Background: The application of Extracorporeal Membrane Oxygenation(ECMO) and Extracorporeal Life support(ECLS) in hospitals is increasing. In the case of high-level skills, the volume of a specific treatment may be related to the outcome. There has been no discussion on the effect of the increasing utilization volume of ECLS in hospitals on the outcome of OHCA patients. Objectives: We want to determine how the hospital's ECMO volume affects the outcome of the overall OHCA patient visits to the hospital. Methods: We used Korean National OHCA Registry, and performed a cross-sectional study that collected adult EMS-treated cardiac origin OHCA patients between 2015 and 2019 in Seoul. We profiled the number of times ECLS, and hospitals that performed more than 20 times during the study period were regarded as high volume centers (HV centers), and the rest hospitals were defined as low volume centers (LV centers). The primary outcome was a neurologically good outcome (CPC 1 or CPC 2). The secondary outcome was survival at discharge. OHCA patients who visited the two groups were compared using a logistic regression model, and an interaction analysis was performed on the ECMO volume of the hospital and whether the patient had received ECLS. Results: Of the 17,248 included, 3,731 (21.63%) were transported to the HV center. The frequency of good neurological survival was not significant in the group transported to the HV center(aOR 1.08, 95% CI 0.9 - 1.29), but the frequency of survival to discharge was significantly higher(aOR 1.19, 95% CI 1.03 - 1.37). According to interaction analysis, OHCA patients who received ECLS at the HV center showed a significantly better neurological survival outcome(aOR 2.217, 95% CI 1.15 - 4.28), and the OHCA patients transported to the HV center, not receive ECLS had significantly better survival to discharge rates than those transported to the LV center (aOR 1.16, 95% CI 1.01 - 1.34). Conclusions: OHCA patients who were transported and received ECLS to hospitals with high ECMO volumes center had a significantly better neurological outcome. Those who were transported to the high-volume center had a better survival to discharge rate than patients transported to the low-volume one, even if they did not receive ECLS.

Scleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA⁺MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA⁺ MFBs is a viable therapy for fibrosis in scleroderma.

Background: The application of Extracorporeal Membrane Oxygenation(ECMO) and Extracorporeal Life support(ECLS) in hospitals is increasing. In the case of high-level skills, the volume of a specific treatment may be related to the outcome. There has been no discussion on the effect of the increasing utilization volume of ECLS in hospitals on the outcome of OHCA patients. Objectives: We want to determine how the hospital's ECMO volume affects the outcome of the overall OHCA patient visits to the hospital. Methods: We used Korean National OHCA Registry, and performed a cross-sectional study that collected adult EMS-treated cardiac origin OHCA patients between 2015 and 2019 in Seoul. We profiled the number of times ECLS, and hospitals that performed more than 20 times during the study period were regarded as high volume centers (HV centers), and the rest hospitals were defined as low volume centers (LV centers). The primary outcome was a neurologically good outcome (CPC 1 or CPC 2). The secondary outcome was survival at discharge. OHCA patients who visited the two groups were compared using a logistic regression model, and an interaction analysis was performed on the ECMO volume of the hospital and whether the patient had received ECLS. Results: Of the 17,248 included, 3,731 (21.63%) were transported to the HV center. The frequency of good neurological survival was not significant in the group transported to the HV center(aOR 1.08, 95% CI 0.9 - 1.29), but the frequency of survival to discharge was significantly higher(aOR 1.19, 95% CI 1.03 - 1.37). According to interaction analysis, OHCA patients who received ECLS at the HV center showed a significantly better neurological survival outcome(aOR 2.217, 95% CI 1.15 - 4.28), and the OHCA patients transported to the HV center, not receive ECLS had significantly better survival to discharge rates than those transported to the LV center (aOR 1.16, 95% CI 1.01 - 1.34). Conclusions: OHCA patients who were transported and received ECLS to hospitals with high ECMO volumes center had a significantly better neurological outcome. Those who were transported to the high-volume center had a better survival to discharge rate than patients transported to the low-volume one, even if they did not receive ECLS.

Scleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA⁺MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA⁺ MFBs is a viable therapy for fibrosis in scleroderma.

Objective: Without cardiopulmonary resuscitation (CPR), cardiac arrest survival declines 5-10% for every minutes. But, there is a limit to reduce the time from collapse to Emergency medical service (EMS) arrival. This study aimed to examine the association between the time interval from collapse to CPR by EMS providers and related outcomes in patients who received bystander CPR. Methods: A population-based observational study was conducted with out-of-hospital cardiac arrests (OHCA) of cardiac etiology who were witnessed by laypersons in Korea between 2012 and 2014. Exposure variable was the proportion of the time interval from collapse to CPR by EMS providers categorized into quartile groups: group 1 (time < 4 min), group 2 (4 ≤ time < 8), group 3 (8 ≤ time< 15), group 4 (15 ≤ time < 30). Primary endpoint was time interval from collapse to CPR by EMS providers and secondary endpoint were survival to discharge and survival with favorable neurological outcome (Cerebral Performance Category (CPC) 1-2). Multivariable logistic regression analysis was performed. The final model was performed to evaluate interactive effect between bystander CPR and the time interval from collapse to CPR by EMS providers. Results: A total of 15,354 OHCAs were analyzed. Bystander CPR was performed in 8,591 (55.95%). The survival to discharge rate was 10.6% (1632) and favorable neurological outcome was 6.5% (996). In an interaction model of bystander CPR patients, AORs (95% CIs) for survival to discharge rate were 0.89 (0.66-1.20) in group 2, 0.76 (0.57-1.02) in group 3, 0.52 (0.37-0.73) in group 4 compared with group 1. For favorable neurological outcome, AORs were 1.12 (0.77-1.62) in group 2, 0.90 (0.62-1.30) in group 3, 0.59 (0.38-0.91) in group 4. Conclusion: Despite of poor ambulance response time, patients who received bystander CPR would show favorable outcomes. Prompt delivered bystander CPR was strongly associated with increased survival. Keywords: Out-of-hospital cardiac arrest; Cardiopulmonary resuscitation; Emergency medical services

Exposure to DBP affects childhood AD via semaphorin-plexin signaling and IL-5.