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Background: Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE., Methods: The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE., Results: The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P < 0.01) and MPE group (10 U/L, P < 0.001). The median pfADA level in the TPE group was 41 (32, 52) U/L; it was lowest in the MPE group at 9 (7, 12) U/L and highest in the PPE group at 43 (23, 145) U/L. The pfLDH level in the PPE group was 2542 (1109, 6219) U/L, which was significantly higher than that in the TPE group 449 (293, 664) U/L. In the differential diagnosis between TPE and non-TPE, the AUC of pfLDH/pfADA for diagnosing TPE was the highest at 0.946 (0.925, 0.966), with an optimal cutoff value of 23.20, sensitivity of 93.9%, specificity of 87.0%, and Youden index of 0.809. In the differential diagnosis of TPE and PPE, the AUC of pfLDH/pfADA was the highest at 0.964 (0.939, 0.989), with an optimal cutoff value of 24.32, sensitivity of 94.6%, and specificity of 94.4%; this indicated significantly better diagnostic efficacy than that of the single index of pfLDH. In the differential diagnosis between TPE and MPE, the AUC of pfLDH/pfADA was 0.926 (0.896, 0.956), with a sensitivity of 93.4% and specificity of 80.0%; this was not significantly different from the diagnostic efficacy of pfADA., Conclusions: Compared with single biomarkers, pfLDH/pfADA has higher diagnostic value for TPE and can identify patients with TPE early, easily, and economically., (© 2024. The Author(s).)

Background: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L., Methods: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively., Results: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP., Conclusion: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE., (© 2023. The Author(s).)

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p  < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10 -3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p  = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.

Background: Pleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE)., Methods: The participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated., Results: Biomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%)., Conclusions: The biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy., (© 2023. The Author(s).)

Introduction: The differential diagnosis of pleural effusion is difficult, and studies have reported on the potential role of adenosine deaminase (ADA) in the differential diagnosis of undiagnosed pleural effusion. This retrospective study aimed to investigate the diagnostic role of ADA in pleural effusion., Methods: 266 patients with pleural effusion from three centers were enrolled. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. The diagnostic performance of ADA-based measurement for tuberculous pleural effusion (TPE), malignant pleural effusion (MPE), and parapneumonic effusion (PPE) was examined by receiver operating characteristic (ROC) curve analysis., Results: An area under the ROC curve (AUC) value of 0.909 was obtained using the pleural ADA values as the indicator for TPE identification (sensitivity: 87.50%, specificity: 87.82%). The ratio of serum LDH to pleural ADA (cancer ratio) provided the predictive capacity with an AUC of 0.879 for MPE diagnosis (sensitivity: 95.04%, specificity: 67.06%). At a cut-off value of 14.29, the pleural ADA/LDH ratio showed a sensitivity and specificity of 81.13% and 83.67%, respectively, and a high AUC value of 0.888 for the differential diagnosis of PPE from TPE., Conclusion: ADA-based measurement is helpful for the differential diagnosis of pleural effusion. Further studies should be performed to validate these results.

Objectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion., Methods: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY)., Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p<0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%., Conclusions: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/L.

Background: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear., Methods: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity., Results: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect., Conclusions: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.

Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].) IMPORTANCE Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.

A 33-year-old woman with a fever, cough, and pharyngitis was admitted after left-sided pleural effusion was detected. The fever and upper respiratory symptoms were confirmed, and she was diagnosed with coronavirus disease (COVID-19) after showing a positive polymerase chain reaction (PCR) test. After thoracentesis, pleural fluid revealed elevated adenosine deaminase values and a positive QuantiFeron test; tuberculous pleurisy was thus suspected. Subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR and anti-SARS-CoV-2 Spike IgG tests were negative, suggesting that the initial PCR result had been erroneous. However, we were unable to confirm this. Data concerning COVID-19 diagnostics are insufficient at present. It is important to make comprehensive judgments regarding the diagnosis and treatment of patients as well as public health.

The objective of this study was to evaluate ruminal microbiome changes associated with feeding Lactobacillus plantarum GB-LP1 as direct-fed microbials (DFM) in high-producing dairy cow diets. A dual-flow continuous culture system was used in a replicated 4 × 4 Latin square design. A basal diet was formulated to meet the requirements of a cow producing 45 kg of milk per day (16% crude protein and 28% starch). There were 4 experimental treatments: the basal diet without any DFM (CTRL); a mixture of Lactobacillus acidophilus, 1 × 10 9 cfu/g, and Propionibacterium freudenreichii, 2 × 10 9 cfu/g [MLP = 0.01% of diet dry matter (DM)]; and 2 different levels of L. plantarum, 1.35 × 10 9 cfu/g (L1 = 0.05% and L2 = 0.10% of diet DM). Bacterial samples were collected from the fluid and particulate effluents before feeding and at 2, 4, 6, and 8 h after feeding; a composite of all time points was made for each fermentor within their respective fractionations. Bacterial community composition was analyzed through sequencing the V4 region of the 16S rRNA gene using the Illumina MiSeq platform. Sequenced data were analyzed on DADA2, and statistical analyses were performed in R (RStudio 3.0.1, https://www.r-project.org/) and SAS 9.4 (SAS Institute Inc.); orthogonal contrasts were used to compare treatments. Different than in other fermentation scenarios (e.g., silage or beef cattle high-grain diets), treatments did not affect pH or lactic acid concentration. Effects were mainly from overall DFM inclusion, and they were mostly observed in the fluid phase. The relative abundance of the phylum Firmicutes, family Lachnospiraceae, and 6 genera decreased with DFM inclusion, with emphasis on Butyrivibrio&#95;2, Saccharofermentans, and Ruminococcus&#95;1 that are fibrolytic and may display peptidase activity during fermentation. Lachnospiraceae&#95;AC2044&#95;group and Lachnospiraceae&#95;XPB1014&#95;group also decreased in the fluid phase, and their relative abundances were positively correlated with NH 3 -N daily outflow from the fermentors. Specific effects of MLP and L. plantarum were mostly in specific bacteria associated with proteolytic and fibrolytic functions in the rumen. These findings help to explain why, in the previous results from this study, DFM inclusion decreased NH 3 -N concentration without altering pH and lactic acid concentration., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background/aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs., Methods: Patients with TPE and MPE with pleural fluid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve., Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965., Conclusion: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Background: Postpartum dysgalactia syndrome (PDS) is associated with a significantly higher activation of the inflammatory and stress response at parturition than in the healthy sow. Therefore, reliable and possibly non-invasive biomarkers for substantial increases of inflammation are searched to support the PDS diagnosis. This report studies the possible changes of the inflammatory marker enzyme adenosine deaminase (ADA) in serum and saliva of 38 PDS positive sows (PDS+) and 38 healthy sows (PDS-). Sampling was performed every 24 h from 60 h before to 36 h after parturition. Isoenzyme 1 (ADA1) and isoenzyme 2 (ADA2), as well as total ADA (tADA), were measured and their statistical association with several serum and saliva biomarkers of inflammation and stress was investigated., Results: Compared to a baseline (60 to 36h prepartum), salivary activities of ADA1, ADA2 and tADA increased significantly over time in both PDS+ and PDS- sows, reaching their peaks after parturition. In serum from PDS- sows, no changes were observed over time in either ADA1, ADA2 or tADA. In PDS+ sows, serum ADA2 activity decreased temporarily after parturition followed by a significant increase compared to baseline. ADA1, ADA2 and tADA were all significantly associated with several inflammatory biomarkers and ADA1 in serum was associated with serum cortisol. Although serum activity was higher in PDS+ than in PDS- sows, the differences were not statistically significant. Further, no difference was noted between the groups in the analyses of saliva., Conclusions: Salivary ADA1 and ADA2 increased in all sows after parturition, potentially as a response to the postpartum inflammation. However, no difference in the activity of ADA1, ADA2 and tADA were found between PDS+ and PDS- sows indicating inability to diagnose PDS under the conditions described in this report., (© 2021. The Author(s).)

Background: A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value., Case Presentation: We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis., Conclusions: This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

Background: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB)., Methods: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results., Results: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ 2  = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB., Conclusion: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.

The differential diagnosis of benign ascites and malignant ascites is incredibly challenging for clinicians. This research aimed to develop a user-friendly predictive model to discriminate malignant ascites from non-malignant ascites through easy-to-obtain clinical parameters. All patients with new-onset ascites fluid were recruited from January 2014 to December 2018. The medical records of 317 patients with ascites for various reasons in Renmin Hospital of Wuhan University were collected and reviewed retrospectively. Thirty-six parameters were included and selected using univariate logistic regression, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses to establish a mathematical model for differential diagnosis, and its diagnostic performance was validated in the other groups. Age, cholesterol, hypersensitivity C-reactive protein (hs-CRP) in serum, ascitic fluid adenosine deaminase (AF ADA), ascitic fluid lactate dehydrogenase (AF LDH) involvement in a 5-marker model. With a cut-off level of 0.83, the sensitivity, specificity, accuracy, and area under the ROC of the model for identifying malignant ascites in the development dataset were 84.7%, 88.8%, 87.6%, and 0.874 (95% confidence interval [CI], 0.822-0.926), respectively, and 80.9%, 82.6%, 81.5%, and 0.863 (95% CI,0.817-0.913) in the validation dataset, respectively. The diagnostic model has a similar high diagnostic performance in both the development and validation datasets. The mathematical diagnostic model based on the five markers is a user-friendly method to differentiate malignant ascites from benign ascites with high efficiency., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Tuberculous pleural effusion (TPE) is the most common extrapulmonary manifestation and may have lasting effect on lung function. However conventional diagnostic tests for TPE register multiple limitations. This study estimates diagnostic efficacy of the interferon gamma release assay (IGRA: T-SPOT.TB) in TPE patients of different characteristics., Methods: We performed a prospective, single-centre study including all suspected pleural effusion patients consecutively enrolled from June 2015 to October 2018. Through receiver operating characteristic (ROC) curves, technical cut-offs and the utility of T-SPOT on pleural fluid (PF) were determined and analysed. Logistic regression analysis was performed to obtain the independent risk factors for TPE, and evaluated the performance of the T-SPOT assay stratified by risk factors in comparison to ADA., Results: A total of 601 individuals were consecutively recruited. The maximum spot-forming cells (SFCs) of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) in the PF T-SPOT assay had the best diagnostic efficiency in our study, which was equal to ADA (0.885 vs 0.887, P = 0.957) and superior to peripheral blood (PB), with a sensitivity of 83.0% and a specificity of 83.1% (The cut-off value was 466 SFCs/10 6 mononuclear cells). Among the TPE patients with low ADA (< 40 IU/L), the sensitivity and specificity of PF T-SPOT were still 87.9 and 90.5%, respectively. The utility of ADA was negatively related to increasing age, but the PF T-SPOT test had a steady performance at all ages. Age (< 45 yrs.; odds ratio (OR) = 5.61, 95% confidence interval (CI) 3.59-8.78; P < 0.001), gender (male; OR = 2.68, 95% CI 1.75-2.88; P < 0.001) and body mass index (BMI) (< 22; OR = 1.93, 95% CI 1.30-2.88; P = 0.001) were independently associated with the risk of TB by multivariate logistic regression analysis. Notably, when stratified by risk factor, the sensitivity of PF T-SPOT was superior to the sensitivity for ADA (76.5% vs. 23.5%, P = 0.016) and had noninferior specificity (84.4% vs. 96.9%, P = 0.370)., Conclusions: In conclusion, the PF T-SPOT assay can effectively discriminate TPE patients whose ADA is lower than 40 IU/L and is superior to ADA in unconventional TPE patients (age ≥ 45 yrs., female or BMI ≥ 22). The PF T-SPOT assay is an excellent choice to supplement ADA to diagnose TPE.

Objectives: The application of Light's criteria misidentifies approximately 30% of transudates as exudates, particularly in patients on diuretics with cardiac effusions. The purpose of this study was to establish a predictive model to effectively identify cardiac effusions misclassified by Light's criteria., Methods: We retrospectively studied 675 consecutive patients with pleural effusion diagnosed by Light's criteria as exudates, of which 43 were heart failure patients. A multivariate logistic model was developed to predict cardiac effusions. The performance of the predictive model was assessed by receiver operating characteristic (ROC) curves, as well as by examining the calibration., Results: It was found that protein gradient of >23 g/L, pleural fluid lactate dehydrogenase (PF-LDH) levels, ratio of pleural fluid LDH to serum LDH level (P/S LDH), pleural fluid adenosine deaminase (PF-ADA) levels, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels had a significant impact on the identification of cardiac effusions, and those were simultaneously analyzed by multivariate regression analysis. The area under the curve (AUC) value of the model was 0.953. The model also had higher discriminatory properties than protein gradients (AUC, 0.760) and NT-pro-BNP (AUC, 0.906), all at a P value of <.01., Conclusion: In cases of suspected cardiac effusion, or where clinicians cannot identify the cause of an exudative effusion, this model may assist in the correct identification of exudative effusions as cardiac effusions., (© American Society for Clinical Pathology 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A simple turn-on fluorescence strategy is proposed for the detection of ATP based on DNA-stabilized copper/silver nanoclusters (DNA-Cu/Ag NCs). The fluorescence intensity of DNA-Cu/Ag NCs increases significantly in the presence of ATP, because the specific interaction between ATP and its aptamer causes two darkish Cu/Ag NCs to be situated at the 5' and 3' termini close to each other. A limit of detection (LOD) of 7.0 μM is found, in a linear range of 2-18 mM, and the proposed sensor is simple, sensitive, and selective. Additionally, the DNA-Cu/Ag NCs/ATP system is further developed into a sensor for ADA detection and demonstrates a linear response to ADA from 5 to 50 U/L with a LOD of 5 U/L. The proposed method is also shown to be successful in detecting ATP and ADA in a solution of fetal bovine serum.

Background: Peritoneal tuberculosis is the most common cause of low albumin gradient ascites in developing countries, but it can be easily confused with other causes of ascites. Peritoneal tuberculosis requires early recognition of symptoms and signs in order to make a quick diagnosis for appropriate treatment. Measurement of adenosine deaminase (ADA) level > 39 in ascites fluid is an established test to diagnose peritoneal tuberculosis. Many low-income countries do not currently test for adenosine deaminase in ascites fluid, including Rwanda., Method: Cross-sectional, descriptive study conducted through the Internal Medicine Department of three university teaching hospitals in Rwanda. Participants were patients older than 16 years presenting to tertiary referral hospitals with ascites of unknown cause., Results: Of 103 ascites fluid samples collected, 52 of them (50.5%) had an elevated ADA, consistent with a presumptive diagnosis of peritoneal TB. Among those 52 subjects diagnosed with peritoneal TB, 39 out of 52 (75%) did not receive anti-TB medications. Among the 17 subjects who were treated with anti-TB medications, 4 of 17 (23.6%) did not have peritoneal TB based on ADA level. Samples with low-albumin gradient ascites were more likely to have high ADA ≥39 IU/L (p = 0.039)., Conclusion: Our findings suggest that 3out of 4 patients with PTB in Rwanda are not getting TB treatment and 1 in 4 patients who are taking TB medications do not need it. Even if the true number of Rwandans who are being undertreated and overtreated is less than our study suggests, these results should prompt a larger study of peritoneal tuberculosis. Adding adenosine deaminase (ADA) to the diagnostic tools available to clinicians could help achieve the goal of correctly putting every Rwandan with tuberculosis on treatment, while avoiding unnecessary tuberculosis medications in those who do not have the disease.

Background: This study is focused on the measurement of trace elements (zinc, copper, cadmium, lead and selenium) in the saliva of pigs in order to study their levels on different porcine pathological conditions in the field. The experiment involved 15 pigs without clinical signs of disease and 42 diseased pigs (suffering from lameness, rectal prolapse, fatigue or growth rate retardation). Individual saliva samples were collected, allowing the pigs to chew a sponge each for trace element quantifications through atomic absorption spectrometry (AAS). Since this is the first report on the measurements of trace elements in porcine saliva, a routine analytical validation study was performed for the quantification of all the studied elements. Moreover, the acute phase proteins C-reactive protein (CRP) and haptoblobin (Hp), the total antioxidant capacity (TAC) and adenosine deaminase (ADA) were quantified in the saliva samples for the animal's health status assessment., Results: Modifications in the levels of acute phase proteins or ADA were only recorded in animals with lameness and rectal prolapse and those with fatigue respectively. Moreover, TAC level changes were observed in pigs with growth-rate retardation. However, alterations in the levels of two or more trace elements were reported for all the different groups of diseased pigs with evident variations within pathologies., Conclusions: The salivary quantification of trace elements could be considered as a complementary tool to acute phase proteins, TAC and ADA determinations for disease detection and differentiation in the pig and should be explored in greater depth.

Background: The aim of this study was to assess the validity of GeneXpert MTB/RIF (Xpert) and adenosine deaminase (ADA) in the diagnosis of tuberculous peritonitis (TBP)., Methods: The laboratory results of peritoneal effusion (PE) specimens from patients with symptoms suggestive of TBP, attending three TB specialized hospitals between January 2016 and December 2018, were included retrospectively. Clinically diagnosed TBP was set as the gold standard to evaluate the performance of these methods., Results: In total, 191 individuals presenting with symptoms suggestive of TBP were included for analysis. The sensitivities of MGIT culture and Xpert were 17.2% and 18.3%, respectively. In addition, the TBP cases (69.8±6.0U/l) had higher amounts of ADA in their PE samples than the non-TBP cases (12.6±1.6U/l; p<0.01). Using a threshold of 31.5U/l to differentiate the TBP group from non-TBP group, the ADA assay provided a sensitivity of 89.6% and a specificity of 92.1%. The mean ADA concentration was significantly higher in bacteria-positive cases than in bacteria-negative cases (p<0.01)., Conclusions: In conclusion, the study data demonstrate the high sensitivity and specificity of the ADA test for the early diagnosis of TBP. In addition, the ADA concentration is directly correlated with the mycobacterial load., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold., Methods: We searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45-65 and >65 IU/L., Results: We retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90-0.93), 0.90 (95% CI 0.88-0.91) and 97.42 (95% CI 74.90-126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90-0.95) and 0.90 (95% CI 0.87-0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61-0.96) and 0.94 (95% CI 0.80-0.99) respectively., Conclusion: ADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds., Competing Interests: The authors have declared that no competing interests exist.

Pleural effusions are a common medical problem not only for pulmonologists but also for general physicians, often needing thoracentesis for a definite diagnosis. However, thoracentesis cannot always reveal malignant cells or microbiological evidence.In this context, we prospectively enrolled a total of 289 patients with pleural effusions due to diverse etiologies: parapneumonic effusion (PPE) (63), empyema (22), tuberculous pleural effusion (TBPE) (54), malignant pleural effusion (MPE) (140), or chronic renal failure (CRF)/congestive heart failure (CHF) (10). The MPE group consisted of lung cancer (adenocarcinoma, n = 90; squamous cell carcinoma, n = 5; small cell carcinoma, n = 4), malignant lymphoma (n = 17), malignant mesothelioma (n = 11), malignant melanoma (n = 3), and metastasis from other organs (n = 10).This study demonstrated that the pleural lactate dehydrogenase (LDH)to adenosine deaminase (ADA) ratios differed significantly between patients with CHF/CRF, MPE, TBPE, empyema, and PPE. We discovered a simple method to differentiate pleural diseases based on the pleural LDH to ADA ratio and carcinoembryonic antigen (CEA). A pleural LDH to ADA ratio greater than 15.5 and a pleural CEA level of less than 5 ng/mL is indicative of PPE or empyema rather than TBPE, MPE, or transudative pleural effusion (CRF, CHF).This method has a sensitivity of 62.0%, a specificity of 91.0%, and an area under the receiver operating characteristic curve of 0.765 (95% confidence interval [CI]: 0678-0.852, P < .001), odds ratio of 16.6 (95% CI: 7.28-37.8, P < .001), a positive likelihood ratio (LR) of 6.8, and a negative LR of 0.02.

Background: The adenosine deaminase (ADA) enzyme is a marker of inflammatory processes whose activity can be measured through a colorimetric method developed as an in-house assay. This validation can reduce costs and expand the alternatives for laboratory diagnosis., Methods: The ADA analysis was achieved through a modified form of Giusti and Galanti's (1984) method. The following parameters were characterized: calibration curve, linearity, analytical sensitivity, limit of detection, limit of quantification, method working range, precision (within-assay and between-assay), bias, total analytical error, and sample stability. The results were statistically evaluated and compared with quality specifications based on biological variations and the performance of commercial tests., Results: The analytical sensitivity and limit of detection (0.013 and 3.0 U/L, respectively) were lower than those of commercial tests. The method's working range was 3.2-100.0 U/L. According to the quality specification, the method showed optimum performance with a bias <3.5%. However, repeatability (2.2% and 1.7% for normal- and high-activity samples, respectively) and reproducibility achieved worse results when compared to commercial tests. The method demonstrated an inappropriate between-assay precision for low enzymatic activity (10.4%) and the minimum and desirable performance for medium (8.8%) and high (5.0%) activities, respectively. It also presented at least a minimum performance (<25%) for the total analytical error of the three analyzed samples. The pleural fluid samples were found to be stable at -20°C for six days., Conclusion: The findings show that the in-house method displays an acceptable performance and is capable of generating results comparable to existing commercial tests., (© 2018 Wiley Periodicals, Inc.)

Background: Tuberculosis (TB) remains a major public health concern on a global scale, especially in developing nations. So far, no formal guidelines are available for the diagnosis and treatment of tuberculosis pleurisy. The diagnosis of TB is worsened by the immense difficulty in differential determination of tuberculosis pleural effusion (TPE) and malignant pleural effusion (MPE). The purpose of this investigation is to assess the differential diagnostic efficiencies of the pleural IFN-γ release assay (IGRA) and widely-used biochemical parameters in the distinction analysis of TPE and MPE., Methods: A cohort of 222 patients with pleural effusion was examined, comprising of 143 TPE and 58 MPE patients. The patients were examined with IGRA, and the widely-used biomarkers in the pleural effusion and peripheral blood., Results: Our results show that the TPE patients have significantly higher M. tuberculosis (Mtb) antigen-specific IFN-γ responses to ESAT-6 protein and peptide pool in the blood compared to MPE patients. TPE patients were also shown to have enriched Mtb antigen-specific IFN-γ responses in pleural effusion than in peripheral blood. Among the widely-used biomarkers, the adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) in pleural effusion were better biomarkers with high sensitivity and specificity to discriminate TPE and MPE. In addition, pleural IGRA could not be affected by the pleural adhesion, and the applications of the pleural IGRA together with ADA and CEA provide a promising approach for the TPE and MPE differential identification., Conclusions: Our study proposes that the integration of pleural IGRA and ADA, CEA detection could add to more effective diagnosis stratagems in the discernment between TPE and MPE.

The incidence of fertile women with missed abortion dramatically increased in recent years, while very few serum indices have been identified for the diagnosis of missed abortion. The aim of this study was to identify related factors for missed abortion through a retrospective study of serum indices.A total of 795 cases of women with missed abortion and 694 cases of women with normal pregnancy between March 2014 and March 2017 were included in the present study. The diagnosis of missed abortion was based on clinical history, clinical examination, and transvaginal ultrasound findings. The final diagnosis of missed abortion was based on assessment of pregnancy structures (i.e., a gestational sac without fetal heart rate) via transvaginal ultrasound. We evaluated the clinical values of 4 serum indices and their relationship to missed abortion: gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), adenosine deaminase (ADA), and fibrinogen (FIB).The serum levels of GGT, ADA, and FIB showed statistically significant differences comparing women who experienced missed abortion with women who had normal pregnancies (controls). Among women with missed abortion, the levels of GGT and ADA were dramatically increased (GGT: P < .0001; ADA: P = .0459), while FIB levels were slightly lower (P = .0084) compared to controls. The LDH levels exhibited a non-significant trend toward lower levels in the missed abortion group (P = .3951). Interestingly, the observed significant increase in serum GTT levels among women with missed abortion was not affected by maternal age.This study found that GTT may be a useful marker which was associated with missed abortion, indicating its potential clinical roles in missed abortion.

ABSTRACT Heroin is known to enhance catabolism and inhibit anabolism of purine nucleotides, leading to purine nucleotide deficiencies in rat brains. Here, we determined the effect of exogenous purine nucleotide administration on purine nucleotide metabolism in the brains of heroin-dependent rats. Heroin was administrated in increasing doses for 9 consecutive days to induce addiction, and the biochemical changes associated with heroin and purine nucleotide administration were compared among the treated groups. HPLC was performed to detect the absolute concentrations of purine nucleotides in the rat brain cortices. The enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the treated rat cortices were analyzed, and qRT-PCR was performed to determine the relative expression of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT), and adenosine kinase (AK). Heroin increased the enzymatic activity of ADA and XO, and up-regulated the transcription of ADA and XO. Alternatively, heroin decreased the transcription of AK, APRT, and HGPRT in the rat cortices. Furthermore, purine nucleotide administration alleviated the effect of heroin on purine nucleotide content, activity of essential purine nucleotide metabolic enzymes, and transcript levels of these genes. Our findings therefore represent a novel, putative approach to the treatment of heroin addiction.

Background: Midkine (MK) level has been shown to be elevated in serum of patients with nonsmall cell lung cancer (NSCLC). However, the diagnostic value of MK in pleural effusion in NSCLC has not been well validated and established., Methods: Samples of NSCLC-associated malignant pleural effusions (MPE) and benign effusions (BPE) were collected. The pleural fluid MK (pMK), pleural fluid adenosine deaminase (pADA), pleural fluid lactate dehydrogenase (pLDH), pleural fluid glucose (pGLU), pleural fluid ferritin (pFER), pleural fluid CA199 (pCA199), pleural fluid CA125 (pCA125), pleural effusion white cell count (pWBC), and pleural effusion red cell count (pRBC) were analyzed, and the clinical data of each group were collected for statistical analysis., Result: The level of pMK, pCA125, pMK + pCA125, and pMK + pCA125 + pADA in the MPE was significantly higher than the BPE group (P = .003, .000, .000, .000). The pADA level in the BPE was significantly higher than the MPE group (P = .003). It showed that the area under the ROC curve (AUC) (0.816) of jointly detection pMK, pCA125, and pADA was significantly higher than other markers for the diagnosis of MPE. Therefore, joint detection of pMK + pCA125 + pADA suggested that the sensitivity, specificity, and AUC was 82.54%, 74.19% at the cutoff 0.47 and diagnostic performance was higher than others., Conclusion: Joint detection of pMK + pCA125 + pADA can be used as a good indicator for the identification of MPE of NSCLC., (© 2018 Wiley Periodicals, Inc.)

An 81-year-old man was admitted with bilateral pleural effusion. A clinical examination showed lymphocytic pleura effusion and elevated serum IgG4 levels, so that IgG4-related disease was suggested, whereas tuberculous pleurisy was suspected because of high adenosine deaminase (ADA) levels in the pleural effusion. A surgical pleural biopsy revealed that there were large numbers of IgG4-positive cells and IgG4/IgG positive cell ratio exceeded 40% in several sites. Accordingly, we diagnosed IgG4-related pleuritis and treated with the patient with glucocorticoid therapy. The ADA levels in pleural effusion can increase in IgG4-related pleuritis, and it is therefore important to perform a pleural biopsy.

Adenosine deaminase (ADA), able to catalyze the irreversible deamination of adenosine into inosine, can be found in almost all tissues and plays an important role in several diseases. In this work, we developed a label-free fluorescence method for the detection of adenosine deaminase activity and inhibition. In the presence of ADA, ATP has been shown to be hydrolyzed. The ATP aptamer was shown to form a G-quadruplex/thioflavin T (ThT) complex with ThT and exhibited an obvious fluorescence signal. However, the ATP aptamer could bind with ATP and exhibited a low fluorescence signal because of the absence of ADA. This assay showed high sensitivity to ADA with a detection limit of 1 U/L based on an SNR of 3 and got a good linear relationship within the range of 1⁻100 U/L with R² = 0.9909. The LOD is lower than ADA cutoff value (4 U/L) in the clinical requirement and more sensitive than most of the reported methods. This technique exhibited high selectivity for ADA against hoGG I, UDG, RNase H and λexo. Moreover, this strategy was successfully applied for assaying the inhibition of ADA using erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and, as such, demonstrated great potential for the future use in the diagnosis of ADA-relevant diseases, particularly in advanced drug development.

Background: Pleural tuberculosis (TB) diagnosis is sometimes controversial because the microbiologic confirmation ratio is very low in pleural fluid. There are few pediatric pleural TB case series in the literature., Methods: We retrospectively evaluated our TB cases below 18 years of age and extracted pleural TB cases., Results: Seven cases with pleural TB were identified. About 42.9% of the patients had isolated pleural TB whereas 57.1% of the patients had accompanying pulmonary TB. Lymphocytic pleural effusion and increased adenosine deaminase (ADA) (>40 U/L) level are found in 85.7% of the patients. Six patients had uncomplicated effusion (transudate) according to Light's criteria and one had complicated effusion (exudate). Lung decortication was needed in three patients. All patients were given 6 months anti-TB medication and recovered completely., Conclusion: In the lymphocyte-predominant pleural effusion, an increased ADA level highly supported TB disease. The complicated effusion (exudate) in pleural TB is not rule; uncomplicated effusion (transudate) could be seen., Competing Interests: There are no conflicts of interest

Introduction In contrast to tuberculous pleurisy (TP), no accurate and commonly accepted biochemical marker of malignant pleural effusion (MPE) has been established. Objectives We aimed to evaluate the ability of a previously reported cancer ratio (CR) to discriminate between MPEs and non-MPEs; to test whether age may have additional value in differentiating MPEs from non-MPEs; and if so, to combine lactate dehydrogenase (LDH) and age with other TP biomarkers in search of an index useful in the identification of MPEs. Patients and methods A retrospective analysis of data from 140 patients with malignant (n = 74), tuberculous (n = 37), and parapneumonic (n = 29) pleural effusions was performed. The diagnostic performance of a test to discriminate between MPEs and non-MPEs was evaluated using the receiver operating characteristic curve analysis. Results Three ratios showed the largest area under the curve (AUC): serum LDH to pleural fluid soluble Fas ligand, age to pleural fluid adenosine deaminase (ADA), and serum LDH to pleural fluid interleukin 18; moreover, the ratios were characterized by high sensitivity (95%, 93.2%, and 92.9%, respectively) and fair specificity (64.8%, 71.2%, and 58.5%, respectively) for differentiating MPEs from non-MPEs. The AUC for CR was lower and showed a sensitivity of 94.6% and a specificity of 68.2%. Conclusions Our study showed a lower specificity of the CR for discriminating between MPEs and non-MPEs than previously reported. We demonstrated that the combinations of serum LDH with other pleural fluid biomarkers of TP have a similar diagnostic performance. We also found that age might be an important factor differentiating between MPEs and non-MPEs and proposed a new age to pleural fluid ADA ratio which has a discriminative potential similar to that of the CR.

Introduction: Pleural fluid adenosine deaminase level can be applied to rapidly detect tuberculous pleural effusion. We aimed to establish a local diagnostic cut-off value for pleural fluid adenosine deaminase to identify patients with tuberculous pleural effusion, and optimise its utility., Methods: We retrospectively reviewed the medical records of consecutive adults with pleural fluid adenosine deaminase level measured by the Diazyme commercial kit (Diazyme Laboratories, San Diego [CA], United States) during 1 January to 31 December 2011 in a cluster of public hospitals in Hong Kong. We considered its level alongside early (within 2 weeks) findings in pleural fluid and pleural biopsy, with and without applying Light's criteria in multiple scenarios. For each scenario, we used the receiver operating characteristic curve to identify a diagnostic cut-off value for pleural fluid adenosine deaminase, and estimated its positive and negative predictive values., Results: A total of 860 medical records were reviewed. Pleural effusion was caused by congestive heart failure, chronic renal failure, or hypoalbuminaemia caused by liver or kidney diseases in 246 (28.6%) patients, malignancy in 198 (23.0%), non-tuberculous infection in 168 (19.5%), tuberculous pleural effusion in 157 (18.3%), and miscellaneous causes in 91 (10.6%). All those with tuberculous pleural effusion had a pleural fluid adenosine deaminase level of ≤100 U/L. When analysis was restricted to 689 patients with pleural fluid adenosine deaminase level of ≤100 U/L and early negative findings for malignancy and non-tuberculous infection in pleural fluid, the positive predictive value was significantly increased and the negative predictive value non-significantly reduced. Using this approach, neither additionally restricting analysis to exudates by Light's criteria nor adding closed pleural biopsy would further enhance predictive values. As such, the diagnostic cut-off value for pleural fluid adenosine deaminase is 26.5 U/L, with a sensitivity of 87.3%, specificity of 93.2%, positive predictive value of 79.2%, negative predictive value of 96.1%, and accuracy of 91.9%. Sex, age, and co-morbidity did not significantly affect prediction of tuberculous pleural effusion using the cut-off value., Conclusion: We have established a diagnostic cut-off level for pleural fluid adenosine deaminase in the diagnosis of tuberculous pleural effusion by restricting analysis to a level of ≤100 U/L, and considering early pleural fluid findings for malignancy and non-tuberculous infection, but not Light's criteria.

Co-infection with cryptococcus and tuberculosis has rarely been reported. We herein report a case of an 80-year-old man with cryptococcal pleuritis concurrent with pulmonary tuberculosis. He was admitted for progression of left pleural effusion and consolidation in the left upper lobe. Culture for Mycobacterium tuberculosis was positive in sputum, and analyses of pleural effusion revealed lymphocyte-predominant high levels of adenosine deaminase (ADA). Medical thoracoscopy revealed massive infiltration of Cryptococcus neoformans in pleura without granuloma. This is the first case report of cryptococcal pleuritis coincident with pulmonary tuberculosis. Cryptococcal pleuritis should be ruled out when the adenosine deaminase levels are elevated in pleural effusion.

Objectives: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru., Methods: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity., Results: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2., Conclusion: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT., (© 2017 John Wiley & Sons Ltd.)

Objective: To evaluate the performance of T cell enzyme-linked immuno-spot assay (T-SPOT) on peripheral blood in combination with adenosine deaminase (ADA) on pleural fluid for diagnosis of tuberculous (TB) pleurisy within different age groups. Methods: The data of patients with pleural effusion from the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from April 2012 to November 2016 were retrospectively analyzed, and the diagnoses of these patients were histopathologically confirmed through medical thoracoscopy. The cases who had confirmed diagnosis, in the same time, received peripheral blood T-SPOT.TB were enrolled. The performance of peripheral blood T-SPOT.TB in combination with pleural fluid ADA on diagnosing TB pleurisy in the younger patients (16-59 years old) and elderly patients (≥60 years old) were analyzed respectively. The sensitivity, specificity and the receiver operating characteristic (ROC) curve were adopted for statistical analysis. Results: A total of 448 cases were finally enrolled, 341(76.1%) confirmed with TB pleurisy, 224 males, 117 females, (47±19) years old; and 107 (23.9%) classified as non-TB pleurisy, 65 males, 42 females, (61±14) years old. There were 285 cases who were classified as younger group, and the other 163 cases were classified as elderly group. The sensitivity and specificity of peripheral blood T-SPOT.TB were 85.4% (204/239) and 71.7% (33/46) in the younger patients, 76.5% (78/102) and 59.0% (36/61) respectively in the elderly patients. The sensitivity of peripheral blood T-SPOT.TB in the younger patients was significantly higher than that in the elderly patients ( P =0.047). The sensitivity and specificity were 99.2% and 95.7% in combination with peripheral blood T-SPOT.TB and pleural fluid ADA respectively in the younger patients. The area under ROC curve (AUC) of T-SPOT.TB in the younger patients was 0.833, AUC of T-SPOT.TB combined with ADA was 0.911. The combination test of 2 tests had the sensitivity of 96.1% and the specificity of 90.2% respectively in the elderly patients. The AUC of T-SPOT.TB in the elderly patients was 0.747, AUC of T-SPOT.TB combined with ADA was 0.911. Conclusion: Peripheral blood T-SPOT.TB combined with pleural fluid ADA can improve the diagnostic performance for TB pleurisy with different ages, especially for elderly patients who can't tolerate pleural biopsy.

Background: Pleural fluid adenosine deaminase (pfADA) is not routinely measured in patients with undiagnosed pleural effusion due to limited evidence of its diagnostic utility in areas of low tuberculosis (TB) prevalence., Methods: We conducted a retrospective consecutive case series analysis of all patients who underwent pfADA testing from 2009 to 2015 at a tertiary service pleural centre in south London. Using receiver operating characteristic (ROC) curve analysis, we identified the optimal threshold at which maximal sensitivity and specificity were achieved., Results: Of the 132 patients tested for pfADA, 27 had confirmed pleural TB and 105 did not, with median pfADA levels of respectively 63 IU/l (interquartile range [IQR] 47-88) and 12 IU/l (IQR 7.5-22.5). ROC curve analysis determined the optimal pfADA cut-off to be 30 IU/l, which had positive and negative predictive values of respectively 60.5% and 98.9%, 96.3% sensitivity (95%CI 0.892-1.000) and 83.8% specificity (95%CI 0.768-0.909). The calculated area under the ROC curve was 0.934 (95%CI 0.893-0.975)., Conclusion: A pfADA level <30 IU/l makes a diagnosis of TB highly unlikely in the South London population. Its high sensitivity and negative predictive values make pfADA a valuable screening test for excluding suspected pleural TB.

Tuberculous pleurisy is one of the most common types of extrapulmonary tuberculosis, but its diagnosis remains difficult. In this study, we report for the first time on the detection of cell-free Mycobacterium tuberculosis DNA in pleural effusion and an evaluation of a newly developed molecular assay for the detection of cell-free Mycobacterium tuberculosis DNA. A total of 78 patients with pleural effusion, 60 patients with tuberculous pleurisy, and 18 patients with alternative diseases were included in this study. Mycobacterial culture, the Xpert MTB/RIF assay, the adenosine deaminase assay, the T-SPOT.TB assay, and the cell-free Mycobacterium tuberculosis DNA assay were performed on all the pleural effusion samples. The cell-free Mycobacterium tuberculosis DNA assay and adenosine deaminase assay showed significantly higher sensitivities of 75.0% and 68.3%, respectively, than mycobacterial culture and the Xpert MTB/RIF assay, which had sensitivities of 26.7% and 20.0%, respectively ( P < 0.01). All four of these tests showed good specificities: 88.9% for the adenosine deaminase assay and 100% for the remaining three assays. The T-SPOT.TB assay with pleural effusion showed the highest sensitivity of 95.0% but the lowest specificity of 38.9%. The cell-free Mycobacterium tuberculosis DNA assay detected as few as 1.25 copies of IS 6110 per ml of pleural effusion and showed good accordance of the results between repeated tests ( r = 0.978, P = 2.84 × 10 -10 ). These data suggest that the cell-free Mycobacterium tuberculosis DNA assay is a rapid and accurate molecular test which provides direct evidence of Mycobacterium tuberculosis etiology., (Copyright © 2017 American Society for Microbiology.)

Background: This study aimed to assess the role of RNA-dependent adenosine deaminase (ADAR1) in cervical squamous cell carcinoma occurrence and progression., Methods: ADAR1 expression levels in stage IA and stage IIA cervical squamous cell carcinoma (group A), cervical intraepithelial neoplasia (CIN) specimens (group B), as well as normal and inflamed cervical tissue samples (group C) were assessed by immunohistochemistry. Clinical and pathological data of cervical squamous cell carcinoma patients undergoing surgery were retrospectively evaluated. Chi-square test, comparative analysis of survival curve, disease-free survival and COX risk assessment method were used to understand the association of ADAR1 with the occurrence and progression and prognostic significance of cervical squamous cell carcinoma., Results: ADAR1 is expressed in the cytoplasm and nuclei. The expression level was high in squamous cell carcinoma tissues (81.18%), while relatively low in the CIN group (21.56%). And there was no expression in non-cancerous tissues. The differences between them were statistically significant using P < 0.05 as criterion. One-factor analysis revealed that ADAR1 was significantly correlated with tumor diameter, horizontal diffusion diameter, vascular invasion, parametrial invasion, vaginal involvement, and pathologically diagnostic criteria for perineural invasion (PNI). Meanwhile, the overall survival rate of ADAR1 positive patients was significantly lower compared with that of patients with no ADAR1 expression (P < 0.05). Analysis also showed that disease-free survival time of ADAR1 positive patients was shorter than that of ADAR1 negative patients, and the difference was significant (P < 0.01). Finally, COX risk assessment showed that parametrical invasion had independent prognostic factors for overall survival of squamous cell carcinoma., Conclusions: Results indicated that ADAR1 might play an important role in the occurrence, progression and prognosis of cervical squamous cancer.

Two general and reliable fluorescence sensors were proposed in this work utilizing aptamer DNA-templated silver nanoclusters (Ag NCs). Both DNA-AgNCs could be used for label-free detecting of ATP with the limits of detection of 0.44 and 0.65mM. One of them was further applied to monitor the activity of adenosine deaminase (ADA). In our effort to elucidate the light-up mechanism, we studied a total of six Ag NCs prepared by different DNA sequences, and found that they showed different sensitivity to ATP. Both BT3T3- and BT3T3(R)-templated Ag NCs were chose to make particular studies by UV-vis, TEM, fluorescence, and TCSPC methods. The results showed that when DNA-Ag NCs was kept for 1.5h and presented a strong fluorescence, the addition of ATP failed to cause a large change of fluorescence intensity; on the contrary, after Ag NCs was kept for 24h and emitted a weak fluorescence, adding ATP was able to result in the large fluorescence enhanced of 43 and 33 times for BT3T3- and BT3T3(R)-templated Ag NCs, respectively. The possible mechanism was also suggested that ATP binding to aptamer segment of template induced the change of the DNA secondary structure, which made the aggregated Ag nanoparticles disperse into Ag NCs with an average diameter of about 2nm that were responsible for the large fluorescence increase. Moreover, ATP could protect the fluorescence intensity of BT3T3(R)-templated Ag NCs from quenching for at least 9h., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Tuberculous peritonitis is rare in the United States but continues to be reported to occur in certain high-risk populations, which include patients with AIDS or cirrhosis, patients on continuous ambulatory peritoneal dialysis, recent immigrants from areas of high endemicity, and those who are immunosuppressed. The diagnosis of this disease requires a high clinical index of suspicion and should be considered in the differential of ascites with a lymphocyte predominance and serum-ascitic albumin gradient of <1.1 mg/dl. Microbiological or pathological confirmation remains the gold standard for diagnosis. Ascitic fluid cultures have low yield, but peritoneoscopy with biopsy or cultures frequently confirms the diagnosis. Newer techniques with future application include determination of adenosine deaminase and interferon gamma levels in ascitic fluid. Ultrasound and computed tomography are frequently used to guide fluid aspiration and biopsies. Six months of treatment with antituberculosis therapy is adequate except in cases of drug-resistant tuberculosis. The role of steroids remains controversial. Surgical approaches may be required to deal with complications including bowel perforation, intestinal obstruction from adhesions, fistula formation, or bleeding.

The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remains difficult despite the availability of numerous diagnostic tools. The current study aimed to evaluate the performance of the whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional laboratory biomarkers in differential diagnosis of TPE and MPE in high tuberculosis prevalence areas. A total of 117 patients with pleural effusions were recruited, including 91 with TPE and 26 with MPE. All of the patients were tested with QFT-GIT, and the conventional biomarkers in both blood and pleural effusion were detected. The level of antigen-stimulated QFT-GIT in the whole blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33 IU/mL, P<0.0001). The sensitivity and specificity of QFT-GIT for the diagnosis of TPE were 93.0% and 60.0%, respectively. Among the biomarkers in blood and pleural effusion, pleural adenosine deaminase (ADA) was the most prominent biomarker, with a cutoff value of 15.35 IU/L. The sensitivity and specificity for the diagnosis of TPE were 93.4% and 96.2%, respectively. The diagnostic classification tree from the combination of these two biomarkers was 97.8% sensitive and 92.3% specific. Ultimately, the combination of whole blood QFT-GIT with pleural ADA improved both the specificity and positive predictive value to 100%. Thus, QFT-GIT is not superior to pleural ADA in the differential diagnosis of TPE and MPE. Combined whole blood QFT-GIT and pleural ADA detection can improve the diagnosis of TPE.

Objectives: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics., Methods: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1) patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2) patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman's correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase., Results: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01). The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01) at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%); a specificity of 73.7% (56.9-86.6%); positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively., Conclusions: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the pleural space, which is useful for the selection of antibiotics.

Objective: To assess the 2012 served available market for tuberculosis (TB) diagnostics in China in the sector served by the China Centre for Disease Control and Prevention (CDC) and the hospital sector in China, including both designated TB hospitals and general hospitals., Design: Test volumes and unit costs were assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs), smear microscopy, serology, cultures, speciation tests, nucleic-acid amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase tests (ADA). Data were obtained from electronic databases (CDC sector) and through surveys (hospital sector), and were estimated for the two sectors and for the country as a whole. Test costs were estimated by staff at China CDC, and using published literature., Results: In 2012, the China CDC and hospital sectors performed a total of 44 million TB diagnostic tests at an overall value of US$294 million. Tests used by the CDC sector were smear microscopy, solid and liquid culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and serology. The hospital sector accounted for 76% of the overall test volume and 94% of the market value., Conclusion: China has a very large TB diagnostic market that encompasses a wide range of diagnostic tests, with the majority being performed in Chinese hospitals.

Objective Although tuberculous pleural effusion (TPE) is commonly characterized by lymphocytic predominance and high adenosine deaminase (ADA) levels, it may present with neutrophilic predominance or low ADA levels, which are more commonly found in parapneumonic effusion (PPE) or malignant pleural effusion (MPE), respectively. A few studies have observed that the atypical pleural fluid profiles of these cases of TPE may resolve at follow-up thoracentesis. However, these observations were incompletely analyzed and lacked comparison with proper control groups. Thus, limited data are available comparing the sequential pleural fluid changes between TPE and PPE or MPE with similar pleural fluid profiles. Methods TPE, PPE, and MPE patients who underwent sequential thoracentesis were retrospectively reviewed. The sequential changes in the pleural fluid profiles were compared between neutrophilic TPE and PPE, and lymphocytic TPE and MPE with low ADA levels. Results Twenty-three TPE patients (16 with neutrophilic exudates, seven with lymphocytic exudates), 72 cases of PPE with neutrophilic exudates, and 18 cases of MPE with lymphocytic exudates were included in the analysis. A sequential shift to lymphocytic exudates occurred significantly more often in TPE than in PPE cases. The initial and follow-up ADA levels in TPE cases with a lymphocytic shift were significantly higher than those in PPE cases with a lymphocytic shift. The ADA levels in the TPE cases with initial lymphocytic exudates and low ADA levels significantly increased at follow-up thoracentesis. For the TPE and MPE cases with initial lymphocytic exudates and ADA levels <40 U/L, the frequency of effusion with ADA levels ≥40 U/L at the second thoracentesis was significantly higher in the TPE cases. Conclusion Follow-up thoracentesis may provide useful information for clinical decision-making in suspected atypical TPE cases with neutrophilic exudates or low ADA levels.

Objective: The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment. Paliperidone is a newly commercialized antipsychotic whose formulation includes the principal active metabolite risperidone, 9-hydroxyrisperidone. Ever since the relationship between schizophrenia and oxidative stress was first demonstrated, many studies have been conducted in order to probe the potential protective effects of antipsychotic drugs on the oxidant-antioxidant system and lipid peroxidation. The basic aim of this study is to determine the effects of the newly marketed drug paliperidone on the activities of the enzymes adenosine deaminase (ADA), xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as on malondialdehyde (MDA) and nitric oxide (NO) levels in rat brain tissues., Methods: Twenty male Sprague-Dawley rats were used for the study, which were divided into two equal groups. The first was the control group (n = 10) and the second was the paliperidone group (n = 10). Saline was administered once daily for 14 days in the control group. In the paliperidone group, paliperidone was administered once daily with a dose of 1 mg/kg for 14 days. All rats were sacrificed at the end of the fourteenth day. Brain samples were collected and then analyzed., Results: Our results demonstrated that paliperidone significantly decreased the activities of ADA (P = 0.015), XO (P = 0.0001), and CAT (P = 0.004) while insignificantly increasing the activity of SOD (P = 0.49), MDA (P = 0.71), and NO (P = 0.26) levels in rat brain tissues. In addition, paliperidone insignificantly decreased the activity of GSH-Px (P = 0.30) compared to the control group in rat brain tissues., Discussion: In conclusion, the data obtained in this study suggest that paliperidone can positively alter antioxidant status and, accordingly, can offer positive outcomes in the treatment of schizophrenia by reducing activity in the enzymes ADA and XO, which are associated with purine metabolism. We believe that such a comprehensive approach used with other antipsychotic drugs warrants further study.

Introduction: Closed needle pleural biopsy (CNPB) has historically been the gold standard procedure for the diagnosis of pleural tuberculosis. Adenosine deaminase (ADA) is an efficient biomarker for tuberculosis that is measurable in pleural fluids., Objective: We compared the diagnostic accuracy of the pleural ADA (P-ADA) level and histopathological findings of CNPB specimens in patients with pleural tuberculosis., Methods: This prospective study consisted of two groups of examinations with a proven diagnosis of pleural effusion. The P-ADA level was measured in 218 patients with pleural effusion due to a number of causes, and 157 CNPB specimens underwent histopathological analysis., Results: CNPBs were performed in patients with tuberculosis (n=122) and other diseases: adenocarcinoma (n=23), lymphoma (n=5), systemic lupus erythematosus (n=4), squamous cell carcinoma (n=2), and small cell lung cancer (n=1). According to the ROC curve, the optimal cut-off value of the P-ADA level (Giusti and Galanti colorimetric method) was equal to or greater than 40.0 U/L. The diagnostic accuracy of the P-ADA test was 83.0%, and that of histopathological examination of the CNPB tissue, was 78.8% (AUC=0.293, P=0.7695). The association between the P-ADA assay and pleural histopathology was 24.41 (P<0.0001). The tetrachoric correlation coefficient was 0.563 (high correlation)., Conclusion: In Brazil and other countries with a high incidence of tuberculosis, P-ADA activity is an accurate test for the diagnosis of tuberculous pleural effusions, and its use should be encouraged. The high diagnostic performance of the P-ADA test could to aid the diagnosis of pleural tuberculosis and render CNPB unnecessary.

Objective: To investigate the diagnostic accuracy of the combination of interleukin-33 (IL-33) and adenosine deaminase (ADA) for differentiating TPE from pleural effusions with the other etiologies., Methods: Pleural effusion samples were collected from 32 TPE patients and 55 non-TPE patients. Pleural levels of IL-33 and ADA were measured by ELISA. The corresponding biochemical indexes were also simultaneously determined., Results: The pleural levels of IL-33 and ADA in the TPE group were significantly higher than those in the non-TPE group. With a cut-off value of 68.3 pg/ml, the sensitivity and specificity for IL-33 were 83.9% and 70.9%, respectively. While for ADA, the sensitivity and specificity were 87.5% and 87.3%, respectively at a cut-off value of 10.25 U/L. Combined use of IL-33 and ADA measurements further increased the sensitivity or specificity., Conclusion: Our study suggests that the applications of new biomarker IL-33, along with ADA, may serve as efficient diagnosis strategies in the management of pleural TB. Further studies at a large scale should be performed to validate our findings.