Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth. Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis

Технология извлечения структур знаний с использованием аппарата расширенных семантических сетей

В статье рассматривается задача извлечения из текстов естественного языка структур знаний: информационных объектов («именованных сущностей»), их свойств, связей и фактов участия в действиях. Для этих целей разработан инструментарий: язык представления знаний (расширенные семантические сети – РСС) и их обработки (язык преобразования структур – ДЕКЛ). На этой основе созданы технологии, которые обладают следующими особенностями. Из текстов извлекаются не отдельные объекты (именованные сущности), а структуры знаний, представляющие связи объектов и их участие в действиях и событиях. Для извлечения структур знаний разработан уникальный семантико-ориентированный лингвистический процессор (ЛП), осуществляющий глубинный анализ текстов ЕЯ и выявляющий десятки типов объектов вместе с их структурами. Процессор ЛП управляется лингвистическими знаниями, представляющими собой декларативные структуры и обеспечивающие быструю настройку ЛП на предметную область и язык. Основой лингвистических знаний являются правила, обладающие высокой степенью избирательности при выявлении объектов («сущностей»), средствами устранения коллизий при их применении. Это позволяет минимизировать шумы и потери.У статті розглядається задача знайдення у текстах природної мови структур знань: інформаційних об’єктів («іменованих сутностей»), їх якостей зв’язків і фактів участі у діях. Для цих цілей розроблений інструментарій: мова представлення знань (розширені семантичні мережі – РСМ) та їх обробки (мова перетворення структур – ДЕКЛ). На цій основі створені технології, що мають наступні особливості. З тестів виділяються не окремі об’єкти (іменовані сутності), а структури знань, що представляють зв’язки об’єктів та їх участь у діях та подіях. З метою виділення структур знань розроблений винятковий семантико-орієнтований лінгвістичний процесор (ЛП), що здійснює глибинний аналіз текстів ЕЯ та виявляє десятки типів об’єктів разом з їх структурами. Процесор ЛП керується лінгвістичними знаннями, які представляють собою декларативні структури та забезпечують швидке настроювання ЛП на предметну сферу та мову. Основою лінгвістичних знань є правила, що мають високий ступінь вибірковості при виявленні об’єктів («сутностей»), засобами усунення колізій при їхньому використанні. Це дозволяє мінімізувати шуми та втрати.The paper is devoted to the extracting of knowledge structures from the natural language texts, i.e. information objects (“Named Entities”), their features, relationships, and participation in the actions and events. For this purpose, the language used for knowledge representation (extended semantic networks/ESN) and tools for processing (language for structure conversion LSC) are considered. On this base, the new technologies are proposed. These technologies have the following features: extraction from the texts of knowledge structures that represent the links of named entities and their participation in actions and events. For the knowledge extraction the unique semantic-oriented language processor (LP) are designed. Processor LP provides the deep analysis of NL-texts and revealing set of objects together with their structures. Processor LP is controlled by the linguistic knowledge, which are declarative structures (on ESN) and which provides the quick tuning of LP on subject area and language, both Russian and English

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment

Background and Purpose—In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods—aEEG patterns and regional cerebral oxygen saturation (rScO 2) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results—In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P<0.05). rScO 2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO 2 asymmetry ratio of 4.5% (interquartile range, −4.3% to 5.9%; P<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO 2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO 2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<−1 SD) at a median of 24.0 (interquartile range, 18.4–24.4) months of age. Conclusions—Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions

Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants

OBJECTIVES. A hemodynamically important patent ductus arteriosus is a common problem in the first week of life in the preterm infant. Although patent ductus arteriosus induces alterations in organ perfusion, scarce information is available of the impact of patent ductus arteriosus and its subsequent treatment on the oxygen supply and oxygen extraction of the brain. We investigated the impact of patent ductus arteriosus and its treatment with indomethacin on regional cerebral oxygen saturation and fractional tissue oxygen extraction by using near-infrared spectroscopy. PATIENTS AND METHODS. Twenty infants with patent ductus arteriosus (gestational age: RESULTS. Mean arterial blood pressure and regional cerebral oxygen saturation were significantly lower and fractional tissue oxygen extraction significantly higher compared with the control infants during patent ductus arteriosus (mean arterial blood pressure: 33 +/- 5 vs 38 +/- 6 mm Hg; regional cerebral oxygen saturation: 62% +/- 9% vs 72% +/- 10%; fractional tissue oxygen extraction: 0.34 +/- 0.1 vs 0.25 +/- 0.1, respectively). Regional cerebral oxygen saturation and fractional tissue oxygen extraction were lower and higher, respectively, up to 24 hours after the start of indomethacin but normalized to control values afterward. Indomethacin had no additional negative effect on cerebral oxygenation. CONCLUSIONS. A hemodynamically significant patent ductus arteriosus has a negative effect on cerebral oxygenation in the premature infant. Subsequent and adequate treatment of a patent ductus arteriosus may prevent diminished cerebral perfusion and subsequent decreased oxygen delivery, which reduces the change of damage to the vulnerable immature brain

Effects of caffeine on the preterm brain : An observational study

BACKGROUND AND AIM: Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. METHODS: Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD. RESULTS: 34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected. CONCLUSION: Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity