ARCH Project and the Global Initiatives of Disaster Health Management.

OBJECTIVE: The prime aim of Project for Strengthening the ASEAN Regional Capacity on Disaster Health Management (ARCH Project) is to strengthen the disaster health management (DHM) capacity in the context of personal level, Emergency Medical Team (EMT), and the regional collaboration. The ARCH Project was implemented with reference to international trends of DHM and seeks to contribute to the development of global standards. METHODS: The project established the Project Working Groups that consisted of representatives of ASEAN Member States (AMS) to develop standard operating procedures (SOP) for international EMT (I-EMT) coordination. Furthermore, it aimed to organize training sessions along with implementation of the regional collaboration drill (RCD) in accordance with I-EMT minimum requirements and in line with coordination standards set by the WHO. RESULTS: The ARCH Project developed the SOP and common platform for I-EMT coordination, organized training, and conducted RCDs with reference to the WHO's EMT initiative. Furthermore, it also contributed to the development of the EMT Minimum Data Set (MDS), an international standard DHM tool that underwent testing at the RCDs before the WHO endorsement and its utilization in actual disaster response. CONCLUSION: In the process of strengthening ASEAN regional capacity in DHM, the project is constantly capturing international trends and also making significant contributions in the development of global systems and tools.

Time-Series Change of Serum Soluble T-Cadherin Concentrations and Its Association with Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction.

AIMS: T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI). METHODS: This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418). RESULTS: Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p＜0.001 and p＜0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p＜0.01). CONCLUSION: Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.

Author Correction: Adiponectin promotes muscle regeneration through binding to T-cadherin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Adiponectin promotes muscle regeneration through binding to T-cadherin.

Skeletal muscle has remarkable regenerative potential and its decline with aging is suggested to be one of the important causes of loss of muscle mass and quality of life in elderly adults. Metabolic abnormalities such as obesity were linked with decline of muscle regeneration. On the other hand, plasma levels of adiponectin are decreased in such metabolic conditions. However, plasma levels of adiponectin have been shown to inversely correlate with muscle mass and strength in elderly people especially with chronic heart failure (CHF). Here we have addressed whether adiponectin has some impact on muscle regeneration after cardiotoxin-induced muscle injury in mice. Muscle regeneration was delayed by angiotensin II infusion, mimicking aging and CHF as reported. Adiponectin overexpression in vivo decreased necrotic region and increased regenerating myofibers. Such enhanced regeneration by excess adiponectin was also observed in adiponectin null mice, but not in T-cadherin null mice. Mechanistically, adiponectin accumulated on plasma membrane of myofibers both in mice and human, and intracellularly colocalized with endosomes positive for a multivesicular bodies/exosomes marker CD63 in regenerating myofibers. Purified high-molecular multimeric adiponectin similarly accumulated intracellularly and colocalized with CD63-positive endosomes and enhanced exosome secretion in differentiating C2C12 myotubes but not in undifferentiated myoblasts. Knockdown of T-cadherin in differentiating C2C12 myotubes attenuated both adiponectin-accumulation and adiponectin-mediated exosome production. Collectively, our studies have firstly demonstrated that adiponectin stimulates muscle regeneration through T-cadherin, where intracellular accumulation and exosome-mediated process of adiponectin may have some roles.

Low-flow time is associated with a favorable neurological outcome in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation.

PROPOSE: The aim of this retrospective study was to investigate the prognostic factors in extracorporeal cardiopulmonary resuscitation (ECPR) patients and to assess their accuracy as predictors of a favorable neurological outcome. MATERIALS AND METHODS: Between October 2009 and December 2017, we retrospectively analyzed witnessed out-of-hospital cardiac arrest patients who were admitted to our hospital and resuscitated with ECPR. We compared the baseline characteristics, pre-hospital clinical course, arrest causes, and blood samples on admission for the favorable and unfavorable outcome groups. RESULTS: Among the 135 patients included, 22 (16%) had a favorable neurological outcome. Low-flow time was shorter (median 38 vs. 48 min, p < 0.001) in the favorable neurological outcome group; in multiple logistic analyses, low-flow time was significantly associated with a favorable neurological outcome (odds ratio, 0.88; 95% confidence interval, 0.82-0.94). The area under the receiver-operating characteristic curve of low-flow time was 0.80 (95% confidence interval, 0.70-0.89), and the cut-off value of 58 min corresponded to a sensitivity of 0.25 and a specificity of 1.0. CONCLUSIONS: In ECPR patients, low-flow time was significantly associated with a favorable neurological outcome, and ECPR should be performed within 58 min of the low-flow time.

Impact of extracorporeal cardiopulmonary resuscitation on outcomes of elderly patients who had out-of-hospital cardiac arrests: a single-centre retrospective analysis.

OBJECTIVES: Little is known about the effectiveness of extracorporeal cardiopulmonary resuscitation (ECPR) for elderly patients who had out-of-hospital cardiac arrest (OHCA). The aim of this study was to examine the impact of age on outcomes among patients who had OHCA treated with ECPR. DESIGN: Single-centre retrospective cohort study. SETTING: A critical care centre that covers a population of approximately 1 million residents. PARTICIPANTS: Patients who had consecutive OHCA aged ≥18 years who underwent ECPR from 2005 to 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were 1 month neurologically favourable outcomes and survival. To determine the association between advanced age and each outcome, we fitted multivariable logistic regression models using: (1) age as a continuous variable and (2) age as a categorical variable (<50 years, 50-59 years, 60-69 years and ≥70 years). RESULTS: Overall, 144 patients who had OHCA who underwent ECPR were eligible for our analyses. The proportion of neurologically favourable outcomes was 7%, while survival was 19% in patients who had OHCA. After the adjustment for potential confounders, while advanced age was non-significantly associated with neurologically favourable outcomes (adjusted OR 0.96 (95% CI 0.91 to 1.01), p=0.08), the association between advanced age and the poor survival rate was significant (adjusted OR 0.96 (95% CI 0.93 to 0.99), p=0.04). Additionally, compared with age <50 years, age ≥70 years was non-significantly associated with poor neurological outcomes (adjusted OR 0.08 (95% CI 0.01 to 1.00), p=0.051), whereas age ≥70 years was significantly associated with worse survival in the adjusted model (adjusted OR 0.14 (95% CI 0.03 to 0.80), p=0.03). CONCLUSIONS: In our analysis of consecutive OHCA data from a critical care hospital in an urban area of Japan, we found that advanced age was associated with the lower rate of 1-month survival in patients who had OHCA who underwent ECPR. Although larger studies are required to confirm these results, our findings suggest that ECPR may not be beneficial for patients who had OHCA aged ≥70 years.

Association of Epicardial, Visceral, and Subcutaneous Fat With Cardiometabolic Diseases.

BACKGROUND: Excess of visceral fat is a central factor in the pathogenesis of metabolic syndrome (MetS) and atherosclerosis. However, little is known about how much epicardial fat affects cardiometabolic disorders in comparison with visceral or subcutaneous fat.Methods and Results:Participants suspected as having angina pectoris underwent cardiac computed tomography (CT) imaging. Of them, 374 subjects were analyzed the association of clinical characteristics and CT-based fat distribution measured as epicardial fat volume (EFV), visceral fat area (VFA), and subcutaneous fat area (SFA). EFV was highly associated with VFA (R=0.58). Serum adiponectin was significantly decreased in high VFA subjects (VFA ≥100 cm2) and was also reduced in the high EFV group (EFV ≥80 cm3). Among the low VFA groups, the numbers of subjects with diabetes and coronary atherosclerosis were increased in high EFV group. Among the low EFV groups, the numbers of subjects with diabetes, hyperuricemia, and coronary atherosclerosis were increased among the high VFA subjects. In an age-, sex-, and body mass index (BMI)-adjusted model, EFV was associated with dyslipidemia and MetS, and VFA was significantly associated with hypertension, dyslipidemia, MetS, and coronary atherosclerosis, while SFA was not related with coronary risks and atherosclerosis. CONCLUSIONS: Epicardial fat accumulation may be a risk for coronary atherosclerosis in subjects without visceral fat accumulation. Visceral fat is the strongest risk for cardiometabolic diseases among the 3 types of fat depot.

D-dimer predicts bleeding complication in out-of-hospital cardiac arrest resuscitated with ECMO.

PURPOSE: In out-of-hospital cardiac arrest (OHCA) patients resuscitated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), known as extracorporeal cardiopulmonary resuscitation (ECPR), bleeding is a common complication. The purpose of this study was to assess the risk factors for bleeding complications in ECPR patients. METHODS: We retrospectively analyzed the data for OHCA patients admitted to our hospital and resuscitated with ECPR between October 2009 and December 2016. We compared patients with and without major bleeding (i.e. the Bleeding Academic Research Consortium class≥3 bleeding) within 24h of hospital admission. Patients, whose bleeding complication was not evaluated, were excluded. RESULTS: During the study period, 133 OHCA patients were resuscitated with ECPR, of whom 102 (77%) were included. In total, 71 (70%) patients experienced major bleeding. There were significant differences in age (median 65 vs. 50years, P<0.001), prior antiplatelet therapy (25% vs. 3%, P=0.008), hemoglobin (median 11.6 vs. 12.6g/dL, P=0.003), platelet count (median 125 vs. 155×103/µL, P=0.001), and D-dimer levels on admission (median 18.8 vs. 6.7µg/mL, P<0.001) among patients with and those without major bleeding. Multivariate analysis showed significant associations between major bleeding and D-dimer levels (odds ratio, 1.066; 95% confidence interval, 1.018-1.116). Area under receiver-operating characteristic curve, which describes the accuracy of D-dimer levels in predicting major bleeding, was 0.76 (95% confidence interval, 0.66-0.87). CONCLUSION: D-dimer levels may predict major bleeding in ECPR patients, suggesting that hyperfibrinolysis may be related to bleeding.

Global Registry of Acute Coronary Events risk score predicts mortality and neurological outcome in out-of hospital cardiac arrest.

PURPOSE: The aim of this study was to assess the usefulness of the Global Registry of Acute Coronary Events (GRACE) risk score in predicting in-hospital mortality and neurological outcome of patients resuscitated after out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively analyzed the data of patients admitted to our hospital between October 2009 and October 2015 with OHCA and shockable initial cardiac rhythm who were resuscitated via conventional cardiopulmonary resuscitation. We calculated the GRACE risk score on admission and assessed its usefulness in predicting in-hospital mortality and neurological outcome. RESULTS: Among 91 patients, 42 (46%) had acute myocardial infarction (AMI), 19 (21%) died in-hospital, and 52 (57%) had favorable neurological outcome. Among all the study patients, GRACE risk score was lower in survivors than in non-survivors (median 211 [interquartile range 176-240] vs. 266 [219-301], p<0.001, respectively) and in favorable than in unfavorable neurological outcome group (202 [167-237] vs. 242 [219-275], p<0.001, respectively). Multivariate analysis showed significant association between GRACE risk score and favorable neurological outcome (odds ratio, 0.975; 95% confidence interval, 0.961-0.990). Areas under receiver-operating characteristic curves, that describe the accuracy of GRACE risk score in predicting in-hospital mortality and favorable neurological outcome, were both 0.79. CONCLUSION: GRACE risk score may predict the in-hospital mortality and neurological outcome associated with resuscitated patients with OHCA and shockable initial cardiac rhythm, regardless of the cause of arrest.

Significant Association of Serum Adiponectin and Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction.

AIMS: Adiponectin, an adipocyte-specific secretory protein, abundantly exists in the blood stream while its concentration paradoxically decreases in obesity. Hypoadiponectinemia is one of risks of cardiovascular diseases. However, impact of serum adiponectin concentration on acute ischemic myocardial damages has not been fully clarified. The present study investigated the association of serum adiponectin and creatine kinase (CK)-MB levels in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS: This study is a physician-initiated observational study and is also registered with the University Hospital Medical Information Network (Number: UMIN 000014418). Patients were admitted to Senri Critical Care Medical Center, given a diagnosis of STEMI, and treated by primary percutaneous coronary intervention (PCI). Finally, 49 patients were enrolled and the association of serum adiponectin, CK-MB, and clinical features were mainly analyzed. RESULTS: Serum adiponectin levels decreased rapidly and reached the bottom at 24 hours after recanalization. Such reduction of serum adiponectin was inversely correlated with the area under the curve (AUC) of serum CK-MB (p=0.013). Serum adiponectin concentrations were inversely correlated with AUC of serum CK-MB. In multivariate analysis, serum adiponectin concentration on admission (p=0.002) and collateral (p=0.037) were significantly and independently correlated with serum AUC of CK-MB. CONCLUSION: Serum AUC of CK-MB in STEMI subjects was significantly associated with serum adiponectin concentration on admission and reduction of serum adiponectin levels from baseline to bottom. The present study may provide a possibility that serum adiponectin levels at acute phase are useful in the prediction for prognosis after PCI-treated STEMI subjects.

Resistance to conventional cardiopulmonary resuscitation in witnessed out-of-hospital cardiac arrest patients with shockable initial cardiac rhythm.

BACKGROUND: Shockable initial cardiac rhythm is a key predictor of survival after out-of-hospital cardiac arrest (OHCA). However, not all patients with shockable OHCA achieve return of spontaneous circulation (ROSC) via conventional cardiopulmonary resuscitation (CPR). Therefore, we retrospectively analyzed patients with witnessed OHCA and shockable initial cardiac rhythm to identify the resistance factors for conventional CPR. METHODS: We retrospectively analyzed consecutive patients with witnessed OHCA and shockable initial cardiac rhythm who were admitted to our hospital between October 2009 and October 2014. We then compared the baseline characteristics, pre-hospital clinical course, and causes of the cardiopulmonary arrest among patients who achieved ROSC via conventional CPR and patients who did not achieve ROSC via conventional CPR and underwent extracorporeal CPR (ECPR). RESULTS: A total of 85 patients achieved ROSC via conventional CPR (non-ECPR group) and 40 patients did not achieve ROSC via conventional CPR and underwent ECPR (ECPR group). Among these 125 patients, 113 had known causes for their cardiopulmonary arrest, including 66 cases (53%) of acute myocardial infarction (AMI). There were no significant differences in the causes of arrest between the non-ECPR and ECPR cases. However, among the 66 cases of AMI (43 non-ECPR and 23 ECPR), the rate of non-recanalization during the initial coronary angiography was significantly higher among the ECPR cases (non-ECPR: 58% vs. ECPR: 87%; p=0.03). CONCLUSIONS: The major cause of witnessed OHCA with shockable initial cardiac rhythm was AMI, and resistance to conventional CPR was related to continuous myocardial ischemia.

Indication for mild therapeutic hypothermia based on an initial Glasgow Coma Scale motor score.

Although neurological evaluation using the Glasgow Coma Scale motor score is mandatory for post-cardiac arrest patients, further study is required to determine if this score can be used as an indicator for mild therapeutic hypothermia. Although the current study conducted by Natsukawa et al. presents interesting data, there are some critical issues regarding study design, selection bias, and interpretation of study results that should be pointed out.

At what level of unconsciousness is mild therapeutic hypothermia indicated for out-of-hospital cardiac arrest: a retrospective, historical cohort study.

BACKGROUND: Appropriate patient selection is very important when initiating mild therapeutic hypothermia (MTH) for patients following out-of-hospital cardiac arrest, and the extent of unconsciousness at implementation must be defined in such cases. However, there are no clear standards regarding the level of unconsciousness at which MTH would be beneficial. The effects of MTH in patients with different degrees of unconsciousness according to the motor response score of the Glasgow Coma Scale (GCS) were investigated. METHODS: The subjects consisted of witnessed non-traumatic adult out-of-hospital cardiac arrest patients admitted to our institute from April 2002 to August 2011. The patients were divided into six groups according to the GCS motor response score: 1 (GCS M1), 2 (GCS M2), 3 (GCS M3), 4 (GCS M4), 5 (GCS M5), and 6 (GCS M6). The neurological outcome was evaluated at 30 days after hospital admission using the Cerebral Performance Category. Chi-squared Automatic Interaction Detection (CHAID) analysis was performed to estimate the threshold GCS M level where therapeutic hypothermia is indicated. Odds ratios were then calculated by multiple logistic-regression analysis using factors including GCS M5-6 and MTH. RESULTS: A total of 289 patients were enrolled in this study. CHAID analysis demonstrated two points of significant increase in percentage of good recovery at 30 days after admission, dividing the GCS M categories into three groups. Patients classified with a GCS motor response score of 5 or higher had the highest percentage of good recovery. The odds ratio for good recovery (CPC1-2) was 2.901 (95 % CI 1.460-5.763, P = 0.002) for MTH, and that for GCS M5-6 was 159.835 (95 % CI 33.592-760.513, P < 0.001). CONCLUSIONS: MTH may be unnecessary in patients with a GCS motor response score of 5 or higher. Consequently, because there are post cardiac arrest patients with a GCS motor response score of 4 or lower who benefit from MTH, MTH may be limited to patients with a GCS motor response score of 4 or lower.

Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.

PURPOSE: In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. METHODS: We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 µg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. RESULTS: As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. CONCLUSION: Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Distal protection during primary coronary intervention can preserve the index of microcirculatory resistance in patients with acute anterior ST-segment elevation myocardial infarction.

BACKGROUND: The objective of this study was to investigate whether a distal protection (DP) device can preserve the index of microcirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study group of 36 consecutive patients with anterior STEMI were randomized into 2 groups of primary PCI with or without DP: stenting without DP (non-DP group, n = 17) and with DP (DP group, n = 19). The DP in all cases was Filtrap (Nipro, Japan). Following final coronary angiography after successful PCI, IMR was measured using PressureWire™ Certus (St Jude Medical, USA) at maximal hyperemia. The averaged IMR of the 36 patients with STEMI after primary PCI was 31.6U. The IMR in the DP group was significantly lower than that in the non-DP group (26.6 ± 25.8U vs. 37.2 ± 23.2U, P = 0.03242). CONCLUSIONS: DP as an adjunctive therapy of PCI for acute anterior STEMI may have beneficial effects on myocardial microcirculation because of preservation of IMR.