Prognostic Implication of Ventricular Volumetry in Early Brain Computed Tomography after Cardiac Arrest.

Brain swelling after cardiac arrest may affect brain ventricular volume. This study aimed to investigate the prognostic implications of ventricular volume on early thin-slice brain computed tomography (CT) after cardiac arrest. We measured the gray-to-white matter ratio (GWR) and the characteristics and volumes of the lateral, third, and fourth ventricles. The primary outcome was a poor 6-month neurological outcome. Of the 166 patients, 115 had a poor outcome. The fourth ventricle was significantly smaller in the poor outcome group (0.58 cm3 [95% CI, 0.43-0.80]) than in the good outcome group (0.74 cm3 [95% CI, 0.68-0.99], p < 0.001). Ventricular characteristics and other ventricular volumes did not differ between outcome groups. The area under the curve for the fourth ventricular volume was 0.68, comparable to 0.69 for GWR. Lower GWR (<1.09) and lower fourth ventricular volume (<0.41 cm3) predicted poor outcomes with 100% specificity and sensitivities of 8.7% (95% CI, 4.2-15.4) and 20.9% (95% CI, 13.9-29.4), respectively. Combining these measures improved the sensitivity to 25.2% (95% CI, 17.6-34.2). After adjusting for covariates, the fourth ventricular volume was independently associated with neurologic outcome. A marked decrease in fourth ventricular volume, with concomitant hypoattenuation on CT scans, more accurately predicted outcomes.

Good outcome prediction after out-of-hospital cardiac arrest: A prospective multicenter observational study in Korea (the KORHN-PRO registry).

AIM: To assess the ability of clinical examination, biomarkers, electrophysiology and brain imaging, individually or in combination to predict good neurological outcomes at 6 months after CA. METHODS: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0, which included adult out-of-hospital cardiac arrest (OHCA) patients (≥18 years). Good outcome predictors were defined as both pupillary light reflex (PLR) and corneal reflex (CR) at admission, Glasgow Coma Scale Motor score (GCS-M) >3 at admission, neuron-specific enolase (NSE) <17 µg/L at 24-72 h, a median nerve somatosensory evoked potential (SSEP) N20/P25 amplitude >4 µV, continuous background without discharges on electroencephalogram (EEG), and absence of anoxic injury on brain CT and diffusion-weighted imaging (DWI). RESULTS: A total of 1327 subjects were included in the final analysis, and their median age was 59 years; among them, 412 subjects had a good neurological outcome at 6 months. GCS-M >3 at admission had the highest specificity of 96.7% (95% CI 95.3-97.8), and normal brain DWI had the highest sensitivity of 96.3% (95% CI 92.9-98.4). When the two predictors were combined, the sensitivities tended to decrease (ranging from 2.7-81.1%), and the specificities tended to increase, ranging from81.3-100%. Through the explorative variation of the 2021 European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) prognostication strategy algorithms, good outcomes were predicted, with a specificity of 83.2% and a sensitivity of 83.5% in patients by the algorithm. CONCLUSIONS: Clinical examination, biomarker, electrophysiology, and brain imaging predicted good outcomes at 6 months after CA. When the two predictors were combined, the specificity further improved. With the 2021 ERC/ESICM guidelines, the number of indeterminate patients and the uncertainty of prognostication can be reduced by using a good outcome prediction algorithm.

Glucose control and outcomes in diabetic and nondiabetic patients treated with targeted temperature management after cardiac arrest.

Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1-6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5-7.8) and admission glucose (314 mg/dL, IQR 257-424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382-9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories.

Association between early lactate-related variables and 6-month neurological outcome in out-of-hospital cardiac arrest patients.

INTRODUCTION: The role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome. METHODS: In OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3-5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis. RESULTS: A total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03-1.18], AOR 1.15 [95% CI, 1.02-1.29], and AOR 1.36 [95% CI, 1.15-1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12-1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86-0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62-0.75]). CONCLUSIONS: Early lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics.

Prognostic Performance of Initial Clinical Examination in Predicting Good Neurological Outcome in Cardiac Arrest Patients Treated with Targeted Temperature Management.

Prognostication studies of cardiac arrest patients have mainly focused on poor neurological outcomes. However, an optimistic prognosis for good outcome could provide both justification to maintain and escalate treatment and evidence-based support to persuade family members or legal surrogates after cardiac arrest. The aim of the study was to evaluate the utility of clinical examinations performed after return of spontaneous circulation (ROSC) in predicting good neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). This retrospective study included OHCA patients treated with TTM from 2009 to 2021. Initial clinical examination findings related to the Glasgow coma scale (GCS) motor score, pupillary light reflex, corneal reflex (CR) and breathing above the set ventilator rate were assessed immediately after ROSC and before the initiation of TTM. The primary outcome was good neurological outcome at 6 months after cardiac arrest. Of 350 patients included in the analysis, 119 (34%) experienced a good neurological outcome at 6 months after cardiac arrest. Among the parameters of the initial clinical examinations, specificity was the highest for the GCS motor score, and sensitivity was the highest for breathing above the set ventilator rate. A GCS motor score of >2 had a sensitivity of 42.0% (95% confidence interval [CI] = 33.0-51.4) and a specificity of 96.5% (95% CI = 93.3-98.5). Breathing above the set ventilator rate had a sensitivity of 84.0% (95% CI = 76.2-90.1) and a specificity of 69.7% (95% CI = 63.3-75.6). As the number of positive responses increased, the proportion of patients with good outcomes increased. Consequently, 87.0% of patients for whom all four examinations were positive experienced good outcomes. As a result, the initial clinical examinations predicted good neurological outcomes with a sensitivity of 42.0-84.0% and a specificity of 69.7-96.5%. When more examinations with positive results are achieved, a good neurological outcome can be expected.

Serum spectrin breakdown product and neurofilament heavy in predicting outcome after cardiac arrest: A diagnostic accuracy study.

Objectives: Spectrin breakdown products 145 kDa (SBDP145) and neurofilament heavy chain (Nf-H) have been identified as potential biomarkers of neuronal injury. However, their ability to predict hypoxic-ischemic brain injury following cardiac arrest in humans is not well understood. This study aimed to investigate whether SBDP145 and Nf-H could be used as biomarkers to predict neurological outcomes after cardiac arrest. Methods: This prospective study was conducted at two academic hospitals and included adults who survived after cardiac arrest. Blood samples were collected at 0, 24, and 48 h after the return of spontaneous circulation, and biomarker analyses were performed to measure SBDP145 and Nf-H. Poor neurological outcome was defined as a modified Rankin Score of 4-6, and diagnostic performance was determined by receiver-operating characteristics analysis. Results: A total of 56 patients were included in this study. There were no significant differences in levels of SBDP145 or Nf-H between the poor and good outcome groups at any time point. Areas under the receiver-operating characteristics curve of SBDP145 and Nf-H were small, ranging from 0.51 to 0.7. At 0, 24, and 48 h, SBDP145 showed very low sensitivity (18.61 %, 13.89 %, and 13.79 %, respectively) and accuracy (33.93 %, 36.74 %, and 39.02 %, respectively) at a cut-off value for 100 % specificity. Nf-H also showed very low sensitivity (9.30 %, 16.67 %, and 0 %, respectively) and accuracy (29.09 %, 36.74 %, and 30.95 %, respectively). Conclusions: SBDP145 and Nf-H were found to be poor predictors of poor neurological outcomes six months after cardiac arrest.

Predictive Validity of a New Triage System for Outcomes in Patients Visiting Pediatric Emergency Departments: A Nationwide Study in Korea.

Triage is essential for rapid and efficient intervention in patients visiting an emergency department. In Korea, since 2016, the Pediatric Korean Triage and Acuity Scale (PedKTAS) has been implemented nationwide for the triage of patients visiting pediatric emergency departments (PEDs). The aim of this study was to evaluate the validity of the PedKTAS in patients who visit PEDs. This study was a retrospective observational study of national registry data collected from all emergency medical centers and institutions throughout Korea. We analyzed data from patients aged <15 years who visited emergency departments nationwide from January 2016 to December 2019. The hospitalization and intensive care unit (ICU) admission rates were analyzed on the basis of triage level. In total, 5,462,964 pediatric patients were included in the analysis. The hospitalization rates for PedKTAS Levels 1-5, were 63.5%, 41.1%, 17.0%, 6.5%, and 3.7%, respectively, and were significantly different (p < 0.001). The ICU admission rates for PedKTAS Levels 1-5 were 14.4%, 6.0%, 0.3%, 0.1%, and 0.1%, respectively, and were significantly different (p < 0.001). The hospitalization and ICU admission rates were highest for PedKTAS Level 1, and differences were significant based on the level. We identified that the PedKTAS is suitable for predicting the emergency status of pediatric patients who visit PEDs.

Novel serum biomarkers for predicting neurological outcomes in postcardiac arrest patients treated with targeted temperature management.

OBJECTIVE: To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM). METHODS: This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron­specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA. RESULTS: A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9-89.6) in predicting poor neurological outcomes while maintaining 100% specificity. CONCLUSION: Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.

A novel cardiac arrest severity score for the early prediction of hypoxic-ischemic brain injury and in-hospital death.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) outcomes are unsatisfactory despite postcardiac arrest care. Early prediction of prognoses might help stratify patients and provide tailored therapy. In this study, we derived and validated a novel scoring system to predict hypoxic-ischemic brain injury (HIBI) and in-hospital death (IHD). METHODS: We retrospectively analyzed Korean Hypothermia Network prospective registry data collected from in Korea between 2015 and 2018. Patients without neuroprognostication data were excluded, and the remaining patients were randomly divided into derivation and validation cohorts. HIBI was defined when at least one prognostication predicted a poor outcome. IHD meant all deaths regardless of cause. In the derivation cohort, stepwise multivariate logistic regression was conducted for the HIBI and IHD scores, and model performance was assessed. We then classified the patients into four categories and analyzed the associations between the categories and cerebral performance categories (CPCs) at hospital discharge. Finally, we validated our models in an internal validation cohort. RESULTS: Among 1373 patients, 240 were excluded, and 1133 were randomized into the derivation (n = 754) and validation cohorts (n = 379). In the derivation cohort, 7 and 8 predictors were selected for HIBI (0-8) and IHD scores (0-11), respectively, and the area under the curves (AUC) were 0.85 (95% CI 0.82-0.87) and 0.80 (95% CI 0.77-0.82), respectively. Applying optimum cutoff values of ≥6 points for HIBI and ≥7 points for IHD, the patients were classified as follows: HIBI (-)/IHD (-), Category 1 (n = 424); HIBI (-)/IHD (+), Category 2 (n = 100); HIBI (+)/IHD (-), Category 3 (n = 21); and HIBI (+)/IHD (+), Category 4 (n = 209). The CPCs at discharge were significantly different in each category (p < 0.001). In the validation cohort, the model showed moderate discrimination (AUC 0.83, 95% CI 0.79-0.87 for HIBI and AUC 0.77, 95% CI 0.72-0.81 for IHD) with good calibration. Each category of the validation cohort showed a significant difference in discharge outcomes (p < 0.001) and a similar trend to the derivation cohort. CONCLUSIONS: We presented a novel approach for assessing illness severity after OHCA. Although external prospective studies are warranted, risk stratification for HIBI and IHD could help provide OHCA patients with appropriate treatment.

Stem cell laden nano and micro collagen/PLGA bimodal fibrous patches for myocardial regeneration.

BACKGROUND: Although the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering . METHODS: Nano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated. RESULTS: Nano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings. CONCLUSION: Col/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

Can Optic Nerve Sheath Images on a Thin-Slice Brain Computed Tomography Reconstruction Predict the Neurological Outcomes in Cardiac Arrest Survivors?

We analyzed the prognostic performance of optic nerve sheath diameter (ONSD) on thin-slice (0.6 mm) brain computed tomography (CT) reconstruction images as compared to routine-slice (4 mm) images. We conducted a retrospective analysis of brain CT images taken within 2 h after cardiac arrest. The maximal ONSD (mONSD) and optic nerve sheath area (ONSA) were measured on thin-slice images, and the routine ONSD (rONSD) and gray-to-white matter ratio (GWR) were measured on routine-slice images. We analyzed their area under the receiver operator characteristic curve (AUC) and the cutoff values for predicting a poor 6-month neurological outcome (a cerebral performance category score of 3-5). Of the 159 patients analyzed, 113 patients had a poor outcome. There was no significant difference in rONSD between the outcome groups (p = 0.116). Compared to rONSD, mONSD (AUC 0.62, 95% CI: 0.54-0.70) and the ONSA (AUC 0.63, 95% CI: 0.55-0.70) showed better prognostic performance and had higher sensitivities to determine a poor outcome (mONSD, 20.4% [95% CI, 13.4-29.0]; ONSA, 16.8% [95% CI, 10.4-25.0]; rONSD, 7.1% [95% CI, 3.1-13.5]), with specificity of 95.7% (95% CI, 85.2-99.5). A combined cutoff value obtained by both the mONSD and GWR improved the sensitivity (31.0% [95% CI, 22.6-40.4]) of determining a poor outcome, while maintaining a high specificity. In conclusion, rONSD was clinically irrelevant, but the mONSD had an increased sensitivity in cutoff having acceptable specificity. Combination of the mONSD and GWR had an improved prognostic performance in these patients.

Development of a Cranial Suture Traction Therapy Program for Facial Asymmetry Correction Using the New Delphi Technique.

Background and Objectives: We aimed to develop a cranial suture traction therapy program, a non-surgical therapeutic method for facial asymmetry correction. Materials and Methods: Six experts, including rehabilitation medicine specialists, oriental medical doctors, dentistry specialists, five experts, including Master's or doctoral degree holders in skin care and cosmetology with more than 10 years of experience in the field, 4 experts including educators in the field of skin care, a total of 15 people participated in the validation of the development of the cranial suture traction therapy program in stages 1 to 3. Open questions were used in the primary survey. In the second survey, the results of the first survey were summarized and the degree of agreement regarding the questions in each category was presented. In the third survey, the degree of agreement for each item in the questionnaire was analyzed statistically. Results: Most of the questions attained a certain level of consensus by the experts (average of ≥ 4.0). The difference between the mean values was the highest for the third survey at 0.33 and was the lowest between the second and third surveys at 0.47. The results regarding the perceived degree of importance for each point of the evaluation in both the second and third stages of the cranial suture traction therapy program were verified using the content validity ratio. The ratio for the 13 evaluation points was within the range of 0.40-1.00; thus, the Delphi program for cranial suture traction therapy verified that the content was valid. Conclusions: As most questions attained a certain level of consensus by the experts, it can be concluded that these questions are suitable, relevant, and important. The commercialization of the cranial suture traction treatment program will contribute to the correction and prevention of facial dislocations or asymmetry, and the developed treatment will be referred to as cranial suture traction therapy (CSTT).

The association of different target temperatures in targeted temperature management with neurological outcome after out-of-hospital cardiac arrest based on a prospective multicenter observational study in Korea (the KORHN-PRO registry): IPTW analysis.

BACKGROUND: Among comatose survivors of out-of-hospital cardiac arrest (OHCA), targeted temperature management (TTM) has improved neurological outcomes. However, although the target temperature shifted from 33°C to 33°C~36°C, the optimal target temperature is still unclear. The goal of this study was to evaluate neurological outcomes at 6 months at target temperatures of 33°C and 36°C. MATERIALS AND METHODS: We analyzed OHCA survivors who underwent TTM and were recorded in the Korean Hypothermia Network, a prospective multicenter registry, from October 2015 to December 2018. The primary outcome was good neurological outcome at six months, defined as a cerebral performance category of 1-2, and the secondary outcome was survival at 6 months. RESULTS: A total of 1339 patients were treated with TTM in twenty-two emergency departments. Of those, 1054 were treated at 33°C, and 285 were treated at 36°C. There was no significant difference in good neurological outcomes at 6 months (30.6% vs. 31.2%, p = 0.850, adjusted OR 0.97, 95% CI = 0.73-1.29]) and survival at six months (41.4% vs. 38.7%, p = 0.401, adjusted HR 1.08, 95% CI = 0.91-1.28]) between TTM 33°C and TTM 36°C. After propensity score matching, good neurological outcomes at 6 months (OR 0.93, 95% CI = 0.74-1.18) and survival at 6 months (HR 1.05, 95% CI = 0.92-1.21) were still not associated with TTM 33°C and TTM 36°C. CONCLUSION: In this study, patients treated with a target temperature of 33°C had similar good neurological outcomes and survival at six months compared with those treated with a target temperature of 36°C.

Impact of COVID-19 pandemic on patients with cardio/cerebrovascular disease who visit the emergency department.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic situation is a state that has had a great impact on the medical system and society. To respond to the pandemic situation, various methods, such as a pre-triage system, are being implemented in the emergency medical field. However, there are insufficient studies on the effects of this pandemic situation on patients visiting the emergency department (ED), especially those with cardio/cerebrovascular diseases (CVD)1 classified as time-dependent emergencies. METHODS: We performed a retrospective analysis of a cohort of patients from April 2020 to December 2020 (April 2020 was when the pre-triage system was established) compared to a parallel comparison patient cohort from 2019. The primary outcome was in-hospital mortality. CVD was defined by the patient's final diagnosis. RESULTS: During the same period, the number of patients who had visited the ED after COVID-19 had decreased to 79.1% of the number of patients who had visited the ED before COVID-19. The overall patient mortality and the mortality in the patients cardiovascular disease had both increased, while the mortality from cerebrovascular disease did not increase. Meanwhile, the ED length of stay had increased in all patients but did not increase in the patients with cardiovascular disease. CONCLUSION: As with prior studies conducted in other regions, in our study, the total number of ED visits were decreased compared to before COVID-19. The overall mortality had increased, particularly in the patients with cardiovascular disease.

External validation of cardiac arrest-specific prognostication scores developed for early prognosis estimation after out-of-hospital cardiac arrest in a Korean multicenter cohort.

We evaluated the performance of cardiac arrest-specific prognostication scores developed for outcome prediction in the early hours after out-of-hospital cardiac arrest (OHCA) in predicting long-term outcomes using independent data. The following scores were calculated for 1,163 OHCA patients who were treated with targeted temperature management (TTM) at 21 hospitals in South Korea: OHCA, cardiac arrest hospital prognosis (CAHP), C-GRApH (named on the basis of its variables), TTM risk, 5-R, NULL-PLEASE (named on the basis of its variables), Serbian quality of life long-term (SR-QOLl), cardiac arrest survival, revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST), Polish hypothermia registry (PHR) risk, and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) scores and prediction score by Aschauer et al. Their accuracies in predicting poor outcome at 6 months after OHCA were determined using the area under the receiver operating characteristic curve (AUC) and calibration belt. In the complete-case analyses, the PROLOGUE score showed the highest AUC (0.923; 95% confidence interval [CI], 0.904-0.941), whereas the SR-QOLl score had the lowest AUC (0.749; 95% CI, 0.711-0.786). The discrimination performances were similar in the analyses after multiple imputation. The PROLOGUE, TTM risk, CAHP, NULL-PLEASE, 5-R, and cardiac arrest survival scores were well calibrated. The rCAST and PHR risk scores showed acceptable overall calibration, although they showed miscalibration under the 80% CI level at extreme prediction values. The OHCA score, C-GRApH score, prediction score by Aschauer et al., and SR-QOLl score showed significant miscalibration in both complete-case (P = 0.026, 0.013, 0.005, and < 0.001, respectively) and multiple-imputation analyses (P = 0.007, 0.018, < 0.001, and < 0.001, respectively). In conclusion, the discrimination performances of the prognostication scores were all acceptable, but some showed significant miscalibration.

External validation of the 2020 ERC/ESICM prognostication strategy algorithm after cardiac arrest.

PURPOSE: To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020. METHODS: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72-96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3-5 at 6 months after ROSC. RESULTS: A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9-64.4) and 100% specificity (95% CI 93.9-100) among patients who were unconscious or had a GCS_M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9-62.3) and 100% specificity (95% CI 96.6-100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0-5.6 for combination of no PR/CR and poor CT, 0-30.8 for combination of No SSEP N20 and NSE 60). CONCLUSION: The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2-60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR.

The relationship between body mass index and neurologic outcomes in survivors of out-of-hospital cardiac arrest treated with targeted temperature management.

BACKGROUND: The association of body mass index with outcome in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) is unclear. The purpose of this study was to examine the effect of body mass index (BMI) on neurological outcomes and mortality in resuscitated patients treated with TTM after OHCA. METHODS: This multicenter, prospective, observational study was performed with data from 22 hospitals included in the Korean Hypothermia Network KORHN-PRO registry. Comatose adult patients treated with TTM after OHCA between October 2015 and December 2018 were enrolled. The BMI of each patient was calculated and classified according to the criteria of the World Health Organization (WHO). Each group was analyzed in terms of demographic characteristics and associations with six-month neurologic outcomes and mortality after cardiac arrest (CA). RESULTS: Of 1,373 patients treated with TTM identified in the registry, 1,315 were included in this study. One hundred two patients were underweight (BMI <18.5 kg/m2), 798 were normal weight (BMI 18.5-24.9 kg/m2), 332 were overweight (BMI 25-29.9 kg/m2), and 73 were obese (BMI ≥ 30 kg/m2). The higher BMI group had younger patients and a greater incidence of diabetes and hypertension. Six-month neurologic outcomes and mortality were not different among the BMI groups (p = 0.111, p = 0.234). Univariate and multivariate analyses showed that BMI classification was not associated with six-month neurologic outcomes or mortality. In the subgroup analysis, the underweight group treated with TTM at 33°C was associated with poor neurologic outcomes six months after CA (OR 2.090, 95% CI 1.010-4.325, p = 0.047), whereas the TTM at 36°C group was not (OR 0.88, 95% CI 0.249-3.112, p = 0.843). CONCLUSIONS: BMI was not associated with six-month neurologic outcomes or mortality in patients surviving OHCA. However, in the subgroup analysis, underweight patients were associated with poor neurologic outcomes when treated with TTM at 33°C.

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Differences in the gray-to-white matter ratio according to different computed tomography scanners for outcome prediction in post-cardiac arrest patients receiving target temperature management.

The gray-to-white matter ratio (GWR) has been used to identify brain damage in comatose patients after cardiac arrest. However, Hounsfield units (HUs), the measurement of brain density on computed tomography (CT) images, may vary depending on the machine type or parameter. Therefore, differences in CT scanners may affect the GWR in post-cardiac arrest patients. We performed a retrospective study on comatose post-cardiac arrest patients who visited the hospital from 2007 to 2017. Two CT, Lightspeed and SOMATOM, scanners were used. Two observers independently measured the HUs of the caudate nucleus, putamen, posterior internal capsule, and corpus callosum using regions of interest. We compared the GWR calculated from the HUs measured at different CT scanners. The analysis of different scanners showed statistically significant differences in the measured HUs and GWR. The HUs and GWR of Lightspeed were measured lower than SOMATOM. The difference between the two CT scanners was also evident in groups divided by neurological prognosis. The area under the curve of the receiver operating characteristic curve to predict poor outcomes of Lightspeed was 0.798, and the cut-off value for 100% specificity was 1.172. The SOMATOM was 0.855, and the cut-off value was 1.269. The difference in scanners affects measurements and performance characteristics of the GWR in post-cardiac arrest patients. Therefore, when applying the results of the GWR study to clinical practice, reference values for each device should be presented, and an integrated plan should be prepared.

The Levels of Circulating MicroRNAs at 6-Hour Cardiac Arrest Can Predict 6-Month Poor Neurological Outcome.

Early prognostication in cardiac arrest survivors is challenging for physicians. Unlike other prognostic modalities, biomarkers are easily accessible and provide an objective assessment method. We hypothesized that in cardiac arrest patients with targeted temperature management (TTM), early circulating microRNA (miRNA) levels are associated with the 6-month neurological outcome. In the discovery phase, we identified candidate miRNAs associated with cardiac arrest patients who underwent TTM by comparing circulating expression levels in patients and healthy controls. Next, using a larger cohort, we validated the prognostic values of the identified early miRNAs by measuring the serum levels of miRNAs, neuron-specific enolase (NSE), and S100 calcium-binding protein B (S100B) 6 h after cardiac arrest. The validation cohort consisted of 54 patients with TTM. The areas under the curve (AUCs) for poor outcome were 0.85 (95% CI (confidence interval), 0.72-0.93), 0.82 (95% CI, 0.70-0.91), 0.78 (95% CI, 0.64-0.88), and 0.77 (95% CI, 0.63-0.87) for miR-6511b-5p, -125b-1-3p, -122-5p, and -124-3p, respectively. When the cut-off was based on miRNA levels predicting poor outcome with 100% specificity, sensitivities were 67.7% (95% CI, 49.5-82.6), 50.0% (95% CI, 32.4-67.7), 35.3% (95% CI, 19.7-53.5), and 26.5% (95% CI, 12.9-44.4) for the above miRNAs, respectively. The models combining early miRNAs with protein biomarkers demonstrated superior prognostic performance to those of protein biomarkers.