Adenosine Deaminase Concentration Research Articles

Salivary and serum haptoglobin, adenosine deaminase, and immunoglobulin G in growing pigs

BackgroundIdentification of animals in need of medical treatment is important in porcine health management, where analytical samples applicable at farm level could be utilized. Several biomarkers are measurable in saliva, which is less stressful to collect than blood. Saliva sampling is easy to learn and repeatable, making it suitable for monitoring purposes. Previous research suggests that porcine health biomarkers are dependent on production stage and gender, and that combining biomarkers improves diagnostic sensitivity. However, proper monitoring of biomarkers during the complete production cycle has not been studied. We aimed to describe the dynamics of salivary and serum haptoglobin (Hp), adenosine deaminase (ADA), and immunoglobulin G (IgG) in four production stages (suckling, early growing, late growing, finishing), on commercial Finnish pig farms using a total of 117 piglets. The relationship between gender and biomarker dynamics was investigated, as well as the relationships between these biomarkers in saliva and serum.ResultsThe highest salivary concentrations of Hp, ADA and IgG were measured in suckling piglets. The differences between production stages were generally larger in saliva than for the corresponding serum biomarkers. All correlation coefficients between salivary biomarkers were positive in each production stage and the strength of the correlation varied from 0.245 to 0.762. No similar trend was observed regarding correlation coefficients either between serum biomarkers or between salivary and serum biomarkers. Gender was associated with some biomarker concentrations.ConclusionsThe biomarker dynamics supported previous findings that collection of analytical samples should be conducted in age-matched populations. Positive and even strong relationships between salivary biomarkers indicate the potential to use especially saliva for health monitoring. Our results also suggest the importance of considering gender effects when assessing some salivary or serum biomarkers.

Decreased circulating CD73 and adenosine deaminase are associated with disease severity in hospitalized patients with COVID-19.

SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity. Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity. Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection. Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.

Serum adenosine deaminase activity and acute cerebral infarction: a retrospective case-control study based on 7913 participants.

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. 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. 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. 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.

Diagnostic value of serum adenosine deaminase in tuberculous lymphadenitis

Background: Extra-pulmonary tuberculosis often requires FNAC or biopsy of lymph node to reach a final diagnosis of tuberculous lymphadenitis, which is invasive, expensive, and needs an advanced setting. Estimation of adenosine deaminase (ADA) in different body fluid and serum has been suggested as a quick, cheap, and reliable test for tuberculosis. Objective: The study was intended to assess the usefulness of serum ADA in the diagnosis of tuberculous lymphadenitis. Methods: This was a cross-sectional observational study, conducted in BSMMU over a two year period and included 68 participants, divided equally into two group e.g. tuberculous lymphadenitis and a healthy comparison group. As tuberculous lymphadenitis, only newly diagnosed cases, labeled on the basis of histopathological findings of epithelioid granuloma with caseation necrosis were included. Serum ADA concentrations were estimated by enzymatic method and compared between groups. Results: The mean serum ADA concentration was found to be 25.52±7.11 U/L in tuberculous lymphadenitis group, which was significantly higher (p=0.000) than that of the healthy comparison group (14.82±3.85 U/L). Three different cut-off values of serum ADA (18.25 U/L, 20.45 U/L, 22.15 U/L) were used to determine the best predictive value for the diagnosis of tuberculous lymphadenitis. Sensitivity and specificity of these cut off values were 91.2% and 82.4%, 79.4% and 88.2%, 67.6% and 97.1% respectively. Conclusion: It is clearly denoted by the study that, tuberculous lymphadenitis patients has significant higher serum ADA then the healthy comparison group. This result indicates that serum ADA can be used as a useful adjunct in the diagnosis of tuberculous lymphadenitis with conventional investigations. Bangladesh Med Res Counc Bull 2021; 47(2): 151-155

Dysfunction of the Purinergic System in Bipolar Disorder

Objective: To verify the purinergic hypothesis of bipolar disorder (BD), we assessed the concentration of various components of the purinergic system in manic and depressed bipolar patients. Methods: Sixty-two patients (19 male and 43 female), aged 22–69 (49 ± 14) years, with BD were studied. Twenty-three patients (9 male and 14 female) were assessed during a manic episode and subsequent remission, and 39 patients (10 male and 29 female) were investigated in a depressive episode and the following remission. Twenty-two healthy subjects (8 male and 14 female), aged 19–70 (41 ± 14) years, served as the control group (CG). The severity of symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The concentrations of uric acid (UA) were estimated by the uricase-based method, whereas xanthine dehydrogenase (XDH), adenosine (Ado), and adenosine deaminase (ADA) by ELISA. Results: The mean score in the acute episode was 32 ± 8 points in the YMRS for mania and 31 ± 8 in the HDRS for depression. UA levels were significantly higher in female bipolar patients compared to the females in the CG. The concentrations of XDH, Ado, and ADA were significantly lower in bipolar patients both during an acute episode and remission compared to CG. Conclusions: A significant dysfunction of the purinergic system in patients with BD was observed. In most instances, the disturbances were not different in the acute episode than in remission what qualifies them as trait dependent. The results may confirm the role of the purinergic system in the pathogenesis of BD.

Dynamics of Salivary Adenosine Deaminase, Haptoglobin, and Cortisol in Lipopolysaccharide-Challenged Growing Pigs.

Infectious and inflammatory conditions are common especially in growing pigs. Lipopolysaccharide (LPS) is an important antigenic structure of Gram-negative bacteria and can be used to induce inflammation experimentally. As pigs are usually group-housed in commercial conditions, it is difficult to detect sick individuals, particularly at an early stage of illness. Acute phase proteins such as haptoglobin (Hp) are known indicators of an activated innate immune system whereas adenosine deaminase (ADA) is a relatively novel inflammatory biomarker in pigs. Both parameters can be measured in saliva and could be used as indicators of inflammation. Compared with blood sampling, saliva sampling is a less stressful procedure that is rapid, non-invasive and easy to perform both at group and at individual level. In this blinded randomized clinical trial, 32 female pigs at their post-weaning phase were allocated to one of four treatments comprising two injections of the following substance combinations: saline-saline (SS), ketoprofen-saline (KS), saline-LPS (SL), and ketoprofen-LPS (KL). First, ketoprofen or saline was administered intramuscularly on average 1 h before either LPS or saline was given through an ear vein catheter. In all groups, saliva was collected prior to injections (baseline) and at 4, 24, 48, and 72 h post-injection for determination of ADA, Hp, and cortisol concentrations. A multivariate model was applied to describe the dynamics of each biomarker. Pairwise relationships between ADA, Hp, and cortisol responses from baseline to 4 h post-injection within the SL group were studied with Spearman correlations. A significant increase in the SL group was seen in all biomarkers 4 h post-injection compared to baseline and other time points (pairwise comparisons, p < 0.01 for all) and ketoprofen alleviated the LPS effect. We found a significant positive correlation between ADA and Hp within the SL group (r = 0.86, p < 0.05). The primary and novel findings of the present study are the response of ADA to LPS, its time course and alleviation by ketoprofen. Our results support the evidence that ADA and Hp can be used as inflammatory biomarkers in pigs. We suggest further studies to be conducted in commercial settings with larger sample sizes.

Diagnostic Importance of Cerebrospinal Fluid Adenosine Deaminase Levels in Tuberculous Meningitis

Introduction: Estimation of Cerebrospinal Fluid (CSF) Adenosine Deaminase (ADA) is used for early diagnosis of Tuberculous Meningitis (TBM) and has got importance in differentiating TBM from bacterial and viral types of meningitis. Hence, estimation of ADA in CSF can be carried out in all clinically suspected meningitis patients, especially in developing countries like India with high prevalence of Tuberculosis (TB). Aim: To evaluate CSF ADA as a diagnostic test for TBM. Materials and Methods: The prospective study was done on 80 cases admitted with meningitis in Government General Hospital Kakinada, Andhra Pradesh, India, in a period of eight months during August 2018 to March 2019. In all the subjects the concentrations of CSF ADA, Glucose, Total proteins, Calcium, and Phosphorus were assayed. Results: The results shows that the mean values of CSF ADA in TBM were significantly increased (15.13±12.2) when compared with other types of meningitis due to stimulation of T-cells by Mycobacterium antigens. Mean values of CSF glucose were significantly decreased in bacterial and TBM. Mean values of CSF total proteins were increased in all three types. Conclusion: Therefore, this study suggests the need for routine measurement of CSF ADA in the diagnosis of TBM and thus helps in early detection of TBM which warrants timely intervention leading to lowered morbidity and mortality.

Starry sky in the abdomen

A Vietnamese woman aged 23 years with a 3-year history of intermittent abdominal pain presented to our outpatient clinic at Okayama City Hospital, Okayama, Japan. She had no previous significant cardiovascular or gastrointestinal problems. She also denied any drug abuse, lead poisoning, allergies, abdominal injury, or psychiatric disorders. Her vital signs were normal. She exhibited mild tenderness of her epigastrium without guarding or rebound tenderness. A chest x-ray showed no abnormality. Abdominal ultrasonography confirmed the presence of intermediate splenic and pelvic ascites, but there was no hepatosplenomegaly. CT showed calcified mediastinal nodes, diffuse thickening and nodularity of the omentum, mesenteric lymphadenopathy, and ascites (figure, A). We were unable to drain abdominal ascites because there was no safe route of access. A subsequent QuantiFERON-TB Gold test was positive. Exploratory laparoscopy showed numerous white, miliary nodules on the peritoneum, round ligament of the liver, and hepatic surface (figure, B). Analyses of ascitic fluid showed an adenosine deaminase concentration of 136·5 U/L. Although ascites culture and PCR for Mycobacterium tuberculosis were negative, caseating granulomas with Langhans giant cells were detected in specimens of omentum. Based on these clinical findings, we made a diagnosis of tuberculous peritonitis. The patient was given anti-tuberculous treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months, followed by rifampicin and isoniazid for 4 months. After treatment, her abdominal symptoms improved, and ascites resolved completely.

Influence of age on the diagnostic accuracy of soluble biomarkers for tuberculous pleural effusion: a post hoc analysis

BackgroundAccurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients’ age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE).MethodsTwo hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages.ResultsData from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884–1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932–0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort.ConclusionsAmong young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.

Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients.

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4+ T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-naïve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-naïve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX® MAP-Luminex® Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-naïve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.

Effect of ontogeny and vaccination on plasma adenosine deaminase (ADA)-1 and -2 levels across the first week of human life

Abstract Introduction Adenosine is a purine metabolite that acts on its leukocyte receptors to inhibit inflammatory and Th1-polarizing cytokine production. Newborns exhibit lower plasma levels of adenosine deaminase (ADA), an enzyme that metabolizes extracellular adenosine, resulting in elevated plasma adenosine levels and a Th2/anti-inflammatory bias. Humans express two ADA isoforms: ADA1 and ADA2. Characterizing the impact of ontogeny and vaccination on levels of ADA1 and ADA2 may provide insight into mechanisms regulating early life immune development. Methods Newborns were recruited at the MRC Unit-Gambia and randomized to either Hepatitis B (HepB), BCG, or the combination of both vaccines. Plasma was collected at birth (day of life (DOL) 0) and at DOL 1, 3, or 7. Plasma levels of ADA1 and ADA2 were measured by a chromogenic assay. Log-transformed ADA concentrations were compared using ANOVA. Results In this interim analysis, we measured n = 51–53 participants per vaccine group per timepoint. ADA2 activity ex vivo in plasma derived from Gambian newborns increased by median fold changes of 1.6 (control), 1.6 (HepB), 1.5 (BCG), and 1.9 (HepB+BCG) over the first week of life. The changes in ADA2 for all groups were statistically significant over DOL 0. HepB and BCG immunizations were both associated with statistically significant 1.5-fold decrease in ADA1 across the first week of life. Conclusions Neonatal plasma ADA2 activity rises across the first week of life, suggestive of ontogeny-specific changes that promote Th2/anti-inflammatory immune status. Immunization at birth with HepB or BCG may be associated with lower ADA1 across the first week of life. ADA isoforms may be useful biomarkers of immune development and vaccine responses.

Multicenter evaluation of the acid-fast bacillus smear, mycobacterial culture, Xpert MTB/RIF assay, and adenosine deaminase for the diagnosis of tuberculous peritonitis in China

BackgroundThe 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). MethodsThe 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. ResultsIn 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). ConclusionsIn 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.

The diagnostic effect of sequential detection of ADA screening and T-SPOT assay in pleural effusion patients

Purpose To evaluate the diagnostic effect of sequential detection of Adenosine deaminase (ADA) screening and T-SPOT assay on tuberculosis (TB) pleurisy in pleural effusion patients. Materials and methods 248 pleural effusion patients (172 TB and 76 non-TB) were retrospectively analyzed in the study. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. T-SPOTT assays were performed in pleural fluids. The relationship between ADA, T-SPOT and the occurrence of TB pleurisy was evaluated using logistic regression analysis. Results The level of pleural ADA and positive rate of T-SPOT were all higher in TB pleurisy group than non-TB pleurisy group (p < .001). The positive rate of T-SPOT detection reached 98.83% in the TB pleurisy group while only 40.7% in non-TB pleurisy group (p < .001). Additionally, 8 patients (4.65%) in the TB pleurisy group showed the level of pleurisy ADA exceeded 40 IU/L while only one patient (1.31%) in the non-TB pleurisy group. Conclusion The sequential detection of ADA screening and T-SPOT assay was found to be an accurate and rapid method for identifying TB pleurisy from pleural effusion, which would promote effective treatment.

Development of a Simple Assay Method for Adenosine Deaminase via Enzymatic Formation of an Inosine-Tb3+ Complex.

Adenosine deaminase (ADA), which catalyzes the irreversible deamination of adenosine to inosine, is related to various human diseases such as tuberculous peritonitis and leukemia. Therefore, the method used to detect ADA activity and screen the effectiveness of various inhibitor candidates has important implications for the diagnosis treatment for various human diseases. A simple and rapid assay method for ADA, based on the enzymatic formation of a luminescent lanthanide complex, is proposed in this study. Inosine, an enzymatic product of ADA with stronger sensitization efficiency for Tb3+ than adenosine, produced a strong luminescence by forming an inosine-Tb3+ complex, and it enabled the direct monitoring of ADA activity in real-time. By introducing only Tb3+ to adenosine and ADA in the buffer, the enhancement of luminescence enabled the detection of a low concentration of ADA (detection limit 1.6 U/L). Moreover, this method could accurately determine the inhibition efficiency (IC50) of the known ADA inhibitor, erhythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), and the inhibition of ADA could be confirmed by the naked eye. Considering its simplicity, this assay could be extended to the high-throughput screening of various ADA inhibitor candidates.

Split aptamer based sensing platform for adenosine deaminase detection by fluorescence resonance energy transfer

In this paper, a split aptamer based fluorescence resonance energy transfer (FRET) platform was constructed for the determination of adenosine deaminase (ADA) activity by using gold nanoclusters (AuNCs) and gold nanoparticles (AuNPs). A single adenosine triphosphate (ATP) aptamer was split into two fragments (referred to as P1 and P2). P1 was covalently attached to the AuNCs at the 5′ end (P1-AuNCs), and P2 was labeled with AuNPs at the 3′ end (P2-AuNPs). In the presence of ATP, ATP bound with the two fragments with high affinity to link P1-AuNCs and P2-AuNPs together, thus the fluorescence of P1-AuNCs was quenched via FRET from P1-AuNCs to P2-AuNPs. With the addition of ADA, ATP was transformed into inosine triphosphate (ITP), and then P1 and P2 were released to cause the fluorescence recovery of the system. So a split aptamer based FRET platform for ADA detection can be established via the fluorescence intensity change of the system. This platform showed a good linear relationship between the fluorescence intensity and ADA concentration in the range of 2–120 U L−1, and the limit of detection (LOD) was 0.72 U L−1. Moreover, the detection of ATP in human serum sample demonstrated the accuracy and applicability of the method for ADA detection in real sample.

Cerebrospinal fluid findings in chronic active Epstein-Barr virus infection with central nervous system involvement

As chronic active Epstein-Barr virus (EBV) infection (CAEBV) progresses, EBV-infected tumor cells invade the central nervous system (CNS). To establish a diagnostic procedure for CNS invasion, we retrospectively analyzed cerebrospinal fluid (CSF) obtained from eight patients. Two patients presented with consciousness disturbance and were diagnosed with CNS invasion based on scan and autopsy results, respectively. The remaining six patients were diagnosed without CNS invasion by clinical findings and scans. In the two patients with CNS invasion, the number of mononuclear cells and the protein concentration were increased, whereas the CSF to serum glucose ratio and the adenosine deaminase concentration were raised. In one of the two patients, however, bacterial meningitis could not be excluded. Cytological examination of CSF demonstrated class 1-3. Notably, the CSF EBV-DNA load was positive in all patients, independent of CNS invasion diagnosis, and the CSF load correlated with that of the peripheral blood. Taken together, this indicates that CSF may lack the specific markers of CNS invasion in CAEBV patients. The CSF EBV-DNA load and the cytological analysis did not reflect CNS invasion; therefore, new biomarkers need to be established.

Wet M1a non-small cell lung cancer: is it possible to predict recurrence of pleural effusion?

The propose was to recognize risk factors of malignant pleural effusion (MPE) recurrence in patients with symptomatic M1a non-small cell lung cancer (NSCLC). All patients with NSCLC and MPE submitted to pleural palliative procedures were enrolled in a prospective study. Group I contained patients who had pleural recurrence, and Group II with no pleural recurrence. Prognostic factors for pleural recurrence were identified by univariable analysis, using Fisher's exact test for categorical variables and Student's t test for quantitative variables. Afterwards the significant variables were entered into a multivariable logistic regression analysis (with P<0.05 considered significant). Receiver operating characteristics (ROC) analysis determined the cutoff points for continuous variables. A total of 82 patients were included in the analysis. There were 15 patients (18.3%) in Group I and 67 patients (81.7%) in Group II. Univariable analysis regarding factors affecting postoperative recurrence was: adenosine deaminase concentration in pleural fluid <16 mg/dL (P=0.04), albumin concentration in pleural fluid <2.4 mg/dL (P=0.03), administration of second-line palliative chemotherapy (P=0.018) and type of procedure [therapeutic pleural aspiration (TPA)] (P=0.023). At the multivariable analysis, only the type of procedure (TPA) (P=0.031) was identified as independent predictor of recurrence. The identification of this factor may assist the choice of the optimal palliative technique; at the first episode of MPE in NSCLC patients and definitive procedure as pleurodesis or indwelling pleural catheter are recommended.

OA21.05 Wet M1a Non-Small Cell Lung Cancer: Is It Possible to Predict Recurrence of Pleural Effusion?

Pleural and oncological treatment options for malignant pleural effusion (MPE) are increasing and hence, more accurate prognosis at presentation may help to identify patients with the higher risk of pleural recurrence, in order to individualize more intensive treatment strategies. The aim of this study was to identify predictors of malignant pleural effusion recurrence in patients with M1a non-small cell lung cancer (NSCLC). All patients with NSCLC and MPE submitted to pleural palliative procedures including simple pleural drainage, videothoracoscopic pleural drainage, pleurodesis and indwelling pleural catheter were enrolled in a prospective study between 2014 and 2015, and divided into two groups. Group I included patients who had pleural recurrence, and Group II with no pleural recurrence after the palliative procedures. Prognostic factors for pleural recurrence were identified by univariate analysis, using Fisher's exact test for the analysis of categorical variables and Student’s t test for quantitative variables. Subsequently the significant variables were entered into a multivariate logistic regression analysis (with p< 0.05 considered significant). The cutoff points for any significant continuous variables were determined by receiver operating characteristics (ROC) analysis. A total of 82 patients were included in the analysis. Median follow-up time for surviving patients was 81 days (range 1 to 1070 days). There were 15 patients (18.3%) in Group I and 67 patients (81.7%) in Group II. Univariate analysis of factors affecting postoperative recurrence were: adenosine deaminase concentration in pleural fluid < 16 mg/dl (p=0.04), albumin concentration in pleural fluid < 2.4 mg/dl (p= 0.03), administration of second-line palliative chemotherapy (p= 0.018) and type of procedure (simple pleural drainage vs. videothoracoscopic pleural drainage, pleurodesis and indwelling pleural catheter) (p= 0.023). At the multivariate analysis, only the type of procedure (simple pleural drainage)(p= 0.031) was identified as independent predictor of recurrence. In our cohort of NSCLC patients with MPE submitted to pleural palliative procedures, simple pleural drainage was the only significantly factor associated with recurrence of MPE. The identification of this factor may assist the choice of the optimal palliative technique, at the first episode of MPE in NSCLC patients. Definitive procedure as pleurodesis is recommended, the indwelling pleural catheter or videothoracoscopic drainage are options for patients whom lung are trapped.

P2.01-042 T Cells Subsets with INF-Gamma, TNF-Alpha and ADA in Distinguishing Tuberculous from Malignant Pleural Effusions

The differential diagnosis of tuberculous and malignant pleural effusion (PE) is extremely difficult and continues to pose clinical challenges. We aimed to evaluate the utility of pleural fluid Interferon gamma (IFN- γ), Adenosine deaminase (ADA), Tumar necrosis factor-alpha (TNF-a) levels with T cells subsets in differential diagnosis of malignant (MPE) and tuberculous pleural effusions (TPE). Forty patients with pleural effusion (20 tuberculous and 20 malignant) were included in the study. The percentages of CD3 lymphocyte, CD4 lymphocyte and Treg (CD4 CD25) T cells in pleural effusion from patients with tuberculous and malignant pleurisy were determined by flow cytometry. The concentrations of TNF-a, IFN-γ and ADA were simultaneously determined in pleural fluids by enzyme linked immunosorbent assay and colorimetric method. The ADA activity, TNF-a and IFN-g concentration were significantly higher in tuberculous than MPE (84.22±41.47 vs. 23.19±17.93 U/l : P<0.0001, 122.45±47.69 vs. 35.03±31.88 pg/ml : P < 0.0001 and 2.26±1.62 vs. 0.3±0.20 IU/ml : P<0.0001 respectively ). T-cells subsets (CD3 T-cells, CD4 T-cells and T reg cells) were significantly higher in TPE than MPE (76.46% vs. 65.29%; P 0.004, 51.21% vs. 43.50%; P 0.044 and 14.60% vs. 12.43%; P 0.032 respectively). CD3 plus CD4 as well as CD3 plus CD4 plus T reg combinations were all 100% specific for discriminating TPE from MPE. TNF-α plus IFN-γ, TNF-α plus ADA, as well as TNF-α plus IFN-γ plus ADA, were 100% specific for discriminating TPE from MPE. Furthermore, the specificity of combined-diagnostic value of TNF-α, IFN-γ, ADA with T cells subsets was > 95 %. The combinations of pleural fluid IFN-γ, ADA, TNF-a levels and T cells subsets could effectively address the challenge of distinguishing tuberculous pleural effusion from malignant pleural effusion.

Elevated circulatingadenosine deaminase activity in women with preeclampsia: association with pro-inflammatory cytokine production and uric acid levels.

Preeclampsia is a specific disorder of human pregnancy that is associated with hyperuricemia and higher levels of pro-inflammatory cytokines. Adenosine deaminase (ADA) is an enzyme present in all human tissues, and is considered an indicator of cellular inflammation. In the present study we assess whether adenosine deaminase (ADA) activity is altered in women with preeclampsia (PE) and contributes to elevated levels of uric acid and pro-inflammatory cytokine production. The population studied consisted of 60 women with PE, 30 normotensive pregnant women (NT) and 20 non-pregnant women (NP). Uric acid concentration and ADA activity were determined in the serum. Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for intracellular nuclear transcription factor kappa B (NF-κB) levels and for endogenous tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. The data were evaluated with parametric or non-parametric tests with significance set at P<0.05. ADA levels were higher in the PE group compared with the NT and NP groups (P<0.001). A positive correlation between ADA and uric acid levels was identified in women with PE (P<0.001). Endogenous production of IL-1β and TNF-α, as well as intracellular NF-κB levels, were higher in PBMCs from the PE group than from NT and NP women (P<0.01) and correlated with the ADA concentration in preeclamptic women (P<0.01). An elevation in ADA activity in women with PE may contribute to their increased levels of uric acid and pro-inflammatory immune activity.