Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's disease: a meta-analysis of randomized controlled trials.

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression - Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.Prospero registry: CRD42023486694.

Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative. AIMS: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms. RESULTS: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality. CONCLUSIONS: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

Replacement of traditional vagus nerve stimulation with cardiac-based device and seizure reduction: A systematic review and meta-analysis.

INTRODUCTION: For patients with drug-resistant epilepsy (DRE) who are not suitable for surgical resection, neuromodulation with vagus nerve stimulation (VNS) is an established approach. However, there is limited evidence of seizure reduction when replacing traditional VNS (tVNS) device with a cardiac-based one (cbVNS). This meta-analysis compares the seizure reduction achieved by replacing tVNS with cbVNS in a population with DRE. METHODS: We systematically searched PubMed, Embase, and Cochrane Central following PRISMA guidelines. The main outcomes were number of patients experiencing a ≥ 50 % and ≥80 % reduction in seizures, as defined by the McHugh scale. Additionally, we assessed the number of patients achieving freedom from seizures. RESULTS: We included 178 patients with DRE from 7 studies who were initially treated with tVNS and subsequently had it replaced by cbVNS. The follow-up for cbVNS ranged from 6 to 37.5 months. There was a statistically significant reduction in seizure frequency with the replacement of tVNS by cbVNS, using a ≥ 50 % (OR 1.79; 95 % CI 1.07 to 2.97; I²=0 %; p = 0.03) and a ≥ 80 % (OR 2.06; 95 % CI 1.17 to 3.62; I²=0 %; p = 0.01) reduction threshold. Nineteen (13 %) participants achieved freedom from seizures after switching to cbVNS. There was no difference in the rate of freedom from seizures between groups (OR 1.85; 95 % CI 0.81 to 4.21; I²=0 %; p = 0.14). CONCLUSION: In patients with DRE undergoing battery replacement, cbVNS might be associated with seizure reduction (≥50 % and ≥80 % threshold) after switching from tVNS. Randomised controlled trials are necessary to validate these findings.

Neuropsychological outcomes in patients with ruptured anterior communicating artery aneurysms treated by clipping versus coiling: a systematic review and meta-analysis.

Ruptured anterior communicating artery (ACoA) aneurysms are frequently associated with neuropsychological deficits. This review aims to compare neuropsychological outcomes between surgical and endovascular approaches to ACoA. We systematically searched PubMed, Embase, and Web of Science for studies comparing the endovascular and surgical approaches to ruptured ACoA aneurysms. Outcomes of interest were the cognitive function, covered by memory, attention, intelligence, executive, and language domains, as well as motor and visual functions. Nine studies, comprising 524 patients were included. Endovascularly-treated patients showed better memory than those treated surgically (Standardized Mean Difference (SMD) = -2; 95% CI: -3.40 to -0.61; p < 0.01). Surgically clipped patients had poorer motor ability than those with coiling embolization (p = 0.01). Executive function (SMD = -0.20; 95% CI: -0.47 to 0.88; p = 0.55), language (SMD = -0.33; 95% CI: -0.95 to 0.30; p = 0.30), visuospatial function (SMD = -1.12; 95% CI: -2.79 to 0.56; p = 0.19), attention (SMD = -0.94; 95% CI: -2.79to 0.91; p = 0.32), intelligence (SMD = -0.25; 95% CI: -0.73 to 0.22; p = 0.30), and self-reported cognitive status (SMD = -0.51; 95% CI: -1.38 to 0.35; p = 0.25) revealed parity between groups. Patients with ACoA treated endovascularly had superior memory and motor abilities. Other cognitive domains, including executive function, language, visuospatial function, attention, intelligence and self-reported cognitive status revealed no statistically significant differences between the two approaches. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42023461283; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461283.

Sepsis death risk factor score based on systemic inflammatory response syndrome, quick sequential organ failure assessment, and comorbidities.

OBJECTIVE: In this study, we aimed to evaluate the death risk factors of patients included in the sepsis protocol bundle, using clinical data from qSOFA, SIRS, and comorbidities, as well as development of a mortality risk score. DESIGN: This retrospective cohort study was conducted between 2016 and 2021. SETTING: Two university hospitals in Brazil. PARTICIPANTS: Patients with sepsis. INTERVENTIONS: Several clinical and laboratory data were collected focused on SIRS, qSOFA, and comorbidities. MAIN VARIABLE OF INTEREST: In-hospital mortality was the primary outcome variable. A mortality risk score was developed after logistic regression analysis. RESULTS: A total of 1,808 patients were included with a death rate of 36%. Ten variables remained independent factors related to death in multivariate analysis: temperature ≥38 °C (odds ratio [OR] = 0.65), previous sepsis (OR = 1.42), qSOFA ≥ 2 (OR = 1.43), leukocytes >12,000 or <4,000 cells/mm3 (OR = 1.61), encephalic vascular accident (OR = 1.88), age >60 years (OR = 1.93), cancer (OR = 2.2), length of hospital stay before sepsis >7 days (OR = 2.22,), dialysis (OR = 2.51), and cirrhosis (OR = 3.97). Considering the equation of the binary regression logistic analysis, the score presented an area under curve of 0.668, is not a potential model for death prediction. CONCLUSIONS: Several risk factors are independently associated with mortality, allowing the development of a prediction score based on qSOFA, SIRS, and comorbidities data, however, the performance of this score is low.

Myocardial tissue expression of mRNA and preoperative neutrophil-lymphocyte ratio in children undergoing congenital heart surgery.

Background: The neutrophil-lymphocyte ratio (NLR) is an easily accessible and inexpensive biomarker that has been shown to predict morbidity and mortality in congenital cardiac surgery. However, its regulatory mechanism remains unclear. This study aims to compare and correlate the tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 messenger RNAs (mRNAs) with the NLR in patients with tetralogy of Fallot (ToF) and ventricular septal defect (VSD). Methods: A prospective translational study was conducted on 10 children with ToF and 10 with VSD, aged between 1 and 24 months. The NLR was calculated from the blood count taken 24 hours before surgery. The expression of these mRNAs was analyzed in the myocardial tissue of the right atrium prior to cardiopulmonary bypass. Results: Patients with ToF exhibited a higher NLR [ToF 0.46 (interquartile range; IQR) 0.90; VSD 0.28 (IQR 0.17); P=0.02], longer mechanical ventilation time [ToF 24 h (IQR 93); VSD 5.5 h (IQR 8); P<0.001], increased use of vasoactive drugs [ToF 2 days (IQR 1.75); VSD 0 (IQR 1); P=0.01], and longer ICU [ToF 5.5 (IQR 1); VSD 2 (IQR 0.75); P=0.02] and hospital length of stays [ToF 18 days (IQR 17.5); VSD 8.5 days (IQR 2.5); P<0.001]. A negative correlation was found between NLR and oxygen saturation (SaO2) (r=-0.44; P=0.002). In terms of mRNA expression, the ToF group showed a lower expression of IL-10 mRNA (P=0.03). A positive correlation was observed between IL-10-mRNA and SaO2 (r=0.40; P=0.07), and a negative correlation with NLR (r=-0.27; P=0.14). Conclusions: Patients with ToF demonstrated a higher preoperative NLR and lower IL-10 mRNA expression by what appears to be a pro-inflammatory phenotype of cyanotic patients.

Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

Does amantadine improve cognitive recovery in severe disorders of consciousness after aneurysmal subarachnoid hemorrhage? A double-blind placebo-controlled study.

BACKGROUND: Severe disorders of consciousness (sDoC) are a common sequela of aneurysmal subarachnoid hemorrhages (aSAH), and amantadine has been used to improve cognitive recovery after traumatic brain injury. OBJECTIVE: This study evaluated the effect of amantadine treatment on consciousness in patients with sDoC secondary to aSAH. METHODS: This double-center, randomized, prospective, cohort study included patients ≥ 18 years old with sDoC after aSAH from February 2020 to September 2023. Individual patient data of patients were pooled to determine the effect of amantadine, in comparison to placebo. The primary outcomes at 3 and 6 months after the ictus were evaluated using the modified Rankin scale (mRS) and Glasgow outcome scale (GOS). In addition to all-cause mortality, secondary endpoints were assessed weekly during intervention by scores on Rappaport's Disability Rating Scale (RDRS) and Coma Recovery Scale-Revised (CRSR). RESULTS: Overall, 37 patients with sDoC and initial Glasgow Coma Scale (GCS) varying between 3 and 11 were recruited and randomized to amantadine (test group, n = 20) or placebo (control group, n = 17). The average age was 59.5 years (28 to 81 year-old), 24 (65%) were women, and the mean GCS at the beginning of intervention was 7.1. Most patients evolved to vasospasm (81%), with ischemia in 73% of them. The intervention was started between 30 to 180 days after the ictus, and administered for 6 weeks, with progressively higher doses. Neither epidemiological characteristics nor considerations regarding the treatment of the aneurysm and its complications differed between both arms. Overall mortality was 10.8% (4 deaths). During the study, four patients had potential adverse drug effects: two presented seizures, one had paralytic ileus, and another evolved with tachycardia; the medication was not suspended, only the dose was not increased. At data opening, 2 were taking amantadine and 2 placebo. CONCLUSION: Despite some good results associated with amantadine in the literature, this study did not find statistically significant positive effects in cognitive recovery in patients with delayed post-aSAH sDoC. Further large randomized clinical trials in patients' subgroups are needed to better define its effectiveness and clarify any therapeutic window where it can be advantageous.

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study.

BACKGROUND: There is very few data regarding homocysteine's influence on the formation and rupture of intracranial aneurysms. OBJECTIVE: To compare homocysteine levels between patients with ruptured and unruptured intracranial aneurysms, and to evaluate possible influences of this molecule on vasospasm and functional outcomes. METHODS: This is a retrospective, case-control study. We evaluated homocysteinemia differences between patients with ruptured and unruptured aneurysms; and the association of homocysteine levels with vasospasm and functional outcomes. Logistic regressions were performed. RESULTS: A total of 348 participants were included: 114 (32.8%) with previous aneurysm rupture and 234 (67.2%) with unruptured aneurysms. Median homocysteine was 10.75µmol/L (IQR = 4.59) in patients with ruptured aneurysms and 11.5µmol/L (IQR = 5.84) in patients with unruptured aneurysms. No significant association was detected between homocysteine levels and rupture status (OR = 0.99, 95% CI = 0.96-1.04). Neither mild (>15µmol/L; OR = 1.25, 95% CI 0.32-4.12) nor moderate (>30µmol/L; OR = 1.0, 95% CI = 0.54-1.81) hyperhomocysteinemia demonstrated significant correlations with ruptured aneurysms. Neither univariate (OR = 0.86; 95% CI 0.71-1.0) nor multivariable age-adjusted (OR = 0.91; 95% CI = 0.75-1.05) models evidenced an association between homocysteine levels and vasospasm. Homocysteinemia did not influence excellent functional outcomes at 6 months (mRS≤1) (OR = 1.04; 95% CI = 0.94-1.16). CONCLUSION: There were no differences regarding homocysteinemia between patients with ruptured and unruptured intracranial aneurysms. In patients with ruptured aneurysms, homocysteinemia was not associated with vasospasm or functional outcomes.

ANTECEDENTES: Existem poucos dados sobre a influência da homocisteína na formação e rotura de aneurismas intracranianos (AI). OBJETIVO: Comparar os níveis de homocisteína entre pacientes com AI rotos e não rotos e influências no vasoespasmo e resultados funcionais. MéTODOS: Estudo caso-controle, que avaliou as diferenças de homocisteinemia entre pacientes com aneurismas rotos e não rotos, além da associação entre níveis de homocisteína, vasoespasmo e estado funcional. Regressões logísticas foram realizadas. RESULTADOS: Um total de 348 participantes foram incluídos: 114 (32,8%) com aneurismas rotos e 234 (67,2%) não rotos. A homocisteína mediana foi de 10,75µmol/L (IQR = 4,59) nos rotos e 11,5µmol/L (IQR = 5,84) nos não rotos. Não houve associação significativa entre os níveis de homocisteína e o status de ruptura (OR = 0,99, 95% CI = 0,96-1,04). Nem a hiperhomocisteinemia leve (>15µmol/L; OR = 1,25, 95% CI = 0,32-4,12) nem a moderada (>30µmol/L; OR = 1,0, 95% CI = 0,54-1,81) mostraram correlações significativas com aneurismas rotos. Modelos univariados (OR = 0,86; 95% CI = 0,71-1,0) e multivariados ajustados por idade (OR = 0,91; 95% CI = 0,75-1,05) não evidenciaram associação entre homocisteína e vasoespasmo. A homocisteinemia não influenciou resultados funcionais excelentes em seis meses (mRS ≤ 1) (OR = 1,04; 95% CI = 0,94-1,16). CONCLUSãO: Não houve diferenças em relação à homocisteinemia entre pacientes com aneurismas intracranianos rotos e não rotos. Em pacientes com aneurismas rotos, a homocisteinemia não foi associada ao vasoespasmo ou resultados funcionais.

Brain tissue oxygen combined with intracranial pressure monitoring versus isolated intracranial pressure monitoring in patients with traumatic brain injury: an updated systematic review and meta-analysis.

Monitoring intracranial pressure (ICP) is pivotal in the management of severe traumatic brain injury (TBI), but secondary brain injuries can arise despite normal ICP levels. Cerebral tissue oxygenation monitoring (PbtO2) may detect neuronal tissue infarction thresholds, enhancing neuroprotection. We performed a systematic review and meta-analysis to evaluate the effects of combined cerebral tissue oxygenation (PbtO2) and ICP compared to isolated ICP monitoring in patients with TBI. PubMed, Embase, Cochrane, and Web of Sciences databases were searched for trials published up to June 2023. A total of 16 studies comprising 37,820 patients were included. ICP monitoring was universal, with additional placement of PbtO2 in 2222 individuals (5.8%). The meta-analysis revealed a reduction in mortality (OR 0.57, 95% CI 0.37-0.89, p = 0.01), a greater likelihood of favorable outcomes (OR 2.28, 95% CI 1.66-3.14, p < 0.01), and a lower chance of poor outcomes (OR 0.51, 95% CI 0.34-0.79, p < 0.01) at 6 months for the PbtO2 plus ICP group. However, these patients experienced a longer length of hospital stay (MD 2.35, 95% CI 0.50-4.20, p = 0.01). No significant difference was found in hospital mortality rates (OR 0.81, 95% CI 0.61-1.08, p = 0.16) or intensive care unit length of stay (MD 2.46, 95% CI - 0.11-5.04, p = 0.06). The integration of PbtO2 to ICP monitoring improved mortality outcomes and functional recovery at 6 months in patients with TBI. PROSPERO (International Prospective Register of Systematic Reviews) CRD42022383937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=383937.

Repercussions of the Emergency neurological life support on scientific literature: a bibliometric study.

BACKGROUND: In 2012, the Neurocritical Care Society launched a compilation of protocols regarding the core issues that should be addressed within the first hours of neurological emergencies - the Emergency neurological life support (ENLS). OBJECTIVE: We aim to evaluate this repercussion through a bibliometric analysis. METHODS: We searched Scopus on October 2022 for articles mentioning ENLS. The following variables were obtained: number of citations; number of citations per year; number of publications per year; year of publication; research type; research subtype; country of corresponding author and its income category and world region; journal of publication and its 5-year impact factor (IF); and section where ENLS appeared. RESULTS: After applying eligibility criteria, we retrieved 421 articles, published from 2012 to 2022. The mean number of citations per article was 17.46 (95% Confidence Interval (CI) = 8.20-26.72), while the mean number of citations per year per article was 4.05 (95% CI = 2.50-5.61). The mean destiny journal 5-year IF was 5.141 (95% CI = 4.189-6.093). The majority of articles were secondary research (57.48%; n = 242/421) of which most were narrative reviews (71.90%; n = 174/242). High-Income countries were the most prominent (80.05%; n = 337/421 articles). There were no papers from low-income countries. There were no trials or systematic reviews from middle-income countries. CONCLUSION: Although still low, the number of publications mentioning ENLS is increasing. Articles were mainly published in journals of intensive care medicine, neurology, neurosurgery, and emergency medicine. Most articles were published by authors from high-income countries. The majority of papers were secondary research, with narrative review as the most frequent subtype.

ANTECEDENTES: Em 2012, a Neurocritical Care Society lançou uma compilação de protocolos sobre as questões centrais que devem ser abordadas nas primeiras horas de emergências neurológicas ­ Emergency neurological life support (ENLS). OBJETIVO: Avaliar a repercussão do ENLS por meio de uma análise bibliométrica. MéTODOS: A base de dados Scopus foi utilizada em outubro de 2022 para a busca por artigos mencionando o ENLS. As seguintes variáveis foram obtidas: número de citações; número de citações por ano; número de publicações por ano; ano de publicação; tipo de pesquisa; país do autor correspondente e sua categoria de renda; revista de publicação e seu fator de impacto de 5 anos (IF); e seção onde o ENLS apareceu. RESULTADOS: Os 421 artigos incluídos foram publicados de 2012 a 2022. A média de citações por artigo foi de 17.46 (intervalo de confiança (IC) 95% = 8.20­26.72), enquanto a de citações por ano por artigo foi de 4.05 (IC95% = 2.50­5.61). O IF médio por revista foi de 5.14 (IC95% = 4.19­6.09). A maioria dos artigos era de pesquisa secundária (57.48%; n = 242/421), dos quais a maioria eram revisões narrativas (71.90%; n = 174/242). Os países de alta renda foram os mais prolíficos (80.05%; n = 337/421 artigos). Não houve publicações de países de baixa ou média renda. CONCLUSãO: Embora ainda baixo, o número de publicações mencionando o ENLS vem aumentando recentemente. A maioria dos artigos foram publicados em revistas de medicina intensiva, neurologia, neurocirurgia e medicina de emergência. Artigos de pesquisa secundária foram os mais comuns, com revisões narrativas sendo o subtipo mais frequente.

Efficacy of transcranial direct current stimulation in patients with dysphagia after stroke: a systematic review.

BACKGROUND: Swallowing is a complex function that can be disrupted after stroke. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation therapy that recently has been tested to treat stroke-related dysphagia. METHODS: The authors performed a search in the literature to review the described evidence of the use of tDCS in dysphagia after stroke. Three electronic databases were searched. The risk of bias evaluation was carried out through the RoB-2 tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was also implemented. RESULTS: Of 265 articles, only nine studies were included in this review. The most common location of the tDCS stimulation was the unaffected hemisphere (44%). Regarding the outcome measure, the Dysphagia Outcome and Severity Scale (DOSS) was the most commonly used (55%). However, due to the high heterogeneity of the protocols, and considering the differences between the types of stroke, the authors opted not to perform a metanalysis. Instead, a systematic review with a thorough analysis of each individual study and the impact of the differences to the outcomes was preferred. CONCLUSIONS: The final considerations are that even though the majority of studies described benefits from tDCS in post-stroke dysphagia, as they present too many methodological differences, it is not possible to compare them. In addition, many articles included patients with less than 6 months after stroke, which is an important bias as the swallowing function can be recovered spontaneously within this period, turning the certainty of the evidence really low.

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study / Homocisteína sérica em pacientes com aneurismas rotos e não rotos: um estudo caso-controle

Abstract Background There is very few data regarding homocysteine's influence on the formation and rupture of intracranial aneurysms. Objective To compare homocysteine levels between patients with ruptured and unruptured intracranial aneurysms, and to evaluate possible influences of this molecule on vasospasm and functional outcomes. Methods This is a retrospective, case-control study. We evaluated homocysteinemia differences between patients with ruptured and unruptured aneurysms; and the association of homocysteine levels with vasospasm and functional outcomes. Logistic regressions were performed. Results A total of 348 participants were included: 114 (32.8%) with previous aneurysm rupture and 234 (67.2%) with unruptured aneurysms. Median homocysteine was 10.75μmol/L (IQR = 4.59) in patients with ruptured aneurysms and 11.5μmol/L (IQR = 5.84) in patients with unruptured aneurysms. No significant association was detected between homocysteine levels and rupture status (OR = 0.99, 95% CI = 0.96-1.04). Neither mild (>15μmol/L; OR = 1.25, 95% CI 0.32-4.12) nor moderate (>30μmol/L; OR = 1.0, 95% CI = 0.54-1.81) hyperhomocysteinemia demonstrated significant correlations with ruptured aneurysms. Neither univariate (OR = 0.86; 95% CI 0.71-1.0) nor multivariable age-adjusted (OR = 0.91; 95% CI = 0.75-1.05) models evidenced an association between homocysteine levels and vasospasm. Homocysteinemia did not influence excellent functional outcomes at 6 months (mRS≤1) (OR = 1.04; 95% CI = 0.94-1.16). Conclusion There were no differences regarding homocysteinemia between patients with ruptured and unruptured intracranial aneurysms. In patients with ruptured aneurysms, homocysteinemia was not associated with vasospasm or functional outcomes.

RESUMO Antecedentes Existem poucos dados sobre a influência da homocisteína na formação e rotura de aneurismas intracranianos (AI). Objetivo Comparar os níveis de homocisteína entre pacientes com AI rotos e não rotos e influências no vasoespasmo e resultados funcionais. Métodos Estudo caso-controle, que avaliou as diferenças de homocisteinemia entre pacientes com aneurismas rotos e não rotos, além da associação entre níveis de homocisteína, vasoespasmo e estado funcional. Regressões logísticas foram realizadas. Resultados Um total de 348 participantes foram incluídos: 114 (32,8%) com aneurismas rotos e 234 (67,2%) não rotos. A homocisteína mediana foi de 10,75μmol/L (IQR = 4,59) nos rotos e 11,5μmol/L (IQR = 5,84) nos não rotos. Não houve associação significativa entre os níveis de homocisteína e o status de ruptura (OR = 0,99, 95% CI = 0,96-1,04). Nem a hiperhomocisteinemia leve (>15μmol/L; OR = 1,25, 95% CI = 0,32-4,12) nem a moderada (>30μmol/L; OR = 1,0, 95% CI = 0,54-1,81) mostraram correlações significativas com aneurismas rotos. Modelos univariados (OR = 0,86; 95% CI = 0,71-1,0) e multivariados ajustados por idade (OR = 0,91; 95% CI = 0,75-1,05) não evidenciaram associação entre homocisteína e vasoespasmo. A homocisteinemia não influenciou resultados funcionais excelentes em seis meses (mRS ≤ 1) (OR = 1,04; 95% CI = 0,94-1,16). Conclusão Não houve diferenças em relação à homocisteinemia entre pacientes com aneurismas intracranianos rotos e não rotos. Em pacientes com aneurismas rotos, a homocisteinemia não foi associada ao vasoespasmo ou resultados funcionais.

Repercussions of the Emergency neurological life support on scientific literature: a bibliometric study / Repercussões do Emergency neurological life support na literatura científica: um estudo bibliométrico

Abstract Background In 2012, the Neurocritical Care Society launched a compilation of protocols regarding the core issues that should be addressed within the first hours of neurological emergencies - the Emergency neurological life support (ENLS). Objective We aim to evaluate this repercussion through a bibliometric analysis. Methods We searched Scopus on October 2022 for articles mentioning ENLS. The following variables were obtained: number of citations; number of citations per year; number of publications per year; year of publication; research type; research subtype; country of corresponding author and its income category and world region; journal of publication and its 5-year impact factor (IF); and section where ENLS appeared. Results After applying eligibility criteria, we retrieved 421 articles, published from 2012 to 2022. The mean number of citations per article was 17.46 (95% Confidence Interval (CI) = 8.20-26.72), while the mean number of citations per year per article was 4.05 (95% CI = 2.50-5.61). The mean destiny journal 5-year IF was 5.141 (95% CI = 4.189-6.093). The majority of articles were secondary research (57.48%; n= 242/421) of which most were narrative reviews (71.90%; n= 174/242). High-Income countries were the most prominent (80.05%; n= 337/421 articles). There were no papers from low-income countries. There were no trials or systematic reviews from middle-income countries. Conclusion Although still low, the number of publications mentioning ENLS is increasing. Articles were mainly published in journals of intensive care medicine, neurology, neurosurgery, and emergency medicine. Most articles were published by authors from high-income countries. The majority of papers were secondary research, with narrative review as the most frequent subtype.

Resumo Antecedentes Em 2012, a Neurocritical Care Society lançou uma compilação de protocolos sobre as questões centrais que devem ser abordadas nas primeiras horas de emergências neurológicas - Emergency neurological life support (ENLS). Objetivo Avaliar a repercussão do ENLS por meio de uma análise bibliométrica. Métodos A base de dados Scopus foi utilizada em outubro de 2022 para a busca por artigos mencionando o ENLS. As seguintes variáveis foram obtidas: número de citações; número de citações por ano; número de publicações por ano; ano de publicação; tipo de pesquisa; país do autor correspondente e sua categoria de renda; revista de publicação e seu fator de impacto de 5 anos (IF); e seção onde o ENLS apareceu. Resultados Os 421 artigos incluídos foram publicados de 2012 a 2022. A média de citações por artigo foi de 17.46 (intervalo de confiança (IC) 95% = 8.20-26.72), enquanto a de citações por ano por artigo foi de 4.05 (IC95% = 2.50-5.61). O IF médio por revista foi de 5.14 (IC95% = 4.19-6.09). A maioria dos artigos era de pesquisa secundária (57.48%; n= 242/421), dos quais a maioria eram revisões narrativas (71.90%; n= 174/242). Os países de alta renda foram os mais prolíficos (80.05%; n= 337/421 artigos). Não houve publicações de países de baixa ou média renda. Conclusão Embora ainda baixo, o número de publicações mencionando o ENLS vem aumentando recentemente. A maioria dos artigos foram publicados em revistas de medicina intensiva, neurologia, neurocirurgia e medicina de emergência. Artigos de pesquisa secundária foram os mais comuns, com revisões narrativas sendo o subtipo mais frequente.

Role of temporary arterial occlusion in subarachnoid hemorrhage outcomes: a prospective cohort study.

PURPOSE: Temporary arterial occlusion (TAO) is a widespread practice in the surgical treatment of intracranial aneurysms. This study aimed to investigate TAO's role during ruptured aneurysm clipping as an independent prognostic factor on short- and long-term outcomes. METHODS: This prospective cohort included 180 patients with ruptured intracranial aneurysms and an indication of microsurgical treatment. Patients who died in the first 12 hours after admission were excluded. RESULTS: TAO was associated with intraoperative rupture (IOR) (odds ratio - OR = 10.54; 95% confidence interval - 95%CI 4.72-23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11-4.07; p = 0.01). The group with TAO and IOR had no significant difference in clinical (p = 0.06) and surgical (p = 0.94) complications compared to the group that had TAO, but no IOR. Among the 111 patients followed six months after treatment, IOR, number of occlusions, and total time of occlusion were not associated with Glasgow Outcome Scale (GOS) in the follow-up (respectively, p = 0.18, p = 0.30, and p = 0.73). Among patients who underwent TAO, IOR was also not associated with GOS in the follow-up (p = 0.29). CONCLUSIONS: TAO was associated with IOR and surgical complications, being the latter independent of IOR occurrence. In long-term analysis, neither TAO nor IOR were associated with poor clinical outcomes.

Pharmacokinetics and Therapeutic Target Attainment of Meropenem in Pediatric Post-Liver Transplant Patients: Extended vs Intermittent Infusion.

PURPOSE: The aim of this study is to characterize the concentration-time profile, pharmacokinetics parameters, and therapeutic target attainment of meropenem in pediatric post-liver transplant patients according to the duration of infusion. METHODS: This is a prospective cohort of pediatric transplant recipients with preserved renal function receiving meropenem 40 mg/kg every 8 hours. The patients were stratified into 2 groups based on infusion duration: G1 (15 minutes of intermittent infusion) and G1 (3 hours of extended infusion). Two blood samples per child were collected during the same interval within 48 hours of starting the antimicrobial. Meropenem concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were assessed using a noncompartmental analysis. The therapeutic target was defined as 100% of the time above the minimum inhibitory concentration. FINDINGS: Fourteen patients with 28 measured meropenem concentrations were included. Lower values of volume of distribution and meropenem clearance compared with other critically ill pediatric populations were found. All patients achieved the therapeutic target against gram-negative pathogens with a minimum inhibitory concentration of ≤8 mg/L. Patients receiving a 15-minute infusion had higher values of peak and trough concentrations, resulting in unnecessary increased total drug exposure when compared to patients receiving a 3-hour infusion (P < .05). CONCLUSIONS: Meropenem at 120 mg/kg/d attained the therapeutic target against sensitive microorganisms in pediatric liver transplant recipients. The extended infusion should be preferred for patient safety. Because of the pharmacokinetic changes resulting from liver transplantation, individualized meropenem dosing regimens may be necessary.

Development and adaptations of the Graded Prognostic Assessment (GPA) scale: a systematic review.

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales.

Modified Atkins diet for drug-resistant epilepsy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.