‐of‐hospital cardiac arrest ( OHCA ) patients be directly transported to cardiac arrest centers ( CAC s) remains under debate. Our study evaluated the impacts of different transport time and destination hospital on the outcomes of OHCA patients. Methods and Results Data were collected from 6655 OHCA patients recorded in the regional prospective OHCA registry database of Taoyuan City, Taiwan, between January 2012 and December 2016. Patients were matched on propensity score, which left 5156 patients, 2578 each in the CAC and non‐ CAC groups. Transport time was dichotomized into <8 and ≥8 minutes. The relations between the transport time to CAC s and good neurological outcome at discharge and survival to discharge were investigated. Of the 5156 patients, 4215 (81.7%) presented with nonshockable rhythms and 941 (18.3%) presented with shockable rhythms. Regardless of transport time, transportation to a CAC increased the likelihoods of survival to discharge (<8 minutes: adjusted odds ratio [aOR], 1.95; 95% CI, 1.11–3.41; ≥8 minutes: aOR, 1.92; 95% CI, 1.25–2.94) and good neurological outcome at discharge (<8 minutes: aOR, 2.70; 95% CI, 1.40–5.22; ≥8 minutes: aOR, 2.20; 95% CI, 1.29–3.75) in OHCA patients with shockable rhythms but not in patients with nonshockable rhythms. Conclusions OHCA patients with shockable rhythms transported to CAC s demonstrated higher probabilities of survival to discharge and a good neurological outcome at discharge. Direct ambulance delivery to CAC s should thus be considered, particularly when OHCA patients present with shockable rhythms.
chip-Jin ng 1 ✉ cardiopulmonary resuscitation (cpR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was −0.04 (95% confidence interval −0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov The survival rate of out-of-hospital cardiac arrest (OHCA) is low. In the United States, it has remained between 7% and 9% for the past decades 1. Meanwhile the 180-day OHCA survival rate was reported to be 9.8% in Taiwan 2. Early defibrillation is a treatment option that can increase OHCA survival rate and survival outcomes 3. Ever since its promotion by the American Heart Association (AHA) 4 , many countries have installed automated external defibrillators (AEDs) in public or private places including tourists spots, shopping malls, airports, casinos, schools, offices and so forth, with increased coverage and accessibility. In Taiwan, up until 2017, a total of 8334 AEDs had been installed nationwide 5. Wang et al. 5 reported that, among the documented OHCA cases with AEDs used, 35% were known to be operated by the employees at the designated AED locations, and long-term care facilities had the highest utilization rate of AED. In addition, high-quality chest compressions during cardiopulmonary resuscitation (CPR) also improve OHCA patient outcomes 6-8. However, studies have shown the quality of CPR to be substandard 9,10. Therefore, training with a focus on cardiopulmonary resuscitation (CPR) quality and AED should be implemented and provided, particularly at the AED locations of high cardiac arrest frequency.
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