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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]

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: 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]

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]

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]

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]

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]

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]