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.

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.

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.

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.

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.

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.

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.

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.

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.

Machine Learning Algorithms to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.

Delayed cerebral ischemia (DCI) is a common and severe complication after subarachnoid hemorrhage (SAH). Logistic regression (LR) is the primary method to predict DCI, but it has low accuracy. This study assessed whether other machine learning (ML) models can predict DCI after SAH more accurately than conventional LR. PubMed, Embase, and Web of Science were systematically searched for studies directly comparing LR and other ML algorithms to forecast DCI in patients with SAH. Our main outcome was the accuracy measurement, represented by sensitivity, specificity, and area under the receiver operating characteristic. In the six studies included, comprising 1828 patients, about 28% (519) developed DCI. For LR models, the pooled sensitivity was 0.71 (95% confidence interval [CI] 0.57-0.84; p < 0.01) and the pooled specificity was 0.63 (95% CI 0.42-0.85; p < 0.01). For ML models, the pooled sensitivity was 0.74 (95% CI 0.61-0.86; p < 0.01) and the pooled specificity was 0.78 (95% CI 0.71-0.86; p = 0.02). Our results suggest that ML algorithms performed better than conventional LR at predicting DCI.Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42023441586; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441586.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study.

BACKGROUND: Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors. OBJECTIVE: We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months. METHODS: This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission. RESULTS: A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm. CONCLUSION: Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field.

ANTECEDENTES: O prognóstico da hemorragia subaracnoidea (HSA) permanece ruim. Vasoespasmo pode estar associado à inflamação. Razões neutrófilo-linfócito (NLR) e plaqueta-linfócito (PLR) têm sido estudadas como marcadores de inflamação e prognóstico. OBJETIVO: Investigar NLR e PLR na admissão como preditores de vasoespasmo angiográfico e desfecho aos 6 meses. MéTODOS: Este estudo de coorte incluiu pacientes consecutivos com HSA aneurismática de um centro terciário. Contagem de leucócitos, neutrófilos, linfócitos e plaquetas, proporção de neutrófilos para linfócitos e de plaquetas para linfócitos foram coletados como variáveis independentes. Ocorrência de vasoespasmo, escala de Rankin modificada, escala de desfecho de Glasgow e o escore de Hunt-Hess na admissão e 6 meses após a mesma foram registradas como variáveis dependentes. Modelos de regressão logística multivariável foram usados para ajustar potenciais fatores de confusão e avaliar valor prognóstico independente de NLR e PLR. RESULTADOS: Um total de 74,1% pacientes eram do sexo feminino, com idade média de 55,6 ± 12,4 anos. Na admissão, a pontuação média de Hunt-Hess foi de 2 (IQR 1) e a mediana de mFisher foi de 3 (IQR 1). Clipagem microcirúrgica foi o tratamento escolhido para 66,2% dos pacientes. A incidência de vasoespasmo angiográfico foi de 16,5%. Aos 6 meses, a escala de desfecho de Glasgow mediana era 4 (IQR 0,75) e a escala de Rankin modificada mediana era 3 (IQR 1,5). Vinte e um pacientes (15,1%) morreram. Os níveis de NLR e PLR não diferiram entre resultados funcionais favoráveis e desfavoráveis (mRS > 2 ou GOS < 4). Nenhuma variável foi significativamente associada ao vasoespasmo angiográfico. CONCLUSãO: Razão neutrófilo-linfócito e a PLR não apresentaram valor preditivo de desfecho funcional ou risco de vasoespasmo angiográfico. Mais pesquisas são necessárias neste campo.

Modifiable risk factors for glioblastoma: a systematic review and meta-analysis.

Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study / Razão neutrófilos-linfócitos e razão plaquetas-linfócitos e o prognóstico de hemorragia subaracnóidea aneurismática: um estudo de coorte

Abstract Background Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors. Objective We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months. Methods This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission. Results A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm. Conclusion Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field.

Resumo Antecedentes O prognóstico da hemorragia subaracnoidea (HSA) permanece ruim. Vasoespasmo pode estar associado à inflamação. Razões neutrófilo-linfócito (NLR) e plaqueta-linfócito (PLR) têm sido estudadas como marcadores de inflamação e prognóstico. Objetivo Investigar NLR e PLR na admissão como preditores de vasoespasmo angiográfico e desfecho aos 6 meses. Métodos Este estudo de coorte incluiu pacientes consecutivos com HSA aneurismática de um centro terciário. Contagem de leucócitos, neutrófilos, linfócitos e plaquetas, proporção de neutrófilos para linfócitos e de plaquetas para linfócitos foram coletados como variáveis independentes. Ocorrência de vasoespasmo, escala de Rankin modificada, escala de desfecho de Glasgow e o escore de Hunt-Hess na admissão e 6 meses após a mesma foram registradas como variáveis dependentes. Modelos de regressão logística multivariável foram usados para ajustar potenciais fatores de confusão e avaliar valor prognóstico independente de NLR e PLR. Resultados Um total de 74,1% pacientes eram do sexo feminino, com idade média de 55,6 ± 12,4 anos. Na admissão, a pontuação média de Hunt-Hess foi de 2 (IQR 1) e a mediana de mFisher foi de 3 (IQR 1). Clipagem microcirúrgica foi o tratamento escolhido para 66,2% dos pacientes. A incidência de vasoespasmo angiográfico foi de 16,5%. Aos 6 meses, a escala de desfecho de Glasgow mediana era 4 (IQR 0,75) e a escala de Rankin modificada mediana era 3 (IQR 1,5). Vinte e um pacientes (15,1%) morreram. Os níveis de NLR e PLR não diferiram entre resultados funcionais favoráveis e desfavoráveis (mRS > 2 ou GOS < 4). Nenhuma variável foi significativamente associada ao vasoespasmo angiográfico. Conclusão Razão neutrófilo-linfócito e a PLR não apresentaram valor preditivo de desfecho funcional ou risco de vasoespasmo angiográfico. Mais pesquisas são necessárias neste campo.

Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis.

BACKGROUND: Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. OBJECTIVE: To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. METHODS: The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). RESULTS: We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02--10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42--14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89--11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. CONCLUSION: Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.

ANTECEDENTES: Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. OBJETIVO: Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. MéTODOS: Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). RESULTADOS: Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = -25.40; intervalo de confiança de 95% [IC95%] = -40.02­-10.78), seguido de suvorexant 20/15mg (SMD = -25.29; IC95% = -36.42­-14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = -23.70; IC95% = -35.89­-11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. CONCLUSãO: Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insônia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insônia crônica.

Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis / Antagonistas duais do receptor de orexina para o tratamento da insônia: revisão sistemática e metanálise em rede

Abstract Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higherdoses relating to a longerTST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = −25.40; 95% confidence interval [95%CI] = −40.02- −10.78), followed by suvorexant 20/15mg (SMD = −25.29; 95%CI = −36.42- −14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = −23.70; 95%CI = −35.89- −11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.

Resumo Antecedentes Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. Objetivo Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. Métodos Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). Resultados Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = −25.40; intervalo de confiança de 95% [IC95%] = −40.02- −10.78), seguido de suvorexant 20/15mg (SMD = −25.29; IC95% = −36.42- −14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = −23.70; IC95% = −35.89- −11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. Conclusão Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insónia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insónia crônica.

Torque Teno virus DNA is found in the intracranial aneurysm wall-Is there a causative role?

Objective: Torque Teno virus (TTV) is a recently discovered virus with high prevalence worldwide, that has been associated with vascular diseases. The aim of this study is to investigate the prevalence of TTV molecular DNA in the intracranial aneurysm (IA) artery walls. Method: Samples of IA walls were collected after microsurgical clipping from 35 patients with IA (22 ruptured/13 unruptured cases). The samples were submitted to molecular DNA extraction using the EasyMag automatized extractor and performed with Qiagen DNA extraction Minikit 250. The samples underwent PCR examination with primers for ß-globin as internal control using the Nanodrop ® 2000 spectrophotometer. A quantitative (real-time) PCR with TTV-specific primers was performed. Clinical and radiological data of patients included was collected. Results: TTV was detected in 15 (42.85%) cases, being 10 (45.4%) ruptured and 5 (38.4%) unruptured (p = 0.732) lesions. Multiple IAs accounted for 14 (40%) cases. Five cases (17.2%) had TTV+ and multiple aneurysms (p = 0.73). Association between presence of virus and aneurysm rupture was not statistically significant (p = 0.96). Conclusion: This study demonstrated a relatively high prevalence of viral DNA in the walls of IAs. This is the first study to identify the presence of TTV DNA in IA's samples, which was found more often in ruptured lesions. This is an exploratory study, therefore, larger studies are required to clarify the relationships between inflammation, viral infection, IA formation and rupture.

Neurocysticercosis: challenges in pediatric neurosurgery practice.

PURPOSE: Neurocysticercosis (NCC) is considered a neglected infectious disease, but the most common parasitic disease of the central nervous system (CNS). Due to oral tendencies in childhood, it is hypothesized that individuals are infected around this age and develop symptoms as lately as during young adulthood. Although it is considered a benign disease, it may cause great impact in the patient's quality of life due to epilepsy, visual symptoms, and hydrocephalus, which eventually requires frequent hospitalizations. The treatment of hydrocephalus is the main challenge for neurosurgeons. METHODS: We performed a concise review on neurocysticercosis in children and the main presentations of NCC in the neurosurgery practice and a systematic review on hydrocephalus secondary to extraparenchymal NCC. RESULTS: Our review showed a rate of complete resolution of hydrocephalus secondary to NCC of around 80% with the first attempt of surgical treatment combined with medication therapy. Endoscopic removal of the intraventricular cysts with third ventriculostomy was the most common treatment modality. Patients previously managed with ventricular shunts are likely to have worse outcomes and complications. CONCLUSION: Endoscopic approach is the gold standard surgical treatment for hydrocephalus secondary to neurocysticercosis.

Predictors of Survival After Stereotactic Radiosurgery for Untreated Single Non-Small Cell Lung Cancer Brain Metastases: 5- and 10-year Results.

BACKGROUND: Stereotactic radiosurgery (SRS) presents as a good treatment option for smaller, deep-seated brain metastases (BMs). This study aims to determine predictors of SRS failure for patients with non-small cell lung cancer BMs. METHODS: This was a retrospective study of single non-small cell lung cancer BMs treated using SRS. We included patients >18 years with a single, previously untreated lesion. Primary outcome was treatment failure, defined as BMs dimension increase above the initial values. Demographic, clinical, and radiological data were collected to study potential predictors of treatment failure. RESULTS: Worse rates of progression-free survival (PFS) were associated with heterogeneous contrast enhancement (18.1 ± 4.1 vs. 41.9 ± 4 months; P < 0.001). Better rates of PFS were associated with volumes <1.06 cm3 (log-rank; P = 0.001). Graded prognostic assessment was significantly associated with survival at 120 months (log-rank; P < 0.001). Karnofsky Performance Scale was evaluated in 3 strata: 90-100, 80, and ≤70. Mean survival rates for these strata were 31.8 ± 3.9, 10.6 ± 2.2, and 9.8 ± 2.3 months, respectively (log-rank; P < 0.001). There were no differences regarding presence of extracranial metastases, age, or lesion location. A multivariable logistic regression found that volume <1.06 cm3 was associated with higher survival rates at 10 years (odds ratio: 3.2, 95% confidence interval: 1.3-8.0). CONCLUSIONS: Contrast-homogeneous metastases and lesions <1.06 cm3 are associated with better rates of PFS. Karnofsky Performance Scale and graded prognostic assessment were associated with more favorable survival rates after 10 years. Volume <1.06 cm3 was the only significant predictor of survival in the multivariable analysis.

Long-Term Safety and Effectiveness of Erenumab in Patients with Migraine: A Systematic Review and Single-Arm Meta-analysis.

BACKGROUND AND OBJECTIVE: Several studies on use of erenumab for migraine treatment have been published over recent years. However, its long-term safety and effectiveness have not been consistently established in the literature yet. We aimed to perform a qualitative and quantitative analysis of the long-term safety and effectiveness of erenumab for the treatment of migraine headaches. METHODS: Long-term follow-up was defined as ≥ 1 year. PubMed, Embase and Cochrane Library were systematically searched from inception to 14 June 2022 for studies meeting the inclusion criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Fourteen studies, comprising 3574 patients, were included. The total follow-up period ranged from 48 to 268 weeks (i.e., 1 year to 5.6 years). Pooled estimate rates for all adverse events (AEs) were 63% (95% CI 46-78); for serious AEs, 3% (95% CI 1-7); and for AEs leading to discontinuation of erenumab, 3% (95% CI 2-5). Reduction in monthly migraine days (MMDs) was -6.98 (95% CI -8.90 to -5.05) and in migraine-specific medication days (MSMDs) was - 6.09 (95% CI - 9.43 to - 2.75). More than half (57%; 95% CI 51-63) and around one-third (35%; 95% CI 28-42) of patients presented with reductions of ≥ 50% and ≥ 75% in MMDs, respectively. Headache Impact Test-6 (HIT-6) score was decreased by -9.68 points (95% CI - 12.03 to - 7.34). Nine studies were considered of poor methodological quality and five of fair quality. CONCLUSIONS: Erenumab has a favorable safety profile, with a low incidence of serious AEs, and sustained efficacy over ≥1 year of follow-up in the treatment of migraine.