Immunogenicity of Golimumab and its Clinical Relevance in Patients With Ulcerative Colitis

2019 ◽  
Vol 25 (9) ◽  
pp. 1532-1540 ◽  
Author(s):  
Omoniyi J Adedokun ◽  
George R Gunn ◽  
Jocelyn H Leu ◽  
Cynthia Gargano ◽  
Zhenhua Xu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
False Negative ◽  
Injection Site Reaction ◽  
High Sensitivity ◽  
Fold Increase ◽  
Drug Interference ◽  
Negative Results ◽  
Drug Concentrations ◽  
Antidrug Antibody ◽  
Antibody Titers

Abstract Background Antidrug antibody (ADA) detection with standard bridging enzyme immunoassays (EIA) can yield false-negative results or underestimate titers through drug interference. A more sensitive assay was needed to determine clinical impact of antigolimumab antibodies. Methods A high-sensitivity, drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original EIA, and samples from induction/maintenance studies in golimumab-treated patients with ulcerative colitis were analyzed for ADAs using both methods. Immunogenicity results were compared, and pharmacokinetic, efficacy, and safety associations were evaluated. Results An 8-fold increase in ADA-positive patients (21.8% DT-EIA vs 2.8% EIA) reflected DT-EIA improved sensitivity and drug tolerance. Most newly detected ADA-positive patients (using DT-EIA) had low antibody titers, whereas most with high antibody titers were ADA-positive with original EIA. With DT-EIA, week 44 median trough serum golimumab concentrations among ADA-positive patients were approximately half vs ADA-negative (0.51 vs 0.85 µg/mL [50 mg q4w]; 0.85 vs 1.60 µg/mL [100 mg q4w]). Antidrug antibody impact on golimumab concentrations was more notable at titers ≥1:100. During induction, ADAs had no notable impact on efficacy. During maintenance, proportions of patients maintaining clinical response through week 54 were lower using DT-EIA: 38.1% ADA-positive and 52.8% ADA-negative. Antidrug antibody status had no impact on injection-site reaction incidence. Conclusions A more sensitive DT-EIA identified higher proportions of ADA-positive patients. A trend of decreasing drug concentrations with increasing ADA titers was observed. Pharmacokinetic impact was better elucidated with DT-EIA. Although development of ADA did not preclude efficacy, a trend toward decreased efficacy in ADA-positive vs ADA-negative patients was observed during maintenance treatment. Antidrug antibody status did not impact safety.

scholarly journals Visualization of Lesions of Metaphyses and Epiphyses of Bones in Newborns and Young Children

2021 ◽  
pp. 82-90
Author(s):  
N. A. Sholokhova
Keyword(s):  
Young Children ◽  
False Negative ◽  
Age Groups ◽  
High Sensitivity ◽  
Negative Results ◽  
False Negative Results ◽  
Inflammatory Processes ◽  
Group 5 ◽  
Magnetic Resonance Imaging Mri ◽  
Diagnostic Capabilities

The aim of this study was to determine the diagnostic capabilities of various methods of radiological diagnostics for lesions of the metaphyses and epiphyses of bones in newborns and young children.The study involved 108 children in the age group 5 days – 12 months with pathological changes in the pineal gland and bone metaphysis. The possibilities and advantages of standard radiography (СR), ultrasound examination (US) and magnetic resonance imaging (MRI) in the early and differential diagnosis of the osteomyelitis process and epiphyseolysis have been determined. High sensitivity (98 %), specificity (99 %) and accuracy (98 %) for ultrasound and sensitivity (94 %), specificity (89 %) and accuracy (95 %) of MRI in diagnosing osteomyelitis in patients of this age groups. At the same time, the possibilities of standard radiography at the stages of early diagnosis of inflammatory processes in the distal parts of the bones were limited due to a number of factors. The use of diagnostic algorithms greatly facilitates the work of a radiologist and reduces the number of false negative results during the initial treatment of patients.

CLINICAL APPLICATION OF COVID-19 REPORTING AND DATA SYSTEM IN COMPUTED TOMOGRAPHY OF BILATERAL PNEUMONIA DIAGNOSTIC

2021 ◽  
Vol 31 (4) ◽  
pp. 40-45
Author(s):  
Ugnė Kulnickaitė ◽  
Laura Dobrovaitė ◽  
Kamilė Grigaitė ◽  
Edvardas Jukna
Keyword(s):  
Computed Tomography ◽  
False Negative ◽  
High Sensitivity ◽  
Chest Ct ◽  
Data System ◽  
Negative Results ◽  
Radiological Society ◽  
Evaluation Scheme ◽  
False Negative Results ◽  
Standardized Reporting

Background: the 2019 coronavirus disease pandemic (COVID-19) has spread at an astonishing speed across the world, causing major morbidity and mortality. Computed tomography (CT) examination plays an important role in crisis areas in the diagnosis of COVID-19. COVID-19 Reporting and Data System (CO-RADS) has a five-point scale of suspicion for COVID-19 pneumonia in chest CT picture which standardizes the evaluation scheme and simplifies reporting. Aim: to summarise and present the role of COVID-19 Reporting and Data System in computed tomography of bilateral pneumonia diagnostic. Materials and methods: recently published studies were reviewed to evaluate COVID-19 Reporting and Data System scale as effective tool to detect COVID-19 pneumonia on chest CT scans. Databases from the subscription list of Lithuanian University of Health Sciences were selected: Medline (PubMed), SpringerLink and ScienceDirect. Results: chest CT features, as bilateral involvement, subpleural or peripherally distributed GGO, consolidation, reticulation, crazy paving pattern, air bronchogram signs, intralobular septal thickening, pulmonary vascular enlargement, are considered to be characteristic manifestations of COVID-19 infection. Studies show that Dutch Radiological Society presented CO-RADS scale sensitivity and specificity may vary from 61-88% and 66,4-98%, respectively. Conclusion: chest CT scan has a high sensitivity for COVID-19 diagnosis and could reduce false negative results obtained from RT-PCR tests. Furthermore, a standardized reporting system could increase clarification, minimize reporting variability and help radiologists recognize the results they observe, especially, for less experienced specialists.

scholarly journals Specific circulating immune complexes in acute chagas' disease

1987 ◽  
Vol 29 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Ricardo Corral ◽  
Héctor Freilij ◽  
Saúl Grinstein
Keyword(s):  
Chagas Disease ◽  
Immune Complexes ◽  
False Negative ◽  
High Sensitivity ◽  
Circulating Immune Complexes ◽  
Chronic Patients ◽  
Negative Results ◽  
Acute Toxoplasmosis ◽  
Acute Chagas Disease ◽  
Cruzi Infection

The presence of circulating immune complexes formed by IgM and IgG (CIC-IgM and CIC-IgG) was investigated, using antigen-specific enzyme-immunoassays (ELISA), in 30 patients with acute Chagas' disease who showed parasitemia and inoculation chagoma. Control population consisted of patients with chronic T. cruzi infection (30), acute toxoplasmosis 10), leishmaniasis (8), rheumatoid arthritis (3) and healthy individuals with negative serology for Chagas* disease (30). Acute chagasic patients were 100% CIC-IgG and 96.66% CIC-IgM positive whereas immunofluorescence tests yielded 90% and 86.66% of positivity for specific IgG and IgM antibodies, respectively. Chronic patients were 68% CIC-IgG and 0% CIC-IgM positive. The 30 negative and the 21 cross-reaction controls proved negative for ELISA (CIC-IgM and CIC-IgG). The high sensitivity of ELISA assays would allow early immunologic diagnosis, as well as prompt treatment, of acute T. cruzi infection, thus eliminating the problem of the false-positive and false-negative results which affects traditional methods for detection of circulating antibodies.

Pearls and Pitfalls of Interpretation in CT Colonography

2020 ◽  
Vol 71 (2) ◽  
pp. 140-148
Author(s):  
Michael Schonberger ◽  
Philippe Lefere ◽  
Abraham H. Dachman
Keyword(s):  
Computed Tomography ◽  
Sensitivity And Specificity ◽  
False Positive ◽  
Ct Colonography ◽  
False Negative ◽  
High Sensitivity ◽  
Negative Results ◽  
False Negative Results ◽  
The Common

The accuracy of computed tomography (CT) colonography (CTC) requires that the radiologist be well trained in the recognition of pitfalls of interpretation. In order to achieve a high sensitivity and specificity, the interpreting radiologist must be well versed in the causes of both false-positive and false-negative results. In this article, we review the common and uncommon pitfalls of interpretation in CTC.

scholarly journals Prozone-like phenomenon in travellers with fatal malaria: report of two cases

2015 ◽  
Vol 9 (03) ◽  
pp. 321-324 ◽  
Author(s):  
Lurdes Santos ◽  
Nuno Rocha Pereira ◽  
Paulo Andrade ◽  
Paulo Figueiredo Dias ◽  
Carlos Lima Alves ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
False Negative ◽  
Specific Antigen ◽  
Malaria Diagnosis ◽  
High Sensitivity ◽  
Rapid Diagnostic Tests ◽  
Microscopy Observation ◽  
Negative Results ◽  
False Negative Results ◽  
Potential Benefits

Malaria diagnosis remains a concern in non-endemic countries, with rapid diagnosis being crucial to improve patients’ outcome. Rapid diagnostic tests have high sensitivity but they also have flaws and false-negative results that might jeopardize malaria diagnosis. Some false-negative results might relate to a prozone-like effect. The authors describe two patients with false-negative rapid diagnostic tests in which a prozone-like effect might have been involved. The authors highlight that these tests should not be used without accompanying light microscopy observation of blood films and discuss potential benefits of using rapid diagnostic tests with more than one specific antigen for Plasmodium falciparum.

Exploring 'best practice' for nucleic acid detection of Neisseria gonorrhoeae

Sexual Health ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
David M. Whiley ◽  
Suzanne M. Garland ◽  
Geoffrey Harnett ◽  
Gary Lum ◽  
David W. Smith ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Neisseria Gonorrhoeae ◽  
Best Practice ◽  
Current Knowledge ◽  
False Negative ◽  
High Sensitivity ◽  
Nucleic Acid Detection ◽  
Predictive Values ◽  
Neisseria Species ◽  
Negative Results

Nucleic acid detection tests (NADT) have considerable benefits for the detection of Neisseria gonorrhoeae (GC), including high sensitivity across a range of specimen types and use under widely differing settings and conditions. However, sexual health practitioners and others who use data generated by NADT for GC should be aware of some important limitations of these tests. False-positive results caused by cross reaction with commensal Neisseria species have been observed in many assays, and have lead to unacceptably low positive-predictive values in some patient populations. Further, false-negative results can be caused by GC sequence variation, with some gonococci lacking certain NADT target sequences. This review examines the issues associated with gonococcal NADT and considers best practice for use of these assays based on current knowledge. We emphasise the need for supplementary testing and extensive assay validation, and suggest appropriate strategies for these requirements irrespective of the setting in which they are used. Further, we highlight the need to maintain culture-based testing for certain specimen sites as well as for antimicrobial resistance surveillance.

scholarly journals Cell-free DNA screening for aneuploidies in 7113 pregnancies: single Italian centre study

2020 ◽  
Vol 102 ◽  
Author(s):  
Alvaro Mesoraca ◽  
Katia Margiotti ◽  
Claudio Dello Russo ◽  
Anthony Cesta ◽  
Antonella Cima ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Clinical Performance ◽  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Sequencing Platform ◽  
Non Invasive ◽  
Negative Results ◽  
False Negative Results

Abstract Introduction Non-invasive prenatal testing (NIPT) using cell-free foetal DNA has been widely accepted in recent years for detecting common foetal chromosome aneuploidies, such as trisomies 13, 18 and 21, and sex chromosome aneuploidies. In this study, the practical clinical performance of our foetal DNA testing was evaluated for analysing all chromosome aberrations among 7113 pregnancies in Italy. Methods This study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing platform obtained from Altamedica Medical Centre in Rome, Italy. Results In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomies 13, 18 and 21. Out of the 7113 samples analysed, 74 cases (1%) were positive by NIPT testing; foetal karyotyping and follow-up results validated 2 trisomy 13 cases, 5 trisomy 18 cases, 58 trisomy 21 cases and 10 sex chromosome aneuploidy cases. There were no false-negative results. Conclusion In our hands, NIPT had high sensitivity and specificity for common chromosomal aneuploidies such as trisomies 13, 18 and 21.

scholarly journals Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
R. Hochstenbach ◽  
G. C. M. L. Page-Christiaens ◽  
A. C. C. van Oppen ◽  
K. D. Lichtenbelt ◽  
J. J. T. van Harssel ◽  
...  
Keyword(s):  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Maternal Weight ◽  
Noninvasive Prenatal Testing ◽  
Root Cause ◽  
Negative Results ◽  
False Negative Results ◽  
Negative Case

Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.

scholarly journals Assessment of the IgA Immunoassay Diagnostic Potential of the Mycobacterium tuberculosis MT10.3-MPT64 Fusion Protein in Tuberculous Pleural Fluid

2010 ◽  
Vol 17 (12) ◽  
pp. 1963-1969 ◽  
Author(s):  
Leonardo Silva Araujo ◽  
Renata Maciel Moraes ◽  
Anete Trajman ◽  
Maria Helena Féres Saad
Keyword(s):  
Pleural Fluid ◽  
Histopathological Examination ◽  
False Negative ◽  
High Sensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Negative Results ◽  
Diagnostic Potential ◽  
False Negative Results ◽  
Sds Page ◽  
Increased Sensitivity

ABSTRACT Pleural tuberculosis (PL-TB) remains difficult to diagnose. An enzyme-linked immunosorbent assay (ELISA) was developed based on a construction containing the fusion of the Rv3019c (MT10.3) and Rv1980c (MPT64) gene sequences, and its performance was evaluated in an area where TB is endemic. A total of 92 pleural fluid (PF) samples at serial dilutions of 1:50 to 1:800 were included in the ELISA IgA MT10.3-MPT64 evaluation: 70 from TB patients and 22 from patients with other pleurisies. Confirmation of the expression and subsequent purification of the protein was made by SDS-PAGE and Western blot assays, resulting in a 36-kDa protein. ELISA IgA MT10.3-MPT64 showed sensitivities of 61.4%, 58.6%, 62.9%, 67.1%, and 70% at each PF dilution, respectively. The cumulative results of all dilutions increased sensitivity to 81.4% without jeopardizing specificity. Similar results were also obtained at the combined dilutions of 1:50, 1:200, and 1:800 or 1:50 plus 1:800 dilutions (80%). The overall sensitivity of the reference test, i.e., histopathological examination, was 74%. But, via the ELISA IgA MT10.3-MPT64 test, sensitivity was high for specimens with a negative culture (23/27; 85.2%) or nonspecific histopathology (17/18; 94.4%). Our findings demonstrated the promising use of this test as an adjunct in PL-TB diagnoses, particularly in cases with lower bacterial loads and false-negative results in the reference tests, since the new test includes such important features as quick and easy application, high sensitivity and, perhaps most importantly, affordability, which is so crucial for its widespread use in developing countries.

scholarly journals Expression Profile of p53 and p21 in Large Bowel Mucosa as Biomarkers of Inflammatory-Related Carcinogenesis in Ulcerative Colitis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Cristiana Popp ◽  
Luciana Nichita ◽  
Theodor Voiosu ◽  
Alexandra Bastian ◽  
Mirela Cioplea ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Epithelial Cells ◽  
False Negative ◽  
Intraepithelial Neoplasia ◽  
Architectural Distortion ◽  
P53 Overexpression ◽  
Negative Results ◽  
False Negative Results ◽  
One Year ◽  
Tissue Biomarker

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results.

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