Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer.
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SUBMITTER: Kilmartin D
PROVIDER: S-EPMC8431498 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThe radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS.MethodsTwo series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA).ResultsMedian Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3-9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91-0.96) to 0.97 (CI 0.96-0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97-0.98), intra-observer LoA were ±0.9 points.ConclusionsReliability and agreement of the PS improved by using a consensus atlas.Key points• Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score.
| S-EPMC4869743 | biostudies-literature
Project description:BackgroundTear lipid morphology is important for normal tear function. Recently, there have been clinical studies using interferometry to assess lipid layer thickness (LLT). The aim of the study is to examine the repeatability of a commercially available interferometer.MethodsTwo observers measured LLT in twenty Asian subjects (20 eyes) using an interferometer (LipiView® ocular surface interferometer, TearScience Inc, Morrisville, NC). Dry eye symptoms, tear break up time (TBUT) and corneal fluorescein staining were also prospectively evaluated.ResultsData for 20 participants are presented for either right or left eye (randomly selected). The mean LLT ± standard deviation of these participants was 53.53 ± 14.59 nm. When a single observer repeated the imaging on the same day, the coefficient of repeatability was 16 nm and the 95% limits of agreement were between -11 nm and 18 nm. When a different observer repeated the scan, the coefficient of repeatability was 13 nm and limits of agreement were -9 nm and 16 nm. LLT was not significantly associated with TBUT, presence of any corneal staining in any corneal zones, or symptomatic status.ConclusionWith the repeatability of measurements being known, the significance of LLT changes measured by this interferometer may be better interpreted. In this small Asian study, the LLT was lower than previously reported studies.
| S-EPMC4462010 | biostudies-literature
Project description:The NIMO TEMPO (Lambda-X, Nivelles, Belgium) is a novel, user-friendly and compact device designed for in vitro optical analysis of refractive and diffractive intraocular lenses (IOLs). This device analyzes the IOL wavefront and generates a synthetic eye model for numerical computation. The objective of this study was to evaluate the precision of this innovative device. Intra- and inter-observer variability were calculated using a two-way analysis of variance (ANOVA) after conducting ten measurements of eight different IOL models, with each measurement being repeated by three distinct operators (resulting in a total of 30 measurements for each IOL). The device demonstrated satisfactory intra- and inter-observer variability in evaluating IOL power and modulation transfer function (MTF) profiles, with values of 0.066 and 0.078 diopters for IOL power and 0.018 and 0.019 for MTF measurements, respectively. Furthermore, this hybrid optical and numerical in vitro IOL wavefront analyzer appears to have several advantages over conventional optical bench devices. It reduces the need for operator manipulation, and allows for numerical modeling of various optical environments, including cornea models and apertures. In conclusion, this novel metrology device designed for refractive and diffractive IOLs appears to provide a satisfactory precision, making it a promising tool in the field of IOL metrology.
| S-EPMC10813881 | biostudies-literature
Project description:Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.
| S-EPMC10208956 | biostudies-literature
Project description:Immunotherapy has emerged as a promising and effective treatment for cancer, yet the clinical benefit is still variable, in part due to insufficient accumulation of immune effector cells in the tumour microenvironment. Better understanding of tumour-infiltrating lymphocytes (TILs) from nonhuman primate tumours could provide insights into improving effector cell accumulation in tumour tissues during immunotherapy. Here, we characterize TILs in a cynomolgus macaque tumour model in which the tumours were infiltrated with CD4+ and CD8+ T cells and were eventually rejected. The majority of CD4+ and CD8+ TILs exhibited a CD45RA-CCR7- effector memory phenotype, but unlike circulating T cells, they expressed CD69, a marker for tissue-resident memory T (TRM) cells. CD69-expressing CD8+ TILs expressed high levels of the cytotoxic molecule granzyme B and the co-inhibitory receptor PD-1. Consistent with the TRM cell phenotype, CD8+ TILs minimally expressed CX3CR1 but expressed CXCR3 at higher levels than circulating CD8+ T cells. Meanwhile, CXCL9, CXCL10 and CXCL11, chemokine ligands for CXCR3, were expressed at high levels in the tumours, thus attracting CXCR3+CD8+ T cells. These results indicate that tumour-transplanted macaques can be a useful preclinical model for studying and optimizing T cell accumulation in tumours for the development of new immunotherapies.
| S-EPMC7242367 | biostudies-literature
Project description:BackgroundMusculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel.MethodsThis inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed an in-vivo observation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as "correct" or "incorrect" following a standardized assessment protocol. Re-testing followed 7-10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model.ResultsInter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain.ConclusionsOur results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain.
| S-EPMC3552977 | biostudies-literature
Project description:To measure the inter-expert and intra-expert agreement in sleep spindle scoring, and to quantify how many experts are needed to build a reliable dataset of sleep spindle scorings.The EEG dataset was comprised of 400 randomly selected 115s segments of stage 2 sleep from 110 sleeping subjects in the general population (57±8, range: 42-72 years). To assess expert agreement, a total of 24 Registered Polysomnographic Technologists (RPSGTs) scored spindles in a subset of the EEG dataset at a single electrode location (C3-M2). Intra-expert and inter-expert agreements were calculated as F1-scores, Cohen's kappa (?), and intra-class correlation coefficient (ICC).We found an average intra-expert F1-score agreement of 72±7% (?: 0.66±0.07). The average inter-expert agreement was 61±6% (?: 0.52±0.07). Amplitude and frequency of discrete spindles were calculated with higher reliability than the estimation of spindle duration. Reliability of sleep spindle scoring can be improved by using qualitative confidence scores, rather than a dichotomous yes/no scoring system.We estimate that 2-3 experts are needed to build a spindle scoring dataset with 'substantial' reliability (?: 0.61-0.8), and 4 or more experts are needed to build a dataset with 'almost perfect' reliability (?: 0.81-1).Spindle scoring is a critical part of sleep staging, and spindles are believed to play an important role in development, aging, and diseases of the nervous system.
| S-EPMC4426257 | biostudies-literature
Project description:Background and purposeThe delineation of the gross tumor volume (GTV) is a critical step for radiation therapy treatment planning. The delineation procedure is typically performed manually which exposes two major issues: cost and reproducibility. Delineation is a time-consuming process that is subject to inter- and intra-observer variability. While methods have been proposed to predict GTV contours, typical approaches ignore variability and therefore fail to utilize the valuable confidence information offered by multiple contours.Materials and methodsIn this work we propose an automatic GTV contouring method for soft-tissue sarcomas from X-ray computed tomography (CT) images, using deep learning by integrating inter- and intra-observer variability in the learned model. Sixty-eight patients with soft tissue and bone sarcomas were considered in this evaluation, all underwent pre-operative CT imaging used to perform GTV delineation. Four radiation oncologists and radiologists performed three contouring trials each for all patients. We quantify variability by defining confidence levels based on the frequency of inclusion of a given voxel into the GTV and use a deep convolutional neural network to learn GTV confidence maps.ResultsResults were compared to confidence maps from the four readers as well as ground-truth consensus contours established jointly by all readers. The resulting continuous Dice score between predicted and true confidence maps was 87% and the Hausdorff distance was 14 mm.ConclusionResults demonstrate the ability of the proposed method to predict accurate contours while utilizing variability and as such it can be used to improve clinical workflow.
| S-EPMC8934266 | biostudies-literature
Project description:BackgroundColon capsule endoscopy is a promising technique for evaluation of the colon, but its reproducibility is still unknown.ObjectiveThis study assesses intra and inter-observer agreement in evaluations of colon capsule endoscopy videos.MethodsForty-two complete colon capsule endoscopy investigations were analysed by three experts and two beginners. Intra-observer agreement was assessed in paired readings of two experts and two beginners. Agreement was determined by the intraclass correlation coefficient: poor (<0.5), moderate (0.5-0.75), good (0.75-0.9) and excellent (>0.9).ResultsAgreement on 'indication for a following colonoscopy' based on the number and size of detected polyps and bowel cleansing quality was poor among all observers. Agreement among experts on the detection of large polyps and number of polyps was moderate, but agreement on bowel cleansing quality was poor. Beginners were in moderate agreement with the experts on polyp detection. Intra-observer agreement in experts was moderate to excellent for the detection of large polyps (≥10 mm), excellent for the number of polyps, and poor to moderate for bowel cleansing quality. Intra-observer agreement in beginners was poor to moderate for all variables.ConclusionsThis study shows a poor agreement on 'indication for a following colonoscopy', but a high intra and inter-observer agreement for polyp detection among experts, as well as a moderate agreement between beginners and experts.Trial registration: NCT02303756.
| S-EPMC6297930 | biostudies-literature
Project description:The purpose of this study was to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) in melanoma and to determine whether a simpler numerical scoring system would be more effective. In total, 655 patients presenting to a UK teaching hospital with primary invasive melanoma were analyzed. TILs were rescored using the standard Clark's method and univariable and multivariable analyses of the effect of TILs on overall survival (OS), disease-specific survival (DSS), and metastasis-free survival (MFS) was assessed using Cox regression. In total, 30 (5%) melanomas showed absent, 464 (71%) nonbrisk, and 161 (24%) brisk TILs. There was a statistically significant relationship between TILs and Breslow thickness, age, melanoma type, mitotic rate, and histologic regression. TIL grade was a significant predictor of MFS in multivariable analysis (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.77) but was not significant for OS or DSS. By contrast, when a simple numerical TIL percentage score was used this was a strong predictor of OS (HR, 0.55; 95% CI, 0.38-0.78), DSS (HR, 0.25; 95% CI, 0.14-0.44), and MFS (HR, 0.32; 95% CI, 0.21-0.51) in multivariable analysis. The percentage TIL score was also significant when adjusted for the prognostic gold standard, American Joint Committee on Cancer stage: OS (HR, 0.66; 95% CI, 0.46-0.95), DSS (HR, 0.33; 95% CI, 0.19-0.60), and MFS (HR, 0.41; 95% CI, 0.26-0.65). The TIL percentage score was subsequently validated in new cases. In summary, this study strongly confirms that higher amounts of TILs are associated with better prognosis and in addition demonstrates the value of a simplified numerical TIL scoring system.
| S-EPMC6171741 | biostudies-literature