bluuebunny/crossref_metadata_2025 huggingface dataset:
TGFβ Blockade Augments PD-1 Inhibition to Promote T-Cell–Mediated Regression of Pancreatic Cancer
Authors: Principe Daniel R. , Park Alex , Dorman Matthew J. , Kumar Sandeep , Viswakarma Navin , Rubin Jonathan , Torres Carolina , McKinney Ronald , Munshi Hidayatullah G. , Grippo Paul J. , Rana Ajay
Published: December 2018

Pancreatic ductal adenocarcinoma (PDAC) remains remarkably lethal with a 5-year survival rate of 8%. This is mainly attributed to the late stage of presentation, as well as widespread resistance to conventional therapy. In addition, PDAC tumors are largely nonimmunogenic, and most patients have displayed incomplete responses to cancer immunotherapies. Our group has previously identified TGFβ as a crucial repressor of antitumor immune function in PDAC, particularly with respect to cytotoxic T lymphocytes. However, pharmacologic inhibition of TGFβ signaling has had limited efficacy in clinical trials, failing to promote a significant antitumor immune response. Hence, in this work, we extend our analysis to identify and circumvent the mechanisms of resistance to TGFβ signal inhibition in PDAC. Consistent with our previous observations, adoptive transfer of TGFβ-insensitive CD8+ T cells led to the near complete regression of neoplastic disease in vivo. However, we demonstrate that this cannot be recapitulated via global reduction in TGFβ signaling, through either genetic ablation or pharmacologic inhibition of TGFBR1. In fact, tumors with TGFβ signal inhibition displayed increased PD-L1 expression and had no observable change in antitumor immunity. Using genetic models of advanced PDAC, we then determined that concomitant inhibition of both TGFβ and PD-L1 receptors led to a reduction in the neoplastic phenotype, improving survival and reducing disease-associated morbidity in vivo. Combined, these data strongly suggest that TGFβ and PD-L1 pathway inhibitors may synergize in PDAC, and this approach warrants clinical consideration.
Sobre a Definição de Res Publica em Cícero (Rep. 1.39)
Authors: Aguiar Márlio
Published: December 2018

A despeito de ser uma das obras sofisticadas de Marco Túlio Cícero, o tratado De Re Publica e o conceito de res publica (Rep. 1.39) permanecem ainda temas pouco debatidos para além da repetição apressada de seus termos. Estão entre os lugares comuns as leituras excessivamente individualizantes, moralizantes ou mesmo atualizantes e anacrônicas do pensamento político e jusnaturalista de Cícero. O objetivo deste artigo é o de oferecer uma leitura da definição de Cipião, trazendo à luz o aspecto institucional (e historicamente localizado) deste conceito. Procedemos por uma análise dos principais elementos que compõem a definição (iuris consensus, utilitatis communio, sociatus-societas), partindo do pressuposto que formam um complexo conceitual que precisa ser lido na sua inteireza.
How many ἀρεταί in Plato's Protagoras?
Authors: Molinelli Sebastiano
Published: December 2018

A large debate around Plato’s Protagoras concerns the so-called ‘unity of virtue’, namely Socrates’ ultimate position on the relation between ἀρετή and the five concepts (justice, piety, prudence, wisdom, and courage) connected with it. In this article, I will draw on the language and ideas of the dialogue to question the semantic presupposition which all the scholars involved in the debate, whatever their views, have been sharing, namely that the five concepts can be considered as ἀρεταί, and not just as ‘good qualities’ (τὰ καλά), or ‘parts’ (μόρια), or ‘names’ (ὀνόματα) of ἀρετή, as Plato terms them.
The Unity of Aristotle’s Metaphysics
Authors: Salis Rita
Published: December 2018

This paper discusses the three ancient commentaries on Book E of Aristotle’s Metaphysics, that have been handed down to us. It aims to demonstrate the fundamental part played by their particular interpretation of Aristotle’s doctrines in the birth of the traditional interpretation of his Metaphysics, according to which all the books comprising the work were written as a function of Book Λ, containing the well-known doctrine of the unmoved mover. Among the main elements supporting this assumption there is Aristotle’s distinction between three types of science - the theoretical, the practical and the productive - and his claiming the primacy of metaphysics as a theological science. According to the ancient commentators, the remainder of Book E would belong to the unitary project of the Metaphysics, since it would indicate what is not encompassed in the object of metaphysics. This would mean that Aristotle’s treatment of accidental being, being as truth and not-being as falsity, and being potentially and actually would take on a negative function. The theological interpretation of Aristotle’s Metaphysics thus retains its ultimate foundations in premises contained in the Aristotelian text itself
Sobre jovens e velhos: Marcos Nobre entre Fenomenologia e Sistema
Authors: Caux Luiz Philipe de
Published: December 2018

Resenha de Como nasce o novo: Experiência e diagnóstico de tempo na Fenomenologia do espírito de Hegel, de Marcos Nobre (São Paulo: Todavia, 2018)
Devir um sujeito crítico: Jürgen Habermas e Axel Honneth
Authors: Aubert Isabelle , Amaral Paulo Fernando Silva
Published: December 2018

Tradução de Devir um sujeito crítico: Jürgen Habermas e Axel Honneth, de Isabelle Aubert, por Paulo Amaral
Sobre o caráter ontológico da ciência: possíveis contribuições de Nicolai Hartmann para um problema do realismo especulativo
Authors: Nasser Eduardo
Published: December 2018

Quentin Meillassoux, um dos nomes mais promissores do realismo especulativo, tendência intelectual de nosso tempo que constitui opção ao legado da filosofia moderna, entende que o correlacionismo (Corrélationisme) só poderá ser desestimulado quando o problema da ancestralidade for seriamente enfrentado, e o prestígio ontológico do discurso matemático, o idioma da ciência, for recuperado. No século passado, Nicolai Hartmann propôs algo similar ao apontar para o enfraquecimento do correlativismo (Korrelativismus) ocasionado pela atitude científica. Todavia, diferentemente de Meillassoux, Hartmann entende que o valor da ciência para a ontologia não está na aptidão de matematizar o discurso, mas na ampliação da intuitividade e no desvelamento das categorias.
O problema da substância na Doutrina da Essência (1813) de Hegel
Authors: Orsini Federico
Published: December 2018

O objetivo deste artigo é esclarecer os termos da apresentação crítica da substância na Doutrina da Essência (1813) de Hegel. Para tanto, procederei em três passos: em primeiro lugar, apresentarei o conteúdo intrinsecamente relacional da categoria da substância na Doutrina da Essência (1813); em segundo lugar, analisarei em que consiste a falha que impulsiona a ciência lógica a ultrapassar a relação da substancialidade; em terceiro lugar, comentarei sobre o sentido geral da refutação hegeliana do sistema espinosista.
A Balalaika de Gonzago: Marília vai à Rússia
Authors: Bonavina Rafael , Siphone Raquel
Published: December 2018

O presente artigo busca compreender as modificações da lira IX da segunda parte de Marília de Dirceu (1792) na passagem do português ao russo. A partir de uma tradução triangulada, que atravessa a via francófona, levantamos alguns aspectos (ambientação, elementos poéticos, personagens etc.) que, durante o percurso, sofreram alterações. Vertida por escritores de diferentes nações – Eugène de Monglave (1796-1878) e P. Chalas, na França; Aleksandr Púchkin (1799-1837), na Rússia –, a lira de Tomás Antônio Gonzaga (1744-1810) ganhou novos tons. Propusemo-nos, portanto, a analisar esses novos textos, aos quais estão expostos os leitores gálicos e russos, em contraste com o original.
As Novas Vozes da Literatura Brasileira Contemporânea
Authors: Andrade Geysiane Aparecida de
Published: December 2018

A era da multiplicidade revela a quebra de fronteiras, com diversos meios de comunicação que possibilitam novos suportes para a escrita e a leitura. A produção literária é mais heterogênea, apresentando novas vozes, com mais autoras, autores negros, LBGT, e grupos marginalizados que também buscam seu espaço. Os leitores mostram-se cada vez mais ativos e exigentes, refletindo na rapidez na sucessão dos modismos. Neste cenário no qual a literatura ainda sobrevive, busca-se apontar neste artigo características predominantes na ficção contemporânea brasileira em relação à estética, aos temas abordados, ao discurso e à construção de personagens, de acordo com a leitura de algumas obras lançadas a partir 2016, como O amor dos homens avulsos (Victor Heringer), O tribunal da quinta-feira (Michel Laub), Correr com Rinocerontes (Cristiano Baldi), Ponciá Vicêncio (Conceição Evaristo - reedição), entre outras.
"SOU UM ESCRITOR SEM LIVRO" - ENTREVISTA COM SULEIMAN CASSAMO
Authors: Pinheiro Vanessa Neves Riambau
Published: December 2018

No depoimento que está transcrito a seguir, o escritor moçambicano Suleiman Cassamo fala sobre o papel da imprensa na divulgação da literatura moçambicana do século XX, papel pouco ativo na atualidade. Confessa a dificuldade de encontrar seus livros em Moçambique e comenta sobre a preocupação com a divulgação das obras, em meio digital ou traduzida, feitas à revelia do autor. Discorre sobre as relações entre o universal e o particular na obra, buscando uma forma de conciliação entre ambos. Reflete também acerca de suas influências literárias e revela sua preferência temática relacionada ao regresso às suas origens, além de relatar suas perspectivas e projetos futuros.
ESCREVENDO EM VOZ ALTA: AS CRÔNICAS METALITERÁRIAS DE CRISTOVÃO TEZZA NO JORNAL GAZETA DO POVO
Authors: Bueno Raquel Illescas , Lima Annalice Del Vecchio de
Published: December 2018

Este trabalho estuda as crônicas do escritor Cristovão Tezza publicadas no jornal Gazeta do Povo entre 2008 e 2014, analisando temáticas, conteúdo, formas estilísticas e relacionando estes textos com a produção ficcional e ensaística do autor, por aproximações ou distanciamentos. O corpus desta análise é formado por crônicas metaliterárias, ou seja, aquelas em que Tezza reflete sobre questões da literatura, estabelecendo um diálogo direto com o romance autobiográfico O filho eterno (2007), a obra ensaística O espírito da prosa – uma autobiografia literária (2012) e as conferências publicadas no livro digital Literatura à Margem (2014).
LITERATURA NOS JORNAIS: DEMOCRATIZAÇÃO NA ESCRITA E NA RECEÇÃO
Authors: Costa Cátia Miriam
Published: December 2018

Os jornais foram um elemento decisivo na democratização do acesso à literatura, tanto na produção do discurso literário como na sua receção. A imprensa periódica, com relevo para os jornais, permitiu um diálogo entre jornalismo e literatura. Nos contextos coloniais, permitiu, ainda, que os centros produtivos se deslocassem para os espaços periféricos, onde surgiram novas oportunidades de escrita e receção. Partindo da análise comparativa das obras e percursos de um jornalista metropolitano que se torna escritor em Angola e de um intelectual angolano, procuramos compreender como os jornais democratizaram a literatura e quais as suas limitações neste processo.
UMA LEITURA DE "ENFERMEIRINHAS ESPERTAS", CRÔNICA DE TEREZA QUADROS, MÁSCARA DE CLARICE LISPECTOR
Authors: Sandroni Tânia
Published: December 2018

Este artigo apresenta uma leitura da crônica “Enfermeirinhas espertas”, de Tereza Quadros (máscara de Clarice Lispector), publicada no semanário Comício, em 1952. A escritora era responsável pela coluna feminina “Entre mulheres” do veículo. Nessa página, a colunista publicou crônicas com incontestável valor literário, sendo que algumas delas deram origem a contos publicados posteriormente na obra lispectoriana.
A PENA E O TIPO: GERVÁSIO LOBATO E A IMPRENSA PORTUGUESA
Authors: Masseran Claudia Barbieri
Published: December 2018

O presente artigo versa sobre um dos grandes vultos do jornalismo oitocentista finissecular português: um cronista, folhetinista, ensaísta, diretor literário e redator-chefe. Versa ainda sobre um alegre romancista e um dos comediógrafos de maior sucesso do seu tempo. Trata este texto de Gervásio Lobato (1850-1895) e de seu ofício de escritor.
O JORNAL COMO FONTE LITERÁRIA NA VIRADA DO SÉCULO XIX PARA O XX: O CASO DE SÃO PAULO
Authors: Ferreira Rafael Rodrigo
Published: December 2018

O seguinte trabalho pretende reivindicar a importância do jornal para os estudos literários da Primeira República (1889-1930), na medida em que expõe particularidades do caso paulista, bem como disserta acerca de possíveis problemas de parcela significativa da crítica literária que, desatenta aos compartilhamentos entre literatura e jornalismo, ofusca, consequentemente, processos indispensáveis para a compreensão da constituição das letras brasileiras.
Taxonomic studies on the gaudy grasshoppers (Orthoptera: Pyrgomorphoidea: Pyrgomorphidae) from the northeastern states of India
Authors: Khan M. Imran , Usmani M. Kamil , Usmani Shahnila , Naz Hira
Published: December 2018

A survey of the northeastern states of India recorded 10 species representing five genera belonging to four tribes of the family Pyrgomorphidae.  For identification, in addition to conventional morphological characters, the detailed structures of male and female genitalia were also included.  All the genera studied are described.  Morphometry and distribution of each species are also given.
First record of the rare Furry Lobster Palinurellus wieneckii (De Man, 1881) (Decapoda: Palinuridae) from the Arabian Sea
Authors: Idreesbabu K. K. , Shanis C.P. Rajool , Sureshkumar S.
Published: December 2018

Two female specimens of the Furry Lobster Palinurellus wieneckii (De Man, 1881) with a total length of 118mm and 114mm, respectively, were obtained from the coral reefs off Kavaratti Island, Laccadive Islands, west of India.  Only two species are currently recognized in this genus, which were described from a small number of specimens.  As P. wieneckii is very rare, the present report from the Lakshadweep Archipelago provides a valuable new distribution point, which is the first record for the Arabian Sea.  Illustrations and photographs are provided for this rare lobster.
Ischnura fountaineae (Insecta: Odonata: Zygoptera) in Oman, eastern Arabia
Authors: Cowan Elaine Mary , Cowan Peter John
Published: December 2018

Abstract: We report new records of Ischnura fountaineae for Oman and present field characters for I. fountaineae visible in a digital photograph.
Cholesterol Mass Efflux Capacity, Incident Cardiovascular Disease, and Progression of Carotid Plaque
Authors: Shea Steven , Stein James H. , Jorgensen Neal W. , McClelland Robyn L. , Tascau Liana , Shrager Sandi , Heinecke Jay W. , Yvan-Charvet Laurent , Tall Alan R.
Published: December 2018

Objective—

To assess the role of HDL (high-density lipoprotein)-mediated cholesterol mass efflux capacity (CMEC) in incident cardiovascular disease and carotid plaque progression.

Approach and Results—

We measured CMEC in 2 cohorts aged 45 to 84 years at baseline derived from the MESA (Multi-Ethnic Study of Atherosclerosis). Cohort 1 comprised 465 cases with incident cardiovascular disease events during 10 years of follow-up and 465 age- and sex-matched controls; cohort 2 comprised 407 cases with progression of carotid plaque measured by ultrasonography at 2 exams >10 years and 407 similarly matched controls. Covariates and outcome events were ascertained according to the MESA protocol. CMEC level was modestly correlated with HDL cholesterol (
R
=0.13;
P
<0.001) but was not associated with age, sex, race/ethnicity, body mass index, diabetes mellitus, alcohol use, smoking status, or statin use. Higher CMEC level was significantly associated with lower odds of cardiovascular disease (odds ratio, 0.82 per SD of CMEC [95% CI, 0.69–0.98;
P
=0.031] in the fully adjusted model) in cohort 1 but higher odds of carotid plaque progression (odds ratio, 1.24 per SD of CMEC [95% CI, 1.04–1.48;
P
=0.018] in the fully adjusted model) in cohort 2 but without dose-response effect. In subgroup analysis within cohort 1, higher CMEC was associated with lower risk of incident coronary heart disease events (odds ratio, 0.72 per SD of CMEC (95% CI, 0.5–0.91;
P
=0.007) while no association was found with stroke events.

Conclusions—

These findings support a role for HDL-mediated cholesterol efflux in an atheroprotective mechanism for coronary heart disease but not stroke.
SM22α (Smooth Muscle 22α) Prevents Aortic Aneurysm Formation by Inhibiting Smooth Muscle Cell Phenotypic Switching Through Suppressing Reactive Oxygen Species/NF-κB (Nuclear Factor-κB)
Authors: Zhong Lintao , He Xiang , Si Xiaoyun , Wang He , Li Bing , Hu Yinlan , Li Mengsha , Chen Xiaoqiang , Liao Wangjun , Liao Yulin , Bin Jianping
Published: December 2018

Objective—

Vascular smooth muscle cell phenotypic transition plays a critical role in the formation of abdominal aortic aneurysms (AAAs). SM22α (smooth muscle 22α) has a vital role in maintaining the smooth muscle cell phenotype and is downregulated in AAA. However, whether manipulation of the
SM22α
gene influences the pathogenesis of AAA is unclear. Here, we investigated whether SM22α prevents AAA formation and explored the underlying mechanisms.

Approach and Results—

In both human and animal AAA tissues, a smooth muscle cell phenotypic switch was confirmed, as manifested by the downregulation of SM22α and α-SMA (α-smooth muscle actin) proteins. The methylation level of the
SM22α
gene promoter was dramatically higher in mouse AAA tissues than in control tissues. SM22α knockdown in ApoE
−/−
(apolipoprotein E–deficient) mice treated with Ang II (angiotensin II) accelerated the formation of AAAs, as evidenced by a larger maximal aortic diameter and more medial elastin degradation than those found in control mice, whereas SM22α overexpression exerted opposite effects. Similar results were obtained in a calcium chloride-induced mouse AAA model. Mechanistically, SM22α deficiency significantly increased reactive oxygen species production and NF-κB (nuclear factor-κB) activation in AAA tissues, whereas SM22α overexpression produced opposite effects. NF-κB antagonist SN50 or antioxidant N-acetyl-L-cysteine partially abrogated the exacerbating effects of SM22α silencing on AAA formation.

Conclusions—

SM22α reduction in AAAs because of the
SM22α
promoter hypermethylation accelerates AAA formation through the reactive oxygen species/NF-κB pathway, and therapeutic approaches to increase SM22α expression are potentially beneficial for preventing AAA formation.
A Systematic Literature Review of Patients With Carotid Web and Acute Ischemic Stroke
Authors: Zhang Andrew J. , Dhruv Parth , Choi Philip , Bakker Caitlin , Koffel Jonathan , Anderson David , Kim Jae , Jagadeesan Bharathi , Menon Bijoy K. , Streib Christopher
Published: December 2018

Background and Purpose—

Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW.

Methods—

Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly.

Results—

Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16–85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0–97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients.

Conclusions—

CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.
Early Prediction of Malignant Brain Edema After Ischemic Stroke
Authors: Wu Simiao , Yuan Ruozhen , Wang Yanan , Wei Chenchen , Zhang Shihong , Yang Xiaoyan , Wu Bo , Liu Ming
Published: December 2018

Background and Purpose—

Malignant brain edema after ischemic stroke has high mortality but limited treatment. Therefore, early prediction is important, and we systematically reviewed predictors and predictive models to identify reliable markers for the development of malignant edema.

Methods—

We searched Medline and Embase from inception to March 2018 and included studies assessing predictors or predictive models for malignant brain edema after ischemic stroke. Study quality was assessed by a 17-item tool. Odds ratios, mean differences, or standardized mean differences were pooled in random-effects modeling. Predictive models were descriptively analyzed.

Results—

We included 38 studies (3278 patients) with 24 clinical factors, 7 domains of imaging markers, 13 serum biomarkers, and 4 models. Generally, the included studies were small and showed potential publication bias. Malignant edema was associated with younger age (n=2075; mean difference, −4.42; 95% CI, −6.63 to −2.22), higher admission National Institutes of Health Stroke Scale scores (n=807, median 17–20 versus 5.5–15), and parenchymal hypoattenuation >50% of the middle cerebral artery territory on initial computed tomography (n=420; odds ratio, 5.33; 95% CI, 2.93–9.68). Revascularization (n=1600, odds ratio, 0.37; 95% CI, 0.24–0.57) were associated with a lower risk for malignant edema. Four predictive models all showed an overall C statistic >0.70, with a risk of overfitting.

Conclusions—

Younger age, higher National Institutes of Health Stroke Scale, and larger parenchymal hypoattenuation on computed tomography are reliable early predictors for malignant edema. Revascularization reduces the risk of malignant edema. Future studies with robust design are needed to explore optimal cutoff age and National Institutes of Health Stroke Scale scores and to validate and improve existing models.
Validation of the Intracerebral Hemorrhage Score in Uganda
Authors: Abdallah Amir , Chang Jonathan L. , O’Carroll Cumara B. , Okello Samson , Olum Sam , Acan Moses , Aden Abdirahim Abdi , Chow Felicia C. , Siedner Mark J.
Published: December 2018

Background and Purpose—

Rates of intracerebral hemorrhage (ICH) are estimated to be highest globally in sub-Saharan Africa. However, outcomes of ICH are poorly described and standard prognostic markers for ICH have not been validated in the region.

Methods—

We enrolled consecutive patients with computed tomography-confirmed ICH at a referral hospital in southwestern Uganda. We recorded demographic, clinical, and radiographic features of ICH, and calculated ICH scores. We fit Poisson regression models with robust variance estimation to determine predictors of case fatality at 30 days.

Results—

We enrolled 73 individuals presenting with computed tomography-confirmed ICH (mean age 60 years, 45% [33/73] female, and 14% [10/73] HIV-positive). The median ICH score was 2 (interquartile range, 1–3; range, 0–5). Case fatality at 30 days was 44% (32/73; 95% CI, 33%–57%). The 30-day case fatality increased with increasing ICH score of 0, 1, and 5 from 17%, 23%, to 100%, respectively. In multivariable-adjusted models, ICH score was associated with case fatality (adjusted relative risk, 1.48; 95% CI, 1.23–1.78), as were HIV infection (adjusted relative risk, 1.92; 95% CI, 1.07–3.43) and female sex (adjusted relative risk, 2.17; 95% CI, 1.32–3.59). The ICH score moderately improved with the addition of a point each for female sex and HIV serostatus (0.81 versus 0.73).

Conclusions—

ICH score at admission is a strong prognostic indicator of 30-day case fatality in Uganda. Our results support its role in guiding the care of patients presenting with ICH in the region.
APOE
and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality
Authors: Satizabal Claudia L. , Samieri Cécilia , Davis-Plourde Kendra L. , Voetsch Barbara , Aparicio Hugo J. , Pase Matthew P. , Romero José Rafael , Helmer Catherine , Vasan Ramachandran S. , Kase Carlos S. , Debette Stéphanie , Beiser Alexa S. , Seshadri Sudha
Published: December 2018

Background and Purpose—

The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by
APOE-ε4
genotype.

Methods—

We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were measured at baseline by gas chromatography. All-cause stroke, ischemic stroke, coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate fatty acid levels to the risk of developing each event during ≤10 years of follow-up adjusting for potential confounders and stratifying by APOE genotype (ε4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models.

Results—

On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were
APOE-ε4
carriers. Meta-analysis results showed that, only among
APOE-ε4
carriers, every SD unit increase in linoleic acid was associated with a reduced risk of all-cause stroke (hazard ratio [HR], 0.54 [95% CI, 0.38–0.78]), ischemic stroke (HR, 0.48 [95% CI, 0.33–0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57–0.85]). In contrast, every SD unit increase in palmitic acid was related to an increased risk of all-cause stroke (HR, 1.58 [95% CI, 1.16–2.17]), ischemic stroke (HR, 1.76 [95% CI, 1.26–2.45]), and coronary heart disease (HR, 1.48 [95% CI, 1.09–2.01]), also in
APOE-ε4
carriers only. Results for docosahexaenoic acid and arachidonic acid were heterogeneous between cohorts.

Conclusions—

These exploratory results suggest that
APOE-ε4
carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality. In this subgroup, higher linoleic acid was protective for stroke and mortality, whereas palmitic acid was a risk factor for stroke and coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.
Weekend Effect in Carotid Endarterectomy
Authors: O’Donnell Thomas F.X. , Schermerhorn Marc L. , Liang Patric , Li Chun , Swerdlow Nicholas J. , Wang Grace J. , Giles Kristina A. , Wyers Mark C.
Published: December 2018

Background and Purpose—

Patients undergoing surgery on the weekend may experience worse outcomes, but this weekend effect has not been studied in carotid endarterectomy (CEA).

Methods—

We identified patients undergoing isolated CEA in the Vascular Quality Initiative between 2003 and 2018. Our primary outcome was in-hospital stroke or perioperative death (stroke/death), stratified by symptom status. For asymptomatic patients, we also compared rates of the Centers for Medicare and Medicaid Services quality metric prolonged length of stay (>2 days or failed discharge home). We calculated propensity scores and used multilevel, inverse probability weighted logistic regression clustering at the hospital level.

Results—

There were 86 123 repairs during the study period, 53% asymptomatic lesions and 47% symptomatic. Only 0.7% of asymptomatic patients underwent CEA on the weekend, compared with 3.1% of symptomatic patients. Patients undergoing weekend repairs were more often white, with lower rates of most comorbidities. In asymptomatic patients, weekend operations were associated significantly higher odds of stroke/death (odds ratio [OR], 2.3 [1.1–4.8];
P
=0.02), and prolonged length of stay (OR, 3.6 [2.7–4.7];
P
<0.001). In symptomatic patients, weekend operations were associated with significantly higher adjusted odds of stroke/death (OR, 1.7 [1.2–2.4];
P
=0.007) and longer postoperative length of stay (3.3 days versus 2.0 days,
P
=0.002). However, the difference in stroke/death was driven by patients presenting with stroke (OR, 2.2 [1.5–2.3];
P
<0.001), rather than those presenting with transient ischemic attack (OR, 1.2 [0.6–2.1];
P
=0.56).

Conclusions—

We found evidence of a significant weekend effect in CEA, as weekend operations in asymptomatic patients and patients who presented with stroke were associated with higher rates of stroke/death and prolonged length of stay. However, there was no evidence of such an effect in patients with transient ischemic attack. These data suggest that weekend CEA should be avoided except in the case of expedited revascularization after transient ischemic attack.
A Novel Staging System to Evaluate Cerebral Hypoperfusion in Patients With Moyamoya Disease
Authors: Yin Hu , Liu Xingju , Zhang Dong , Zhang Yan , Wang Rong , Zhao Meng , Zhao Jizong
Published: December 2018

Background and Purpose—

The study goal was to evaluate cerebral perfusion in moyamoya patients with a novel staging system and investigate the association between differences of perfusion status and clinical outcomes in patients treated with revascularization.

Methods—

About 506 consecutive patients from 2009 to 2015 were enrolled. The perfusion status was evaluated by a staging system-the stage of preinfarction period based on the result of computed tomography perfusion. Hemisphere in different perfusion stage was compared between hemorrhagic patients (n=155) and ischemic patients (n=351). The modified Rankin Scale was applied to evaluate the prognosis of patients.

Results—

In the enrolled 506 patients: 229 hemispheres (22.6%) with normal perfusion, 72 hemispheres (7.1%) in stage I, 205 hemispheres (20.3%) in stage II, 308 hemispheres (30.4%) in stage III, and 198 hemispheres (19.6%) in stage IV. Significant difference was observed in stage distribution between hemorrhagic patients and ischemic patients (
P
<0.01). The ratio of hemispheres with normal perfusion in hemorrhagic group is more than the ischemic group (
P
<0.05; odds ratio, 1.440; 95% CI, 1.144–1.811). The ratio of hemispheres in stage III in ischemic group is more than the hemorrhagic group (
P
<0.01; odds ratio, 0.618, 95% CI, 0.487–0.783). In the prognosis-related analysis, the stage I group has the highest improved ratio (73.9%) and the normal perfusion group has the lowest improved ratio (33.3%). The improved ratio has a decreasing tendency from stage I to stage IV.

Conclusions—

The novel preinfarction staging system is a valuable assessment tool to evaluate cerebral perfusion status in moyamoya patients and predict the efficacy of revascularization. Ischemic patients suffer more from hypoperfusion. Patients in stage I and stage II are more likely to obtain improvement after revascularization. This is a retrospective study.
Increased Risk of Traffic Injury After a Cerebrovascular Event
Authors: Yu Amy Y.X. , Kapral Moira K. , Fang Jiming , Redelmeier Donald A.
Published: December 2018

Background and Purpose—

We aimed to determine the long-term risks of a motor vehicle collision after a cerebrovascular event and whether the risks were similar after left- or right-hemispheric events.

Methods—

We used a population-based registry to identify patients diagnosed with a transient ischemic attack or stroke (hemorrhagic or ischemic) between 2003 and 2013 in Ontario, Canada. Hemispheric laterality was determined using radiological and clinical findings. We identified subsequent serious injuries involving the patient as a driver using linked administrative data. Secondary outcomes included serious injuries involving the patient as a pedestrian, as a passenger, or other traumatic events (fall, fracture, ankle sprain). We used proportional hazard models accounting for death as a competing risk to test the association of hemispheric laterality and outcomes with and without adjustment for age, sex, discharge modified Rankin Scale score, home location, and prior driving record. Patients were followed through to 2017.

Results—

Among 26 144 patients with hemispheric cerebrovascular events, 377 subsequent serious traffic injuries as a driver (2.2 per 1000 person-year) were identified over a median follow-up of 6.4 person-years. The rate did not differ by laterality (adjusted hazard ratio, 1.00; 95% CI, 0.82–1.23). The risk of a serious traffic injury as a pedestrian was significantly higher after a right-sided than left-sided event (adjusted hazard ratio, 1.27; 95% CI, 1.02–1.58). Subsequent risks for other traumatic injuries did not differ by laterality of cerebrovascular event.

Conclusions—

The risk of a serious traffic injury as a pedestrian is substantially higher after a right-hemispheric cerebrovascular event compared with a left-sided event. Walking should be promoted for exercise in survivors of a stroke or transient ischemic attack, but these vulnerable road users may benefit from additional poststroke rehabilitation to optimize safety.
Iron Status and Risk of Stroke
Authors: Gill Dipender , Monori Grace , Tzoulaki Ioanna , Dehghan Abbas
Published: December 2018

Background and Purpose—

Both iron deficiency and excess have been associated with stroke risk in observational studies. However, such associations may be attributable to confounding from environmental factors. This study uses the Mendelian randomization technique to overcome these limitations by investigating the association between genetic variants related to iron status and stroke risk.

Methods—

A study of 48 972 subjects performed by the Genetics of Iron Status consortium identified genetic variants with concordant relations to 4 biomarkers of iron status (serum iron, transferrin saturation, ferritin, and transferrin) that supported their use as instruments for overall iron status. Genetic estimates from the MEGASTROKE consortium were used to investigate the association between the same genetic variants and stroke risk. The 2-sample ratio method Mendelian randomization approach was used for the main analysis, with the MR-Egger and weighted median techniques used in sensitivity analyses.

Results—

The main results, reported as odds ratio (OR) of stroke per SD unit increase in genetically determined iron status biomarker, showed a detrimental effect of increased iron status on stroke risk (serum iron OR, 1.07; 95% CI, 1.01–1.14; [log-transformed] ferritin OR, 1.18; 95% CI, 1.02–1.36; and transferrin saturation OR, 1.06; 95% CI, 1.01–1.11). A higher transferrin, indicative of lower iron status, was also associated with decreased stroke risk (OR, 0.92; 95% CI, 0.86–0.99). Examining ischemic stroke subtypes, we found the detrimental effect of iron status to be driven by cardioembolic stroke. These results were supported in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants.

Conclusions—

This study provides Mendelian randomization evidence that higher iron status is associated with increased stroke risk and, in particular, cardioembolic stroke. Further work is required to investigate the underlying mechanism and whether this can be targeted in preventative strategies.
Determinants of Stroke in a General Male Population
Authors: Persson Carina U. , Svärdsudd Kurt , Rusek Linnéa , Blomstrand Christian , Blomstrand Ann , Welin Lennart , Wilhelmsen Lars , Hansson Per-Olof
Published: December 2018

Background and Purpose—

To further improve preventive strategies against stroke, there is a need for epidemiological long-term studies. The study aimed at a prospective investigation of stroke determinants in the general male population.

Methods—

During a period of 48 years, from 50 to 98 years of age, a population-based sample of 854 men was followed using repeated medical examinations, lifestyle questionnaires, data from hospital records and the National Cause of Death Register.

Results—

Determinants of ischemic stroke were atrial fibrillation (hazard ratio [HR], 6.61; 95% CI, 4.47–9.77); mother dead from cardiovascular disease (HR, 1.53; 1.09–2.17); high education (HR, 0.81; 0.69–0.96); and high physical activity level during leisure time (HR, 0.68; 0.50–0.93). For hemorrhagic stroke heart rate (HR, 1.04; 1.01–1.06) and mother dead from stroke (HR, 3.56; 1.43–8.87) constituted an increased risk. Statistically significant determinants for all stroke were atrial fibrillation (HR, 5.34; 3.68–7.75); high diastolic blood pressure (HR, 1.02; 1.01–1.03); high body weight (HR, 0.96; 0.94–0.99); high educational level (HR, 0.79; 0.68–0.92); wide waist circumference (HR, 1.04; 1.01–1.07); smoking (HR, 1.25; 1.06–1.48); mother dead from cerebrovascular disease (HR, 1.43; 1.05–1.94); and diabetes mellitus (HR, 1.65; 1.02–2.68). Of all men diagnosed with atrial fibrillation, 88% had a stroke during follow-up.

Conclusions—

Atrial fibrillation was by far the strongest determinant of stroke during 48 years of follow-up in a male population sample followed until the age of 98 years. The results warrant improved prophylaxis through intense treatment of modifiable determinants.
Has Outcome of Subarachnoid Hemorrhage Changed With Improvements in Neurosurgical Services?
Authors: Dhandapani Sivashanmugam , Singh Apinderpreet , Singla Navneet , Praneeth Kokkula , Aggarwal Ashish , Sodhi Harsimrat B. , Pal Sudhir S. , Goudihalli Sachin , Salunke Pravin , Mohindra Sandeep , Kumar Ajay , Gupta Vivek , Chhabra Rajesh , Mukherjee Kanchan K. , Tewari Manoj K. , Khandelwal Niranjan , Mathuriya Suresh N. , Khosla Virender K. , Gupta Sunil K.
Published: December 2018

Background and Purpose—

Though reports suggest decreasing fatality rates of subarachnoid hemorrhage with time, trends in outcome are not reported much especially from developing countries. This study was to analyze changes in outcome across 2 decades and elucidate probable factors.

Methods—

Prospective databases during 1996 to 2015 were reviewed for neurological outcome at 3 months in relation to demographics, Hunt and Hess grade, Fisher grade, and definitive treatment; and compared between 2 decades, contrasted by establishment of intensive care unit with continuous monitoring and other advancements. Univariate and multivariate analyses were performed.

Results—

Of the total 2039 patients, 1035 were managed in the former and 1004 in the recent decades. Compared with the former decade, there is delayed age at presentation (46 versus 49 years,
P
<0.001), poorer Fisher grades (81% versus 87%,
P
<0.001), and more patients with Hunt and Hess grade 2 (24% versus 39%,
P
<0.001) in the recent decade. While all patients in databases of the former decade had undergone clipping, 6% in the recent decade underwent coiling. 11% in the recent decade could not undergo definitive treatment. Despite this, there was significantly higher overall favorable outcome (50% versus 60%; odds ratio, 1.5;
P
<0.001) in recent decade. Favorable outcome of surgical clipping per se improved significantly from 50% to 67% (odds ratio 2.0;
P
<0.001). Though the improvement was across subgroups, it was more marked among Hunt and Hess grade 3 and Fisher grades 3 and 4. In multivariate analyses, both overall outcome (adjusted odds ratio, 1.7; 95% CI, 1.4–2.1;
P
<0.001) and surgical outcome (adjusted odds ratio, 1.8; 95% CI, 1.5–2.2;
P
<0.001) were significantly better in recent decade, independent of known prognostic factors.

Conclusions—

This is probably the first report to show independent improvement in outcome of subarachnoid hemorrhage with betterment in neurosurgical services from developing country. Dedicated intensive care unit care and focused management protocols could be the likely causes for improvement. Resource-constrained institutions may target patients in Hunt and Hess grade 3 and Fisher grades 3 and 4 for optimal intensive care unit utilization.
Survival and Outcome After Poor-Grade Aneurysmal Subarachnoid Hemorrhage in Elderly Patients
Authors: Goldberg Johannes , Schoeni Daniel , Mordasini Pasquale , Z’Graggen Werner , Gralla Jan , Raabe Andreas , Beck Jürgen , Fung Christian
Published: December 2018

Background and Purpose—

Whether maximal treatment should be offered to elderly patients suffering from poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is controversial. The survival of patients in this subgroup beyond the usual outcome measurements 6 to 12 months after aSAH is unclear. The purpose of this study is to provide survival and outcome data to support clinicians making decisions on treatment for this subgroup of patients.

Methods—

We performed a retrospective analysis of the Bernese SAH database for poor-grade (World Federation of Neurosurgical Societies grade IV and V) elderly patients (age ≥60 years) suffering from aSAH admitted to our institution from 2005 to 2017. Patients were divided into 3 age groups (60–69, 70–79, and 80–90 years). Survival analysis was performed to estimate mean survival and hazard ratios for death. Binary logarithmic regression was used to estimate the odds ratio for favorable (modified Rankin Scale score of 0–3) and unfavorable (modified Rankin Scale score of 4–6) outcome.

Results—

Increasing age was associated with an increasing risk of death after aSAH. The hazard ratio increased by 6% per year of age (
P
<0.001; hazard ratio, 1.06; 95% CI, 1.03–1.09) and 76% per decade (
P
<0.001; hazard ratio, 1.76; 95% CI, 1.35–2.29). Mean survival was 56.3±8 months (patients aged 60–69 years), 31.6±7.6 months (70–79 years), and 7.6±5.8 months (80–90 years). Unfavorable outcomes 6 to 12 months after aSAH were strongly related to older age. The odds ratio increased by 11% per year of age (
P
<0.001; odds ratio, 1.11; 95% CI, 1.05–1.18) and 192% per decade (
P
<0.001; odds ratio, 2.92; 95% CI, 1.63–5.26).

Conclusions—

Risk for death and unfavorable outcome increases markedly with older age in elderly patients with poor-grade aSAH. Despite a high initial mortality, treatment resulted in a reasonable proportion of favorable outcomes up to 79 years of age and only a small number of patients who were moderately or severely disabled 6 to 12 months after aSAH. Mean survival and proportion of favorable outcomes decreased markedly in patients older than 80 years.
Increased Use of Ticagrelor After Myocardial Infarction Is Not Associated With Intracranial Hemorrhage
Authors: Graipe Anna , Söderström Lars , Mooe Thomas
Published: December 2018

Background and Purpose—

Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction.

Methods—

Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH.

Results—

The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49–0.69]) versus 0.52% (97 cases [95% CI, 0.43–0.61]) during the second period (
P
=0.83).

In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH.

Conclusions—

The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.
Feasibility of Thrombectomy in Treating Acute Ischemic Stroke Because of Cervical Artery Dissection
Authors: Li Shun , Zi Wenjie , Chen Jingjing , Zhang Shuai , Bai Yongjie , Guo Yongtao , Shang Xianjin , Sun Bo , Liang Meng , Liu Yong , Wan Yue , Wang Mengmeng , Zhao Min , Liu Rui , Zhu Wusheng , Liu Xinfeng , Xu Gelin
Published: December 2018

Background and Purpose—

Acute ischemic stroke caused by cervical artery dissection tend to result in unfavorable outcomes even with appropriate medical treatment. This study evaluated the safety and effectiveness of endovascular thrombectomy in treating acute ischemic stroke associated with cervical artery dissection.

Methods—

Patients with acute ischemic stroke and with large artery occlusion associated with dissection were selected. Propensity score matching was performed to increase the comparability. Patients with a 90-day modified Rankin Scale score of 0 to 2 were defined as with favorable outcome.

Results—

Eighty patients with and 80 patients without thrombectomy were enrolled. After propensity score matching, 48 patients with and 48 patients without thrombectomy were matched for further analysis. Proportion of favorable outcome (modified Rankin Scale score of 0–2) was higher in patients with thrombectomy than in those without (66.7% versus 39.6%;
P
=0.008). There were no significance differences about the incidence of symptomatic intracranial hemorrhage (8.3% versus 4.2%;
P
=0.677) and the 90-day mortality (10.4% versus 6.3%;
P
=0.714) between matched patients with and without thrombectomy.

Conclusions—

Endovascular thrombectomy seems to be an effective treatment in selected patients with acute ischemic stroke associated with cervical artery dissection, but the safety of thrombectomy needs further research.