Acetate supplementation improves neurological outcomes by preventing hyperglycemia and suppressing Serpina3n expression in CA1 region after cardiac arrest and cardiopulmonary resuscitation.

BACKGROUND: Hyperglycemia is common after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). More importantly, it is associated with a worse neurological outcome after CA/CPR. Acetate has been proven to be of great value to reprogram glucose metabolism in the whole body. Nevertheless, the impact of acetate on hyperglycemia and neurological outcomes after CA/CPR remains largely unexplored. METHODS: Glucose metabolism-related parameters were examined to assess the changes of glucose metabolism in our CA/CPR model. Survival and neurological function were measured after return of spontaneous circulation. Acetate supplementation was achieved by gavage to assess the impact of acetate on CA/CPR-induced hyperglycemia. Proteomics investigation of the changes in proteins of the CA1 region were performed to explore the differences of protein expression. The correlation between acetate supplementation and improvement of neurological outcomes after CA/CPR was elucidated by Serpina3n over-expression and knockdown in CA1 region. RESULTS: CA/CPR induces hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance with upregulation of Serpina3n in CA1 region. Acetate supplementation could attenuate hyperglycemia, reduce protein levels of Serpina3n in CA1 region, and improves neurological outcomes after CA/CPR. Mechanistically, the acetate-dependent improvement of neurological outcomes after CA/CPR and attenuation of CA/CPR-induced hyperglycemia were correlated with the down-regulation of Serpina3n in CA1 region. CONCLUSIONS: Our findings suggest that acetate supplementation improves neurological outcomes of CA/CPR mice by maintaining glucose homeostasis in the whole body and suppression of Serpina3n expression in CA1 region.

Impacts of Maternal Preeclampsia Exposure on Offspring Neuronal Development: Recent Insights and Interventional Approaches.

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders.

NSE and S100ß 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 ß (S100ß), 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, S100ß 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 S100ß, 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 S100ß were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100ß combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA.

Validation of CASPRI, GO-FAR, PIHCA scores in predicting favorable neurological outcomes after in-hospital cardiac arrest; A five-year three center retrospective study in IRAN.

BACKGROUND: Predicting neurological outcomes following in-hospital cardiac arrest is crucial for guiding subsequent clinical treatments. This study seeks to validate the effectiveness of the CASPRI, GO-FAR, and PIHCA tools in predicting favorable neurological outcomes after in-hospital cardiac arrest. METHOD: This retrospective study utilized a Utstein-style structured form to review the medical records of patients who experienced in-hospital cardiac arrest between March 2018 and March 2023. Predictors were examined using multivariable logistic regression, and the validity of the tools was assessed using ROC curves. Statistical analysis was conducted using SPSS version 25 software. RESULTS: Out of the 1100 patients included in the study, 42 individuals (3.8%) achieved a favorable neurological outcome. multivariable regression analysis revealed that age, respiratory failure, resuscitation shift, duration of renal failure, and CPC score 24 h before cardiac arrest were significantly associated with favorable neurological outcomes. The predictive abilities of the CASPRI, GO-FAR, and PIHCA scores were calculated as 0.99 (95% CI, 0.98-1.00), 0.98 (95% CI, 0.97-0.99), and 0.96 (95% CI, 0.94-0.99) respectively. A statistically significant difference was observed in the predictive abilities of the CASPRI and PIHCA scores (P = 0.001), while the difference between CASPRI and GO-FAR did not reach significance (P = 0.057). Additionally, there was no significant difference between the predictive abilities of GO-FAR and PIHCA scores (P = 0.159). CONCLUSION: The study concludes that CASPRI and GO-FAR scores show strong potential as objective measures for predicting favorable neurological outcomes post-cardiac arrest. Integrating these scores into clinical decision-making may enhance treatment and care strategies, in the Iranian healthcare context.

The Role of Early Intervention Therapy in Neurodevelopmental Outcomes of Premature Infants.

Neurodevelopmental impairments are known to be more common in premature infants. Premature and low birth weight babies are now more likely to survive because of modern technologies and advancements in perinatal and postnatal care. However, long stays and exposure to harsh stimuli in neonatal intensive care units are known to have a negative impact on the developing neonatal brain. Therefore, the goal of early intervention (EI) is to assist an infant and their family in achieving the greatest potential outcome. This encompasses a broad spectrum of strategies and structured programs that might differ in many aspects, such as who should implement them, where they should take place, and when they should begin. They aid in minimizing brain damage and optimizing growth via varied sensory and motor stimuli. Current evidence supports the initiation of EI therapy soon after birth, starting from neonatal intensive care units and continuing post-discharge. This research is important, especially in developing countries like ours, owing to the increasing number of premature deliveries due to multiple reasons. The focus of this article is to analyze the various protocols and applications available to us for the implementation of EI therapies and their benefits.

Vitamin B12 Deficiency in Patients Taking Metformin: Pathogenesis and Recommendations.

Metformin is a cornerstone therapy for type 2 diabetes mellitus due to its glucose-lowering efficacy and additional benefits such as reducing cardiovascular mortality. However, accumulating evidence suggests an association between long-term metformin use and vitamin B12 deficiency, which can lead to serious clinical consequences. This review aims to synthesize current knowledge on the pathogenesis, prevalence, clinical implications, and management of metformin-induced vitamin B12 deficiency. Given the significant clinical implications, it is crucial to monitor and manage vitamin B12 levels in patients using metformin. This review emphasizes the importance of early detection and supplementation to prevent adverse outcomes. By analyzing the current evidence, the review aims to inform healthcare professionals about best practices for managing vitamin B12 deficiency in patients on metformin, offering insights to guide future clinical practices and research directions.

Galectin-3 Predicts Long-Term Risk of Cerebral Disability and Mortality in Out-of-Hospital Cardiac Arrest Survivors.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and cerebral disability in survivors. Current models of risk prediction and survival are mainly based on resuscitation duration. We examined the prognostic value of circulating biomarkers in predicting mortality and severe cerebral disability for OHCA survivors, alongside traditional clinical risk indicators. METHODS: Biomarkers including BNP, troponin I, and galectin-3 were measured at hospital admission in resuscitated OHCA patients. Prognostic significance for mortality and cerebral disability involving circulating biomarkers, resuscitation duration, demographics, and laboratory and clinical characteristics was examined via univariate and multivariate Cox proportional hazards regression models. The incremental prognostic value of the index covariates was examined through model diagnostics, focusing on the Akaike information criterion (AIC) and Harrell's concordance statistic (c-statistic). RESULTS: In a combinatorial analysis of 144 OHCA survivors (median follow-up 5.7 years (IQR 2.9-6.6)), BNP, galectin-3, arterial pH, and resuscitation time were significant predictors of all-cause death and severe cerebral disability, whereas troponin I levels were not. Multivariate regression, adjusting for BNP, arterial pH, and resuscitation time, identified galectin-3 as an independent predictor of long-term mortality. Multiple linear regression models also confirmed galectin-3 as the strongest predictor of cerebral disability. The incorporation of galectin-3 into models for predicting mortality and cerebral disability enhanced fit and discrimination, demonstrating the incremental value of galectin-3 beyond traditional risk predictors. CONCLUSIONS: Galectin-3 is a significant, independent long-term risk predictor of cerebral disability and mortality in OHCA survivors. Incorporating galectin-3 into current risk stratification models may enhance early prognostication and guide targeted clinical interventions.

Association between bystander automated external defibrillator use and survival in witnessed out-of-hospital cardiac arrest: A nationwide observational study in South Korea.

AIM: Sudden cardiac arrest is a global health issue, with out-of-hospital cardiac arrest (OHCA) posing a major challenge. Bystander cardiopulmonary resuscitation (CPR) and automated external defibrillators (AEDs) improve survival and neurological outcomes. However, their actual usage involves numerous constraints. Therefore, to determine the association between bystander AED use and survival of patients with OHCA, we analyzed South Korea's national OHCA database. METHODS: This retrospective study included cases from the Korea Disease Control and Prevention Agency's Out-of-Hospital Cardiac Arrest Surveillance database from January 2016 to December 2021. Adult OHCA cases treated with bystander intervention were categorized into two groups, CPR with AEDs and without AEDs. Propensity score matching was employed to control for confounders and analyze bystander AED use's impact on survival to discharge and neurological outcomes. RESULTS: Of 182,508 OHCA cases, 35,840 met the inclusion criteria, with 234 (0.7%) receiving bystander CPR with AEDs. The survival rate to discharge in the AED and non-AED group was 46.6% and 23.0%, respectively. However, after adjusting for potential confounders, bystander AED use did not significantly affect survival to discharge (adjusted odds ratio [aOR] 1.01, 95% confidence interval [CI] 0.70-1.44) or favorable neurological outcomes (aOR 1.08, 95% CI 0.99-1.18). CONCLUSION: Survival to discharge or favorable neurological outcomes of patients with OHCA managed using bystander-applied AEDs and those without showed no significant difference. Factors such as AED accessibility and bystander preparedness influence the impact of bystander AED use. Further research should optimize AED deployment and usage strategies to enhance patient survival rate.

Neurological monitoring and management for adult extracorporeal membrane oxygenation patients: Extracorporeal Life Support Organization consensus guidelines.

BACKGROUND: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Targeted Temperature Management for Out-of-Hospital Cardiac Arrest Survivors.

Targeted temperature management (TTM), specifically therapeutic hypothermia, has been proposed to provide neuroprotective and mortality benefits for out-of-hospital cardiac arrest (OHCA) survivors. This proposition was based on small-scale trials from the early 2000s, leading to its incorporation into various international guidelines. The proposed neuroprotective mechanisms include reducing cerebral metabolic rate, stabilizing the blood-brain barrier, reducing the release of excitatory neurotransmitters, and suppressing apoptotic pathways. However, these early trials have been criticized for their high risk of bias and lack of standardized protocols. Recent evidence from more rigorously controlled randomized trials indicates no significant association between hypothermia and improved neurological outcomes or survival rates. This review explores the latest clinical evidence on TTM for OHCA patients, discussing the pathophysiology, evaluating the effectiveness of hypothermia through various clinical trials, and providing recommendations for future research and clinical practice.

Efficacy of decompressive craniectomy: A retrospective case series study with 321 patients and an update on controversies.

Decompressive craniectomy (DC) is considered a cornerstone in the management of refractory intracranial hypertension. For decades, DC was known as an occasionally lifesaving procedure; however, it was associated with numerous severe complications. The present study is a single-center retrospective case series study on with 321 patients who underwent DC between January, 2010 and December, 2020. All patients were divided into four groups as follows: Group A included patients who suffered from a space-occupying middle cerebral artery (MCA) ischemic event; group B included individuals who developed intracerebral hemorrhage; group C included patients admitted for traumatic brain injury; and group D included patients with other neurosurgical entities that underwent DC, such as subarachnoid hemorrhage, tumors, brain abscess and cerebral ventricular sinus thrombosis events. The present study enrolled a total of 321 patients who underwent DC. Group A included 52 out of the 321 (16.1%) patients, group B included 51 (15.8%) patients, group C included 164 (51.0%) patients, and group D included 54 (16.8%) patients. Of the 321 patients, 235 (73.2%) were males, and the median age was 53.7 years. Multivariate analysis revealed that only the group A parameter was an independent factor associated with a Glasgow outcome scale score >2 during follow-up (P<0.05). On the whole, the results of the present study suggest that among patients who underwent DC with different neurological entities, those who had experienced MCA events had more favorable outcomes.

Amiodarone Administration during Cardiopulmonary Resuscitation Is Not Associated with Changes in Short-Term Mortality or Neurological Outcomes in Cardiac Arrest Patients with Shockable Rhythms.

Background: The search for the best therapeutic approach in cardiopulmonary resuscitations (CPR) remains open to question. In this study, we evaluated if Amiodarone administration during CPR was associated with short-term mortality or neurological development. Methods: A total of 232 patients with sudden cardiac arrest (CA) with shockable rhythms were included in our analysis. Propensity score matching based on age, gender, type of CA, and CPR duration was used to stratify between patients with and without Amiodarone during CPR. Primary endpoints were short-term mortality (30-day) and neurological outcomes assessed by the cerebral performance category. Secondary endpoints were plasma lactate, phosphate levels at hospital admission, and the peak Neuron-specific enolase. Results: Propensity score matching was successful with a caliper size used for matching of 0.089 and a sample size of n = 82 per group. The 30-day mortality rates were similar between both groups (p = 0.24). There were no significant differences in lactate levels at hospital admission and during the following five days between the groups. Patients receiving Amiodarone showed slightly higher phosphate levels at hospital admission, while the levels decreased to a similar value during the following days. Among CA survivors to hospital discharge, no differences between the proportion of good neurological outcomes were detected between the two groups (p = 0.58), despite slightly higher peak neuron-specific enolase levels in CA patients receiving Amiodarone (p = 0.03). Conclusions: Amiodarone administration is not associated with short-term mortality or neurological outcomes in CA patients with shockable rhythms receiving CPR.

Intraoperative goal-directed fluid therapy in adult patients undergoing craniotomies under general anaesthesia: A systematic review and meta-analysis with trial sequential analysis.

Background and Aims: Goal-directed fluid therapy (GDFT) has conflicting evidence regarding outcomes in neurosurgical patients. This meta-analysis aimed to compare the effect of GDFT and conventional fluid therapy on various perioperative outcomes in patients undergoing neurosurgical procedures. Methods: A comprehensive literature search was conducted using PubMed, EMBASE, Scopus, ProQuest, Web of Science, EBSCOhost, Cochrane and preprint servers. The search was conducted up until 16 October 2023, following PROSPERO registration. The search strategy included terms related to GDFT, neurosurgery and perioperative outcomes. Only randomised controlled trials involving adult humans and comparing GDFT with standard/liberal/traditional/restricted fluid therapy were included. The studies were evaluated for risk of bias (RoB), and pooled estimates of the outcomes were measured in terms of risk ratio (RR) and mean difference (MD). Results: No statistically significant difference was observed in neurological outcomes between GDFT and conventional fluid therapy [RR with 95% confidence interval (CI) was 1.10 (0.69, 1.75), two studies, 90 patients, low certainty of evidence using GRADEpro]. GDFT reduced postoperative complications [RR = 0.67 (0.54, 0.82), six studies, 392 participants] and intensive care unit (ICU) and hospital stay [MD (95% CI) were -1.65 (-3.02, -0.28) and -0.94 (-1.47, -0.42), respectively] with high certainty of evidence. The pulmonary complications were significantly lower in the GDFT group [RR (95% CI) = 0.55 (0.38, 0.79), seven studies, 442 patients, high certainty of evidence]. Other outcomes, including total intraoperative fluids administered and blood loss, were comparable in GDFT and conventional therapy groups [MD (95% CI) were -303.87 (-912.56, 304.82) and -14.79 (-49.05, 19.46), respectively]. Conclusion: The perioperative GDFT did not influence the neurological outcome. The postoperative complications and hospital and ICU stay were significantly reduced in the GDFT group.

Prevalence and Neurological Outcomes of Comatose Patients With Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients. DESIGN: Retrospective observational. SETTING: Tertiary academic hospital. PARTICIPANTS: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (comaoff) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (comaon) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced comaoff. Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had comaon. Comaoff was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas comaon only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for comaoff after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation). CONCLUSIONS: Comaoff was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor.

Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Series of 14 Cases and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare type of tumor characterized by spindle-shaped cells originating from mesenchymal tissue. This case series presents a collection of 14 intracranial solitary fibrous tumors treated between 2014 and 2022 in our institute in Bucharest, Romania. Through a systematic investigation, key aspects spanning the preoperative, intraoperative, and postoperative phases of patient care were highlighted. Our study examines various factors including tumor location (which was very heterogeneous), size (median of 49 mm, ranging between 22 mm and 70 mm), surgical techniques employed, and recurrence rates. The data was analyzed using Python version 3.10 (Python Software Foundation, Wilmington, Delaware, United States). Gender disparities in SFT were noted, particularly the male-to-female ratio which was 5:9. The use of the Medical Research Council (MRC) Scale for Muscle Strength aided in evaluating severity and postoperative outcomes. GTR was achieved in nine out of 14 cases (64.28%), prolonging the period of recurrence-free survival.

Lactate-to-albumin ratio and cholesterol levels predict neurological outcome in cardiac arrest survivors.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear. METHODS: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed. RESULTS: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively. CONCLUSIONS: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02633358.

Machine Learning from Veno-Venous Extracorporeal Membrane Oxygenation Identifies Factors Associated with Neurological Outcomes.

BACKGROUND: Neurological complications are common in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) support. We used machine learning (ML) algorithms to identify predictors for neurological outcomes for these patients. METHODS: All demographic, clinical, and circuit-related variables were extracted for adults with VV-ECMO support at a tertiary care center from 2016 to 2022. The primary outcome was good neurological outcome (GNO) at discharge defined as a modified Rankin Scale of 0-3. RESULTS: Of 99 total VV-ECMO patients (median age = 48 years; 65% male), 37% had a GNO. The best performing ML model achieved an area under the receiver operating characteristic curve of 0.87. Feature importance analysis identified down-trending gas/sweep/blender flow, FiO2, and pump speed as the most salient features for predicting GNO. CONCLUSION: Utilizing pre- as well as post-initiation variables, ML identified on-ECMO physiologic and pulmonary conditions that best predicted neurological outcomes.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Long-term neurological outcomes of offspring misdiagnosed with fetal growth restriction.

OBJECTIVE: Fetal growth restriction (FGR) is a major determinant of adverse short- and long-term perinatal outcomes. The current definition of FGR (estimated fetal weight measurement < 10th percentile) may lead, at times, to a false diagnosis of fetuses that are eventually born appropriate for gestational age (AGA). Our objective was to investigate the potential association between a misdiagnosis of antepartum fetal growth restriction and long-term neurological outcomes in offspring. STUDY DESIGN: A population-based cohort analysis was performed including deliveries between the years 1991-2020 in a tertiary medical center. We compared neurological hospitalization during childhood among AGA infants falsely diagnosed as FGR versus AGA infants without a false FGR diagnosis. A Kaplan-Meier survival curve was used to assess cumulative morbidity and a Cox proportional hazards model was employed to control for confounders. RESULTS: During the study period, 324,620 AGA infants met the inclusion criteria; 3249 of them were falsely classified as FGR. These offspring had higher rates of hospitalizations due to various neurological conditions, as compared to those without an FGR diagnosis (OR 1.431, 95% CI 1.278-1.608; P < 0.001). In addition, cumulative hospitalization incidence was elevated in the FGR group (log-rank P-value < 0.001). When controlling for confounders, a false FGR diagnosis remained independently associated with long-term neurological morbidities (adjusted HR 1.086, 95% CI 1.003-1.177, P = 0.043). CONCLUSION: Misdiagnosis of FGR in the antepartum period is associated with an increased risk for offspring long-term neurological morbidities.