Search

Abstract: Carbon nanomaterials, such as single-walled carbon nanohorns (SWCNHs) and carbon nanotubes, demonstrate great potential as drug delivery systems. However, no reports to date have detailed the use of SWCNHs as oral drug carriers. This study shows for the first time the actions of orally-administered SWCNHs in normal mice and mice with dextran sulfate sodium (DSS)-induced colitis. SWCNHs labeled with gadolinium oxide for quantification purposes were detected in the gastrointestinal tract and the feces of mice, but not in the blood or other bodily organs. These results indicate that the nanohorns were not absorbed into the body from the gastrointestinal tract. SWCNH absorption was not influenced by the functionalization or size control of SWCNH. Neither death nor behavioral aberrations were observed in normal mice following SWCNH administration. However, histological observation of mice with DSS-induced colitis at 24h after oral administration of SWCNHs revealed the presence of black particles, presumed to be SWCNHs, in the inflamed areas of the colon and the cecum. Thus, SWCNHs might serve as efficacious drug delivery carriers for the treatment of ulcerative colitis. [Copyright &y& Elsevier]

Context: The spectrum of the etiology of out-of-hospital cardiopulmonary arrest (OHCPA) has not been established. We have performed perimortem computed tomography (CT) during cardiopulmonary resuscitation. Aims: To clarify the incidence of non-cardiac etiology (NCE), actual distribution of the causes of OHCPA via perimortem CT and its usefulness. Settings and Design: Population-based observational case series study. Materials and Methods: We reviewed the medical records of 1846 consecutive OHCPA cases and divided them into two groups: 370 showing an obvious cause of OHCPA with NCE (trauma, neck hanging, terminal stage of malignancy, and gastrointestinal bleeding) and others. Results: Of a total OHCPA, perimortem CT was performed in 57.5% and 62.5% were finally diagnosed as NCE: Acute aortic dissection (AAD) 8.07%, pulmonary thrombo-embolization (PTE) 1.46%, hypoxia due to pneumonia 5.25%, asthma and acute worsening of chronic obstructive pulmonary disease 2.06%, cerebrovascular disorder (CVD) 4.48%, airway obstruction 7.64%, and submersion 5.63%. The rates of patients who survived to hospital discharge were 6-14% in patients with NCE. Out of the 1476 cases excluding obvious NCE of OHCPA, 66.3% underwent perimortem CT, 14.6% of cases without obvious NCE and 22.1% of cases with perimortem CT were confirmed as having some NCE. Conclusions: Of the total OHCPA the incidences of NCE was 62.5%; the leading etiologies were AAD, airway obstruction, submersion, hypoxia and CVD. The rates of cases converted from cardiac etiology to NCE using perimortem CT were 14.6% of cases without an obvious NCE. [ABSTRACT FROM AUTHOR]

Abstract: Cellular responses to graphene-based, nanometer-sized materials, such as carbon nanotubes and single-walled carbon nanohorns (SWNHs), have previously been studied at low-uptake levels. Here, by exploiting the availability of large quantities of SWNHs, cytotoxicity and the immunological responses induced by the abundant uptake of these structures were studied in RAW 264.7 murine macrophages. As much as half the cell interior was pigmented black by SWNHs, which were preferentially localized to lysosomes. High-uptake was shown to destabilize lysosomal membranes and generate reactive oxygen species that resulted in apoptotic, as well as necrotic, cell death. Despite these dramatic responses, only low levels of cytokines were released. The results will be interesting for future studies of the nanocarbon toxicity mechanisms and for medical applications of nanocarbons, especially those relying on lysosomes as target organelles for drug delivery or imaging. [Copyright &y& Elsevier]

Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP). Although they showed levels of serum cholesterol and triglyceride similar to those of apoE-deficient mice, apoE-/-TP-/- mice exhibited a significant delay in atherogenesis, and apoE-/-IP-/- mice exhibited a significant acceleration in atherogenesis compared with mice deficient in apoE alone. The plaques in apoE-/-IP-/- mice showed partial endothelial disruption and exhibited enhanced expression of ICAM-1 and decreased expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the overlying endothelial cells compared with those of apoE-/-TP-/- mice. Platelet activation with thrombin ex vivo revealed higher and lower sensitivity for surface P-selectin expression in platelets of apoE-/-IP-/- and apoE-/-TP-/- mice, respectively, than in those of apoE-/- mice. Intravital microscopy of the common carotid artery revealed a significantly greater number of leukocytes rolling on the vessel walls in apoE-/- mice than in either apoE-/-TP-/- or apoE-/- mice. We conclude that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction. [ABSTRACT FROM AUTHOR]

This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018–2019) and pandemic (2020–2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1–13.1%, p =.020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1–65.8%, 22.3–13.0%, respectively; both p <.001), while bystander-initiated automated external defibrillator (AED) use increased (3.7–4.9%, p =.029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care. [ABSTRACT FROM AUTHOR]

Real-world evidence of out-of-hospital ventricular fibrillation (VF), especially regarding intra-day change, remains unclear. We aimed to investigate that age- and gender-dependent difference of intra-day change of VF occurrence. We enrolled 71,692 patients (males: 56,419 [78.7%], females: 15,273 [21.3%]) in whom cardiac VF had been documented from the 2005–2015 All-Japan Utstein Registry data. Subjects were divided into four groups: group-I (<18 years old), group-II (18–39), group-III (40–69), and group-IV (≥70). Among four groups in each of male and female, we compared the intra-day change of VF occurrence, and evaluated the risk factors of the unfavorable neurologic outcomes at 1 month after VF. Regardless of age, the incidence of VF was significantly greater in male than in female subjects. In male subjects, VF in group-I, III and IV occurred higher at daytime, however, group-II had no intra-day difference because group-II had a higher VF events at midnight~ early morning compared with other aged groups (Poisson regression analysis, p =.03). While in female, each group showed similar intra-day pattern of VF occurrence. Logistic regression analysis revealed that some of the clinical parameters such as time periods from call receipt to first shock and the presence of bystander cardiopulmonary resuscitation were important for risk of 30-day neurologically unfavorable outcomes. The intra-day change of VF occurrence was age-dependently different in males but not in females, suggesting age- and gender-dependent differences in underlying cardiac diseases. These might affect the significant difference in unfavorable neurologic outcome. • VF occurred higher in male than in female subjects. • VF occurred higher at daytime than at nighttime except for 18–39-year old male. • No age-dependent difference in intra-day change of VF was observed in female. • Time to first shock may affect better neurological outcomes for 18–69 years old subjects. [ABSTRACT FROM AUTHOR]

Acute coronary syndrome (ACS) remains one of the leading causes of mortality worldwide. Appropriate management of ACS will lead to a lower incidence of cardiac arrest. Percutaneous coronary intervention (PCI) is the first-line treatment for patients with ACS. PCI techniques have become established. Thus, the establishment of a system of health care in the prehospital and emergency department settings is needed to reduce mortality in patients with ACS. In this review, evidence on how to achieve earlier diagnosis, therapeutic intervention, and decision to reperfuse with a focus on the prehospital and emergency department settings is systematically summarized. The purpose of this review is to generate current, evidence-based consensus on scientific and treatment recommendations for health care providers who are the initial points of contact for patients with signs and symptoms suggestive of ACS. [ABSTRACT FROM AUTHOR]

Background: More than 80% of public-access defibrillation attempts do not result in sustained return of spontaneous circulation in patients who have had an out-of-hospital cardiac arrest (OHCA) and a shockable heart rhythm before arrival of emergency medical service (EMS) personnel. Neurological and survival outcomes in such patients have not been evaluated. We aimed to assess the neurological status and survival outcomes in such patients.Methods: This is a retropective analysis of a cohort study from a prospective, nationwide, population-based registry of 1 299 784 patients who had an OHCA event between Jan 1, 2005, and Dec 31, 2015 in Japan. The primary outcome was favourable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after the OHCA and the secondary outcome was survival at 30 days following the OHCA. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000009918.Findings: We identified 28 019 patients with bystander-witnessed OHCA and shockable heart rhythm who had received CPR from a bystander. Of these, 2242 (8·0%) patients did not achieve return of spontaneous circulation with CPR plus public-access defibrillation, and 25 087 (89·5%) patients did not achieve return of spontaneous circulation with CPR alone before EMS arrival. The proportion of patients with a favourable neurological outcome was significantly higher in those who received public-access defibrillation than those who did not (845 [37·7%] vs 5676 [22·6%]; adjusted odds ratio [OR] after propensity score-matching, 1·45 [95% CI 1·24-1·69], p<0·0001). The proportion of patients who survived at 30 days after the OHCA was also significantly higher in those who received public-access defibrillation than those who did not (987 [44·0%] vs 7976 [31·8%]; adjusted OR after propensity score-matching, 1·31 [95% CI 1·13-1·52], p<0·0001).Interpretation: Our findings support the benefits of public-access defibrillation and greater accessibility and availability of automated external defibrillators in the community.Funding: None. [ABSTRACT FROM AUTHOR]

Background: Gasping during resuscitation has been reported as a favorable factor for out-of-hospital cardiac arrest. We examined whether gasping during resuscitation is independently associated with favorable neurological outcomes in patients with refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) undergoing extracorporeal cardiopulmonary resuscitation ECPR. Methods: Data from a 2014 study on advanced cardiac life support for ventricular fibrillation with extracorporeal circulation in Japan (SAVE-J), which examined the efficacy of ECPR for refractory VF/pVT, were analyzed. The primary endpoint was survival with a 6-month favorable neurological outcome in patients who underwent ECPR with or without gasping during resuscitation. Multivariate logistic regression analysis was performed to evaluate the association between gasping and outcomes. Results: Of the 454 patients included in the SAVE-J study, data from 212 patients were analyzed in this study after excluding those with missing information and those who did not undergo ECPR. Gasping has been observed in 47 patients during resuscitation; 11 (23.4%) had a favorable neurological outcome at 6 months. Multivariate logistic regression analysis showed that gasping during resuscitation was independently associated with a favorable neurological outcome (odds ratio [OR], 10.58 [95% confidence interval (CI) 3.22–34.74]). The adjusted OR for gasping during emergency medical service transport and on arrival at the hospital was 27.44 (95% CI 5.65–133.41). Conclusions: Gasping during resuscitation is a favorable factor in patients with refractory VF/pVT. Patients with refractory VF/pVT with continuously preserved gasping during EMS transportation to the hospital are expected to have more favorable outcomes. [ABSTRACT FROM AUTHOR]

The effect of prehospital factors on favorable neurological outcomes remains unclear in patients with witnessed out-of-hospital cardiac arrest (OHCA) and a shockable rhythm. We developed a decision tree model for these patients by using prehospital factors. Using a nationwide OHCA registry database between 2005 and 2020, we retrospectively analyzed a cohort of 1,930,273 patients, of whom 86,495 with witnessed OHCA and an initial shockable rhythm were included. The primary endpoint was defined as favorable neurological survival (cerebral performance category score of 1 or 2 at 1 month). A decision tree model was developed from randomly selected 77,845 patients (development cohort) and validated in 8650 patients (validation cohort). In the development cohort, the presence of prehospital return of spontaneous circulation was the best predictor of favorable neurological survival, followed by the absence of adrenaline administration and age. The patients were categorized into 9 groups with probabilities of favorable neurological survival ranging from 5.7 to 70.8% (areas under the receiver operating characteristic curve of 0.851 and 0.844 in the development and validation cohorts, respectively). Our model is potentially helpful in stratifying the probability of favorable neurological survival in patients with witnessed OHCA and an initial shockable rhythm. [ABSTRACT FROM AUTHOR]

Prednisolone (PSL), an anti-inflammatory glucocorticoid drug, was adsorbed on oxidized single-walled carbon nanohorns (oxSWNHs) in ethanol–water solvent. The quantity of adsorbed PSL on the oxSWNHs was 0.35–0.54 g/g depending on the sizes and numbers of holes on the oxSWNHs. PSL was adsorbed on both the outside and the inside of the oxSWNHs, and released quickly in a couple of hours and slowly within about one day from the respective places. The released quantity in culture medium strongly depended on the concentration of the PSL–oxSWNH complexes, suggesting that PSL adsorbing on oxSWNHs and PSL in the culture medium were in concentration equilibrium. The local injection of PSL–oxSWNHs into the tarsal joint of rats with collagen-induced arthritis (CIA) slightly retarded the progression of the arthritis compared with controls. By histological analysis of the ankle joint, the anti-inflammatory effect of PSL–oxSWNHs was also observed. [ABSTRACT FROM AUTHOR]

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53–1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49–0.73)], 3-day [0.75 (95% CI 0.60–0.94)], 4-day [0.43 (95% CI 0.31–0.60)] and 5-day support [0.62 (95% CI 0.44–0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2–5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies. [ABSTRACT FROM AUTHOR]

Background: The distal radial approach (DRA) is a novel catheter cannulation technique to access the distal radial artery for coronary angiography (CAG). It is associated with less occurrence of puncture site occlusion than the conventional transradial approach. However, cannulation failure occasionally occurs due to difficulty in puncturing the smaller distal radial artery. Nitroglycerin is expected to improve the rate of successful DRA via its vasodilative and vasospasm-preventive effects.Methods: The DRA in CAG using transdermal NitroGlycerin patch (DRANG) study is a single-center, double-arm, parallel-assignment, double-blinded, randomized, controlled trial. Eligible patients with angina pectoris who are scheduled to receive CAG via DRA at the National Cerebral and Cardiovascular Center will be enrolled and allocated to the nitroglycerin group (n = 46) or the no-treatment group (n = 46). The nitroglycerin group will receive a transdermal nitroglycerin patch pre-integrated with a covering material that completely conceals the patch on their upper arm on the puncture side. The no-treatment group will receive only the covering material. Applications are performed 2-8 h before puncture while the patient wears an eye mask. Physicians who are blinded to the allocation and have similar experience with DRA puncture will perform DRA using the Seldinger technique with a 22-gauge needle. The primary outcome is the rate of successful palpation-guided distal radial artery cannulation with the first puncture. The secondary outcomes are the rate of successful distal radial artery cannulation, number of punctures, procedure time, use of ultrasound guidance, diameter of the distal radial artery and changes before and after patch application, and occurrence of arterial vasospasm, occlusion, or hypotension.Conclusions: This study will allow us to determine the impact of a transdermal nitroglycerin patch on the rate of successful DRA and validate its effectiveness as a DRA pretreatment.Trial Registration: jRCTs051210128. [ABSTRACT FROM AUTHOR]

The R-EDByUS score for a 1-month neurological outcome prediction after cardiogenic OHCA. Abbreviations: CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation; ER, emergency room; EMS, emergency medical services. [Display omitted] • Newly developed R-EDByUS score which consists solely of prehospital resuscitation features, could be a prompt, and accurate prognostic prediction model in patients with OHCA of presumed cardiac aetiology. • The R-EDByUS score can be applied for patients in whom prehospital ROSC had been obtained and in whom CPR was continued upon hospital arrival using the same prehospital features. • Both the Regression-based R-EDByUS and Simplified R-EDByUS scores can estimate the probability of the unfavorable neurological outcomes while maintaining high accuracy. To develop a new scoring model for patients with cardiogenic out-of-hospital cardiac arrest (OHCA) to facilitate neurological prognosis prediction upon hospital arrival by using prehospital resuscitation features alone. Between 2005 and 2019, we enrolled 942,891 adult patients with OHCA of presumed cardiac aetiology from the All-Japan Utstein Registry. Scoring models applied prehospital resuscitation features a priori from the variables the American College of Cardiology algorithm including age, duration to return of spontaneous circulation (ROSC) or hospital arrival, no bystander cardiopulmonary resuscitation (CPR), unwitnessed arrest, and nonshockable rhythm (R-EDByUS score) to predict unfavorable neurological outcomes defined as Cerebral Performance Category 3, 4, or 5 at 1 month. We created nomograms as a "Regression-based model," and created a "Simplified model" in which points were assigned by category for predicting unfavorable neurological outcomes for both the prehospital ROSC cohort (67,064 patients) and the ongoing CPR cohort (875,827 patients). For internal validation, bootstrap optimism-corrected estimates of predictive performance were calculated. A total of 46,971 (70.0%) and 870,991 (99.4%) patients in the prehospital ROSC and ongoing CPR cohorts, respectively, had unfavorable neurological outcomes. In the prehospital ROSC cohort, the C-statistics of the Regression-based and Simplified models were 0.851 and 0.842, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. In the ongoing CPR cohort, the C-statistics of the Regression-based and Simplified models were 0.872 and 0.865, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. The R-EDByUS score accurately predicted the neurological prognosis of cardiogenic OHCA upon hospital arrival. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms responsible for the cytotoxic effects of carbon nanomaterials is important for their future biomedical applications. Carbon nanotubular materials induce the generation of reactive oxygen species (ROS), which causes cell death; however, the exact details of this process are still unclear. Here, we identify a mechanism of ROS generation that is involved in the apoptosis of RAW264.7 macrophages caused by excess uptake of carbon nanohorns (CNHs), a typical type of carbon nanotubule. CNH accumulated in the lysosomes, where they induced lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteases, such as cathepsins, which in turn caused mitochondrial dysfunction and triggered the generation of ROS in the mitochondria. The nicotinamide adenine dinucleotide phosphate oxidase was not directly involved in CNH-related ROS production, and the ROS generation cannot be regulated by mitochondrial electron transport chain. ROS fed back to amplify the mitochondrial dysfunction, leading to the subsequent activation of caspases and cell apoptosis. Carbon nanotubules commonly accumulate in the lysosomes after internalization in cells; however, lysosomal dysfunction has not attracted much attention in toxicity studies of these materials. These results suggest that LMP, a neglected mechanism, may be the primary reason for carbon nanotubule toxicity. [ABSTRACT FROM AUTHOR]

The impact of a national initiative to provide cardiopulmonary resuscitation (CPR) education to the public on the rates of citizen-initiated CPR and survival following out-of-hospital cardiac arrest (OHCA) remains uncertain. We examined 358,025 cases of citizen-witnessed OHCA with presumed cardiac origin, recorded in the Japanese nationwide registry from 2005 to 2020. We assessed the relationship between the number of individuals certified in CPR courses, citizen interventions, and neurologically favorable survival at one month. The cumulative number of certified citizens has linearly increased from 9,930,327 in 2005 to 34,938,322 in 2020 (incidence rate ratio for annual number = 1.03, p < 0.001), encompassing 32.3% of the Japanese population aged 15 and above. Similarly, the prevalence of citizen-initiated CPR has consistently increased from 40.6% in 2005 to 56.8% in 2020 (P for trend < 0.001). Greater citizen CPR engagement was significantly associated with better outcome in initial shockable rhythm patients [chest compression only: odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02–1.51; P = 0.029; chest compression with rescue breathing: OR 1.33; 95% CI 1.08–1.62; P = 0.006; defibrillation with chest compression: OR 2.27; 95% CI 1.83–2.83; P < 0.001; defibrillation with chest compression and rescue breathing: OR 2.15; 95% CI 1.70–2.73; P < 0.001 vs. no citizen CPR]. The incidence of citizen-initiated CPR across Japan has consistently and proportionately increased with the rising number of individuals certified in CPR courses. Greater citizen CPR involvement has been linked to neurologically favorable survival, particularly in cases with an initial shockable rhythm. [ABSTRACT FROM AUTHOR]

Abstract: Background: Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). Selection of post-CA patients for TH remains problematic, as there are no clinically validated tools to determine who might benefit from the therapy. Objective: The aim of this study was to investigate retrospectively whether laboratory findings or other patient data obtained during the early phase of hospital admission could be correlated with neurological outcome after TH in comatose survivors of CA. Methods: Medical charts of witnessed CA patients admitted between June 2003 and July 2009 who were treated with TH were reviewed retrospectively. The subjects were grouped based on their cerebral performance category (CPC) 6 months after CA, as either good recovery (GR) for CPC 1–2 or non-good recovery (non-GR) for CPC 3–5. The following well-known determinants of outcome obtained during the early phase of hospital admission were evaluated: age, gender, body mass index, cardiac origin, presence of ventricular fibrillation (VF), time from collapse to cardiopulmonary resuscitation, time from collapse to return of spontaneous circulation, body temperature, arterial blood gases, and blood test results. Results: We analyzed a total of 50 (25 GR and 25 non-GR) patients. Multivariate logistic analysis showed that initial heart rhythm and pH levels were significantly higher in the GR group than in the non-GR group (ventricular tachycardia/VF rate: p = 0.055, 95% confidence interval [CI] 0.768–84.272, odds ratio [OR] 8.047; pH: 7.155 ± 0.139 vs. 6.895 ± 0.100, respectively, p < 0.001, 95% CI 1.838–25.827; OR 6.89). Conclusion: These results imply that in addition to initial heart rhythm, pH level may be a good candidate for neurological outcome predictor even though previous research has found no correlation between initial pH value and neurological outcome. [Copyright &y& Elsevier]

Background: Blood transfusion therapy (BTT), which represents transplantation of living cells, poses several risks. Although BTT is necessary for trauma victims with hemorrhagic shock, it may be futile for patients with blunt traumatic cardiopulmonary arrest (BT-CPA). Materials and Methods: We retrospectively examined the medical records of consecutive patients with T-CPA. The study period was divided into two periods: The first from 1995-1998, when we used packed red cells (PRC) regardless of the return of spontaneous circulation (ROSC), and the second from 1999-2004, when we did not use PRC before ROSC. The rates of ROSC, admission to the ICU, and survival-to-discharge were compared between these two periods. Results: We studied the records of 464 patients with BT-CPA (175 in the first period and 289 in the second period). Although the rates of ROSC and admission to the ICU were statistically higher in the first period, there was no statistical difference in the rate of survival-to-discharge between these two periods. In the first period, the rate of ROSC was statistically higher in the non-BTT group than the BTT group. However, for cases in which ROSC was performed and was successful, there were no statistical differences in the rate of admission and survival-to-discharge between the first and second group, and between the BTT and non-BTT group. Conclusion: Our retrospective consecutive study shows the possibility that BTT before ROSC for BT-CPA and a treatment strategy that includes this treatment improves the success rate of ROSC, but not the survival rate. BTT is thought to be futile as a treatment for BT-CPA before ROSC. [ABSTRACT FROM AUTHOR]

Background: Insufficient knowledge of the risks and complications of cardiopulmonary resuscitation (CPR) may be an obstructive factor for CPR, however, particularly for patients who are not clearly suffering out of hospital cardiopulmonary arrest (OHCPA). The object of this study was to clarify the potential complication, the safety of bystander CPR in such cases. Materials and Methods: This study was a population-based observational case series. To be enrolled, patients had to have undergone CPR with chest compressions performed by lay persons, had to be confirmed not to have suffered OHCPA. Complications of bystander CPR were identified from the patients' medical records and included rib fracture, lung injury, abdominal organ injury, and chest and/or abdominal pain requiring analgesics. In our emergency department, one doctor gathered information while others performed X-ray and blood examinations, electrocardiograms, and chest and abdominal ultrasonography. Results: A total of 26 cases were the subjects. The mean duration of bystander CPR was 6.5 minutes (ranging from 1 to 26). Nine patients died of a causative pathological condition and pneumonia, and the remaining 17 survived to discharge. Three patients suffered from complications (tracheal bleeding, minor gastric mucosal laceration, and chest pain), all of which were minimal and easily treated. No case required special examination or treatment for the complication itself. Conclusion: The risk and frequency of complications due to bystander CPR is thought to be very low. It is reasonable to perform immediate CPR for unconscious victims with inadequate respiration, and to help bystanders perform CPR using the T-CPR system. [ABSTRACT FROM AUTHOR]

Existing studies have yielded conflicting results regarding the relationship between the time of occurrence of out-of-hospital cardiac arrests and the associated outcomes. We examined whether the one-month survival rate for out-of-hospital cardiac arrests differed depending on whether the cardiac arrest occurred during the day or night. Further, we examined whether this rate differed when comparing the period succeeding the 2005 International Resuscitation Guidelines (2006–2010) with that following the 2010 guidelines (2011–2015). Using data from the All-Japan Utstein Registry for 2006–2015, adult out-of-hospital cardiac arrest patients whose collapse was witnessed and for whom the collapse-to-hospital-arrival interval was shorter than 120 min were included in this study. Patients were categorized in terms of whether their arrest occurred during the post-2005- or post-2010-guideline period. The primary measure was the one-month survival with a favorable neurological outcome. Of 481,624 cases analyzed, 20% occurred at night. For both guideline periods, nighttime out-of-hospital cardiac arrests were associated with significantly lower one-month survival rates than daytime incidents (used as a reference; adjusted odds ratio: 0.69 and 0.63, 95% confidence interval: 0.65–0.73 and 0.60–0.65, and P < 0.001 and <0.001 for the 2005 and 2010 guideline periods, respectively). One-month survival with a favorable neurological outcome was significantly lower for patients who experienced nighttime out-of-hospital cardiac arrests, compared to daytime out-of-hospital cardiac arrests. This could be addressed by improving cardiopulmonary resuscitation training for bystanders and expanding and improving nighttime emergency medical services. • Of all cardiac arrests analyzed, 20% occurred at night. • Nighttime occurrence negatively impacted one-month survival rate. • Daytime occurrence was linked to higher survival rates. [ABSTRACT FROM AUTHOR]

Calcified nodule (CN) is an eruptive calcified mass causing acute coronary syndrome (ACS). Since coronary calcification is associated with an elevated cardiac event's risk, ACS attributable to CN may exhibit worse clinical outcome following percutaneous coronary intervention (PCI). We retrospectively analyzed 657 ACS patients receiving PCI with newer-generation drug-eluting stent (DES) implantation under intravascular ultrasound (IVUS) guidance. CN was defined as (1) protruding calcification with its irregular surface and (2) the presence of calcification at adjacent proximal and distal segments. The primary endpoint was a composite of major adverse cardiac event [MACE = cardiac death + ACS recurrence + target lesion revascularization (TLR)]. CN was identified in 5.3% (=35/657) of the study subjects. CN patients were more likely to have coronary risk factors including hypertension (p = 0.005), chronic kidney disease (p < 0.001), maintenance hemodialysis (p < 0.001) and a history of PCI (p < 0.001). During the observational period (median = 1304 days), CN was associated with an increased risk of MACE (HR = 7.68, 95%CI = 4.61–12.80, p < 0.001), ACS recurrence (HR = 12.32, 95%CI = 6.05–25.11, p < 0.001) and TLR (HR = 10.48, 95%CI = 5.80–18.94, p < 0.001). These cardiac risks related to CN were consistently observed by Cox proportional hazards model (MACE: p < 0.001, ACS recurrence: p < 0.001, TLR: p < 0.001) and a propensity score–matched cohort analysis (MACE: p = 0.002, ACS recurrence: p = 0.01, TLR: p = 0.005). Of note, over 80% of TLR at the CN lesion was driven by its re-appearance within the implanted DES. ACS patients attributable to CN have an increased risk of ACS recurrence and TLR, mainly driven by the continuous growth and protrusion of the calcified mass. Image 1 • Acute coronary syndrome (ACS) patients attributable to calcified nodule (CN) exhibited significant heightened risk of adverse cardiac events compared to those without. • In ACS patients attributable to calcified nodule, recurrence of ACS occurred mainly due to in-stent restenosis. • Over 80% of in-stent restenosis at lesions containing CN exhibited its re-appearance within the implanted stent.. • Our findings suggest the need for additional therapeutic approach to modify CN in ACS subjects.. [ABSTRACT FROM AUTHOR]

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is an evolving resuscitative method for refractory cardiopulmonary arrests. However, considering the substantial healthcare costs and resources involved, there is an urgent need for a full economic evaluation. We therefore assessed the cost-effectiveness of ECPR for refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT).Methods: We developed a decision model to estimate lifetime costs and outcomes for out-of-hospital cardiac arrest patients with VF/pVT who received either ECPR or conventional cardiopulmonary resuscitation. Quality-adjusted life-years (QALY) was used as the main outcome measure. This model was a combination of a decision tree model for the acute phase based on a prospective observational study (SAVE-J study), together with a Markov model for long-term follow-up periods extrapolated from published data. To evaluate the robustness of this model, we conducted a comprehensive deterministic sensitivity analysis (DSA) and a probabilistic sensitivity analysis (PSA).Results: ECPR was cost-effective, with an incremental cost of ¥3,521,189 (Є30,227), an incremental effectiveness of 1.34 QALY, and an incremental cost-effectiveness ratio of ¥2,619,692 (Є22,489) per QALY gained. DSA revealed that the present model was most sensitive to probability of Cerebral Performance Category 1 after ECPR (¥2,153,977/QALY to ¥3,186,475/QALY), patient age (¥2,170,112/QALY to ¥3,334,252/QALY), and long-term medical cost for modified Rankin Scale 0 (¥2,280,352/QALY to ¥2,855,330/QALY). PSA indicated ECPR to be cost-effective and below the willingness-to-pay threshold of ¥5,000,000 with an 86.7 % possibility.Conclusions: ECPR was an economically acceptable resuscitative strategy, and the results of the present study were robust even when considering the uncertainty of all parameters. [ABSTRACT FROM AUTHOR]

Background: Emergency life-saving technicians (ELSTs) are specially trained prehospital medical providers believed to provide better care than basic emergency medical technicians (BEMTs). ELSTs are certified to perform techniques such as administration of advanced airways or adrenaline and are considered to have more knowledge; nevertheless, ELSTs' effectiveness over BEMTs regarding out-of-hospital cardiac arrest (OHCA) remains unclear. We investigated whether the presence of an ELST improves OHCA patient outcomes.Methods: In a retrospective study of adult OHCA patients treated in Japan from 2011 to 2015, we compared two OHCA patient groups: patients transported with at least one ELST and patients transported by only BEMTs. The primary outcome measure was one-month favorable neurological outcomes, defined as Cerebral Performance Category ≤ 2. A multivariable logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs) to evaluate the effect of ELSTs.Results: Included were 552,337 OHCA patients, with 538,222 patients in the ELST group and 14,115 in the BEMT group. The ELST group had a significantly higher odds of favorable neurological outcomes (2.5% vs. 2.1%, adjusted OR 1.39, 95% CI 1.17-1.66), one-month survival (4.9% vs. 4.1%, adjusted OR 1.37, 95% CI 1.22-1.54), and return of spontaneous circulation (8.1% vs. 5.1%, adjusted OR 1.90, 95% CI 1.72-2.11) compared with the BEMT group. However, ELSTs' limited procedure range (adrenaline administration or advanced airway management) did not promote favorable neurological outcomes.Conclusions: Compared with the BEMT group, transport by the ELST group was associated with better neurological outcomes in OHCA. [ABSTRACT FROM AUTHOR]

Abstract: Percutaneous endoscopic gastrostomy (PEG) is a common and safe procedure for enteral nutrition. There are few reports concerning its complications. We managed a 31-y-old bedridden case with punched out duodenal perforation without inflammation, from which the tip of the PEG tube protruded. Simple x-ray and computed tomography showed incarceration of the balloon in the duodenal bulb and extravasation of the tip of the tube. We performed simple closure with omental patching for duodenal perforation. Postoperative gastrointestinal fiberscopy on the 11th day revealed scar phase. Some PEG tubes have a balloon, which can prevent the removal of the tube, fix the position of the tube, and prevent the leakage of gastric contents from fistula. However, in our case, the inflated balloon was transferred into the duodenal bulb according to gastric strong peristalsis. This pathophysiologic mechanism is the same as ball bulb syndrome, which is known as gastroduodenal obstruction by incarceration of the gastric submucosal tumor. There is a risk of wedging of the inflated balloon of the PEG tube and perforation of the duodenum. We must not insert the tube too deeply, must not continue to inflate the balloon for a long time, and must check its position using a stethoscope, simple x-ray examination, or ultrasound. [Copyright &y& Elsevier]

The article presents a retrospective study on patients with gastrointestinal performation (GIP) who had cardiopulmonary arrest (CPA). The condition of the 12 subjects in the study are described as well as their estimated collapse time. Conclusion of the study is that survival rates of GIP patients that go into CPA is weak but if CPAs are immediately observed, resuscitation is ideal.

Cancer immunotherapy using chimeric antigen receptor–armed T (CAR T) cells have been shown to improve outcomes significantly in patients with hematological malignancies. However, cytokine release syndrome (CRS) remains a risk. CRS is characterized by the excessive activation of CAR T cells and macrophages. Signs and symptoms of CRS are usually resolved after steroid administration, but steroids abrogate the expansion and persistence of CAR T cell populations. Tocilizumab is a humanized monoclonal antibody (mAb) that attenuates CRS without significant loss of CAR T cell activity. However, interleukin-6 (IL-6)/IL-6 receptor (IL-6R) blockade alone cannot relieve CRS symptoms fully, and novel treatments are needed to prevent or cure CRS. TO-207 is an N-benzoyl-L-phenylalanine derivative that significantly inhibits inflammatory cytokine production in human monocyte and macrophage-specific manner. We investigated whether TO-207 could inhibit cytokine production without impairing CAR T cell function in a CRS-simulating co-culture system. [ABSTRACT FROM AUTHOR]

Aim: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH.Methods: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5.Results: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032].Conclusion: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH. [ABSTRACT FROM AUTHOR]

Background/objective: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients.Methods: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed.Results: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome.Conclusions: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset. [ABSTRACT FROM AUTHOR]

Defibrillation plays a crucial role in early return of spontaneous circulation (ROSC) and survival of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm. Prehospital adrenaline administration increases the probability of prehospital ROSC. However, little is known about the relationship between number of prehospital defibrillation attempts and neurologically favourable survival in patients treated with and without adrenaline. Using a nationwide Japanese OHCA registry database from 2006 to 2020, 1,802,084 patients with OHCA were retrospectively analysed, among whom 81,056 with witnessed OHCA and initial shockable rhythm were included. The relationship between the number of defibrillation attempts before hospital admission and neurologically favourable survival rate (cerebral performance category score of 1 or 2) at 1 month was evaluated with subgroup analysis for patients treated with and without adrenaline. At 1 month, 18,080 (22.3%) patients had a cerebral performance category score of 1 or 2. In the study population, the probability of prehospital ROSC and favourable neurological survival rate were inversely associated with number of defibrillation attempts. Similar trends were observed in patients treated without adrenaline, whereas a greater number of defibrillation attempts was counterintuitively associated with favourable neurological survival rate in patients treated with prehospital adrenaline. Overall, a greater number of prehospital defibrillation attempts was associated with lower neurologically favourable survival at 1 month in patients with OHCA and shockable rhythm. However, an increasing number of shocks (up to the 4th shock) was associated with better neurological outcomes when considering only patients treated with adrenaline. [ABSTRACT FROM AUTHOR]

Background and purpose Stanford type A aortic dissection (AAD) sometimes causes acute ischemic stroke (AIS) or transient ischemic attack (TIA). There is little understanding of cerebrovascular imaging of AIS or TIA in patients with AAD. Methods Consecutive AIS/TIA patients with AAD who were admitted within 4.5 h of onset were reviewed. We compared findings of MRI/MRA between these and consecutive AIS/TIA patients without AAD within 4.5 h of onset. Results Seventeen AAD and 249 non-AAD patients were identified. Compared to non-AAD patients, AAD patients had infarcts more frequently in the right anterior cerebral artery (ACA) territory (18% vs. 2%, P  = 0.007) and the right middle cerebral artery (MCA) territory (71% vs. 29%, P  < 0.001). There was no difference between the groups regarding whether it was perforator or cortical infarct, single or multiple infarcts, unilateral or bilateral infarcts, or ischemic change extension. On the MRA imaging, the AAD patients more frequently had poor visualization of the right internal carotid artery (ICA) (47% vs. 6%, P  < 0.001). After adjustment for sex, age and confounding factors, the right ACA territory infarct [odds ratio (OR), 12.2; 95% confidence interval (CI), 1.4–119.4], the MCA territory infarct (OR, 4.9; 95% CI, 1.0–25.0) and poor visualization of the right ICA (OR, 18.1; 95% CI, 4.0–101.9) were independently associated with AAD. Conclusion In emergency AIS/TIA patients, right anterior circulation infarct and poor visualization of the right ICA on cerebrovascular imaging are potential imaging markers of AAD. [ABSTRACT FROM AUTHOR]

Background: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment.Methods/design: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group.Discussion: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy.Trial Registration: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Japanese cedar (Cryptomeria japonica) pollinosis is the most prevalent seasonal rhinitis in Japan. A standardized Japanese cedar pollen extract (CPE) containing 1.5-4.2 μg of Cry j 1 is currently the highest-concentration extract available for allergen-specific immunotherapy (SIT) against this pollinosis. Therefore, we developed a PEGylated fusion protein as a more effective SIT vaccine against Japanese cedar pollinosis. Methods: The fusion protein of major allergens for Japanese cedar pollen, Cry j 1 and Cry j 2, was expressed in Escherichia coli and conjugated with polyethylene glycol (PEG). The purified PEGylated Cry j 1/2 fusion protein (PEG-fusion) was subcutaneously injected four times into Cry j 1- sensitized mice and CPE-sensitized monkeys. The mice were then subcutaneously challenged with Cry j 1 and serum levels of Cry j 1-specific immunoglobulin, and the proliferation and cytokine production of splenocytes were analyzed. The monkeys were intranasally challenged with CPE and analyzed for Cry j 1-specific immunoglobulin levels in plasma. Results: Cry j 1-specific IgE was significantly attenuated in the PEG-fusion-treated group after Cry j 1-challenge and Cry j 1-specific IgG was significantly increased following PEG-fusion treatment in mice and monkeys. Proliferation and Th2-type cytokine production in splenocytes stimulated with Cry j 1 were also reduced in PEG-fusion-treated mice. IL10 and IL2 production were reduced, but not significantly, while IFN-γ was significantly increased in the PEG-fusion-treated group. Conclusions: A high-dose injection of PEG-fusion appears to be a valid candidate for a safer and more effective vaccine than the conventional SIT extract for Japanese cedar pollinosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) on the initial electrocardiogram (ECG). However, in patients without pre-hospital restoration of spontaneous circulation despite the initial VF/VT, the outcome is extremely low by conventional cardiopulmonary resuscitation (CPR). Extracorporeal CPR (ECPR) may enhance cerebral blood flow and recovery of neurological function. We prospectively examined how ECPR for OHCA with VF/VT would affect neurological outcomes. Methods and results: The design of this trial was a prospective, observational study. We compared differences of outcome at 1 and 6 months after OHCA between ECPR group (26 hospitals) and non-ECPR group (20 hospitals). Primary endpoints were the rate of favorable outcomes defined by the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories (CPC) 1 or 2 at 1 and 6 months after OHCA. Based on intention-to-treat analysis, CPC 1 or 2 were 12.3% (32/260) in the ECPR group and 1.5% (3/194) in the non-ECPR group at 1 month (P <0.0001), and 11.2% (29/260) and 2.6% (5/194) at 6 months (P =0.001), respectively. By per protocol analysis, CPC 1 or 2 were 13.7% (32/234) in the ECPR group and 1.9% (3/159) in the non-ECPR group at 1 month (P <0.0001), and 12.4% (29/234) and 3.1% (5/159) at 6 months (P =0.002), respectively. Conclusions: In OHCA patients with VF/VT on the initial ECG, a treatment bundle including ECPR, therapeutic hypothermia and IABP was associated with improved neurological outcome at 1 and 6 months after OHCA. [Copyright &y& Elsevier]

Algicidal and growth-inhibiting bacteria (GIB) are promising tools for mitigating the negative impacts of harmful algal blooms in coastal environments; however, there is a paucity of quantitative data describing their ecological effects. Here, we investigate their temporal and spatial distribution in the southwest Yatsushiro Sea during the summer of 2011, by co-culturing bacterial isolates with an axenic culture of a fish-killing raphidophyte Chattonella antiqua. This novel co-culturing method excludes other biological influences, such as promotion of algal growth by some bacteria. The highest density (1.6 × 104 cells mL−1) of algicidal bacteria (AB) was detected at the surface of the nearshore station on 3 August 2011 when the maximum chlorophyll a concentration was observed, associated with the high abundance of two centric diatoms, low abundance of dinoflagellates and the absence of C. antiqua. On 10 August, total bacterial abundance increased at 10 m, suggesting that the bacteria used decaying organic matter derived from dead microalgae sinking to the bottom to promote their growth. Most of AB (87.5%) were found to be particle associated, suggesting these bacteria attached to the dead phytoplankton particles after killing them. Two types of GIB impaired co-cultured C. antiqua by inducing unusual cell deformations, including round and elongated cell morphologies. Partial 16S rRNA sequencing showed that algicidal and GIB were mainly comprised of “γ- and a-proteobacteria”. This study provides a new perspective on the dynamics of AB, suggesting that they play a significant role in regulating microalgal composition, physiology and abundance in coastal marine environments. [ABSTRACT FROM PUBLISHER]

• Maoto and its constituent ephedrine inhibited systemic inflammatory responses. • The anti-inflammatory effects of maoto were T-cell-independent. • Maoto increased IL-10 levels independent of its anti-inflammatory effects. • Maoto did not act directly on inflammatory cells. • Maoto exerted its anti-inflammatory effects via β-adrenergic receptors. Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a β-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via β-adrenergic receptors in vivo. [ABSTRACT FROM AUTHOR]

Abstract: A harmful bloom due to the raphidophycean flagellate, Chattonella antiqua, was found in the Yatsushiro Sea, western Kyushu, Japan, from the end of July to the beginning of August 2009. The bloom resulted in enormous economic damage to cultured finfish production in aquaculture farms concentrated in the southwestern area. To investigate the factors controlling the spatio-temporal distribution of the bloom, data analysis and numerical simulations were conducted using field monitoring data and a three-dimensional hydrodynamic model coupled to a Lagrangian particle-tracking model. Results of the monitoring data analysis showed that the initial development of the C. antiqua bloom occurred in Kusuura Bay and the northeastern area near the mouth of the Kuma River, and subsequently the bloom expanded rapidly to the whole area. The simulation results indicated that the source region of the widespread bloom was not Kusuura Bay but the northeastern area. The southwestward evolution of the bloom was primarily controlled by the passive transport due to the surface residual current driven by fresh water discharge from the Kuma River and northeasterly winds. On the favorable conditions of river discharge and wind, the massive bloom of C. antiqua that formed in the northeastern area was quickly transported southwestward within a few days. [Copyright &y& Elsevier]

Abstract: Objective: To assess the role of percutaneous cardiopulmonary support (PCPS) for the resuscitation of patients with massive pulmonary embolism (PE) with circulatory collapse. We also compared outcomes for PCPS between patients with massive PE with circulatory collapse and patients with AMI with cardiogenic shock. Background: The effectiveness of PCPS for acute myocardial infarction (AMI) complicated with cardiogenic shock has been reported, but there are few reports on the use of PCPS for massive PE with circulatory collapse. Method: We studied 12 consecutive patients with massive PE and 16 patients with AMI, who required PCPS for resuscitation either during cardiopulmonary resuscitation (CPR) or after successful CPR. Results: Twelve patients with PE and 16 patients with AMI were identified. There were no differences in age, the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score at admission, rate of cardiac arrest on arrival, and time from first circulatory collapse to PCPS between the two groups. However, the proportion of men with PE (33%) was smaller than those with AMI (87%, p <0.05). The duration of PCPS was shorter in PE (38h) compared with AMI (83h, p =0.051) patients. The proportion of patients successfully weaned from PCPS (100% vs. 37.5%, p <0.01), survival rate at discharge (83.3% vs. 12.5%, p <0.001) and good neurological outcome (58.3% vs. 6.3%, p =0.004) was significantly higher for PE compared to AMI patients. Conclusion: In our small case series, percutaneous cardiopulmonary support (PCPS) had a life saving role in patients with massive PE and cardiac arrest. PCPS was also more effective in patients with massive PE with cardiac arrest than in patients with AMI and cardiac arrest. [Copyright &y& Elsevier]

Abstract: Aims: GPR61 is an orphan G protein-coupled receptor whose function remains unknown. The purpose of the present study is to elucidate the importance of GPR61 in metabolism by characterization of GPR61-deficient mice. Main methods: Male GPR61-deficient mice were characterized regarding various metabolic parameters, including food intake, body weight, oxygen consumption, body temperature, locomotor activity, and in a pair feeding study. Hypothalamic gene expression was analyzed using real-time quantitative RT-PCR. Key findings: GPR61-deficient mice exhibited marked hyperphagia and heavier body weight than wild-type mice. Hyperphagia of GPR61-deficient mice was observed before the differences in body weight became apparent between the genotypes. When body weight difference did become apparent between genotypes, increases in visceral fat pad weight, liver weight, liver triglyceride (TG) content, plasma leptin, and plasma insulin were observed in GPR61-deficient mice, suggesting that GPR61 deficiency caused obesity associated with hyperphagia. Oxygen consumption, body temperature, and locomotor activity were not significantly different between GPR61-deficient and wild-type mice. Pair-fed GPR61-deficient mice had a greater fat mass than wild-type mice despite comparable body weight in both genotypes. The mRNA levels of proopiomelanocortin (POMC) and brain-derived neurotropic factor (BDNF) in the hypothalamus of GPR61-deficient mice were significantly lower than those of wild-type mice. Significance: GPR61-deficient mice exhibited obesity associated with hyperphagia. These findings suggest that GPR61 is involved in the regulation of food intake and body weight, and may be of importance when considering GPR61 as a therapeutic target for obesity or eating disorders. [Copyright &y& Elsevier]

Background: There are few strategies for treating patients who have suffered cardiopulmonary arrest due to blunt trauma (BT-CPA). The aim of this population-based case series observational study was to clarify the outcome of BT-CPA patients treated with a standardized strategy that included an emergency department thoracotomy (EDT) under an emergency medical service (EMS) system with a rapid transportation system. Methods: The 477 BT-CPA registry data were augmented by a review of the detailed medical records in our emergency department (ED) and action reports in the prehospital EMS records. Results: Of those, 76% were witnessed and 20% were CPA after leaving the scene. In all, 18% of the patients went to the intensive care unit (ICU), the transcatheter arterial embolization (TAE) room, or the operating room (OR). Only 3% survived to be discharged. Among the 363 witnessed patients-11 of whom had ventricular fibrillation (VF) as the initial rhythm, 134 exhibiting pulseless electrical activity (PEA), and 221 with asystole-13, 1, and 3%, respectively, survived to discharge. The most common initial rhythm just after collapse was not VF but PEA, and asystole increased over the 7 min after collapse. There were no differences in the interval between arrival at the hospital and the return of spontaneous circulation between the patients that survived to discharge and deceased patients in the ED, OR, TAE room, or ICU. The longest interval was 17 min. Conclusions: In BT-CPA patients, a 20-min resuscitation effort and termination of the effort are thought to be relevant. The initial rhythm is not a prognostic indicator. We believe that the decision on whether to undertake aggressive resuscitation efforts should be made on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Although favourable outcomes in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest have been frequently reported in Japanese journals since the late 1980s, there has been no meta-analysis of ECPR in Japan. This study reviewed and analysed all previous studies in Japan to clarify the survival rate of patients receiving ECPR. Material and methods: Case reports, case series and abstracts of scientific meetings of ECPR for out-of-hospital cardiac arrest written in Japanese between 1983 and 2008 were collected. The characteristics and outcomes of patients were investigated, and the influence of publication bias of the case-series studies was examined by the funnel-plot method. Results: There were 1282 out-of-hospital cardiac arrest patients, who received ECPR in 105 reports during the period. The survival rate at discharge given for 516 cases was 26.7±1.4%. The funnel plot presented the relationship between the number of cases of each report and the survival rate at discharge as the reverse-funnel type that centred on the average survival rate. In-depth review of 139 cases found that the rates of good recovery, mild disability, severe disability, vegetative state, death at hospital discharge and non-recorded in all cases were 48.2%, 2.9%, 2.2%, 2.9%, 37.4% and 6.4%, respectively. Conclusions: Based on the results of previous reports with low publication bias in Japan, ECPR appears to provide a higher survival rate with excellent neurological outcome in patients with out-of-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and evaluation of a series of 2,4-diaminopyridine-based neuropeptide Y Y1 (NPY Y1) receptor antagonists are described. Compound 1 was previously reported by our laboratory to be a potent and selective Y1 antagonist; however, 1 was also found to have potent hERG inhibitory activity. The main focus of this communication is structure–activity relationship development aimed at eliminating the hERG activity of 1. This resulted in the identification of compound 3d as a potent and selective NPY Y1 antagonist with reduced hERG liability. [Copyright &y& Elsevier]

To identify an early, simple, noninvasive predictor of left main (LM) or 3-vessel disease (3-VD), we retrospectively studied clinical variables on admission in 310 patients with acute coronary syndromes with non–ST-segment elevation. Univariate analysis indicated that many factors were related to LM/3-VD. Multivariate analysis showed that ST-segment elevation in lead aVR of ≥0.5 mm was the strongest predictor of LM/3-VD, followed by positive troponin T (odds ratio 19.7, p &#60;0.001, and odds ratio 3.08, p = 0.048, respectively). ST-segment elevation in lead aVR of ≥0.5 mm and positive troponin T identified LM/3-VD with sensitivities of 78% and 62%, specificities of 86% and 59%, positive predictive values of 57% and 26%, and negative predictive values of 95% and 87%, respectively (p &#60;0.05). Our findings suggest that in patients with non–ST-segment elevation acute coronary syndromes, ST-segment elevation in lead aVR of ≥0.5 mm and positive troponin T on admission (especially the former) are useful predictors of LM/3-VD. [Copyright &y& Elsevier]

Background: While studies have shown that the first documented rhythm is associated with clinical outcome in patients with cardiac arrest, little is known about the difference in clinical outcomes between two types of shockable rhythm (i.e., pulseless ventricular tachycardia [p-VT] and ventricular fibrillation [VF]) among patients with out-of-hospital cardiac arrest (OHCA). Methods: Using a nationwide, prospective population-based OHCA database from 2011 to 2015, we included witnessed adult (aged ≥18 years) patients. Patients who were used public-automated external defibrillator were excluded because of the unavailability of the first documented rhythm. The primary outcome was favorable 30-day neurological survival. To determine the association of the first documented rhythm with outcome, we used logistic regression model with adjustment for patient-level factors (age, sex, etiology of OHCA and incidence year) and prehospital care-related factors (type of witness, bystander cardiopulmonary resuscitation status, and time interval from collapse to the first defibrillation). Results: A total of 22,506 witnessed OHCA patients (median age, 68 years; male, 77%) having shockable rhythm as the first documented rhythm were included: 809 (3.6%) were p-VT and 21,697 (96.4%) were VF. Compared to VF patients, p-VT patients were older (median, 77 years vs. 67 years, p<0.0001), less likely to be male (61.6% vs. 77.6%, P<0.001), less likely to be cardiogenic (69.3% vs. 89.0%, p<0.001), more likely to be witnessed by EMS personnel (43.1% vs. 11.1%, P<0.001) and had shorter time from collapse to the first defibrillation (median, 6 min vs. 11 min, p<0.001). P-VT patients had a higher ROSC rate (40.2% vs. 33.9%, P<0.001), but there was no difference in favorable 30-day neurological survival (23.4% vs. 22.1%, P=0.38). After adjustment for patient-level and prehospital care-related factors, p-VT was associated with better ROSC and favorable 30-day neurological survivalrates with corresponding adjusted odds ratios of 1.86 (95% CI, 1.52-2.27, P<0.001) and 1.59 (95% CI 1.27-1.99, P<0.001). Conclusion: In this nation-wide population-based study of OHCA, patients with p-VT as the first documented rhythm had significantly better outcome compared to those with VF. [ABSTRACT FROM AUTHOR]

Objectives: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest.Design: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study.Setting: Fourteen hospitals throughout Japan.Patients: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011.Intervention: None.Measurements and Main Results: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004).Conclusions: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]