Poor Neurological Outcome Research Articles

Therapeutic hypothermia after out-of-hospital cardiac arrest in comatose patients with acute myocardial infarction

Abstract Background Comatous survivors of out-of-hospital cardiac arrest (OHCA) have a high risk of death or poor neurological outcome. Therapeutic hypothermia is recommended for these patients after OHCA. However, there is a lack of data regarding outcomes of therapeutic hypothermia after OHCA in comatose patients with acute myocardial infarction (AMI). Purpose This study aimed to investigate the impact of therapeutic hypothermia on clinical outcomes in comatose patients who underwent primary percutaneous coronary intervention (PCI) for AMI after OHCA. Methods Using a prospective nationwide registry from 2016 to 2021, we examined 2,925 consecutive comatose patients experiencing OHCA in patients with AMI. These patients were categorized into groups receiving hypothermia treatment (n=624) and those without hypothermia treatment (n=2,301). The primary endpoint was the mortality rate upon discharge. The secondary endpoints were mortality rates at 6 or 24 hours, and neurological outcomes at hospital discharge. Results Overall, 624 (21.3%) patients were classified into the hypothermia group. This group showed a notably reduced mortality rate (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.58-0.78, p<0.001) after IPTW analysis (Figure 1). While the worse neurological outcome (as indicated by cerebral performance category [CPC] category 3-5) at hospital discharge was not significantly different between groups after IPTW analysis (odds ratio [OR]: 1.04, 95% CI: 0.93-1.15, p=0.499), early hypothermia within 180 minutes after hospital arrival showed significantly lower mortality rates (HR: 0.64, 95% CI: 0.44-0.95, p=0.027) and reduced occurrence of worse neurological outcome (OR: 0.75, 95% CI: 0.59-0.96, p=0.021) after IPTW analysis (Figure 2). Detailed hypothermia protocol including a targeted temperature of 33°C vs. 36°C or hypothermia duration of 48 hours vs. 24 hours did not significantly reduce the rate of death or poor neurological outcome at discharge. Conclusions Therapeutic hypothermia in OHCA patients complicating AMI was associated with lower mortality rates and comparable neurologic outcomes. However, early hypothermia within 180 minutes after hospital arrival showed significantly improved the mortality and neurological outcomes.all-cause deathAll-cause death and neurological outcome

Increased miRNA-related inflammation markers and pro-inflammatory circulating cell profile in patients with poor neurological outcome after out-of-hospital cardiac arrest

Abstract Background Out-of-Hospital Cardiac Arrest (OHCA) supposes a main cause of disability and mortality worldwide. Between patients suffering OHCA, only a 10-20% can be successfully resuscitated and, between them, a 50% suffers of neurological sequelae. Mechanisms underlying brain damage seems to be strongly related with neuroinflammation, mediated by classical (PCR, NLR) and novel (miRNAs) agents at play. Even there are studies suggesting the relevance of miRNA-mediated inflammatory response in ECA, no consistent conclusions about its role in ECA outcomes have been obtained. Purpose The aim of the present investigation is to study the temporal patterns of classical (PCR, NLR) and novel (miRNAs) inflammation markers during hospitalization of ECA patients and to correlate them with neurological outcome. Methods Consecutive OHCA patients were prospectively recruited at the Acute Cardiac Care Unit (ACCU) of the hospital Clinic of Barcelona from March 2019 to December 2023. Serum samples were obtained at 0, 24 and 72 hours after hospital admission. Patients were grouped according to their neurological outcome, measured by Cerebral Performance Category (CPC), at hospital discharge. Classical inflammation markers (PCR and NLR) were measured and in silico pre-targeted serum circulating-miRNAs were analysed by qPCR. Results A total of 120 patients (60 ± 13 years, 20% female) were included for the analysis. At hospital discharge, 55 (45%) patients survived with good NO (GNO; CPC 1-2) and 65 (55%) patients presented a poor NO (PNO; CPC 3-5). Classical inflammation markers such as PCR and NLR were significant higher in PNO than in GNO Group (P-value = 0.0042 and p-ANOVA = 0.0444, respectively) (Figure 1A). 11 inflammation-related miRNAs with strong correlation with OHCA-related conditions such as cardiovascular and coronary artery disease, hypoxic encephalopathy and neuro-inflammation were pre-targeted by in silico analysis. Five of the pre-targetedmiRNAs (miR-21-5p, miR-23a-3p, miR-146-5p, miR-155-5p and miR-181a-5p) presented significant differences between GNO and PNO groups (p-ANOVA = 0.0001, 0.0027, 0.0001, 0.0023 and 0.0002 respectively) in at least one time point, with an reduced expression in all cases in the PNO respect the GNO group (Figure 1B). Conclusions Patients with PNO after OHCA presents a downregulation of inflammation-regulatory miRNAs that leads an increase of clinical inflammation-related mediators such as PCR and NLR, with potential neuro-inflammatory consequences.

The severity of metabolic derangement predicts survival of out-of-hospital cardiac arrest and the benefit of extracorporeal life support

Abstract Aims This study aimed to develop Metabolic Derangement score and validate its prognostic performance in patients with out-of-Hospital Cardiac Arrest (OHCA) and also its discriminative performance in guiding the application of extracorporeal life support (ECLS). Methods and Results From 5,100 patients (average age 67 years, 69% male), Metabolic Derangement score was developed to predict primary outcome (death or poor neurologic outcome, cerebral performance category ≥ 3 at day 30) from initial blood laboratory test including pH, PaCO2, PaO2, potassium, haemoglobin, lactate, and creatinine. It was created using machine learning algorithms and a training set (60%), and validated with a test set (40%). The risk of primary outcome consistently increased from 34% to 100% as the Metabolic Derangement score ranged from 0 to 7. Patients with Metabolic Derangement score ≤ 2 showed no difference in the primary outcome risk between those with or without ECLS. Conversely, those with a Metabolic Derangement score ≥3 had a lower risk with ECLS (difference of restricted mean survival time=6.5 days, 95% CI=3.3-9.6 days, ratio of restricted mean time lost=0.76, 95%CI=0.65-0.88, all p<0.001). Clinical subgroup analyses showed generally consistent results. Metabolic Derangement score also outperformed OHCA-, CAHP-, and NULL-PLEASE-scores in prediction the primary outcome (p<0.05, all). Conclusions The severity of metabolic derangement predicted the clinical outcome of OHCA, and could also identify patients likely to benefit from ECLS.Metabolic Derangement score

Association between arterial oxygen tension with clinical outcomes in patients undergoing VA-ECMO support: a systematic review and dose-response meta-analysis

Abstract Background Arterial hyperoxia has been associated with a worse prognosis in critically ill patients. However, studies conducted in patients undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) used inconsistent and arbitrary thresholds for defining hyperoxia, which impeded the determination of the optimal target for arterial oxygen tension (PaO2) in this population. Purpose To investigate and visualise the dose-response relationship between post-ECMO level of PaO2 with early mortality (in-hospital and 1-month) and poor neurological outcomes in adult patients undergoing VA-ECMO support, including Extracorporeal Cardiopulmonary Resuscitation (ECPR). Methods A systematic search was conducted through Pubmed and Embase to include studies that stratified patients based on PaO2 levels and evaluated relevant outcomes. We utilised either adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) when available, or unadjusted OR against the lowest exposure category. The median, mean, or midpoint value of PaO2 was assigned as the corresponding dose. A random-effects one-stage dose-response meta-analysis was performed to assess linear association for every 10 mmHg increase in PaO2, while potential non-linear relationship was explored with restricted cubic splines at 3 knots (10th, 50th, and 90th percentile). Non-linearity was assessed by using Wald test with p value <0.05 considered significant. Statistical analyses were performed using STATA 17.0. Results Fourteen eligible records were identified (cardiogenic shock/CS = 5 records; ECPR = 8 records; both = 1 record). Only four studies classified a separate category for hypoxemic patients (<60 mmHg). PaO2 levels were measured within 24-72 hours of VA-ECMO initiation, except in one study. PaO2 level was not associated with early mortality (9 studies; OR 1.021 [95% CI 0.988–1.055]; p for non-linearity = 0.893), but found to have a linear association with composite poor neurological outcomes (6 studies; OR 1.016 [1.009–1.024]; p for non-linearity = 0.346). Subgroup analysis of CS patients revealed a linear association between PaO2 >100 mmHg and early mortality (4 studies; OR 1.025 [95%CI 1.018–1.032]; p for non-linearity = 0.255). For ECPR patients, a J-shaped relationship was observed between PaO2 and early mortality (5 studies; p for non-linearity = 0.004), with the lowest odds being at PaO2 level of 110-210 mmHg, while PaO2 level >110 mmHg showed a linear trend towards higher odds of poor neurological function (4 studies; OR 1.091 [95%CI 0.938–1.269]; p for non-linearity = 0.257). Conclusion Pooled data from observational studies suggest that PaO2 >100 mmHg should be avoided in CS patients on VA-ECMO support, given its linear association with mortality, but it cannot be extrapolated to hypoxemic patients. In ECPR patients, PaO2 level around 110-210 mmHg conferred the best clinical outcomes. However, these findings should be confirmed through randomised controlled trials.

Characterisation of plasma proteins and circulating microRNAs in out-of-hospital cardiac arrest patients - approaches for predicting outcome

Abstract Rationale: Early prognostication after out-of-hospital cardiac arrest (OHCA) is an unmet clinical need. There is limited data on serial release kinetics of cardiac, brain and systemic biomarkers such as Neuron Specific Enolase (NSE) and S-100B. miRNAs are sensitive biomarker candidates in acute myocardial infarction (MI). Objective The objective was to characterise circulating biomolecules in the early release kinetics after OHCA, compared with a STEMI control group and assessed with clinical outcome. Methods and Results Serial blood samples of patients with OHCA with STEMI (n=20) and STEMI control (n=20) were collected at baseline and at 6, 12, 24 and 48h after admission. Untargeted plasma proteomics were performed using data-independent acquisition–mass spectrometry (DIA–MS). Candidate proteins and miRNAs were quantified. Proteomics returned n=156 proteins with significantly different kinetics between OHCA and STEMI. Six clusters, depicting distinct biological pathways, with characteristic differences between OHCA and STEMI were identified. The most distinct and significant differences between OHCA and STEMI patients were seen for acute phase reactants LBP, AACT, CRP and the lipid metabolite A2GL as well as endothelial and platelet miR-126 and cardiomyocyte-apoptosis/ischemia-reperfusion related miR-320a. Cardiogenic shock was best characterised by differential kinetics of coagulation and complement related proteins FA9, HRG, FHR1 and inflammation related miR-146. The primary endpoint was poor neurological recovery at 30-days. Individuals with good outcome showed distinct differences in adaptive immune response, complement and coagulation cascades and hemostasis. Circulating plasma levels of hypoxia-associated miR-101, miR-210 and S-100B protein were significantly elevated at baseline in OHCA patients. These molecules further showed higher baseline values in patients with poor outcome. For current prognosis marker NSE, this difference only develops after 48h. Cardiac/muscle miRNAs followed an early release-pattern similar to high-sensitivity cardiac troponin-T (hs-cTnT). Machine learning models were used to calculate the AUC for the prediction of poor neurological outcome at baseline. This was highest for hypoxia-induced miR-210 (AUC: 0.854), which performed significantly better than the protein biomarkers NSE (AUC: 0.646) and S-100B (AUC:0.656). Conclusions Untargeted mass spectrometry reveals distinct biological pathways and candidate biomolecules affected in patients suffering from OHCA compared with STEMI controls, in patients developing cardiogenic shock and in those with adverse versus good neurological outcome. Platelet-, inflammation and hypoxia associated miRNAs are associated with OHCA, cardiogenic shock and prognostication of adverse neurological outcome. Pronounced differences in early release kinetics of RNA and protein biomarkers may improve identification of OHCA patients at risk of poor outcome.

NSE and S100β as serum alarmins in predicting neurological outcomes after cardiac arrest

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1–2: full recovery or moderate disability) and poor neurological outcome (CPC 3–5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA.

Optimal timing of ultra-early diffusion-weighted MRI in out-of-hospital cardiac arrest patients based on a retrospective multicenter cohort study

Diffusion-weighted magnetic resonance imaging (DW-MRI) performed before target temperature management, within 6 h of return of spontaneous circulation (ROSC), is defined as ultra-early DW-MRI. In previous studies, high-signal intensity (HSI) on ultra-early DW-MRI can predict poor neurological outcomes (Cerebral Performance Category 3–5 at 6-months post-ROSC). We aimed to assess the optimal-timing for ultra-early DW-MRI to avoid false-negative outcomes post out-of-hospital cardiac arrest, considering cardiopulmonary resuscitation (CPR) factors. The primary outcomes were HSI in the cerebral cortex or deep gray matter on ultra-early DW-MRI. The impact of CPR factors and ROSC to DW-MRI scan-interval on HSI-presence was assessed. Of 206 included patients, 108 exhibited HSI-presence, exclusively associated with poor neurological outcomes. In multivariate regression analysis, ROSC to DW-MRI scan-interval (adjusted odds ratio [aOR], 1.509; 95% confidence interval (CI): 1.113–2.046; P = 0.008), low-flow time (aOR, 1.176; 95%CI: 1.121–1.233; P < 0.001), and non-shockable rhythm (aOR, 9.974; 95%CI: 3.363–29.578; P < 0.001) were independently associated with HSI-presence. ROSC to DW-MRI scan-interval cutoff of ≥ 2.2 h was particularly significant in low-flow time ≤ 21 min or shockable rhythm group. In conclusion, short low-flow time and shockable rhythm require a longer ROSC to DW-MRI scan-interval. Prolonged low-flow time and non-shockable rhythm reduce the need to consider scan-interval.

Role of artificial intelligence in predicting neurological outcomes in post cardiac resuscitation

Being an extremely high mortality rate condition, cardiac arrest cases have rightfully been evaluated via various studies and scoring factors for effective resuscitative practices and neurological outcomes post resuscitation. This narrative review aims to explore the role of Artificial Intelligence (AI) in predicting neurological outcomes post cardiac resuscitation. Methodology involved detailed review of all relevant recent studies of AI, different machine learning algorithms, prediction tools and assessing their benefit in predicting neurological outcomes in post cardiac resuscitation cases as compared to more traditional prognostic scoring systems and tools. Previously, outcome determining clinical, blood and radiological factors were prone to other influencing factors like limited accuracy and time constraints. Studies conducted also emphasized that to predict poor neurological outcomes, a more multimodal approach helped adjust for confounding factors, interpret diverse datasets and provide a reliable prognosis which only demonstrates need for AI to help overcome challenges faced. Advanced machine learning algorithms like Artificial Neural Networks (ANN) using supervised learning by AI have improved accuracy of prognostic models outperforming conventional models. Several real-world cases of effective AI powered algorithm models have been cited here. Studies comparing machine learning tools like XGBoost, AI Watson, hyperspectral imaging, ChatGPT-4 and AI based gradient boosting have noted their beneficial uses. AI could help reduce workload, healthcare costs and help personalize care, process vast genetic and lifestyle data and help reduce side effects from treatments. Limitations of AI have been covered extensively in this article including data quality, bias, privacy issues and transparency. Our objectives should be to use more diverse data sources, use interpretable data output giving process explanation, validation method and implement policies to safeguard patient data. Despite the limitations, the advancements already made by AI and its potential in predicting neurological outcomes in post cardiac resuscitation cases has been quite promising and boosts a continually improving system, albeit requiring close human supervision with training and improving models, with plans to educate clinicians, the public and sharing collected data.

Short-term neurologic outcomes in pediatric extracorporeal membrane oxygenation are proportional to bleeding severity graded by a novel bleeding scale.

This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO. Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies. A novel ECMO bleeding scale was utilized to categorize daily bleeding events. Poor short-term neurologic outcome was defined as an unfavorable Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) (score of >3) at hospital discharge. This study included 283 pediatric ECMO patients with a median (interquartile range [IQR]) age of 1.3years [0.1, 9.0], ECMO duration of 5days [3.0, 9.5], and 44.1% mortality. Unfavorable PCPC and POPC were observed in 48.4% and 51.3% of patients at discharge, respectively. Multivariable logistic regression analysis included patient's age, cannulation type, duration of ECMO, need for cardiopulmonary resuscitation, acute kidney injury, new infection, and vasoactive-inotropic score. As the severity of bleeding increased, there was a corresponding increase in the likelihood of poor neurologic recovery, shown by increasing odds of unfavorable neurologic outcome (PCPC), with an adjusted odds ratio (aOR) of 0.77 (confidence interval [CI] 0.36-1.62), 1.87 (0.54-6.45), 2.97 (1.32-6.69), and 5.56 (0.59-52.25) for increasing bleeding severity (grade 1 to 4 events, respectively). Similarly, unfavorable POPC aOR (CI) was 1.02 (0.48-2.17), 2.05 (0.63-6.70), 5.29 (2.12-13.23), and 5.11 (0.66-39.64) for bleeding grade 1 to 4 events. Short-term neurologic outcomes in pediatric ECMO are proportional to the severity of bleeding events. Strategies to mitigate bleeding events could improve neurologic recovery in pediatric ECMO.

Long-Term Outcomes in Antibody-Negative Autoimmune Encephalitis: A Retrospective Study.

To characterize the long-term outcomes of patients with "possible only" or "probable" autoimmune encephalitis (AE). Despite comprising one-third of AE cases, antibody-negative cases lacking typical AE-defining features are understudied. We conducted a retrospective analysis of adult patients evaluated at a tertiary center neuroimmunology practice from 2006 to 2020, meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with at least one year of follow-up. All patients underwent neural antibody testing. Forty-five patients (median age, 61 years [range, 20-88]; female, 21 [47%]) were included, with a median follow-up of 36 months (range, 12-174). A change in diagnosis was noted in six additional patients, who were excluded from further analysis, with only two receiving a non-autoimmune diagnosis during follow-up. The majority (41/45 [91%]) presented with significant disability (modified Rankin Scale [mRS] ≥3) at baseline. CSF was inflammatory in 20/44 (45%) and MRI was abnormal in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two cases (4%) had a paraneoplastic cause. The median time from onset to immunotherapy initiation was two months (range, 0-21), resulting in at least partial improvement in all 44 (98%) treated cases. Clinical relapses occurred in 14/45 (31%). At last follow-up, the most common symptoms were memory dysfunction (31/45 [69%]), attention deficits (17/45 [38%]), gait instability (13/45 [29%]), and visuospatial dysfunction (10/45 [22%]). Most patients achieved independence (median mRS, 2 [range, 0-6]); however, 11 patients had poor neurological outcome (mRS ≥3). Higher mRS score and gait assistance requirement at three months were predictive of poor outcome (P ≤0.01). Despite significant disability at initial stages, patients with antibody-negative but clinically presumed AE show potential for improvement with immunotherapy, highlighting the importance of early intervention. Early functional status and gait assistance requirements may assist in predicting long-term prognosis.

Contribution of an Automatic Algorithm for Quantifying the Volume of Aneurysmal Subarachnoid Hemorrhage to the Evaluation of the Risk of Occurrence of Delayed Cerebral Ischemia: A Cohort Study.

This study focuses on aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of delayed cerebral ischemia (DCI) and acute hydrocephalus (AH). The aim was to compare the performance of an automatic algorithm for quantifying the volume of intracranial blood with the reference radiological scales to predict DCI, AH, and neurological outcome. This was a single-center retrospective observational study of a cohort of patients with aSAH. We developed an automated blood detection algorithm based on the specific density of the blood clot. The blood clot was segmented on the first brain scan (total, supratentorial, cisternal, intraventricular). The predictive value of our model was compared, using the area under the receiver operating characteristic curve (ROCAUC), to eight radiological scales: Fisher, modified Fisher, Claassen, Barrow Neurological Institute, Hijdra, Graeb, LeRoux scales, and intraventricular hemorrhage score. We analyzed the scans of 145 patients with aSAH. In our cohort, 51 patients (43%) had DCI and 70 patients (54%) had AH. At 3 months, 22% of patients had died and 19% had poor outcome (Glasgow Outcome Scale extended 2-4). Cisternal blood volume was significantly correlated with cisternal Hijdra scale (R2 = 0.79; P < 0.001). The ROCAUC of cisternal blood volume was comparable to the ROCAUC of the Hijdra scale in predicting the occurrence of DCI (ROCAUC = 0.83 [95% confidence interval {CI} 0.75-0.89] vs. 0.86 [95% CI 0.79-0.9]; P = 0.23). The ROCAUC of intraventricular blood volume was not significantly different from the intraventricular hemorrhage score in predicting the occurrence of AH (ROCAUC = 0.78 [95% CI 0.70-0.84] vs. 0.79 [95% CI 0.72-0.85]; P = 0.28). The ROCAUC and supratentorial blood volumes were not significantly different from the Simplified Acute Physiology Score II in predicting the occurrence of poor neurological outcome at 3 months (ROCAUC = 0.75 [95% CI 0.67-0.82] vs. 0.81 [95% CI 0.74-0.87]; P = 0.073). With no manual intervention, our algorithm performed as well as the best radiological scores in predicting the occurrence of DCI, AH, and neurological outcome.

Tranexamic Acid in Pediatric Traumatic Brain Injury: A Multicenter Retrospective Observational Study

ObjectiveTranexamic acid (TXA) can be used after trauma to prevent bleeding. Our goal was to examine the impact of TXA on morbidity and mortality for children with severe traumatic brain injury (TBI). MethodsWe identified children aged <18 years with a severe TBI [Glasgow Coma Scale score <8) presenting to one of the 291 hospitals contributing to the Japanese Trauma Data Bank between 2019 and 2023. The primary outcomes was in-hospital death and the secondary outcome was poor neurologic outcome defined with Glasgow Outcome Scale score of 1–3 at hospital discharge. Our primary exposure was any TXA administered in the hospital. Using propensity score-based inverse probability weighting, we used logistic regression to measure the association between TXA administration and death as well as poor neurologic outcome. ResultsOf the 342 included patients, 30 (14%) died and 102 (45%) had a GCS score <8 at discharge. After inverse propensity weighting, TXA administration was not associated with either mortality [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 0.61–2.54) or poor neurologic outcome (aOR 0.86, 95% CI 0.47–1.56). ConclusionsTXA administration was not associated with either death or poor neurologic outcome. Prospective clinical trials of TXA usage in children with severe TBI are needed.

A Study on 24-hour Monitoring of Blood Pressure in Acute Stroke and Its Correlation with Short Term Neurological Outcome.

The association between blood pressure (BP) at admission and clinical outcomes in patients with acute stroke has been investigated; however, results from these studies are contradictory. Hence, we designed this study to monitor circadian variation of BP in acute stroke and study its correlation with neurological outcome. A total of 108 cases of acute stroke (both ischemic and hemorrhagic) admitted within 24 hours were included in the study. On admission, three casual supine BP measurements were taken at 5-minute intervals, and the mean value was recorded. Ambulatory BP monitoring (ABPM) was done on day 1, and all the BP variables were recorded. On the day of admission, the functional status of all the cases was assessed using the Modified Rankin Scale (MRS 0-6). On day 6, again, three casual BP measurements were taken, and MRS was done. The 24-hour BP profile and neurological outcome were correlated on day 1 and day 6. On follow-up at 1 month, all the patients were thoroughly examined, and MRS was done to reassess the functional status post stroke. Circadian variation of BP shows that the majority of our cases were nondippers, followed by reverse dippers and dippers. It was seen that a higher mean 24-hour systolic BP (SBP), daytime SBP, as well as nighttime SBP, were all significantly associated with a poorer MRS score (4-6) both at day 6 and 1 month. Similarly, a higher mean value of the casual SBP, as well as diastolic BP (DBP) readings obtained on day 1 of stroke, adversely affected the outcome in terms of MRS scores both at day 6 and 1 month. It was also seen that the higher mean values of both the casual SBP and DBP readings obtained on day 6 of stroke adversely affected the outcome in terms of MRS scores at 1 month. A higher mean 24-hour SBP, mean daytime SBP, and mean nighttime SBP were associated with poor neurological outcomes at day 6 and 1 month.

Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-MyD88 Pathway in Mice.

People with type 1 diabetes (T1D) have a significantly elevated risk of stroke, but the mechanism through which T1D worsens ischemic stroke remains unclear. This study was aimed at investigating the roles of T1D-associated changes in the gut microbiota in aggravating ischemic stroke and the underlying mechanism. Fecal 16SrRNA sequencing indicated that T1D mice and mice with transplantation of T1D mouse gut microbiota had lower relative abundance of butyric acid producers, f_Erysipelotrichaceae and g_Allobaculum, and lower content of butyric acid in feces. After middle cerebral artery occlusion (MCAO), these mice had poorer neurological outcomes and more severe inflammation, but higher expression of myeloid differentiation factor 88 (MyD88) in the ischemic penumbra; moreover, the microglia were inclined to polarize toward the pro-inflammatory type. Administration of butyrate to T1D mice in the drinking water alleviated the neurological damage after MCAO. Butyrate influenced the response and polarization of BV2 and decreased the production of inflammatory cytokines via MyD88 after oxygen-glucose deprivation/reoxygenation. Knocking down MyD88 in the brain alleviated neurological outcomes and decreased the concentrations of inflammatory cytokines in the brain after stroke in mice with transplantation of T1D mouse gut microbiota. Poor neurological outcomes and aggravated inflammatory responses of T1D mice after ischemic stroke may be partly due to differences in microglial polarization mediated by the gut microbiota-butyrate-MyD88 pathway. These findings provide new ideas and potential intervention targets for alleviating neurological damage after ischemic stroke in T1D.

The Association between Disseminated Intravascular Coagulation Profiles and Neurologic Outcome in Patients with In-Hospital Cardiac Arrest.

The relationship between disseminated intravascular coagulation (DIC) profiles and survival or neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients is well known. In contrast, the relationship between DIC profiles and neurological outcomes in patients with in-hospital cardiac arrest (IHCA) remains unclear. This study sought to examine the correlation between DIC profiles and neurological outcomes in IHCA patients. A retrospective observational study was conducted on comatose adult IHCA patients treated with targeted temperature management between January 2017 and December 2022. DIC profiles were used to calculate the DIC score, and were measured immediately after the return of spontaneous circulation (ROSC). The primary endpoint was a poor neurological outcome at six months, defined by cerebral performance in categories 3, 4, or 5. Multivariate analysis was used to evaluate the association between DIC profiles and poor neurological outcomes. The study included 136 patients, of which 107 (78.7%) patients demonstrated poor neurological outcomes. These patients had higher fibrinogen (3.2 g/L vs. 2.3 g/L) and fibrin degradation product levels (50.7 mg/L vs. 30.1 mg/L) and lower anti-thrombin III (ATIII) levels (65.7% vs. 82.3%). The DIC score did not differ between the good and poor outcome groups. In multivariable analysis, fibrinogen (odds ratio [OR], 1.009; 95% confidence intervals [CI], 1.003-1.016) and ATIII levels (OR, 0.965; 95% CI, 0.942-0.989) were independently associated with poor neurological outcomes. Decreased fibrinogen and ATIII levels after ROSC were an independent risk factor for unfavorable neurological outcomes in IHCA. The DIC score is unlikely to play a significant role in IHCA prognosis in contrast to OHCA.

Effect of targeted temperature management on systemic inflammatory responses after out-of-hospital cardiac arrest: A prospective cohort study.

Interleukin (IL)-6 is a major inflammatory cytokine that predicts mortality after out-of-hospital cardiac arrest (OHCA). Targeted temperature management (TTM) is associated with improved all-cause mortality in patients with OHCA. However, the effect of TTM on IL-6 production remains unclear. This study investigated whether TTM has additional anti-inflammatory effects after OHCA. This prospective cohort study included a total of 141 hospitalized patients with OHCA who were treated between January 2015 and June 2023. The study was conducted in the intensive care unit of China Medical University Hospital, Taichung. Postcardiac arrest care included TTM or the control approach (no TTM). The primary outcomes included the 90-day mortality rate and neurologic outcomes after OHCA. Differences between the TTM and control groups were examined using Student t test, chi-square test, and Kaplan-Meier survival curve analysis. Multivariate analysis of variance model was used to examine interaction effects. Plasma IL-6 and IL-6/soluble IL-6 receptor complex levels were measured at 6 and 24 hours after resuscitation. IL-6 and IL-6/soluble IL-6 receptor complex production was lower in the TTM group than in the control group (-50.0% vs +136.7%, P < .001; +26.3% vs +102.40%, P < .001, respectively). In addition, the 90-day mortality rate and poor neurologic outcomes were lower in the TTM group than in the control group (36.8% vs 63.0%, relative risk 0.39, 95% confidence interval 0.24-0.64, P < .001; 65.5% vs 81.5%, relative risk 0.80, 95% confidence interval 0.66-0.98, P = .04). TTM improves both the mortality rate and neurologic outcomes in patients resuscitated from OHCA, possibly by reducing IL-6-induced proinflammatory responses.

Derivation of a clinical decision rule for termination of resuscitation in non-traumatic pediatric out-of-hospital cardiac arrest

AimPrehospital termination of resuscitation (ToR) rules are used to predict medical futility in adult out-of-hospital cardiac arrest (OHCA), however, the available evidence for pediatric patients is limited. The primary aim of this study is to derive a Pediatric Termination of Resuscitation (PToR) prediction rule for use in pediatric non-traumatic OHCA patients. MethodsWe analyzed a retrospective cohort of pediatric OHCA patients within the CARES database over a 10-year period (2013–2022). We split the dataset into training and test datasets and fit logistic regressions with Least Absolute Shrinkage and Selection Operator (LASSO) to select predictor variables and estimate predictive test characteristics for the primary outcome of death and a secondary composite outcome of death or survival to hospital discharge with unfavorable neurologic status. ResultsWe analyzed a sample of 21,240 children where 2,326 (11.0%) survived to hospital discharge, and 1,894 (8.9%) survived to hospital discharge with favorable neurologic status. We derived a PToR rule for death demonstrating a specificity of 99.1% and a positive predictive value (PPV) of 99.8% and a PToR rule for death or survival with poor neurologic status with a specificity of 99.7% and PPV of 99.9% within the test dataset. ConclusionWe derived a clinical prediction rule with high specificity and positive predictive value in prehospital settings utilizing Advanced Life Support (ALS) providers which may inform termination of resuscitation considerations in pediatric patients. Further prospective and validation studies will be necessary to define the appropriateness and applicability of these PToR criteria for routine use.

Long-term outcomes in antibody-negative autoimmune encephalitis: a retrospective study.

Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of "possible only" and "probable" AE cases. We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006-12/31/2020), meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with ≥ 1year of follow-up. All patients underwent neural antibody testing. Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61years (range 20-88); female, 21 (47%); median follow-up, 36months (range 12-174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3months were predictive of poor outcome (P ≤ 0.01). Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis.

Effectiveness of Extracorporeal Cardiopulmonary Resuscitation for Non-Shockable Out-of-Hospital Cardiac Arrest: An Analysis From the SOS-KANTO 2017 Study.

Extracorporeal cardiopulmonary resuscitation (ECPR) using veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has the potential as a viable treatment for refractory out-of-hospital cardiac arrest (OHCA). While mechanical circulatory support devices, such as Impella® and left ventricular assist devices, are being increasingly used, initial ECPR often relies on V-A ECMO. Previous studies, including randomized controlled trials, reported the prognostic benefits of ECPR for shockable OHCA (SOHCA); however, its effectiveness for non-SOHCA (NSOHCA) remains unclear, with poorer neurological outcomes and the lower return of spontaneous circulation rates than for SOHCA being reported. The present study utilized data from the SOS-KANTO 2017 study to examine the impact of ECPR on the neurological outcomes of NSOHCA. Data from 2,502 OHCA cases were analyzed, with a focus on the relationship between ECPR and 90-day neurological outcomes. The results obtained showed significantly higher survival rates at 30 and 90 days and significantly better 90-day neurological outcomes in the ECMO attempt group than in the non-ECMO attempt group. A multivariate analysis identified ECPR as one of the significant independent predictors of favorable neurological outcomes. The prognosis of NSOHCA cases with CA was improved by ECPR using V-A ECMO, particularly in those where CPR was initiated within one minute of onset and the patient arrived at the hospital within 45 minutes. Factors associated with a favorable prognosis included a shorter time from onset to hospital arrival and the likelihood of acute coronary syndrome being the cause of CA. The present results suggest the potential of ECPR to improve the survival and the 90-day prognosis of NSOHCA, particularly when bystander CPR is initiated quickly and hospital arrival is prompt.

Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100µg/kg/day) for 5days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE.