Impact of Updating the Cardiopulmonary Resuscitation Guidelines on Out-of-Hospital Shockable Cardiac Arrest: A Population-Based Cohort Study in Japan.

BACKGROUND: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science and treatment recommendations (CoSTR) have reported updates on CPR maneuvers every 5 years since 2000. However, few national population-based studies have investigated the comprehensive effectiveness of those updates for out-of-hospital cardiac arrest due to shockable rhythms. The primary objective of the present study was to determine whether CPR based on CoSTR 2005 or 2010 was associated with improved outcomes in Japan, as compared with CPR based on Guidelines 2000. METHODS AND RESULTS: From the All-Japan Utstein Registry between 2005 and 2015, we included 73 578 adults who had shockable out-of-hospital cardiac arrest witnessed by bystanders or emergency medical service responders. The study outcomes over an 11-year period were compared between 2005 of the Guidelines 2000 era, from 2006 to 2010 of the CoSTR 2005 era, and from 2011 to 2015 of the CoSTR 2010 era. In the bystander-witnessed group, the adjusted odds ratios for favorable neurological outcomes at 30 days after out-of-hospital cardiac arrest by enrollment year increased year by year (1.19 in 2006, and 3.01 in 2015). Similar results were seen in the emergency medical service responder-witnessed group and several subgroups. CONCLUSIONS: Compared with CPR maneuvers for shockable out-of-hospital cardiac arrest recommended in the Guidelines 2000, CPR maneuver updates in CoSTR 2005 and 2010 were associated with improved neurologically intact survival year by year in Japan. Increased public awareness and greater dissemination of basic life support may be responsible for the observed improvement in outcomes. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: 000009918.

Triglyceride/high-density lipoprotein cholesterol ratio may be a better index of cardiometabolic risk in women than in men in Japan.

BACKGROUND AND AIMS: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts. METHODS AND RESULTS: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis. CONCLUSION: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations.

Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Association of Higher N-3 Polyunsaturated Fatty Acid Consumption and Aerobic Exercise with Lower Neutrophil-to-Lymphocyte Ratio: Implications of Anti-Atherosclerotic Effect of Fish Consumption.

INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker. METHODS: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey. RESULTS: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits. CONCLUSION: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk.

Neurological Improvement via Lysophosphatidic Acid Administration in a Rodent Model of Cardiac Arrest-Induced Brain Injury.

Lysophosphatidic acid (LPA) serves as a fundamental constituent of phospholipids. While prior studies have shown detrimental effects of LPA in a range of pathological conditions, including brain ischemia, no studies have explored the impact of LPA in the context of cardiac arrest (CA). The aim of this study is to evaluate the effects of the intravenous administration of an LPA species containing oleic acid, LPA (18:1) on the neurological function of rats (male, Sprague Dawley) following 8 min of asphyxial CA. Baseline characteristics, including body weight, surgical procedure time, and vital signs before cardiac arrest, were similar between LPA (18:1)-treated (n = 10) and vehicle-treated (n = 10) groups. There was no statistically significant difference in 24 h survival between the two groups. However, LPA (18:1)-treated rats exhibited significantly improved neurological function at 24 h examination (LPA (18:1), 85.4% ± 3.1 vs. vehicle, 74.0% ± 3.3, p = 0.045). This difference was most apparent in the retention of coordination ability in the LPA (18:1) group (LPA (18:1), 71.9% ± 7.4 vs. vehicle, 25.0% ± 9.1, p < 0.001). Overall, LPA (18:1) administration in post-cardiac arrest rats significantly improved neurological function, especially coordination ability at 24 h after cardiac arrest. LPA (18:1) has the potential to serve as a novel therapeutic in cardiac arrest.

Impaired consciousness and unilateral limb movement due to acute limb ischemia complicated by acute cerebral infarction: A case report.

RATIONALE: The symptoms of impaired consciousness and unilateral motor impairments are a perfect scenario for cerebral infarction, and a physician can easily miss the findings of limb ischemia on the patient paralyzed side even if acute limb ischemia (ALI) occurs on that side. The purpose of this case report is to reiterate the need to suspect ALI in patients with impaired consciousness who cannot complain of symptoms such as abnormal limb paresthesia or pain. PATIENT CONCERNS: An 89-year-old woman with impaired consciousness and motor impairment of the left upper and lower extremities was transported to our hospital. DIAGNOSES: Brain magnetic resonance imaging showed a suspected cerebral infarction in the posterior circulation; contrast-enhanced computed tomography showed occlusion of the left axillary artery and left femoral artery; and ultrasonography showed occlusion of the right popliteal artery. INTERVENTIONS: Cerebral angiography was performed simultaneously with surgical thrombectomy to treat the ALI. Mechanical thrombectomy was not performed for cerebral infarction. OUTCOMES: Although motor impairment of the left upper and lower extremities persisted, the patient successfully underwent limb salvage. LESSONS: Both cerebral infarction and ALI require early diagnosis and treatment. This rare case of cerebral infarction complicated by ALI emphasizes the need to avoid missing the signs of ALI in patients with impaired consciousness.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Successful Therapeutic Hypothermia in a Patient with Drug-Induced J Waves and Cardiac Arrest: A Case Report.

A 50-year-old man was admitted to our hospital with hypotension and bradycardia after receiving high doses of atenolol, amlodipine, and etizolam. He had a drug-induced J wave on electrocardiography and subsequently underwent cardiac arrest. The patient was successfully rescued by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and a good neurological outcome was achieved with therapeutic hypothermia (TH). In patients with J waves, TH is thought to increase the J waves and cause fatal arrhythmias, but in this case, rapid cooling with VA-ECMO allowed the patient to successfully complete TH.

Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Higher frequency of fish intake and healthy lifestyle behaviors may be associated with a lower platelet count in Japan: Implication for the anti-atherosclerotic effect of fish intake.

BACKGROUND: Habitual fish intake and healthier lifestyles are associated with a lower risk of atherosclerotic cardiovascular disease (ASCVD). Higher platelet counts (PLCs) are reportedly associated with higher ASCVD events. We aimed to investigate the association between fish intake and lifestyle with PLCs. METHODS: We conducted a cross-sectional study in a cohort of 9329 participants (average age: 46.9 ± 12.9 years; 58.9% men) with no history of ASCVD registered at the Health Planning Center of Nihon University Hospital in 2019. RESULTS: The average fish intake frequency was 2.15 ± 1.28 days/week. As fish intake frequency increased (0, 1, 2, 3, 4, 5, 6, and 7 days), PLC decreased significantly (p < 0.0001). Multivariable logistic regression analysis showed that higher fish intake frequency tended to be a determinant of lower PLC. Aerobic exercise habits and sleep duration were independent negative determinants of PLC. Cigarette smoking habits were a positive independent determinant of PLC. Furthermore, with increasing fish intake frequency, the proportion of participants with habitual aerobic exercise, non-smoking habits, and longer sleep duration increased (p < 0.0001 for all). Higher n-3 polyunsaturated fatty acid (n-3 PUFA), calculated based on data from the Japanese National Health and Nutrition Survey, intake was associated with a lower PLC. CONCLUSION: Higher fish intake and healthier lifestyle behaviors may be comprehensively associated with lower PLCs. The intake of N-3 PUFA with anti-inflammatory effects, rich in fish, may also be related to the lower PLC. This association may explain the preventive effects of fish intake on ASCVD risk.

Habitual fish consumption and healthy lifestyle behaviours may be associated with higher total serum bilirubin level and anti-inflammatory activity: a cross-sectional study.

Habitual fish consumption and a healthy lifestyle are associated with lower atherosclerotic CVD (ASCVD) risk. Mildly elevated bilirubin, an end product of Hb metabolism, may be associated with anti-inflammatory effects, suppressing ASCVD risk. No data exist on the relationship between fish consumption, total serum bilirubin (TSB) and inflammation in clinical settings. We conducted a cross-sectional study between April 2019 and March 2020 in a cohort of 8292 participants (average age, 46·7 (sd 12·9) years and 58·9 % men) with no history of ASCVD and TSB concentrations < 2·0 mg/dl. Multiple stepwise regression analysis showed Hb concentrations were a solid positive determinant of TSB concentrations (ß = 0·302, P< 0·0001). Fish consumption (ß = 0·025, P= 0·019) and aerobic exercise (ß = 0·021, P= 0·043) were statistically weak but significantly positive determinants of TSB concentrations. Cigarette smoking negatively affected TSB concentrations (ß = −0·104, P< 0·0001). Moreover, with increasing fish consumption, the proportion of participants with a habit of cigarette smoking decreased, and that of participants who engaged in aerobic exercises increased (P< 0·0001 for both). Furthermore, as TSB concentrations increased, the leukocyte counts and C-reactive protein concentrations decreased (P< 0·0001 for both). In conclusion, despite the lesser relevance given to TSB concentrations than Hb concentrations, higher fish consumption and healthier lifestyle behaviours related to fish consumption habits may be additively or synergistically associated with higher TSB concentrations and anti-inflammatory activity, leading to attenuated ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.

Clinical picture of the duration of venoarterial extracorporeal membrane oxygenation: analysis from JROAD-DPC.

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.

Effect of Atorvastatin on Microcirculation Evaluated by Vascular Occlusion Test with Peripheral Near-Infrared Spectroscopy.

The vascular occlusion test (VOT) with peripheral near-infrared spectroscopy (NIRS) is a non-invasive method to evaluate peripheral microcirculation. Statin therapy is widely used for patients with dyslipidaemia and contributes to reducing low-density lipoprotein cholesterol (LDL-C) levels and adverse cardiovascular events. However, it is not yet clear whether statin treatment improves peripheral microcirculation assessed by VOT with NIRS. In the present study, using VOT with NIRS, we evaluated the effect of statin therapy on peripheral microcirculation in patients with dyslipidaemia before and after statin therapy. METHODS: A total of six consecutive patients with dyslipidaemia who had not received statin therapy (6 males, mean age 71.8 ± 7.4 years) were enrolled. All patients were administered atorvastatin and their peripheral microcirculation assessed using VOT with NIRS (NIRO-200NX, Hamamatsu Photonics K.K., Japan) before and after statin therapy. The NIRS probe was attached to the right thenar eminence and brachial artery blood flow was blocked for 3 min at 50 mmHg above the resting systolic blood pressure. Maximum and minimum values of NIRS parameters after the VOT were used to determine concentration changes for total haemoglobin (ΔcHb), oxyhaemoglobin (ΔO2Hb), deoxyhaemoglobin (ΔHHb), and tissue oxygenation index (ΔTOI). RESULTS: During the follow-up period (mean 30.3 ± 6.5 days), LDL-C level decreased from 129.7 ± 26.3 to 67.5 ± 20.2 mg/dL (p-value = 0.031), ΔTOI increased from 24.0 ± 5.3 to 33.7 ± 6.3% (p-value = 0.023), and ΔO2Hb increased from 16.4 ± 5.3 to 20.0 ± 6.6 µmol/L (p-value = 0.007). ΔcHb and ΔHHb did not change significantly. CONCLUSION: ΔO2Hb and ΔTOI were significantly increased during the follow-up period. These findings suggest that ΔO2Hb and ΔTOI could assess the improvement of peripheral microcirculation by statin therapy. Compared to ΔTOI, ΔO2Hb seems to be a more useful parameter to evaluate peripheral microcirculation.

Oxyhaemoglobin Level Measured Using Near-Infrared Spectrometer Is Associated with Brain Mitochondrial Dysfunction After Cardiac Arrest in Rats.

Cerebral blood oxygenation (CBO), measured using near-infrared spectroscopy (NIRS), can play an important role in post-cardiac arrest (CA) care as this emerging technology allows for noninvasive real-time monitoring of the dynamic changes of tissue oxygenation. We recently reported that oxyhaemoglobin (oxy-Hb), measured using NIRS, may be used to evaluate the quality of chest compressions by monitoring the brain tissue oxygenation, which is a critical component for successful resuscitation. Mitochondria are the key to understanding the pathophysiology of post-CA oxygen metabolism. In this study, we focused on mitochondrial dysfunction, aiming to explore its association with CBO parameters such as oxy-Hb and deoxyhaemoglobin (deoxy-Hb) or tissue oxygenation index (TOI). Male Sprague-Dawley rats were used in the study. We applied NIRS between the nasion and the upper cervical spine. Following 10 min of CA, the rats underwent cardiopulmonary resuscitation (CPR) with a bolus injection of 20 µg/kg epinephrine. At 10 and 20 min after CPR, brain, and kidney tissues were collected. We isolated mitochondria from these tissues and evaluated the association between CBO and mitochondrial oxygen consumption ratios. There were no significant differences in the mitochondrial yields (10 vs. 20 min after resuscitation: brain, 1.33 ± 0.68 vs. 1.30 ± 0.75 mg/g; kidney, 19.5 ± 3.2 vs. 16.9 ± 5.3 mg/g, respectively). State 3 mitochondrial oxygen consumption rates, known as ADP-stimulated respiration, demonstrated a significant difference at 10 vs. 20 min after CPR (brain, 170 ± 26 vs. 115 ± 17 nmol/min/mg protein; kidney, 170 ± 20 vs. 130 ± 16 nmol/min/mg protein, respectively), whereas there was no significant difference in ADP non-dependent state 4 oxygen consumption rates (brain, 34.0 ± 6.7 vs. 31.8 ± 10 nmol/min/mg protein; kidney, 29.8 ± 4.8 vs. 21.0 ± 2.6 nmol/min/mg protein, respectively). Consequently, the respiratory control ratio (RCR = state 3/state 4) showed a significant difference over time, but this was only noted in the brain (brain, 5.0 ± 0.29 vs. 3.8 ± 0.64; kidney, 5.8 ± 0.53 vs. 6.2 ± 0.25 nmol/min/mg protein, respectively). The oxy-Hb levels had a dynamic change after resuscitation, and they had a significant association with the RCR of the brain mitochondria (r = 0.8311, p = 0.0102), whereas deoxy-Hb and TOI did not (r = -0.1252, p = 0.7677; r = 0.4186, p = 0.302, respectively). The RCRs of the kidney mitochondria did not have a significant association with CBO (oxy-Hb, r = -0.1087, p = 0.7977; deoxy-Hb, r = 0.1565, p = 0.7113; TOI, r = -0.1687, p = 0.6896, respectively). The brain mitochondrial respiratory dysfunction occurred over time, and it was seen at the time points between 10 and 20 min after CPR. The oxy-Hb level was associated with brain mitochondrial dysfunction during the early post-resuscitation period.

Inadequate sleep duration may attenuate the anti-inflammatory effects of fish consumption in a healthy Japanese population: a cross-sectional study.

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (ß = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (ß = 0·059, P < 0·0001) or cigarette smoking (ß = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (ß = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (ß = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6­7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.

Associations of higher fish consumption and lifestyle with lower monocyte/HDL-C ratio in a Japanese population: Implication for the anti-atherosclerotic effect of fish consumption.

BACKGROUND: High fish consumption may be involved in lowering inflammation, resulting in the suppression of atherosclerotic cardiovascular disease (ASCVD) development. The monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is reported as a novel inflammatory marker of the development of atherosclerosis. We investigated the relationship between fish consumption, MHR, and lifestyle behaviors and explored the foundation of risk stratification of ASCVD using serum HDL-C, MHR, and fish consumption. METHODS: We conducted a cross-sectional study among 6841 adults at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020. We calculated the amount of fish consumption based on Japan's National Nutrition Survey results. RESULTS: The median (interquartile range) fish consumption was 111.4 (67.2/169.2) g per week. As fish consumption increased, MHR decreased significantly (p < 0.0001). Multivariate linear regression analysis identified increased fish consumption as an independent negative determinant of a decreased MHR (ß = -0.050, p < 0.0001). Additionally, healthier lifestyle behaviors (sleep duration and cigarette smoking habit) were also significantly associated with MHR (ß = -0.025, p = 0.027 and ß = 0.146, p < 0.0001, respectively). Furthermore, risk stratification of ASCVD could be developed by combining the HDL-C level and fish consumption with the MHR, indicating that even with similar HDL-C levels, higher MHR and lower fish consumption are associated with a higher risk of ASCVD. Multi-logistic regression analysis with the MHR quartile as an independent variable also showed that the increase in quartile was associated with the exacerbation of visceral obesity and glucose/lipid markers. CONCLUSIONS: A higher fish consumption may be associated with a lower MHR as well as healthier lifestyle behaviors. Moreover, we proposed the concept of risk stratification through relationships with MHR, HDL-C, and fish consumption to reduce ASCVD risk. Further studies are required to dissect the causal relationships between these results.

The Frequency and Amount of Fish Intake Are Correlated with the White Blood Cell Count and Aerobic Exercise Habit: A Cross-sectional Study.

Objective We investigated the relationship between the amount and frequency of fish intake, and the white blood cell (WBC) count and aerobic exercise habits. Methods We conducted a cross-sectional study between April 2019 and March 2020 at the Health Planning Center of Nihon University Hospital on a cohort of 8,981 male subjects. Results The average amount and frequency of fish intake were 134±85 g/week and 2.14±1.28 days/week, respectively. The WBC count decreased significantly as the amount of fish intake increased (p<0.0001). According to a multivariate regression analysis, a high fish intake amount (ß=-0.082, p<0.0001) and regular aerobic exercise (ß=-0.083, p<0.0001) were independent determinants of a low WBC count. The proportion of subjects engaged in regular aerobic exercise increased with an increase in the amount of fish intake (p<0.0001). Furthermore, the amount and frequency of fish intake significantly correlated with the amount of n-3 polyunsaturated fatty acid intake determined using the Japan's National Nutrition Survey results (both r=0.962 and 0.958). Therefore, the amount of fish intake could be substituted by the average number of days of fish intake per week. Conclusion A high fish intake was an independent determinant of a low WBC count and engagement in regular aerobic exercise, regardless of whether the fish intake was defined by the amount or frequency of fish intake. However, since fish intake frequency can be measured more easily, this may be used to measure the fish intake.

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC-DHA), was significantly decreased in plasma post-CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC-DHA supplementation on the brain post-CA. METHODS: We first evaluated associations between the plasma level of LPC-DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC-DHA supplementation. RESULTS: We found that decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased levels of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. INTERPRETATION: The observed neuroprotection accompanied with normalized brain LPC-DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC-DHA post-CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC-DHA for brain damage after CA. ANN NEUROL 2022;91:389-403.

Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

OBJECTIVES: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. DESIGN: Clinical case control study followed by translational laboratory study. SETTING: Research institution. PATIENTS/SUBJECTS: Adult cardiac arrest patients and male Sprague-Dawley rats. INTERVENTIONS: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. MEASUREMENTS AND MAIN RESULTS: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. CONCLUSIONS: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome due to an acute type B aortic dissection: a case report.

Acute type B aortic dissection is sometimes complicated by acute respiratory failure requiring mechanical ventilation. Herein, we describe our experience in a rare acute type B aortic dissection-associated respiratory failure case culminating in acute respiratory distress syndrome. The patient was a 45-year-old man admitted with a complaint of sudden chest pain radiating to his back. On computed tomography, an acute type B aortic dissection was diagnosed. He had no dyspnea on admission, but his respiratory function subsequently deteriorated, and severe acute respiratory distress syndrome was diagnosed on Day 4. Venovenous extracorporeal membrane oxygenation with anticoagulation plus continuous renal replacement therapy for oliguria improved the oxygenation, and the patient was weaned from the extracorporeal membrane oxygenation on Day 8. This patient fully recovered without worsening the aortic dissection, using venovenous extracorporeal membrane oxygenation with anticoagulation plus a continuous renal replacement therapy.