Adenosine Deaminase Levels Research Articles

EXPRESS: Demographic, Clinical and Laboratory Characteristics of Extrapulmonary Tuberculosis: Eight-year Results of a Multicentre Retrospective Study in Turkey.

Extrapulmonary tuberculosis (EPTB) is an important public health problem due to its diverse clinical presentations, diagnostic complexities and significant impact on patient outcomes and public health. Our study aimed to understand the sociodemographic, clinical and laboratory characteristics as well as diagnostic and treatment modalities of adult patients with EPTB. This is a multicentric retrospective study that covers patients with EPTB cases followed up from January 2015 to December 2022 among TB dispensaries and Infectious Diseases and Clinical Microbiology clinics of 15 hospitals located in various regions of Turkey. The study included 64.6% women with a mean age of 44 years and a mortality rate of 3.5% within one year of diagnosis. Initial constitutional symptoms were predominantly fatigue (57%), anorexia (53.7%). The most commonly affected sites were the lymph nodes (49.1%) and pleura (9.7%). The lumbar region was particularly involved in cases with spinal TB. Diagnostic findings included acid-fast bacilli positivity in 27.5% of cases, TB PCR positivity in 41%, elevated adenosine deaminase levels in 91.2% (especially in pleural and peritoneal fluids) and mycobacterial culture positivity in 40.9%. Pathology slides showed granulomatous inflammation in 97.7%. Increased C-reactive protein levels correlated with the number of organs affected. Anti-TB treatment-related hepatotoxicity was detected in 8.9% of patients. In this study, it is important to note that the lumbar region is predominantly affected with involment in spinal region. C-reactive protein level was consistent with the number of organ involvements was one of the most critical results of this study.

ASSOCIATION OF SERUM ADENOSINE DEAMINASE LEVELS WITH ACUTE KIDNEY INJURY IN DIABETIC PATIENTS

Diabetes mellitus is a significant global health issue, and complications such as acute kidney injury (AKI) are prevalent in patients with type 2 diabetes. Serum adenosine deaminase (ADA) has been suggested as a potential biomarker for various metabolic conditions, including inflammation and kidney injury, but its association with diabetic kidney health remains understudied. Objective: To assess the association of serum adenosine deaminase (ADA) levels with acute kidney injury (AKI) in patients with type 2 diabetes. Methods: This observational comparative study was conducted at DHQ Teaching Hospital KDA, Kohat, from February 7, 2023, to August 7, 2023, following ethical approval. A total of 120 participants were enrolled, including 60 patients with type 2 diabetes and 60 non-diabetic controls. Laboratory investigations for both groups included serum ADA (U/L), HbA1c (%), and estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²). Statistical comparisons between groups were made using appropriate tests, and correlations between serum ADA and other parameters were assessed. Results: The mean age of diabetic patients was 55.40 ± 8.29 years, and that of controls was 54.58 ± 21.64 years. The mean serum ADA level in diabetic patients was significantly higher at 43 ± 4.29 U/L compared to 16.32 ± 1.20 U/L in controls (p = 0.0001). Diabetic patients had a mean HbA1c of 8.30 ± 0.59%, significantly higher than that of controls (5.28 ± 0.59%) (p = 0.0001). The mean eGFR in diabetic patients was 82.61 ± 17.22 mL/min/1.73 m², lower than in controls (105.97 ± 12.07 mL/min/1.73 m²) (p = 0.0001). In diabetic patients, serum ADA levels were positively correlated with HbA1c (indicating poorer glycemic control) and negatively correlated with eGFR (suggesting declining kidney function). Conclusion: Elevated serum adenosine deaminase levels in type 2 diabetic patients are significantly associated with poor glycemic control and decreased kidney function. These findings indicate that serum ADA could serve as a potential biomarker for monitoring glycemic status and kidney health in diabetic patients at risk for acute kidney injury.

Diagnostic values of adenosine deaminase cytokines in fluid contributed to the detection of extrapulmonary tuberculosis

Tuberculosis (TB) is a serious global public health problem. Detecting the changes of adenosine deaminase (ADA), interleukin (IL)-1β, IL-2, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) released from macrophages and monocytes is greatly valuable in the diagnosis of TB. Hence, this study was designed to determine the optimal cut-off points of ADA, IL-1β, IL-2, TNF-α, and IFN-γ, allowing to differentiate pleural TB (PLTB), peritoneal TB (PTB), and meningeal TB (MTB). The study included 386 patients with pleural effusion, 47 patients with peritoneal effusion, and 134 patients with encephalitis and meningoencephalitis suspect of TB. ADA was determined by an enzyme kinetics method; cytokine concentration was measured by a test based on the competitive enzyme-linked immunosorbent assay principle. Sensitivity, specificity, and positive and negative predictive value were calculated and described. In the aspiration fluid, ADA activity was greatly different between PLTB, PTB, and MTB groups with values of 37.5 U/L, 30.5 U/L, and 8.1 U/L and sensitivity and specificity of 87.7% and 83.4%; 100% and 88.9%; 97.3% and 98.6%, respectively. Similar, IFN-γ concentrations were distinctively different between PLTB, PTB, and MTB patients (with values of 120 pg/mL, 200 pg/mL, and 30 pg/mL with sensitivity and specificity of 80.3% and 80.9%; 80.0% and 92.6%; 98.6% and 61.7%, respectively). The determination of ADA and IFN-γ levels in the aspiration fluid is potentially considered a highly sensitive and specific test for differentiating PLTB, PTB, and MTB.

Exploring the Diagnostic Challenges of Pseudotumoral Peritoneal Tuberculosis That Mimics Advanced Ovarian Cancer in Women: The Role of Laparoscopy in a Case Study

This case involves a 63-year-old multiparous woman with no significant medical history and no known exposure to tuberculosis. She presented with chronic abdominal pain and weight loss, anorexia, and subjective fevers. During the clinical examination, the patient was found to have ascites, bilateral pleural effusion, fever, and a general deterioration in her condition. Blood tests revealed normochromic normocytic anemia. The C-reactive protein was elevated, and the erythrocyte sedimentation rate was accelerated. Ferritin levels were raised. Her blood sugar, hepatic and renal functions were normals. The electrolyte panel showed no abnormalities. Serologies for hepatitis B, C, and HIV were negative, and the immunological profile was normal. The ascitic tap yielded a citrine-yellow fluid, and the cytochemical analysis indicated that the ascites were exudative. Analysis of the ascitic fluid revealed that the DNA test for Mycobacterium tuberculosis was negative, but the adenosine deaminase (ADA) level was elevated. Additionally, the CA125 level was significantly elevated, exceeding 600 UI/ml. A pelvic ultrasound identified a cystic pelvic mass with thick septations but without any solid tissue component, measuring 92x69 mm. The complementary CT (Computed Tomography) scan revealed enlarged ovaries, heterogeneous on the left, associated with a moderately abundant peritoneal effusion. The laparoscopic exploration revealed inflammatory peritoneal nodules, parietal adhesions, and serous ascites. Anatomopathology confirmed peritoneal tuberculosis. The peritoneal form, particularly in its pseudotumoral manifestation, can mimic ovarian cancer. Definitive diagnosis often requires invasive procedures.

A Prospective Cross-Sectional Study on the Correlation of Adenosine Deaminase and HbA1c With Microvascular Complications in Type 2 Diabetes Mellitus at a Tertiary Care Hospital in Central India.

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition characterized by hyperglycemia, which can lead to various microvascular complications, including diabetic nephropathy, neuropathy, and retinopathy. Identifying reliable biomarkers for early detection and risk stratification of these complications is crucial for improving patient outcomes. Adenosine deaminase (ADA) and HbA1c have emerged as potential markers associated with immune function, inflammation, and long-term glycemic control. This study investigates the correlation between ADA and HbA1c levels and microvascular complications in patients with T2DM. Material and methods This prospective observational cross-sectional study involved 150 patients diagnosed with T2DM, focusing on those with diabetic nephropathy, neuropathy, and retinopathy. Clinical data were collected through patient interviews, clinical examinations, and laboratory tests, including measurements of fasting blood glucose, HbA1c, serum creatinine, ADA levels, and urine protein creatinine ratio (UPCR). Fundus examinations and nerve conduction velocity (NCV) tests were performed to assess diabetic retinopathy and neuropathy, respectively. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, New York), with statistical tests to evaluate the correlation between ADA and HbA1c levels and microvascular complications. Results The study found a significant correlation between elevated ADA and HbA1c levels and microvascular complications in patients with T2DM. Higher ADA levels were particularly associated with diabetic nephropathy (p=0.003), while HbA1c levels showed a positive correlation with all three complications: nephropathy, neuropathy, and retinopathy. The findings suggest that ADA and HbA1c levels can serve as valuable biomarkers for identifying patients at higher risk of developing these complications. Conclusion This study highlights the potential of ADA and HbA1c as biomarkers for early detection and risk assessment of microvascular complications in T2DM patients. Routine monitoring of these markers could improve the management and prognosis of diabetic patients by enabling timely interventions to prevent or mitigate the progression of complications. Further research is needed to explore the underlying mechanisms linking ADA with diabetic complications and to validate its clinical utility.

State of Adenosine Deaminase in Patients with Dyslipidemia

ABSTRACT: Background: Dyslipidemia is becoming more common across all age groups mainly in young individuals because of imbalanced diets, low physical activity, and sedentary work culture. Several studies reported that elevated serum adenosine deaminase activity was associated with dyslipidemia, but the results were not consistent. Aim: It is aimed to correlate adenosine deaminase and lipid profile parameters in patients with dyslipidemia. Material and Methods: In this case-control study, a total of 60 subjects (30 diagnosed dyslipidemia patients and 30 age and gender-matched healthy individuals) were enrolled. Serum lipid profile parameters and adenosine deaminase levels were estimated in each subject. Results: The mean levels of lipid profiles, mainly triacylglycerol (TG), low-density lipoprotein-cholesterol (LDL-C), and adenosine deaminase, were found to be significantly high, while high-density lipoprotein-cholesterol (HDL-C) was found significantly low in cases than controls (p <0.001). adenosine deaminase has not shown any significant correlation with lipid profile parameters in patients with dyslipidemia and controls. Conclusion: The result showed that the serum adenosine deaminase and serum lipid profile levels were altered in patients with dyslipidemia.

Role of Medical Thoracoscopy in undiagnosed exudative pleural effusion with low Adenosine Deaminase level: Prospective Observational study in a tertiary care hospital from Eastern India

Role of Medical Thoracoscopy in undiagnosed exudative pleural effusion with low Adenosine Deaminase level: Prospective Observational study in a tertiary care hospital from Eastern India

Adenosine deaminase is a risk factor for mortality after discharge in patients with acute myocardial infarction: Long-term clinical follow-up

BackgroundVariations in adenosine deaminase (ADA) activity have been detected in numerous cardiovascular diseases (CVDs), but there is limited research on its role in the prognosis of CVDs. In this study, we explored the role of ADA in the prognosis of patients with acute myocardial infarction (AMI). MethodIn this study, a total of 1,574 patients with a first diagnosis of acute myocardial infarction (AMI) were followed up for a median (interquartile range [IQR]) of 77.0 (50.0, 95.0) months after discharge. Cox proportional hazards regression models were used to identify factors that are substantially valuable for patient prognosis. ResultsDuring the follow-up period, the mortality rate of AMI was 12.5 %. The 3-year and 5-year overall survival (OS) rates of AMI patients were 93.8 % and 91.0 %, respectively. Multivariate Cox regression analysis revealed that serum ADA (hazard ratio [HR] = 1.166, 95 % confidence interval [CI]: 1.006–1.352) was an independent risk factor for 5-year OS after discharge in AMI patients. When serum ADA was assessed in quartiles, compared with the reference group (Quartile 1), the adjusted HR for death was 2.498 (95 % CI: 1.344–4.642) in Quartile 4 for 5-year OS and 2.508 (95 % CI: 1.145–5.496) in Quartile 4 for 3-year OS. ConclusionsSerum ADA levels at admission are a risk factor that affects the long-term prognosis of AMI patients after hospital discharge.

Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis.

Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM). An ecto-5'-nucleotidase (CD73) inhibitor, adenosine receptor agonists, a hypoxia-inducible factor-1α (HIF-1α) inhibitor or a vehicle were administered to control and EAM mice. Murine splenic CD4+ or regulatory T cells (Tregs) were isolated using magnetic beads and subsequently stimulated with an adenosine A2B receptor agonist, a HIF-1α inhibitor, or vehicle in vitro. In cross-sectional studies, we collected 64 serum samples (69% female, 49±9years), 63 peripheral blood samples (70% female, 50±11years), and 34 skeletal muscle samples (71% female, 63±6years) from patients with IIM. Additionally, 35 serum samples and 30 peripheral blood samples were obtained from age- and sex-matched healthy controls, and six quadriceps muscle samples were collected from patients with osteoarthritis to serve as the normal group. Patients with IIM exhibited increased CD73 [dermatomyositis (DM), polymyositis (PM): P<0.01; immune-mediated necrotizing myopathy (IMNM): P<0.0001] and adenosine deaminase (ADA) expression (DM: P<0.001; PM, IMNM: P<0.0001) in the skeletal muscles, and serum ADA levels [56.7 (95% CI: 53.7, 58.7) vs. 198.8 (95% CI: 186.2, 237.3) ng/μL, P<0.0001]. Intervention with a CD73 inhibitor exacerbated (P=0.0461), whereas adenosine receptor agonists (A1: P=0.0009; A2B: P<0.0001; A3: P=0.0001) and the HIF-1α inhibitor (P=0.0044) alleviated skeletal muscle injury in EAM mice. Elevated expression of programmed cell death protein-1 (PD1: P=0.0023) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3: P<0.0001) in skeletal muscles of patients with IIM were correlated with creatine kinase levels (PD1, r=0.7072, P<0.0001; TIM3, r=0.4808, P=0.0046). PD1+CD4+ (r=0.3243, P=0.0115) and PD1+CD8+ (r=0.3959, P=0.0017) T cells were correlated with Myositis Disease Activity Assessment Visual Analogue Scale scores (muscle) in IIM. The exhausted Tregs were identified in the skeletal muscles of patients with IIM. Activation of the A2B adenosine receptor downregulated HIF-1α (protein or mRNA level, P<0.01), resulting in decreased T helper cell 17 (Th17) (13.58% vs. 5.43%, P=0.0201) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3)+ Th17 (16.32% vs. 6.73%, P=0.0029), decreased exhausted Tregs (PD1+ Tregs: 53.55% vs. 40.28%, P=0.0005; TIM3+ Tregs: 3.93% vs. 3.11%, P=0.0029), and increased Tregs (0.45% vs. 2.89%, P=0.0006) in EAM mice. The exhausted T cells may be pathogenic in IIM,andthe activation of adenosine A2B receptor signalling pathway can regulate Th17/Treg balance and inhibit Tregsexhaustion, thereby slowing EAM disease progression.

Kinetic Determination of Cerebrospinal Fluid Adenosine Deaminase Activity for the Diagnosis of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is a common infectious disease of the central nervous system. Detection of cerebrospinal fluid (CSF) adenosine deaminase (ADA) activity for the diagnosis of TBM has a relatively high accuracy. Most previous reports determined ADA levels by following the colorimetric method of Giusti (endpoint assay). Recently, a Diazyme ADA assay kit was developed to determine CSF ADA levels. This study aimed to define the cutoff value of CSF ADA that is diagnostic for TBM with the Diazyme ADA assay kit. Adults with meningitis were included in the study. The diagnostic properties of CSF ADA for TBM as determined by the Diazyme ADA assay kit were assessed by the receiver operating characteristic curve, area under the curve, sensitivity, specificity, and likelihood ratios. There were 97 patients enrolled in the study, comprising 15 cases of TBM and 82 cases of non-TBM meningitis. The median CSF ADA activity level in the TBM group was significantly higher than in the non-TBM group (P = 0.002), with a mean difference of 14.5 U/L (95% CI: 5.3-23.8 U/L). A CSF ADA level of 6.1 U/L was the best cutoff value to differentiate between the TBM and non-TBM groups, with a sensitivity of 53.33%, a specificity of 89.02%, a positive likelihood ratio of 4.86, a negative likelihood ratio of 0.52, and an area under the curve of 0.75. A CSF ADA level of 6.1 U/L determined by the Diazyme ADA assay kit could be used as a diagnostic tool in the early diagnosis of TBM.

Increased levels of serum Adenosine deaminase (ADA) enzyme and increased risk of T cell activation markers in type 2 diabetes

Increased levels of serum Adenosine deaminase (ADA) enzyme and increased risk of T cell activation markers in type 2 diabetes

Validation of a diagnostic flowchart for tuberculous pleurisy in pleural fluid with high levels of adenosine deaminase

IntroductionAdenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart. Materials and methodsWe retrospectively collected data from 458 patients with pleural fluid ADA concentrations ≥40 U/L across eight institutions from January 2019 to December 2023. The diagnostic accuracy rate, sensitivity, and specificity of the diagnostic flowchart were analysed and compared to those in the original study. ResultsEighty-seven patients were diagnosed with tuberculous pleurisy, and 371 patients were diagnosed with other diseases. The diagnostic accuracy, sensitivity, and specificity for diagnosing tuberculous pleurisy were 77.7%, 86.2%, and 75.7%, respectively. Compared with that in the original study, the rate of tuberculous pleurisy was lower (19.0% vs. 44.5%, p < 0.001), but the diagnostic accuracy rates were not significantly different (p = 0.253). On the basis of the findings from this validation study, we have revised the flowchart to enhance its utility. ConclusionThe diagnostic flowchart exhibited high diagnostic accuracy in this validation study, comparable to that in the original study. This validation confirms the effectiveness of the flowchart, even in settings with a low incidence of tuberculosis.

Inside the Brain: Cerebrospinal Fluid Insights in Meningitis.

Background Our study focused on meningitis, an infection that can spread through the bloodstream as a primary or secondary infection from other body parts, such as sinuses, ears, and lungs. It can affect patients who have experienced trauma or surgery, as well as those with congenital defects like spina bifida. Specifically, we examined bacterial, viral, and tuberculous meningitis (TBM) cases. The primary method for confirming the diagnosis of these types of meningitis is to analyze the cerebrospinal fluid (CSF). Early diagnosis can utilize cytological and biochemical parameters. Our objective is to determine CSF's cytological and biochemical profile in patients with these specific types of meningitis. Methods A study was carried out at the central pathology lab from October 24, 2017, to April 24, 2018.CSF samples from suspected meningitis patients were examined for various parameters, including hematological, biochemical, microbiological, and cytomorphological aspects and specific tests for bacterial, fungal, and TBM. The study focused on patients aged 16 and above, excluding those under 16, non-compliant patients, and individuals with specific health conditions. Data were analyzed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States), and the results were presented through the use of mean, standard deviation, and percentages. Statistical tests were utilized to compare categorical variables and mean, with a significance level of p<0.05. Results We included a total of 156 cases, with the mean age of presentation being 56.628 years. The male-to-female ratio was 1.0526:1. Of the patients, 81 (52.1%) had been diagnosed with TBM, had elevated adenosine deaminase (ADA) levels of 48.8733±37.43740 IU/L, and CSF lymphocytosis (99%). Additionally, cases of bacterial meningitis showed markedly raised mean total leukocyte count (TLC) of 2085.50±445.47727 cells/mm3 and mean CSF protein levels of 349.45±113.73105 mg/dL. The study found a significant increase in protein levels and a decrease in glucose levels in the CSF of TBM and bacterial meningitis patients compared to those with other causes of meningitis (p<0.001). Guillain-Barre syndrome (GBS)and multiple sclerosis (MS) patients had TLC and ADA within normal limits.CSF ADA level greater than 6 IU/L showed a sensitivity of 97.53% and a specificity of 96.0%, making it the most specific test. A protein level in the CSF greater than 45 mg/dL demonstrated a sensitivity of 98.78% and a specificity of 24.32%, indicating it is sensitive but less specific in diagnosing TBM. Lymphocytic predominance, defined as TLCof more than 5 cells/mm3 with at least 50% of the cells being lymphocytes in the CSF of TBM patients, showed a sensitivity of 97.53% and a specificity of 6.67%. CSF glucose had a sensitivity of 38.27%, making it the least reliable indicator for diagnosing meningitis. Conclusion The CSF analysis is the primary diagnostic method for detecting meningitis. Its cost-effectiveness is a key factor, especially for patients from lower socioeconomic backgrounds in government medical colleges in India, where access to expensive diagnostic tests is limited. The efficiency of CSF analysis for early diagnosing different types of meningitis aids in management, helping to prevent complications and fatal outcomes.

Anti-hyperuricemia effect of Clerodendranthus spicatus: a molecular biology study combined with metabolomics

Hyperuricemia (HUA), a metabolic disease caused by excessive production or decreased excretion of uric acid (UA), has been reported to be closely associated with a variety of UA transporters. Clerodendranthus spicatus (C. spicatus) is an herbal widely used in China for the treatment of HUA. However, the mechanism has not been clarified. Here, the rat model of HUA was induced via 10% fructose. The levels of biochemical indicators, including UA, xanthine oxidase (XOD), adenosine deaminase (ADA), blood urea nitrogen (BUN), and creatinine (Cre), were measured. Western blotting was applied to explore its effect on renal UA transporters, such as urate transporter1 (URAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette super-family G member 2 (ABCG2). Furthermore, the effect of C. spicatus on plasma metabolites was identified by metabolomics. Our results showed that C. spicatus could significantly reduce the serum levels of UA, XOD, ADA and Cre, and improve the renal pathological changes in HUA rats. Meanwhile, C. spicatus significantly inhibited the expression of URAT1 and GLUT9, while increased the expression of ABCG2 in a dose-dependent manner. Metabolomics showed that 13 components, including 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PE, Tyr-Leu and N-cis-15-Tetracosenoyl-C18-sphingosine, were identified as potential biomarkers for the UA-lowering effect of C. spicatus. In addition, pathway enrichment analysis revealed that arginine biosynthesis, biosynthesis of amino acids, pyrimidine metabolism and other metabolic pathways might be involved in the protection of C. spicatus against HUA. This study is the first to explore the mechanism of anti-HUA of C. spicatus through molecular biology and metabolomics analysis, which provides new ideas for the treatment of HUA.

To Study the Combined Use of Pleural Fluid Lymphocyte / Neutrophil Ratio and ADA for the Diagnosis of Tuberculous Pleural Effusion

INTRODUCTION - Pleural effusion is the abnormal collection of fluid in the pleural space. It is classified into exudates and transudates based on Light's criteria. Among the extra pulmonary presentations after tuberculous lymphadenitis, pleural TB is the second frequent. Although many biochemical parameters, such as lactate dehydrogenase (LDH), C-reactive protein (CRP), adenosine deaminase (ADA), interferon-gamma, and procalcitonin levels have been studied in the context of the diagnosis of exudative pleural effusion, its diagnosis is still challenging. AIMS &amp; OBJECTIVES- To determine whether the combined use of ADA activity and lymphocyte/neutrophil ratio would provide a more efficient means for diagnosing tuberculous pleural effusion than the use of ADA alone. MATERIAL &amp; METHODS- Hospital based Observational study was conducted over 8 months with total number of 100 Patients diagnosed as having pleural effusion based on clinical features and chest radiography in GEMS MEDICAL COLLEGE AND HOSPITAL. Biochemical, cytological and microbiology studies were done by obtaining pleural fluid by thoracocentesis. RESULTS - out of 100 cases, 84 cases were tubercular and had high level of ADA in comparison to rest of 16 non tubercular cases. At level of 50 IU/L of ADA activity test had sensitivity of 97.6%, specificity 87.5% which was increased to 100% and 92.8% in combination with test of Lymphocytic/Neutrophilic ratio - 0.75 CONCLUSION- The combined use of ADA along with the L/N ratio would provide a more efficient means for diagnosing tuberculous pleural effusion than the use of ADA alone.

Evaluation of polymerase chain reaction and adenosine deaminase levels for rapid diagnosis of clinically suspected tuberculous pleural effusion

ABSTRACT Background: Tuberculosis (TB) often leads to pleural effusion, particularly prevalent in developing nations such as India. There has been a global rise in TB cases. Although lymphocytic predominant fluid is commonly associated with tubercular pleural effusion, it is essential to note that not all lymphocytic predominant fluids indicate TB. The diagnosis of pleural TB has benefited significantly from the use of biochemical markers. Conventional bacteriological methods are not very useful in diagnosing tubercular effusion and rarely identify Mycobacterium tuberculosis in pleural fluid. Owing to diagnostic difficulties, newer investigations, such as TB polymerase chain reaction (TB-PCR), adenosine deaminase (ADA) and culture, are amongst the most recent techniques currently used due to the challenges associated with diagnosis. Aims: This study aimed to measure the sensitivity and specificity of TB-PCR and compare them with those of ADA and TB cultures for suspected TB pleural effusion. Methods: This study included 50 patients diagnosed with pleural effusion who underwent pleural fluid analysis. Patients exhibiting exudative effusion with lymphocyte predominance also underwent a pleural biopsy. Pleural fluid ADA levels were also measured, and TB-PCR tests were conducted. Results: Eighteen patients were confirmed to have TB by biopsy. ADA was both sensitive and specific at 67% and 62.5%, respectively. However, PCR showed a sensitivity of 16.6% and a specificity of 100%. Conclusion: This study found a statistically significant association (P &lt; 0.05) between ADA levels and distinguishing pleural effusion, which is tubercular in origin, from non-tubercular effusion. Therefore, the pleural ADA estimate appears to have the potential to be a reliable test for diagnosing TB pleural effusion. It has sufficient sensitivity and specificity while being cost-effective and easily executable compared to pleural biopsy. Our study also compared the sensitivity of PCR with pleural biopsy and discovered that PCR was more specific and less sensitive.

Cerebrospinal Fluid Parameters Predicting Contralateral Isolated Lateral Ventricle in Adult Tuberculous Meningitis with Hydrocephalus Post-Ventriculoperitoneal Shunt

Hydrocephalus, a major complication in tuberculous meningitis (TBM) patients, often necessitates treatment via ventriculoperitoneal shunt (VPS). However, post-VPS, some patients develop a complication called contralateral isolated lateral ventricle (CILV), leading to persistent hydrocephalus symptoms. This study aims to evaluate cerebrospinal fluid (CSF) parameters in predicting CILV occurrence post-VPS in adult TBM patients. A retrospective analysis was conducted, focusing on the relationship between preoperative CSF parameters and the development of CILV in 40 adult TBM patients who underwent VPS. The study compared CSF parameters from lumbar puncture after admission with those from ventricular CSF post-external ventricular drainage tube insertion. CILV was observed in 6 of the 40 patients following VPS. Statistical analysis showed no significant difference between the CSF parameters obtained via lumbar and ventricular punctures. Notably, the mean CSF glucose level in patients with CILV was significantly lower (1.92mmol/L) compared to the non-CILV group (3.03mmol/L). Conversely, the median adenosine deaminase (ADA) level in the CILV group was higher (5.69 U/L) compared to the non-CILV group (3.18 U/L). The optimal cutoff values for CSF glucose and ADA levels were 1.90mmol/L and 4.80 U/L, respectively, with a sensitivity of 66.67% and 83.33% and a specificity of 88.24% and 79.41%. The study identified elevated ADA levels and decreased glucose levels in CSF as potential risk factors for CILV development in adult TBM patients post-VPS. These findings suggest the necessity for more tailored surgical approaches, in patients with altered CSF parameters to mitigate the risk of CILV.

Prospective Evaluation of Safety and Diagnostic Efficacy of Medical Thoracoscopy in Undiagnosed Exudative Pleural Effusion: Experience From a Tuberculosis High-Burden Country.

Pleural effusion is due to the pathological accumulation of pleural fluid in the pleural space, 25%-30% of which may remain undiagnosed despite the combination of biochemical, microbiological, and pathological tests and closed pleural biopsy. Medical thoracoscopy may help physicians diagnose such cases. We aimed to study the diagnostic yield of medical thoracoscopy in patients with undiagnosed exudative pleural effusion and assess the safety profile of the medical thoracoscopy. A cross-sectional descriptive study was conducted on 105 patients with undiagnosed pleural effusion. Medical thoracoscopy was performed using an Olympus semi-rigid thoracoscope (LTF 160 Evis Pleurovideoscope, Japan) as per standard protocol. Multiple pleural biopsies were taken and sent for histopathology examination, NAAT (nucleic acid amplification test), and MGIT (mycobacteria growth indicator tube). Post-procedure, the patients were evaluated for any complications. A total of 105 patients were enrolled in the study. The mean ± SDage was 55.1 ± 13.6 years. Sixty-three (60%) patients were males. The diagnostic utility of medical thoracoscopy was found in 94 (89.5%) patients. The diagnosis of tuberculosis (TB) was made in 34 (32.3%) patients, and 48 (45.7%) patients were diagnosed with malignant pleural effusion. Adenocarcinoma of the lung was the most common malignancy diagnosed (32 patients, 66.6%). Five (5.31%) patients had dual etiology of pleural effusion:tubercular and malignancy. The most common complication was chest pain following the procedure (99.4%). One patient developed pneumomediastinum and was managed conservatively. There were no major adverse events after the procedure. Medical thoracoscopy has a high diagnostic yield and favorable safety profile with minimal complications. Excessive reliance on the level of ADA (adenosine deaminase) may further delay the diagnosis. Dual etiologies like TB coexisting with malignancy should be considered in TB high-burden countries.

Clinical Significance of Serum ADA Combined with GLB, CREA, β2-MG and HGB in Newly Diagnosed Multiple Myeloma

To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), β2-microglobulin (β2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM. A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA. ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and β2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), β2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and β2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased β2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, β2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide. The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, β2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.

Identification of cytokines in benign and malignant thymus tumors: based on Mendelian randomization and proteomics.

The aim of this study was to identify potential causal cytokines in thymic malignancies and benign tumors from the FinnGen database using Mendelian randomization (MR). In this study, data from genome-wide association studies (GWAS) of 91 cytokines were used as exposure factors, and those of thymic malignant tumors and thymic benign tumors were the outcome variables. Two methods were used to determine the causal relationship between exposure factors and outcome variables: inverse variance weighting (IVW) and MR-Egger regression. Sensitivity analysis was performed using three methods, namely, the heterogeneity test, the pleiotropy test, and the leave-one-out test. There was a causal relationship between the expression of fibroblast growth factor 5, which is a risk factor for thymic malignant tumors, and thymic malignant tumors. C-C motif chemokine 19 expression, T-cell surface glycoprotein CD5 levels, and interleukin-12 subunit beta levels were causally related to thymic malignant tumors and were protective. Adenosine deaminase levels, interleukin-10 receptor subunit beta expression, tumor necrosis factor (TNF)-related apoptosis-inducing ligand levels, and TNF-related activation-induced cytokine levels showed a causal relationship with thymic benign tumors, which are its risk factors. Caspase 8 levels, C-C motif chemokine 28 levels, interleukin-12 subunit beta levels, latency-associated peptide transforming growth factor beta 1 levels, and programmed cell death 1 ligand 1 expression showed a causal relationship with thymic benign tumors, which are protective factors. Sensitivity analysis showed no heterogeneity. Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.