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Objective: Current guidelines for cardiopulmonary resuscitation (CPR) recommend that standard-dose epinephrine be administered every 3–5 minutes during cardiac arrest. However, there is a knowledge gap regarding the optimal epinephrine dosing interval. This study aimed to examine the association between epinephrine dosing intervals and outcomes after out-of-hospital cardiac arrest (OHCA). Methods: This was a nationwide population-based observational study using data from a Japanese government-led registry of OHCA, including patients who experienced OHCA in Japan from 2011 to 2017. We defined the epinephrine dosing interval as the time interval between the first epinephrine administration and return of spontaneous circulation in the prehospital setting, divided by the total number of epinephrine doses. The primary outcome was 1-month neurologically favorable survival. Results: A total of 10,965 patients (mean (SD) age, 75.8 (14.3) years; 59.8% male) were included. The median epinephrine dosing interval was 3.5 minutes (IQR, 2.5–4.5; mean (SD), 3.6 (1.8)). Only approximately half of the patients received epinephrine administration with a standard dosing interval, as recommended in the current CPR guidelines. After multivariable adjustment, compared with the standard dosing interval, neither shorter nor longer epinephrine dosing intervals were associated with neurologically favorable survival after OHCA (Short vs Standard: adjusted OR 0.87 [95%CI 0.66–1.15]; and Long vs Standard: adjusted OR 1.08 [95%CI 0.76–1.55]). Similar associations were observed in propensity score-matched analyses. Conclusions: The epinephrine dosing interval was not associated with 1-month neurologically favorable survival after OHCA. Our findings do not deny the recommended epinephrine dosing interval in the current CPR guidelines.

Anticoagulation plays a major role in reducing the risk of systematic thrombosis in patients with severe COVID-19. Serious hemorrhagic complications, such as intracranial hemorrhage, have also been recognized. However, intra-abdominal hemorrhage is under-recognized because of its rare occurrence, despite high mortality. Here, we discuss two cases of spontaneous iliopsoas hematoma (IPH) likely caused by anticoagulants during the clinical course of COVID-19. We also explored published case reports to identify clinical characteristics of IPH in COVID-19 patients. The use of anticoagulants may increase the risk of lethal IPH among COVID-19 patients becsuse of scarce data on optimal dosage and adequate monitoring of anticoagulant effects. Rapid diagnosis and timely intervention are crucial to ensure good patient outcomes.

Background: The process of care for traumatic out-of-hospital cardiac arrest (OHCA) may be different at night and on the weekend. However, little is known about whether the rate of survival after OHCA is affected by the time of day and day of the week. Methods: This observational study analyzed the Japanese government-led nationwide population-based registry data of OHCA patients. Patients who experienced traumatic OHCA following traffic collisions from 2013 to 2017 were included in the study. A multivariable logistic regression model was used to examine the association of both time of day (day/evening vs. night) and day of the week (weekday vs. weekend) with outcomes after traumatic OHCA. Night was defined as 23:00 p.m. to 6:59 a.m., and weekends were defined as Saturday and Sunday. The primary outcome was one-month survival. Results: A total of 8500 patients (mean [SD] age, 57.7 [22.3] years; 68.6% male) were included. 2267 events (26.7%) occurred at night, and 2482 events (29.2%) occurred on weekends. Overall, 173 patients (2.0%) survived one month after OHCA. After adjusting for potential confounders, one-month survival during the day/evening (148/6233 [2.4%]) was significantly higher than during the night (25/2267 [1.1%]) (adjusted OR, 1.95 [95%CI, 1.24–3.07]), whereas there was no significant difference in one-month survival between weekdays (121/6018 [2.0%]) and weekends (52/2482 [2.1%]) (adjusted OR, 0.97 [95%CI, 0.69–1.38]). Conclusions: One-month survival after traumatic OHCA was significantly lower during the night than during the day/evening, although there was no difference in one-month survival between weekdays and weekends. Further studies are warranted to investigate the underlying mechanisms of decreased survival at night.

Background Early initiation of cardiopulmonary resuscitation (CPR) performed by bystanders is essential in patients with out-of-hospital cardiac arrest (OHCA) due to primary cardiac cause. However, evidence about the effect of bystander CPR on neurologically favorable survival after OHCA due to drowning is scarce and controversial. Methods This nationwide population-based observational study using prospectively collected government-led registry data included patients with OHCA due to drowning who were transported to an emergency hospital between 2013 and 2016. The primary outcome was one-month neurologically favorable survival defined as Glasgow-Pittsburgh Cerebral Performance Category score of 1-2. The secondary outcomes were one-month survival and prehospital return of spontaneous circulation (ROSC). Results The full cohort (n = 12,139) comprised 6291 (51.8%) male patients, and the mean age was 73.7 (standard deviation [SD], 18.8). Of these, 5157 (42.5%) received bystander CPR, and 6982 (57.5%) did not. 4345 patients receiving bystander CPR were propensity-matched with 4345 patients not receiving bystander CPR. In the propensity score-matched cohort, bystander CPR was associated with increased chance of one-month neurologically favorable survival (0.4% vs. 0.8%; risk ratio [RR], 2.19; 95%confidence interval [CI], 1.21–3.95; P = 0.0076), one-month survival (1.1% vs. 1.7%; RR, 1.55; 95%CI, 1.09–2.22; P = 0.0150), and prehospital ROSC (2.7% vs. 3.5%; RR, 1.30; 95%CI, 1.03–1.65; P = 0.0296). Similar association was observed across a variety of sensitivity analyses. In subgroup analysis, statistically significant difference was not observed in pediatric OHCA due to drowning, although the sample size was too small (n = 218). Conclusions Among patients with OHCA due to drowning, bystander CPR was associated with increased chance of neurologically favorable survival.

Key Clinical Message In our case reports, we mentioned about the utility of NPPV therapy in addition to standard pharmacologic therapy for acute asthma exacerbations in pregnant women with dyspnea and hypoxemia compared with that of oxygen therapy alone. Careful patient selection and clinicians’ NPPV experience are crucial in optimizing patient outcomes.

Disparities in survival after pediatric out-of-hospital cardiac arrest (OHCA) between on-duty hours and off-duty hours have previously been reported. However, little is known about whether these disparities have remained in recent years.This study aimed to examine the association of outcomes after pediatric OHCA with time of day and day of week.This observational study analyzed the Japanese government-led nationwide population-based registry data of OHCA patients. Pediatric (18 years) patients who experienced OHCA between 2012 and 2017 were included. A multivariable logistic regression model was used to examine the association of both time of day (day/evening vs night) and day of week (weekday vs weekend) with outcomes after OHCA. The primary outcome was 1-month survival.A total of 7,106 patients (mean age, 5.7 ± 6.5 years; 60.9% male) were included. 1,897 events (26.7%) occurred during night hours, and 2,096 events (29.5%) occurred on weekends. Overall, 1,192 (16.8%) survived 1 month after OHCA. After adjusting for potential confounders, 1-month survival during day/evening (1,047/5,209 [20.1%]) was significantly higher than that at night (145/1,897 [7.6%]) (adjusted odds ratio: 2.31 [95% CI: 1.87-2.86]), whereas there was no significant difference in 1-month survival between weekdays (845/5,010 [16.9%]) and weekends (347/2,096 [16.6%]) (adjusted odds ratio: 1.04 [95% CI: 0.88-1.23]).One-month survival after pediatric OHCA remained significantly lower during night than during day/evening, although disparities in 1-month survival between weekdays and weekends have been eliminated over time. Further studies are warranted to investigate the mechanisms underlying decreased survival at night.

BACKGROUND Current guidelines for cardiopulmonary resuscitation recommend that standard dose of epinephrine be administered every 3 to 5 min during cardiac arrest. However, there is controversy about the association between timing of epinephrine administration and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether the timing of intravenous epinephrine administration is associated with outcomes after OHCA. METHODS We analyzed Japanese government-led nationwide population-based registry data for OHCA. Adult OHCA patients who received intravenous epinephrine by emergency medical service personnel in the prehospital setting from 2011 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to first epinephrine administration and outcomes after OHCA. Subsequently, associations between early (≤20 min) versus delayed (>20 min) epinephrine administration and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was 1-month neurologically favorable survival. RESULTS A total of 119,946 patients (mean [SD] age, 75.2 [14.8] years; 61.4% male) were included. The median time to epinephrine was 23 min (interquartile range, 19-29). Longer time to epinephrine was significantly associated with a decreased chance of 1-month neurologically favorable survival (multivariable adjusted OR per minute delay, 0.91 [95% CI, 0.90-0.92]). In the propensity score-matched cohort, when compared with early (≤20 min) epinephrine, delayed (>20 min) epinephrine was associated with a decreased chance of 1-month neurologically favorable survival (959/42,804 [2.2%] vs. 330/42,804 [0.8%]; RR, 0.34; 95% CI, 0.30-0.39; NNT, 69). CONCLUSIONS Delay in epinephrine administration was associated with a decreased chance of 1-month neurologically favorable survival among patients with OHCA.

The activity of the trapezius muscle is reportedly higher than that of other neck accessory muscles under a condition of increased inspiratory pressure in the standing position. The present study aimed to compare the activity of the trapezius muscle with those of the scalene and sternocleidomastoid muscles under a condition of increased inspiratory pressure in the supine position. This study included 40 subjects, and the muscle activity was measured using surface electromyography. Regarding the results, there was a significant difference in the muscle activity between the trapezius muscle and the scalene and sternocleidomastoid muscles (p = 0.003) in both men and women. Post-hoc analysis showed significant differences between trapezius and the other muscles. Moreover, there was no difference between the scalene and sternocleidomastoid muscles (p = 0.596). The increase in the change in electromyography activity of the muscle is greater in the trapezius muscle than in other muscles when the level of inspiratory pressure increases in the supine position., 論文

Background: There is controversy as to which is superior, basic or advanced airway management (AAM), for out-of-hospital cardiac arrest (OHCA) in the prehospital setting. The effect of AAM may differ depending on the timing. Aim: We sought to determine whether time to AAM is associated with a neurological status after OHCA. Methods: This was a nationwide population-based study based on the government-led registry data of OHCA. We included OHCA patients who received prehospital AAM by EMS personnel in Japan from 2014 to 2017. The primary outcome was 1-month neurologically favorable survival. Outcomes were compared with logistic regression with treating time to AAM as both categorical and continuous variable and for a propensity-matched subset of patients. Results: A total of 16445 patients were included. Of these, 1618 (1.0%) survived without sequelae. The median time to AAM was 17min (IQR, 14–22min). Longer time to AAM was associated with a decreased chance of neurologically favorable survival as in the Figure when treated as categorical variable. When treated as continuous variable, multivariable-adjusted OR per minute delay in time to AAM was 0.90 (95%CI 0.90–0.91). In a propensity score-matched analysis (Time to AAM ≤20 vs >20min), similar association was observed (RR 0.43, 95%CI 0.36–0.50). Conclusion: Delayed AAM was associated with a decreased chance of neurologically favorable survival after OHCA.

Introduction: Prognosis of cardiopulmonary arrest occurring in patients with blunt trauma is very poor; patients rarely recover from this condition. We either do not attempt cardiopulmonary resuscitation or terminate it after some time in blunt trauma–cardiopulmonary arrest cases. We presented a rare case of successful resuscitation of a patient with blunt trauma–cardiopulmonary arrest. Case presentation: A 54-year-old man was admitted to our emergency department after being injured in a traffic accident. The patient suffered from ventricular fibrillation, and spontaneous circulation was restored by a defibrillator. The estimated arrest time was 20 min. Discussion: On arrival of our emergency department, the patient showed intra-abdominal hemorrhage and we performed emergency surgery; 10 days after admission, the patient suffered from pulseless ventricular tachycardia—coronary angiography was performed, which revealed that the patient had coronary artery stenosis. Conclusion: We experienced trauma patients concealed with coronary artery stenosis. In traumatic arrest with ventricular fibrillation, it may be due to a medical reason, and more prolonged and intensive resuscitation may be considered.

Aims Delay in administration of epinephrine is associated with decreased survival among children with in-hospital cardiac arrest with an initial non-shockable rhythm. Whether this association is applicable to paediatric out-of-hospital cardiac arrest (OHCA) population remains unknown. We aimed to determine whether time to epinephrine administration is associated with outcomes in paediatric OHCA. Methods and results This was a nation-wide population-based study of paediatric OHCA in Japan from 2005 to 2012 based on data from the All-Japan Utstein Registry. We included paediatric OHCA patients (aged between 1 and 17 years) who received at least one dose of epinephrine. The primary outcome was 30-day survival. A total of 225 patients were included in the final cohort. Among the 225 patients, 23 (10.2%) survived 30 days after OHCA. The median time from emergency call to first epinephrine administration was 26 min [interquartile range, 20-32; range, 9-128; mean (standard deviation), 28.7 (15.5) min]. Longer time to epinephrine administration was associated with decreased chance of survival: 50.0, 41.2, 13.0, 11.6, 3.9, and 3.1%, respectively, when time to epinephrine was treated as a categorical variable categorized into ≤10, 11-15, 16-20, 21-25, 26-30, or > 30 min (P for trend

Introduction: The American Heart Association (AHA) is pursuing higher-quality simulation training with the goal of “Optimizing educational strategies for healthcare providers” as one of the Science Gaps in the 2015 Cardiac Arrest Guidelines. The latest guidelines suggest that increasing CCF as much as possible during CPR increases the chance of ROSC. However, in simulation training, it is important to evaluate the percentage of CCF and maintain high-quality CPR. We evaluated CPR for 10 minutes in a “High-Performance Teams Activity” of an AHA-BLS course using the HQCPR quotient and CCF indexes. Methods: We measured the rhythm chest compressions (CCs), duration of two breaths, and chest rise two times using a bag valve mask, interruption and alternation time of CC, CC resumption time after AED (shock or no shock), and CCF, which was calculated from CPR recorded for 10 minutes using the video camera. This data was evaluated using the criteria of high-quality CPR based on AHA-BLS guidelines comprising 7 items, such as “100-120 frequency per min for CC,” and the HQCPR quotient was determined. The HQCPR quotient and CCF of each team were analyzed using logistic analysis. Moreover, the BLS techniques of each teams, such as the rhythm CCs were compared with the CCF of each teams, respectively. This study was approved by the Ethics Committee of Ryukyu University and the Japan ACLS Association. Results and Conclusions: Overall, 48 teams comprising 215 subjects participated in the study. The HQCPR achievement rate for the 48 teams was 65.9%. There was no correlation between the HQCPR quotient and CCF (R2 = 0.0003). In simulation training, the CCF height did not necessarily guarantee high-quality CPR (Figure 1). In particular, as CCF increased, the duration of two breaths decreased (R2 = 0.46). An adverse effect of breaths for a very short time was noted. We propose that it is essential to evaluate CCF with HQCPR quotient to achieve “Optimizing educational strategies for healthcare providers.”

Introduction: Specialized care is essential for successful resuscitation after traumatic out-of-hospital cardiac arrest (OHCA). However, the effect of early specialized care by healthcare professional for traumatic OHCA in the prehospital setting is unknown. Hypothesis: We sought to determine whether time to specialized prehospital care by healthcare professional is associated with a neurological status after traumatic OHCA. Methods: This was a nationwide population-based study of traumatic OHCA based on data from the All-Japan Utstein Registry. We included patients who experienced traumatic OHCA in Japan from 2013 to 2016. The primary outcome was 1-month neurologically favorable survival. Results: A total of 8,470 patients were included. Among these patients, 50 (0.6%) survived with a favorable neurological status one month after OHCA. The median time to specialized prehospital care by healthcare professional was 9 minutes (IQR, 7-13; mean [SD], 10.7 [6.3] minutes). Longer time to specialized prehospital care was associated with a decreased chance of neurologically favorable survival: 2.6, 1.2, 0.9, 0.5, 0.2, and 0.0%, respectively, when time to specialized prehospital care was treated as a categorical variable categorized into ≤2, 3-5, 6-8, 9-11, 12-14, and ≥15 minutes (P for trend Conclusion: In traumatic OHCA, delayed specialized prehospital care by healthcare professional was associated with a decreased chance of neurologically favorable survival, especially when a physician was involved in prehospital ALS.

Introduction Cardiopulmonary resuscitation (CPR) guidelines have been updated every 5 years since 2000. Significant changes have been made in each update, and every time a guideline is changed, the instructors of each country that ratify the American Heart Association (AHA) must review the contents of the revised guideline to understand the changes made in the concept of CPR. The purpose of this study was to use a computerized data mining method to identify and characterize the changes in the key concepts of the AHA-Basic Life Support (BLS) updates between 2000 and 2015. Methods We analyzed the guidelines of the AHA-BLS provider manual of 2000, 2005, 2010, and 2015 using a computerized data mining method and attempted to identify the changes in keywords along with changes in the guideline. Results In particular, the 2000 guideline has focused on the detailed BLS technique of an individual health care provider, whereas the 2005 and 2010 guidelines have focused on changing the ratio of chest compressions and breathing and changing the BLS sequence, respectively. In the most recent 2015 guideline, the CPR team was the central topic. We observed that as the guidelines were updated over the years, keywords related to CPR and automated external defibrillators (AED) associated with co-occurrence network continued to appear. Conclusions Analysis revealed that keywords related to CPR and AED associated with the co-occurrence network continued to appear. We believe that the results of this study will ultimately contribute to optimizing AHA's educational strategies for health care providers.

Background Great emphasis has been placed on rescue breathing in out-of-hospital cardiac arrest (OHCA) due to drowning. However, there is no evidence about the effect of rescue breathing on neurologically favorable survival after OHCA due to drowning. The aim of this study is to examine the effect of bystander-initiated conventional (with rescue breathing) versus compression-only (without rescue breathing) cardiopulmonary resuscitation (CPR) in OHCA due to drowning. Methods This nationwide population-based observational study using prospectively collected government-led registry data included patients with OHCA due to drowning who were transported to an emergency hospital in Japan between 2013 and 2016. The primary outcome was one-month neurologically favorable survival. Results The full cohort (n = 5121) comprised 2486 (48.5%) male patients, and the mean age was 72.4 years (standard deviation, 21.6). Of these, 968 (18.9%) received conventional CPR, and 4153 (81.1%) received compression-only CPR. 928 patients receiving conventional CPR were propensity-matched with 928 patients receiving compression-only CPR. In the propensity score-matched cohort, one-month neurologically favorable survival was not significantly different between the two groups (7.5% in the conventional CPR group vs. 6.6% in the compression-only CPR group; risk ratio, 1.15; 95% confidence interval, 0.82–1.60; P = 0.4147). This association was consistent across a variety of subgroup analyses. Conclusions Among patients with OHCA due to drowning, there were no differences in one-month neurologically favorable survival between bystander-initiated conventional and compression-only CPR groups, although several important data (e.g., water temperature, submersion duration, or body of water) could not be addressed. Further study is warranted to confirm our findings.

Background Advanced airway management (AAM) is commonly performed as part of advanced life support. However, there is controversy about the association between the timing of AAM and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether time to AAM is associated with outcomes after OHCA. Methods This was a nationwide population-based observational study using the Japanese government-led registry of OHCA. Adults who experienced OHCA and received AAM by EMS personnel in the prehospital setting from 2014 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to AAM (defined as time in minutes from emergency call to the first successful AAM) and outcomes after OHCA. Then, associations between early (≤ 20 min) vs. delayed (> 20 min) AAM and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was one-month neurologically favourable survival. Results A total of 164,223 patients (median [IQR] age, 80 [69−86] years; 57.7% male) were included. The median time to AAM was 17 min (IQR, 14−22). Longer time to AAM was significantly associated with a decreased chance of one-month neurologically favourable survival (multivariable adjusted OR per minute delay, 0.90 [95% CI, 0.90−0.91]). In the propensity score-matched cohort, compared with early AAM, delayed AAM was associated with a decreased chance of one-month neurologically favourable survival (516 of 50,997 [1.0%] vs. 226 of 50,997 [0.4%]; RR, 0.44; 95% CI, 0.37−0.51; NNT, 176). Conclusions Delay in AAM was associated with a decreased chance of one-month neurologically favourable survival among patients with OHCA.

This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman’s rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.

Introduction: Lay rescuers have a crucial role in successful cardiopulmonary resuscitation (CPR), specifically the first three links in the chain of survival, for out-of-hospital cardiac arrest (OHCA). However, randomized controlled trials on the priority of emergency call (Call first) versus bystander CPR (CPR first) do not exist, and comparative data are very limited. We aimed to assess the association between the priority of bystander’s action (Call first vs. CPR first) and neurologic outcome after OHCA. Methods: This nationwide population-based study of patients who experienced OHCA from January 2005 to December 2014 was based on the data from the Japanese government-managed registry of OHCA. Patients provided bystander’s action (both emergency call and bystander CPR) within 1 minute of witness were included, and Call first strategy was compared with CPR first strategy. The primary outcome was one-month neurologically favorable survival, defined as a Glasgow-Pittsburgh cerebral performance category (CPC) score of 1(good performance) or 2(moderate disability). The secondary outcomes were prehospital return of spontaneous circulation (ROSC) and one-month overall survival. Results: A total of 25,840 patients were included; 4,430 (17.1%) were treated with Call first approach, and 21,410 (82.9%) were treated with CPR first approach. Among total cohort, 2,696 (10.4%) survived with neurologically favorable status one month after OHCA. In the propensity score-matched cohort, one-month neurologically favorable survival was lower among Call first group compared with CPR first group: 364 of 4,430 patients (8.2%) vs. 457 of 4,430 patients (10.3%), respectively (Risk ratio [RR], 0.80; 95% confidence interval [CI], 0.70-0.91). Similar associations were observed for one-month overall survival (RR, 0.90; 95%CI, 0.82-0.99), although there were no significant differences in prehospital ROSC (RR, 0.94; 95%CI, 0.86-1.02) between the Call first and CPR first groups. In subgroup analyses, the association between delayed bystander CPR and worse neurological outcome did not change regardless of subgroup characteristics. Conclusions: In witnessed OHCA, Call first approach was associated with a decreased chance of one-month neurologically favorable survival compared with CPR first approach. These observational findings warrant a randomized clinical trial to determine the priority of emergency call or bystander CPR for OHCA.

Toll-like receptor 5 (TLR5) is a receptor for flagellin and is present on the basolateral surface of intestinal epithelial cells. However, the pathological roles of TLR5 in intestinal epithelial cells are not clear at present. In previous reports, we demonstrated that treatment of cultured alveolar epithelial cells with flagellin activated the p38 mitogen-activated protein kinase (MAPK) pathway and enhanced epithelial-mesenchymal transition induced by transforming growth factor beta 1 (TGF-β1). In translating our findings in alveolar epithelial cells to intestinal epithelial cells, we found that both flagellin and TGF-β1 activated p38 MAPK and its downstream protein kinase, MAPK-activated protein kinase-2 (MAPKAPK-2) in an IEC-6 intestinal epithelial cell line. The phosphorylation of HSP27, one of the substrates for MAPKAPK-2, was also increased. TGF-β1 increased the protein level of α-smooth muscle actin (αSMA), and flagellin enhanced the effect of TGF-β1. A wound healing assay revealed that flagellin and TGF-β1 stimulated the migration of cells. SB203580, an inhibitor of p38 MAPK, and an inhibitor of MAPKAPK-2 inhibited flagellin-stimulated migration. These results suggested that TLR5 is involved in the migration of intestinal epithelial cells through activation of the p38 MAPK pathway.

Case We describe the case of a female patient who ingested approximately 100 mL of toilet bowl cleaner containing 9.5% hydrochloric acid in a suicide attempt. Upon admission for hematemesis and epigastric pain, she was alert and oriented with stable vital signs. Initial contrast-enhanced computed tomography (CT) demonstrated edematous changes with no evidence of upper gastrointestinal tract perforation. Endoscopy was not performed owing to the high risk of perforation. We managed this patient conservatively. Repeat contrast-enhanced CT revealed mediastinal emphysema on day 2, which resolved by day 6. The patient was subsequently discharged with no apparent strictures of the upper gastrointestinal tract. Outcome Surgical interventions are frequently required following the ingestion of large amounts of highly concentrated hydrochloric acid; however, this patient was successfully managed conservatively. Conclusion Contrast-enhanced CT is useful in the assessment of the respiratory and digestive systems and the prediction of potential complications.

Until now, we routinely administered oxygen to trauma patients in prehospital settings irrespective of whether oxygen delivery affected the prognosis. To determine the necessity of prehospital oxygen administration (POA) to trauma patients, we aimed to assess whether POA contributed to in-hospital mortality. This was a multicenter propensity-matched cohort study involving 172 major emergency hospitals in Japan. During 2004 to 2010, 70,683 patients with trauma aged ≥15 years were eligible for enrolment. The main outcome measures were survival until hospital discharge after POA, and propensity score analyses were used to adjust for patient factors and hospital site. Of 32,225 trauma patients, 19,985 (62.0%) were administered oxygen by the emergency medical services in prehospital settings and 12,240 (38.0%) did not receive oxygen. Overall, 29,555 patients (90.7%) survived till hospital discharge. In the multivariable unconditional logistic regression, POA had an odds ratio (OR) of 0.33 (95% confidence interval [CI], 0.30–0.37; P

Four transmembrane tyrosine kinases constitute the ErbB protein family: epidermal growth factor receptor (EGFR) or ErbB1, ErbB2, ErbB3, and ErbB4. In general, the structure and mechanism of the activation of these members are similar. However, significant differences in homologous desensitization are known between EGFR and ErbB4. Desensitization of ligand-occupied EGFR occurs by endocytosis, while that of ErbB4 occurs by selective cleavage at the cell surface. Because ErbB4 is abundantly expressed in neurons from fetal to adult brains, elucidation of the desensitization mechanism is important to understand neuronal development and synaptic functions. Recently, it has become clear that heterologous desensitization of EGFR and ErbB4 are induced by endocytosis and cleavage, respectively, similar to homologous desensitization. It has been reported that heterologous desensitization of EGFR is induced by serine phosphorylation of EGFR via the p38 mitogen-activated protein kinase (p38 MAP kinase) pathway in various cell lines, including alveolar epithelial cells. In contrast, the protein kinase C pathway is involved in ErbB4 cleavage. In this review, we will describe recent advances in the desensitization mechanisms of EGFR and ErbB4, mainly in alveolar epithelial cells and hypothalamic neurons, respectively. Keywords:: alveolar epithelial cell, epidermal growth factor receptor (EGFR), ErbB4, Gonadotropin-releasing hormone (GnRH), hypothalamic neuron

Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and activates host inflammatory responses, mainly through activation of the NF-κB pathway. Although pulmonary fibrosis occurs in some cases of lung infection by flagellated bacteria, the pathological roles of TLR5 stimulation in pulmonary fibrosis have yet to be elucidated. In the present study, we first confirmed that flagellin activated the NF-κB pathway in cultured A549 alveolar epithelial cells. Next, we examined the types of genes whose expression was modulated by flagellin in the cells. Microarray analysis of gene expression indicated that flagellin induced a change in gene expression that had a similar trend to transforming growth factor-β1 (TGF-β1), a key factor in the induction of epithelial-mesenchymal transition (EMT). Biochemical analysis revealed that TGF-β1and flagellin increased the level of fibronectin protein, while they reduced the level of E-cadherin protein after 30 h of treatment. Interestingly, simultaneous treatment with TGF-β1and flagellin significantly augmented these EMT-related changes. Flagellin strongly activated p38 MAP kinase, and the activation was sustained for longer than 30 h. SB203580, an inhibitor of p38 MAP kinase, inhibited the upregulation of fibronectin by both flagellin and TGF-β1. Simultaneous treatment with TGF-β1and flagellin augmented the activation of p38 MAP kinase by TGF-β1or flagellin alone. These results strongly suggest that flagellin cooperates with TGF-β1in the induction of EMT in alveolar epithelial cells.

Importance Controversy remains as to whether advanced life support (ALS) or basic life support (BLS) is superior for critically ill and injured patients, including out-of-hospital cardiac arrest (OHCA) and major trauma, in the prehospital setting. Objective To assess whether prehospital ALS should be provided for traumatic OHCA and who should perform it. Design, Setting, and Participants Japanese government-managed nationwide population-based registry data of patients with OHCA transported to an emergency hospital were analyzed. Patients who experienced traumatic OHCA following a traffic collision from 2013 to 2014 were included. Patients provided prehospital ALS by a physician were compared with both patients provided ALS by emergency medical service (EMS) personnel and patients with only BLS. The data were analyzed on May 1, 2017. Exposures Advanced life support by physician, ALS by EMS personnel, or BLS only. Main Outcomes and Measures The primary outcome was 1-month survival. The secondary outcomes were prehospital return of spontaneous circulation and favorable neurologic outcomes with the Glasgow-Pittsburgh cerebral performance category score of 1 or 2. Results A total of 4382 patients were included (mean [SD] age, 57.5 [22.2] years; 67.9% male); 828 (18.9%) received prehospital ALS by physician, 1591 (36.3%) received prehospital ALS by EMS personnel, and 1963 (44.8%) received BLS only. Among these patients, 96 (2.2%) survived 1 month after OHCA, including 26 of 828 (3.1%) for ALS by physician, 25 of 1591 (1.6%) for ALS by EMS personnel, and 45 of 1963 (2.3%) for BLS. After adjusting for potential confounders using multivariable logistic regression, ALS by physician was significantly associated with higher odds for 1-month survival compared with both ALS by EMS personnel and BLS (adjusted OR, 2.13; 95% CI, 1.20-3.78; and adjusted OR, 1.94; 95% CI, 1.14-3.25; respectively), whereas there was no significant difference between ALS by EMS personnel and BLS (adjusted OR, 0.91; 95% CI, 0.54-1.51). A propensity score–matched analysis in the ALS cohort showed that ALS by physician was associated with increased chance of 1-month survival compared with ALS by EMS personnel (risk ratio, 2.00; 95% CI, 1.01-3.97;P = .04). This association was consistent across a variety of sensitivity analyses. Conclusions and Relevance In traumatic OHCA, ALS by physician was associated with increased chance of 1-month survival compared with both ALS by EMS personnel and BLS.

Toll-like receptor 5 (TLR5) is a receptor for flagellin and is present on the basolateral surface of intestinal epithelial cells. However, the pathological roles of TLR5 in intestinal epithelial cells are not clear at present. In previous reports, we demonstrated that treatment of cultured alveolar epithelial cells with flagellin activated the p38 mitogen-activated protein kinase (MAPK) pathway and enhanced epithelial-mesenchymal transition induced by transforming growth factor beta 1 (TGF-β1). In translating our findings in alveolar epithelial cells to intestinal epithelial cells, we found that both flagellin and TGF-β1 activated p38 MAPK and its downstream protein kinase, MAPK-activated protein kinase-2 (MAPKAPK-2) in an IEC-6 intestinal epithelial cell line. The phosphorylation of HSP27, one of the substrates for MAPKAPK-2, was also increased. TGF-β1 increased the protein level of α-smooth muscle actin (αSMA), and flagellin enhanced the effect of TGF-β1. A wound healing assay revealed that flagellin and TGF-β1 stimulated the migration of cells. SB203580, an inhibitor of p38 MAPK, and an inhibitor of MAPKAPK-2 inhibited flagellin-stimulated migration. These results suggested that TLR5 is involved in the migration of intestinal epithelial cells through activation of the p38 MAPK pathway.

The aim of this study was to determine whether the medicinal herbs growing in Okinawa and possessing a radical-scavenging activity would exert cardioprotective effects against ischemia-reperfusion injury using isolated perfused rat hearts. Effects of the aqueous extracts from Psidium guajava L. and Limonium wrightii at concentrations having an equipotent radical-scavenging activity on myocardial injury produced by global ischemia followed by reperfusion were tested and were further compared with those of quercetin and gallic acid, major antioxidative components of P. guajava L. and L. wrightii, respectively. Both extracts significantly attenuated ischemic contracture during ischemia and improved myocardial dysfunction after reperfusion. Decreases in high-energy phosphates and increases in malondialdehyde in the reperfused hearts were significantly lessened with both plant extracts. Quercetin and gallic acid also exerted similar beneficial effects. These results indicate that P. guajava L. and L. wrightii both have cardioprotective effects against myocardial ischemia-reperfusion injury in isolated rat hearts, primarily through their radical-scavenging actions.

Decompression illness (DCI) develops during or after diving. Pulmonary decompression illness ('Chokes') is rarely seen because the affected individual usually dies in the water. We encountered a rare and interesting case. A 60-year-old man complained of leg pain after diving. Despite rapid transfer to a nearby hospital, advanced respiratory failure and shock had set in. He was then transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of his poor general condition, we initially treated him in the intensive care unit without HBOT, where he showed extreme hyperpermeability and a high level of serum procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe intravascular dehydration and shock status remained. We assume that the injured endothelial cells induced vascular hyperpermeability and increased levels of inflammatory cytokines leading to the high serum PCT level. PCT might be a useful stress marker of endothelial damage and severity in DCI, including Chokes.

A 36-year-old man presented with tetraplegia and hyperventilation after diving. On arrival, he was in shock and an echocardiogram showed air bubbles in the right ventricle. Pulmonary decompression illness was suspected and hyperbaric oxygen therapy (100% oxygen, 2.8 ATA for 60 minutes) was administered. However, the patient’s respiratory status gradually worsened. He also showed right ventricle load D-shape during cardiac ultrasonography, which was attributed to the presence of air bubbles. Chest radiograph revealed a bilateral butterfly shadow (Figure 1). Because the patient’s oxygen saturation level was almost 60%, we decided to initiate extracorporeal membrane oxygenation (ECMO) therapy [1]. Considering that the patient had a hyperdynamic cardiac function and that bubbles generally diminish within 24 hours, we selected venovenous ECMO therapy rather than venoarterial ECMO therapy. This therapy was surprisingly effective, and the patient’s respiratory failure gradually ameliorated. Venovenous ECMO was discontinued on day 7, when a chest X-ray revealed only a small area of consolidation. Figure 1 Chest radiograph at the time of initiating extracorporeal membrane oxygenation therapy. Pulmonary decompression illness is rarely observed in clinical settings, and most patients die prior to hospitalization [2,3]. We administered ECMO therapy to rescue the patient, even though this therapy has rarely been reported with good outcome in patients with decompression illness. In addition, we had to select venovenous ECMO even with the patient showing right ventricular failure. A lot of physicians may select venoarterial ECMO if the patient shows right ventricular failure, but the important physiological mechanism of pulmonary decompression illness is massive air embolism in the pulmonary arteries, and the bubbles diminish within the first 24 hours. The management of decompression illness therefore differs substantially from the usual right-sided heart failure. ECMO may be considered as one of the treatments for severe decompression illness.

Transport of a patient with acute respiratory distress syndrome (ARDS) is a crucial problem. A 17-year-old severe hypoxemic woman was transported successfully using mobile extracorporeal lung assist (mobile ECLA). The patient was injured in a massive landslide and admitted to a municipal hospital far about 103km away from our hospital. On admission, a right tension pneumothorax, hemothorax, 2-7 rib fractures and pulmonary contusion were diagnosed. Although intensive therapies were performed, ARDS developed and her oxygenation deteriorated on the 5th hospital day. Arterial oxygen tension (PaO2) was 35 mmHg with a fractional inspired oxygen (FIO2) of 1.0 and a positive end-expiratory pressure (PEEP) of 8cmH2O. After the initiation of veno-venous ECLA with a centrifugal pump, her PaO2 increased to 232mmHg. She was successfully transported under mobile ECLA during the 2.5 hour transport from the municipal hospital to our ICU. We believe that mobile ECLA is a useful method for inter-hospital transport of a patient with ARDS. To our knowledge, this may be the first case of long distant inter-hospital transport on mobile ECLA in Japan.

Cyanamide is a known alcohol deterrent, and it may cause severe cyanamide-ethanol reaction if a patient consumes high amounts of alcohol during treatment. We report a rare case of cyanamide-ethanol reaction-induced shock in a 73-year-old man who was taking cyanamide for the treatment of alcohol dependence. The patient complained of acute onset of dyspnea after drinking. On arrival, he was in a state of shock. We immediately started hydration and administered 0.3 mg adrenaline by intramuscular injection. However, the patient's general condition did not improve. We could rescue him only after a high dose of adrenaline was administered by continuous intravascular injection. In general, in the treatment of cyanamide-ethanol reaction-induced shock, adrenaline or noradrenaline should be used instead of dopamine. Some cases of severe cyanamide-ethanol reactions have been recently reported in Japan. We performed a literature review and have discussed these cases in the text.

Extracorporeal life support (ECLS) was used to treat three patients with near-fatal status asthmaticus who did not respond to aggressive medical therapies and mechanical ventilation under controlled permissive hypercapnia. ECLS was instituted in patient 1 because Paco 2 was excessively high and pH was excessively low, in patient 2 because hypoxemia and shock were not responsive to treatment, and in patient 3 because of sustained severe hypotension. ECLS supported adequate gas exchange until pulmonary function improved, diminishing the need for mechanical ventilation and preventing pulmonary complications. Pulmonary dysfunction improved markedly after only 21 to 86 hours of ECLS. Aggressive medical treatments were continued during ECLS. Our findings indicate that ECLS is a useful method for preventing death in patients with near-fatal status asthmaticus.

During nitric oxide (NO) inhalation therapy, toxicity may be produced by the reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was to determine the NO2 concentration in a NO inhalation system used for respiratory failure in children at relatively low concentrations of NO (< 20 ppm). The production of NO2 in the NO inhalation system using the Servo Ventilator 900C connected to the test lung under each of 30 combinations of NO concentrations (0, 4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60, 80, and 100%). Pressure controlled ventilation was used with a respiratory rate of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side of the Y-piece connected to the test lung. At a given NO level, increases in the concentration of inspired O2 resulted in increases in the concentration of NO2 produced, as did increases in the amount of NO at a given concentration of O2. The mean NO2 concentration at the inspiratory site of the Y-piece did not exceed 0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO inhalation therapy for children with severe respiratory failure using the Servo Ventilator 900C can be performed safely when the concentration of NO does not exceed 8 ppm.

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO2) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO2 concentration was increased when either the O2 or the NO concentration was increased. The interposition of the endotracheal tubes increased NO2 concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO2 production at 4 p.p.m. NO. The increase in NO2 production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.

We present a case of pharyngeal foreign body in an infant. A 6-month-old girl whose oropharyngeal space was occupied by a cuttlefish hook, was sent to our intensive care unit. The double-banked, radial needles were stuck in the base of the tongue as well as the middle pharynx and were seen on a roentgenogram. Neither a laryngoscope nor even a small bronchofiberscope could be inserted into the oral space occupied by the foreign body. Prior to transoral removal of the foreign body, tracheostomy was performed. Intravenous anesthesia using ketamine and diazepam combined with the local anesthesia was chosen for the tracheostomy. A small dose of atropine was effective in reducing secretions and maintaining the patency of the upper airway. Induction of anesthesia was followed by isoflurane, nitrous oxide, and oxygen after tracheostomy, then surgery was performed successfully within 90 minutes. Tracheostomy is indicated for a patient in whom endotracheal intubation is difficult to perform. Upper airway management during tracheostomy is the main issue in such a case, especially in an infant with a large pharyngeal foreign body.

Over the past 50 years hyperbaric oxygen (HBO2) therapy has been used in a wide variety of medical conditions, and one of them is cancer. Many clinical studies have been conducted to evaluate potential therapeutic effects of HBO2 as a part of cancer treatment. This review briefly summaries the potential role of HBO2 therapy in the treatment of malignant tumors and radiation injury of the brain. HBO2 therapy is used for the enhancement of radiosensitivity in the treatment of some cancers, including malignant brain tumors. Radiotherapy within 15 minutes following HBO2 exposure, a relatively new treatment regimen, has been studied at several institutes and has demonstrated promising clinical results for malignant gliomas of the brain. HBO2 therapy also increases sensitivity to some antineoplastic agents; non-randomized clinical trials using carboplatin-based chemotherapy combined with HBO2 show a significant advantage in survival for recurrent malignant gliomas. The possibilities of combining HBO2 therapy with radiotherapy and/or chemotherapy to overcome newly diagnosed and recurrent malignant gliomas deserve extensive clinical trials. HBO2 therapy also shows promising potential for the treatment and/or prevention of radiation injury of the brain after stereotactic radiosurgery for brain lesions. The possibilities with HBO2 to enhance the therapeutic effect of irradiation per se, and to even increase the radiation dose if there are ways to combat the side effects, should boost new scientific interest into the whole field of oncology looking for new armamentaria to fight cancer.

We investigated the factors associated with cerebral dysfunction in patients undergoing extracorporeal life support (ECLS) following conventional advanced cardiac life support (ACLS). The subjects were 9 patients in whom ECLS was started following ACLS because of intractable cardiac arrest. We investigated whether the irreversibility of cerebral dysfunction during ECLS was related to the cardiopulmonary resuscitation (CPR) time, arterial pH and blood gases, hemoglobin concentration (Hb), peak arterial pressure (PAP) before the start of ECLS and total doses of epinephrine and sodium bicarbonate administered during CPR. Two of the 3 patients who recovered consciousness were weaned from ECLS and survived, while all 6 patients who did not recover from coma were not weaned and died. There was no difference in the CPR time, Hb and PAP before the start of ECLS along with total doses of epinephrine and sodium bicarbonate administered during CPR between the patients who recovered consciousness and those who did not. In addition, there was no difference in arterial pH and blood gases except the arterial oxygen tension (PaO2) between the groups. The PaO2 values before the start of ECLS in the patients who remained in coma ranged from 34 to 58 mmHg, whereas those in the patients who recovered consciousness ranged from 132 to 442 mmHg. The PaO2 values before the start of ECLS in the patients who remained in coma were less than 60 mmHg, whereas those in the patients who recovered consciousness were over 60 mmHg. The present study suggests that hypoxemia during CPR may play a major role in severe cerebral dysfunction in patients undergoing ECLS and PaO2 during CPR.

We examined the incidence of nasel MRSA carriers who were admitted to the ICU during about 6 months. The nasal organisms of 25 medical staffs were also examined during this period. Of 83 patients, 8 (9.6%) had MRSA. Of 25 medical staffs, 1 (4%) had MRSA. Patients who had MRSA were isolated to the single room and their nasal cavities were wiped with 10% popidon iodine solution.The routine inspection of nasal organisms in critically-ill patients on admission to the ICU and in staffs was useful to determine MRSA carrier and to prevent the prevalence of MRSA infections.Three adult patients received intravenous infusion of 0.5g vancomycin for 90 minutes twice a day. This prescription was sufficient to maintain the minimum inhibitory concentration of vancomycin for adult patients without impairing renal function.

A 7-year-old boy with Down syndrome developed severe acute respiratory distress syndrome after a respiratory infection with Mycoplasma pneumoniae with an unusually high agglutination titre (1:10240). Initially, mechanical ventilation and nitric oxide inhalation were used, but these did not improve the alveolar-arterial oxygen gradient. Extracorporeal membrane oxygenation for 152 h improved the lung condition. Conclusion: our case suggests that Mycoplasma pneumoniae should be considered as an aetiological agent in acute respiratory distress syndrome. Extracorporeal membrane oxygenation might have a valuable role in the management.

Decompression illness (DCI) develops during or after diving. Pulmonary decompression illness ('Chokes') is rarely seen because the affected individual usually dies in the water. We encountered a rare and interesting case. A 60-year-old man complained of leg pain after diving. Despite rapid transfer to a nearby hospital, advanced respiratory failure and shock had set in. He was then transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of his poor general condition, we initially treated him in the intensive care unit without HBOT, where he showed extreme hyperpermeability and a high level of serum procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe intravascular dehydration and shock status remained. We assume that the injured endothelial cells induced vascular hyperpermeability and increased levels of inflammatory cytokines leading to the high serum PCT level. PCT might be a useful stress marker of endothelial damage and severity in DCI, including Chokes.