Dasatinib-Induced Chylothorax Beyond 5 Years of Treatment: Is There Actually Any Limit?

Dasatinib is a tyrosine kinase inhibitor used for treatment of some specific types of leukaemia. The development of pleural effusion is a known adverse effect of dasatinib and chylothorax is exceptional. No case has been reported beyond 5 years of treatment and extensive search for an alternative diagnosis is currently suggested in such scenario. The underlying mechanism is not currently clear. We describe a woman on dasatinib treatment for more than 10 years who developed chylothorax. Drug withdrawal resolved the chylous pleural effusion. We were able to find 14 additional cases of dasatinib-related chylothorax reported up until now. LEARNING POINTS: Dasatinib is a tyrosine kinase inhibitor used for the treatment of some specific types of leukaemia.Development of pleural effusion is a potential adverse effect, mostly in the first 6 years of treatment. The underlying mechanism is not known.Chylothorax is exceptional, and no case had been described beyond 5 years of treatment; our case would be the first one. We found 14 additional cases of dasatinib-related chylothoraces in a PubMed research.

Diagnostic accuracy of adenosine deaminase for pleural tuberculosis in a low prevalence setting: A machine learning approach within a 7-year prospective multi-center study.

OBJECTIVE: To analyze the performance of adenosine deaminase in pleural fluid combined with other parameters routinely measured in clinical practice and assisted by machine learning algorithms for the diagnosis of pleural tuberculosis in a low prevalence setting, and secondly, to identify effusions that are non-tuberculous and most likely malignant. PATIENTS AND METHODS: We prospectively analyzed 230 consecutive patients diagnosed with lymphocytic exudative pleural effusion from March 2013 to June 2020. Diagnosis according to the composite reference standard was achieved in all cases. Pre-test probability of pleural tuberculosis was 3.8% throughout the study period. Parameters included were: levels of adenosine deaminase, pH, glucose, proteins, and lactate dehydrogenase, red and white cell counts and lymphocyte percentage in pleural fluid, as well as age. We tested six different machine learning-based classifiers to categorize the patients. Two different classifications were performed: a) tuberculous/non-tuberculous and b) tuberculous/malignant/other. RESULTS: Out of a total of 230 patients with pleural effusion included in the study, 124 were diagnosed with malignant effusion and 44 with pleural tuberculosis, while 62 were given other diagnoses. In the tuberculous/non-tuberculous classification, and taking into account the validation predictions, the support vector machine yielded the best result: an AUC of 0.98, accuracy of 97%, sensitivity of 91%, and specificity of 98%, whilst in the tuberculous/malignant/other classification, this type of classifier yielded an overall accuracy of 80%. With this three-class classifier, the same sensitivity and specificity was achieved in the tuberculous/other classification, but it also allowed the correct classification of 90% of malignant cases. CONCLUSION: The level of adenosine deaminase in pleural fluid together with cell count, other routine biochemical parameters and age, combined with a machine-learning approach, is suitable for the diagnosis of pleural tuberculosis in a low prevalence scenario. Secondly, non-tuberculous effusions that are suspected to be malignant may also be identified with adequate accuracy.

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.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.

New Case of Endotipsitis: Urgent Need for Clinical Practice Guidelines.

Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure used for the decompression of portal pressure since the early 1990s. Bacteremia with an infection of the TIPS or endotipsitis is a serious complication with 32% mortality. To date and including the present case, only 56 cases have been reported in the literature. There are concerns regarding underdiagnosis. We report a case of a patient with endotipsitis and recurrent bacteremia treated successfully in our institution. In addition, previous reported cases were reviewed regarding microbiological data and mortality. Clinical practice guidelines including uniform disease definition, prophylaxis, and treatment of this nosocomial prosthetic-related infection are urgently needed.

Development and Validation of the COMPLES Score for Differentiating Between Tuberculous Effusions with Low Pleural pH or Glucose and Complicated Parapneumonic Effusions.

BACKGROUND: The frequency of "complicated" pleural effusions (CPE) (i.e., pleural fluid pH ≤ 7.2 and/or glucose ≤60 mg/dL) of tuberculous origin (CTPE) is not well reported. This study aims to quantify their prevalence, and develop a score to differentiate CTPE from complicated parapneumonic effusions (CPPE). METHODS: Retrospective analysis of databases from three Spanish hospitals which included patients with CTPE and CPPE. Forty percent of the study population served to generate a scoring system (COMPLES, COMplicated PLeural Effusion Score) that was further validated in the remaining 60 %. RESULTS: During the study period (1992-2015) 549 patients were diagnosed with tuberculous effusions and 434 parapneumonic effusions, of whom 25 and 64 %, respectively, had CPE. COMPLES was based on the combination of pleural fluid adenosine deaminase (ADA), the percentage of mononuclear cells (MNC %), pH, and age. The cutoff values and assigned scores were: ADA (<46 IU/L [0 points], 46-100 IU/L [4 points], ≥100 IU/L [6 points]), MNC % (<10 % [0 points], 10-50 [3 points], >50 [8 points]), pH (<7.07 [0 points], 7.07-7.20 [3 points], >7.20 [5 points]), and age (≥30 [0 points], <30 years [3 points]). A sum of 12 or more points had 97 % sensitivity, 92 % specificity, likelihood ratio positive 12.3, likelihood ratio negative 0.03, and area under the curve of 0.947 for identifying CTPE versus CPPE in the validation set. CONCLUSIONS: CPE is not an unusual presentation of tuberculosis. A simple new scoring system provides a reliable tool for differentiating between CTPE and CPPE.

Diagnostic accuracy of adenosine deaminase and lymphocyte proportion in pleural fluid for tuberculous pleurisy in different prevalence scenarios.

BACKGROUND: Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥ 40 U/l (ADA(40)) and LP ≥ 50% (LP(50)) in three different prevalence scenarios over 11 years in our area. MATERIALS AND METHODS: Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998-2000 (31.3%), 2001-2004 (11.8%), and 2005-2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA(40) were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA(40)+LP(50) the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods. CONCLUSIONS/SIGNIFICANCE: ADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion.

Valor diagnóstico del ada para tuberculosis pleural en diferentes escenarios de prevalencia de enfermedad / No disponible

La tuberculosis pleural es una manifestación común extrapulmonar de la enfermedad. Su diagnóstico de certeza se basa en la demostración del bacilo o en el hallazgo degranulomas en la biopsia pleural. En las últimas décadas se han desarrollado parámetros alternativos que pueden establecer el diagnóstico con certeza razonable, destacando la Adenosina Desaminasa (ADA) en líquido pleural por su excelente coste-efectividad. En teoría, el valor diagnóstico del ADA se ve disminuido en escenarios de baja prevalencia de enfermedad. Por otro lado la combinación del ADA con el ratio linfocitos/neutrófilos aumenta su especificidad. Analizamos de forma retrospectiva en nuestra comarca el valor de ambas variables combinadas en el diagnóstico de la tuberculosis pleural entres escenarios distintos de prevalencia de TBC pleural en el periodo 1996-2009 (AU)

Bilateral pleural effusion and interstitial lung disease as unusual manifestations of Kikuchi-Fujimoto disease: case report and literature review.

BACKGROUND: Kikuchi-Fujimoto's disease (KFD), also called histiocytic necrotizing lymphadenitis, is a rare, idiopathic and self-limited condition usually characterized by cervical lymphadenopathy and fever, most often affecting young patients. Aetiology is unknown. Differential diagnosis includes mainly malignant lymphoma, tuberculous lymphadenitis and systemic lupus erythematosus (SLE), so early diagnosis is crucial. Pleuropulmonary involvement due to isolated KFD has been seldom reported. CASE PRESENTATION: a 32-year-old man, on treatment for iatrogenic hypothyroidism, was admitted due to high grade fever and painful cervical lymphadenopathies. KFD was diagnosed by lymph node biopsy. Some days after admission the patient got worse, he developed generalized lymphadenopathy, bilateral pleural effusion and interstitial lung disease. All of them resolved with prednisone and after two years of following up he remains asymptomatic and without evidence of any other associated disease. CONCLUSION: Pleural effusion and interstitial lung disease are very uncommon manifestations of KFD. In our experience, treatment with oral prednisone was effective.

[Tuberculosis in the Bajo Deba area (Guipúzcoa, Spain) from 1995 to 2006]. / Tuberculosis en la comarca del Bajo Deba (Guipúzcoa) en el período 1995-2006.

BACKGROUND: Within the Multicenter Project on Tuberculosis Research performed in Spain in 1996-1997, the Bajo Deba Area reported the highest incidence of tuberculosis in the Basque Country. We analyzed the clinical and epidemiological characteristics of the tuberculosis population diagnosed in our area during the period of 1995 to 2006. METHODS: Ambispective, observational study. RESULTS: A total of 584 patients were diagnosed with tuberculosis. The disease affected the respiratory tract in 509 cases and other sites in 75 cases. The mean annual incidence rate of tuberculosis was 64.5 cases per 100 000 inhabitants (91.6 in 1995-1998; 34.9 in 2003-2006). The mean annual incidence rate of smear-positive patients was 20.7 cases per 100 000 inhabitants (33.8 in 1995-1998; 12.9 in 2003-2006). The 15 to 24-year-old group was the most highly affected during the period of 1995 to 1998 (mean annual incidence rate 199.4 cases per 100 000); in contrast, the > 75-year-old group was the most highly affected during the period of 2003 to 2006 (121.1 cases per 100 000 inhabitants). Fifty-three patients were co-infected by HIV (9%) (yearly mean of 11.6% in 1995-1998 and 7% in 2003-2006). Löwenstein culture was positive in 431 cases (73.8%). Resistance to isoniazid was detected in 1.4% out of a total of 287 strains tested, and multidrug resistance was not observed. Nine patients were immigrants (1.5%). Treatment completion was greater in our area (505 patients, 86.4%), as compared to that recorded in the Guipuzcoa province during the same period (1956 of 2525 patients, 77.5%) (P < .01). CONCLUSIONS: The Bajo Deba Area presented a high incidence of tuberculosis in the 1995 to 2006 period. Epidemiological trends showed a progressive decrease in the number of tuberculosis patients, with a shift from younger to older persons as the most highly affected age group. The impact of drug resistance and immigration was negligible on tuberculosis rates. The percentage of microbiologically confirmed cases was high. Treatment completion was satisfactory.

Tuberculosis en la comarca del Bajo Deba (Guipúzcoa) en el período 1995-2006 / Tuberculosis in the Bajo Deba Area (Guipúzcoa, Spain) from 1995 to 2006

Introducción. La comarca del Bajo Deba comunicó la incidencia más elevada de la comunidad autónoma vasca en el Proyecto Multicéntrico de Investigación en Tuberculosis (PMIT) realizado en España en 1996-1997. Analizamos las características clínicas y epidemiológicas de la población tuberculosa diagnosticada en nuestra comarca en el período en estudio. Métodos. Estudio ambispectivo observacional. Resultados. Se han diagnosticado 584 pacientes; 509 casos han sido de localización respiratoria, y 75 casos, extrarrespiratorios. La tasa media de incidencia por año ha sido 64,5 casos por 100.000 habitantes (91,6 en 1995-1998; 34,9 en 2003-2006). La tasa media de casos bacilíferos ha sido 20,7 por 100.000 y año (33,8 en 1995-1998; 12,9 en 2003-2006). El grupo etario más afectado en el cuatrienio 1995-1998 fue el de 15-24 años (tasa de incidencia media de 199,4 casos por 100.000 y por año); en 2003-2006 lo ha sido el de mayores de 75 años (121,1 casos por 100.000 y por año). Se hallaban coinfectados por el VIH 53 pacientes (9%) (porcentaje medio anual del 11,6% en 1995-1998; el 7% en 2003-2006). Se ha obtenido un cultivo de Löwenstein positivo en 431 pacientes (73,8%). La resistencia a isoniacida ha sido del 1,4% de entre 287 cepas analizadas y no se ha detectado multirresistencia. Nueve pacientes eran inmigrantes (1,5%). El cumplimiento del tratamiento en el Bajo Deba en el período 1995-2006 ha sido satisfactorio en 505 pacientes (86,4%), mientras en la provincia de Guipúzcoa lo era en 1.956 de 2.525 pacientes diagnosticados y tratados en el mismo lapso de tiempo (77,5%) (p < 0,01). Conclusiones. La comarca del Bajo Deba presenta una alta incidencia de tuberculosis en el período estudiado. La evolución epidemiológica ha sido positiva con disminución de la incidencia de tuberculosis, de la contagiosidad, de la coinfección por el virus de la inmunodeficiencia humana (VIH), y con desplazamiento de las mayores tasas de enfermedad desde los grupos jóvenes a la tercera edad. La resistencia a tuberculostáticos y la inmigración no han tenido un papel determinante en la epidemiología. El porcentaje de casos confirmados microbiológicamente ha sido alto y el cumplimiento del tratamiento, satisfactorio (AU)

Within the Multicenter Project on Tuberculosis Research performed in Spain in 1996-1997, the Bajo Deba Area reported the highest incidence of tuberculosis in the Basque Country. We analyzed the clinical and epidemiological characteristics of the tuberculosis population diagnosed in our area during the period of 1995 to 2006. Methods. Ambispective, observational study. Results. A total of 584 patients were diagnosed with tuberculosis. The disease affected the respiratory tract in 509 cases and other sites in 75 cases. The mean annual incidence rate of tuberculosis was 64.5 cases per 100 000 inhabitants (91.6 in 1995-1998; 34.9 in 2003-2006). The mean annual incidence rate of smear-positive patients was 20.7 cases per 100 000 inhabitants (33.8 in 1995-1998; 12.9 in 2003-2006). The 15 to 24-year-old group was the most highly affected during the period of 1995 to 1998 (mean annual incidence rate 199.4 cases per 100 000); in contrast, the > 75-year-old group was the most highly affected during the period of 2003 to 2006 (121.1 cases per 100 000 inhabitants). Fifty-three patients were co-infected by HIV (9%) (yearly mean of 11.6% in 1995-1998 and 7% in 2003-2006). Löwenstein culture was positive in 431 cases (73.8%). Resistance to isoniazid was detected in 1.4% out of a total of 287 strains tested, and multidrug resistance was not observed. Nine patients were immigrants (1.5%). Treatment completion was greater in our area (505 patients, 86.4%), as compared to that recorded in the Guipuzcoa province during the same period (1956 of 2525 patients, 77.5%) (P <.01). Conclusions. The Bajo Deba Area presented a high incidence of tuberculosis in the 1995 to 2006 period. Epidemiological trends showed a progressive decrease in the number of tuberculosis patients, with a shift from younger to older persons as the most highly affected age group. The impact of drug resistance and immigration was negligible on tuberculosis rates. The percentage of microbiologically confirmed cases was high. Treatment completion was satisfactory (AU)