Activity of capecitabine for central nervous system metastases from breast cancer.

Purpose: Central nervous system (CNS) metastases are a significant burden in breast cancer (BC). Capecitabine is a frequent choice in this scenario, but data supporting its single-agent activity are scarce. We aimed to evaluate the intracranial efficacy of capecitabine in CNS metastases from BC. Methods: This retrospective cohort included patients with CNS metastases from BC treated with capecitabine at a single centre. Study endpoints were intracranial CNS objective response rate (CNS-ORR), intracranial CNS disease control rate (CNS-DCR), intracranial CNS progression-free survival (CNS-PFS) and overall survival (OS). Results: 209 patients were included; 41.6% hormone receptor-positive HER2-negative (HR + HER2-), 33.9% human epidermal growth factor receptor 2 positive (HER2+), and 26.4% triple-negative breast cancer (TNBC). Radiotherapy was performed in 90.4% and CNS surgery in 27.5%. Among patients accessible for intracranial response, 3-month CNS-ORR and CNS-DCR were 41.6% and 81.2%. CNS-ORR was numerically higher among TNBC (61% versus 38% in HR + HER2-BC and 35% in HER2 + BC) (p = 0.194). When considering patients who were not evaluable at 3-month as non-responders, the 3-month CNS-ORR was 19.1% (18.4% in HR + HER2-, 18.3% in HER2+, and 21.6% in TNBC). Nevertheless, TNBC was associated with lower CNS-PFS (p < 0.001) and OS (p < 0.001). Median PFS was 8.3 months in HR + HER2-, 5.0 months in HER2+, and 3.0 months in TNBC. Median OS was 8.7, 9.1 and 4.5 months, respectively. Conclusion: Among patients with BC and CNS metastases accessible for intracranial response at 3 months, intracranial activity was observed with capecitabine. These patients have a poor prognosis regardless of the BC subtype, especially in scenarios where newer therapeutic options are unavailable.

Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury / Eletroencefalograma de amplitude integrada precoce no monitoramento de neonatos com risco elevado de lesão cerebral

Abstract Objective: This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort of infants at high risk for brain injury in this center in Brazil. Methods: This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude-integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed. Results: In the preterm group, pathological trace or discontinuous low-voltage pattern (p = 0.03) and absence of sleep-wake cycling (p = 0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p = 0.005). Conclusion: This study supports previous results and demonstrates the utility of amplitude-integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.

Resumo Objetivo: Este estudo visou correlacionar os achados do eletroencefalograma de amplitude integrada (aEEG) com resultados precoces, medidos por mortalidade e achados de neuroimagem, em uma coorte prospectiva de neonatos com risco elevado de lesão cerebral em nosso centro no Brasil. Métodos: O estudo prospectivo de coorte cego avaliou 23 neonatos prematuros abaixo de 31 semanas de idade gestacional (IG) e 17 neonatos diagnosticados com encefalopatia hipóxico-isquêmica (EHI) secundária à asfixia perinatal, com IG superior a 36 semanas, monitorados com aEEG em um centro terciário público de fevereiro de 2014 a janeiro de 2015. Foram avaliadas a atividade de fundo (classificada como padrão contínuo, descontínuo de alta voltagem, descontínuo de baixa voltagem, supressão de explosão, contínuo de baixa voltagem ou traço plano), a presença de ciclo do sono-vigília e a presença de convulsões. Foram feitas a ultrassonografia craniana em prematuros e a ressonância magnética (RMI) craniana em neonatos com EHI. Resultados: No grupo de prematuros, o traço patológico ou padrão descontínuo de baixa voltagem (p = 0,03) e a ausência de ciclo do sono-vigília (p = 0,019) foram associados a mortalidade e lesão cerebral avaliada por ultrassonografia craniana. Em pacientes com EHI, os padrões de convulsão nos traços do aEEG foram associados a mortalidade ou lesão cerebral na RMI craniana (p = 0,005). Conclusão: Este estudo corrobora os resultados anteriores e demonstra a utilidade do aEEG no monitoramento da função cerebral e na predição de alterações precoces nos grupos de neonatos estudados com risco elevado de lesão cerebral.

Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury.

OBJECTIVE: This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort of infants at high risk for brain injury in this center in Brazil. METHODS: This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude-integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed. RESULTS: In the preterm group, pathological trace or discontinuous low-voltage pattern (p=0.03) and absence of sleep-wake cycling (p=0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p=0.005). CONCLUSION: This study supports previous results and demonstrates the utility of amplitude-integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.

Collateral blood vessels in acute ischemic stroke: a physiological window to predict future outcomes / Circulação colateral no acidente vascular cerebral isquêmico: uma janela fisiológica para prever resultados futuros

ABSTRACT Collateral circulation is a physiologic pathway that protects the brain against ischemic injury and can potentially bypass the effect of a blocked artery, thereby influencing ischemic lesion size and growth. Several recent stroke trials have provided information about the role of collaterals in stroke pathophysiology, and collateral perfusion has been recognized to influence arterial recanalization, reperfusion, hemorrhagic transformation, and neurological outcomes after stroke. Our current aim is to summarize the anatomy and physiology of the collateral circulation and to present and discuss a comprehensible review of the related knowledge, particularly the effects of collateral circulation on the time course of ischemic injury and stroke severity, as well as imaging findings and therapeutic implications.

RESUMO A circulação colateral é um circuito fisiológico de proteção contra alterações isquêmicas que, potencialmente, evita os efeitos de uma oclusão arterial e com isso pode influenciar nas dimensões e no crescimento de uma lesão isquêmica. Vários estudos recentes forneceram informações a respeito do papel das colaterais na fisiopatologia do acidente vascular encefálico isquêmico e demonstraram a capacidade da circulação colateral de influenciar as taxas de reperfusão, recanalização, transformação hemorrágica e com isso desfecho clínico dos pacientes. O objetivo desta revisão é sintetizar a anatomia e a fisiologia da circulação colateral encefálica, apresentando e discutindo, o que se conhece atualmente acerca do seu efeito na cronologia e gravidade da lesão isquêmica, além dos achados de imagens e implicações terapêuticas.

Collateral blood vessels in acute ischemic stroke: a physiological window to predict future outcomes.

Collateral circulation is a physiologic pathway that protects the brain against ischemic injury and can potentially bypass the effect of a blocked artery, thereby influencing ischemic lesion size and growth. Several recent stroke trials have provided information about the role of collaterals in stroke pathophysiology, and collateral perfusion has been recognized to influence arterial recanalization, reperfusion, hemorrhagic transformation, and neurological outcomes after stroke. Our current aim is to summarize the anatomy and physiology of the collateral circulation and to present and discuss a comprehensible review of the related knowledge, particularly the effects of collateral circulation on the time course of ischemic injury and stroke severity, as well as imaging findings and therapeutic implications.