[Incidence of pneumococcal disease admissions in children with risk conditions in Catalonia (2005-2012)]. / Incidencia de hospitalizaciones por enfermedad neumocócica en niños con condiciones de riesgo en Cataluña (2005-2012).

INTRODUCTION: Streptococcus pneumoniae is a significant cause of morbidity and mortality. Children with certain conditions are at risk of developing pneumococcal disease, including invasive pneumococcal disease (IPD). The aim of this study is to estimate admission rates for IPD in children with risk conditions in Catalonia, and to describe their characteristics. MATERIAL AND METHOD: Retrospective longitudinal study of admission rates due to IPD between 2005 and 2012 in children younger than 16 years referred by Primary Care Centres of the Catalan Institute of Health, with risk conditions for invasive pneumococcal disease. Information was obtained from electronic medical records in the Primary Care Centres and from the Minimum Basic Data Set (MBDS) of acute hospital admissions. RESULTS: The overall IPD hospital admission rate in children with underlying conditions was 43.1 cases per 100,000 persons-year (95% CI: 32.2-57.7). The rate was higher in children <2 years old (107.8 per 100,000 persons-year; 95% CI: 69-168.3), and in those with neuromuscular disease and/or cerebrospinal fluid leak (141.6 per 100,000 persons-year), and Down's syndrome (133.5 per 100,000 persons-year). CONCLUSIONS: The hospital admission rate due to IPD in children with risk conditions in Catalonia is similar to that observed in other series, and higher than that described in the general population. It is necessary to implement immunisation strategies aimed directly at these risk groups.

[Pneumococcal vaccination coverage in at-risk children in Catalonia]. / Cobertura de vacunación antineumocócica en niños con condiciones de riesgo en Cataluña.

INTRODUCTION: The public health system in Catalonia only funds pneumococcal vaccination in paediatrics for children at-risk. The aim of this study was to determine pneumococcal vaccination coverage and its association with age, sociodemographic factors and other variables. MATERIAL AND METHOD: Descriptive cross-sectional study of children aged between 2 months and 15 years old assigned to primary care centres in Catalonia and with diseases that are included for pneumococcal vaccine in the official vaccination program. The information on vaccination status and study variables were obtained from data registered in the electronic medical records in the primary care centres. An analysis was made of the association between pneumococcal vaccination and demographic and medical variables using bivariate analysis and a multiple logistic regression model. The adjusted odds ratio (aOR), with a confidence interval of 95%, was used to measure the relationships. RESULTS: Pneumococcal vaccination coverage was 47.7%. Variables which predicted pneumococcal vaccination were: age (aOR: 9.2 [7.9-10.7] in children 2 months-2 years old; aOR 8.1 [7.0-9.3] in children 3-5 years; aOR: 4.6 [4.0-5.2] in children 6-10 years), Spanish nationality (aOR: 3.9 [3.5-4.3]), correct immunisation according to systematic immunisation schedule (aOR: 2.5 [2.1-3.0]), and number of risk conditions (aOR: 3.2 [2.5-4.1] in children with 2 or more conditions). CONCLUSIONS: Pneumococcal vaccination coverage in children with risk conditions is low in Catalonia. Strategies need to be implemented to increase coverage.

[Susceptibility to measles and varicella in healthcare workers in a tertiary hospital in Catalonia]. / Susceptibilidad frente a sarampión y varicela en el personal sanitario de un hospital de tercer nivel en Cataluña.

INTRODUCTION: To estimate the susceptibility to measles and varicella (chickenpox) in healthcare workers in a public tertiary level teaching hospital, in Catalonia. METHODS: A prevalence study was conducted from January 2006 to December 2008 on 2,752 workers who had serology performed for the determination of measles or varicella by ELISA test during a health examination. Data were analysed by, sex, age, professional category and work unit. RESULTS: A total of 153 healthcare workers were susceptible to measles and 187 to varicella. The susceptibility of healthcare workers to measles was 6.04% (95% CI: 5.78 to 6.30), and to varicella it was 7.45% (95% CI: 7.14 to 7.75). The highest susceptibility to measles was in resident physicians with 14% (95% CI: 10.8 to 18.5). In high-risk services, where highly immunocompromised patients are attended, the susceptibility of workers was slightly higher than the rest to measles (6.32% vs 5.93%) and varicella (8.34% vs 7.09%). Healthcare workers born after 1980 were 20 times (95% CI: 11.0 to 37.2) more likely to be susceptible to measles, and 2 times (95% CI: 1.2 to 3.2) more likely to be susceptible to varicella than those those born before 1965. CONCLUSIONS: The susceptibility to measles in healthcare workers in our centre is higher in younger cohorts, with values higher than expected in a community with high vaccination coverage against measles, mumps, rubella vaccine (MMR) in the paediatric population for many years.

Reactogenicity to the mRNA-1273 Booster According to Previous mRNA COVID-19 Vaccination.

The objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00-2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers.

Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with inactive ulcerative colitis.

BACKGROUND: We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been established. The aim of this study was to determine the stability of fecal DNA in inactive ulcerative colitis and its potential value as an indicator of relapse. METHODS: The 54 patients with clinically quiescent ulcerative colitis in this prospective study were followed for 12 months or until clinical relapse (clinical activity index > 7). Fecal calprotectin concentration was determined by ELISA, and fecal DNA concentration was determined by quantitative PCR. RESULTS: During the year of follow-up, 23 of the 54 patients relapsed, with a median increase in the colitis activity index from 1.0 to 8.0 (P < 0.01). Median fecal DNA remained unchanged in patients with stable, inactive colitis, ranging from 6.8 copies/microg at inclusion to 1.7 copies/microg at the end of follow-up. Fecal calprotectin level also was unchanged, ranging from 414.0 microg/g at inclusion to 128.9 microg/g at the end of follow-up. In contrast, fecal DNA concentration increased significantly in patients who relapsed (259.0 versus 3.9 copies/microg at entry; P < 0.01). Similar increases in relapsing patients were also observed with fecal calprotectin. ROC curve analysis to assess the accuracy of fecal DNA and calprotectin in detecting relapses during follow-up yielded similar results. CONCLUSIONS: Fecal DNA concentration remained stable in patients with inactive ulcerative colitis but increased significantly with relapses. Determining fecal DNA concentration may be a new objective instrument to use in the follow-up of patients.

A molecular epidemiological study of human parainfluenza virus type 3 at a tertiary university hospital during 2013-2015 in Catalonia, Spain.

Human parainfluenza virus type 3 (HPIV-3) is one of the most common respiratory viruses particularly among young children and immunocompromised patients. The seasonality, prevalence and genetic diversity of HPIV-3 at a Spanish tertiary-hospital from 2013 to 2015 are reported. HPIV-3 infection was laboratory-confirmed in 102 patients (76%, under 5 years of age). Among <5 years-old patients, 9 (11.5%) were under any degree of immunosuppression, whereas this percentage was significantly higher (19; 79.2%) among patients older than 5 years. HPIV-3 was detected at varying levels, but mainly during spring and summer. All characterized HN/F sequences fell within C1b, C5 and in other two closely C3a-related groups. Furthermore, a new genetic lineage (C1c) was described. Genetic similarity and epidemiological data confirmed some nosocomial infections, highlighting the importance of the HPIV-3 surveillance, particularly in high-risk patients. This study provides valuable information on HPIV-3 diversity due to the scarce information in Europe.

Molecular epidemiology and molecular characterization of respiratory syncytial viruses at a tertiary care university hospital in Catalonia (Spain) during the 2013-2014 season.

BACKGROUND: Human respiratory syncytial virus (HRSV) is the main cause of lower respiratory tract infections among infants and young children. OBJECTIVES: The molecular epidemiology and characterization of HRSV strains detected at a Spanish tertiary hospital during the 2013-2014 season is reported. STUDY DESIGN: Phylogenetic analysis and molecular characterization of HRSV laboratory-confirmed respiratory samples were performed, based on coding sequences of G and F proteins. RESULTS: HRSV infection was laboratory-confirmed in respiratory samples from 320 patients of which 223 (70%) were less than 2 years of age and none undergoing Palivizumab treatment. HRSV was detected at varying levels throughout the season with a maximum rate in the week 52/2013, right before the beginning of the influenza epidemic. Whilst both HRSV groups were found co-circulating, HRSV-B group clearly predominated. The phylogenetic analyses from 139 HVR-2 sequences revealed that most characterized strains belonged to ON1 and BA9 genotypes. Three different phylogenetic subgroups could be distinguished within these genotypes. In addition, three strains (out of the 52 randomly selected) were carrying amino acid substitutions in the epitope A of the F protein, one of them previously related to Palivizumab resistance. CONCLUSIONS: The results of the present study highlight the importance of a continuous HRSV surveillance to monitor not only the introduction of new genotypes on circulation but also the emergence of viral variants with new genetic characteristics that can affect the antigenicity features and the susceptibility to the only current prophylaxis treatment and also for the future development of HRSV vaccines.

[Prospective multicenter study of adverse drug reactions in hospitalized elderly patients]. / Estudio multicéntrico prospectivo de reacciones adversas a medicamentos en pacientes ancianos hospitalizados.

BACKGROUND AND OBJECTIVE: The incidence of adverse drug reactions (ADRs) in hospitalized elderly patients is an important clinical problem. The purpose of this study was to determine the incidence of ADRs in elderly in-patients, to analyze the factors involved in their presentation and to evaluate the reactions detected. PATIENTS AND METHOD: Prospective multicenter study in patients older than 65 years during their stay in hospital or nursing home. The assessment consisted of a complete geriatric evaluation and a protocol for collecting information on suspected ADRs during hospitalization or nursing home stay. A multivariate analysis by multiple logistic regression was performed. RESULTS: The study included 865 patients: 185 (21%) from 5 hospital units; 325 (38%) from 8 convalescent centers; and 355 (41%) from 8 long-term centers. The incidence of ADRs was 9%. In acute units the incidence was 15%; in post-acute units, 5%; and in long-term centers, 10% (p < 0.004). In the global multivariate analysis, the risk of experiencing an ADR was associated with a greater use of medications (OR = 1.15; 1.07 1.23 for each additional drug), the presentation of delirium (OR = 3.6; 1.95-6.85) and the type of unit (acute OR = 2.6; 1.16-6.01; long-term OR = 3.3; 1.62-7.05). Fifty type A ADRs were detected (65%). With regard to severity, 36 (47%) were moderate, 27 (35%) were mild, and 14 (18%) were severe. Causality: 58 (76%) probable and 17 (20%) possible. Potential avoidability: 39 (51%) were unavoidable and 38 (49%) were totally or partially avoidable; of these, 15 (39%) were the result of an interaction with another drug. CONCLUSIONS: The incidence of ADRs in our study was close to 10%. ADRs were associated with the frequency of use, presence of delirium and type of unit, and occurred most frequently in acute and long-term units. ADRs were principally type A, moderate severity, probable causality and partially avoidable.

[Hypertrophic cardiomyopathy in adult patients. Clinical course and prognostic factors in 119 patients]. / Miocardiopatía hipertrófica en el adulto. Curso clínico y factores pronósticos de 119 pacientes.

BACKGROUND AND OBJECTIVE: The purpose of this study was to characterize adult patients with hypertrophic cardiomyopathy (HCM), to compare their mortality with that of the general population and to establish a prognosis based on clinical and noninvasive techniques. PATIENTS AND METHOD: One hundred nineteen consecutive patients (60 women, mean: 52 [12] years) with HCM were prospectively studied by ECG, Holter, echo-Doppler, exercise testing, myocardial perfusion SPET and radionuclide ventriculography. Prognostic variables included clinical data and parameters derived from these noninvasive techniques. RESULTS: During a mean follow-up of 10 [6.7] years, 7 patients (5.8%) died of cardiovascular causes (4 cardiac failure and 3 sudden death). The annual mortality rate was 0.6% and the actuarial survival curve for patients with HCM was significantly worse compared with the expected survival curve derived from the general population after adjustment for age and sex (p = 0.008). The presence of atrial fibrillation (p = 0.04), moderate or severe mitral regurgitation (p = 0.02), dynamic gradient > 50 mmHg (p = 0.02), left atrial diameter > 45 mm (p = 0.02), and interventricular septal thickness > 25 mm (p = 0.04) were all predictive of mortality. CONCLUSIONS: The mortality rate of adult patients with HCM is significantly higher than that expected for the general population and heart failure and sudden death are almost evenly distributed as a cause of death in these patients. Atrial fibrillation, magnitude of mitral regurgitation, dynamic gradient, left atrial dilatation and interventricular septal thickness are the main predictors of death.

Association of HLA class II genes with systemic sclerosis in Spanish patients.

OBJECTIVE: To examine the role of HLA-DRB1 and HLA-DQB1 alleles in the susceptibility to systemic sclerosis (SSc) and its clinical expression in a Spanish population. METHODS: One hundred Spanish Caucasian patients with SSc and 130 controls were studied. Molecular HLA-DRB1 and HLA-DQB1 typing was performed by polymerase chain reaction (PCR) sequence-based typing and PCR sequence-specific oligonucleotide. RESULTS: HLA-DRB1*11 was associated with genetic susceptibility to SSc, whereas HLA-DRB1*07 (HLA-DRB1*0701) showed a protective effect. A significant increase in the frequency of the DRB1*1104 allele was observed in patients with anti-topoisomerase I autoantibodies (anti-Topo I) while HLA-DRB1*01 and HLA-DQB1*05 alleles were significantly increased in patients with anti-centromere antibodies (ACA). The HLA-DRB1*11 allele was more frequent in patients with pulmonary fibrosis; however, no significant association with any HLA-DRB1 or DQB1 alleles was identified in patients with pulmonary arterial hypertension. CONCLUSION: HLA alleles play a role in genetic susceptibility to SSc in Spanish patients. Some alleles are more prevalent in patients with pulmonary fibrosis and in patients with certain SSc-specific autoantibodies (anti-Topo I and ACA).

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.

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.

Do myocardial perfusion SPECT and radionuclide angiography studies in adult patients with hypertrophic cardiomyopathy have prognostic implications?

BACKGROUND: Some myocardial perfusion single photon emission computed tomography (SPECT) and radionuclide ventriculography studies have suggested that the presence of regional perfusion defects and diastolic abnormalities could have prognostic implications in patients with hypertrophic cardiomyopathy (HC). The aim of this prospective study was to analyze the prognostic value of these techniques in adult patients with HC. METHODS AND RESULTS: One hundred one patients with HC (44 women; mean age, 54 +/- 16 years; 55% obstructive) were prospectively studied by means of myocardial perfusion SPECT and radionuclide angiography. Of these patients, 55 (54.4%) had an abnormal myocardial perfusion SPECT study: 28 (27.7%) had fixed defects and 41 (40.6%) had reversible defects; 15 (14.8%) of these patients had both types of defect. Of the patients, 16% had left ventricular ejection fraction lower than 60%, 25.7% had an abnormal peak filling rate, and 51% had an abnormal time to peak filling rate. During 5.6 +/- 2.7 years of follow-up, 13 patients (12.8%) died (heart failure 8 and sudden death in 5) and 14 had one or more severe complications develop (syncope in 6, angina III-IV in 4, dyspnea III-IV in 10, and acute myocardial infarction in 3). The summed difference score was higher in patients with cardiac death (2.2 +/- 2.3 vs 1.1 +/- 1.3, P = .008), and fixed defects were more prevalent in patients with severe complications (57% vs 21%, P = .01). In the Kaplan-Meier survival plot analysis, severe complications were more likely in patients with fixed defects (P = .01) or ejection fraction lower than 60% ( P = .01). CONCLUSIONS: Prognostic information from myocardial perfusion SPECT and radionuclide angiography has limited clinical significance with regard to cardiac death in adult patients with HC. However, the presence of fixed defects and lower ejection fraction in these patients has an adverse prognostic meaning for severe complications.

Allogeneic and autologous bone marrow transplantation after consolidation therapy in high-risk acute myeloid leukemia in children. Towards a risk-oriented therapy.

BACKGROUND AND OBJECTIVES: Although chemotherapy in childhood acute myeloid leukemia (AML) has improved in the last decade, except for a group of better-risk patients (approximately one third), more than half the other patients relapse. The main objective of this study was to evaluate the results obtained with bone marrow transplants, either allogeneic (allo-BMT) or autologous (auto-BMT), following two intensive consolidation courses in a series of children with high-risk (HR) AML according to morphologic and early-response BFM criteria. A second objective was to compare the results of auto-BMT with those of allo-BMT. DESIGN AND METHODS: From April 1988 to May 2001, 79 children (< 15 years old) with de novo AML entered the prospective AML-88 trial in a single institution: 50 (63%) were qualified as having high-risk disease and are the subject of this study. After 1 or 2 induction courses, depending on early response, and two consolidations, patients with an HLA-identical sibling received an allo-BMT and all the others an auto-BMT. The conditioning regimen was cyclophosphamide and total body irradiation (TBI) in children over 3 years old and busulfan and etoposide in younger children. Bone marrow was purged with mafosfamide in auto-BMT and cyclosporine alone was given as graft-versus-host disease (GVHD) prophylaxis in allo-BMT. RESULTS: At the end of the chemotherapy phase (induction and consolidation ), 46 of the 50 HR patients (92%) had attained complete remission (CR) after one (n=29), two (n=11) or three (n=6) courses; 2 more were in partial remission (PR) and 2 had died. The 48 patients in CR or PR received either an allo-BMT (17) or an auto-BMT (31). Hematologic reconstitution was significantly slower in auto-BMT recipients. Forty-one percent of patients who received allo-BMT suffered acute GVHD grades II-IV. Toxic deaths and relapse rates were 5.9% and 17.6%, respectively, in allo-BMT and 3.2% and 25.8%, respectively, in auto-BMT. Post-transplant 8-year event-free survival (EFS) was 74.5% (54-96) in allo-BMT and 74.2% (59-89) in auto-BMT. EFS and OS in all the series (50 patients) were 71% (59-83) and 73% (61-85), respectively, with a median follow-up of 7.2 years. INTERPRETATION AND CONCLUSIONS: This study indicates that improved results in children with HR-AML can be obtained by either allo- or auto-BMT performed after two courses of intensive consolidation therapy provided good supportive therapy is given and reduced transplant -related mortality (TRM) is minimized.

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.

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.