José Alegre

The value of chest roentgenography in the diagnosis of pneumothorax after thoracentesis

PURPOSE We sought to assess the yield of chest roentgenography for the detection of pneumothorax among hospitalized patients with pleural effusion who have undergone diagnostic or therapeutic thoracentesis. SUBJECTS AND METHODS We performed a prospective study of 506 thoracentesis procedures in 370 patients. After the procedure, each operator filled out a note recording patient data and the characteristics of the thoracentesis. A chest radiograph was performed within 12 hours after the procedure in all patients. RESULTS Eighteen (4%) pneumothoraces occurred in 17 patients, 9 (2%) of which required chest tube drainage. Of the 488 patients without symptoms, only 5 (1%) developed a pneumothorax, only 1 of which required chest tube drainage. By contrast, of the 18 patients with symptoms, 13 developed a pneumothorax, 8 of which required chest tubes. There were two independent predictors of pneumothorax: presence of symptoms (odds ratio [OR] = 250; 95% confidence interval [CI]: 65 to 980) and male gender (OR = 5.4; 95% CI: 1.9 to 69). CONCLUSIONS Among the symptom-free patients in our sample, the risk of developing pneumothorax with clinical consequences was so low that the practice of routine chest roentgenography may not be justified.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome

BackgroundChronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability.MethodsImmunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups.ResultsCFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals.ConclusionsOur findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

Documento de consenso sobre el diagnóstico y tratamiento del síndrome de fatiga crónica en Catalunya

La fatiga prolongada, entendida como una sensación persistente de agotamiento o dificultad para realizar una actividad física o intelectual continuada, es un síntoma prevalente, tanto en atención primaria como especializada, además de motivo de considerable preocupación tanto para el paciente que la sufre como para el médico que le atiende. Se considera que de un 5 a un 20% de la población general puede presentar fatiga durante más de un mes en algún momento de su vida, hecho que suele estar en relación con enfermedades o situaciones intercurrentes1. Entendemos por fatiga crónica la que se presenta de forma continuada o intermitente durante más de 6 meses, lo que acontece entre un 1 y un 10% de la población general1. Si esta situación tiene una causa conocida o relacionable se denominará fatiga crónica secundaria. El síndrome de fatiga crónica (SFC) debe diferenciarse de las dos situaciones previamente referidas y su definición requiere el cumplimiento de unos criterios específicos2,3. Estos criterios incluyen la presencia de fatiga persistente o intermitente, inexplicada e invalidante, que no es producto de un esfuerzo excesivo y no mejora con el descanso. Además, el paciente debe presentar de forma crónica y concurrente 4 o más síntomas de los relacionados como criterios asociados en la definición establecida para esta enfermedad (tabla 1)4. Los pacientes que presentan fatiga crónica no explicada pero que no reúnen los criterios de SFC entrarían en la situación de fatiga crónica idiopática3. Aunque en España se desconoce la prevalencia real del SFC, en un estudio poblacional realizado en 1995 en Estados Unidos5 se objetivó que era de 75 a 267 casos por 100.000 habitantes. En otro estudio poblacional australiano efectuado en 1990 se objetivó una prevalencia de 37 casos por 100.000 habitantes6. Extrapolando las cifras obtenidas en estas series a la población catalana de más de 16 años, la prevalencia estimada en Catalunya oscilaría entre 2.012 y 13.429 casos3. En los últimos años hemos asistido a un notable incremento de consultas de pacientes con fatiga, algunos de ellos con fatiga prolongada o SFC. Este hecho, junto con la ausencia de una clara etiología de este proceso3,7,8 y, por tanto, de un tratamiento satisfactorio, la importante morbilidad asociada, así como la falta de una conducta y actitud diagnóstico-terapéutica homogéneas por parte del personal asistencial, ha movido a este grupo multidisciplinario de trabajo a elaborar este documento de consenso con el fin de constatar el estado del SFC en Catalunya, así como a confeccionar una guía práctica de actuación que facilite y homogeneice la conducta a seguir en este grupo de pacientes.

Randomized Clinical Trial of the Effectiveness of a Home-Based Intervention in Patients With Heart Failure: The IC-DOM Study

INTRODUCTION AND OBJECTIVES The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure. METHODS A randomized clinical trial was carried out between January 2004 and October 2006. In total, 283 patients admitted to hospital with a diagnosis of heart failure were randomly allocated to a home-based intervention (intervention group) or usual care (control group). The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up. RESULTS The primary end-point was observed in 41.7% of patients in the intervention group and in 54.3% in the control group. The hazard ratio was 0.70 (95% confidence interval [CI] 0.55-0.99). Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 (95% CI 0.50-0.87). At the end of the study, the quality of life of patients in the intervention group was better than in the control group (18.57 vs. 31.11; P< .001). CONCLUSIONS A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life.

Cluster analysis of clinical data identifies fibromyalgia subgroups.

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

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 µg/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.

Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.

Summary Variants in NRXN3 and MYT1L are associated with fibromyalgia. Our results point to a role for the central nervous system in susceptibility to fibromyalgia. ABSTRACT Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome‐wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2 × 400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P = 4.28 × 10−5, odds ratio [95% confidence interval] = 0.58 [0.44–0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P = .021, odds ratio [95% confidence interval] = 1.46 [1.05–2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.

Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study

BACKGROUND Chronic fatigue syndrome (CFS) is a disabling illness of unknown etiology that is characterized by fatigue associated with a reduced ability to work, lasting for more than 6 months, and accompanied by a specific set of symptoms. The diagnosis remains difficult because of the absence of laboratory tests and is, therefore, made largely on the basis of the symptoms reported by the patient. The aim of this study was to analyze differences in blood nitrate levels in CFS patients and a matched control group after a physical exercise test. METHODS Forty-four consecutive female patients with CFS and 25 healthy women performed an exercise test using a cycle ergometer with monitoring of cardiopulmonary response. Blood samples were obtained for biochemical analyses of glucose, lactate, and nitrates at the beginning (under resting conditions) and after the maximal and supramaximal tests. RESULTS Plasma nitrates differed between the groups, with higher values in the CFS group (F = 6.93, p = 0.003). Nitrate concentration increased in relation to workload and reached higher values in the CFS group, the maximum difference with respect to the control group being 295% (t = 4.88, p < 0.001). CONCLUSIONS The main result of the present study is that nitric oxide (NO) metabolites (nitrates) showed a much higher increase after a maximal physical test in CFS patients than in a group of matched subjects. This combination (exercise plus NO response evaluation) may be useful in the assessment of CFS.

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.

Relationship between poor decision-making process and fatigue perception in Parkinson's disease patients.

BACKGROUND Fatigue is a common non-motor symptom in Parkinsons disease patients. The reasons for its perception are not completely understood. One suggested possibility might be that perceived fatigue is related with abnormal interpretation of somatic symptoms. It has been described that somatic markers misinterpretation leads to poor decision-making. We hypothesized that fatigued Parkinsons disease patients would show poorer performance than non-fatigued in a decision-making task. METHODS To test our hypothesis, 89 Parkinsons disease patients were assessed for the presence of fatigue using the Parkinson Fatigue Scale. All patients were also administered scales evaluating psychopathology and neuropsychological tests, including the Iowa Gambling Task. RESULTS 33 (37.1%) patients fulfilled the established criteria for fatigue. In the univariate analysis, fatigued patients showed higher levels of anxiety (state: p = 0.001, trait: p < 0.001), impulsivity (p = 0.051), and depression (p < 0.001) than non-fatigued patients. No statistically significant differences in other neuropsychological test results (Stroop, Trail Making Test, Tower of London) were found between fatigued and non-fatigued patients except for the Iowa Gambling Task, in which fatigued patients showed poorer performance (p = 0.001) after controlling for confounding factors. CONCLUSIONS These results suggest that fatigued Parkinsons disease patients may present abnormal decision-making process, which may reflect abnormal processing of somatic markers when faced with an activity that requires effort.