High Adenosine Deaminase Levels Research Articles

Role of Pleural Fluid Lactate Dehydrogenase to Adenosine Deaminase Ratio in the Etiological Differentiation of Exudative Pleural Effusion

Abstract Background: Although pleural fluid adenosine deaminase (ADA) level >70 U/L suggestive tuberculous pleural effusion (TPE). High ADA levels can also be seen in pneumonia, empyema, lymphoma, malignancy, and rheumatoid pleuritis. Elevated pleural fluid lactate dehydrogenase (LDH) is seen in tubercular pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). Therefore, it is challenging distinguish between TPE, PPE, and MPE based on elevated pleural fluid ADA and LDH levels. In this study, we evaluated the use of pleural fluid LDH/ADA ratio as a new parameter for etiological differentiation of exudative pleural effusions. Materials and Methods: A retrospective hospital-based observational study conducted in GHCCD, Visakhapatnam. A total of 52 patients (TPE – 19, PPE – 16, and MPE – 17) with exudative pleural effusion who fulfilled inclusion criteria were taken into study. Qualitative variables have been described in the form of frequency and percentages. Median and interquartile ranges were used for nonnormal distribution values. Receiver operating curve (ROC) curves with area under the curve (AUC) were calculated. P ≤ 0.05 was considered statistically significant. Results: The mean ADA value for TPE was 75.4 U/L (25–195 U/L), PPE was 59.1 U/L (13–180 U/L), and for MPE was 35.52 U/L (10–75 U/L). The mean LDH value for TPE was 887.8 U/L (139–2213 U/L), PPE was 1128 U/L (334–3110 U/L), and for MPE was 1470 U/L (234–4285 U/L). On ROC analysis, pleural LDH/ADA ratio ≤20.81 diagnose TPE with (sensitivity – 84.2%, specificity – 63.6%) with AUC of 0.758 (95% confidence interval [CI]: 0.619–0.866) (P = 0.0001) whereas LDH/ADA ratio in the diagnosis of PPE was found to be >23.39 (sensitivity – 50%, specificity – 66.7%) with AUC of 0.535 (95% CI: 0.391–0.674) (P = 0.689) and the cutoff LDH/ADA ratio in the diagnosis of MPE was found to be >20.86 (sensitivity – 70.6%, specificity – 68.6%) with AUC of 0.724 (95% CI: 0.583–0.839) (P = 0.007). The cutoff value of the LDH/ADA ratio in PPE does not reach the statistical significant value. Conclusion: Pleural fluid LDH/ADA ratio ≤20.81 U/L is predictive of TPE, and >20.86 U/L is predictive of MPE and the cutoff value of 20.8 U/L can be used for etiological differentiation of pleural effusion.

In-silico Analysis of Adenosine Deaminase: From Gene Sequence Retrieval to Clinical Implications and Drug Targets

Background: Adenosine Deaminase (ADA) plays a critical role in purine metabolism and immune function. Its genetic and molecular characterization is essential for understanding its involvement in various physiological and pathological processes. The ADA gene has been implicated in immune system disorders and offers a potential target for therapeutic intervention. Objective: This study aims to comprehensively analyze the ADA gene and its protein product, detailing the genetic structure, physiochemical properties, subcellular localization, expression patterns, clinical variations, functional domains, splice variants, and potential as a drug target, to enhance the understanding of its function in human health. Methods: We utilized an array of in silico tools for gene sequence retrieval, including analysis of genomic databases for ADA's chromosomal location and gene structure. Physiochemical properties were determined using ProtParam, and subcellular localization was predicted with CELLO v.2.5. Gene expression levels across various tissues were ascertained using the Archive Ensemble TOOL. Clinical variations were categorized based on their potential pathogenicity, while splice variants and functional domains were predicted using domain-specific databases. Post-translational modifications were analyzed with prediction tools from the CBS server, and the STRING database facilitated protein interaction network analysis. Additionally, the DoG-Site Scorer predicted ADA's druggability profile. Results: ADA was localized to chromosome 12 (20q13.12), comprising 45940 base pairs encoding 363 amino acids. The protein's molecular weight was calculated as 37948.09, with a total atom count of 5396. Predictive localization indicated periplasmic and cytoplasmic presence with reliability scores of 1.437*, 1.210*, and 1.058*. Expression profiling revealed high ADA levels in the duodenum, with a notable expression in the lymphatic node. Clinical variations identified included 21 insertions and 23 inversions, with two pathogenic instances. Splice variant analysis predicted nine sites, and drug-binding potential was identified with scores as high as 0.81. Conclusion: Our study provides a detailed analysis of ADA, highlighting its genetic complexity and biological significance. The identification of clinically relevant gene variations and drug-binding pockets offers potential pathways for therapeutic intervention, emphasizing the importance of ADA in medical research and treatment strategies.

A Study of Tuberculous Pleural Effusion in Province 2, Southern Nepal

Introduction: Tuberculosis (TB) is a major public health problem in developing countries. Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis (TB) (after lymphatic involvement) and is the most common cause of pleural effusion in areas where TB is endemic. The aim of this study is to depict the pattern of the Tuberculous Pleural Effusion (TPE) with its clinical presentation and diagnosis along with the different laboratory parameters of the TB patients at a tertiary care center of the Southern Nepal. Materials and Methods: A prospective hospital based cross-sectional study enrolling 107 subjects diagnosed as TBPE presenting to the Department of Internal Medicine, National Medical College was carried out from 15th March, 2023 to 14th October, 2023 (7 months). The different data collected were put in Excel Sheet and analyzed using SPSS version 26. The formal written and verbal consent was taken from the participants and ethical clearance was taken from Institutional Review Committee (IRC), National Medical College, Birgunj (Ref. F-NMC/633/079-080).Results: A total of 107 subjects diagnosed with TBPE showed 67.3 % (n=72) male and 32.7% (n=35) female participants. Majority of the participants (88.8%) presented with fever, and approximately 59% of the participants had chest pain. Almost 65% of them had dyspnea and 77% presented with frank cough. Majority of the participants had right sided effusion. Pleural ,fluid examination showed increased total leukocyte count (mean 3191 cells/cu mm) and with lymphocytic predominance and increased protein content (5.07±0.91 g/dL). Pleural fluid Adenosine Deaminase (ADA)was found to be elevated (86.5±26.4 U/L).Conclusion: The common presentation of the Tuberculous pleural effusion is deranged laboratory parameters of pleural fluid with increased fluid total leukocyte count having lymphocytic predominance and increased protein content along with high ADA levels.

LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy.

Pleural effusion (PE) is a common medical concern, often requiring thoracentesis for a definitive diagnosis. An elevated pleural fluid adenosine deaminase (ADA) may indicate tuberculosis, but this is not always the case. This study aimed to evaluate the accuracy of biomarkers determined in pleural fluid and propose a new diagnostic strategy for PE in patients with high levels of ADA in pleural fluid. This retrospective analysis studied patients with PE who received thoracentesis for the first time with an ADA level of > 33 U/L in the pleural fluid analysis at two tertiary hospitals from March 2019 to March 2023. Demographic and clinical data, as well as pleural fluid biomarkers and their ratios, were studied and compared between different PE groups, and a decision tree was developed. During the study period, 259 patients were enrolled, with four different types of PE: parapneumonic (PPE) 155, tuberculosis (TPE) 41, malignant (MPE) 50, and miscellaneous 13. Biomarkers and their ratios performed well in the differential diagnosis of PE, with the LDH/ADA ratio distinguishing between PPE and non-PPE with sensitivity and specificity of 98.06% and 98.08%, respectively. The combination of LDH/ADA ratio, ADA, and mononuclear cell percentage was identified as important factors for creating a decision tree with an overall accuracy of 89.96%. The pleural fluid LDH/ADA ratio was a useful diagnostic for distinguishing PPE from non-PPE, and a decision tree with an accuracy of 89.96% was created to differentiate the four forms of PE in clinical situations.

Primary Effusion Lymphoma-like Lymphoma Mimicking Tuberculous Pleural Effusion: Three Case Reports and a Literature Review.

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare lymphoma, localized in the body cavity without detectable tumor masses. Tuberculous pleural effusion is a form of extra pulmonary tuberculous. We herein report three cases of PEL-LL in patients with a history of pulmonary tuberculosis. Despite the presentation with lymphocyte predominance and high levels of adenosine deaminase, a notable characteristic of tuberculous pleural effusion, the patients were ultimately diagnosed with PEL-LL. Pleural fluid laboratory tests yield similar results for PEL-LL and tuberculous pleural effusion; therefore, cytological and immunophenotyping examinations are useful for their differential diagnosis and the determination of treatment.

Detection of drug-resistant Mycobacterium tuberculosis in pericardial fluid culture and its correlation with cartridge based nucleic acid amplification test and adenosine deaminase activity

BackgroundPericardial effusion is the accumulation of fluid in the pericardial cavity. In nations with high tuberculosis (TB) load, TB is the most common cause of pericardial effusion. 1–2% of patients with pulmonary TB develop Pericardial TB worldwide. Multi-drug-resistant (MDR) TB, including extrapulmonary TB (EPTB) cases, are rising in number. Adenosine Deaminase (ADA) is an enzyme in lymphocytes and myeloid cells, which has certain immune functions in the body. ADA levels are increased in inflammatory conditions, like pleural, pericardial, or joint effusions, of bacterial etiology, granulomatous conditions, neoplasms, and autoimmune pathologies. TB is the only lymphocytosis involving disease with increased ADA levels. MDR EPTB is rare, but cases are on the rise, and tuberculous pericardial effusion is one such example. Hence, it is important to know the percentage of cases detected by a culture that can be identified by cartridge-based nucleic acid amplification test (CBNAAT), their resistance patterns, and to identify potential markers like ADA, which can help in early identification of cases. The objectives of this study were to identify the Mycobacterium tuberculosis (MTB) bacilli in culture, and correlate them with cartridge-based nucleic acid amplification test (CBNAAT) results and their drug-resistance, in the Pericardial tubercular effusion, and to find if Adenosine Deaminase (ADA) levels can be used as a predictor of the presence of MTB in pericardial fluid. MethodologyWe enrolled 52 patients with moderate to large tuberculous pericardial effusion, based on pericardial fluid analysis, CBNAAT, and culture methods, between January 2021 and December 2021. ResultsThe mean age of the patients was 41.85 + 17.88 years, with a median of 38 years. Males made up 57.7% of the total patients. MTB was detected in 16 (30.8%) patients in the CBNAAT evaluations. 14 (87.5%) of the CBNAAT-positive TB patients were sensitive to Rifampicin, whereas the remaining 2 (12.5%) were resistant to Rifampicin on CBNAAT. MTB was found to be growing in 8 (15.38%) drug sensitivity test cultures. Out of these 8, 6 were sensitive to first-line drugs, whereas 2 were resistant to both Isoniazid and Rifampicin. The presence of cough was found to have a significant difference between CBNAAT-detected MTB positive and negative patients (p = 0.020), whereas an insignificant difference was found for the presence of hypertension, diabetes mellitus, obesity, dyspnea, or fever. There was also an insignificant difference between the number of patients positive for the Tuberculin skin test, between the two groups. ADA was significantly higher in the MTB-detected CBNAAT group (85.91 + 37.60U/L vs 39.78 + 24.31U/L, p = 0.005), whereas the total leukocyte count, lymphocytes, neutrophils, random blood sugar levels, and serum protein levels had no significant difference. The area under the Receiver Operator Curve (CBNAAT positive: dependent variable; ADA: test result variable) was 0.854 (null hypothesis rejected), with a standard error of 0.078. ConclusionsCulture is the gold standard method to diagnose tuberculosis. Detection of MTB on pericardial fluid culture is very uncommon, though in our study, culture came out positive in 16% of patients, and 4% were resistant to rifampicin and isoniazid. Higher ADA levels in pericardial fluid are an indicator of tuberculous pericardial effusion.

High Adenosine Deaminase Level and Erythrocyte Sedimentation Rate of Intestinal Tuberculosis Patients

BACKGROUND: Currently, laboratory diagnosis of intestinal tuberculosis (ITB) is limited based on clinical manifestations, providing opportunities for alternative laboratory tests to diagnose ITB. At the present time, the role of serum adenosine deaminase (ADA) and hematological tests in ITB patients are not widely known. The objective of this study was to determine the role of ADA and hematological tests in patients suspected with ITB.METHODS: Subjects that were suspected of ITB were classified as ITB group, while subjects with inflammatory bowel disease, hemorrhoid, and intestinal malignancy were classified as non-ITB group. Colonoscopy, histopathological examinations, and hematological test were performed. ADA measurement was also performed with clinical chemistry analyzer based on enzymatic colorimetry principle.RESULTS: Out of 143 subjects, 16 (11.2%) subjects were diagnosed with ITB and 127 (88.8%) subjects were classified as non-ITB group. ADA level and erythrocyte sedimentation rate (ESR) of ITB group were significantly higher than the ones of non-ITB group (p<0.05). Cut-off, sensitivity, and specificity of ADA level were 12.56 IU/L, 75%, and 57%, respectively. Cut-off, sensitivity, and specificity of ESR were 32.5 mm/hour, 81%, and 62%, respectively. Colonoscopy of ITB subjects displayed multiple ulcerations, edema, and hyperemic mucosa. Histopathological examination of ITB subjects exhibited granulomatous inflammation, epitheloid cells, giant cells, and lymphocyte aggregates.CONCLUSION: ADA level and ESR were significantly higher among ITB patients compared with non-ITB patients. Since the sensitivities of ADA and ESR tests were high, the ADA and ESR tests could be considered as a screening test for ITB.KEYWORDS: intestinal tuberculosis, adenosine deaminase, hematological tests

Pleuropulmonary Aspergillosis Presenting as Hydropneumothorax in Second Trimester Pregnancy

Pleuropulmonary aspergillosis is a rare entity and usually occurs in a patient with preexisting lung disease or surgery. A 29-year-old pregnant woman with 16 weeks of gestation presented with shortness of breath, right-sided chest pain, and productive cough of 2 weeks' duration. A chest radiograph done with abdominal shield revealed right hydropneumothorax. Intercostal drainage insertion was done under ultrasound guidance. Pleural fluid was exudative with high adenosine deaminase levels, and GeneXpert test was negative for Mycobacterium tuberculosis. Pleural fluid and sputum culture revealed significant growth of Aspergillus fumigatus. She was treated with voriconazole intravenously followed by oral route. The patient improved clinically with good lung expansion, and she delivered a normal live baby by elective cesarean section. We report this case in view of the rarity of pleuropulmonary aspergillosis occurring in a young pregnant female with no evidence of prior lung pathology.

Clinical and Etiological Profile of an Exudative Pleural Effusion in a Tertiary Care Center

Background: Pleural effusion is common clinical entity in day-to-day clinical practice. There are various etiologies for pleural effusion. Among those tubercular pleural effusion, parapneumonic effusion, malignant effusion, and congestive heart failure were the most common causes of pleural effusion. Here, we have done a retrospective study to see the etiology of pleural effusion in our tertiary care center. Patients and Methods: This retrospective study conducted in a tertiary care center over 1 year period. A total of 63 patients were included in this study after verifying in patient records of all patients who were admitted with exudative pleural effusion. The demographic data collected and complete history was obtained. Investigations such as complete hemogram, random blood sugar; renal function tests, serum proteins, chest x-ray, and pleural fluid analysis and investigations such as ultrasonogram of the chest and abdomen, echocardiogram, computed tomography scan of chest, fine-needle aspiration cytology, and pleural biopsy reports (if done) were collected. Results: Among the study participants, 40 were male and 23 were female patients with male-to-female ratio of 1.7:1. Mean age of the study population was 48.8 ± 18.7 years. The most common presenting symptom was dyspnea (84%) followed by cough (80%), fever (65%), and chest pain (43%). The most frequent cause of pleural effusion was tuberculosis in 38% of patients, followed by parapneumonic effusion (28.5%) and malignant pleural effusion (22.2%). Three patients had chylothorax, two patients had pancreatic pleural effusion and the diagnosis was unknown in two patients. Mean ± standard deviation (SD) adenosine deaminase (ADA) value of the study population was 45.3 ± 28.1. Mean ± SD of ADA values in tuberculous, parapneumonic, and malignant pleural effusion was 54.5 ± 16.8, 65.2 ± 30.7, and 18.2 ± 11.0, respectively. Conclusions: Tuberculosis is one of the common causes of exudative effusions along with parapneumonic effusions and malignancy. Pleural fluid ADA levels are highly sensitive with good specificity for the diagnosis of etiology of tubercular effusions. However in view of high levels of ADA in pleural fluid in parapneumonic effusions also, other measures such as clinical evaluation, lymphocyte to neutrophil ratio, and glucose levels are necessary to separate both these entities.

S3127 Peritoneal Tuberculosis in an Immunocompetent Patient With Findings of Chronic Liver Disease and Peritoneal Carcinomatosis

Introduction: Peritoneal tuberculosis (PT) accounts for 1-2% of all tuberculosis cases. Diagnosis of PT can be challenging due to non-specific symptoms, insidious onset, and variable imaging findings. We present a case of PT presenting with ascites and imaging studies suggestive of chronic liver disease (CLD), and peritoneal carcinomatosis. Case Description/Methods: A 48-year-old man presented to our clinic with complaints of increased abdominal girth, weight loss, and night sweats for the past 3 months. Physical exam revealed soft and distended abdomen with shifting dullness. Laboratory tests showed a mild anemia of Hb at 13.0 g/dL (13.1-17.2) and ESR at 34 mm/h (0-15). Abdominal ultrasound (US) revealed the presence of free abdominal fluid, and diffuse heterogenous granular liver parenchyma supporting the diagnosis of CLD. His liver tests were within normal ranges. Ascitic fluid analysis revealed serum ascites albumin gradient (SAAG) of 0.2 g/dL, WBCs of 1.70 × 103 cells/dL (91.8% lymphocytes). Ascitic fluid cytology was negative for malignant cells. Ascitic fluid acid-fast bacilli (AFB) test and mycobacterial culture were negative. Adenosine deaminase (ADA) level in ascitic fluid was 108.5 U/L (0-40). Interferon-gamma release assay (IGRA) test was positive. Contrast-enhanced computed tomography (CT) scan revealed normal liver parenchyma, diffuse thickening and nodularity of the peritoneum, and thickening of omentum with omental cake appearance. CT scan was suggestive of peritoneal carcinomatosis. EGD and colonoscopy were unremarkable. With consistent clinical history, SAAG < 1.1, ascitic fluid with lymphocytic predominance, high ADA levels, and positive IGRA, a diagnosis of PT was made. Anti-tuberculosis treatment was initiated, and the patient’s clinical symptoms have improved. CT scan at the end of treatment showed the resolution of ascites and peritoneal findings (Figure 1). Discussion: Ascites is the most common presenting symptom of PT. High suspicion of PT is important in the setting of ascites of unknown origin. Despite the US findings were suggestive of CLD in this patient, CT scan revealed normal liver findings. Differing PT from peritoneal carcinomatosis might be challenging due to overlapping findings on imaging. Ascitic fluid analysis of SAAG < 1.1, high ADA levels, positive IGRA test should lead towards the diagnosis of PT. AFB and mycobacterial culture of the ascitic fluid may often have low diagnostic yield in PT. Early diagnosis and treatment are important to prevent complications.Figure 1.: A1, A2, Before treatment; axial contrast-enhanced computed tomography scan showing moderate ascites, and diffuse thickening and nodularity of peritoneum. Imaging is suggestive of peritoneal carcinomatosis. B1, B2, After treatment; resolution of ascites and peritoneal findings.

PLEURAL EFFUSION AS AN INITIAL PRESENTATION OF EXTRAMEDULLARY ACUTE MYELOID LEUKEMIA: A RARE PHENOMENON

PLEURAL EFFUSION AS AN INITIAL PRESENTATION OF EXTRAMEDULLARY ACUTE MYELOID LEUKEMIA: A RARE PHENOMENON

Characteristics of pleural effusion with a high adenosine deaminase level: a case–control study

BackgroundIncreased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion.MethodsWe retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors.ResultsThe most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2–104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3–108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8–66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9–58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively.ConclusionCases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Abstract WP150: Influence Of Body Mass Index On Adenosine Deaminase And Infarct Volume In Mechanical Thrombectomy Subjects

Background: Emergent Large Vessel Occlusion (ELVO) strokes are devastating ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Methods: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) from stroke patients undergoing mechanical thrombectomy (MT). N=61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Results: The 61 subjects studied were broken into three categories: Normal weight (BMI 18.5-24.9) which contained 19 subjects, Overweight (BMI 25-30) which contained 25 subjects, and Obese (BMI ≥30) which contained 17 subjects. When compared to Normal weight and Overweight categories, the Obese category had significantly higher levels of adenosine deaminase (ADA) expression (p=0.01 and p=0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p=0.013 and p=0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke-related disability (mRS on discharge) with significance of p=0.053 and p=0.032, respectively). When controlling for age and sex, increased infarct volumes were predicted by higher ADA levels in the Obese population (p=0.009), while increased ADA levels were not predictive of increased infarct volumes in the Normal weight category. Conclusions: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins including ADA. The protein ADA is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. Increased levels of ADA in the Obese group were predictive of increased infarct volumes. Further testing will explore the relationship of BMI and ADA on cognitive function outcomes. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects

BackgroundEmergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. MethodsThe Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N ​= ​61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. ResultsThe 61 subjects studied were broken into three categories: normal weight (BMI 18.5–24.9) which contained 19 subjects, overweight (BMI 25–30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p ​= ​0.041 and p ​= ​0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p ​= ​0.01 and p ​= ​0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p ​= ​0.013 and p ​= ​0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p ​= ​0.053 and p ​= ​0.032, respectively. ConclusionsWhen examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

The role of pleural fluid lactate dehydrogenase-to-adenosine deaminase ratio in differentiating the etiology of pleural effusions.

Exudative pleural effusion includes tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). An elevated pleural fluid adenosine deaminase (ADA) typically implies TPE, but the rule may not apply to every individual case. Recent studies proposed that the pleural fluid lactate dehydrogenase (LDH)-to-ADA ratio showed a higher diagnostic power than pleural fluid ADA alone in differentiating the etiology of pleural effusion. Hence, we aimed to investigate the performance of pleural fluid LDH-to-ADA ratio as a biomarker in assistance with the diagnosis of TPE, PPE, and MPE. All patients who underwent thoracentesis for the first time with a pleural fluid ADA >40 U/L were included in this retrospective study. The clinical data including pleural fluid ADA and LDH-to-ADA ratio were analyzed. A total of 311 patients were enrolled during the study interval. The pleural fluid LDH-to-ADA ratio <14.2 (sensitivity: 74.2%; specificity: 90.4%) favored TPE, while the pleural fluid LDH-to-ADA ratio >14.5 (sensitivity: 79.9%; specificity: 78.5%) favored PPE. Besides, the pleural fluid LDH-to-ADA ratio >46.7 (sensitivity: 56.3%; specificity: 78.3%) favored MPE owing to primary lung cancers. In conclusion, the pleural fluid LDH-to-ADA ratio was an effective indicator in differentiating the etiology of pleural effusions in the cases of high ADA level in the pleural fluid.

Changed signals of blood adenosine and cytokines are associated with parameters of sleep and/or cognition in the patients with chronic insomnia disorder

ObjectivesThis study aimed to investigate whether plasma levels of adenosine, adenosine deaminase (ADA), and certain cytokines change in patients with chronic insomnia disorder (CID), and if so, whether these alterations are associated with poor sleep quality and cognitive dysfunction. MethodsFifty-five CID patients were selected for the study, along with fifty-five healthy controls (HC) matched to the patients according to their basic data. All subjects completed sleep, emotion, and cognition assessments, with some CID patients also completing an overnight polysomnography. The plasma level of adenosine was measured using liquid chromatography–tandem mass spectrometry, while ADA level was quantified using a quantitative sandwich enzyme-linked immunosorbent assay. Levels of cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ, were measured using Luminex liquid chip technology. ResultsCID patients had a lower adenosine level, and higher levels of ADA and some of the cytokines (IL-1β, IL-2, IL-6, IL-10 and TNF-α) compared with controls. In the CID group, plasma concentrations of adenosine were negatively correlated with Pittsburgh Sleep Quality Index scores, while concentrations of IL-1β, IL-6 and TNF-α were positively correlated with these scores. Concentrations of IL-1β and TNF-α were negatively correlated with scores on the Chinese-Beijing Version of the Montreal Cognitive Assessment. Moreover, levels of IL-1β, TNF-α, IL-6, and IL-2 were positively correlated with memory test errors by CID patients after controlling for confounding factors. ConclusionsThe reduced adenosine and elevated cytokine levels of CID patients were associated with the severity of insomnia and/or cognitive dysfunction.

Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels.

Background/AimsPleural 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.MethodsPatients 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.ResultsA 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.ConclusionsA scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Elevated Adenosine Deaminase in Pleural Effusion A Case of Non-Hodgkin Lymphoma Misdiagnosis.

Despite a recent decline, tuberculosis (TB) infection is still a frequent diagnosis in Portugal. Adenosine deaminase (ADA) measurement has become an important tool in the timely diagnosis of this infection. However, ADA elevation in bodily fluids is not pathognomonic of TB infection.We present the case of a 70-year-old woman, undergoing treatment for pleural TB, diagnosed based on elevated ADA levels in a pleural effusion. Due to worsening symptoms she was readmitted, and the previous diagnosis was reconsidered. Thoracocentesis was repeated and cytometry analysis of the fluid was performed, showing the presence of diffuse large B cell lymphoma (DLBCL).DLBCL is the most frequently occurring non-Hodgkin lymphoma (NHL). Pleural involvement is rare in the initial stages. ADA elevation >250 U/l should raise suspicion of malignancy, especially in association with markedly elevated LDH levels. The purpose of this case report is to highlight that in the absence of microbiologic or histologic confirmation, a presumptive TB diagnosis should not be lightly made, and alternative diagnoses should be systematically ruled out.LEARNING POINTSElevated ADA levels are not pathognomonic of TB infection.Lymphocytic pleural effusion requires a systematic diagnostic approach.Very high levels of ADA should arouse suspicion of lymphoma.

Clinical and pathological differences between polymorphonuclear-rich and lymphocyte-rich tuberculous pleural effusion.

OBJECTIVE:Analysis of the occurrence factors and disease characteristics of tuberculous (TB) pleural effusion (TPE) dominated by neutrophils.METHODS:We retrospectively analyzed the clinical data of 304 patients with two types of TB pleurisy. The clinical, laboratory, and pathological features of TB pleurisy separately dominated by lymphocytes and neutrophils were analyzed.RESULTS:Neutrophil-predominant effusion was observed in 33 (10.9%) patients. The patients with TPE with polymorphonuclear leukocytes (PMNLs) had higher fever rates and higher decortication rates than those with lymphocyte-predominant TPE. Otherwise, they had lower chest distress rates and lower positive rates of pulmonary TB and lower biopsy tissue culture-positive rates than patients with lymphocyte-predominant TPE. PMNL TPE patients had higher lactic acid dehydrogenase (LDH) (1297 vs. 410 U/l, P < 0.001) and adenosine deaminase (ADA) levels (54.1 vs. 42.9 U/l, P = 0.043) and lower pleural fluid glucose (1.92 vs. 4.70 mmol/L, P < 0.001) and protein (47.4 vs. 48.4 g/L, P = 0.024) levels than that of lymphocyte-predominant TPE. Otherwise, they had lower blood ALB levels and higher C-reactive protein levels than lymphocyte-predominant TPE. Finally, PMNL TPE patients had lower rates of granuloma formation (27.2% vs. 75.2%, P < 0.001) and pleural nodules than patients with lymphocyte-predominant TPE and more frequent findings of pus, caseous exudate, and necrosis.CONCLUSION:The TB pleurisy patients dominated by neutrophils show strong inflammatory reactions and higher ADA levels in pleural effusion. These findings can significantly improve the positive rate of Mycobacterium tuberculosis in neutrophil-predominant TPE under thoracoscopy.

Rapid Decline of IFN-γ Spot-Forming Cells in Pleural Lymphocytes during Treatment in a Patient with Suspected Tuberculosis Pleurisy

A differential diagnosis of tuberculosis pleurisy is often difficult. A 48-year-old Japanese man with no previous medical history visited the outpatient department for dyspnea and fever. His chest-XP and laboratory findings, especially high C-reactive protein levels, indicated pleuritis with pleural effusion. Pleural lymphocytes showed high numbers of spot forming responses in interferon gamma release assay (IGRA). Pleural effusion contained high levels of adenosine deaminase and hyaluronic acid, but no Mycobacterium tuberculosis (TB) antigen was detected by culture or polymerase chain reaction (PCR). Although the infectious agent was not detected, the clinical and laboratory findings strongly suggested that he was suffering from tuberculosis pleurisy. After treatment with anti-TB drugs, a rapid decline of spot-forming cells (SFCs) of pleural lymphocyte was observed, despite persistently high levels of other biomarkers and increased pleural lymphocytes. This case demonstrates that an IGRA of pleural lymphocytes would be useful for therapeutic diagnosis for TB pleurisy suspected for TB.