Survival From Pediatric Out-of-Hospital Cardiac Arrest During Nights and Weekends: An Updated Japanese Registry-Based Study.

Background: 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. Objectives: This study aimed to examine the association of outcomes after pediatric OHCA with time of day and day of week. Methods: 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. Results: 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]). Conclusions: 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.

Epinephrine dosing interval and neurological outcome in out-of-hospital cardiac arrest.

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.

Association of Nights and Weekends with Survival of Traumatic Out-of-Hospital Cardiac Arrest following Traffic Collisions: Japanese Registry-Based Study.

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.

Association between time to advanced airway management and neurologically favourable survival during out-of-hospital cardiac arrest.

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.

Case Report: Iliopsoas Hematoma during the Clinical Course of Severe COVID-19 in Two Male Patients.

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.

Timing of Intravenous Epinephrine Administration During Out-of-Hospital Cardiac Arrest.

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.

Difference in electromyographic activity between the trapezius muscle and other neck accessory muscles under an increase in inspiratory resistive loading in the supine position.

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.

Type of advanced airway and survival after pediatric out-of-hospital cardiac arrest.

BACKGROUND: There is a knowledge gap about advanced airway management (AAM) after pediatric out-of-hospital cardiac arrest (OHCA) in the prehospital setting. We assessed which AAM strategy would be associated with an increased chance of survival after pediatric OHCA. METHODS: A nationwide population-based observational study was conducted using the Japanese government-led registry data of OHCA. Pediatric OHCA patients (aged 1-17 years) who received prehospital AAM via endotracheal intubation (ETI) or supraglottic airway (SGA) insertion by emergency medical service (EMS) personnel from 2011 to 2017 were included. Patients who received ETI were compared with those who received SGA insertion. The primary outcome was one-month survival after OHCA. RESULTS: A total of 967 patients (mean [SD] age, 12.2 [5.1] years; 66.6% male) were included; 113 received ETI, and 854 received SGA insertion. Among the total cohort, 118 (12.2%) survived one month after OHCA. In the propensity score-matched cohort, no difference was observed in one-month survival between the ETI and SGA insertion groups: 13 of 113 patients (11.5%) vs 12 of 113 patients (10.6%); RR, 1.08; 95%CI, 0.52-2.27. This lack of association between AAM strategy and survival was observed across a variety of subgroup and sensitivity analyses, and also for neurologically favorable survival (P = 0.5611) in the propensity score-matched analysis. CONCLUSIONS: In Japan, among pediatric OHCA patients, there was no significant difference in one-month survival between prehospital ETI and SGA insertion by EMS personnel. Although an adequately powered randomized controlled trial is needed, EMS personnel may choose their familiar strategy when prehospital AAM was performed during pediatric OHCA.

Computerized data mining analysis of keywords as indicators of the concepts in AHA-BLS guideline updates.

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.

Bystander-initiated conventional vs compression-only cardiopulmonary resuscitation and outcomes after out-of-hospital cardiac arrest due to drowning.

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.

Association of prehospital oxygen administration and mortality in severe trauma patients (PROMIS): A nationwide cohort study.

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 <.001) for favorable in-hospital mortality. Furthermore, there were significant differences in all the important variables between the POA and no POA groups (P <.001); therefore, we used propensity score matching analysis. After adjustment for the covariates of selected variables, we found that POA was not associated with a higher rate of survival after hospitalization (adjusted OR, 1.02; 95% CI, 0.99-1.04; P = .27). Even after adjustment for all covariates, POA did not improve in-hospital mortality (adjusted OR, 1.01; 95% CI, 0.99-1.03; P = .08).In this study, POA did not improve in-hospital mortality in trauma patients. However, further studies are needed to validate our results.

Association of bystander cardiopulmonary resuscitation and neurological outcome after out-of-hospital cardiac arrest due to drowning in Japan, 2013-2016.

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.

Noninvasive positive pressure ventilation for treating acute asthmatic attacks in three pregnant women with dyspnea and hypoxemia.

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.

Association of Prehospital Advanced Life Support by Physician With Survival After Out-of-Hospital Cardiac Arrest With Blunt Trauma Following Traffic Collisions: Japanese Registry-Based Study.

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.

Time to epinephrine and survival after paediatric out-of-hospital cardiac arrest.

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 <0.0001), and adjusted odds ratio 0.90 (95% confidence interval 0.82-0.96, P = 0.0011) when time to epinephrine was treated as a linear and continuous variable in a multivariable logistic regression model. Similar trends were observed for prehospital return of spontaneous circulation (P = 0.0032) and neurologically favourable survival (P = 0.0014). Conclusions: Among paediatric OHCA patients, delayed administration of epinephrine was associated with a decreased chance of favourable outcomes.

Successful conservative management of a case of caustic esophagitis based on computed tomography assessment.

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.

Stimulation of Cell Migration by Flagellin Through the p38 MAP Kinase Pathway in Cultured Intestinal Epithelial Cells.

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-ß1). In translating our findings in alveolar epithelial cells to intestinal epithelial cells, we found that both flagellin and TGF-ß1 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-ß1 increased the protein level of α-smooth muscle actin (αSMA), and flagellin enhanced the effect of TGF-ß1. A wound healing assay revealed that flagellin and TGF-ß1 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.

Desensitization by different strategies of epidermal growth factor receptor and ErbB4.

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.

Potential roles of hyperbaric oxygenation in the treatments of brain tumors.

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.