Comparison of Modified Chandler, Roller Pump, and Ball Valve Circulation Models for In Vitro Testing in High Blood Flow Conditions: Application in Thrombogenicity Testing of Different Materials for Vascular Applications

Three different models, a modified Chandler loop, roller pump, and a new ball valve model (Hemobile), were compared with regard to intrinsic damage of blood components and activation of platelets. The Hemobile was used for testing of polymer tubes. High flow was not possible with the Chandler loop. The roller pump and the Hemobile could be adjusted to high flow, but he pump induced hemolysis. Platelet numbers were reduced in the roller pump and Chandler loop (P < 0.05), but remained high in the Hemobile. Platelet aggregation was reduced in all models. The Hemobile was applied for testing vascular graft materials, and allowed different circuits circulated simultaneously at 37°C. ePTFE, Dyneema Purity UHMWPE fiber and PET fiber based tubes, all showed hemolysis below 0.2% and reduced platelet count and function. Binding of fibrin and platelets was higer on PET, inflammatory markers were lowest on Dyneema Purity UHMWPE. We concluded that the Hemobile minimally affects blood and could be adjusted to high blood flows, simulating arterial shear stress. The Hemobile was used to measure hemocompatibility of graft material and showed Dyneema Purity UHMWPE fiber in many ways more hemocompatible than ePTFE and PET

Glomerular and Tubular Damage Markers Are Elevated in Patients With Diabetes

OBJECTIVE: We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid-binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: Damage markers were measured in triplicate in fresh morning urine samples and in plasma. RESULTS: Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87; all P ≤ 0.001). All urinary damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between -0.38 and -0.21; all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β -0.26; P = 0.037). CONCLUSIONS: Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease

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

Clinical use of cerebral oximetry in extremely preterm infants is feasible

Introduction: The research programme Safeguarding the Brains of our smallest Children (SafeBoosC) aims to test the benefits and harms of cerebral near-infrared spectroscopy (NIRS) oximetry in infants born before 28 weeks of gestation. In a phase II trial, infants will be randomised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to standard care with blinded NIRS-monitoring. The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin (rStO2) of 55 to 85% in percentage hours (burden). This study was a pilot of the Visible ­Oximetry Group. Material and methods: This was an observational study including ten infants. Results: The median gestational age was 26 weeks + three days, and the median start-up time was 133 minutes after delivery. The median recording time was 69.7 hours, mean rStO2 was 64.2 ± 4.5%, median burden of hyper- and hy­poxia was 30.3% hours (range 2.8-112.3). Clinical staff responded to an out of range value 29 times – only once to values above 85%. In comparison, there were 83 periods of more than ten minutes with an rStO2 below 55% and four episodes with an rStO2 above 85%. These periods accounted for 72% of the total hypoxia burden. A total of 18 of the 29 interventions were adjustments of FiO2 which in 13 of the 18 times resulted in an out-of-range SpO2. Two infants suffered second-degree burns from the sensor. Five infants died. In all cases, this was unrelated to NIRS monitoring and treatment. Conclusion: The intervention of early cerebral NIRS monitoring proved feasible, but prolonged periods of hypoxia went untreated. Thus, a revision of the treatment guideline and an alarm system is required

Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial

Objective To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in eight European countries. Participants 166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support. Interventions Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).Main outcome measures The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography. Randomisation Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (26 weeks).Blinding Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation. Results The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P&lt;0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device. Conclusions Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the ‘burden of hypoxia and hyperoxia’ expressed in ‘%hours’. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. Trial registration: ClinicalTrial.gov, NCT0159031

A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial.

BACKGROUND: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2. METHODS/DESIGN: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. DISCUSSION: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01590316.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A new system for right atrial cooling

Purpose. Controlled hypothermia of the right atrium has been shown to reduce postoperative atrial fibrillation after on-pump coronary artery bypass grafting. A device has been developed that couples right atrial and nodal cooling with modified dual-stage venous drainage by circulating cold sterile saline through an intracavity, shape-memory balloon. Description. The atrial cooling device was used in 41 patients undergoing elective coronary artery bypass grafting. Systemic temperatures were held at 36 degrees C, and temperatures of atrial structures were reduced to about 19 degrees to 20 degrees C at 30 minutes. Evaluation. Electrical activity was effectively suppressed during cross-clamp by controlled cooling of the right atrium. Hemodilution was reduced by right atrial isolation and collection of crystalloid cardioplegia. Cardiac electrical activity returned without sustained arrhythmias in all patients. Postoperative atrial fibrillation developed in only 3 of the 38 patients. Conclusions. The results indicate that local atrial cooling may contribute to protection of the right atrium, subsequently reducing the incidence of transient postoperative atrial fibrillation

Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity.

INTRODUCTION: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with the activation of inflammatory mediators that possess prothrombotic activity and could cause postoperative haemostatic disorders. This study was conducted to investigate the effect of cardiac surgery on prothrombotic activity in children undergoing cardiac surgery for complex cardiac defects. METHODS: Eighteen children (ages 3 to 163 months) undergoing univentricular palliation with total cavopulmonary connection (TCPC) (n = 10) or a biventricular repair (n = 8) for complex cardiac defects were studied. Prothrombotic activity was evaluated by measuring plasma levels of prothrombin fragment 1+2 (F1+2), thromboxane B2 (TxB2), and monocyte chemoattractant protein-1 (MCP-1). Anti-thrombotic activity was evaluated by measuring levels of tissue factor pathway inhibitor (TFPI) before, during, and after cardiac surgery. RESULTS: In all patients, cardiac surgery was associated with a significant but transient increase of F1+2, TxB2, TFPI, and MCP-1. Maximal values of F1+2, TxB2, and MCP-1 were found at the end of CPB. In contrast, maximal levels of TFPI were observed at the beginning of CPB. Concentrations of F1+2 at the end of CPB correlated negatively with the minimal oesophageal temperature during CPB. Markers of prothrombotic activity returned to preoperative values from the first postoperative day on. Early postoperative TFPI levels were significantly lower and TxB2 levels significantly higher in patients with TCPC than in those with biventricular repair. Thromboembolic events were not observed. CONCLUSION: Our data suggest that children with complex cardiac defects undergoing cardiac surgery show profound but transient imbalance between pro- and anti-thrombotic activity, which could lead to thromboembolic complications. These alterations are more important after TCPC than after biventricular repair but seem to be determined mainly by low antithrombin III