Accuracy of Plateau Pressure and Stress Index to Identify Injurious Ventilation in Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Guidelines suggest a plateau pressure (PPLAT) of 30 cm H(2)O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. METHODS: Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a "reference standard." Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics ("training set," N = 30). Accuracy of these values was assessed in a second group of patients ("validation set," N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; "physiological set," N = 50). RESULTS: Sensitivity and specificity of PPLAT of greater than 30 cm H(2)O were 0.06 (95% CI, 0.002-0.30) and 1.0 (95% CI, 0.87-1.00). PPLAT of greater than 25 cm H(2)O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35-0.97) and 0.75 (95% CI, 0.43-0.95) for PPLAT greater than 25 cm H(2)O versus 0.88 (95% CI, 0.47-1.00) and 0.50 (95% CI, 0.21-0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R(2) = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R(2) = 0.762). CONCLUSIONS: The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H(2)O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L

APHRODITE: Design and Preliminary Tests of an Autonomous and Reusable Photo-sensing Device for Immunological Test aboard the International Space Station

Preliminary results of the design and manufacturing of APHRODITE, a compact and versatile device for carrying out analyses of biological fluids during space missions that will be used as a technological demonstrator on board the International Space Station (ISS) for the quantitative determination of salivary biomarkers indicators of alterations of functionality of the immune system. The paper addresses the design of the main subsystems of the analytical device and the preliminary results obtained during the first implementations of the device subsystems and testing measurements. In particular, the system design and the experiment data output of the lab-on-chip photosensors and of the front-end readout electronics are reported in detail

Circulating Angiopoietins-1 and -2, Angiopoietin Receptor Tie-2 and Vascular Endothelial Growth Factor-A as Biomarkers of Acute Myocardial Infarction: a Prospective Nested Case-Control Study

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is up-regulated in myocardial ischemia. However, limited data exist assessing the value of circulating angiogenic biomarkers in predicting future incidence of acute myocardial infarction (AMI). Our aim was to examine the association between circulating levels of markers of angiogenesis with risk of incident acute myocardial infarction (AMI) in men and women.</p> <p>Methods</p> <p>We performed a case-control study (nested within a large cohort of persons receiving care within Kaiser Permanente of Northern California) including 695 AMI cases and 690 controls individually matched on age, gender and race/ethnicity.</p> <p>Results</p> <p>Median [inter-quartile range] serum concentrations of vascular endothelial growth factor-A (VEGF-A; 260 [252] vs. 235 [224] pg/mL; p = 0.01) and angiopoietin-2 (Ang-2; 1.18 [0.66] vs. 1.05 [0.58] ng/mL; p < 0.0001) were significantly higher in AMI cases than in controls. By contrast, endothelium-specific receptor tyrosine kinase (Tie-2; 14.2 [3.7] vs. 14.0 [3.1] ng/mL; p = 0.07) and angiopoietin-1 levels (Ang-1; 33.1 [13.6] vs. 32.5 [12.7] ng/mL; p = 0.52) did not differ significantly by case-control status. After adjustment for educational attainment, hypertension, diabetes, smoking, alcohol consumption, body mass index, LDL-C, HDL-C, triglycerides and C-reactive protein, each increment of 1 unit of Ang-2 as a Z score was associated with 1.17-fold (95 percent confidence interval, 1.02 to 1.35) increased odds of AMI, and the upper quartile of Ang-2, relative to the lowest quartile, was associated with 1.63-fold (95 percent confidence interval, 1.09 to 2.45) increased odds of AMI.</p> <p>Conclusions</p> <p>Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors.</p

Regulation of Endothelial Cell Adhesion Molecule Expression by Mast Cells, Macrophages, and Neutrophils

Leukocyte adhesion to the vascular endothelium and subsequent transendothelial migration play essential roles in the pathogenesis of cardiovascular diseases such as atherosclerosis. The leukocyte adhesion is mediated by localized activation of the endothelium through the action of inflammatory cytokines. The exact proinflammatory factors, however, that activate the endothelium and their cellular sources remain incompletely defined.Using bone marrow-derived mast cells from wild-type, Tnf(-/-), Ifng(-/-), Il6(-/-) mice, we demonstrated that all three of these pro-inflammatory cytokines from mast cells induced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, and E-selectin in murine heart endothelial cells (MHEC) at both mRNA and protein levels. Compared with TNF-α and IL6, IFN-γ appeared weaker in the induction of the mRNA levels, but at protein levels, both IL6 and IFN-γ were weaker inducers than TNF-α. Under physiological shear flow conditions, mast cell-derived TNF-α and IL6 were more potent than IFN-γ in activating MHEC and in promoting neutrophil adhesion. Similar observations were made when neutrophils or macrophages were used. Neutrophils and macrophages produced the same sets of pro-inflammatory cytokines as did mast cells to induce MHEC adhesion molecule expression, with the exception that macrophage-derived IFN-γ showed negligible effect in inducing VCAM-1 expression in MHEC.Mast cells, neutrophils, and macrophages release pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL6 that induce expression of adhesion molecules in endothelium and recruit of leukocytes, which is essential to the pathogenesis of vascular inflammatory diseases

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Extracorporeal CO2 removal and O2 transfer: A review of the concept, improvements and future development

Since the 70s, the extracorporeal carbon dioxide removal concept played a role in adjusting respiratory acidosis associated with Tidal Volume reduction in protective ventilation settings.Kolobow and Gattinoni in 1977 were the first in introducing extracorporeal support, with the intent to separate carbon dioxide removal from oxygen uptake: carbon dioxide was removed by a pump-driven modified ECMO with veno-venous bypass, while oxygenation was accomplished by high levels of PEEP, applying only a few ventilator breaths at low volumes and low peak inspiratory pressures (" lung rest" ) to prevent damage of the compromised lungs.Nevertheless extracorporeal support was restricted to controlled clinical trials because of the high incidence of serious complications like hemorrhage, hemolysis and neurological impairments.Technological improvement led to the implementation of different devices less invasive for the patient and less complex for clinician (however unable to transfer oxygen): the interventional Lung Assist (iLA) and the Veno-venous ECCO2R, which brought back attention to the CO2 removal concept.Is foreseeable the future development of more efficient devices capable of removing a substantial amount of carbon dioxide allowing a more protective ventilation. This would embody the modern mechanical ventilation philosophy: avoid tracheal tubes, minimize sedation, prevent VILI and hospital acquired infections. \ua9 2011 Elsevier Ltd

Comparison against current standards of a DNA aptamer for the label-free quantification of tobramycin in human sera employed for therapeutic drug monitoring.

The use of DNA aptamers in biosensors for the quantification of pharmaceuticals in the clinics would help to overcome the limitations of antibody-based detection for small molecules. The interest for such systems is proven by the ever-increasing number of aptamer-based solutions for analytics proposed in the literature as proof-of-concept demonstrators. Despite such diversity, these platforms often lack a comparative assessment of their performances against the current standard of practice in the clinics when using real samples. We employed an aptamer against tobramycin discovered in our laboratory to quantify through surface plasmon resonance the concentration of the antibiotic in clinical samples obtained from patients treated with tobramycin and undergoing therapeutic drug monitoring. We then compared the performances of our detection strategy against the current standard of practice. Our results show how, using adequate calibration and matrix complexity reduction, DNA aptamer-based direct assays can assess clinically relevant concentrations of small molecules in patient serum and with good correlation to current standards used in the clinics