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. . (ENLS) bibliométrica 202 obtidas (IF) apareceu 42 201 1746 17 46 17.4 intervalo IC (IC 95 8.20–26.72, 8202672 8.20–26.72 , 8 20 26 72 8.20–26.72) 405 4 05 4.0 IC95% IC95 (IC95 2.50–5.61. 250561 2.50–5.61 2 50 61 2.50–5.61) 514 14 5.1 4.19–6.09. 419609 4.19–6.09 19 6 09 4.19–6.09) 57.48% 5748 57 48 (57.48% n 242/421, 242421 242/421 242 242/421) 71.90% 7190 71 90 (71.90% 174/242. 174242 174/242 174 174/242) 80.05% 8005 80 (80.05% 337421 337 337/42 artigos. artigos) baixo recentemente intensiva neurologia emergência comuns frequente (ENLS (IF 1 17. 9 820267 8.20–26.7 7 40 0 4. IC9 (IC9 25056 2.50–5.6 51 5. 41960 4.19–6.0 57.48 574 (57.48 24242 242/42 24 71.90 719 (71.90 17424 174/24 80.05 800 (80.05 33742 33 337/4 82026 8.20–26. 2505 2.50–5. 4196 4.19–6. 57.4 (57.4 2424 242/4 71.9 (71.9 1742 174/2 80.0 (80.0 3374 3 337/ 8202 8.20–26 250 2.50–5 419 4.19–6 57. (57. 242/ 71. (71. 174/ 80. (80. 820 8.20–2 25 2.50– 41 4.19– (57 (71 (80 82 8.20– 2.50 4.19 (5 (7 (8 8.20 2.5 4.1 ( 8.2 2. 8.

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. . (ENLS) analysis 202 obtained type subtype region 5year 5 (IF) appeared criteria 42 201 1746 17 46 17.4 95% 95 (95 (CI 8.20–26.72, 8202672 8.20–26.72 , 8 20 26 72 8.20–26.72) 405 4 05 4.0 2.50–5.61. 250561 2.50–5.61 2 50 61 2.50–5.61) 5141 141 5.14 4.189–6.093. 41896093 4.189–6.093 189 6 093 4.189–6.093) 57.48% 5748 57 48 (57.48% n 242/421 242421 242 71.90% 7190 71 90 (71.90% 174/242. 174242 174/242 174 174/242) HighIncome High Income 80.05% 8005 80 (80.05% 337421 337 337/42 articles. articles) lowincome low middleincome middle increasing medicine neurology neurosurgery highincome high (ENLS (IF 1 17. 9 (9 820267 8.20–26.7 7 40 0 4. 25056 2.50–5.6 514 14 5.1 4189609 4.189–6.09 18 09 57.48 574 (57.48 242/42 24242 24 71.90 719 (71.90 17424 174/24 80.05 800 (80.05 33742 33 337/4 ( 82026 8.20–26. 2505 2.50–5. 51 5. 418960 4.189–6.0 57.4 (57.4 242/4 2424 71.9 (71.9 1742 174/2 80.0 (80.0 3374 3 337/ 8202 8.20–26 250 2.50–5 41896 4.189–6. 57. (57. 242/ 71. (71. 174/ 80. (80. 820 8.20–2 25 2.50– 4189 4.189–6 (57 (71 (80 82 8.20– 2.50 418 4.189– (5 (7 (8 8.20 2.5 41 4.189 8.2 2. 4.18 8. 4.1

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. AI. . (AI) casocontrole, casocontrole caso controle, controle caso-controle funcional realizadas 34 incluídos 11 32,8% 328 32 8 (32,8% 23 67,2% 672 67 2 (67,2% 1075μmolL μmolL 10 75μmol L μmol IQR 4,59 459 4 59 115μmolL 5μmol 5,84 584 5 84 099 0 99 0,99 95 0,961,04. 096104 0,96 1,04 96 1 04 0,96-1,04) >15μmol/L 15μmolL 15μmol (>15μmol/L 125 25 1,25 0,324,12 032412 0,32 4,12 12 0,32-4,12 >30μmol/L 30μmolL 30μmol (>30μmol/L 1,0 0,541,81 054181 0,54 1,81 54 81 0,54-1,81 0,86 086 86 0,711,0 07110 0,71 71 0,71-1,0 0,91 091 91 0,751,05 075105 0,75 1,05 75 05 0,75-1,05 mRS 104 0,941,16. 094116 0,94 1,16 94 16 0,94-1,16) (AI 3 32,8 (32,8 67,2 6 (67,2 4,5 45 5,8 58 09 9 0,9 961 0,961,04 09610 096 0,96-1,04 1,2 324 0,324,1 03241 032 0,3 412 4,1 0,32-4,1 1, 541 0,541,8 05418 054 0,5 181 1,8 0,54-1,8 0,8 08 711 0,711, 0711 071 0,7 7 0,71-1, 751 0,751,0 07510 075 105 0,75-1,0 941 0,941,16 09411 094 116 1,1 0,94-1,16 32, (32, 67, (67, 4, 5, 0, 0,961,0 0961 0,96-1,0 0,324, 0324 03 41 0,32-4, 0,541, 0541 18 0,54-1, 0,711 07 0,71-1 0,751, 0751 0,75-1, 0,941,1 0941 0,94-1,1 (32 (67 0,961, 0,96-1, 0,324 0,32-4 0,541 0,54-1 0,71- 0,751 0,75-1 0,941, 0,94-1, (3 (6 0,961 0,96-1 0,32- 0,54- 0,75- 0,941 0,94-1 ( 0,96- 0,94-

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. homocysteines s retrospective casecontrol case control study performed 34 included 11 32.8% 328 32 8 (32.8% 23 67.2% 672 67 2 (67.2% 1075μmolL μmolL 10 75μmol L μmol IQR 4.59 459 4 59 115μmolL 5μmol 5.84 584 5 84 099 0 99 0.99 95 0.961.04. 096104 0.96 1.04 . 96 1 04 0.96-1.04) >15μmol/L 15μmolL 15μmol (>15μmol/L 125 25 1.25 0.324.12 032412 0.32 4.12 12 0.32-4.12 >30μmol/L 30μmolL 30μmol (>30μmol/L 1.0 0.541.81 054181 0.54 1.81 54 81 0.54-1.81 0.86 086 86 0.711.0 07110 0.71 71 0.71-1.0 ageadjusted age adjusted 0.91 091 91 0.751.05 075105 0.75 1.05 75 05 0.75-1.05 mRS≤1 mRS1 mRS (mRS≤1 104 0.941.16. 094116 0.94 1.16 94 16 0.94-1.16) 3 32.8 (32.8 67.2 (67.2 4.5 45 5.8 58 09 9 0.9 961 0.961.04 09610 096 0.96-1.04 1.2 324 0.324.1 03241 032 0.3 412 4.1 0.32-4.1 1. 541 0.541.8 05418 054 0.5 181 1.8 0.54-1.8 0.8 08 711 0.711. 0711 071 0.7 7 0.71-1. 751 0.751.0 07510 075 105 0.75-1.0 mRS≤ (mRS≤ 941 0.941.16 09411 094 116 1.1 0.94-1.16 32. (32. 67. (67. 4. 5. 0. 0.961.0 0961 0.96-1.0 0.324. 0324 03 41 0.32-4. 0.541. 0541 18 0.54-1. 0.711 07 0.71-1 0.751. 0751 0.75-1. (mRS 0.941.1 0941 0.94-1.1 (32 (67 0.961. 0.96-1. 0.324 0.32-4 0.541 0.54-1 0.71- 0.751 0.75-1 0.941. 0.94-1. (3 (6 0.961 0.96-1 0.32- 0.54- 0.75- 0.941 0.94-1 ( 0.96- 0.94-

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. (HSA ruim neutrófilolinfócito neutrófilo linfócito (NLR plaquetalinfócito plaqueta (PLR terciário leucócitos independentes HuntHess Hunt Hess dependentes 741 74 1 74,1 feminino 556 55 55, 124 12 12, anos IQR 1. . 662 66 66,2 165 16 5 16,5% 0,75 075 0 75 1,5. 15 1,5 1,5) 15,1% 151 (15,1% morreram mRS 4. 4) campo 7 74, 66, 16,5 0,7 07 1, 15,1 (15,1 16, 0, 15, (15, (15 (1 (

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. (SAH poor Neutrophiltolymphocyte Neutrophil (NLR platelettolymphocyte (PLR center occurrencemodified occurrence modified mRS, , (mRS) GOS, (GOS) HuntHess Hunt Hess 741 74 1 74.1 female 556 55 55. 124 12 12. years interquartile IQR [IQR 1, 1) 1. . 662 66 66.2 165 16 5 16.5% 0.75, 075 0.75 0 75 0.75) 1.5. 15 1.5 1.5) Twentyone Twenty one 15.1% 151 (15.1% died outcomes risk field (GOS 7 74. 66. 16.5 07 0.7 15.1 (15.1 16. 0. 15. (15. (15 (1 (

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. (ECRs dual antagonists inglês insônia Contudo outros metaanálise meta análise Medline 1 selecionados wake onset inglês, , latency LPS TST EAs. . (EAs) 7806 7 806 7,80 4849 4 849 4,84 intervenção analisados identificado mês diferença standardized difference SMD, SMD [SMD] −25.40 2540 25 40 95 IC95 IC [IC95% 4002 02 −40.02 −10.78, 1078 −10.78 78 −10.78) 2015mg 20 15mg −25.29 2529 29 3642 36 42 −36.42 −14.15, 1415 −14.15 14 15 −14.15) −23.70 2370 23 70 3589 35 89 −35.89 −11.51. 1151 −11.51 11 51 −11.51) sonolência cefaleia 148 8 14.8% 2 horas disso crônica (EAs 780 80 7,8 484 84 4,8 [SMD −25.4 254 9 IC9 [IC95 400 0 −40.0 107 −10.7 −25.2 252 364 3 −36.4 141 −14.1 −23.7 237 358 −35.8 115 −11.5 5 14.8 7, 48 4, −25. [IC9 −40. −10. −36. −14. −23. −35. −11. 14. −25 [IC −40 −10 −36 −14 −23 −35 −11 −2 −4 −1 −3 −

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. (RCTs (DORAs However unclear metaanalysis meta analysis Medline Embase 1 disorder WASO, , (WASO) LPS, LPS (LPS) TST (TST) AEs. . (AEs) 7806 7 806 7,80 4849 4 849 4,84 intervention Overall dosedependent dose dependent noticed longerTST mg at standardized SMD [SMD −25.40 2540 25 40 95 95CI CI [95%CI 4002 02 −40.02 −10.78, 1078 −10.78 78 −10.78) 2015mg 20 15mg −25.29 2529 29 3642 36 42 −36.42 −14.15, 1415 −14.15 14 15 −14.15) longterm long term −23.70 2370 23 70 3589 35 89 −35.89 −11.51. 1151 −11.51 11 51 −11.51) somnolence nasopharyngitis headache 148 8 14.8% 24hour hour 24 Additionally (WASO (LPS (TST (AEs 780 80 7,8 484 84 4,8 −25.4 254 2 9 400 0 −40.0 107 −10.7 −25.2 252 364 3 −36.4 141 −14.1 −23.7 237 358 −35.8 115 −11.5 5 14.8 7, 48 4, −25. −40. −10. −36. −14. −23. −35. −11. 14. −25 −40 −10 −36 −14 −23 −35 −11 −2 −4 −1 −3 −

Resumo Antecedentes Coinfecções neurológicas em pessoas que vivem com HIV/AIDS (PVHA) é um tema que não foi suficientemente avaliado em estudos clínicos prospectivos. Nosso objetivo foi identificar as características clínicas e os desfechos de PVHA com toxoplasmose cerebral e coinfecções neurológicas. Métodos Estudo prospectivo de coorte observacional conduzido em um centro de ensino terciário de São Paulo, Brasil, entre janeiro e julho de 2017. Foram incluídos consecutivamente PVHA internadas com ≥ 18 anos e toxoplasmose cerebral. Realizou-se exame neurológico padronizado na admissão e semanalmente até a alta/óbito. Tanto o diagnóstico quanto o tratamento seguiram a rotina institucional; neurorradiologia, diagnóstico molecular, neurocirurgia e Unidade de Terapia Intensiva (UTI) estavam disponíveis. Os principais desfechos foram coinfecções neurológicas e óbitos hospitalares. Resultados Incluímos 44 (4,3%) casos entre 1.032 pacientes internados. A idade mediana foi de 44 (intervalo interquartil [IIQ]: : 35-50) anos, e 50% (n = 22) dos pacientes eram do sexo masculino. A contagem mediana de linfócitos T CD4+ foi de 50 (IIQ:15-94) células/mm3. Múltiplas lesões na tomografia computadorizada foram observadas em 59% dos casos. Coinfecções neurológicas foram diagnosticadas em 20% (n = 9) dos casos, sendo o citomegalovírus a etiologia mais comum (encefalite: n = 3; polirradiculopatia: n = 2). Observou-se maior tempo de internação (26 versus 62 dias; p= 0,021) e uma taxa mais alta de admissão à UTI (14% versus 44%; p= 0,045) em PVHA com coinfecções neurológicas em comparação àquelas sem coinfecção. A mortalidade intra-hospitalar foi de 13,6% (n = 6) (grupo com coinfecções: 33% versus grupo sem coinfecção: 8,6%; p= 0,054). Conclusão Coinfecções neurológicas foram comuns em PVHA com toxoplasmose cerebral, sendo o citomegalovírus o principal copatógeno. O grupo de PVHA com coinfecções neurológicas apresentou maior tempo de internação, maior taxa de internações na UTI, e tendência a maior taxa de mortalidade intra-hospitalar. HIVAIDS HIV AIDS (PVHA prospectivos Paulo Brasil 2017 1 Realizouse Realizou se altaóbito óbito alta/óbito institucional neurorradiologia molecular (UTI disponíveis hospitalares 4 4,3% 43 3 (4,3% 1032 032 1.03 internados intervalo IIQ [IIQ] 3550 35 35-50 22 masculino CD4 CD 5 IIQ1594 15 94 (IIQ:15-94 célulasmm3 célulasmm células mm3 mm células/mm3 59 20 9 encefalite (encefalite polirradiculopatia 2. 2 . 2) Observouse Observou 26 (2 6 dias p 0,021 0021 0 021 14% 14 (14 44% 0,045 0045 045 coinfecção intrahospitalar intra hospitalar 136 13 13,6 33 8,6% 86 8 0,054. 0054 0,054 054 0,054) copatógeno intrahospitalar. hospitalar. 201 4,3 (4,3 103 03 1.0 [IIQ 355 35-5 IIQ159 (IIQ:15-9 células/mm ( 0,02 002 02 (1 0,04 004 04 13, 8,6 005 0,05 05 4, (4, 10 1. 35- IIQ15 (IIQ:15- 0,0 00 8, (4 IIQ1 (IIQ:15 0, (IIQ:1 (IIQ: (IIQ

Abstract Background Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections. Methods We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death. Results We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm3. Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p= 0.021) and a higher rate of ICU admissions (14% versus 44%; p= 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p= 0.054). Conclusion Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate. HIVAIDS HIV AIDS (PLWHA studies coinfections. co infections. infections Paulo Brazil 2017 1 enrolled death routines neuroradiology diagnosis neurosurgery (ICU available inhospital 4 4.3% 43 3 (4.3% 1032 032 1,03 interquartile IQR [IQR] 3550 35 35-50 22 male CD4 CD 5 (IQR 1594 15 94 15-94 cellsmm3 cellsmm cells mm3 mm cells/mm3 59 20 9 encephalitis (encephalitis polyradiculopathy 2. 2 . 2) 30 (3 6 days p 0.021 0021 0 021 14% 14 (14 44% 0.045 0045 045 them 136 13 13.6 33% 33 8.6% 86 8 0.054. 0054 0.054 054 0.054) cinfections c copathogen Additionally 201 4.3 (4.3 103 03 1,0 [IQR 355 35-5 159 15-9 cells/mm ( 0.02 002 02 (1 0.04 004 04 13. 8.6 005 0.05 05 4. (4. 10 1, 35- 15- 0.0 00 8. (4 0.

ABSTRACT 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. Purpose (TAO TAOs s short longterm long term outcomes Methods 18 1 excluded Results (IOR odds 10.54 1054 10 54 95 95CI CI 4.72–23.55 4722355 4 72 23 55 0.001 0001 0 001 2.14 214 2 14 1.11–4.07 111407 11 07 0.01. 0.01 . 01 0.01) 0.06 006 06 0.94 094 94 occlusions (GOS followup follow up respectively, respectively (respectively 018 0.18 030 30 0.30 0.73. 073 0.73 73 0.73) 0.29. 029 0.29 29 0.29) Conclusions occurrence analysis 10.5 105 5 9 4.72–23.5 472235 7 0.00 000 00 2.1 21 1.11–4.0 11140 0.0 0.9 09 0.1 03 3 0.3 0.7 02 0.2 10. 4.72–23. 47223 2. 1.11–4. 1114 0. 4.72–23 4722 1.11–4 4.72–2 472 1.11– 4.72– 47 1.11 4.72 1.1 4.7 1. 4.

Resumo Objetivo Avaliar a sensibilidade e a especificidade da reação em cadeia de polimerase em tempo real quantitativa (quantitative real-time polymerase chain reaction, qPCR, em inglês) para a triagem do gene rDNA 16S, com a utilização do fluido sonicado de implantes ortopédicos. Métodos Um estudo retrospectivo foi realizado em 73 fluidos sonicados obtidos de pacientes com infecção associada aos implantes ortopédicos. As amostras foram submetidas a cultura convencional e a teste molecular utilizando ionização e dessorção a laser assistida por matriz com espectrometria de massa por tempo de voo (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF MS, em inglês) e qPCR para o gene rDNA 16S. Os valores limiares do ciclo foram usados para definir um ponto de corte para a qPCR do gene rDNA 16S para culturas negativas e positivas. Resultados Não foram observadas diferenças estatísticas entre os grupos de cultura positiva e negativa com base no tempo desde a primeira cirurgia até a infecção (p= 0,958), na idade (p= 0,269), ou nas comorbidades em geral. No entanto, uma diferença estatística foi encontrada entre a duração média do uso de antibióticos antes da remoção do dispositivo (3,41 versus 0,94; p= 0,016). O DNA bacteriano foi identificado em todas as amostras dos fluidos sonicados. Os limiares do ciclo médio de culturas positivas e negativas foram de 25,6 e 27,3, respectivamente (p< 0,001). Como uma ferramenta de diagnóstico, um corte do limite do ciclo de 26,89 demonstrou uma área sob a curva da característica de operação do receptor de 0,877 (p ≤ 0,001). Conclusão A presença de agentes antimicrobianos por mais de 72 horas diminuiu a positividade da cultura, mas não influenciou os resultados da qPCR. Apesar disso, a amplificação do rDNA 16S pode sobrestimar o diagnóstico de infecção.

Abstract Objective To evaluate the sensitivity and specificity of the quantitative real-time polymerase chain reaction (qPCR) for 16S rDNA gene screening using sonicated fluid from orthopedic implants. Methods A retrospective study was conducted on 73 sonicated fluids obtained from patients with infection associated with orthopedic implants. The samples were subjected to conventional culture and molecular testing using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and qPCR for 16S rDNA. The cycle threshold values were used to define a cut-off of the qPCR of the 16S rDNA for negative and positive cultures. Results No statistical differences were observed between the positive and negative culture groups based on the time from the first surgery to infection (p= 0.958), age (p =0.269), or general comorbidities. Nevertheless, a statistical difference was found between the mean duration of antibiotic use before device removal (3.41 versus 0.94; p =0.016). Bacterial DNA was identified in every sample from the sonicated fluids. The median cycle thresholds of the positive and negative cultures were of 25.6 and 27.3 respectively (p< 0.001). As a diagnostic tool, a cycle threshold cut-off of 26.89 demonstrated an area under the curve of the receiver operating characteristic of 0.877 (p≤ 0.001). Conclusion The presence of antimicrobial agents for more than 72 hours decreased culture positivity, but did not influence the qPCR results. Despite this, amplification of the 16S rDNA may overestimate infection diagnosis.

ABSTRACT Purpose: To evaluate the risk factors for poor outcomes after surgical and endovascular treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with ≥ 18-years of age and aSAH were included, while patients who died within 12 h of admission or lost follow-up were excluded. All participants underwent standardized clinical and radiological assessment on admission and were reassessed at discharge and at 6-months follow-up using the Glasgow Outcome Scale (GOS). Results: Death at discharge was associated with female gender, anterior communication artery (ACoA) aneurysm location and presence of atherosclerotic plaque in the surgical group, and with age in the endovascular group. Both groups had clinical condition on follow-up associated with mFisher score on admission and hypertension. GOS on follow-up was also associated with presence of atherosclerotic plaque and multiple aneurysms in surgical group, and with age in endovascular group. Conclusions: Subjects treated surgically are prone to unfavorable outcomes if atherosclerotic plaques and multiple aneurysms are present. In patients with endovascular treatment, age was the main predictor of clinical outcome.

ABSTRACT Purpose: To analyze the role of serum creatinine levels as a biomarker of intracranial aneurysm outcomes. Methods: This is a prospective analysis of outcomes of patients with intracranial aneurysm. One hundred forty-seven patients with serum creatinine at admission and 6 months follow up were included. Linear and logistic regressions were used to analyze the data. Modified Rankin scale (mRS) was used to assess outcome. Results: Creatinine level was not directly related to aneurysm outcome nor aneurysm rupture (p > 0.05). However, patients with a glomerular filtration rate (GFR) lower than 72.50 mL·min–1 had an odds ratio (OR) of 3.049 (p = 0.006) for worse outcome. Similarly, aneurysm rupture had an OR of 2.957 (p = 0.014) for worse outcomes. Stepwise selection model selected 4 variables for outcomes prediction: serum creatinine, sex, hypertension and treatment. Hypertensive patients had, on average, an increase in 0.588 in mRS (p = 0.022), while treatment with microsurgery had a decrease in 0.555 (p = 0.038). Conclusions: Patients with higher GFR had better outcomes after 6 months. Patients with higher GFR had better outcomes after 6 months. Creatinine presented an indirect role in GFR values and should be included in models for outcome prediction.

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: “status epilepticus”, “refractory”, “treatment” e “topiramate”. Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were “status epilepticus”, “refractory”, “treatment” and “topiramate”. No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

SUMMARY OBJECTIVE: Decompressive craniectomy may be a life-saving measure in ischemic stroke patients, who still have several associated complications. The objective of this study is to evaluate a novel decompressive surgery technique for severe hemispheric ischemic stroke. METHODS: For the hinge decompressive craniectomy (HDC), linear durotomies were performed. Vertical (one or two frontal and two parietal), and two horizontal (temporal), with approximately 5 cm long, linear durotomies were carried out. Duroplasty was performed using an autologous subgaleal tissue graft fixed with separate sutures to avoid CSF leak and direct contact of the cortex with the bone flap. The bone flap was fixed in three parietal locations. We compared 10 patients who underwent our modified HDC with 9 patients submitted to classical decompressive craniectomy (CDC). The primary outcome of this study was mortality. RESULTS: Nineteen patients were included, with a mean age of 52.3 years (±8.2). Four (44%) patients from the HDC group had to be reoperated to remove the bone flap because of brain swelling worsening, but none of them died. The average time of HDC was 90 minutes. Overall 14-days mortality was 21.1% (n=4), and cumulative six-months mortality was 42.1% (n=8). Five (50%) patients submitted to CDC died, while 3 (33.3%) submitted to HDC died (χ2=0.07, p=0.79). The mean length of stay was 46.7 days (±32.1) for HDC and 38.7 (±27.1) for CDC (p=0.60). CONCLUSIONS: We present a modified technique of hinge craniectomy with linear vertical and horizontal durotomies, which seems to have reduced operative time and mortality compared to classical decompressive craniotomy, although the difference was not statistically significant.

OBJECTIVES: This study proposed a structured microsurgical training program and evaluated it with the assistance of a large sample of surgeons. METHODS: The practical course comprised 16 sessions of approximately 4 hours each. This included two sessions for suturing rubber gloves and two sessions for suturing arteries, veins, and nerves in chicken thighs. The other sessions were performed on the femoral vessels of rats: 5 sessions for end-to-end arterial anastomosis, 5 for end-to-end venous anastomosis, 1 for arterial grafting, and 1 for end-to-side anastomosis. We conducted a structured assessment of the microsurgical skills in each training session. RESULTS: In this study, 89 surgeons were evaluated. The mean scores for the different procedures were as follows: glove suturing, 33.3±0.59; chicken nerve end-to-end anastomosis, 40.3±0.49; chicken artery suturing, 40.9±0.36; chicken vein suturing, 42.3±0.36; graft interposition, 44.8±0.7; and end-to-side anastomosis, 43.7±0.63 (p<0.05 for all). The chicken thigh suturing scores were significantly higher than the rubber gloves suturing scores (p<0.01). There were no differences between scores of the rat artery and chicken thigh suturing procedures (p=0.24). The rat venous anastomosis scores were higher than the rat arterial anastomosis scores (p=0.02), as were graft interposition scores when compared with end-to-end venous anastomosis scores. The end-to-side anastomosis scores did not differ significantly from the grafting scores (p=0.85). The most common errors were inadequate knotting technique and suture rupture due to inadequate technique (both n=88 [98.9%]). CONCLUSION: We propose a 16-step, progressive microsurgical training program to learn the basic microsurgical techniques comprehensively and reliably. The program was evaluated in a large sample of trainees, and it demonstrated the adequacy of the training sequence and results.

Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52–28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27–18.12] and on 25-hour was 17.58 µg/mL [12.5–22.5]. Medians AUC24–48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.