Clinical significance of pleural fluid lactate dehydrogenase/adenosine deaminase ratio in the diagnosis of tuberculous pleural effusion.

BACKGROUND: Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE. METHODS: The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE. RESULTS: The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P < 0.01) and MPE group (10 U/L, P < 0.001). The median pfADA level in the TPE group was 41 (32, 52) U/L; it was lowest in the MPE group at 9 (7, 12) U/L and highest in the PPE group at 43 (23, 145) U/L. The pfLDH level in the PPE group was 2542 (1109, 6219) U/L, which was significantly higher than that in the TPE group 449 (293, 664) U/L. In the differential diagnosis between TPE and non-TPE, the AUC of pfLDH/pfADA for diagnosing TPE was the highest at 0.946 (0.925, 0.966), with an optimal cutoff value of 23.20, sensitivity of 93.9%, specificity of 87.0%, and Youden index of 0.809. In the differential diagnosis of TPE and PPE, the AUC of pfLDH/pfADA was the highest at 0.964 (0.939, 0.989), with an optimal cutoff value of 24.32, sensitivity of 94.6%, and specificity of 94.4%; this indicated significantly better diagnostic efficacy than that of the single index of pfLDH. In the differential diagnosis between TPE and MPE, the AUC of pfLDH/pfADA was 0.926 (0.896, 0.956), with a sensitivity of 93.4% and specificity of 80.0%; this was not significantly different from the diagnostic efficacy of pfADA. CONCLUSIONS: Compared with single biomarkers, pfLDH/pfADA has higher diagnostic value for TPE and can identify patients with TPE early, easily, and economically.

Diagnostic value of soluble biomarkers for parapneumonic pleural effusion.

Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.

Analysis of clinical characteristics and risk factors of community-acquired pneumonia complicated by parapneumonic pleural effusion in elderly patients.

BACKGROUND: Community-acquired pneumonia (CAP) patients usually present with parapneumonic pleural effusion (PPE), which complicates the treatment of pneumonia. This study aims to investigate the clinical characteristics and risk factors of elderly CAP patients hospitalised with PPE. METHODS: The clinical data of 132 elderly patients with CAP were retrospectively analysed. A total of 54 patients with PPE (PPE group) and 78 patients without PPE (NPPE group) were included in this study. Clinical data, laboratory examinations, treatments and other relevant indicators were collected. Univariate analysis and multivariate logistic regression analysis will be used to explore the possible risk factors for PPE. RESULTS: The proportion of PPE in elderly patients with CAP was 40.9%. PPE patients were significantly more likely to be older, have comorbid neurological diseases, experience chest tightness, and have a lasting fever (P < 0.05). In contrast to NPPE patients, the total number of lymphocytes, serum albumin and blood sodium levels in the PPE group were significantly lower (P < 0.05). The blood D-dimer, C-reactive protein and CURB-65 score of PPE patients were significantly higher (P < 0.05) than those of NPPE patients. Multivariate logistic regression identified chest tightness (OR = 3.964, 95% CI: 1.254-12.537, P = 0.019), long duration of fever (OR = 1.108, 95%CI: 1.009-1.217, P = 0.03), low serum albumin (OR = 0.876, 95%CI: 0.790- 0.971, P = 0.012) or low blood sodium (OR = 0.896, 95%CI: 0.828-0.969, P = 0.006) as independently associated with the development of parapneumonic pleural effusion in the elderly. CONCLUSION: This study has identified several clinical factors, such as chest tightness, long duration of fever, low serum albumin, and low blood sodium, as risk factors for the development of pleural effusion in elderly patients with CAP. Early identification and prompt management of these patients can prevent inappropriate treatment and reduce morbidity and mortality.

The pleural fluid lactate dehydrogenase/adenosine deaminase ratio differentiates between tuberculous and parapneumonic pleural effusions.

BACKGROUND: Although pleural fluid lactate dehydrogenase (LDH) and adenosine deaminase (ADA) levels are often used to distinguish between tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE), this can be challenging as the LDH level may vary from normal to severely increased in PPE and a significantly elevated ADA is frequently measured in both conditions. In this study, we evaluated use of the pleural fluid LDH/ADA ratio as a new parameter to discriminate TPE from PPE. METHODS: A retrospective study was conducted in patients with pathologically-confirmed TPE (n = 72) and PPE (n = 47) to compare pleural fluid LDH and ADA levels and LDH/ADA ratios between the 2 groups. A receiver operating characteristic (ROC) curve was constructed for identifying TPE. RESULTS: The median pleural fluid LDH and ADA levels and LDH/ADA ratios in the TPE and PPE groups were: 364.5 U/L vs 4037 U/L (P < .001), 33.5 U/L vs 43.3 U/L (P = .249), and 10.88 vs 66.91 (P < .0001), respectively. An area under the ROC curve of 0.9663 was obtained using the LDH/ADA ratio as the indicator for TPE identification, and the sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were, respectively, 93.62%, 93.06%, 13.48, and 0.068 at a cut-off level of 16.20. CONCLUSIONS: The pleural fluid LDH/ADA ratio, which can be determined from routine biochemical analysis, is highly predictive of TPE at a cut-off level of 16.20. Measurement of this parameter may be helpful for clinicians in distinguishing between TPE and PPE.

Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study.

BACKGROUND: Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population. METHODS: Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality. RESULTS: A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events. CONCLUSIONS: If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

A study of the proteomic expression in patients with complicated parapneumonic pleural effusion.

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation.

Intrapleural Thrombolytics as First Line Therapy for Complicated Parapneumonic Effusions and Empyema in Patients with Prohibitive Surgical Risk: A Cases Series.

OBJECTIVE: In complicated parapneumonic effusion or Empyema, approximately 25% of patients require surgical intervention which can be associated with a mortality risk of almost 20%. However, the use combination of rt-tPA and DNase in elderly patients with prohibitive surgical risk has improved outcomes. The main goal of our study is to highlight the utility of intrapleural thrombolysis in patients with prohibitive risk for surgery. METHODS: A retrospective record review study of patients (n=23) with complicated parapneumonic pleural effusion or empyema treated with tPA and DNase from January 1st of 2015 to March 18th, 2019 at VACHCS. Data collected to describe the outcome of intrapleural thrombolytics included demographic, pleural fluid analysis, surgical risk assessment, diagnosis and initiation treatment day, doses, chest imaging, drainage rate, chest tube size and average days in place, inflammatory markers, microbiology, antibiotics, and complications. RESULTS: Only 21.7% of patients were considered surgical candidates. Seventy-four percent had a 30-day post-surgical mortality risk of > 2.5% using the National Surgery Office (NSO) risk calculator. Post-operative inpatient stay was 99.7% and estimated post operative ICU stay average was >80%. Primary outcome (pleural drainage improvement) obtained in 73.9%. Most common serious complications included sepsis (52.2%) and nonserious was residual hydropneumothorax (47.8%). CONCLUSION: This study demonstrates that administration of intrapleural thrombolytics through a percutaneous pleural catheter achieved successful drainage safely and without the need for surgical interventions in a selected group of advanced age, elderly patients with pleural infections who were deemed to be high surgical risk.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

The role of thyroid hormones in the differential diagnosis of tuberculous and parapneumonic pleural effusions.

BACKGROUND: The differential diagnosis of tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE) is challenging due to similar clinical manifestations and body fluid biochemical profiles. Thyroid hormone levels change in response to lymphocyte proliferation in the peripheral blood of patients with mycobacterial infections such as tuberculosis; therefore, this study aimed to investigate the utility of assessing thyroid hormone levels to aid in the differential diagnosis of TPE and PPE. METHODS: We measured free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels in the pleural effusions of 59 newly admitted patients (32 and 27 with TPE and PPE, respectively). Hormone levels were assessed using an electrochemiluminescence technique, and the diagnostic parameters for tuberculosis were evaluated. Differences in hormone levels between patients with TPE and PPE were assessed by t-tests, and their diagnostic value for a differential diagnosis was evaluated by receiver operating characteristic curve analyses. RESULTS: FT3 and FT4 levels in patients with TPE were significantly higher than those in patients with PPE (p < 0.01 and p < 0.05, respectively), whereas TSH expression did not significantly differ between the two groups (p > 0.05). FT3 and FT4 levels showed no correlation with sex or history of smoking, although FT3 levels decreased with age. The highest sensitivity was observed for the quantification of FT3 levels (84.38%). CONCLUSIONS: Increased FT3 and FT4 levels could potentially be used for the differential diagnosis of TPE and PPE.

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.

[Successful treatment of a stage III pleural empyema following a COVID-19 infection]. / Erfolgreiche Behandlung eines drittgradigen Pleuraempyems infolge einer COVID-19-Infektion.

Parapneumonic pleural effusion is a common complication of pneumonia and can progress to empyema. Pleural empyema is a life-threatening infection, which can be treated with antibiotics and interventional drainage but in later stages often requires surgery. Here we describe the first case of pleural empyema following a COVID-19 infection with no respiratory failure in a previously healthy and athletic patient. The patient was initially treated with antibiotics and interventional drainage but was readmitted to hospital with symptom deterioration. He was then referred for surgery and underwent an uneventful thoracoscopic washout with partial decortication. The preoperative SARS-CoV­2 swab was negative. The patient recovered fully and could be discharged.

Incidence trends of parapneumonic pleural effusions/empyema in children 2009 to 2018 from health insurance data: Only temporal reduction after the introduction of PCV13.

BACKGROUND: Recently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear. METHODS: Annual incidence of PPE/PE in children were determined using secondary health care data for 2009-2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models. RESULTS: Overall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0-1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41-17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2-5 year olds (15.85; 95% CI: 11.27-20.43) and the 6-18 year olds (12.29; 95% CI: 10.23-14.36) was also in 2013, whereas for the 0-1 year olds it was found in 2014 (32.66; 95% CI: 23.79-41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013. DISCUSSION: We found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.

Biomarkers of Distinguishing Neutrophil-Predominant Tuberculous Pleural Effusion from Parapneumonic Pleural Effusion.

BACKGROUND: Tuberculous pleural effusion (TPE) is usually characterized by lymphocytic predominance and high pleural fluid adenosine deaminase (pfADA), while parapneumonic pleural effusion (PPE) is usually characterized by neutrophilic predominance. However, in some cases, neutrophils can be predominant in TPE. In such cases, the differential diagnosis between TPE and PPE is challenging and has been rarely investigated. The aim of this study was to evaluate the accuracy of pfADA, pleural fluid lactate dehydrogenase (pfLDH) and other parameters, such as age/pfADA in the differential diagnosis of neutrophil-predominant TPE (NP-TPE) and PPE. METHODS: Between January 2003 and August 2018, 19 patients with NP-TPE and 54 patients with PPE at Shanghai Jiao Tong University Affiliated Sixth People's Hospital were retrospectively reviewed. Age, blood and pleural fluid findings, and eight ratios that consisted of routine biomarkers were compared between the two groups in ≤50 and >50 years old groups. ROC curve analysis was used to evaluate diagnostic performance. RESULTS: The three parameters with the largest AUC were age/pfADA, pfADA and pfLDH in ≤ 50 years old group, and pfADA, age/pfADA and the percentage of neutrophils in pleural fluid (pfN%) in >50 years old group. For patients ≤ 50 years old, pfADA combined with pfLDH or age/pfADA combined with pfLDH could increase the specificity to 100%, while the sensitivity of the former was high (84.6% vs 76.9%). For patients >50 years old, both pfADA combined with pfN% and age/pfADA combined with pfN% could increase the specificity to 90.3% with the same sensitivity. CONCLUSIONS: Although pfADA played an important role in the discrimination of NP-TPE from PPE, combining pfADA with pfLDH for patients ≤50 years old or combining pfADA with pfN% for patients >50 years old might improve diagnostic performance.

Pleural fluid lactate as a point-of-care adjunct diagnostic aid to distinguish tuberculous and complicated parapneumonic pleural effusions during initial thoracentesis: Potential use in a tuberculosis endemic setting.

BACKGROUND: Tuberculous pleural effusions (TBEs) and parapneumonic pleural effusion (PPEs) have similar clinical presentations and fluid biochemistry. A pleural biopsy is usually required to diagnose TBE but complete fluid evacuation may not be necessary, contrasting with complicated PPE (CPPE). A point-of-care test that distinguishes between TBE and CPPE enables the appropriate procedures to be performed during the initial diagnostic thoracentesis. Lactate is a metabolic product measurable by a blood-gas analyzer. This study measured pleural fluid (Pf) lactate levels in TBE and compared them with those in PPE/CPPE. We hypothesized that Pf lactate would be significantly higher in PPE because of active metabolic activities than in TBE which is driven by delayed hypersensitivity. METHODS: All patients undergoing an initial diagnostic thoracentesis over 18 months with Pf lactate measured using a calibrated point-of-care blood gas analyzer were assessed. RESULTS: The diagnoses of the enrolled patients (n = 170) included TBE (n = 49), PPE (n = 47), malignancy (n = 63), and transudate (n = 11). Pf lactate level in TBE, median 3.70 (inter-quartile range 2.65-4.90) mmol/l, was significantly lower than in PPE and CPPE. In the subgroup of TBE and CPPE patients whose initial Pf pH and glucose could suggest either condition, Pf lactate was significantly higher in those with CPPE. Pf lactate (cutoff ≥7.25 mmol/l) had a sensitivity of 79.3%, specificity 100%, positive predictive value 100%, and negative predictive value 89.1% for discriminating CPPE from TBE (area under the curve 0.947, p < 0.001, 95% confidence interval 0.89-0.99). CONCLUSIONS: Point-of-care Pf lactate measurements may have practical value in early separation of TBE or CPPE during initial thoracentesis, and warrants further investigation.

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.

Clinical Impact of a Pleural Unit in a Tertiary Level Hospital. / Impacto clínico de una unidad de patología pleural en un hospital de tercer nivel.

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P=.004); SSP: 13.2 to 8.6 (P=.005), MPE: 10.3 to 12.3 (P=.05); and CPPE: 18.3 to 11.3 (P=.001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P=.021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality.

Diagnostic performance of C-reactive protein for parapneumonic pleural effusion: a meta-analysis.

BACKGROUND: Parapneumonic pleural effusion (PPE) refers to effusion secondary to lung infection, the accurate diagnosis of which remains a clinical challenge. Many studies have suggested that the C-reactive protein (CRP) may be useful for diagnosing PPE, but the results have varied. This study aimed to summarize the overall diagnostic ability of serum/pleural CRP for PPE through a meta-analysis. METHODS: Eligible studies were searched for within PubMed, EMBASE, and other databases up to March 1, 2018. The main diagnostic indexes, sensitivity, specificity, positive likelihood ratio/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR), were then pooled from the individual studies. The summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize the overall test performance. RESULTS: Eighteen publications were included in this meta-analysis. Summary estimates of the diagnostic performance of pleural CRP for PPE were as follows: sensitivity, 0.80; specificity, 0.82; PLR, 4.51; NLR, 0.25; DOR, 18.26; and AUC, 0.88. The AUC of serum CRP in diagnosing PPE was 0.79. The diagnostic indexes for pleural CRP in differentiating complicated PPE (CPPE) from uncomplicated PPE were as follows: sensitivity, 0.65; specificity, 0.85; PLR, 4.26; NLR, 0.41; DOR, 10.38; and AUC, 0.83. There was no evidence of publication bias. CONCLUSIONS: Both serum and pleural CRP help to diagnose PPE but with moderate diagnostic ability. Pleural CRP measurements also can aid in differentiating CPPE from uncomplicated PPE. However, the results of the CRP assay should be interpreted with additional biomarker tests.

Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study.

OBJECTIVES: Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. METHODS: Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. RESULTS: The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87%); these were most frequently Streptococcus pneumoniae (41%), Streptococcus pyogenes (19%) and Staphylococcus aureus (6%). Serotype 3 accounted for 45% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95%CI 12-16) and 18 (95%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95%CI 1.5-3.2) by 2016/17 (p 0.205). CONCLUSIONS: In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.

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.

Management of pleural infections.

INTRODUCTION: The management of infected pleural effusion is complex. Therapeutic resolution requires determining the following: appropriate antibiotic regimen, the need for pleural drainage, the optimal drainage tube size, and the need for intrapleural therapy or surgery. Areas covered: An updating of the latest advances in the management of parapneumonic pleural effusion based on the best evidence available is provided. Expert commentary: The correct management of parapneumonic pleural effusion is based on selecting an antibiotic regimen according to the origin of the pleural infection (community-acquired or nosocomial). If pleural drainage is indicated, a small-bore chest tube is appropriate. Although the administration of fibrinolytics is not required in all cases, when necessary, recombinant t-PA in combination with deoxyribonuclease is the preferred therapy. If surgery is indicated, video-assisted thoracoscopic surgery is as effective - if not superior - as open decortication. All these therapies should be complemented with appropriate nutritional support. Further clinical trials are needed to confirm whether new therapeutic strategies such as a pleural cavity saline wash are more effective in the management of this disease.