| 891. |
- Kallner, Anders, et al.
(author)
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Repeatability imprecision from analysis of duplicates of patient samples and control materials
- 2020
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 80:3, s. 210-214
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Journal article (peer-reviewed)abstract
- Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.
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| 892. |
- Kankel, Jennifer, et al.
(author)
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Differential effects of low dose lidocaine on C-fiber classes in humans
- 2012
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In: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 13:12, s. 1232-1241
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Journal article (peer-reviewed)abstract
- The nonselective sodium channel blocker lidocaine is widely used as a local anesthetic but also systemically for treatment of postoperative and neuropathic pain. Voltage-gated sodium channels are crucial for action potential generation and conduction, and their availability controls the amount of activity-dependent conduction velocity slowing. This important axonal property, as assessed by microneurography, is used to differentiate human mechanoinsensitive (silent) nociceptors from the classical polymodal nociceptors. In the current study, microneurography was used to assess axonal properties of the 2 main nociceptor classes in humans, before and after intradermal injection of lidocaine .1% or control saline solution in the receptive field. In mechanosensitive nociceptors, lidocaine reduced baseline conduction velocity and turned activity-dependent slowing into speeding of conduction. In contrast, mechanoinsensitive fibers were not affected in their baseline conduction velocity or their activity-dependent slowing, but probability of conduction block with repetitive stimulation increased. Recovery cycles showed reduced hyperpolarization in all C-fiber classes after lidocaine injections. These results support our hypothesis that sodium channel subtypes are differentially expressed in the 2 nociceptor classes of mechanosensitive C-fibers (CMs) and mechanoinsensitive C-fibers (CMis).Perspective: This study reveals that microneurography can be used to assess pharmacologicaleffects on single C-fibers directly in humans.
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| 893. |
- Karamanakos, Petros N., et al.
(author)
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Malignant giant cell tumor in the posterior fossa of a neonate : case report
- 2010
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In: Journal of Neurosurgery. - 1933-0707 .- 1933-0715. ; 5:3, s. 277-282
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Journal article (peer-reviewed)abstract
- Giant cell tumors (GCTs) of the bone are rare, usually benign but locally aggressive neoplasms that primarily occur in the epiphyses of long bones. They seldom develop in the cranium; when they do, they involve principally the sphenoid and temporal bones. These tumors usually affect young adults, and few reports in children have been published. Primary malignant GCTs of the skull are even more uncommon. The 3 published cases all involved adults over 40 years of age. Herein, the authors present a case of a highly aggressive primary malignant GCT of the posterior fossa in a 5-week old preterm infant. One month after the gross-total resection of the tumor found in the bone, the infant's condition rapidly deteriorated and she died. Magnetic resonance imaging and postmortem examination revealed a tumor larger than it had been before the operation, with expansion toward the brain. To the best of the authors' knowledge, this is the youngest patient reported with a primary malignant GCT of the skull, and actually the first case in a pediatric patient. In addition, the extremely high growth rate of the tumor in the postoperative period renders this case the most aggressive primary malignant GCT of the cranium described so far.
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| 894. |
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| 895. |
- Karawajczyk, Malgorzata, et al.
(author)
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The Near-Patient Testing Instrument HemoScreen can be used for Rapid Evaluation of Peripheral Blood Cell Counts in Patients with COVID-19
- 2023
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In: Family Medicine and Primary Care: Open Access. - : Gavin Publishers. - 2688-7460. ; 7:1, s. 1-7
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Journal article (peer-reviewed)abstract
- Objectives: Analysis of peripheral blood cell counts are important in the workup of patients with suspected Corona virus disease 2019 (COVID-19). Blood cell counts are usually analyzed on large cell counters that require transport of the samples. Point-of-care (POC) testing reduces the test-turnaround times. The aim of the present study was to evaluate if the HemoScreen™instrument could be used for point of care testing of blood samples from COVID-19 patients. Methods: We compared CBC results from 49 patients with COVID-19 infections analyzed with HemoScreen™ and Sysmex XN-9000. Results: There were strong correlations between the results obtained with Sysmex XN-9000 and HemoScreen™ according to Deming correlations for White Blood Cells (WBC): WBCHemoScreen™ = 0.944* WBCSysmex - 0.093; r2 = 0.988, Neutrophils: NeutrophilsHemoScreen™= 1.029* NeutrophilsSysmex + 0.090; r2 = 0.957, Lymphocytes: LymphocytesHemoScreen™ = 0.944* LymphocytesSysmex - 0.107; r2 = 0.964, Platelets (PLT): PLTHemoScreen™ = 1.056* PLTSysmex + 9.468; r2 = 0.988, and Red blood cells (RBC) RBCHemoScreen™ = 0.955* RBCSysmex - 0.003; r2 = 0.991. Conclusions: The HemoScreen™ instrument provided fast and accurate test results when analyzing blood samples from COVID-19 patients. This instrument can be used in settings where the transport time to the central laboratory from remote locations such as field hospitals can be long.
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| 896. |
- Karimi, Nasibeh, et al.
(author)
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Tetraspanins distinguish separate extracellular vesicle subpopulations in human serum and plasma - Contributions of platelet extracellular vesicles in plasma samples
- 2022
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 11:5
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Journal article (peer-reviewed)abstract
- Background: The ability to isolate extracellular vesicles (EVs) from blood is vital in the development of EVs as disease biomarkers. Both serum and plasma can be used, but few studies have compared these sources in terms of the type of EVs that are obtained. The aim of this study was to determine the presence of different subpopulations of EVs in plasma and serum. Method: Blood was collected from healthy subjects, and plasma and serum were isolated in parallel. ACD or EDTA tubes were used for the collection of plasma, while serum was obtained in clot activator tubes. EVs were isolated utilising a combination of density cushion and SEC, a combination of density cushion and gradient or by a bead antibody capturing system (anti-CD63, anti-CD9 and anti-CD81 beads). The subpopulations of EVs were analysed by NTA, Western blot, SP-IRIS, conventional and nano flow cytometry, magnetic bead E LISA and mass spectrometry. Additionally, different isolation protocols for plasma were compared to determine the contribution of residual platelets in the analysis. Results: This study shows that a higher number of CD9(+) EVs were present in EDTA-plasma compared to ACD-plasma and to serum, and the presence of CD41a on these EVs suggests that they were released from platelets. Furthermore, only a very small number of EVs in blood were double-positive for CD63 and CD81. The CD63(+) EVs were enriched in serum, while CD81(+) vesicles were the rarest subpopulation in both plasma and serum. Additionally, EDTA-plasma contained more residual platelets than ACD-plasma and serum, and two centrifugation steps were crucial to reduce the number of platelets in plasma prior to EV isolation. Conclusion: These results show that human blood contains multiple subpopulations of EVs that carry different tetraspanins. Blood sampling methods, including the use of anti-coagulants and choice of centrifugation protocols, can affect EV analyses and should always be reported in detail.
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| 897. |
- Karlsson, Mats G., 1960-, et al.
(author)
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Quantitative computerized image analysis of immunostained lymphocytes : A methodological approach
- 1994
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In: Pathology, Research and Practice. - München, Germany : Elsevier. - 0344-0338 .- 1618-0631. ; 190:8, s. 799-807
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Journal article (peer-reviewed)abstract
- A methodological approach by computerized image analysis to quantify immunostained objects in histological sections is described. We have investigated antibodies against CD4, CD8, CD20, CD23 and CD25 in frozen sections of human nasal mucosa; however, the methodology of standardization is of general validity. The study was designed particularly to investigate the following points: 1) light intensity, 2) the grey level for counter staining intensity, 3) the grey level threshold value for positive objects, 4) the minimal acceptable size of a positive object, 5) the influence of the brightness of the light on both the number and the area of objects. Furthermore, random sampling and determination of 6) the area per section, and 7) the number of histological sections to be measured per biopsy. Finally, a study of reproducibility of immunostaining intensity was performed. The influence of the different parameters mentioned above was studied and the values (eg. threshold value) for our particular setting of microscope, image analysis equipment, computer software etc, were defined. The method was then tested for intra- and interindividual variation which was found to be less than 5%. Correlation analysis of the reproducibility gave coefficients of correlation of 0.99, both concerning number of immunopositive objects and immunopositive area. We emphasize the importance of a highly standardized methodology if the numeric data obtained from computer assisted image analysis are to be more accurate than semiquantitative assessments by experienced observers. With a thorough standardization as described in this method it is possible to obtain numeric values, and data with low deviations, which are two obvious and important advantages.
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| 898. |
- Kaviani, Sepideh, et al.
(author)
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Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique
- 2018
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In: Nutrition in Clinical Practice. - : Wiley. - 0884-5336. ; 33:2, s. 206-216
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Journal article (peer-reviewed)abstract
- Background: Several indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion. Methods: Eight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2 and CO2 recovery were calculated. Results: For accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1 Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were reliable for at least 1 variable (CV ≤ 3%). For multiple regression, humidity and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P <.001). Temperature and amount of burned methanol were significant predictors of O2 recovery (R2 = 0.18, P <.001); only humidity was a predictor for CO2 recovery (R2 = 0.15, P <.001). Conclusions: Omnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions.
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| 899. |
- Kaviani, Sepideh, et al.
(author)
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Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique
- 2017
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In: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 31:S1
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Journal article (peer-reviewed)abstract
- ObjectiveThere are several indirect calorimetry (IC) instruments commercially available but validity and reliability data is lacking. Site-to-site inconsistencies in protocols and subject characteristics, and comparisons to a “gold standard” instrument or method which may no longer be accurate enough, have put restraints on drawing conclusions about instruments' performance.PurposeTo compare the accuracy and reliability of different metabolic carts using the methanol combustion technique as the criterion measure.MethodsA total of eight, 20-minute methanol burn trials were completed on 12 metabolic carts (2 Cosmed Quark CPET, 2 DeltaTrac II, 2 Parvo Medics TrueOne 2400, 2 Iaeger Oxycon Pros, 2 Omnicals, a Vmax Encore, and a Max-II Metabolic System) at 11 international study sites. Methanol tests were performed at 0700, 1000, 1300, and 1600 hours on 2 consecutive days. Respiratory Exchange Ratio (RER) and percent (%) recovery of O2 and CO2 were calculated after each test.ResultsAccuracy – 1 Omnical, Cosmed, and Parvo were accurate in measuring RER and % recovery O2, while 1 DeltaTrac was also accurate for % recovery O2. The same Cosmed and Parvo, and the other DeltaTrac were accurate in measuring % recovery CO2. Reliability – 8 instruments were shown to be reliable with the two Omnicals ranking best based on the smallest coefficient of variation (CV) (all CV(s) 1.26%). Both Cosmeds, Parvos, DeltaTracs and 1 Vmax were the reliable instruments for at least one variable (CV(s) 3%). Multiple Regression– Humidity, amount of methanol combusted, and temperature were tested as predictors of IC outcomes. Humidity and amount of combusted methanol were significant predictors of RER (F (2, 60) =10.91, p<0.001, R2=0.33). Temperature and amount of burned methanol were significant predictors of % recovery O2 (F (2, 60) =8.32, p<0.001, R2=0.18) while only humidity was a predictor for % recovery CO2 (F (1, 61) =21.10, p<0.001, R2=0.15).ConclusionOmnical, Cosmed, and Parvo showed superior accuracy and reliability; however, accuracy was only found at one of two study sites. Exogenous factors such as humidity and temperature may be influencing instrument performance and could be modified in the lab to optimize IC conditions.
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| 900. |
- Kerr, Keith M, et al.
(author)
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Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer : In what state is this art?
- 2015
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In: Journal of Thoracic Oncology. - 1556-0864 .- 1556-1380. ; 10:7, s. 985-989
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Journal article (peer-reviewed)abstract
- Therapeutic antibodies to programmed death receptor 1 (PD-1) and its ligand PD-L1 show promising clinical results. Anti-PD-L1 immunohistochemistry (IHC) may be a biomarker to select patients more likely to respond to these treatments. However, the development of at least four different therapeutics, each with a different anti-PD-L1 IHC assay, has raised concerns among pathologists and oncologists alike. This article reviews existing data on the IHC biomarker aspects of studies using these drugs in non-small-cell lung cancer (NSCLC) and considers the challenges ahead, should these drug/IHC assay combinations reach routine practice. For each the known biomarker assays in development, there is a different monoclonal IHC antibody clone, produced by one of two diagnostics companies. Each test requires proprietary staining platforms and uses different definitions of a "positive" test for PD-L1 expression, on tumor cells and, in one test, also on tumor infiltrating immune cells. There are still considerable gaps in our knowledge of the technical aspects of these tests, and of the biological implications and associations of PD-L1 expression in NSCLC, considering heterogeneity of expression, dynamic changes in expression, and prognostic implications among other factors. The International Association for the Study of Lung Cancer Pathology Committee raises the prospect of trying not only to harmonize and standardize testing for PD-L1 by IHC, at least at a technical level, but also, ideally, as a predictive marker, to facilitate availability of this test and a promising treatment for patients with NSCLC.
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