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Respiratory Research Jan 2024Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other... (Observational Study)
Observational Study
BACKGROUND
Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L.
METHODS
This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively.
RESULTS
Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP.
CONCLUSION
In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.
Topics: Humans; Adenosine Deaminase; Tuberculosis, Pleural; Pleural Effusion; Pleural Effusion, Malignant; Hematologic Neoplasms
PubMed: 38178065
DOI: 10.1186/s12931-023-02645-6 -
Journal of Hematopathology Dec 2023Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new addition to the list of large B-cell lymphomas in the 5th edition of the World Health Organization...
Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new addition to the list of large B-cell lymphomas in the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5). This report presents an unusual case of FO-LBCL with partial B cell antigen loss at relapse and reviews the characteristics, treatment, and prognosis of these patients to enhance our understanding of this disease. Immunophenotyping was performed through immunohistochemistry and flow cytometry. Immunoglobulin gene rearrangements were analyzed using BIOMED-2 multiplex primers. MYC, BCL2, and BCL6 gene rearrangements were detected by fluorescent in situ hybridization (FISH). Cell-free DNA (cfDNA) from pleural effusion and peripheral blood was subjected to somatic mutation evaluation using next-generation sequencing (NGS). In 2020, the patient was initially diagnosed with tuberculous pleurisy and received anti-tuberculous drugs. Subsequent testing of the pleural effusion cell block revealed that the large cells to be positive for CD10, CD20, CD79a, PAX5, MUM1, Bcl-2, Bcl-6, and c-myc and negative for CD3, CD30, Cyclin D1, and HHV8. In situ hybridization for Epstein-Barr virus (EBV)-associated mRNA (EBER-ISH) was negative. Additionally, a clonal rearrangement of immunoglobulin heavy locus (IGH) FR2-JH was detected; the results of MYC, BCL2, and BCL6 gene rearrangements were all negative. Following pleural drainage treatment, the patient achieved symptom remission and was diagnosed with large B-cell lymphoma (HHV8-unrelated PEL-like lymphoma). In 2022, the patient was readmitted due to the recurrence of pleural effusion. The pleural effusion cell block revealed a distinct immunophenotype compared to previous findings, positivity for PAX5 and negativity for CD20, CD10, CD3, CD5, CD30, CD38, CD138, CD79a, MUM1, Bcl-2, Bcl-6, Cyclin D1, c-myc, ALK, and HHV8. Identical IGH FR2-JH clonal rearrangement suggested the recurrence of the original clone. CfDNA analysis showed mutations in CD79B, MYD88, CCND3, and DTX1. The patient was ultimately diagnosed with FO-LBCL based on the WHO-HAEM5 classification. Diagnosis of FO-LBCL should be differentiated from primary effusion lymphoma (PEL). The features of this case align with the description of "FO-LBCL" in WHO-HAEM5 and "HHV8 and EBV-negative primary effusion-based lymphoma" in International Consensus Classification (ICC). FO-LBCL patients generally have a more favorable prognosis compared to PEL. In this case, the patient exhibited a favorable prognosis for over 22 months without additional treatment apart from pleural drainage.
Topics: Humans; Cyclin D1; Epstein-Barr Virus Infections; In Situ Hybridization, Fluorescence; Herpesvirus 4, Human; Proto-Oncogene Proteins c-bcl-2; Lymphoma, Large B-Cell, Diffuse; Chronic Disease; Pleural Effusion; Recurrence; Cell-Free Nucleic Acids
PubMed: 38175437
DOI: 10.1007/s12308-023-00566-3 -
Journal of Immunotherapy and Precision... Nov 2023Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby...
INTRODUCTION
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, immune-related adverse events (irAEs) increase morbidity and mortality and thereby limit therapeutic utility. The real-world incidence of the entire spectrum of pulmonary irAEs has not been systematically described. The objective of this study is to assess the risk of developing pulmonary irAEs (pneumonitis, pleural events [i.e., effusion and pleurisy], exacerbations of airway disease [i.e., bronchitis and bronchiectasis], and sarcoidosis) with exposure to five commonly used ICIs: nivolumab, pembrolizumab, durvalumab, avelumab, and atezolizumab.
METHODS
We conducted a retrospective review of the Food and Drug Administration Adverse Events Reporting System (FAERS) pharmacovigilance database. We collected data from 2012 to 2021 to assess the risk of pulmonary irAEs and performed a disproportionality analysis using Open-Vigil, a software package used for analysis of pharmacovigilance data, to calculate reporting odds ratios (RORs). We used 95% CIs to evaluate the precision of RORs. An ROR greater than 1 and the upper limit of the 95% CI indicated statistical significance.
RESULTS
A total of 17,273,403 events were reported in FAERS between 2012 and 2021. Of these, 88,099 (0.5%) were attributed to the PD-1 (programmed cell death protein 1) inhibitors and 21,905 (0.1%) to PD-L1 (programmed death ligand 1) inhibitors of interest. The most common indication for using the ICIs of interest was lung cancer: a total of 2832 (46.70%) for the PD-1 inhibitors and 1311 (70.9%) for the PD-L1 inhibitors. In the anti-PD-1 group, 2342 (38.6%) patients were hospitalized, and 1962 (32.4%) patients died from the lung adverse event. In the PD-L1 group, 744 (40.3%) patients were hospitalized, and 520 (28.1%) patients died from the event. Nivolumab resulted in the highest statistically significant risk (ROR, 10.5; 95% CI, 10.1-10.9) for pneumonitis. Avelumab had a lesser risk for pneumonitis (ROR, 0.2; 95% CI, 0.2-0.3). The risk for pleural events was highest with nivolumab (ROR, 3.6; 95% CI, 3.4-3.9), followed by pembrolizumab (ROR, 1.8; 95% CI; 1.6-2.0) ( < 0.001), with the lowest risks from durvalumab, atezolizumab, and avelumab. For ICI-related sarcoidosis, the risk was most significant with pembrolizumab (ROR, 3.6; 95% CI, 2.8-4.7), followed by nivolumab (ROR, 2.5; 95% CI, 1.9-3.5) ( < 0.001). The RORs for all five ICIs were less than 1 for exacerbations of airway diseases as compared with other drugs.
CONCLUSION
Using a pharmacovigilance database, we found an increased risk of multiple pulmonary irAEs after ICI therapy, particularly with PD-1 inhibitors. Further work is needed to investigate the incidence of pulmonary irAEs other than pneumonitis.
PubMed: 38143955
DOI: 10.36401/JIPO-22-38 -
Respiratory Investigation Jan 2024Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this...
BACKGROUND
Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers.
METHODS
We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers.
RESULTS
The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/μL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion.
CONCLUSION
This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.
Topics: Humans; Tuberculosis, Pleural; Pleural Effusion, Malignant; Retrospective Studies; Software Design; Pleural Effusion; Biomarkers; Diagnosis, Differential; Pleurisy; Sensitivity and Specificity
PubMed: 38141528
DOI: 10.1016/j.resinv.2023.11.005 -
Pathogens (Basel, Switzerland) Dec 2023Artificial-intelligence-based methods are regularly used in the biomedical sciences, mainly in the field of diagnostic imaging. Recently, convolutional neural networks...
Artificial-intelligence-based methods are regularly used in the biomedical sciences, mainly in the field of diagnostic imaging. Recently, convolutional neural networks have been trained to score pleurisy and pneumonia in slaughtered pigs. The aim of this study is to further evaluate the performance of a convolutional neural network when compared with the gold standard (i.e., scores provided by a skilled operator along the slaughter chain through visual inspection and palpation). In total, 441 lungs (180 healthy and 261 diseased) are included in this study. Each lung was scored according to traditional methods, which represent the gold standard (Madec's and Christensen's grids). Moreover, the same lungs were photographed and thereafter scored by a trained convolutional neural network. Overall, the results reveal that the convolutional neural network is very specific (95.55%) and quite sensitive (85.05%), showing a rather high correlation when compared with the scores provided by a skilled veterinarian (Spearman's coefficient = 0.831, < 0.01). In summary, this study suggests that convolutional neural networks could be effectively used at slaughterhouses and stimulates further investigation in this field of research.
PubMed: 38133343
DOI: 10.3390/pathogens12121460 -
Cureus Nov 2023Tuberculosis is a highly infectious respiratory disease due to (MTb). The most common manifestation of MTb is pulmonary tuberculosis, but some patients can present with...
Tuberculosis is a highly infectious respiratory disease due to (MTb). The most common manifestation of MTb is pulmonary tuberculosis, but some patients can present with extrapulmonary manifestations as their initial presentation. Tuberculous pleurisy and pleural effusion are among the most common extrapulmonary manifestations of MTb. The treatment of pleural MTb is the same as the treatment for pulmonary disease, with a four-drug regimen with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) under directly observed therapy (DOT). Drainage of the pleural effusion is usually not recommended in tuberculosis pleural effusion. We present a case of a complex, loculated pleural effusion due to MTb in an otherwise healthy middle-aged male who responded rapidly and completely to an early, short course of intrapleural tissue plasminogen activator and dornase alfa (TPA/DNase) therapy.
PubMed: 38125208
DOI: 10.7759/cureus.49125 -
Frontiers in Immunology 2023Emerging infectious diseases pose a significant threat to both human and animal populations. Rapid identification of protective antigens from a clinical isolate and...
BACKGROUND
Emerging infectious diseases pose a significant threat to both human and animal populations. Rapid identification of protective antigens from a clinical isolate and development of an antigen-matched vaccine is a golden strategy to prevent the spread of emerging novel pathogens.
METHODS
Here, we focused on , which poses a serious threat to the pig industry, and developed a general workflow by integrating proteosurfaceomics, secretomics, and BacScan technologies for the rapid identification of bacterial protective proteins from a clinical isolate.
RESULTS
As a proof of concept, we identified 3 novel protective proteins of . Using the protective protein HBS1_14 and toxin proteins, we have developed a promising multivalent subunit vaccine against .
DISCUSSION
We believe that our strategy can be applied to any bacterial pathogen and has the potential to significantly accelerate the development of antigen-matched vaccines to prevent the spread of an emerging novel bacterial pathogen.
Topics: Animals; Humans; Swine; Antigens, Bacterial; Bacterial Vaccines; Bacterial Proteins; Pleuropneumonia; Actinobacillus pleuropneumoniae
PubMed: 38098490
DOI: 10.3389/fimmu.2023.1274027 -
Frontiers in Medicine 2023Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease with the potential to involve virtually all organs, including the pancreas, kidneys,...
Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease with the potential to involve virtually all organs, including the pancreas, kidneys, lungs, and pleura, amongst others. IgG4-RD pleural involvement may cause diverse complications such as pleural effusion, pleural thickening, pleural nodules, and additional lesions, which can be presented in many clinical diseases. However, isolated cases of pleurisy are still rare in IgG4-RD. We report a 72-year-old patient who was admitted to our hospital with cough, expectoration, and fatigue. He had a right-sided pleural effusion, and the tissue evaluation of the pleural biopsy by medical thoracoscopy met the diagnostic criteria of IgG4-RD. His serum IgG4 levels were elevated and he was finally diagnosed with IgG4-RD pleural involvement. He was subsequently started on prednisone 40 mg daily and his pleural effusion was almost disappeared 2 weeks later. This paper reported a case of IgG4-RD who had exclusive involvement of the pleura and highlighted the significance of considering IgG4-RD as a potential diagnosis in patients with unexplained pleural effusion.
PubMed: 38089862
DOI: 10.3389/fmed.2023.1247884 -
Frontiers in Cellular and Infection... 2023There is a clinical challenge in diagnosing tuberculous pleurisy accurately and promptly, highlighting the urgent need for a rapid and sensitive diagnostic method. This...
INTRODUCTION
There is a clinical challenge in diagnosing tuberculous pleurisy accurately and promptly, highlighting the urgent need for a rapid and sensitive diagnostic method. This study aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) and GeneXpert (MTB) for identifying tuberculous pleurisy and analyzing the microbial profiles of both tuberculous and non-tuberculous pleural effusions.
METHODS
The study enrolled 31 patients with suspected tuberculous pleurisy, of which 15 were confirmed to have tuberculous pleurisy and subsequently allocated to the tuberculous pleurisy group (TP group), while the remaining 16 individuals were assigned to the non-tuberculous pleurisy group (NTP group). mNGS and GeneXpert MTB were performed on pleural effusion samples, and the diagnostic accuracy of both tests was compared. We employed established formulas to compute crucial indicators, including sensitivity, specificity, missed diagnosis rate, misdiagnosed rate, positive predictive value (PPV), and negative predictive value (NPV).
RESULTS
The results showed that both tests had high specificity (100%) and positive predictive value (100%) for detecting tuberculous pleurisy, along with comparable sensitivity (46.67% for mNGS and 40.0% for GeneXpert MTB). Further analysis of the combined efficacy of mNGS and GeneXpert MTB showed that the combined test had a sensitivity of 66.67% and a specificity of 100%. mNGS analysis revealed that MTB was detected in 7 out of 15 patients with tuberculous pleural effusions, while non-tuberculous pleural effusions were associated with a diverse range of microbial genera and species. The most frequently detected genera at the microbial genus level in the NTP group were spp. (6/16), spp. (5/16), and spp. (5/16).
DISCUSSION
These findings suggest that mNGS and GeneXpert MTB are useful diagnostic tools for identifying patients with tuberculous pleurisy, and mNGS can provide valuable insights into the microbial profiles of both tuberculous and non-tuberculous pleural effusions.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis, Pleural; High-Throughput Nucleotide Sequencing; Sensitivity and Specificity; Pleural Effusion
PubMed: 38089819
DOI: 10.3389/fcimb.2023.1243441 -
Journal of Medical Biochemistry Oct 2023Tuberculous pleuritis (TP) is one of the most common extra-pulmonary tuberculosis form. Because of tuberculous pleurisy is hard to diagnose due to slow course of disease...
Tuberculous pleuritis (TP) is one of the most common extra-pulmonary tuberculosis form. Because of tuberculous pleurisy is hard to diagnose due to slow course of disease and lack of specificity in symptoms and diagnostic methods. In that reason, we need multidisciplinary approach and efficient biomarkers. Acid-fast bacilli (AFB) staining, cultures and pathophysiological biopsy finding from the majority of patients are positive only in less than 10%. Löwenstein culture results need time about 6-8 weeks what delays diagnosis. Adenosine deaminase (ADA) is biomarker with high sensitivity and specificity (more than 90%) and considered as gold standard of biomarkers in the diagnosis of TP. It is very hard to distinguish malignant from TP with lymphocyte predomination, but in patient with malignant pleural effusion the level of ADA is decreased, opposite from TP. ADA in pleural punctate is a fast, simple, efficient and economical way for clarification the etiology of the pleural effusion as tuberculous pleurisy. Also, many studies have proved the role of ADA in the response to treatment for tuberculosis at follow up period.
PubMed: 38084235
DOI: 10.5937/jomb0-44018