Incidence, aetiology and clinical features of eosinophilic pleural effusion: a retrospective study.

BACKGROUND: Eosinophilic pleural effusion (EPE) is a distinct entity among pleural effusions, but its diagnostic and prognostic significance is still controversial. This study aimed to evaluate the incidence and aetiological distribution of EPE in our institution and to assess the relationship between EPE and malignancy and other underlying diseases and the relevance of the percentage of eosinophils and other laboratory parameters. METHODS: A retrospective study was conducted by reviewing the medical records of 252 patients with PE from September 2017 to January 2021. RESULTS: EPE was found in 34 (13.49%) out of 252 patients. There were 20 (58.82%) males and 14 (41.18%) females in the EPE group. The mean percentage of eosinophils in EPE (21.7%, range (10.0-67.5%)) was significantly higher than the percentage of eosinophils in peripheral blood (5.65%, range (0-34.60%); p < 0.05). The most common cause of EPE was malignant disease (52.94%), followed by idiopathy (14.71%), parasites (8.82%), pneumonia (8.82%) and others (14.71%). Comparative analysis of patients with malignant versus nonmalignant EPE showed that patients with malignant EPE were significantly older, and had a lower white blood cell (WBC) count in the pleural fluid (1.8 vs 4.7 cells × 109/L, p < 0.05). However, the percentage of eosinophils in PE was not significantly different between malignant EPE and nonmalignant EPE (p = 0.66). There was no correlation between the percentage of eosinophils in PE and peripheral blood (r = 0.29; p = 0.09). CONCLUSIONS: Malignant disease ranks as the leading cause of EPE. The presence of EPE should not be considered as a predictive factor of benign conditions. Pleural parasitic infestation (PPI) should be emphasized in areas with a high incidence of parasitic disease.

Levels of lactic acid's concordance with pH in pediatric parapneumonic pleural effusion.

Purpose of the article: The indication of pleural drainage in parapneumonic pleural effusion (PPE) is still controversial. Pleural fluid's (PF) pH is widely used as an indicator of the need for pleural drainage. We hypothesized that PF's lactate will have a high concordance with pH, and thus, may be a valuable tool to determine the need for pleural drainage in pediatric PPE. MATERIALS AND METHODS: We performed a descriptive, prospective study sequentially enrolling those pediatric patients admitted to a tertiary University Hospital with a PPE between 2008 and 2018. Patients were classified in two groups: drainable PPE (pH < 7) and non-drainable PPE (pH > 7). Correlation with the pH, the area under the curve (AUC), and the sensitivity and specificity values for lactate and other parameters (glucose, and LDH) were analysed too. RESULTS: 72 patients with a median age of 4 years (interquartile range 2.25-6) were included. Both groups were homogeneous. Lactate levels were higher in the drainable PPE group (p < 0.001), and a strong inverse correlation between pH and lactate was found (r: -0.7; p < 0.001). A lactate cut-off value of 60.5 mmol/L, exhibit an AUC of 0.86 with a sensitivity of 70% and a high specificity (97.9%) to predict a pH < 7. CONCLUSIONS: Our data indicates that lactate in PF presents a strong correlation with pH and could potentially serve as a highly specific biomarker of the need for pleural drainage.

Tissue-Resident Memory-Like CD8+ T Cells Exhibit Heterogeneous Characteristics in Tuberculous Pleural Effusion.

Tissue-resident memory T (TRM) cells are well known to play critical roles in peripheral tissues during virus infection and tumor immunology. Our previous studies indicated that CD69+CD4+ and CD69+CD8+ T cells in tuberculous pleural effusion (TPE) were antigen-specific memory T cells. However, the phenotypical and functional characteristics of CD8+ TRM cells in tuberculosis remain unknown. We found that CD103+CD8+ T cells were the predominant subset of CD103+ lymphocytes in TPE; both CD103 and CD69 expressed on memory CD8+ T cells from TPE were significantly increased compared with those from paired peripheral blood. Phenotypically, CD103+CD69+ and CD103+CD69-CD8+ T cells expressed higher levels of CD45RO than CD103-CD69+CD8+ T cells did; CD103+CD69-CD8+ T cells highly expressed CD27, CD127, and CD62L and some chemokine receptors. We further compared the functional differences among the four distinct CD45RO+CD8+ T subsets identified by CD103 and CD69 expression. In consist with our published results, CD69+CD8+ T cells, but not CD103+CD8+, produced high levels of IFN-γ after treatment with BCG in the presence of BFA. Nevertheless, CD103-CD69+ and CD103+CD69+ memory CD8+ T cells expressed higher levels of Granzyme B, while CD103+CD69- memory CD8+ T cells were characterized as a possibly immunosuppressive subset by highly expressing CTLA-4, CD25, and FoxP3. Furthermore, TGF-ß extremely increased CD103 expression but not CD69 in vitro. Together, CD103+CD8+ T cells form the predominant subset of CD103+ lymphocytes in TPE; CD103 and CD69 expression defines distinct CD8+ TRM-like subsets exhibiting phenotypical and functional heterogeneity. Our findings provide an important theoretical basis to optimize and evaluate new tuberculosis vaccines.

IgG4-related pleural effusion with high adenosine deaminase levels: A case report and literature review.

RATIONALE: Levels of pleural fluid adenosine deaminase (ADA), a useful marker for the diagnosis of tuberculous pleurisy, are elevated in some reports of immunoglobulin G4 (IgG4)-related pleural effusion. We describe a patient with IgG4-related pleural effusion who exhibited a high concentration of ADA. Furthermore, we reviewed the literature to compare patients with IgG4-related pleural effusion and tuberculous pleurisy. PATIENT CONCERNS: A 75-year-old male patient had dyspnea for 1 month with a left pleural effusion that was exudative, lymphocyte dominant. The pleural fluid test results revealed a total protein (TP) concentration of 6.60 g/dl, a lactate dehydrogenase (LDH) level of 383 IU/dl, and an ADA concentration of 54.5 U/L. An interferon gamma release assay showed a negative result. DIAGNOSES: Histological analysis of the thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration, with 80 IgG4-positive plasma cells/high-power field, and an IgG4/IgG ratio of approximately 40% to 50%. Other diseases were ruled out based on symptoms, negative autoimmune antigen results, and histopathologic findings. Thus, he was diagnosed with IgG4-related pleural effusion. INTERVENTIONS: He received 15 mg of prednisolone as therapy. OUTCOMES: His pleural effusion and symptoms improved gradually within several months, and prednisolone was tapered to 6 mg daily. LESSONS: It is important to distinguish between IgG4-related pleural effusion and tuberculous pleurisy. Therefore, we compared 22 patients with IgG4-related pleural effusion from PubMed and the Japan Medical Abstracts Society to 40 patients with tuberculous pleurisy at Fukujuji Hospital from January 2017 to May 2019. According to thoracentesis findings, 14 of 18 patients with IgG4-related pleural effusion had high ADA more than 40 U/L. The pleural effusion of patients with IgG4-related pleural effusion showed higher TP levels (P < .001) and lower LDH (P < .001) and ADA levels (P = .002) than those with tuberculous pleurisy. Moreover, the pleural fluid ADA/TP ratio was a good predictor for differentiating IgG4-related pleural effusion and tuberculous pleurisy (area under the receiver operating characteristic curve of 0.909; 95% confidence level: 0.824-0.994).

Serum Creatinine as a Potential Biomarker for the Diagnosis of Tuberculous Pleural Effusion.

BACKGROUND: Previous studies have revealed the disadvantages of traditional methods for the diagnosis of tuberculous pleural effusions (TPEs) and have created interest in exploring other effective biomarkers. Many studies have focused on the correlation between pulmonary diseases and serum creatinine (Cr), a representative biomarker of renal function, but little is known about the direct relationship between Cr and TPE. Our study aimed to explore whether Cr can act as a biomarker for the diagnosis of TPE and to evaluate the correlation between Cr and TPE. MATERIALS AND METHODS: Patients with pleural effusions (PEs) were enrolled in this study. By comparing the concentrations of Cr and adenosine deaminase (ADA) in patients with TPEs and non-TPEs, we determined the sensitivity, specificity, Youden index, and area under the curve for these biomarkers. We generated receiver operating characteristic curves and quantifications to evaluate the diagnostic accuracy. RESULTS: In total, 86 patients (44 with TPE, 25 with malignant pleural effusion (MPE) and 17 with non-tuberculosis infectious PE (NTIPE)) were enrolled in the study. The concentrations of Cr in TPE were significantly higher than those in non-TPE. However, a similar trend was not observed for NTIPE and MPE. The levels of ADA in TPE were significantly higher than those in NTIPE and MPE. CONCLUSION: Cr has the potential for the diagnosis of TPE to some extent though its accuracy is not as good as that of ADA. Further studies are necessary for Cr to be applied in clinical practice for the diagnosis of TPE.

Levels of YKL-40 in pleural effusion and blood from patients with pleuritis.

INTRODUCTION: In recent years, there have been a significant increase in the tests and biomarkers available for pleural fluid analysis. YKL-40 is one of the inflammatory biomarkers that is used for this purpose. The aim of our study is to assess the levels and diagnostic values of YKL-40 in patients with different types of pleural effusions (PE). MATERIALS AND METHODS: This was a prospective, observational and crosssectional study. Pleural and serum YKL-40 levels were measured using enzyme-linked immunosorbent assay in 119 patients with PEs, including 23 transudates PE, 47 malignant PE, 26 parapneumonic PE (PPPE), 17 paramalignant PE (PME) and 6 tuberculous PE (TBPE). RESULT: Median pleural YKL-40 level was higher in exudates (390.3 ng/mL) than in transudates (369.5 ng/mL) (p<0.02). For a cut-off level of 378 ng/mL, it was found to predict exudates with 70% sensitivity and 64% specificity. [area under the curve (AUC)= 0.660, p= 0.01]. Median pleural YKL-40 level was highest in PMEs (407.1 ng/mL) and the lowest in transudates (369.5 ng/ mL) and high levels, with a cut-off value of 396 ng/mL, differentiated PMEs from other subgroups with 65% sensitivity and 68% specificity. (AUC= 0.680, p= 0.02). Median serum YKL-40 level was the highest in PPPEs (351.4 ng/mL) and the lowest in TBPEs (114.2 ng/mL) (p= 0.01). For a cut-off level of 284 ng/mL, it differentiated PPPEs from TBPEs with 61% sensitivity and 100% specificity (AUC= 0.830, p= 0.01). In TBPEs, pleural/serum YKL-40 ratio was strongly related with pleural ADA (r= 1, p= 0.04). CONCLUSIONS: Pleural YKL-40 may be useful for differentiating exudates and detecting PMEs. Serum YKL-40 may be good diagnostic biomarker for differentiating PPPEs and TBPEs. Additionally, measuring serum and pleural YKL-40 and pleural ADA may be reliable way to diagnose TBPEs.

Pleural and serum markers for diagnosis of malignant pleural effusion.

BACKGROUND: Differentiation between benign and malignant exudative pleural effusion remains a clinical challenge. Recently, several markers have been reported to increase the diagnostic accuracy of malignant pleural effusion, with controversial results. METHODS: Patients with exudative pleural effusion were divided into 2 groups: a malignant pleural effusion group (39 patients) diagnosed by malignant cells in pleural fluid cytology or by malignant infiltration of the pleura on pleural biopsy, and a benign pleural effusion group (51 patients) with neither malignant cells in pleural fluid cytology nor malignant infiltration of the pleura on pleural biopsy. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were determined in both serum and pleural fluid samples, using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The etiology of malignant pleural effusion in the malignant group was breast cancer in 43.6% and bronchogenic carcinoma in 25.6%. There was a statistically significant difference between the 2 groups regarding sex, with more males in the benign group. There was no significant difference between groups regarding age. The median levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were higher in the malignant group than in the benign group, and the differences were highly significant in both pleural fluid (p < 0.001) and serum (p < 0.001). CONCLUSION: Matrix metaloproteinase-9 and tissue inhibitor of metalloproteinase-1 in serum and pleural fluid samples might be valuable markers for differentiating benign from malignant pleural effusions.

Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients.

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Diagnostic significance of biochemical markers and pentraxin-3 in the differential diagnosis of malign, benign pleural effusion and empyema.

OBJECTIVE: To investigate the diagnostic significance of biochemical markers and pentraxin-3 in the differential diagnosis of pleural effusions. METHODS: The prospective clinical study was conducted at the Suleyman Demirel University, Isparta, Turkey, from January 2013 to June 2014, and comprised patients with pleural effusion. Pleural effusions were tested for glucose, protein, lactate dehydrogenase, and pentraxin 3 while simultaneous C-reactive protein and white blood cell levels were studied in the serums. Data was analysed using SPSS 22. RESULTS: Of the 96 patients, 48(50%) had malignant disease, 33(34%) had benign pleural effusion, and 15(16%) had empyema. In terms of glucose, protein, lactate dehydrogenase in the pleural effusions and C-reactive protein values in serums, significant differences were observed among the three groups (p<0.05). The pentraxin-3 levels in the empyema group was significantly higher than in the benign cases (p<0.033). No significant difference was observed in terms of the other variables between the groups (p>0.05). CONCLUSIONS: Serum C-reactive protein and pentraxin-3 levels were not found to be individually conclusive in the differential diagnosis of pleural effusion. Also, lactate dehydrogenase levels were higher and glucose levels were lower in empyema.

Long-term stability of clinically relevant chemistry analytes in pleural and peritoneal fluid.

INTRODUCTION: Our aim was to investigate the stability of clinically relevant analytes in pleural and peritoneal fluids stored in variable time periods and variable storage temperatures prior to analysis. MATERIALS AND METHODS: Baseline total proteins (TP), albumin (ALB), lactate dehydrogenase (LD), cholesterol (CHOL), triglycerides (TRIG), creatinine (CREA), urea, glucose and amylase (AMY) were measured using standard methods in residual samples from 29 pleural and 12 peritoneal fluids referred to our laboratory. Aliquots were stored for 6 hours at room temperature (RT); 3, 7, 14 and 30 days at - 20°C. At the end of each storage period, all analytes were re-measured. Deviations were calculated and compared to stability limits (SL). RESULTS: Pleural fluid TP and CHOL did not differ in the observed storage periods (P = 0.265 and P = 0.170, respectively). Statistically significant differences were found for ALB, LD, TRIG, CREA, urea, glucose and AMY. Peritoneal fluid TP, ALB, TRIG, urea and AMY were not statistically different after storage, contrary to LD, CHOL, CREA and glucose. Deviations for TP, ALB, CHOL, TRIG, CREA, urea and AMY in all storage periods tested for both serous fluids were within the SL. Deviations exceeding SL were observed for LD and glucose when stored for 3 and 7 days at - 20°C, respectively. CONCLUSIONS: TP, ALB, CHOL, TRIG, CREA, urea and AMY are stable in serous samples stored up to 6 hours at RT and/or 30 days at - 20°C. Glucose is stable up to 6 hours at RT and 3 days at - 20°C. The stability of LD in is limited to 6 hours at RT.

Distinguishment of parasite-infected children from pediatric inpatients with both eosinophilia and effusion.

Patients with both serous effusion and eosinophilia are rarely reported and geographically distributed; their early diagnosis is difficult.According to the ultimate diagnosis, patients (≤14 years) in West China Second hospital with serous effusion and eosinophilia were divided into two groups including a parasitic group and a non-parasitic group. Clinical data were collected and analyzed between the two groups. Subsequently, significant measurement indicators were evaluated by receiver operating characteristic (ROC) curve to explore the optimal cut-off points for the most appropriate sensitivity and specificity.A total of 884 patients were diagnosed with serous effusion and 61 of them displayed co-morbidity with eosinophilia during enrolled time. Among 61 patients, 34 patients had parasitic infection and 27 had non-parasitic diseases. There were statistical difference in effusion position, the levels of white blood cell count (WBC), eosinophil (EOS), EOS%, C-reactive protein (CRP) between parasitic group and non-parasitic group. ROC curve demonstrated that the areas under the curve of EOS count and EOS% were >80%, and the corresponding optimal cut-off values were 1.71 × 10/L and 25.6% for distinguishing between parasitic and non-parasitic infections in our patients.This study provided a quantified index for potentially quick and convenient indicators of pediatric patients presenting with both eosinophilia and effusion. Eosinophils were helpful to improve the initial diagnosis with awareness of parasitic diseases. For the cases with EOS > 1.71 × 10/L or EOS% > 25.6%, parasitic infection should be considered and serological tests are recommended in our region.

Prognostic Value of Hematological Inflammatory Markers in Patients with Pleural Effusion Due to Heart Failure.

BACKGROUND: Pleural effusions due to heart failure are associated with a high 1-year mortality. Several hematological parameters have been shown to provide prognostic information in patients with cardiovascular diseases. The objective was to assess whether hematological markers can also provide prognostic information in patients with pleural effusion caused by heart failure. METHODS: This was a retrospective study of patients with pleural effusion due to heart failure who underwent a diagnostic thoracentesis. The hematological parameters evaluated were as follows: neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, platelet count, platelet-to-lymphocyte ratio, mean platelet volume (MPV), and MPV-to-platelet ratio. Patients were divided into two groups: those who died within 1 year and survivors of more than 1 year. Differences and possible correlations were analyzed with non-parametric tests. Diagnostic values were estimated. Survival analysis was performed using the Kaplan-Meier method. Cox regression analysis was performed to identify independent variables. RESULTS: Twenty five of 55 (45%) patients died within 1-year from thoracentesis. Patients who died in this period were older, aged 83 years (73 - 87, median and interquartile range, IQR) vs. 74 (65 - 82); with lower platelet count: 181 x 103 (140 - 258 x 103) vs. 241 x 103 (198 - 324 x 103); and higher MPV/platelet: 48.1 (34.9 - 75.6) vs. 35.6 (27.1 - 42.9). In the regression analysis only the MPV/platelet had statistical significance (p = 0.002). MPV/platelet > 50 had a specificity of 87% for 1-year mortality, and a ratio > 30 had a sensitivity of 84%. CONCLUSIONS: Simple hematological parameters such as platelet count and MPV/platelet, may provide useful prognostic information for predicting 1-year mortality in patients with pleural effusion due to heart failure.

Hematogenous pleural infection caused by Achromobacter xylosoxidans in a patient undergoing maintenance hemodialysis.

A 78-year-old Japanese man, undergoing maintenance hemodialysis for 20 years and having received coronary artery bypass grafting two months before, was hospitalized because of fever with subclinical left-sided pleurisy. Achromobacter xylosoxidans strains exhibiting identical genomic patterns on a macrorestriction analysis were isolated from the blood and the pleural effusion obtained on admission. Physical and radiological examinations did not reveal any lesions in either chest wall or lung adjacent to the effusion, indicating that the organism in the effusion had entered the pleural space via the bloodstream. Immunocompromising conditions due to undergoing maintenance hemodialysis and the presence of the antecedently accumulated pleural effusion may have been associated with the development of hematogenous dissemination. The patient fully recovered only with antibiotic therapy. To our knowledge, the present report is the first describing a case of hematogenous pleural infection caused by A. xylosoxidans.

Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany.

INTRODUCTION: Pediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs). METHODS: In a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped. RESULTS: S. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1-4.3 years] vs. median 5.6 years [IQR 3.8-8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1. CONCLUSION: Following the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.

High-throughput autoantibody analysis in malignant pleural effusion and tuberculosis pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) and tuberculosis pleural effusion (TPE) are 2 kinds of common pleural diseases. Finding efficient and accurate biomarkers to distinguish the 2 is of benefit to basic and clinical research. In the present study, we carried out the first high-throughput autoantibody chip to screen the beneficial biomarker with samples of MPE and TPE and the corresponding serum. METHODS: We collected pleural effusion and serum of patients with MPE (n = 10) and TPE (n = 10) who had been in Beijing Chao-Yang hospital from June 2013 to August 2014. Using RayBio Human Protein Array-G2 to measure the concentration of 487 defined autoantibodies. RESULTS: Fold changes of Bcl-2-like protein 11 (BIM) autoantibody in MPE-serum/TPE-serum and MPE/TPE groups were 10 (P = .019) and 6 (P = .001); for decorin autoantibody, MPE-serum/TPE-serum ratio was 0.6 (P = .029), and MPE/TPE ratio was 0.3 (P < .001). CONCLUSION: BIM autoantibody is a promising MPE biomarker by high-throughput autoantibody analysis in MPE and TPE.

Laboratory Discrimination Between Neutrophilic Malignant and Parapneumonic Pleural Effusions.

BACKGROUND: Malignant pleural effusion (MPE) occasionally demonstrates neutrophilic predominance, commonly found in parapneumonic pleural effusion (PPE). In comparison with lymphocytic MPE, neutrophilic MPE may have different characteristics associated with a more intense inflammatory response and poor prognosis. These characteristics of neutrophilic MPE may lead to inappropriate management and delayed diagnosis. Moreover, the limited diagnostic yield of microbiologic and cytologic tests makes early differential diagnosis between neutrophilic MPE and PPE more challenging. This study investigated objective laboratory findings to help distinguish neutrophilic MPE from PPE. MATERIALS AND METHODS: A retrospective study was conducted on patients with neutrophilic MPE and PPE. Routine blood and pleural fluid data of the 2 groups were compared, and the diagnostic performances of predictors for neutrophilic MPE were assessed using receiver-operating characteristic curves. RESULTS: Forty-one and 140 patients with neutrophilic MPE and PPE, respectively, were included. In final analysis, serum C-reactive protein, pleural fluid neutrophil-to-lymphocyte ratio, and pleural fluid carcinoembryonic antigen were significantly different between the 2 groups. With cut-off values of C-reactive protein <6.0 mg/dL, neutrophil-to-lymphocyte ratio <3.0 and carcinoembryonic antigen >8.0 ng/mL, the presence of any 2 or more parameters provided an area under the curve of 0.928 (95% CI, 0.851-0.999), yielding a sensitivity of 88%, specificity of 98%, positive predictive value of 92% and negative predictive value of 96% for identifying MPE. CONCLUSIONS: MPE should be considered even in patients with neutrophilic exudative effusion, especially if at least 1 predictor for neutrophilic MPE is present. Our results may help guide differentiation of neutrophilic MPE from PPE.

Serial Observation of Blood Alcohol Concentration post Ethanol Pleurodesis (SOBER) Study: A Prospective Observational Study.

OBJECTIVES: To measure the blood alcohol concentration levels in patients after chemical pleurodesis with ethanol sclerosant via video-assisted thoracoscopic surgery. DESIGN: Prospective observational study. SETTING: Single tertiary university hospital. PARTICIPANTS: Eight patients undergoing chemical pleurodesis with ethanol sclerosant for management of recurrent pneumothoraces or pleural effusions. INTERVENTIONS: After ethics board approval, written informed consent was obtained from 8 patients undergoing chemical pleurodesis with ethanol sclerosant for management of recurrent pneumothoraces or pleural effusions. Five patients received a dose of 100 mL of 70% ethanol/1% iodine, and 3 patients received 30 mL. Blood alcohol concentration measurement was obtained at 30, 60, 90, and 120 minutes after the ethanol was instilled in the interpleural space. The postoperative quality of recovery scale was conducted preoperatively and then at 30 and 60 minutes postoperatively and on postoperative days 1 and 3. MEASUREMENTS AND MAIN RESULTS: The highest observed blood alcohol concentration was recorded at 30 minutes post-instillation of ethanol in all patients. The blood alcohol concentration peak for 75% of patients (6/8) was >0.05 g/dL at 30 minutes post-instillation of ethanol, and for 4 patients (50%), this remained >0.05 g/dL at 60 minutes. The median area under curve of ethanol absorbed was 5.66 g/dL/min (3.24-7.29). CONCLUSIONS: Significant systemic absorption of ethanol can occur after instillation of ethanol sclerosant, which potentially may affect the quality of recovery in patients. Postoperative management of these patients may need to be specifically tailored to take into account these observations.

Comparison of cobas EGFR Mutation Test v2 and PANAMutyper-R-EGFR for Detection and Semi-Quantification of Epidermal Growth Factor Receptor Mutations in Plasma and Pleural Effusion Supernatant.

BACKGROUND: Plasma epidermal growth factor receptor (EGFR) mutation tests are less invasive than tissue EGFR mutation tests. We determined which of two kits is more efficient: cobas EGFR Mutation test v2 (cobasv2; Roche Molecular Systems, Pleasanton, CA, USA) or PANAMutyper-R-EGFR (Mutyper; Panagene, Daejeon, Korea). We also evaluated whether pleural effusion supernatant (PE-SUP) samples are assayable, similar to plasma samples, using these two kits. METHODS: We analyzed 156 plasma and PE-SUP samples (31 paired samples) from 116 individuals. We compared the kits in terms of accuracy, assessed genotype concordance (weighted κ with 95% confidence intervals), and calculated Spearman's rho between semi-quantitatively measured EGFR-mutant levels (SQIs) measured by each kit. We also compared sensitivity using 47 EGFR-mutant harboring samples divided into more-dilute and less-dilute samples (dilution ratio: ≥ or <1:1,000). RESULTS: cobasv2 tended to have higher accuracy than Mutyper (73% vs 69%, P=0.53), and PE-SUP samples had significantly higher accuracy than plasma samples (97% vs 55-71%) for both kits. Genotype concordance was 98% (κ=0.92, 0.88-0.96). SQIs showed strong positive correlations (P<0.0001). In less-dilute samples, accuracy and sensitivity did not differ significantly between kits. In more-dilute samples, cobasv2 tended to have higher sensitivity than Mutyper (43% vs 20%, P=0.07). CONCLUSIONS: The kits have similar performance in terms of EGFR mutation detection and semi-quantification in plasma and PE-SUP samples. cobasv2 tends to outperform Mutyper in detecting less-abundant EGFR-mutants. PE-SUP samples are assayable using either kit.

Diagnosis of Parapneumonia Pleural Effusion with Serum and Pleural Fluid Cell-Free DNA.

OBJECTIVE: As cell-free DNA levels in the pleural fluid and serum of parapneumonic pleural effusion (PPE) patients have not been thoroughly explored, we evaluated their diagnostic potential. METHODS: Twenty-two PPE and 16 non-PPE patients were evaluated. Serum and pleural fluids were collected, and cell-free DNA was quantified. All biomarkers were assessed for correlation with days after admission. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic accuracy and optimal cut-off point. RESULTS: Nuclear and mitochondrial DNA levels in the pleural fluid and nuclear DNA levels in serum of PPE patients were significantly higher than in those of the non-PPE patients. However, only cell-free DNA levels in pleural fluid correlated with days after admission among PPE patients (r= 0.464, 0.538, respectively). ROC curve analysis showed that nuclear and mitochondrial DNA in pleural fluid had AUCs of 0.945 and 0.889, respectively. With cut-off values of 134.9 and 17.8 ng/ml for nuclear and mitochondrial DNA in pleural fluid, respectively, 96% sensitivity and 81% specificity were observed for PPE diagnosis. CONCLUSION: Nuclear and mitochondrial DNA in pleural fluid possess PPE diagnostic potential and correlated with disease severity. Serum nuclear DNA could also be used to distinguish freshly admitted PPE patients (Day 1) from non-PPE patients, but with less accuracy.