Autoantibodies to intrinsic factor can jeopardize pernicious anemia diagnosis: a case report.

Vitamin B12 deficiency may cause neurological and hematological alterations. Its assessment should be easy considering that the access to its measurement is available in majority of the clinical laboratories. The presence of technical interference when measuring vitamin B12 can lead to an erroneous or a more difficult diagnosis of conditions as pernicious anemia. We report a case in which an interference in the evaluation of vitamin B12 concentration led to the realization of invasive tests and almost a misdiagnosis of a patient who actually had pernicious anemia. Professionals need to be aware of these interferences when we assess outcomes.

Some pleural effusions labeled as idiopathic could be produced by the inhalation of silica.

Objectives: Exposure to silica nanoparticles has been associated with pleural effusions (PEs) in animal models and case series. We hypothesized that some PEs labelled as "idiopathic" could, in fact, be secondary to inhalation of silica. Methods: A retrospective case control study was designed utilizing a prospectively maintained pleural database. Cases, represented by idiopathic PEs, were matched by age and gender to control patients who had been diagnosed with malignant, cardiac, or infectious PEs. A survey consisting of questions about occupational life and possibility of silica inhalation was conducted. In a subgroup of patients, pleural fluid concentrations of silica were quantified by plasma atomic emission spectrometry analysis. Also, the pleural biopsy of a silica-exposed case was subjected to an energy dispersive X-ray spectroscopy (EDX) to identify the mineral, the size of which was determined by electron microscopy. Results: A total of 118 patients (59 cases and 59 controls) completed the survey. There were 25 (42%, 95% CI 31-55%) and 13 (22%, 95% CI 13-34%) silica-exposed workers in case and control groups, respectively. The exposure attributable fraction was 0.62 (95% CI 0.14-0.83). Four of eight exposed cases showed detectable levels of silica in the pleural fluid (mean 2.37 mg/L), as compared to none of 16 tested controls. Silica nanoparticles of 6-7 nm were identified in the pleural biopsy of an exposed case patient. Conclusions: It is plausible that some idiopathic PEs could actually be caused by occupational silica inhalation.

Coeliac Disease in Elderly Patients: Value of Coeliac Lymphogram for Diagnosis.

(1) Background: Although a meta-analysis reported that the sensitivity of CD3+ TCRγδ+ cells for coeliac disease diagnosis was >93%, a recent study has suggested that sensitivity decreased to 65% in elderly patients. (2) Aim: To evaluate whether the sensitivity of intraepithelial lymphocyte cytometric patterns for coeliac disease diagnosis changes with advanced age. (3) Methods: We performed a multicentre study including 127 coeliac disease patients ≥ 50 years: 87 with baseline cytometry (45 aged 50-59 years; 23 aged 60-69 years; 19 aged ≥ 70 years), 16 also with a follow-up cytometry (on a gluten-free diet); and 40 with only follow-up cytometry. (4) Results: In Marsh 3 patients, a sensitivity of 94.7%, 88.9% and 86.7% was observed for each age group using a cut-off value of TCRγδ+ >10% (p = 0.27); and a sensitivity of 84.2%, 83.4% and 53.3% for a cut-off value >14% (p = 0.02; 50-69 vs. ≥70 years), with difference between applying a cut-off of 10% or 14% (p = 0.008). The TCRγδ+ count in the ≥70 years group was lower than in the other groups (p = 0.014). (5) Conclusion: In coeliac patients ≥ 70 years, the TCRγδ+ count decreases and the cut-off point of >10% is more accurate than >14%.

Experimental supporting data on the influence of platelet-derived factors of malignant pleural effusions on T cell effector functions and their relevance in predicting prognosis of lung adenocarcinoma patients with pleural metastasis.

The data described in this article are supplementary to our primary article "Platelet factor 4 regulates T cell effector functions in malignant pleural effusions". Malignant pleural effusion (MPE) is a common complication of advanced lung adenocarcinoma (LAC) associated with a poor life expectancy [1]. Several challenges need to be addressed to identify non-invasive molecular biomarkers that help to predict the prognosis of LAC patients with MPE [2]. In the primary publication, we proposed that platelet-derived factors, especially platelet factor 4 (PF4), can negatively regulate T lymphocyte activation and granzyme B expression in pleural metastasis and its levels were associated with a worse prognosis. Here, we provide data on the influence of other platelet-derived factors, including transforming growth factor ß (TGF-ß), vascular endothelial factor (VEGF), and P-selectin on T lymphocyte response in MPE and their relevance as prognostic factors in lung cancer patients with pleural metastasis. Pleural fluids from 35 lung adenocarcinoma (LAC) and 20 heart failure (HF) patients were collected by thoracentesis and its platelet-derived factors' content was measured by specific enzyme-linked immunosorbent assay (ELISAs). Correlations between pleural levels of platelet-derived factors and T cell functions were analyzed by Pearson coefficients. Kaplan-Meier curves were used to estimate the effect of pleural concentrations of platelet-derived factors on overall survival of LAC patients with pleural metastasis. These analyses showed that the concentration of platelet-derived factors was not associated with T cell proliferation and cytotoxicity. Furthermore, their levels do not predict the survival of LAC with MPE.

Platelet factor 4 regulates T cell effector functions in malignant pleural effusions.

Malignant pleural effusion (MPE) is defined as the presence of tumor cells in pleural fluid and it is a fatal complication of advanced lung adenocarcinoma (LAC). To understand the immune response to the tumor in MPE, we compared the concentration of immunomodulatory factors in MPE of LAC and pleural effusion of heart failure (HF) patients by ELISA, and the proliferation and cytotoxic phenotype of T cells stimulated in the presence of LAC and HF pleural fluids by cytometry. Platelet factor 4 (PF4), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-ß) and P-selectin levels were higher in LAC than in HF pleural fluids. However, plasmatic PF4 and P-selectin levels were similar in LAC and HF. VEGF positively correlated with TGF-ß and sPD-L1 in LAC but not in HF pleural fluids. LAC pleural fluids also inhibited T lymphocyte proliferation and cytotoxicity and reduced IL-17 production. PF4 levels inversely correlated with T cell function. The high content of PF4 in MPE was associated with poor prognosis. Our findings suggest that an impaired response of T lymphocytes induced by PF4 provides a significant advantage for tumor progression.

Epithelial cell adhesion molecule (EpCAM) from pleural fluid cell lysates is a highly accurate diagnostic biomarker of adenocarcinomatous effusions.

BACKGROUND AND OBJECTIVE: The discovery of highly accurate pleural fluid (PF) biomarkers of malignancy remains elusive. We assessed the operating characteristics of the PF epithelial cell adhesion molecule (EpCAM), claudin 4 (CL4) and human epididymis protein 4 (HE4) as potential markers of epithelial malignancies. METHODS: The three markers were quantified by immunoassays in the supernatants (s) and cell lysates (cl) of 175 PF samples. The cut-off values with 100% specificity were selected for malignant-benign discrimination. An immunocytochemical staining index score for each marker was also evaluated on PF cell blocks. The resulting best biomarker was further validated in two independent populations of 73 and 48 patients with pleural effusions (PE). RESULTS: An EpCAM(cl) >98 pg/g total lysate protein yielded 75% sensitivity, 100% specificity, negative likelihood ratio of 0.25 and area under the curve of 0.94 for labelling adenocarcinomatous effusions. Sensitivity reached 88% if EpCAM(cl) was combined with EpCAM immunostaining. One-third or more of the malignant effusions exhibiting a false-negative cytological fluid examination were correctly classified by EpCAM(cl) concentrations. Immunoassays for CL4 and HE4 were diagnostically useless. CONCLUSION: EpCAM(cl) is a new biomarker of adenocarcinomatous PE with meaningful discriminating properties.

Diagnostic Accuracy of Pleural Fluid Adenosine Deaminase for Diagnosing Tuberculosis. Meta-analysis of Spanish Studies. / Eficacia diagnóstica de la adenosina desaminasa en líquido pleural para diagnosticar tuberculosis. Metaanálisis de estudios españoles.

OBJECTIVE: To evaluate the usefulness of pleural fluid adenosine deaminase (ADA) for diagnosing tuberculous pleural effusions in the Spanish population, according to laboratory technique and cut-off point, and to compare the results with other populations. METHODS: Meta-analysis of diagnostic studies on pleural fluid ADA in the Spanish population, extracted from the PubMed and Embase databases from inception until July 2017, with no language restrictions. The overall diagnostic accuracy of ADA and that of each of the measurement techniques (Giusti, manual and automated kinetic methods) and selected cut-offs were analyzed. The QUADAS-2 tool was used to evaluate the quality of studies. A bivariate random effects model was used. Results were compared with those obtained from previous meta-analyses in non-Spanish populations. RESULTS: Sixteen studies in a total of 4,147 patients, 1,172 of whom had tuberculous pleural effusions, were included. ADA had 93% sensitivity, 92% specificity, positive likelihood ratio of 12, negative likelihood ratio of 0.08, and an area-under-the-curve of 0.968 for identifying tuberculosis. There were no differences in diagnostic accuracy between the techniques used for ADA measurement or the selected cut-offs. In 73 studies from non-Spanish populations a trend toward lower ADA sensitivity (88%, 95% CI:86%-90%) and specificity (88%, 95% CI: 86%-90%) was noted, but differences did not reach statistical significance. CONCLUSIONS: Pleural fluid ADA in the Spanish population shows good diagnostic accuracy (regardless of the measurement technique or cut-off), similar to that reported in non-Spanish populations.

Eficacia diagnóstica de la adenosina desaminasa en líquido pleural para diagnosticar tuberculosis. Metaanálisis de estudios españoles / Diagnostic Accuracy of Pleural Fluid Adenosine Deaminase for Diagnosing Tuberculosis. Meta-analysis of Spanish Studies

Objetivo: Determinar la utilidad de la adenosina desaminasa (ADA) pleural para diagnosticar derrame pleural tuberculoso en población española, según la técnica de medición y punto de corte utilizados, y compararla con la descrita para otras poblaciones. Métodos: Metaanálisis de estudios diagnósticos sobre ADA pleural en población española, extraídos de PubMed y Embase desde sus comienzos hasta julio de 2017, sin restricciones de lenguaje. Se analizó la eficacia diagnóstica global de la ADA, según sus técnicas de medición (Giusti, métodos cinéticos manuales y métodos cinéticos automatizados) y el punto de corte seleccionado. La herramienta QUADAS-2 evaluó la calidad de los estudios. Se utilizó un método bivariante de efectos aleatorios. Se compararon los resultados con los descritos en metaanálisis previos sobre población no española. Resultados: Se incluyeron 16 estudios, con 4.147 pacientes, de los que 1.172 tenían derrame pleural tuberculoso. La ADA tuvo una sensibilidad del 93%, especificidad del 92%, likelihood ratio positiva de 12, likelihood ratio negativa de 0,08, y área bajo la curva de 0,968 para identificar tuberculosis. No hubo diferencias de eficacia diagnóstica entre las técnicas de medición de ADA o el punto de corte escogido. En 73 estudios de población no española se observó una tendencia hacia una menor sensibilidad (88%, IC95%: 86-90%) y especificidad (88%, IC95% 86-90%) de la ADA, pero las diferencias no alcanzaron significación estadística. Conclusiones: La ADA pleural en población española tiene una buena precisión diagnóstica (independientemente de la técnica de medición o punto de corte empleados), similar a la reportada en población no española

Objective: To evaluate the usefulness of pleural fluid adenosine deaminase (ADA) for diagnosing tuberculous pleural effusions in the Spanish population, according to laboratory technique and cut-off point, and to compare the results with other populations. Methods: Meta-analysis of diagnostic studies on pleural fluid ADA in the Spanish population, extracted from the PubMed and Embase databases from inception until July 2017, with no language restrictions. The overall diagnostic accuracy of ADA and that of each of the measurement techniques (Giusti, manual and automated kinetic methods) and selected cut-offs were analyzed. The QUADAS-2 tool was used to evaluate the quality of studies. A bivariate random effects model was used. Results were compared with those obtained from previous meta-analyses in non-Spanish populations. Results: Sixteen studies in a total of 4,147 patients, 1,172 of whom had tuberculous pleural effusions, were included. ADA had 93% sensitivity, 92% specificity, positive likelihood ratio of 12, negative likelihood ratio of 0.08, and an area-under-the-curve of 0.968 for identifying tuberculosis. There were no differences in diagnostic accuracy between the techniques used for ADA measurement or the selected cut-offs. In 73 studies from non-Spanish populations a trend toward lower ADA sensitivity (88%, 95% CI:86%-90%) and specificity (88%, 95% CI: 86%-90%) was noted, but differences did not reach statistical significance. Conclusions: Pleural fluid ADA in the Spanish population shows good diagnostic accuracy (regardless of the measurement technique or cut-off), similar to that reported in non-Spanish populations

Cambios en los parámetros bioquímicos del líquido pleural entre 2 toracocentesis consecutivas para diferenciar derrames malignos de benignos / Detection of Pleural Fluid Biochemistry Changes in Two Consecutive Thoracenteses for Differentiating Malignant from Benign Effusions

Objetivo: Evaluar si los cambios en los parámetros bioquímicos del líquido pleural (LP) entre 2 toracocentesis sucesivas permiten predecir derrames pleurales (DP) malignos o benignos. Métodos: Estudio retrospectivo de los pacientes con exudado linfocitario y citología negativa para malignidad que se sometieron a una segunda toracocentesis en nuestro centro durante los últimos 15 años (muestra de derivación), y en los que se alcanzó un diagnóstico final. Las diferencias absolutas (Δa) o porcentuales (Δp) de diferentes parámetros bioquímicos del LP capaces de predecir la naturaleza maligna o benigna del DP en la muestra de derivación se evaluaron en una población independiente. Resultados: Se incluyeron 214 pacientes con DP (70 malignos y 144 benignos) en la muestra de derivación. Las Δp LDH (lactato deshidrogenasa) > 0%, Δp neutrófilos > -10% (cualquier aumento o bien un descenso inferior al 10%), y Δa proteínas < 0,1 g/dL (cualquier descenso o bien un aumento inferior a 0,1 g/dL) entre la segunda y primera toracocentesis mostraron unas odds ratio de 6,4, 3,9 y 2,1 para discriminar DP maligno de benigno, respectivamente. La presencia de las 3 condiciones conjuntamente se asoció con una likelihood ratio positiva de 5,6, mientras que la ausencia de cualquiera ellas se asoció con una likelihood ratio negativa de 0,04 para predecir malignidad. Los resultados se reprodujeron en la población de validación. Conclusión: El aumento de LDH y neutrófilos, junto con el descenso de proteínas en una segunda toracocentesis, aumenta la probabilidad de que el origen del DP sea neoplásico, mientras que lo contrario la reduce significativamente

Objective: To assess whether changes in pleural fluid (PF) biochemistries between two consecutive thoracenteses enable clinicians to predict malignant or benign pleural effusions (PE). Methods: Retrospective study of patients with lymphocytic exudates and negative PF cytology, who underwent a second thoracentesis in our center in the last 15 years in whom a final diagnosis was reached (derivation sample). Absolute (Δa) and percentage differences (Δp) in PF biochemistries which predicted a malignant or benign PE in the derivation sample were evaluated in an independent population (validation sample). Results: The derivation sample included 214 PE patients (70 malignant and 144 benign PE). Δp lactate dehydrogenase (LDH) >0%, Δp neutrophils >-10% (any increase or less than 10% decrease) and Δa protein <0.1g/dL (any increase or less than 0.1g/dL decrease) between the second and the first thoracentesis had an odds ratio of 6.4, 3.9 and 2.1, respectively, to discriminate malignant from benign PE. The presence of the three conditions together had a positive likelihood ratio of 5.6, whereas the absence of any of the 3 parameters had a likelihood ratio of 0.04 for predicting malignancy. These results were reproduced in the validation sample. Conclusion: An increase in LDH and neutrophils along with a decrease in protein in a second thoracentesis increase the probability of malignant PE, while the opposite reduces it significantly

Detection of Pleural Fluid Biochemistry Changes in Two Consecutive Thoracenteses for Differentiating Malignant from Benign Effusions. / Cambios en los parámetros bioquímicos del líquido pleural entre 2 toracocentesis consecutivas para diferenciar derrames malignos de benignos.

OBJECTIVE: To assess whether changes in pleural fluid (PF) biochemistries between two consecutive thoracenteses enable clinicians to predict malignant or benign pleural effusions (PE). METHODS: Retrospective study of patients with lymphocytic exudates and negative PF cytology, who underwent a second thoracentesis in our center in the last 15 years in whom a final diagnosis was reached (derivation sample). Absolute (Δa) and percentage differences (Δp) in PF biochemistries which predicted a malignant or benign PE in the derivation sample were evaluated in an independent population (validation sample). RESULTS: The derivation sample included 214 PE patients (70 malignant and 144 benign PE). Δp lactate dehydrogenase (LDH) >0%, Δp neutrophils >-10% (any increase or less than 10% decrease) and Δa protein <0.1g/dL (any increase or less than 0.1g/dL decrease) between the second and the first thoracentesis had an odds ratio of 6.4, 3.9 and 2.1, respectively, to discriminate malignant from benign PE. The presence of the three conditions together had a positive likelihood ratio of 5.6, whereas the absence of any of the 3 parameters had a likelihood ratio of 0.04 for predicting malignancy. These results were reproduced in the validation sample. CONCLUSION: An increase in LDH and neutrophils along with a decrease in protein in a second thoracentesis increase the probability of malignant PE, while the opposite reduces it significantly.

Vitamin D deficiency is associated with poorer satisfaction with diabetes-related treatment and quality of life in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: In this cross-sectional study, we assessed the possible association of vitamin D deficiency with self-reported treatment satisfaction and health-related quality of life in patients with type 2 diabetes. METHODS: We performed a sub-analysis of a previous study and included a total of 292 type 2 diabetic patients. We evaluated treatment satisfaction and health-related quality of life through specific tools: the Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life. Vitamin D deficiency was defined as 25 (OH) D serum levels < 15 ng/mL. RESULTS: Multivariable linear regression models were used to estimate the relationship of vitamin D deficiency with both outcomes once adjusted for self-reported patient characteristics. Vitamin D deficiency was significantly associated with the final score of the Diabetes Treatment Satisfaction Questionnaire and the single "diabetes-specific quality of life" dimension of the Audit of Diabetes-Dependent Quality of Life (p = 0.0198 and p = 0.0070, respectively). However, lower concentrations of 25-OH vitamin D were not associated with the overall quality of life score or the perceived frequency of hyperglycaemia and hypoglycaemia. CONCLUSIONS: Our study shows the association between vitamin D deficiency and both the self-reported diabetes treatment satisfaction and the diabetes-specific quality of life in patients with type 2 diabetes.

Low-grade Inflammatory Marker Profile May Help to Differentiate Patients With LADA, Classic Adult-Onset Type 1 Diabetes, and Type 2 Diabetes.

OBJECTIVE: To test whether differences in serum concentrations of adiposity-related low-grade inflammatory mediators could help to differentiate patients with latent autoimmune diabetes in adults (LADA), classic adult-onset type 1 diabetes, and type 2 diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional study involved 75 patients with LADA, 67 with classic adult-onset type 1 diabetes, and 390 with type 2 diabetes. Serum concentrations of adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFRII), interleukin-6, hs-CRP, and total leukocyte number were measured. To evaluate the differences of these markers among diabetes types, we performed logistic regression models and evaluated area under the receiver-operating characteristic curve (AUCROC) values. RESULTS: The profile of innate immunity-related inflammatory markers correlated with metabolic syndrome components. LADA versus classic adult-onset type 1 diabetes was independently related to sTNFRII (odds ratio [OR] 1.9 [95% CI 1.01-3.97]; P = 0.047) and hs-CRP levels (OR 0.78 [95% CI 0.62-0.96]; P = 0.019), and a higher number of total leukocytes lowered the risk of LADA compared with type 2 diabetes (OR 0.98 [95% CI 0.97-0.99]; P = 0.036). The logistic regression model including explanatory biomarkers explained 35% of the variation for LADA versus classic adult-onset type 1 diabetes (AUCROC 0.83 [95% CI 0.74-0.92]; P < 0.001) and 15% of the variation for LADA versus type 2 diabetes (AUCROC 0.73 [95% CI 0.70-0.80]; P < 0.001). CONCLUSIONS: Inflammatory, adiposity, and immune-related markers could help to differentiate a LADA diagnosis from that of classic adult-onset type 1 diabetes, and also LADA from that of type 2 diabetes, along with islet autoantibody positivity.

Development and validation of a scoring system for the identification of pleural exudates of cardiac origin.

BACKGROUND: Light's criteria misclassify about 30% of cardiac effusions as exudates, possibly leading to unnecessary testing. Our purpose was to derive and validate a scoring model to effectively identify these falsely categorized cardiac effusions, in the setting of natriuretic peptide lacking data. METHODS: We retrospectively analyzed data from 3182 patients with exudative pleural effusions based on Light's criteria, of whom 276 had heart failure (derivation set). A scoring model was generated with those variables identified as independent predictors of cardiac effusions in a logistic regression analysis, and further evaluated in an independent population of 1165 patients. RESULTS: The score consisted of age ≥75years (3 points), albumin gradient >1.2g/dL (3 points), pleural fluid lactate dehydrogenase <250U/L (2 points), bilateral effusions on chest radiograph (2 points), and protein gradient >2.5g/dL (1 point). At the best cutoff of ≥7 points, the score yielded 92% diagnostic accuracy, a likelihood ratio positive of 12.7 and a likelihood ratio negative of 0.39 for labeling cardiac effusions in the derivation sample. The respective figures in the validation sample were 87%, 6.5 and 0.33. Notably, the score had higher discriminatory properties than protein and albumin gradients in both the derivation (respective area under the curve - AUC - of 0.925, 0.825, and 0.801) and validation (respective AUC of 0.908 0.862 and 0.802; all p≤0.01) cohorts. CONCLUSIONS: A simple scoring system can assist clinicians in accurately identifying false cardiac exudates when natriuretic peptides are not available.

Calcium Phosphate Product Is Associated with Subclinical Carotid Atherosclerosis in Type 2 Diabetes.

AIMS: To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. METHODS: We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. RESULTS: We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017-1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) (ßadj ± SE = -0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.

Utilidad de la medición de CEA y CA 15-3 en los exudados pleurales no purulentos para diagnosticar malignidad: experiencia de un único centro / Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience

Objetivo: Establecer la rentabilidad diagnóstica de la medición de CEA y CA 15-3 en el líquido pleural (LP) para identificar malignidad, así como el valor adicional de estos marcadores en pacientes con derrame pleural maligno (DPM) y citología pleural falsamente negativa. Método: Se determinaron las concentraciones de CEA o CA 15-3 en el LP de 1.575 pacientes con exudados no purulentos, de los que 549 tenían DPM demostrados, 284 derrames probablemente malignos y 742 derrames benignos. Se buscaron puntos de corte 100% específicos para dichos marcadores, de forma que no pudieran ser superados por ningún derrame benigno. Resultados: El 41, 40 y el 60% de los pacientes con DPM tenían concentraciones pleurales elevadas de CEA (>45 ng/mL), CA 15-3 (>77 UI/L), o de alguno de los anteriores, respectivamente. Estos porcentajes fueron del 30, 19 y 41% en los DPM con biopsia pleural positiva y estudios citológicos del LP negativos; y del 24, 13 y 35% en los derrames considerados clínicamente malignos, pero sin demostración citohistológica. Los marcadores tumorales no tuvieron utilidad en linfomas ni mesoteliomas. El área bajo la curva de eficacia diagnóstica (AUC) del CEA fue de 0,819 (IC 95%: 0,793-0,845) y la del CA 15-3 de 0,822 (IC 95%: 0,796-0,847). Globalmente, el uso adicional de los marcadores tumorales incrementó el diagnóstico de malignidad un 14% respecto a la citología pleural de forma aislada. Conclusiones: La determinación de CEA y CA 15-3 en LP puede complementar a la citología pleural en la identificación de los DPM (AU)

Objective: To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination. Methods: PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion. Results: The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45 ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%. Conclusions: Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs (AU)

Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience. / Utilidad de la medición de CEA y CA 15-3 en los exudados pleurales no purulentos para diagnosticar malignidad: experiencia de un único centro.

OBJECTIVE: To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination. METHODS: PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion. RESULTS: The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%. CONCLUSIONS: Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs.

Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model.

The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.

Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

There is very few evidences on the role of vitamin D in the development of diabetic retinopathy. The aim of the current study was to explore whether there is an association of vitamin D status and diabetic retinopathy in type 2 diabetes. Two groups of patients were selected: 139 and 144 patients with and without retinopathy, respectively, as assessed by an experienced ophthalmologist. Subjects with advanced late diabetic complications were excluded to avoid confounding biases. 25-Hydroxy-vitamin D3 (25(OH)D) concentrations and vitamin D deficiency were associated with the presence of diabetic retinopathy. Additionally, patients with more advanced stages of retinopathy (grades 2-4) had lower concentrations of 25(OH)D and were more frequently vitamin D deficient as compared with patients not carrying this eye complication. In conclusion, our study confirms the association of vitamin D deficiency with the presence and severity of diabetic retinopathy in type 2 diabetes. Further experimental and prospective studies on this issue are clearly warranted.

TTF-1 and napsin A on cell blocks and supernatants of pleural fluids for labeling malignant effusions.

In this retrospective study of 80 pleural effusions, the combination of thyroid transcription factor 1 (TTF-1) and napsin A immunostaining on fluid cell blocks was positive in 80% of lung adenocarcinomas. Although measuring TTF-1 pleural fluid concentrations was of no value, quantification of napsin A levels allowed the identification of one third of the double-negative stained lung adenocarcinomas, with an overall accuracy similar to classical tumour markers for malignant-benign discrimination (sensitivity 40%, specificity 100%).

Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9.

BACKGROUND: The study of endogenous insulin secretion may provide relevant insight into the comparison of the natural history of adult onset latent autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this study was to compare the results of the C-peptide response to mixed-meal stimulation in LADA patients with different disease durations and subjects with type 2 and adult-onset type 1 diabetes. METHODS: Stimulated C-peptide secretion was assessed using the mixed-meal tolerance test in patients with LADA (n = 32), type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All patients were 30 to 70 years old at disease onset. The duration of diabetes in all groups ranged from 6 months to 10 years. The recruitment strategy was predefined to include at least 10 subjects in the following 3 disease onset categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10 years. RESULTS: At all time-points of the mixed-meal tolerance test, patients with LADA had a lower stimulated C-peptide response than the type 2 diabetes group and a higher response than the type 1 diabetes group. The same results were found when the peak or area under the C-peptide curve was measured. When the results were stratified by time since disease onset, a similar pattern of residual insulin secretory capacity was observed. CONCLUSIONS: The present study shows that the magnitude of stimulated insulin secretion in LADA is intermediate between that of type 1 and type 2 diabetes mellitus.