Diagnostic utility of serum and pleural levels of adenosine deaminase 1–2, and interferon-γ in the diagnosis of pleural tuberculosis

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2014.369 ◽

2014 ◽

Vol 9 ◽

Author(s):

Sibel Yurt ◽

Canan Küçükergin ◽

Burcu Arpinar Yigitbas ◽

Şule Seçkin ◽

Hüseyin Cem Tigin ◽

...

Keyword(s):

Adenosine Deaminase ◽

Sensitivity And Specificity ◽

Operating Characteristic ◽

Roc Curves ◽

Interferon Γ ◽

Diagnostic Efficiency ◽

Pleural Tuberculosis ◽

Study Population ◽

Ifn Γ ◽

Underlying Diseases

Background: To evaluate and compare the diagnostic efficiency of serum (s) and pleural (p) levels of adenosine deaminase (ADA)-1, ADA-2, total ADA, and interferon-gamma (IFN-γ) for the differential diagnosis of pleural tuberculosis (TB). Methods: Clinical and analytic data of 93 consecutive patients with pleural effusions from May 2012 to February 2013 were prospectively evaluated. The study population included 43 pleural TB, 23 malignancies, and 27 other exudates. The median and interquartile range of ADA-1, ADA-2, total ADA, and IFN-γ were evaluated according to their underlying diseases. Results: There were no significant differences in sADA-1 and sIFN-γ values among each group. pADA-1, pADA-2, total pADA, and pIFN-γ levels were significantly higher in patients with pleural TB than in other patients (p < 0.0001). As for pleural TB receiving operating characteristic (ROC) curves identified the following results. The best cut-off value for pADA-2 was 20.37 U/L and it yielded a sensitivity and specificity of 95.35% and 86%, respectively. Taking a cut-off value of 40.68 U/L for total pADA, the sensitivity and the specificity were found to be 88.37% and 88%, respectively. ROC curve identified 110 U/L as the best cut-off value for pμg/ml, while the sensitivity and the specificity were 74.42% and 68%, respectively. Finally, the best cut-off value for pADA-1 was 16.8 U/L and yielded a sensitivity and specificity of 69.77% and 68%, respectively. Conclusions: To distinguish pleural TB, pleural levels of ADA-2 have the highest sensitivity among the different diagnostic parameters and may find a place as routine investigation for early detection of TB in the future.

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The Utility of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio in Pleural Tuberculosis

Respiration ◽

10.1159/000509555 ◽

2020 ◽

pp. 1-5

Author(s):

Amanda Beukes ◽

Jane Alexandra Shaw ◽

Andreas H. Diacon ◽

Elvis M. Irusen ◽

Coenraad F.N. Koegelenberg

Keyword(s):

Lactate Dehydrogenase ◽

Adenosine Deaminase ◽

Pleural Fluid ◽

Operating Characteristic ◽

Retrospective Studies ◽

Characteristic Curve ◽

Diagnostic Efficiency ◽

Pleural Tuberculosis ◽

High Incidence ◽

The Mean

In high-burden settings, the diagnosis of pleural tuberculosis (TB) is frequently inferred in patients who present with lymphocyte predominant exudative effusions and high adenosine deaminase (ADA) levels. Two recent small retrospective studies suggested that the lactate dehydrogenase (LDH)/ADA ratio is significantly lower in TB than in non-TB pleural effusions and that the LDH/ADA ratio may be useful in differentiating pleural TB from other pleural exudates. We compared the pleural LDH/ADA ratios, ADA levels, and lymphocyte predominance of a prospectively collected cohort of patients with proven pleural TB (n = 160) to those with a definitive alternative diagnosis (n = 68). The mean pleural fluid LDH/ADA ratio was lower in patients with pleural TB than alternative diagnoses (6.2 vs. 34.3, p < 0.001). The area under the receiver operating characteristic curve was 0.92 (p < 0.001) for LDH/ADA ratio and 0.88 (p < 0.001) for an ADA ≥40 U/L alone. A ratio of ≤12.5 had the best overall diagnostic efficiency, while a ratio of ≤10 had a specificity of 90% and a positive predictive value of 95%, with a sensitivity of 78%, making it a clinically useful “rule in” value for pleural TB in high incidence settings. When comparing the LDH/ADA ratio to an ADA level ≥40 U/L in the presence of a lymphocyte predominant effusion, the latter performed better. When lymphocyte values are unavailable, our data suggest that the LDH/ADA ratio is valuable in distinguishing TB effusions from other pleural exudates.

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Combining interferon-γ release assays with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection

Journal of International Medical Research ◽

10.1177/0300060520925660 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052092566

Author(s):

Dingfeng Lv ◽

Yanqing Liu ◽

Fei Guo ◽

Aihua Wu ◽

Yijun Mo ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Operating Characteristic ◽

Early Stage ◽

Roc Curves ◽

Interferon Γ ◽

Tuberculosis Infection ◽

Mycobacterium Tuberculosis Infection ◽

Ifn Γ ◽

Extra Pulmonary ◽

Youden’S Index

Objective To investigate the possibility of combining tuberculosis (TB)-interferon (IFN)-γ release assays (IGRAs) with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection. Methods We performed a retrospective study of 166 TB patients [68 patients with pulmonary tuberculosis TB (PTB) and 98 patients with extra-pulmonary TB (EPTB)] diagnosed in our hospital between January 2016 and May 2018 along with 377 non-TB patients. The diagnostic performance of the TB-IGRA was evaluated using receiver operating characteristic (ROC) curves. Youden’s index was used to determine the optimal cut-off threshold. Results IFN-γ release in patients with PTB and EPTB were dramatically higher compared with non-TB patients (203.58±18.00 pg/mL, 201.83±14.56 pg/mL and 32.12±4.36 pg/mL, respectively). IFN-γ release was positively correlated with lymphocyte counts and percentages in patients with PTB (r = 0.252 and r = 0.278, respectively) and EPTB (r = 0.229 and r = 0.298, respectively). No correlation was observed in non-TB patients. The area under the ROC curve for TB-IGRA was 0.884. When the optimal cut-off value for IFN-γ (14 pg/mL, Youden’s index 0.661) was applied, the sensitivity was 88.6% and the specificity was 77.5%. Conclusions Combining TB-IGRA with lymphocyte enumeration was effective for diagnosis of early-stage Mycobacterium tuberculosis infection.

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Diagnostic performances of manual and automated reticulocyte parameters in anaemic cats

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x17699067 ◽

2017 ◽

Vol 20 (2) ◽

pp. 122-127 ◽

Cited By ~ 2

Author(s):

Saverio Paltrinieri ◽

Marco Fossati ◽

Valentina Menaballi

Keyword(s):

Receiver Operating Characteristic ◽

Sensitivity And Specificity ◽

Operating Characteristic ◽

Positive Likelihood Ratio ◽

Roc Curves ◽

Blood Samples ◽

Production Index ◽

Instrumental Measurement ◽

Sensitivity Specificity ◽

Reticulocyte Production

Objectives The objective of this study was to evaluate the diagnostic performances of manual and instrumental measurement of reticulocyte percentage (Ret%), reticulocyte number (Ret#) and reticulocyte production index (RPI) to differentiate regenerative anaemia (RA) from non-regenerative anaemia (NRA) in cats. Methods Data from 106 blood samples from anaemic cats with manual counts (n = 74; 68 NRA, six RA) or instrumental counts of reticulocytes (n = 32; 25 NRA, seven RA) collected between 1995 and 2013 were retrospectively analysed. Sensitivity, specificity and positive likelihood ratio (LR+) were calculated using either cut-offs reported in the literature or cut-offs determined from receiver operating characteristic (ROC) curves. Results All the reticulocyte parameters were significantly higher in cats with RA than in cats with NRA. All the ROC curves were significantly different ( P <0.001) from the line of no discrimination, without significant differences between the three parameters. Using the cut-offs published in literature, the Ret% (cut-off: 0.5%) was sensitive (100%) but not specific (<75%), the RPI (cut-off: 1.0) was specific (>92%) but not sensitive (<15%), and the Ret# (cut-off: 50 × 10³/µl) had a sensitivity and specificity >80% and the highest LR+ (manual count: 14; instrumental count: 6). For all the parameters, sensitivity and specificity approached 100% using the cut-offs determined by the ROC curves. These cut-offs were higher than those reported in the literature for Ret% (manual: 1.70%; instrumental: 3.06%), lower for RPI (manual: 0.39; instrumental: 0.59) and variably different, depending on the method (manual: 41 × 10³/µl; instrumental: 57 × 10³/µl), for Ret#. Using these cut-offs, the RPI had the highest LR+ (manual: 22.7; instrumental: 12.5). Conclusions and relevance This study indicated that all the reticulocyte parameters may confirm regeneration when the pretest probability is high, while when this probability is moderate, RA should be identified using the RPI providing that cut-offs <1.0 are used.

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Comparative accuracy of pleural fluid unstimulated interferon-gamma and adenosine deaminase for diagnosing pleural tuberculosis: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0253525 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253525

Author(s):

Ashutosh Nath Aggarwal ◽

Ritesh Agarwal ◽

Sahajal Dhooria ◽

Kuruswamy Thurai Prasad ◽

Inderpaul Singh Sehgal ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Adenosine Deaminase ◽

Pleural Fluid ◽

Sensitivity And Specificity ◽

Interferon Gamma ◽

Meta Analysis ◽

Paired Data ◽

Ifn Γ ◽

Meta Regression

Objective We compared diagnostic accuracy of pleural fluid adenosine deaminase (ADA) and interferon-gamma (IFN-γ) in diagnosing tuberculous pleural effusion (TPE) through systematic review and comparative meta-analysis. Methods We queried PubMed and Embase databases to identify studies providing paired data for sensitivity and specificity of both pleural fluid ADA and IFN-γ for diagnosing TPE. We used hierarchical summary receiver operating characteristic (HSROC) plots and HSROC meta-regression to model individual and comparative diagnostic performance of the two tests. Results We retrieved 376 citations and included 45 datasets from 44 publications (4974 patients) in our review. Summary estimates for sensitivity and specificity for ADA were 0.88 (95% CI 0.85–0.91) and 0.91 (95% CI 0.89–0.92), while for IFN-γ they were 0.91 (95% CI 0.89–0.94) and 0.96 (95% CI 0.94–0.97), respectively. HSROC plots showed consistently greater diagnostic accuracy for IFN-γ over ADA across the entire range of observations. HSROC meta-regression using test-type as covariate yielded a relative diagnostic odds ratio of 2.22 (95% CI 1.68–2.94) in favour of IFN-γ, along with better summary sensitivity and specificity figures. No prespecified subgroup variable significantly influenced the summary diagnostic accuracy estimates. Conclusion Pleural fluid IFN-γ estimation has better diagnostic accuracy than ADA estimation for diagnosis of TPE.

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Comparative analysis of the morphological and biomechanical properties of normal cornea and keratoconus at different stages

International Ophthalmology ◽

10.1007/s10792-021-01929-4 ◽

2021 ◽

Author(s):

Ying Wu ◽

Li-Li Guo ◽

Lei Tian ◽

Ze-Quan Xu ◽

Qian Li ◽

...

Keyword(s):

Operating Characteristic ◽

High Efficiency ◽

Stage Iv ◽

Roc Curves ◽

Normal Subjects ◽

Biomechanical Properties ◽

Stage I ◽

Morphological Parameters ◽

Diagnostic Efficiency ◽

Biomechanical Parameters

Abstract Purpose To compare the morphological and biomechanical properties of normal cornea and keratoconus at different stages. Methods A total of 408 patients (517 eyes) with keratoconus were included in this study. According to the Topographic Keratoconus (TKC) grading method, keratoconus was divided into stage I (TKC = 1, 130 eyes), stage II (TKC = 1–2, 2, 164 eyes), stage III (TKC = 2–3, 3, 125 eyes) and stage IV (TKC = 3–4, 4, 98 eyes). A total of 158 normal subjects (158 eyes) were recruited as the normal group. The corneal morphological parameters and biomechanical parameters were obtained with Scheimpflug tomography (Pentacam) and corneal visualization Scheimpflug technology (Corvis ST), and the receiver operating characteristic (ROC) curves were drawn. Results Each corneal morphological and most biomechanical parameters of the keratoconic eyes were significantly different from those of the normal eyes in this study (p < 0.001). ROC curve demonstrated that most parameters in this study showed high efficiency in diagnosing keratoconus (the area under the ROC (AUC) was > 0.9), with the Belin-Ambrósio deviation (BAD-D) and Tomographic and Biomechanical Index (TBI) showing higher efficiency. The efficiency of BAD-D and TBI was high in differentiating keratoconus at different stages (AUC > 0.963). The comparison of ROC curves of keratoconus at different stages did not reveal statistically significant differences for TBI. Conclusion BAD-D and TBI can effectively diagnose stage I keratoconus. Moreover, the efficiency of TBI is the same in diagnosing keratoconus at all stages, while the diagnostic efficiency of other parameters increases with the increase in keratoconus stages.

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Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

PLoS ONE ◽

10.1371/journal.pone.0202481 ◽

2018 ◽

Vol 13 (8) ◽

pp. e0202481 ◽

Cited By ~ 9

Author(s):

Ana Paula Santos ◽

Raquel da Silva Corrêa ◽

Marcelo Ribeiro-Alves ◽

Ana Carolina Oliveira Soares da Silva ◽

Thiago Thomaz Mafort ◽

...

Keyword(s):

Adenosine Deaminase ◽

Pleural Tuberculosis ◽

Ifn Γ

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Evaluation on the Diagnostic Efficiency of Different Methods in Detecting COVID-19.

10.21203/rs.3.rs-100604/v1 ◽

2020 ◽

Author(s):

Haitao Yang ◽

Yuzhu Lan ◽

Xiujuan Yao ◽

Sheng Lin ◽

Baosong Xie

Keyword(s):

Sensitivity And Specificity ◽

Operating Characteristic ◽

Web Of Science ◽

Characteristic Curve ◽

Positive Likelihood Ratio ◽

Diagnostic Odds Ratio ◽

Diagnostic Efficiency ◽

Summary Receiver Operating Characteristic ◽

Operating Characteristic Curve ◽

Higher Sensitivity

Abstract Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19.Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. EPlex: pooled sensitivity was 0.94; specificity 1.0; PLR 90.91; NLR 0.07; DOR 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity 0.98; PLR 42.46; NLR 0.02; DOR 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity 0.97; PLR 26.67; NLR 0.01; DOR 3100.93; AUC=0.9970, Q*=0.9800. Cobas®: pooled sensitivity was 0.99; specificity 0.96; PLR 37.82; NLR 0.02; DOR 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity 0.99; PLR 36.22; NLR 0.04; DOR 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity 0.97; PLR 27.44; NLR 0.01; DOR 3488.15; AUC=0.9977, Q*=0.9829.Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas®, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.

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SAT0205 A MORE SPECIFIC INTEGRATED MODEL FOR IDENTIFYING BACTERIAL INFECTION IN SYSTEMIC LUPUS ERYTHEMATOSUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5376 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1045-1046

Author(s):

M. Feng ◽

X. C. Zhao ◽

J. Luo

Keyword(s):

Systemic Lupus Erythematosus ◽

Bacterial Infection ◽

Disease Activity ◽

Sensitivity And Specificity ◽

Lupus Erythematosus ◽

Roc Curves ◽

Systemic Lupus ◽

Routine Examination ◽

Tnf Α ◽

Ifn Γ

Background:Systemic lupus erythematosus (SLE) is a multisystemic inflammatory disorder [1]. Given that immunosuppressive therapy is adopted as the predominant treatment option for SLE, up to half of SLE patients develop infections during their disease progress, and bacterial infection serves as the leading cause of morbidity and mortality in SLE patients [2]. Owing to the therapeutic regimen to bacterial infection and SLE flare are absolutely opposite, timely diagnosis and correct treatment are of vital importance, and improper treatment strategy may be fatal. No single biomarker, however, has exhibited sufficient sensitivity and specificity to serve as a standard tool for distinguishing bacterial infection from SLE flare.Objectives:To find a method by integrating cytokines, lymphocyte cells and routine examination biomarkers to observe its capacity for identifying bacterially infected SLE patients.Methods:Total 175 SLE patients (65 infected and 110 flare) were recruited into our study. The criteria of bacterial infection was positive isolation of bacteria, typical clinical symptoms and signs, imaging positive results and positive feedback on antibacterial treatment and lupus flare was regarded as three points higher than their previous SLEDAI. The disease activity of SLE patients was evaluated based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Lymphocyte cells (CD3+T, CD4+T, CD8+T, B, NK, Th1, Th2, Th17 and Treg) and cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-17] were measured by flow cytometry. Blood routine examination, erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP) Complement 3 (C3), C4, procalcitonin (PCT), immunoglobulin M (IgM), IgA and IgG were also evaluated. Partial least square discriminant analysis (PLS-DA) and supervised orthogonal PLS-DA (OPLS-DA) were applied to perform multivariate analysis of the data and further group the patients with bacterial infection. Receiver operating characteristic (ROC) curves were also plotted to investigate the ability of individual indicator and the combination of multiple indicators to identify bacterial infection.Results:The PLS-DA model showed a clear identification effect by the performance of R2Y=0.991 and Q2=0.970. The OPLS-DA model (R2Y=0.996 and Q2=0.991) exhibited a better separation of patients with bacterial infection. And the Observed vs. predicted plot of the OPLS-DA model demonstrated that all SLE patients were correctly separated into infected or flare groups, indicating that the model had a strong predictive ability for bacterial infection. For single indicator, infected patients had higher WBC, neutrophil (NEUT), ESR, CRP and PCT (P=0.002, 0.019, 0.002, <0.001, <0.001, respectively), and lower Treg cells (P=0.012). The levels of serum IL-6, IL-10, IFN-γ and TNF-α (P<0.001, =0.022, 0.014, 0.011, respectively) were significantly increased in infected group. ROC curves showed that the combination of the ten indicators showed the largest AUC and the highest accuracy, as well as balanced and relatively high sensitivity and specificity. Furthermore, the AUC of the combination was greatly higher than that of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α (P<0.001).Conclusion:PLS-DA, OPLS-DA models including cytokines, lymphocyte cells and routine biomarkers and combination of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α in ROC curve may be more predictive for finding bacterial infection in SLE and may prompt clinicians more promptly and accurately to help them make correct medication.References:[1]Illescas-Montes R, Corona-Castro CC, Melguizo-Rodríguez L, et al. Infectious processes and systemic lupus erythematosus. Immunology 2019;158:153-160.[2]Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases. Ann Rheum Dis 2002; 61: ii2–7.Disclosure of Interests:None declared

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The utility of six serum tumor markers in early detection of lung cancer

10.21203/rs.2.18342/v1 ◽

2019 ◽

Author(s):

Qingwen Jiang ◽

Xu Zheng ◽

Yiting Li ◽

Weina Huang ◽

Xinjian Li ◽

...

Keyword(s):

Lung Cancer ◽

Sensitivity And Specificity ◽

Operating Characteristic ◽

Early Stage ◽

High Sensitivity ◽

Roc Curves ◽

Serum Levels ◽

Benign Diseases ◽

Significant Difference ◽

Diagnosis Of Lung Cancer

Abstract Background: Lung cancer has become the leading cause of cancer-related death in China. However, most of patients were diagnosed at advanced stage. Thus, novel lung cancer diagnostic tests, which can be used to screen individuals in early stage, are required.Methods: A total of 208 patients involving 161 cases of lung cancer and 47 cases of benign diseases were enrolled. Serum concentration of GTM, CETM, PTM, CTM, ETM and HTM were analyzed by kits according to the manufacturer’s guidelines.Results: The results showed significant difference in serum concentrations of GTM, CETM, PTM, CTM, ETM, and HTM between patients with lung cancer and benign diseases. In addition, when compared with benign diseases, higher levels of those six markers were also observed in patient with SCC and SCLC, but not for ADC. Receiver operating characteristic (ROC) curves were further suggested a high sensitivity and specificity of six markers to identify lung cancer.Conclusion: The serum levels of GTM, CETM, PTM, CTM, ETM and HTM in lung cancer were significantly higher than those of benign diseases. Moreover, these six biomarkers showed a high sensitivity and specificity to identify a patient with malignant. These findings suggested that detection of those six biomarkers in serum might be helpful for differential diagnosis of lung cancer.

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