Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome.

Oxidative stress plays a key role in the pathophysiology of post-cardiac arrest syndrome. Molecular hydrogen reduces oxidative stress and exerts anti-inflammatory effects in an animal model of cardiac arrest. However, its effect on human post-cardiac arrest syndrome is unclear. We consecutively enrolled five comatose post-cardiac arrest patients (three males; mean age, 65 ± 15 years; four cardiogenic, one septic cardiac arrest) and evaluated temporal changes in oxidative stress markers and cytokines with inhaled hydrogen. All patients were treated with target temperature management. Hydrogen gas inhalation (2% hydrogen with titrated oxygen) was initiated upon admission for 18 h. Blood hydrogen concentrations, plasma and urine oxidative stress markers (derivatives of reactive oxygen metabolites, biological antioxidant potential, 8-hydroxy-2'-deoxyguanosine, N ɛ-hexanoyl-lysine, lipid hydroperoxide), and cytokines (interleukin-6 and tumor necrosis factor-α) were measured before and 3, 9, 18, and 24 h after hydrogen gas inhalation. Arterial hydrogen concentration was measurable and it was equilibrated with inhaled hydrogen. Oxidative stress was reduced and cytokine levels were unchanged in cardiogenic patients, whereas oxidative stress was unchanged and cytokine levels were diminished in the septic patient. The effect of inhaled hydrogen on oxidative stress and cytokines in comatose post-cardiac arrest patients remains indefinite because of methodological weaknesses.

Incidence and Characteristics of Bath-related Accidents.

Objective Bath-related sudden cardiac arrests frequently occur in Japan. This study aimed to describe the actual incidence and characteristics of bath-related accidents, including non-fatal events, and to establish the etiology of bath-related sudden cardiac arrest. Methods This prospective cross-sectional observational study was conducted in Tokyo Metropolis and Saga and Yamagata Prefectures between October 2012 and March 2013. Emergency personnel enrolled events in this study when they recognized that activation of the emergency medical system was related to bathing. Surveillance cards were delivered and collected from the emergency personnel and attending physicians. Results In total, 4,593 events were enrolled (1,528 cardiac arrests, 935 survivors in need of help, 1,553 patients with acute illnesses, and 577 patients with injuries) in this study. In the group of survivors in need of help and with acute illness, consciousness disturbance and lethargy without any organic disease were recognized as the main symptoms. Acute coronary syndrome and stroke were infrequently diagnosed. Of the survivors, 30% had a body temperature above 38°C. Their consciousness level significantly correlated with their body temperature. Emergency personnel reported that 79% of sudden cardiac arrests were from victims whose faces were submerged in the tub water, while 18% of survivors had their faces submerged in the tub water. Conclusion This study revealed that accidents, including non-lethal events, frequently occur. The key symptoms were consciousness disturbance and lethargy characterized as a functional disorder and accompanied by an elevated body temperature. Those findings suggest that heat illness during hot water immersion causes drowning.

Early Complications Following Facial Laceration Repair Performed by Emergency Physicians After One Year of Wound Closure Training.

OBJECTIVE: Facial lacerations, which are common in the emergency department, have usually been repaired by non-facial trauma specialists, such as emergency physicians. Given the ongoing discussion regarding quality assurance or the optimal training model on facial laceration repair for nonspecialists, we sought to determine the impact of a 1-year wound closure training provided to emergency physicians. We hypothesized a decrease in early complications following facial wound closure after the training. METHODS: A retrospective observational study was conducted between 2013 and 2015 at an academic center. We included patients with isolated facial lacerations that were repaired by emergency physicians and reviewed by board-certified plastic surgeons during a follow-up visit. Patients whose wounds were not reviewed within 3 days were excluded. The 1-year training curriculum, which consisted of several sessions of lecture, hands-on practice, and case review, had been developed by a multidisciplinary team and provided to emergency physicians. Patient data were divided between nonparticipant and participant groups, and a propensity score was developed to estimate the probability of being assigned to the participant group. The incidence of early complications, defined as the need for additional suturing or resuturing due to wound dehiscence, was compared among the groups after propensity score matching. RESULTS: Although 132 patients satisfied all the inclusion criteria, 11 were excluded due to delayed initial wound review. Among the 70 patients who were eventually included in the participant group, 40 were matched with those in the nonparticipant group. The incidence of early complications was significantly lower in the participant group than in the nonparticipant group (5.0% vs. 20.0%, odds ratio = 0.21, 95% confidence interval = 0.07-0.61, p = 0.04). CONCLUSIONS: The 1-year training provided to emergency physicians reduced the incidence of early complications following facial laceration repair. Accordingly, future wound closure training models should consider the 1-year training curriculum presented herein.

Relationship between Bath-related Deaths and Low Air Temperature.

Objective Bath-related sudden cardiac arrests occur frequently in Japan. Although previous studies have reported that most fatal events occurr in winter, the reason why such events exhibit a seasonal variation has not been elucidated. In this study, we hypothesized that the occurrence of bath-related deaths was correlated with a low air temperature. Methods This prospective cross-sectional observational study was conducted in the Tokyo Metropolitan area between October 2012 and March 2013. Data were collected for all cases involving the activation of the emergency medical system because of an accident or acute illness related to bathing that occurred in Tokyo during the study period. In particular, elderly (≥65 years) cardiac arrest victims who had been found in a bathtub filled with water were enrolled. The relationship between the daily number of cardiac arrest events and the lowest daily air temperature in Tokyo was studied using a nonlinear regression model. Results A total of 3,624 bath-related events were registered in this study. Among these events, 1,081 deaths of elderly individuals who had been found in a bathtub filled with water were recorded. A close correlation was observed between the daily number of events and the lowest daily air temperature. This correlation was described by the following equation: y=8.38e-0.07x, where y was the daily number of cardiac arrests and x was the lowest daily air temperature. Conclusion A low air temperature was closely correlated with the occurrence of bath-related cardiac arrest.

Effect of Retroperitoneal Pelvic Packing on Pelvic Cavity Pressure: A Cadaveric Study.

Limited clinical evidence demonstrates the effectiveness of direct retroperitoneal pelvic packing for hemorrhage control in pelvic fractures due to the difficulty in measuring pressure on the pelvic walls within the pelvic cavity after retroperitoneal pelvic packing. Using a cadaver model, the authors aimed to assess whether retroperitoneal pelvic packing generates pressure that exceeds the venous return and arterial pressure in the pelvis. The pressure on the pelvic wall was measured in 5 fresh Japanese cadavers. Sensors were placed at 4 points on the pelvic wall, and the pressure at each point was measured after the insertion of each of 3 sponges, per the procedure originally described for direct retroperitoneal pelvic packing. In each specimen, the average pressure across all 4 points on the pelvic wall increased with the addition of each sponge, reaching 12.3±4.5 mm Hg when all 3 sponges were inserted. Furthermore, the pressure at the pelvic floor and posterior pelvic brim increased significantly, whereas the pressure at the anterior and middle pelvic brim increased nonsignificantly. The results of this study suggest that retroperitoneal pelvic packing provides pressure on the pelvic wall that exceeds the venous pressure and is thus effective for the control of venous hemorrhage in pelvic fractures. Currently, the recommended procedure combines external fixation for venous bleeding, transcatheter arterial embolization, and pelvic packing; however, the authors' results suggest that pelvic packing alone may be effective for controlling venous hemorrhage in pelvic fracture. [Orthopedics. 2017; 40(6);e947-e951.].

Sudden Death Phenomenon While Bathing in Japan　- Mortality Data.

BACKGROUND: Bath-related sudden cardiac arrest frequently occurs in Japan, but the mortality data have not been sufficiently reported.Methods and Results:This prospective cross-sectional observational study was conducted in the Tokyo Metropolis, Saga Prefecture and Yamagata Prefecture between October 2012 and March 2013 (i.e., in winter). We investigated the data for all occurrences in these areas for which the emergency medical system needed to be activated because of an accident or acute illness related to bathing. Emergency personnel enrolled the event when activation of the emergency medical system was related to bathing. Of the 4,599 registered bath-related events, 1,527 (33%) were identified as bath-related cardiac arrest events. Crude mortality (no. deaths per 100,000) during the observational period was 10.0 in Tokyo, 11.6 in Yamagata and 8.5 in Saga. According to the mortality data for age and sex, the estimated number of bath-related deaths nationwide was 13,369 in winter, for the 6 months from October (95% CI: 10,862-16,887). Most cardiac arrest events occurred in tubs filled with water with the face submerged in the water. This suggests that drowning plays a crucial role in the etiology of such phenomena. CONCLUSIONS: The estimated nationwide number of deaths was 13,369 (95% CI: 10,862-16,887) in winter, for the 6 months from October. Crude mortality during the winter season was 10.0 in Tokyo, 11.6 in Yamagata and 8.5 in Saga.

Early Lactate Clearance Is Associated With Improved Outcomes in Patients With Postcardiac Arrest Syndrome: A Prospective, Multicenter Observational Study (SOS-KANTO 2012 Study).

OBJECTIVES: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest. DESIGN: Ad hoc data analysis of a prospective, multicenter observational study. SETTING: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013. PATIENTS: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified. INTERVENTIONS: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement. MEASUREMENTS AND MAIN RESULTS: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14-4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46-3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01-2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission. CONCLUSIONS: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.

The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction　- First Pilot Study in Humans.

BACKGROUND: Hydrogen gas inhalation (HI) reduced infarct size and mitigated adverse left ventricular (LV) remodeling in a rat model of acute myocardial infarction (AMI). We designed a prospective, open-label, rater-blinded clinical pilot study in patients experiencing ST-elevated MI (STEMI).Methods and Results:The 20 patients with an initial diagnosis of STEMI were assigned to either an HI group (1.3% H2with 26% oxygen) or a control group (26% oxygen). There were no HI-related severe adverse events. In the full analysis set, the cardiac salvage index as evaluated using cardiac magnetic resonance imaging at 7 days after primary percutaneous coronary intervention (PCI), showed no significant between-group difference (HI: 50.0±24.3%; control: 60.1±20.1%; P=0.43). However, the improvement from day 7 in the HI group was numerically greater than that in the control group in some of the surrogate outcomes at 6-month follow-up, including the LV stroke volume index (HI: 9.2±7.1 mL/m2; control: -1.4±7.2 mL/m2; P=0.03) and the LV ejection fraction (HI: 11.0%±9.3%; control: 1.7%±8.3%; P=0.11). CONCLUSIONS: The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).

Generation of kidney tubular organoids from human pluripotent stem cells.

Recent advances in stem cell research have resulted in methods to generate kidney organoids from human pluripotent stem cells (hPSCs), which contain cells of multiple lineages including nephron epithelial cells. Methods to purify specific types of cells from differentiated hPSCs, however, have not been established well. For bioengineering, cell transplantation, and disease modeling, it would be useful to establish those methods to obtain pure populations of specific types of kidney cells. Here, we report a simple two-step differentiation protocol to generate kidney tubular organoids from hPSCs with direct purification of KSP (kidney specific protein)-positive cells using anti-KSP antibody. We first differentiated hPSCs into mesoderm cells using a glycogen synthase kinase-3ß inhibitor for 3 days, then cultured cells in renal epithelial growth medium to induce KSP+ cells. We purified KSP+ cells using flow cytometry with anti-KSP antibody, which exhibited characteristics of all segments of kidney tubular cells and cultured KSP+ cells in 3D Matrigel, which formed tubular organoids in vitro. The formation of tubular organoids by KSP+ cells induced the acquisition of functional kidney tubules. KSP+ cells also allowed for the generation of chimeric kidney cultures in which human cells self-assembled into 3D tubular structures in combination with mouse embryonic kidney cells.

Notch2 Signaling Regulates the Proliferation of Murine Bone Marrow-Derived Mesenchymal Stem/Stromal Cells via c-Myc Expression.

Mesenchymal stem/stromal cells (MSCs) reside in the bone marrow and maintain their stemness under hypoxic conditions. However, the mechanism underlying the effects of hypoxia on MSCs remains to be elucidated. This study attempted to uncover the signaling pathway of MSC proliferation. Under low-oxygen culture conditions, MSCs maintained their proliferation and differentiation abilities for a long term. The Notch2 receptor was up-regulated in MSCs under hypoxic conditions. Notch2-knockdown (Notch2-KD) MSCs lost their cellular proliferation ability and showed reduced gene expression of hypoxia-inducible transcription factor (HIF)-1α, HIF-2α, and c-Myc. Overexpression of the c-Myc gene in Notch2-KD MSCs allowed the cells to regain their proliferation capacity. These results suggested that Notch2 signaling is linked to c-Myc expression and plays a key role in the regulation of MSC proliferation. Our findings provide important knowledge for elucidating the self-replication competence of MSCs in the bone marrow microenvironment.

Cardiopulmonary Resuscitation Training in Schools: A Comparison of Trainee Satisfaction among Different Age Groups.

Cardiopulmonary resuscitation (CPR) has recently been added to the school curriculum worldwide and is currently taught to students between the ages of 10 and 16 years. The effect of the age of trainees on their satisfaction with CPR training has yet been elucidated. The aim of this study was to compare the satisfaction of trainees of different ages who participated in CPR training in schools in Japan. In total, 392 primary school students (10-11 years old), 1798 junior high school students (12-13 years old), and 4162 high schools students (15-16 years old) underwent the same 3-h course of CPR training, according to the guidelines of 2000 for Emergency Cardiovascular Care and CPR. The course was evaluated by a questionnaire completed by the participants. Primary school students responded most positively to all questions, including those reflecting enjoyment and the confidence of participants to apply CPR (Jonckheere-Terpstra test: P < 0.01). Exploratory factor analysis defined three latent variables (reaction, concentration, and naïveté) based on the seven variables addressed in the questionnaire. In the causal relationships analyzed by structural equation modeling (SEM), naïveté (which is related to age) directly affected the other latent variables. The current model suggested that the students' satisfaction with CPR training was strongly related to their age. Primary school students enjoyed CPR training more and were more confident in their ability to perform CPR than junior high and high school students were. Therefore, children aged 10-11 years may be the most appropriate candidates for the introduction of CPR training in schools.

Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome　- First-in-Human Pilot Study.

BACKGROUND: Hydrogen gas inhalation (HI) ameliorates cerebral and cardiac dysfunction in animal models of post-cardiac arrest syndrome (PCAS). HI for human patients with PCAS has never been studied. METHODS AND RESULTS: Between January 2014 and January 2015, 21 of 107 patients with out-of-hospital cardiac arrest achieved spontaneous return of circulation. After excluding 16 patients with specific criteria, 5 patients underwent HI together with target temperature management (TTM). No undesirable effects attributable to HI were observed and 4 patients survived 90 days with a favorable neurological outcome. CONCLUSIONS: HI in combination with TTM is a feasible therapy for patients with PCAS. (Circ J 2016; 80: 1870-1873).

Prognostic factors of Streptococcus pneumoniae infection in adults.

OBJECTIVES: The mortality of severe sepsis has markedly decreased since the implementation of the Surviving Sepsis Campaign guidelines. The next logical step is to examine the necessity of individualized management guidelines for targeted therapy against specific bacteria. Streptococcus pneumoniae is the leading cause of community-acquired severe sepsis; however, little is known regarding the prognostic factors in adult patients with S pneumoniae sepsis. We aimed to identify prognostic factors in patients with S pneumoniae sepsis and to explore a subgroup of patients at high risk for death with detailed Sequential Organ Failure Assessment (SOFA) score analysis. METHODS: We retrospectively reviewed the records of patients with S pneumoniae infection treated between 1st January 2006 and 31st July 2012. We identified prognostic factors for 28-day mortality using univariate and multivariate logistic regression models. RESULTS: Of 171 patients (median age, 72 years) with S pneumoniae infection who were included in this study, the 28-day mortality was 17% (29/171). The SOFA score (odds ratio, 2.25; 95% confidence interval, 1.60-3.18; P < .001) and bacteremia (odds ratio, 19.0; 95% confidence interval, 4.06-90.20; P < .001) were identified as prognostic factors for the 28-day mortality. In a subgroup analysis with a cutoff value of the SOFA score determined by receiver operating characteristic analysis, patients with bacteremia and a SOFA score of at least 7 had a significantly higher mortality than did patients without bacteremia and a SOFA score lower than 7 (84% vs 0%, respectively). CONCLUSIONS: Bacteremia and a SOFA score at least 7 were independent prognostic factors of poor outcome in S pneumoniae sepsis.

Emergency medicine as a specialty in Asia.

Aim: We aim to examine the similarities and differences in areas of EM development, workload, workforce, and capabilities and support in the Asia region. Emerging challenges faced by our EM community are also discussed. Methods: The National Societies for Emergency Medicine of Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand and Turkey participated in the joint Japanese Association of Acute Medicine (JAAM) and Asian Conference of Emergency Medicine (ACEM) Special Symposium held in October 2013 at Tokyo, Japan. The findings are reviewed in this paper. Results: Emergency medicine (EM) has over the years evolved into a distinct and recognized medical discipline requiring a unique set of cognitive, administrative and technical skills for managing all types of patients with acute illness or injury. EM has contributed to healthcare by providing effective, safe, efficient and cost-effective patient care. Integrated systems have developed to allow continuity of emergency care from the community into emergency departments. Structured training curriculum for undergraduates, and specialty training programs for postgraduates are in place to equip trainees with the knowledge and skills required for the unique practice of EM. Conclusion: The practice of EM still varies among the Asian countries. However, as a region, we strive to continue in our efforts to develop the specialty and improve the delivery of EM.

Crowned dens syndrome: reports of six cases and review of the literature.

Case: We have reported six cases of Crowned dens syndrome (CDS) diagnosed by computed tomography (CT). Presenting cases were three male and three female, aged from 45 to 89 (averaged in 72). Outcome: All cases showed calcification around the dens of axis in CTs. Neck pain in all cases relieved within at least 10 days, treated by non-steroidal anti-inflammatory drugs (NSAIDs) in five cases, and one by acetaminophens. Conclusion: Bouvet et al. first reported CDS in 1985, as acute pseudogout of the neck, which causes neck pain. CDS is a radioclinical syndrome defined by the radiographic calcifications in a crown-like configuration around the odontoid process, accompanied clinically by acute neck pain, often with neck stiffness, fevers and raised inflammatory markers. CDS is thought to be a rare condition; however, it is frequently misdiagnosed. CDS is an important differential diagnosis in patients presenting with acute neck pain.

Investigation and treatment of pulmonary embolism as a potential etiology may be important to improve post-resuscitation prognosis in non-shockable out-of-hospital cardiopulmonary arrest: report on an analysis of the SOS-KANTO 2012 study.

Background: The prognosis of non-shockable out-of-hospital cardiac arrest is worse than that of shockable out-of-hospital cardiac arrest. We investigated the associations between the etiology and prognosis of non-shockable out-of-hospital cardiac arrest patients who experienced the return of spontaneous circulation after arriving at hospital. Methods and Results: All subjects were extracted from the SOS-KANTO 2012 study population. The subjects were 3,031 adults: (i) who had suffered out-of-hospital cardiac arrest, (ii) for whom there were no pre-hospital data on ventricular fibrillation/pulseless ventricular tachycardia until arrival at hospital, (iii) who experienced the return of spontaneous circulation after arriving at hospital. We compared the patients' prognosis after 1 and 3 months between various etiological and presumed cardiac factors. The proportion of the favorable brain function patients that developed pulmonary embolism or incidental hypothermia was significantly higher than that of the patients with presumed cardiac factors (1 month, P < 0.0001 and P < 0.0001, respectively; 3 months, P = 0.0018 and P < 0.0001, respectively). In multiple logistic regression analysis, pulmonary embolism and incidental hypothermia were found to be significant independent prognostic factors for 1- and 3-month survival and the favorable brain function rate. Conclusions: In patients who suffer non-shockable out-of-hospital cardiac arrest, but who experience the return of spontaneous circulation after arriving at hospital, the investigation and treatment of pulmonary embolism as a potential etiology may be important for improving post-resuscitation prognosis.

Double traction method-an easy and safe reduction method for anterior shoulder dislocations, even for non-orthopedic surgeons.

Cases: Forty-three male and 27 female patients with anterior shoulder dislocation, with an average age of 45 years, were treated with the "double traction method". The reduction is carried out by two operators, with the patient in a supine position. The first operator holds the patient's wrist and pulls gently longitudinally. After the patient's muscle spasm adequately subsides, the second operator tows the humerus head laterally by using a towel wrapped around the proximal arm. Outcome: Reduction was successful in 63 patients (90%). No iatrogenic fracture or neurovascular deficit occurred. Conclusion: Movement of the patient's arm position causes pain-related muscle spasm. The double traction method is distinctive compared to other manual relocation maneuvers in that the patient's arm is kept at the same position throughout the whole procedure. This maneuver is an easy and safe reduction method for anterior shoulder dislocations, even for non-orthopedic surgeons. It should be an option worth considering for closed reduction in shoulder dislocations.

Vitamin K, fresh frozen plasma, and platelet transfusion used to arrest progression of intracranial hemorrhage after traumatic brain injury in a patient taking anticoagulant and antiplatelet agents.

Case: An 89-year-old man fell from stairs and sustained head trauma. He was taking warfarin and aspirin. Upon arrival at our hospital, his Glasgow Coma Scale score was 14. Initial head computed tomography showed small acute subdural hematoma. We immediately administered vitamin K and ordered fresh-frozen plasma. Repeat computed tomography 3 and 6 h after trauma revealed the acute subdural hematoma had increased to 14 and 20 mm, respectively, and there were several new intracranial hemorrhages. Fresh-frozen plasma and platelet transfusion were initiated. Outcome: Follow-up computed tomography revealed no further progression of intracranial hemorrhages, and the patient's consciousness did not deteriorate further. Conclusion: Appropriate administration of vitamin K, fresh-frozen plasma, and platelets successfully arrested progression of traumatic intracranial hemorrhages in this patient taking anticoagulant/antiplatelet agents and may have averted brain surgery.