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- Bao, J, et al.
(författare)
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Spa-RQ: an Image Analysis Tool to Visualise and Quantify Spatial Phenotypes Applied to Non-Small Cell Lung Cancer
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 17613-
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Tidskriftsartikel (refereegranskat)abstract
- To facilitate analysis of spatial tissue phenotypes, we created an open-source tool package named ‘Spa-RQ’ for ‘Spatial tissue analysis: image Registration & Quantification’. Spa-RQ contains software for image registration (Spa-R) and quantitative analysis of DAB staining overlap (Spa-Q). It provides an easy-to-implement workflow for serial sectioning and staining as an alternative to multiplexed techniques. To demonstrate Spa-RQ’s applicability, we analysed the spatial aspects of oncogenic KRAS-related signalling activities in non-small cell lung cancer (NSCLC). Using Spa-R in conjunction with ImageJ/Fiji, we first performed annotation-guided tumour-by-tumour phenotyping using multiple signalling markers. This analysis showed histopathology-selective activation of PI3K/AKT and MAPK signalling in Kras mutant murine tumours, as well as high p38MAPK stress signalling in p53 null murine NSCLC. Subsequently, Spa-RQ was applied to measure the co-activation of MAPK, AKT, and their mutual effector mTOR pathway in individual tumours. Both murine and clinical NSCLC samples could be stratified into ‘MAPK/mTOR’, ‘AKT/mTOR’, and ‘Null’ signature subclasses, suggesting mutually exclusive MAPK and AKT signalling activities. Spa-RQ thus provides a robust and easy to use tool that can be employed to identify spatially-distributed tissue phenotypes.
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- Blom, S, et al.
(författare)
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Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 15580-
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Tidskriftsartikel (refereegranskat)abstract
- The paradigm of molecular histopathology is shifting from a single-marker immunohistochemistry towards multiplexed detection of markers to better understand the complex pathological processes. However, there are no systems allowing multiplexed IHC (mIHC) with high-resolution whole-slide tissue imaging and analysis, yet providing feasible throughput for routine use. We present an mIHC platform combining fluorescent and chromogenic staining with automated whole-slide imaging and integrated whole-slide image analysis, enabling simultaneous detection of six protein markers and nuclei, and automatic quantification and classification of hundreds of thousands of cells in situ in formalin-fixed paraffin-embedded tissues. In the first proof-of-concept, we detected immune cells at cell-level resolution (n = 128,894 cells) in human prostate cancer, and analysed T cell subpopulations in different tumour compartments (epithelium vs. stroma). In the second proof-of-concept, we demonstrated an automatic classification of epithelial cell populations (n = 83,558) and glands (benign vs. cancer) in prostate cancer with simultaneous analysis of androgen receptor (AR) and alpha-methylacyl-CoA (AMACR) expression at cell-level resolution. We conclude that the open-source combination of 8-plex mIHC detection, whole-slide image acquisition and analysis provides a robust tool allowing quantitative, spatially resolved whole-slide tissue cytometry directly in formalin-fixed human tumour tissues for improved characterization of histology and the tumour microenvironment.
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- Bluth, Thomas, et al.
(författare)
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Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients : A Randomized Clinical Trial.
- 2019
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 321:23, s. 2292-2305
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Tidskriftsartikel (refereegranskat)abstract
- Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.
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- Bluth, T., et al.
(författare)
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Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE) : study protocol for a randomized controlled trial
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients.Methods/design: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index >= 35 kg/m(2) scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH(2)O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH(2)O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint.Discussion: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs.
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- Peelen, W. H. A., et al.
(författare)
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CO2 dissolution into a 52/48 mol % Li/Na carbonate melt and the molten carbonate fuel cell cathode
- 2000
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 147:6, s. 2122-2125
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Tidskriftsartikel (refereegranskat)abstract
- O2- concentration relaxation experiments in a 52/48 moi % Li/Na molten carbonate melt saturated with NiO were performed. The Ni2+ was added to act as a probe for the O2- concentration. The dynamic behavior of the CO2 and O2- concentration during the relaxation of the melt back to the initial equilibrium was studied by recording square wave voltammograms. Our experiments show clearly that CO2 dissolution is the slowest step in the relaxation. Consequently the values for the recombination reaction rate obtained in other studies are not correct, since in them a fast CO2 dissolution was assumed.(1,2) A CO2 gas dissolution rate of 25(+/-5) 10(-4) cm/s and Henry's constant for CO2 of 20(+/-3) mu mol atm(-1) cm(-3) at 650 degrees C could be determined. Our numbers were used in simple calculations of the performance of the porous molten carbonate fuel cell cathode, and indicate that the CO2 dissolution rate determines the lower limit for p(CO2) Of 0.05 arm at 150 mA/cm(2) for proper cathode operation.
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- Serpa Neto, Ary, et al.
(författare)
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Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT) : an international, multicentre, prospective study
- 2016
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600 .- 2213-2619. ; 4:11, s. 882-893
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Tidskriftsartikel (refereegranskat)abstract
- Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [V-T] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27-33), representing 0.14 cases per ICU bed over a 1-week period. V-T was similar for patients at risk and not at risk of ARDS (median 7.6 mL/kg PBW [IQR 6.7-9.1] vs 7.9 mL/kg PBW [6.8-9.1]; p=0.346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6.0 cm H2O [IQR 5.0-8.0] vs 5.0 cm H2O [5.0-7.0]; p<0.0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0.004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p<0.0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p<0.0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p<0. 0001). V-T did not differ between patients who did and did not develop ARDS (p=0.471 for those at risk of ARDS; p=0.323 for those not at risk). Interpretation Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS.
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| 11. |
- Simonis, Fabienne D., et al.
(författare)
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Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS : a secondary analysis of PRoVENT
- 2018
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Ingår i: Annals of Intensive Care. - : Springer Berlin/Heidelberg. - 2110-5820. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients. Methods: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality. Results: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the 'Lung Injury Prediction Score' and received lower maximum airway pressure (P-max), driving pressure (Delta P), positive end-expiratory pressure, and FiO(2) levels. Tidal volume size was similar between the groups. Higher P-max was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. Delta P was not independently associated with in-hospital mortality, but reliable values for Delta P were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence. Conclusions: Higher P-max was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS.
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