Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional ...lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.
Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, and most cases are caused by mutations affecting the type I collagen genes. ...Here, we describe a new mouse model for Osteogenesis imperfecta termed Aga2 (abnormal gait 2) that was isolated from the Munich N-ethyl-N-nitrosourea mutagenesis program and exhibited phenotypic variability, including reduced bone mass, multiple fractures, and early lethality. The causal gene was mapped to Chromosome 11 by linkage analysis, and a C-terminal frameshift mutation was identified in the Col1a1 (procollagen type I, alpha 1) gene as the cause of the disorder. Aga2 heterozygous animals had markedly increased bone turnover and a disrupted native collagen network. Further studies showed that abnormal proalpha1(I) chains accumulated intracellularly in Aga2/+ dermal fibroblasts and were poorly secreted extracellularly. This was associated with the induction of an endoplasmic reticulum stress-specific unfolded protein response involving upregulation of BiP, Hsp47, and Gadd153 with caspases-12 and -3 activation and apoptosis of osteoblasts both in vitro and in vivo. These studies resulted in the identification of a new model for Osteogenesis imperfecta, and identified a role for intracellular modulation of the endoplasmic reticulum stress-associated unfolded protein response machinery toward osteoblast apoptosis during the pathogenesis of disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:To utilize real-time electrical impedance tomography to guide lung protective ventilation in an animal model of acute respiratory distress syndrome.
DESIGN:Prospective animal study.
...SETTING:Animal research center.
SUBJECTS:Twelve Yorkshire swine (15 kg).
INTERVENTIONS:Lung injury was induced with saline lavage and augmented using large tidal volumes. The control group (n = 6) was ventilated using ARDSnet guidelines, and the electrical impedance tomography–guided group (n = 6) was ventilated using guidance with real-time electrical impedance tomography lung imaging. Regional electrical impedance tomography–derived compliance was used to maximize the recruitment of dependent lung and minimize overdistension of nondependent lung areas. Tidal volume was 6 mL/kg in both groups. Computed tomography was performed in a subset of animals to define the anatomic correlates of electrical impedance tomography imaging (n = 5). Interleukin-8 was quantified in serum and bronchoalveolar lavage samples. Sections of dependent and nondependent regions of the lung were fixed in formalin for histopathologic analysis.
MEASUREMENTS AND MAIN RESULTS:Positive end-expiratory pressure levels were higher in the electrical impedance tomography–guided group (14.3 cm H2O vs. 8.6 cm H2O; p < 0.0001), whereas plateau pressures did not differ. Global respiratory system compliance was improved in the electrical impedance tomography–guided group (6.9 mL/cm H2O vs. 4.7 mL/cm H2O; p = 0.013). Regional electrical impedance tomography–derived compliance of the most dependent lung region was increased in the electrical impedance tomography group (1.78 mL/cm H2O vs. 0.99 mL/cm H2O; p = 0.001). Pao2/FIO2 ratio was higher and oxygenation index was lower in the electrical impedance tomography–guided group (Pao2/FIO2388 mm Hg vs. 113 mm Hg, p < 0.0001; oxygentation index, 6.4 vs. 15.7; p = 0.02) (all averages over the 6-hr time course). The presence of hyaline membranes (HM) and airway fibrin (AF) was significantly reduced in the electrical impedance tomography–guided group (HMEIT 42% samples vs. HMCONTROL 67% samples, p < 0.01; AFEIT 75% samples vs. AFCONTROL 100% samples, p < 0.01). Interleukin-8 level (bronchoalveolar lavage) did not differ between the groups. The upper and lower 95% limits of agreement between electrical impedance tomography and computed tomography were ± 16%.
CONCLUSIONS:Electrical impedance tomography–guided ventilation resulted in improved respiratory mechanics, improved gas exchange, and reduced histologic evidence of ventilator-induced lung injury in an animal model. This is the first prospective use of electrical impedance tomography–derived variables to improve outcomes in the setting of acute lung injury.
Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary ...impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use.
Atelectasis during general anesthesia is a risk for perioperative complications. EIT measurements were performed in mechanically ventilated healthy children during elective surgery to demonstrate the ...changes in ventilation distribution during general anesthesia. The ventilation distribution was quantified by calculating the Global Inhomogeneity index (GI).
EIT measurements were performed in 23 children (9 weeks-10 years) without lung disease to detect changes in regional ventilation during elective surgery. Three previously defined time points were marked during the measurement: after intubation and start of pressure-controlled ventilation (PCV), change to pressure support ventilation (PSV), and after extubation (spontaneous breathing-SB). Ventilation distribution based on regions of interest (ROI) and changes in end-expiratory volume (∆EELV) were collected at these time points and compared. The Global Inhomogeneity index was calculated at the beginning of pressure-controlled ventilation (PCV).
With increasing spontaneous breathing, dorsal recruitment of atelectasis occurred. The dorsal ventilation fraction increased over the time of general anesthesia with increasing spontaneous breathing, whereas the ventral fraction decreased relatively (Difference ± 5.5 percentage points respectively; 95% CI; 3.5-7.4; p < 0.001). With the onset of spontaneous breathing, there was a significant reduction in end-expiratory volume (Difference: 105 ml; 95% CI, 75-135; p < 0.001). The GI of the lung-healthy ventilated children is 47% (SD ± 4%).
Controlled ventilation of healthy children resulted in increased ventilation of the ventral and collapse of the dorsal lung areas. Restart of spontaneous breathing after cessation of surgery resulted in an increase in ventilation in the dorsal with decrease in the ventral lung areas. By calculating the GI, representing the ratio of more to less ventilated lung areas, revealed the presumed homogeneous distribution of ventilation.
ClinicalTrials.gov Registration ID: NCT04873999. First registration: 05/05/2021.
We describe two adolescents (13 and 16 years old) with severe tick-borne encephalitis (TBE) and vaccination breakthrough (VBT). Both suffer from severe persistent neurologic sequelae. Both patients ...had high TBE-IgG-titers after vaccination at the beginning of the infection and a low or missing TBE-IgM response (Type 2 vaccine failure). Neutralization tests show low titers against the respective infecting TBE virus strain and higher titers against the vaccine strain at the beginning of the infection implying an individual weak or impaired immune response to the respective virus as possible cause of TBE vaccine failure.
We do not know of any similar observation or explanation for the phenomenon and at the moment can only speculate of a severe course correlated to highly mismatched IgG. This constellation of high TBE IgGs, the lack of immune response and a severe course strongly resembles the severe TBE courses that occurred in the past after TBE immunoglobulin administration.
To our knowledge differentiation between structural and functional antibodies by neutralization tests with a) the affecting TBE virus strain and b) the vaccine virus strain in TBE vaccine failures has never been described before. We conclude (1) to consider a TBE virus infection also in vaccinated children presenting with meningoencephalitis, (2) to perform a broad immunological work-up in severe TBE especially after VBT, (3) to further study if high mismatch IgG's are a possible reason for vaccine failure.
Patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) are vulnerable to ventilator-induced lung injury. Although this syndrome affects the lung heterogeneously, mechanical ...ventilation is not guided by regional indicators of potential lung injury. We used electrical impedance tomography (EIT) to estimate the extent of regional lung overdistension and atelectasis during mechanical ventilation. Techniques for tidal breath detection, lung identification, and regional compliance estimation were combined with the Graz consensus on EIT lung imaging (GREIT) algorithm. Nine ALI/ARDS patients were monitored during stepwise increases and decreases in airway pressure. Our method detected individual breaths with 96.0% sensitivity and 97.6% specificity. The duration and volume of tidal breaths erred on average by 0.2 s and 5%, respectively. Respiratory system compliance from EIT and ventilator measurements had a correlation coefficient of 0.80. Stepwise increases in pressure could reverse atelectasis in 17% of the lung. At the highest pressures, 73% of the lung became overdistended. During stepwise decreases in pressure, previously-atelectatic regions remained open at sub-baseline pressures. We recommend that the proposed approach be used in collaborative research of EIT-guided ventilation strategies for ALI/ARDS.
Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients ...indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes.
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