Impact of Lactate Clearance on Clinical and Neurological Outcomes of Patients With Out-of-Hospital Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis.

OBJECTIVES: Serial evaluations of lactate concentration may be more useful in predicting outcomes in patients with out-of-hospital cardiac arrest (OHCA) than a single measurement. This study aimed to evaluate the impact of lactate clearance (LC) on clinical and neurologic outcomes in patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Retrospective multicenter observational study. SETTING: Patients with OHCA receiving ECPR at 36 hospitals in Japan between January 1, 2013, and December 31, 2018. PATIENTS: This study evaluated 1227 patients, with lactate initial assessed upon emergency department admission and lactate second measured subsequently. To adjust for the disparity in the time between lactate measurements, the modified 6-hour LC was defined as follows: ([lactate initial -lactate second ]/lactate initial ) × 100 × (6/the duration between the initial and second measurements [hr]). The patients were divided into four groups according to the modified 6-hour LC with an equivalent number of patients among LC quartiles: Q1 (LC < 18.8), Q2 (18.8 < LC < 59.9), Q3 (60.0 < LC < 101.2), and Q4 (101.2 < LC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 30-day survival rates increased as the 6-hour LC increased (Q1, 21.2%; Q2, 36.8%; Q3, 41.4%; Q4, 53.6%; p for trend < 0.001). In the multivariate analysis, the modified 6-hour LC was significantly associated with a 30-day survival rate (adjusted odds ratio [AOR], 1.003; 95% CI, 1.001-1.005; p < 0.001) and favorable neurologic outcome (AOR, 1.002; 95% CI, 1.000-1.004; p = 0.027). CONCLUSIONS: In patients with OHCA who underwent ECPR, an increase in the modified 6-hour LC was associated with favorable clinical and neurologic outcome. Thus, LC can be a criterion to assess whether ECPR should be continued.

Prognostic Significance of Signs of Life in Out-of-Hospital Cardiac Arrest Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: Signs of life (SOLs) during cardiac arrest (gasping, pupillary light reaction, or any form of body movement) are suggested to be associated with favorable neurologic outcomes in out-of-hospital cardiac arrest (OHCA). While data has demonstrated that extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes in cases of refractory cardiac arrest, it is expected that other contributing factors lead to positive outcomes. This study aimed to investigate whether SOL on arrival is associated with neurologic outcomes in patients with OHCA who have undergone ECPR. DESIGN: Retrospective multicenter registry study. SETTING: Thirty-six facilities participating in the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan II (SAVE-J II). PATIENTS: Consecutive patients older than 18 years old who were admitted to the Emergency Department with OHCA between January 1, 2013, and December 31, 2018, and received ECPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into two groups according to the presence or absence of SOL on arrival. The primary outcome was a favorable neurologic outcome (Cerebral Performance Category 1 or 2) at discharge. Of the 2157 patients registered in the SAVE-J II database, 1395 met the inclusion criteria, and 250 (17.9%) had SOL upon arrival. Patients with SOL had more favorable neurologic outcomes than those without SOL (38.0% vs. 8.1%; p < 0.001). Multivariate analysis showed that SOL on arrival was independently associated with favorable neurologic outcomes (odds ratio, 5.65 [95% CI, 3.97-8.03]; p < 0.001). CONCLUSIONS: SOL on arrival was associated with favorable neurologic outcomes in patients with OHCA undergoing ECPR. In patients considered for ECPR, the presence of SOL on arrival can assist the decision to perform ECPR.

Prophylactic distal perfusion catheter and survival in patients with out-of-hospital cardiac arrest: Secondary analysis of the SAVE-J II study.

PURPOSE: The effect of a prophylactic distal perfusion catheter (DPC) after extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, we aimed to clarify the association between prophylactic DPC and prognosis in patients with OHCA undergoing ECPR. MATERIALS AND METHODS: A secondary analysis of the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J II) database was performed to compare groups of patients with and without prophylactic DPCs. A multivariate analysis of survival at discharge was performed using factors that were significant in the two-arm comparison. RESULTS: A total of 2044 patients were included in the analysis after excluding those who met the exclusion criteria. Survival at discharge was observed in 548 (26.9%) patients. In total, 100 (4.9%) patients developed limb ischemia, among whom 14 (0.7%) required therapeutic intervention. Multivariate analysis showed that prophylactic DPC did not result in a significant difference in survival at discharge (odds ratio: 0.898 [0.652-1.236], p = 0.509). CONCLUSIONS: The implementation of prophylactic DPC after ECPR for patients with OHCA may not contribute to survival at discharge.

The association between blood glucose levels on arrival at the hospital and patient outcomes after out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND: This study aimed to investigate the association between blood glucose levels on arrival at the hospital and 1-month survival and favorable neurological outcomes in patients with OHCA using a large Japanese dataset. METHODS: This study was a secondary analysis of data from the JAAM-OHCA Registry. Adult (≥18 years) patients with witnessed OHCA transported to emergency departments and registered in the database from June 2014 to December 2019 were included in the study. The primary and secondary endpoints were 1-month survival and 1-month favorable neurological outcomes (Glasgow-Pittsburgh Cerebral Performance Category score 1 or 2), respectively. Patients were categorized into the following four groups based on blood glucose levels on arrival at the hospital: <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥300 mg/dL. RESULTS: This study included 11,387 patients. Survival rates were 1.3%, 3.1%, 7.0%, and 5.7% in the <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥ 300 mg/dL blood glucose groups, respectively. The rates of favorable neurological outcomes in each group were 0.4%, 1.5%, 3.3%, and 2.5%, respectively. Multivariable analysis showed that 180-299 mg/dL glucose was significantly associated with 1-month survival and favorable neurological outcomes compared with 80-179 mg/dL glucose (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.34-2.31; p < 0.001 and OR, 1.52; 95 % Cl, 1.02-2.25; p = 0.035, respectively). In this study, blood glucose levels with the best outcomes likely ranged from 200 to 250 mg/dL based on the cubic spline regression model. CONCLUSIONS: Blood glucose level of 180-299 mg/dL on arrival at the hospital was significantly associated with 1-month survival and favorable neurological outcomes compared to blood glucose level of 80-179 mg/dL in patients with OHCA.

Optimal chest compression for cardiac arrest until the establishment of ECPR: Secondary analysis of the SAVE-J II study.

INTRODUCTION: The widespread incorporation of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest requires the delivery of effective and high-quality chest compressions prior to the initiation of ECPR. The aim of this study was to evaluate and compare the effectiveness of mechanical and manual chest compressions until the initiation of ECPR. METHODS: This study was a secondary analysis of the Japanese retrospective multicenter registry "Study of Advanced Life Support for Ventricular Fibrillation by Extracorporeal Circulation II (SAVE-J II)". Patients were divided into two groups, one receiving mechanical chest compressions and the other receiving manual chest compressions. The primary outcome measure was mortality at hospital discharge, while the secondary outcome was the cerebral performance category (CPC) score at discharge. RESULTS: Of the 2157 patients enrolled in the SAVE-J II trial, 453 patients (329 in the manual compression group and 124 in the mechanical compression group) were included in the final analysis. Univariate analysis showed a significantly higher mortality rate at hospital discharge in the mechanical compression group compared to the manual compression group (odds ratio [95% CI] = 2.32 [1.34-4.02], p = 0.0026). Multivariate analysis showed that mechanical chest compressions were an independent factor associated with increased mortality at hospital discharge (adjusted odds ratio [95% CI] = 2.00 [1.11-3.58], p = 0.02). There was no statistically significant difference in CPC between the two groups. CONCLUSION: For patients with out-of-hospital cardiopulmonary arrest who require ECPR, extreme caution should be used when performing mechanical chest compressions.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR. METHODS: We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined. RESULTS: We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions. CONCLUSION: For approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.

Potential Interaction Between Sepsis and Acute Respiratory Distress Syndrome and Effect on the 6-Month Clinical Outcomes: A Preliminary Secondary Analysis of a Prospective Observational Study.

BACKGROUND: This study aimed to investigate the effect of the potential interaction between sepsis and acute respiratory distress syndrome (ARDS) on the 6-month clinical outcomes. METHODS: This secondary analysis of a prospective multicenter observational study included patients who were expected to receive mechanical ventilation for more than 48 h. Patients were stratified based on the incidence of sepsis and further subdivided according to the presence of ARDS. The primary endpoints for patients whose follow-up information was available included mortality (n = 162) and the occurrence of PICS (n = 96) at six months. The diagnosis of PICS was based on any of the following criteria: (1) decrease ≥ 10 points in the physical component score of the 36-item Short Form (SF36) questionnaire; (2) decrease ≥ 10 points in the mental component score of the SF-36; or (3) decline in the Short Memory Questionnaire (SMQ) score and SMQ score < 40 at six months after ICU admission. We conducted multivariate logistic regression analyses to assess the effect of the potential interaction between ARDS and sepsis on the 6-month clinical outcomes. RESULTS: The mortality in the ARDS sub-group was higher than that in the non-ARDS subgroup [47% (7/15) versus 21% (18/85)] in the non-sepsis group. However, the mortality in the ARDS and non-ARDS subgroups was similar in the sepsis group. Multivariate logistic regression analyses revealed that ARDS was significantly associated with mortality in the non-sepsis group (adjusted OR: 5.25; 95% CI: 1.45-19.09; p = .012), but not in the sepsis group (P for interaction = .087). Multivariate logistic regression analyses showed ARDS was not associated with PICS occurrence in the non-sepsis and sepsis groups (P-value for the interaction = .039). CONCLUSIONS: This hypothesis-generating study suggested that the effect of ARDS on the 6-month outcomes depended on the presence or absence of sepsis. TRIAL REGISTRATION: Not applicable.

Long-Term Outcomes of Patients with Stroke Predicted by Clinicians to have no Chance of Meaningful Recovery: A Japanese Cohort Study.

BACKGROUND: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon. METHODS: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1-4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury. RESULTS: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64-85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5). CONCLUSIONS: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication.

Gallstones in patients with severe motor and intellectual disability.

BACKGROUND: Asymptomatic gallbladder stones may be detected with ultrasound; some gallstones produce symptomatic diseases, such as cholecystitis, cholangitis, or pancreatitis. Identifying the clinical features of symptomatic gallstones may help prevent severe complications by providing intervention for asymptomatic gallstones. We aimed to investigate risk factors associated with developing symptomatic disease in pediatric patients with severe motor and intellectual disabilities (SMID). METHODS: This retrospective study enrolled 30 patients with SMID who were treated at the Nara Medical University between March 2016 and March 2019. We examined the prevalence of gallstones, and the rate at which associated symptoms of gallstones were observed in patients. Furthermore, we compared the clinical features of patients with and without gallstones. RESULTS: Among 30 patients with SMID, 7 (23%) had gallstones, with 6 (86%) of them being symptomatic: 3 patients had acute pancreatitis and 3 had cholecystitis or cholangitis. Among 23 patients without gallstones, 2 had acute pancreatitis and 2 had biliary sludge. Patients with gallstones had significantly lower daily calorie intake than those without gallstones (P = 0.042). Furthermore, the incidence of gallstones was higher in patients who received total parenteral nutrition than in those who did not (P = 0.031). Comparative analysis between symptomatic and asymptomatic patients was not performed because almost all cases were symptomatic. CONCLUSION: Gallstones were detected in 23% of patients with SMID. The gallstones were symptomatic at a very high rate. Considering this fact, patients with SMID should be surveyed for gallstones; careful management may be needed in such patients.

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial.

BACKGROUND: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. METHODS: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. RESULTS: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. CONCLUSIONS: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.

Impact of Induced Therapeutic Hypothermia by Intravenous Infusion of Ice-Cold Fluids After Hospital Arrival in Comatose Survivors of Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm.

BACKGROUND: The effect of in-hospital rapid cooling by intravenous ice-cold fluids for comatose survivors of out-of-hospital cardiac arrest (OHCA) is unclear.Methods and Results:From the J-PULSE-HYPO study registry, data for 248 comatose survivors with return of spontaneous circulation (ROSC) who were treated with therapeutic hypothermia (34℃ for 12-72 h) after witnessed shockable OHCA were extracted. Patients were divided into 2 groups by the median collapse-to-ROSC interval (18 min), and then into 2 groups by cooling method (rapid cooling by intravenous ice-cold fluids vs. standard cooling). The primary endpoint was favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after OHCA. In the whole cohort, the shorter collapse-to-ROSC interval group had significantly higher favorable neurological outcome than the longer collapse-to-ROSC interval group (78.2% vs. 46.8%, P<0.001). In the shorter collapse-to-ROSC interval group, no significant difference was observed in favorable neurological outcome between the 2 cooling groups (rapid cooling group: 79.4% vs. standard cooling group: 77.0%, P=0.75). In the longer collapse-to-ROSC interval group, however, favorable neurological outcome was significant higher in the rapid cooling group than in the standard cooling group (60.7% vs. 33.3%, P<0.01) and the adjusted odds ratio after rapid cooling was 3.069 (95% confidence interval 1.423-6.616, P=0.004). CONCLUSIONS: In-hospital rapid cooling by intravenous ice-cold fluids improved neurologically intact survival in comatose survivors whose collapse-to-ROSC interval was delayed over 18 min after shockable OHCA.

AFP-L3 as a Prognostic Predictor of Recurrence in Hepatoblastoma: A Pilot Study.

The α-fetoprotein (AFP) level is a sensitive biomarker of active hepatoblastoma (HB). This study aimed to clarify whether the Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) after complete resection is a prognostic predictor of HB recurrence. Fourteen HB patients who underwent complete resection of HB were divided into the recurrence group (RG, n=4) and the non-recurrence group (NRG, n=10). The AFP level and AFP-L3 before and after radical surgery were compared between the 2 groups. There was no significant difference in AFP levels in the early postoperative period between the 2 groups (P=0.54), and AFP was not an early prognostic factor for HB recurrence. At 2 months after surgery, the AFP-L3 fell below the detection limit only in the NRG (7/10 cases) (NRG=70.0% vs. RG=0%, P=0.03). In addition, there were some cases of recurrence in those whose AFP level decreased to the normal range, but none in those whose AFP-L3 fell below the detection limit. In conclusion, the AFP-L3 decreased earlier than did the AFP level; thus, the AFP-L3 after complete resection may be a predictor for HB recurrence.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. METHODS: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). RESULTS: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018). CONCLUSIONS: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

The association between neuromuscular blockade use during target temperature management and neurological outcomes.

BACKGROUND: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. 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. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. RESULTS: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. CONCLUSIONS: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.

Uterine sarcoma with posterior reversible encephalopathy syndrome associated with pazopanib.

WHAT IS KNOWN AND OBJECTIVE: Our objective is to report on a case of posterior reversible encephalopathy syndrome associated with pazopanib. CASE DESCRIPTION: A 64-year-old patient with uterine sarcoma developed PRES 3 days after pazopanib was initiated. After the discontinuation of pazopanib, the symptoms of PRES improved. WHAT IS NEW AND CONCLUSION: The first report worldwide to describe a patient with uterine sarcoma experiencing PRES caused by pazopanib. Patients with uterine sarcoma may experience PRES, even in the early phase of pazopanib therapy.

Diagnostic Reliability of Headset-Type Continuous Video EEG Monitoring for Detection of ICU Patterns and NCSE in Patients with Altered Mental Status with Unknown Etiology.

BACKGROUND/OBJECTIVE: Simplified continuous electroencephalogram (cEEG) monitoring has shown improvement in detecting seizures; however, it is insufficient in detecting abnormal EEG patterns, such as periodic discharges (PDs), rhythmic delta activity (RDA), spikes and waves (SW), and continuous slow wave (CS), as well as nonconvulsive status epilepticus (NCSE). Headset-type continuous video EEG monitoring (HS-cv EEG monitoring; AE-120A EEG Headset™, Nihon Kohden, Tokyo, Japan) is a recently developed easy-to-use technology with eight channels. However, its ability to detect abnormal EEG patterns with raw EEG data has not been comprehensively evaluated. We aimed to examine the diagnostic accuracy of HS-cv EEG monitoring in detecting abnormal EEG patterns and NCSE in patients with altered mental status (AMS) with unknown etiology. We also evaluated the time required to initiate HS-cv EEG monitoring in these patients. METHODS: We prospectively observed and retrospectively examined patients who were admitted with AMS between January and December 2017 at the neurointensive care unit at Asakadai Central General Hospital, Saitama, Japan. We excluded patients whose data were missing for various reasons, such as difficulties in recording, and those whose consciousness had recovered between HS-cv EEG and conventional cEEG (C-cEEG) monitoring. For the included patients, we performed HS-cv EEG monitoring followed by C-cEEG monitoring. Definitive diagnosis was confirmed by C-cEEG monitoring with the international 10-20 system. As the primary outcome, we verified the sensitivity and specificity of HS-cv EEG monitoring in detecting abnormal EEG patterns including PDs, RDA, SW, and CS, in detecting the presence of PDs, and in detecting NCSE. As the secondary outcome, we calculated the time to initiate HS-cv EEG monitoring after making the decision. RESULTS: Fifty patients (76.9%) were included in the final analyses. The median age was 72 years, and 66% of the patients were male. The sensitivity and specificity of HS-cv EEG monitoring for detecting abnormal EEG patterns were 0.974 (0.865-0.999) and 0.909 (0.587-0.998), respectively, and for detecting PDs were 0.824 (0.566-0.926) and 0.970 (0.842-0.999), respectively. We diagnosed 13 (26%) patients with NCSE using HS-cv EEG monitoring and could detect NCSE with a sensitivity and specificity of 0.706 (0.440-0.897) and 0.970 (0.842-0.999), respectively. The median time needed to initiate HS-cv EEG was 57 min (5-142). CONCLUSIONS: HS-cv EEG monitoring is highly reliable in detecting abnormal EEG patterns, with moderate reliability for PDs and NCSE, and rapidly initiates cEEG monitoring in patients with AMS with unknown etiology.

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project.

IMPORTANCE: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. OBJECTIVE: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. PROCESS: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. EVIDENCE SYNTHESIS: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. RECOMMENDATIONS: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. CONCLUSIONS AND RELEVANCE: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

In vitro activation and maturation of human mononuclear phagocytes by stimulation with liposomes coated with a neoglycolipid containing α1-3, α1-6-mannotriose.

In this study, we assessed the potential of liposomes coated with a neoglycolipid containing α1-3,α1-6-mannotriose residues (Man3-DPPE; Manα1-6(Manα1-3)Manitol-DPPE) for in vitro activation and maturation of human mononuclear phagocytes. In response to treatment with Man3-DPPE-coated liposomes (Man3-OMLs), PMA-stimulated human THP-1 cells showed enhanced expression of CD40, CD80 and HLA-DR and secreted significant levels of IL-12p40. Among various linkages of Man2-DPPE-coated liposomes, only liposomes coated with Manα1-6Manitol-DPPE (α1-6Man2-DPPE) induced these cellular responses similarly to Man3-OML treatment. Liposomes coated with Manα1-6(Manα1-3)Manα1-6(Manα1-3)Manitol-DPPE (Man5-DPPE) failed to activate the cells. These results suggest that an unsubstituted α1-6Man branch bound to a mannitol unit at the reducing end in Man3-DPPE is required for in vitro activation of human mononuclear phagocytes. Man3-OML-induced IL-12p40 production was not inhibited by BAY11-7082, an inhibitor of the MyD88-dependent signaling network, suggesting that TLRs are not involved in activation of human mononuclear phagocytes by Man3-OMLs. Stimulation of inflammatory monocytes or monocyte-derived dendritic cells (moDCs) with Man3-OMLs also induced enhanced expression of co-stimulatory molecules, HLA-DR, and CCR7, and IL-12p40 production from both types of cells. In response to Man3-OML treatment, moDCs but not inflammatory monocytes produced bioactive IL-12p70, which was enhanced by CD40 ligation. Thus, Man3-OMLs can activate naïve human mononuclear phagocytes and lead human moDCs to a fully matured status in vitro to elicit CTLs and a Th1 response without addition of inflammatory cytokines or TLR agonists.

Chest Compression Depth and Rate　- Effect on Instructor Visual Assessment of Chest Compression Quality.

BACKGROUND: The aim of the present study was to determine whether instructors could accurately assess chest compression quality visually, considering the association between chest compression depth and rate. Methods and Results: In this prospective, observational study, the quality of chest compressions performed by a simulated actor in a video was visually assessed by certified instructors. The film consisted of 14 case scenarios, each including a combination of depth (2 patterns: adequate, 5-6 cm; and inadequate, <5 cm) and rate (7 categories: compressions 90-150 times/min in increments of 10 times/min). The participants evaluated whether the compression depth was adequate, deep, or inadequate; and whether the compression rate was appropriate, fast, or slow. Of 198 instructors, 56% of participants misidentified adequate depth as deep at a chest compression rate of 120/min (the tendency toward this response increased as chest compression rate increased), and 64.1% of participants incorrectly determined 130/min to be appropriate. On generalized linear mixed-effects model analysis, perceived chest compression depth and rate were significant factors for a correct response (P<0.01, both). A significant interaction between chest compression depth and rate was observed (P<0.01). CONCLUSIONS: In the visual assessment of chest compression quality, recognition of chest compression depth was closely associated with compression rate. Misidentification of adequate chest compression depth as deep increased as the compression rate increased.