Tolerating higher partial pressures of carbon dioxide (PCO
) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term ...neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial.
Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO
or to a control group with mildly elevated PCO
targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI).
There were no differences in body weight, length and head circumference between the two PCO
target groups. Median Mental Developmental Index (MDI) values were 82 (60-96, high target) and 84 (58-96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57-100) and 84 (65-96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment.
A higher PCO
target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO
targets to optimise short-term outcomes is a safe option.
ISRCTN56143743.
•Robust Methodology with Real Scans: Real scans were used to robustly compare the performance of DLDand IR.•Objective and Subjective Metrics Validate DLD: Objective metrics and subjective ratings ...confirm DLD's effectiveness.•Strong Inter-Rater Agreement Validates Subjective Assessments: Radiologists agree on DLD quality at 25% radiation dose.•Significant Reduction in Radiation Dose: DLD allows significant radiation dose reduction of up to 75% with maintained image quality.
Computed tomography (CT) scans are a significant source of medically induced radiation exposure. Novel deep learning-based denoising (DLD) algorithms have been shown to enable diagnostic image quality at lower radiation doses than iterative reconstruction (IR) methods. However, most comparative studies employ low-dose simulations due to ethical constraints. We used real intraindividual animal scans to investigate the dose-reduction capabilities of a DLD algorithm in comparison to IR.
Fourteen veterinarian-sedated alive pigs underwent 2 CT scans on the same 3rd generation dual-source scanner with two months between each scan. Four additional scans ensued each time, with mAs reduced to 50 %, 25 %, 10 %, and 5 %. All scans were reconstructed ADMIRE levels 2 (IR2) and a novel DLD algorithm, resulting in 280 datasets. Objective image quality (CT numbers stability, noise, and contrast-to-noise ratio) was measured via consistent regions of interest. Three radiologists independently rated all possible dataset combinations per time point for subjective image quality (−1 = inferior, 0 = equal, 1 = superior). The points were averaged for a semiquantitative score, and inter-rater agreement was measured using Spearman's correlation coefficient and adequately corrected mixed-effects modeling analyzed objective and subjective image quality.
Neither dose-reduction nor reconstruction method negatively impacted CT number stability (p > 0.999). In objective image quality assessment, the lowest radiation dose achievable by DLD when comparing noise (p = 0.544) and CNR (p = 0.115) to 100 % IR2 was 25 %. Overall, inter-rater agreement of the subjective image quality ratings was strong (r ≥ 0.69, mean 0.93 ± 0.05, 95 % CI 0.92–0.94; each p < 0.001), and subjective assessments corroborated that DLD at 25 % radiation dose was comparable to 100 % IR2 in image quality, sharpness, and contrast (p ≥ 0.281).
The DLD algorithm can achieve image quality comparable to the standard IR method but with a significant dose reduction of up to 75%. This suggests a promising avenue for lowering patient radiation exposure without sacrificing diagnostic quality.
The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients.
A total of 134 patients (62 females; age range, 26 to 83 years) ...underwent the erythromycin breath test as a phenotyping probe of CYP3A. Genomic DNA was screened for six variants of suspected functional relevance in CYP3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*17, and CYP3A4*18) and CYP3A5 (CYP3A5*3C and CYP3A5*6).
CYP3A activity (AUC(0-40 min)) varied up to 14-fold in this population. No variants in the CYP3A4 and CYP3A5 genes were a significant predictor of CYP3A activity (P > 0.2954). CYP3A activity was reduced by approximately 50% in patients with concurrent elevations in liver transaminases and alkaline phosphatase or elevated total bilirubin (P < 0.001). In a multivariate analysis, CYP3A activity was not significantly influenced by age, sex, and body size measures (P > 0.05), but liver function combined with the concentration of the acute-phase reactant, alpha-1 acid glycoprotein, explained approximately 18% of overall variation in CYP3A activity (P < 0.001).
These data suggest that baseline demographic, physiologic, and chosen genetic polymorphisms have a minor impact on phenotypic CYP3A activity in patients with cancer. Consideration of additional factors, including the inflammation marker C-reactive protein, as well as concomitant use of other drugs, food constituents, and complementary and alternative medicine with inhibitory and inducible effects on CYP3A, is needed to reduce variation in CYP3A and treatment outcome to anticancer therapy.
CT low-dose simulation methods have gained significant traction in protocol development, as they lack the risk of increased patient exposure. However, in-vivo validations of low-dose simulations are ...as uncommon as prospective low-dose image acquisition itself. Therefore, we investigated the extent to which simulated low-dose CT datasets resemble their real-dose counterparts.
Fourteen veterinarian-sedated alive pigs underwent three CT scans on the same third generation dual-source scanner with 2 months between each scan. At each time, three additional scans ensued, with mAs reduced to 50%, 25%, and 10%. All scans were reconstructed using wFBP and ADMIRE levels 1-5. Matching low-dose datasets were generated from the 100% scans using reconstruction-based and DICOM-based simulations. Objective image quality (CT numbers stability, noise, and signal-to-noise ratio) was measured via consistent regions of interest. Three radiologists independently rated all possible dataset combinations per time point for subjective image quality (-1=inferior, 0=equal, 1=superior). The points were averaged for a semiquantitative score, and inter-rater-agreement was measured using Spearman's correlation coefficient. A structural similarity index (SSIM) analyzed the voxel-wise similarity of the volumes. Adequately corrected mixed-effects analysis compared objective and subjective image quality. Multiple linear regression with three-way interactions measured the contribution of dose, reconstruction mode, simulation method, and rater to subjective image quality.
There were no significant differences between objective and subjective image quality of reconstruction-based and DICOM-based simulation on all dose levels (p≥0.137). However, both simulation methods produced significantly lower objective image quality than real-dose images below 25% mAs due to noise overestimation (p<0.001; SSIM≤89±3). Overall, inter-rater-agreement was strong (r≥0.68, mean 0.93±0.05, 95% CI 0.92-0.94; each p<0.001). In regression analysis, significant decreases in subjective image quality were observed for lower radiation doses (b ≤ -0.387, 95%CI -0.399 to -0.358; p<0.001) but not for reconstruction modes, simulation methods, raters, or three-way interactions (p≥0.103).
Simulated low-dose CT datasets are subjectively and objectively indistinguishable from their real-dose counterparts down to 25% mAs, making them an invaluable tool for efficient low-dose protocol development.
Management of a patient's body temperature is an important aspect of care that should be addressed by targeted temperature management (TTM). Often, non-invasive methods like forced-air blankets are ...used. Especially in the operating room this management may be a subsidiary and repetitive task requiring constant observation of the patient's body temperature and adaption using the limited set of available settings. Thus, automation of TTM is a feasible target to improve patient outcome and reduce caregiver workload.
A Philips IntelliVue MP 50 patient monitor with an arterial PiCCO catheter system was used to measure patient blood temperature. Thermal management was performed with a 3M Bair Hugger 755 warming unit with forced air blankets. The warming unit was extended by a computer interface to allow for remote and automated control. A proposed closed-loop algorithm reads the measured temperature and performs automated control of the 3M Bair Hugger. Evaluation was performed in an experimental intensive care setting for animal studies. Two fully automated trials are compared with two manual and two uncontrolled trials in the same study setting using six female pigs for prolonged observation times of up to 90 hours in each trial.
The developed system and proposed algorithm allow more precise temperature management by keeping a set target temperature within a range of ± 0.5 °C in 88% of the observation time and within a range of ± 1.0 °C at all times. The proposed algorithm yielded better performance than did manual control or uncontrolled trials. It was able to adapt to individual patient needs as it is more dynamic than look-up table approaches with fixed settings for various temperatures.
Closed-loop TTM using non-invasive forced-air warming blankets was successfully tested in a porcine study with the proposed hardware interface and control algorithm. This automation can be beneficial for patient outcome and can reduce caregiver workload and patient risk in clinical settings. As temperature readings are most often available, existing devices like the 3M Bair Hugger can easily be expanded. However, even if clinical application is feasible, open questions regarding approval and certification of such automated systems within the current legal situation still need to be answered.
AIM To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.METHODS Eight pigs underwent a midline laparotomy ...following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy.RESULTS Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 m L/min) increased to a maximum flow of 1873 ± 175 m L/min at manifestation of ALF, which was significantly elevated(P < 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 m L/min at study end. Thrombocyte values (baseline 307 × 103/μL± 34 × 103/μL) of intoxicated animals declined slowly to values of 145 × 103/μL± 46 × 103/μL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 103/μL± 3 × 103/μL preceding fatality within few hours which was significant(P > 0.01).CONCLUSION Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.
•Cerebral oxygenation during the course of AAP-induced ALF in pigs was monitored.•PtiO2 increased 2h after ALF and stayed stable until nine hours before death.•A strong negative linear correlation ...was found between PtiO2 and ICP.•ICP and PtiO2 indicate impending damage before serious complications occur.•Their use should be considered in order to protect endangered brain function.
Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF.
ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs. All animals underwent invasive hemodynamic and neuromonitoring and were maintained under standardized intensive care support. Neuromonitoring consisted of continuous intraparenchymatous recording of intracranial pressure and brain partial oxygen pressure. Hemodynamic and ventilation parameters were continuously recorded; laboratory parameters were analysed every eight hours. Mean values were compared using the Wilcoxon test.
Acute liver failure occurred in all intoxicated animals after 23±2h, resulting in death due to ALF after further 15±2h. Continuous neuromonitoring was performed in all animals during the whole experiment without observing signs of intracranial haemorrhage. Two hours after manifestation of ALF an increase in brain tissue oxygen (PtiO2) was observed. Brain oxygenation stayed stable until nine hours before death. Intracranial pressure (ICP) remained basically at a plateau level until manifestation of ALF. In the following ten hours a linear and slow increase was observed until five hours before death, followed by a fast and continuous rise in ICP to a final level of 35±1mmHg. Cerebral perfusion pressure (CPP) began to decrease 25h prior to exitus, further decreasing to 18±2mmHg at the end of the experiment. A strong negative linear correlation was found between PtiO2 and ICP (R=0.97). Arterial partial pressure of oxygen (PaO2) below 100mmHg was associated with lower PtiO2 levels. Changes in arterial partial pressure of carbon dioxide (PaC02) did not influence PtiO2 values. Hemoglobin values below 7g/dl were associated with lower PtiO2 values.
The results of our experiments demonstrate that ICP and PtiO2 measurements indicate impending damage well before serious complications occur and their use should be considered in order to protect endangered brain function in the presence of acetaminophen-induced ALF.
Background
Automated systems are available in various application areas all over the world for the purpose of reducing workload and increasing safety. However, such support systems that would aid ...caregivers are still lacking in the medical sector. With respect to workload and safety, especially, the intensive care unit appears to be an important and challenging application field. Whereas many closed-loop subsystems for single applications already exist, no comprehensive system covering multiple therapeutic aspects and interactions is available yet. This paper describes a fully closed-loop intensive care therapy and presents a feasibility analysis performed in three healthy pigs over a period of 72 h each to demonstrate the technical and practical implementation of automated intensive care therapy.
Methods
The study was performed in three healthy, female German Landrace pigs under general anesthesia with endotracheal intubation. An arterial and a central venous line were implemented, and a suprapubic urinary catheter was inserted. Electrolytes, glucose levels, acid-base balance, and respiratory management were completely controlled by an automated fuzzy logic system based on individual targets. Fluid management by adaption of the respective infusion rates for the individual parameters was included.
Results
During the study, no manual modification of the device settings was allowed or required. Homoeostasis in all animals was kept stable during the entire observation period. All remote-controlled parameters were maintained within physiological ranges for most of the time (free arterial calcium 73%, glucose 98%, arterial base excess 89%, and etCO
2
98%). Subsystem interaction was analyzed.
Conclusions
In the presented study, we demonstrate the feasibility of a fully closed-loop system, for which we collected high-resolution data on the interaction and response of the different subsystems. Further studies should use big data approaches to analyze and investigate the interactions between the subsystems in more detail.
Rossit et al. (2011) showed that neglect patients perform normally in a propointing task but not in an antipointing task which requires pointing towards the mirrored position of a target. It is ...assumed that antipointing relies on information from the perceptual pathway of our visual brain. Therefore, this finding supports the notion that neglect is a disorder that primarily affects perceptual spatial representations within the brain leaving spatial maps used for visuomotor guidance intact. Alternatively, performance of patients might be compromised in both tasks, but only obviously so in tasks in which online corrections are made more difficult. It can be argued that online-corrections via visual feedback are less effective in antipointing because a direct comparison between hand and target is not possible in this condition. Secondly, it is also known that neglect patients have a pronounced egocentric bias which is assumed to be associated with a deviation of the perceived body midline. Since the midline is used to compute the end-position in the antipointing task this could also explain why patients are worse in antipointing. We investigated the influence of visual feedback on pro- and antipointing and the effect of providing a visual reference line for the antipointing task in right-brain damaged patients with neglect (n = 20), right-brain damaged patients without neglect (n = 23) and in a group of healthy participants (n = 22). The withdrawal of visual feedback had a stronger effect on propointing compared to antipointing. This effect was stronger in neglect patients than in patients without neglect or healthy controls. The introduction of a reference line reduced errors in antipointing performance, particularly in neglect patients with a strong egocentric bias. The results support our alternative account and challenge the hypothesis that the spatial disorder in neglect affects primarily perceptual maps within the visual system.
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