A PET-CT score for discriminating malignant from benign pleural effusions.

BACKGROUND AND OBJECTIVES: The results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions. PATIENTS AND METHODS: We conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021. RESULTS: One hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV>7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV>4.5 (5 points) and cardiomegaly (-1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients. CONCLUSIONS: PET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.

TNFSF4 is a risk factor to systemic lupus erythematosus in a Latin American population.

OBJECTIVE: The aim of this study was to examine the association of three TNFSF4 single nucleotide variants (SNVs) with systemic lupus erythematosus (SLE) susceptibility in Mexican patients. METHODS: Genotypes of the TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G SNVs were determined using a TaqMan assay. In our study, we included 395 patients with SLE and 500 controls. RESULTS: Our information shows a significant difference in the allelic and genotypic frequency of the three TNFSF4 SNVs between cases and controls. Thus, our data showed an association between TNFSF4 rs1234315T/C (T vs. C, OR 1.40, p = 0.00087), rs2205960G/T (G vs. T, OR 1.32, p = 0.0037), and rs704840T/G (T vs. G, OR 1.41, p = 0.0003) and SLE susceptibility in Mexican subjects. Besides, we conducted a meta-analysis to determine the role of TNFSF4 rs2205960G/T and SLE susceptibility; our results showed that this variant is a risk factor for SLE in Latin Americans and Asians. CONCLUSION: Our results show that TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G are risk factors to SLE in Mexicans. This is the first study to document an association between TNFSF4 rs704840T/G and SLE in a Latin American population. In addition, our meta-analysis showed that TNFSF4 rs2205960G/T is a risk factor for Asians and Latin Americans. Key Point • The TNFSF4 rs1234315T/C, rs2205960G/T, and rs704849T/G SNVs are risk factors to SLE in patients from Mexico.

Computed tomography scoring system for discriminating between parapneumonic effusions eventually drained and those cured only with antibiotics.

BACKGROUND AND OBJECTIVE: Due to limited data, we aimed to develop and validate a computed tomography (CT)-based scoring system for identifying those parapneumonic effusions (PPEs) requiring drainage. METHODS: A retrospective review of all patients with PPE who underwent thoracentesis and a chest CT scan before any attempt to place a tube thoracostomy, if applicable, over an 8-year period was conducted. Eleven chest CT characteristics were compared between 90 patients with complicated PPEs (CPPEs), defined as those which eventually required chest drainage, and 60 with non-complicated effusions (derivation sample). A scoring system was devised with those CT findings identified as independent predictors of CPPE in a logistic regression analysis, and further validated in an independent population of 59 PPE patients. RESULTS: CT scores predicting CPPE were pleural contrast enhancement (3 points), pleural microbubbles, increased extrapleural fat attenuation and fluid volume ≥400 mL (1 point each). A sum score of ≥4 yielded 84% sensitivity (95% CI: 62-85%), 75% specificity (95% CI: 62-85%), 81% diagnostic accuracy (95% CI: 73-86%), likelihood ratio (LR) positive of 3.4 (95% CI: 2.1-5.4), LR negative of 0.22 (95% CI: 0.13-0.36) and area under the receiver operating characteristic curve (AUC) of 0.829 (95% CI: 0.754-0.904) for labelling CPPE in the derivation set. These results were reproduced in the validation sample. The CT grading scale also exhibited a fair ability to identify patients who needed surgery or would die from the pleural infection (AUC: 0.76, 95% CI: 0.61-0.9). CONCLUSION: A novel CT scoring system for adults with PPE may allow clinicians to predict the need for chest tube drainage with good accuracy.

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.

[Population analysis by area of health of changes in consumption, price and expenditure of cardiovascular drugs in eight autonomous communities, Spain, 2005]. / Análisis poblacional por áreas de salud de las variaciones en consumo, precio y gasto de medicamentos cardiovasculares en 8 comunidades autónomas, españa, 2005.

BACKGROUND: Variability in cardiovascular drugs is of great interest because of its high population use, its high expenditure and the availability of strong evidence supporting its use. The aim of this study is to describe variation in dispensation, price and pharmaceutical expenditure for 11 subgroups of cardiovascular drugs by healthcare areas. METHODS: This was a population study describing dispensation for 11 subgroups of cardiovascular drugs among healthcare areas in 2005. POPULATION: 93 healthcare areas of the 8 participant Autonomous Regions. ANALYSIS: Descriptive analysis of dispensation (Defined Daily Dose (DDD) per 1,000 pensioners and day (DDD/1000P/Day), average price (euros per DDD), pharmaceutical expenditure (euros per 100 pensioners) and standardized consumption ratios. Small-area variation analysis was used to analyze observed variability. RESULTS: Consumption of cardiovascular drugs oscillated between 324 DDD/1000p/Day for drugs with action on the renin-angiotensin system, and 6.5 DDD/1000p/Day for anti-aldosterone diuretics. Variation in consumption for areas in the 5th and 95th percentiles went from 1.8 times (digitalics) to 17.2 times (flavonoids), although most of the groups showed an extremal quotient of around 5. Variation in average prices was lower than in consumption (1.1 times for doxazosin and 3.7 for flavonoids) and variations in pharmaceutical expenditure was similar to variation in consumption (from 2.0 timesfor digitalics to 13.0 times for flavonoids). CONCLUSIONS: Major variations in the consumption of cardiovascular drugs between healthcare areas, together with discreet variations in price mean there are big differences in pharmaceutical expenditure from one population to another.

A review of programs to alleviate the burden of informal caregivers of dependent persons.

The review of interventions currently available to alleviate the burden of informal caregivers of dependent persons has both social and political relevance considering the increasing number of elderly dependent persons. Respite services and programs for psycho-social intervention are the main methods of dealing with this burden. Study of the main research carried out to date on such interventions enables us to organize more efficient services, especially considering the enactment of the Law on Dependence in Spain in January 2007 and the need for other European and international governments to establish systems to meet the needs of the growing dependent population.

Pleural fluid mesothelin for the differential diagnosis of exudative pleural effusions.

BACKGROUND: Malignant mesothelioma (MM) is a highly aggressive tumor that can be difficult to diagnose, resulting in a delayed diagnosis in some cases. Recent studies have reported that determination of soluble mesothelin-related peptides (SMRP) in pleural fluid may be a promising marker for use in the diagnosis of MM. PATIENTS AND METHODS: Pleural fluid SMRP concentration was measured in 68 patients: 47 had malignant pleural effusions (18 MM and 29 metastatic effusion) and 21 had benign pleural effusion (8 infectious disease and 13 idiopathic effusion). Mann-Whitney analysis was used to compare SMRP values according to the etiology of the effusion. RESULTS: Pleural fluid SMRP concentration was significantly higher in patients with malignant pleural effusion than in those with benign effusion (P=0.02). When malignant pleural effusions were analyzed separately, MM patients had the highest median pleural fluid SMRP concentration, with significant differences as compared to patients with idiopathic pleural effusion. CONCLUSIONS: Soluble mesothelin-related peptide measurement in pleural fluid may aid in the diagnosis of patients presenting with pleural effusion.

A decision tree for differentiating tuberculous from malignant pleural effusions.

OBJECTIVE: To improve physicians' ability to discriminate tuberculous from malignant pleural effusions through a simple clinical algorithm that avoids pleural biopsy. DESIGN: We retrospectively compared the clinical and pleural fluid features of 238 adults with pleural effusion who satisfied diagnostic criteria for tuberculosis (n=64) or malignancy (n=174) at one academic center (derivation cohort). Then, we built a decision tree model to predict tuberculosis using the C4.5 algorithm. The model was validated with an independent sample set from another center that included 74 tuberculous and 293 malignant effusions (validation cohort). RESULTS: Among 12 potential predictor variables, the classification tree analysis selected four discriminant parameters (age>35 years, pleural fluid adenosine deaminase>38U/L, temperature>or=37.8 degrees C, and pleural fluid LDH>320U/L) from the derivation cohort. The generated flowchart had 92.2% sensitivity, 98.3% specificity, and an area under the ROC curve of 0.976 for diagnosing tuberculosis. The corresponding operating characteristics for the validation cohort were 85.1%, 96.9% and 0.958. CONCLUSIONS: Applying a decision tree analysis that contains simple clinical and laboratory data can help in the differential diagnosis of tuberculous and malignant pleural effusions.

Angiogenic factors and angiogenesis inhibitors in exudative pleural effusions.

The angiogenesis system has been implicated in inflammatory and neoplastic processes; nevertheless, it has been little studied in relation to the pleural space. Our aim is to analyze pleural and plasma levels of the activators--vascular endothelial growth factor, basic fibroblastic growth factor, and inhibitors--endostatin and thrombospondin-1 and to estimate the association between these factors and related biochemical markers. We analyzed pleural fluid from 105 patients with one of the following types of pleural effusion: empyema or complicated parapneumonic, non-complicated parapneumonic, tuberculous, neoplastic and transudative. Angiogenesis activators were higher in exudates than in transudates (p < 0.001) and in empyema than in non-complicated parapneumonic patients (p < 0.001). Endostatin showed no significant differences. Trombospondin-1 showed higher levels in exudates than in transudates and in empyema than in non-complicated parapneumonic effusions (p < 0.001). In pleural exudates there was a positive correlation of angiogenesis activators and trombospondin-1 with low glucose and pH and high LDH. There was no correlation between pleural and plasma levels of the angiogenesis factors. We conclude that exudative pleural effusions showed higher vascular endothelial growth factor, basic-fibroblastic growth factor and trombospondin-1 values than transudative effusions that associated to low glucose and pH, and high LDH. There was no correlation between pleural and plasma concentrations, suggesting a compartmentalized response.

Accuracy of chest sonography and polymorphonuclear elastase in the assessment of bacterial pleural effusion.

Background: The relationship between chest sonography findings and inflammatory markers for assessing bacterial pleural effusion is not well established. We decided to study the accuracy of chest sonography in determining the nature of bacterial pleural effusion and its relationship with polymorphonuclear elastase (PMN-E) results. Methods: Pleural sonography and PMN-E were evaluated in a prospective study of 144 consecutive patients with pleural effusion of various etiologies: 25 complicated parapneumonic, 18 uncomplicated parapneumonic, 33 tuberculous, 17 malignant, 12 transudates, and 39 of unknown etiology. The sonographer distinguished between anechoic and septated pattern. The relationship between sonographic appearance and inflammatory markers was evaluated. Results: All of the complicated parapneumonic, 11 uncomplicated parapneumonic, and 28 tuberculous effusions were septated. Septated pattern and PMN-E value were independent predictors of infectious pleural disease (p <0.05). The simultaneous presence of a septated pattern and a PMN-E higher than 100 microg/l had a sensitivity of 79.1% and a specificity of 91.1% for the diagnosis of bacterial effusions. Conclusions: PMN-E level and the sonographic pattern of pleural fluid may be useful in the diagnosis of bacterial pleural effusions.

Polymorphonuclear elastase in the early diagnosis of complicated pyogenic pleural effusions.

BACKGROUND: Polymorphonuclear elastase (PMN-E) is a neutrophilic marker that has been implicated in acute inflammatory responses. OBJECTIVES: To evaluate the accuracy of PMN-E in the diagnosis of complicated pyogenic effusions. PATIENTS AND METHOD: We studied 536 patients with pleural effusion of various etiologies. There were 125 pyogenic bacterial effusions (42 typical parapneumonic, 17 borderline complicated parapneumonic and 66 complicated parapneumonic or empyema), 83 tuberculous, 91 malignant, 42 paramalignant, 95 transudates, 28 miscellaneous and 72 effusions of unknown origin. Classic markers (pH, glucose, proteins, adenosine deaminase, LDH, leukocytes and differential count) and the PMN-E level were quantified in pleural fluid. The accuracy of PMN-E as an early marker in the diagnosis of complicated pyogenic infectious effusions was evaluated among pleural effusions that were not diagnosed with classic biochemical markers, radiological findings or Gram stain. Since results of pleural fluid culture and cytological examination are generally available after a 48-hour delay, they were not included as early markers in the initial diagnosis of pleural effusions. RESULTS: Early diagnosis of complicated pyogenic bacterial effusions was achieved in only 48 of 66 cases with classic markers. Among those that were not diagnosed with these parameters, a pleural PMN-E value >3,500 microg/l discriminated between complicated and noncomplicated pyogenic bacterial effusions with a sensitivity of 67% and a specificity of 97%. CONCLUSIONS: PMN-E is useful in the early diagnosis and management of complicated pyogenic infectious effusions, which may be delayed with classic markers.

Association between inflammatory mediators and the fibrinolysis system in infectious pleural effusions.

The response of the fibrinolytic system to inflammatory mediators in empyema and complicated parapneumonic pleural effusions is still uncertain. We prospectively analysed 100 patients with pleural effusion: 25 with empyema or complicated parapneumonic effusion, 22 with tuberculous effusion, 28 with malignant effusion and 25 with transudate effusion. Inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and polymorphonuclear elastase, were measured in serum and pleural fluid. Fibrinolytic system parameters, plasminogen, tissue-type plasminogen activator (t-PA) and urokinase PA, PA inhibitor type 1 (PAI 1) and PAI type 2 concentrations and PAI 1 activity, were quantified in plasma and pleural fluid. The Wilcoxon signed-rank test was used to compare plasma and pleural values and to compare pleural values according to the aetiology of the effusion. The Pearson correlation coefficient was used to assess the relationship between fibrinolytic and inflammatory markers in pleural fluid. Significant differences were found between pleural and plasma fibrinolytic system levels. Pleural fluid exudates had higher fibrinolytic levels than transudates. Among exudates, tuberculous, empyema and complicated parapneumonic effusions demonstrated higher pleural PAI levels than malignant effusions, whereas t-PA was lowest in empyema and complicated parapneumonic pleural effusions. PAI concentrations correlated with TNF-alpha, IL-8 and polymorphonuclear elastase when all exudative effusions were analysed, but the association was not maintained in empyema and complicated parapneumonic effusions. A negative association found between t-PA and both IL-8 and polymorphonuclear elastase in exudative effusions was strongest in empyema and complicated parapneumonic effusions. Blockage of fibrin clearance in empyema and complicated parapneumonic effusions was associated with both enhanced levels of PAIs and decreased levels of t-PA.