TIMECARD score: An easily operated prediction model of unfavorable neurological outcomes in out-of-hospital cardiac arrest patients with targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) is recommended for comatose out-of-hospital cardiac arrest (OHCA) survivors. Several prediction models have been proposed; however, most of these tools require data conversion and complex calculations. Early and easy predictive model of neurological prognosis in OHCA survivors with TTM warrant investigation. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 408 non-traumatic adult OHCA survivors with TTM from the TaIwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry during January 2014 to June 2019. The primary outcome was unfavorable neurological outcome at discharge. The clinical variables associated with unfavorable neurological outcomes were identified and a risk prediction score-TIMECARD score was developed. The model was validated with data from National Taiwan University Hospital. RESULTS: There were 319 (78.2%) patients presented unfavorable neurological outcomes at hospital discharge. Eight independent variables, including malignancy, no bystander cardiopulmonary resuscitation (CPR), non-shockable rhythm, call-to-start CPR duration >5 min, CPR duration >20 min, sodium bicarbonate use during resuscitation, Glasgow Coma Scale motor score of 1 at return of spontaneous circulation, and no emergent coronary angiography, revealed a significant correlation with unfavorable neurological prognosis in TTM-treated OHCA survivors. The TIMECARD score was established and demonstrated good discriminatory performance in the development cohort (area under the receiver operating characteristic curve [AUC] = 0.855) and validation cohorts (AUC = 0.918 and 0.877, respectively). CONCLUSION: In emergency settings, the TIMECARD score is a practical and simple-to-calculate tool for predicting neurological prognosis in OHCA survivors, and may help determine whether to initiate TTM in indicated patients.

Poststroke Cognitive Impairment: A Longitudinal Follow-Up and Pre/Poststroke Mini-Mental State Examination Comparison.

BACKGROUND: Poststroke cognitive impairment (PSCI) is a prevalent cause of disability in people with stroke. PSCI results from either lesion-dependent loss of cognitive function or augmentation of Alzheimer's pathology due to vascular insufficiency. The lack of prestroke cognitive assessments limits the clear understanding of the impact of PSCI on cognition. OBJECTIVE: The present study aims to make a direct comparison of longitudinal cognitive assessment results to clarify the impact of ischemic stroke on PSCI and assess the cognitive decline in PSCI compared to people with Alzheimer's disease (AD). METHODS: All study participants had their Mini-Mental State Examination (MMSE) at the chronic poststroke stage (≥6 months after stroke), which was compared with prestroke or acute poststroke (<6 months after stroke) MMSE to investigate the two aspects of PSCI. A group of patients with AD was used to reference the speed of neurodegenerative cognitive deterioration. Repeated measures analysis of variance was used to compare the longitudinal change of MMSE. RESULTS: MMSE score between acute and chronic poststroke revealed a 1.8 ± 6.49 decline per year (n=76), which was not significantly different from the AD patients who underwent cholinesterase inhibitors treatment (-1.11 ± 2.61, p=0.35, n=232). MMSE score between prestroke and chronic poststroke (n=33) revealed a significant decline (-6.52 ± 6.86, p < 0.001). In addition, their cognitive deterioration was significantly associated with sex, age, and stroke over the white matter or basal ganglia. CONCLUSION: Ischemic stroke substantially affects cognition with an average six-point drop in MMSE. The rate of cognitive decline in PSCI was similar to AD, and those with white matter or basal ganglia infarct were at greater risk of PSCI.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

BACKGROUND AND OBJECTIVES: Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings. METHODS: Patients with RSE treated with midazolam or propofol between January 2015 and December 2018 were retrospectively identified among 9 centers across 4 continents from upper-middle-income economies in Latin America and high-income economies in North America, Europe, and Asia. Demographics, Status Epilepticus Severity Score, etiology, treatment details, and discharge modified Rankin Scale (mRS) were collected. The primary outcome measure was good functional outcome defined as a mRS score of 0-2 at hospital discharge. RESULTS: Three hundred eighty-seven episodes of RSE (386 patients) were included, with 162 (42%) from upper-middle-income and 225 (58%) from high-income economies. Three hundred six (79%) had acute and 79 (21%) remote etiologies. Initial RSE management included midazolam in 266 (69%) and propofol in 121 episodes (31%). Seventy episodes (26%) that were initially treated with midazolam and 42 (35%) with propofol required the addition of a second anesthetic to treat RSE. Baseline characteristics and outcomes of patients treated with midazolam or propofol were similar. Breakthrough (odds ratio [OR] 1.6, 95% CI 1.3-2.0) and withdrawal seizures (OR 2.0, 95% CI 1.7-2.5) were associated with an increased number of days requiring continuous intravenous anticonvulsant medications (cIV-ACMs). Prolonged EEG monitoring was associated with fewer days of cIV-ACMs (1-24 hours OR 0.5, 95% CI 0.2-0.9, and >24 hours OR 0.7, 95% CI 0.5-1.0; reference EEG <1 hour). This association was seen in both, high-income and upper-middle-income economies, but was particularly prominent in high-income countries. One hundred ten patients (28%) were dead, and 80 (21%) had good functional outcomes at hospital discharge. DISCUSSION: Outcomes of patients with RSE managed in the intensive care unit with propofol or midazolam infusions are comparable. Prolonged EEG monitoring may allow physicians to decrease the duration of anesthetic infusions safely, but this will depend on the implementation of RSE management protocols. Goal-directed management approaches including EEG targets may hold promise for patients with RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III data that propofol and midazolam are equivalently efficacious for RSE.

Artificial neural network-boosted Cardiac Arrest Survival Post-Resuscitation In-hospital (CASPRI) score accurately predicts outcome in cardiac arrest patients treated with targeted temperature management.

Existing prognostic models to predict the neurological recovery in patients with cardiac arrest receiving targeted temperature management (TTM) either exhibit moderate accuracy or are too complicated for clinical application. This necessitates the development of a simple and generalizable prediction model to inform clinical decision-making for patients receiving TTM. The present study explores the predictive validity of the Cardiac Arrest Survival Post-resuscitation In-hospital (CASPRI) score in cardiac arrest patients receiving TTM, regardless of cardiac event location, and uses artificial neural network (ANN) algorithms to boost the prediction performance. This retrospective observational study evaluated the prognostic relevance of the CASPRI score and applied ANN to develop outcome prediction models in a cohort of 570 patients with cardiac arrest and treated with TTM between 2014 and 2019 in a nationwide multicenter registry in Taiwan. In univariate logistic regression analysis, the CASPRI score was significantly associated with neurological outcome, with the area under the receiver operating characteristics curve (AUC) of 0.811. The generated ANN model, based on 10 items of the CASPRI score, achieved a training AUC of 0.976 and validation AUC of 0.921, with the accuracy, precision, sensitivity, and specificity of 89.2%, 91.6%, 87.6%, and 91.2%, respectively, for the validation set. CASPRI score has prognostic relevance in patients who received TTM after cardiac arrest. The generated ANN-boosted, CASPRI-based model exhibited good performance for predicting TTM neurological outcome, thus, we propose its clinical application to improve outcome prediction, facilitate decision-making, and formulate individualized therapeutic plans for patients receiving TTM.

The Differences of CPR duration between Shockable and Nonshockable Rhythms in Predicting the Benefit of Target Temperature Management.

BACKGROUND: Among cardiac arrest (CA) survivors, whether the combination of duration of cardiopulmonary resuscitation (CPR) and shockable/nonshockable rhythms during resuscitation can help predict the benefit of targeted temperature management (TTM) remains un-investigated. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 479 nontraumatic adult CA survivors with TTM and CPR duration < 60 min during January 2014 to June 2019 from the Taiwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry. The differences of CPR duration between shockable and nonshockable rhythms in predicting outcomes in the studied population was evaluated. RESULTS: We observed that 205 patients (42.8%) survived to hospital discharge and 100 patients (20.9%) presented favorable neurological outcomes at discharge. The enrolled patients were further re-classified into four groups according to shockable/nonshockable rhythms and CPR duration. Patients with shockable rhythms and shorter CPR duration had better survival-to-discharge (adjusted odds ratio [OR] = 2.729, 95% confidence interval [CI] = 1.384-5.383, P = 0.004) and neurological recovery (adjusted OR = 9.029, 95%CI = 3.263-24.983, P  < 0.001) than did those with nonshockable rhythms and longer CPR duration. CONCLUSION: The CPR duration for predicting outcomes differs between CA patients with shockable and nonshockable rhythms. The combination of shockable/nonshockable rhythms and CPR duration may help predict the prognosis in CA survivors undergoing TTM.

Predicting the survivals and favorable neurologic outcomes after targeted temperature management by artificial neural networks.

BACKGROUND: To identify the outcome-associated predictors and develop predictive models for patients receiving targeted temperature management (TTM) by artificial neural network (ANN). METHODS: The derived cohort consisted of 580 patients with cardiac arrest and ROSC treated with TTM between January 2014 and August 2019. We evaluated the predictive value of parameters associated with survival and favorable neurologic outcome. ANN were applied for developing outcome prediction models. The generalizability of the models was assessed through 5-fold cross-validation. The performance of the models was assessed according to the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: The parameters associated with survival were age, duration of cardiopulmonary resuscitation, history of diabetes mellitus (DM), heart failure, end-stage renal disease (ESRD), systolic blood pressure (BP), diastolic BP, body temperature, motor response after ROSC, emergent coronary angiography or percutaneous coronary intervention (PCI), and the cooling methods. The parameters associated with the favorable neurologic outcomes were age, sex, DM, chronic obstructive pulmonary disease, ESRD, stroke, pre-arrest cerebral-performance category, BP, body temperature, motor response after ROSC, emergent coronary angiography or PCI, and cooling methods. After adequate training, ANN Model 1 to predict survival achieved an AUC of 0.80. Accuracy, sensitivity, and specificity were 75.9%, 71.6%, and 79.3%, respectively. ANN Model 4 to predict the favorable neurologic outcome achieved an AUC of 0.87, with accuracy, sensitivity, and specificity of 86.7%, 77.7%, and 88.0%, respectively. CONCLUSION: The ANN-based models achieved good performance to predict the survival and favorable neurologic outcomes after TTM. The models proposed have clinical value to assist in decision-making.

Electrocerebral Signature of Cardiac Death.

BACKGROUND: Electroencephalography (EEG) findings following cardiovascular collapse in death are uncertain. We aimed to characterize EEG changes immediately preceding and following cardiac death. METHODS: We retrospectively analyzed EEGs of patients who died from cardiac arrest while undergoing standard EEG monitoring in an intensive care unit. Patients with brain death preceding cardiac death were excluded. Three events during fatal cardiovascular failure were investigated: (1) last recorded QRS complex on electrocardiogram (QRS0), (2) cessation of cerebral blood flow (CBF0) estimated as the time that blood pressure and heart rate dropped below set thresholds, and (3) electrocerebral silence on EEG (EEG0). We evaluated EEG spectral power, coherence, and permutation entropy at these time points. RESULTS: Among 19 patients who died while undergoing EEG monitoring, seven (37%) had a comfort-measures-only status and 18 (95%) had a do-not-resuscitate status in place at the time of death. EEG0 occurred at the time of QRS0 in five patients and after QRS0 in two patients (cohort median - 2.0, interquartile range - 8.0 to 0.0), whereas EEG0 was seen at the time of CBF0 in six patients and following CBF0 in 11 patients (cohort median 2.0 min, interquartile range - 1.5 to 6.0). After CBF0, full-spectrum log power (p < 0.001) and coherence (p < 0.001) decreased on EEG, whereas delta (p = 0.007) and theta (p < 0.001) permutation entropy increased. CONCLUSIONS: Rarely may patients have transient electrocerebral activity following the last recorded QRS (less than 5 min) and estimated cessation of cerebral blood flow. These results may have implications for discussions around cardiopulmonary resuscitation and organ donation.

Identifying prognostic factors and developing accurate outcome predictions for in-hospital cardiac arrest by using artificial neural networks.

BACKGROUND: Accurate estimation of neurological outcomes after in-hospital cardiac arrest (IHCA) provides crucial information for clinical management. This study used artificial neural networks (ANNs) to determine the prognostic factors and develop prediction models for IHCA based on immediate preresuscitation parameters. METHODS: The derived cohort comprised 796 patients with IHCA between 2006 and 2014. We applied ANNs to develop prediction models and evaluated the significance of each parameter associated with favorable neurological outcomes. An independent dataset of 108 IHCA patients receiving targeted temperature management was used to validate the identified parameters. The generalizability of the models was assessed through fivefold cross-validation. The performance of the models was assessed using the area under the curve (AUC). RESULTS: ANN model 1, based on 19 baseline parameters, and model 2, based on 11 prearrest parameters, achieved validation AUCs of 0.978 and 0.947, respectively. ANN model 3 based on 30 baseline and prearrest parameters achieved an AUC of 0.997. The key factors associated with favorable outcomes were the duration of cardiopulmonary resuscitation; initial cardiac arrest rhythm; arrest location; and whether the patient had a malignant disease, pneumonia, and respiratory insufficiency. On the basis of these parameters, the validation performance of the ANN models achieved an AUC of 0.906 for IHCA patients who received targeted temperature management. CONCLUSION: The ANN models achieved highly accurate and reliable performance for predicting the neurological outcomes of successfully resuscitated patients with IHCA. These models can be of significant clinical value in assisting with decision-making, especially regarding optimal postresuscitation strategies.

Quantum Monte Carlo Simulations of the 2D Su-Schrieffer-Heeger Model.

Over the past several years, a new generation of quantum simulations has greatly expanded our understanding of charge density wave phase transitions in Hamiltonians with coupling between local phonon modes and the on-site charge density. A quite different, and interesting, case is one in which the phonons live on the bonds, and hence modulate the electron hopping. This situation, described by the Su-Schrieffer-Heeger (SSH) Hamiltonian, has so far only been studied with quantum Monte Carlo in one dimension. Here we present results for the 2D SSH model, show that a bond ordered wave (BOW) insulator is present in the ground state at half filling, and argue that a critical value of the electron-phonon coupling is required for its onset, in contradistinction with the 1D case where BOW exists for any nonzero coupling. We determine the precise nature of the bond ordering pattern, which has hitherto been controversial, and the critical transition temperature, which is associated with a spontaneous breaking of Z_{4} symmetry.

Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine.

BACKGROUND: Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines. METHODS: With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care. RESULTS: High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus CONCLUSION: The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.

Ketamine to treat super-refractory status epilepticus.

OBJECTIVE: To test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), we studied patients with SRSE who were treated with ketamine retrospectively. We also studied the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM). METHODS: We studied a consecutive series of 68 patients with SRSE who were admitted between 2009 and 2018, treated with ketamine, and monitored with scalp EEG. Eleven of these patients underwent MMM at the time of ketamine administration. We compared patients who had seizure cessation after ketamine initiation to those who did not. RESULTS: Mean age was 53 ± 18 years and 46% of patients were female. Seizure burden decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with median duration of 2 (1-4) days. Average dose of midazolam was 1.0 ± 0.8 mg/kg/h at the time of ketamine initiation and was started at a median of 0.4 (0.1-1.0) days before ketamine. Using a generalized linear mixed effect model, ketamine was associated with stable mean arterial pressure (odds ratio 1.39, 95% confidence interval 1.38-1.40) and with decreased vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, or cerebral perfusion pressure. CONCLUSION: Ketamine treatment was associated with a decrease in seizure burden in patients with SRSE. Our data support the notion that high-dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ketamine decreases seizures in patients with SRSE.

Deep cerebral microbleeds are associated with poor cholinesterase inhibitor treatment response in people with Alzheimer disease.

OBJECTIVES: Cholinesterase inhibitors (ChEIs) are the most effective treatment for Alzheimer disease (AD), but the response to treatment varies. Vascular lesions are associated with the pathogenesis of AD, and cerebral microbleeds (CMBs) are an indicator of hemorrhagic vascular pathology, which can be detected through susceptibility-weighted magnetic resonance imaging (SWMRI). This study investigated the association between CMBs and ChEI treatment response in patients with AD. PATIENTS AND METHODS: We reviewed the medical records of 112 Taiwanese people with mild to moderate AD and at least 2 years of ChEI treatment between 2009 and 2016. Their baseline CMBs were quantified using the Microbleed Anatomical Rating Scale on SWMRI. Cognitive function of the patients was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student t test and multivariable logistic regression were used to analyze the association between cognitive decline and CMBs. RESULTS: The mean age of the study population was 76.0 ±â€¯8.0 years. In total, 79 out of 112 patients were women. The presence of deep, but not lobar CMBs at baseline was associated with a significant cognitive decline according to the MMSE and CASI, particularly in long-term memory, attention, orientation, mental manipulation, and verbal fluency. Among deep CMBs, those in the basal ganglia and thalamus were significantly associated with cognitive decline. CONCLUSIONS: Deep CMBs, particularly those in the basal ganglia and thalamus, but not lobar CMBs, are associated with poor response to ChEI treatment in people with AD. This can serve as a biomarker for predicting ChEI treatment response.

Low-density lipoprotein level on admission is not associated with postintravenous thrombolysis intracranial hemorrhage in patients with acute ischemic stroke.

Intravenous thrombolysis with the tissue plasminogen activator (tPA) is the gold standard for acute ischemic stroke. However, its application is limited because of the concern of the post-tPA intracranial hemorrhage (ICH). Low low-density lipoprotein (LDL) has been speculated to increase the risk of hemorrhagic transformation after ischemic stroke. However, whether LDL is associated with post-tPA ICH remains controversial. The present study obtained the medical records from Shuang Ho Hospital and retrospectively reviewed for the period between August 2009 and December 2016 to investigate the association between LDL and the risk of post-tPA ICH. The differences were analyzed using the Student's t-test, Fisher's exact test, the univariate and stepwise multiple regression model, and p<0.05 was considered statistically significant. Among 218 patients, post-tPA ICH was noted in 23 (10.5%) patients. Patients with post-tPA ICH tended to have a lower LDL level (ICH group: 102.00±24.56, non-ICH group: 117.02±37.60 mg/dL, p=0.063). However, after adjustment for the factors might affect the risk of post-tPA ICH, such as stroke severity, onset-to-treatment time interval, and atrial fibrillation (AF), LDL level was not associated with post-tPA ICH whereas AF was the only significant factor increased the risk of post-tPA ICH (adjusted OR: 1.177, 95% CI 1.080 to 1.283). In addition, patients with AF had significant lower LDL level and for patients without AF, LDL was not associated with the post-tPA ICH. In conclusion, LDL level is not associated with the risk of post-tPA ICH in Taiwanese patients with stroke.

Cerebral Microbleeds are Associated with Postural Instability and Gait Disturbance Subtype in People with Parkinson's Disease.

OBJECTIVES: The motor symptoms of Parkinson's disease (PD) vary among patients and have been categorized into 3 subtypes: tremor dominant, akinetic rigidity, and postural instability and gait disturbance (PIGD). Cerebral microbleed (CMB) is prevalent in people with PD and is associated with some nonmotor symptoms. The present study investigated the association between CMB and the motor subtypes of PD. MATERIALS AND METHODS: From 2009 to 2017, medical records and brain magnetic resonance imaging (MRI) reports of 134 Taiwanese people with early- and mid-stage PD were reviewed. CMBs were quantified according to the Microbleed Anatomical Rating Scale through susceptibility-weighted MRI. Motor subtypes were determined by medical chart review. Student's t test and multivariable logistic regression were used to analyze the association between the motor subtypes and CMB. Statistical analyses were performed using SPSS 19.0. RESULTS: Overall, 72 (53.7%) participants were women with a mean age of 69.5 ± 9.8 years. The prevalence of CMB was 33.6%, and lobar, deep, and infratentorial CMBs comprised 21.6, 19.4, and 11.9% of cases, respectively. PIGD subtype PD was associated with a significantly higher prevalence of any CMB as well as deep or lobar CMB. After adjustment for age and sex, the PIGD subtype was significantly positively associated with the presence of any, deep, and white matter (WM) and thalamic CMB. CONCLUSIONS: CMB was prevalent in Taiwanese people with early- and mid-stage PD, especially the PIGD subtype. Deep, especially thalamic and WM, CMBs exhibited the highest association with the PIGD subtype.

The risk of intravenous thrombolysis-induced intracranial hemorrhage in Taiwanese patients with unruptured intracranial aneurysm.

BACKGROUND: The presence of an intracranial aneurysm is contraindicated to recombinant tissue plasminogen activator (r-tPA) treatment for acute ischemic stroke. However, it is difficult to exclude asymptomatic intracranial aneurysms by using conventional, noncontrast head computed tomography (CT), which is the only neuroimaging suggested before r-tPA. Recent case reports and series have shown that administering r-tPA to patients with a pre-existing aneurysm does not increase the bleeding risk. However, Asians are known to have a relatively higher bleeding risk, and little evidence is available regarding the risk of using r-tPA on Asian patients with intracranial aneurysms. METHODS: Medical records from the Shuang Ho hospital stroke registration between July 2010 and December 2014 were retrospectively reviewed, and 144 patients received r-tPA. Unruptured intracranial aneurysms were detected using CT, or magnetic resonance or conventional angiography after r-tPA. The primary and secondary outcomes were the difference in overall intracranial hemorrhage (ICH) and symptomatic ICH after r-tPA. The differences were analyzed using Fisher's exact or Mann-Whitney U tests, and p < 0.05 was defined as the statistical significance. RESULTS: A total of 144 patients were reviewed, and incidental unruptured intracranial aneurysms were found in 11 of them (7.6%). No significant difference was observed in baseline demographic data between the aneurysm and nonaneurysm groups. Among patients with an unruptured aneurysm, two had giant aneurysms (7.7 and 7.4 mm, respectively). The bleeding risk was not significant different between aneurysm group (2 out of 11, 18%) with nonaneurysm group (7 out of 133, 5.3%) (p = 0.14). None of the patients with an unruptured aneurysm had symptomatic ICH, whereas one patient without an aneurysm exhibited symptomatic ICH. CONCLUSIONS: The presence of an unruptured intracranial aneurysm did not significantly increase the risk of overall and symptomatic ICH in Taiwanese patients after they received r-tPA.