Salmonella Typhi Vaccination Response as a Tool for the Stratification of Risk in Patients with Predominantly Antibody Deficiencies.

Predominantly antibody deficiencies are the most frequent type of primary immunodeficiency (PID). Diagnosis requires evaluation of the immune function by distinguishing the presence or absence of a response against polysaccharide antigens. Salmonella enterica serovar Typhi-based vaccines have proved to be a suitable tool. We studied a group of patients with suspicion of primary immunodeficiency and classified them by final diagnosis. We analyzed the vaccination response to S. Typhi and other immune biomarkers and clinical data. The aim of this study was to classify patients regarding the intensity of their immune response measured as the difference between specific immunoglobulin G levels before and after vaccination and antibody levels in the post-vaccination sample in order to improve clinical decisions regarding follow up and treatment of immunodeficiency patients. We established four groups of response: Non responders (NR), Low responders (LR), Intermediate responders (IR), and High responders (HR), where we found differences in IgG, IgG1, IgG2, IgG4, IgA, IgA1, IgA2, and IgM, and where the finally achieved diagnosis was also different and corresponding to the level of vaccination response.

Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study.

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml-1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml-1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml-1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml-1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml-1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

¿Se basan las recomendaciones en la evidencia científica? A propósito de la neumonía atípica. Respuesta de los autores / Atypical pneumonia: are the recommendations evidence-based?. Authors’ reply

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[Tobacco smoking and sputum smear conversion in pulmonary tuberculosis]. / Tabaquismo y negativización bacteriológica del esputo en la tuberculosis pulmonar.

BACKGROUND AND OBJECTIVE: To analyze if cigarette smoking delays the sputum smear conversion in pulmonary tuberculosis. PATIENTS AND METHOD: Ninety eight patients were diagnosed with pulmonary tuberculosis. Patients were all not immunosuppressed, infected by human immunodeficiecy virus (HIV) or drug resistant. Sixty four of them were smokers with a pack-year index (standard deviation) of 33.69 (23.12). Delayed sputum smear conversion (DC) was considered when 2 positive sputum culture results were obtained in the second month of anti-tuberculous treatment and was associated with the following variables in 2 groups: a) total group (in which all the patients were included): age, sex, smoking habits, risk factors (alcohol consumption, diabetes mellitus, immunosuppression, drug addicion, malnutrition), time with symptoms, radiologic presentation and bacterial load, and b) smokers: age, sex, risk factors, time with symptoms, radiologic presentation, bacterial load and pack-year index. For the statistical analysis, chi2 test, Student t test and logistic regression model were used, considering the dependant variable DC. RESULTS: In the total group, 17 patients (17.3%) had DC, 16 of them had a history of smoking and in the univariate analysis it was associated with: alcohol consumption, time with symptoms, radiologic presentation as bilateral cavitary infiltrates and smoking habits. The logistic regression analysis showed an association with smoking habits (odds ratio = 9.8; p = 0.03) and bilateral cavitary infiltrates (odds ratio = 3.61; p = 0.02). In the group of smokers, DC was associated in the univariate analysis with the female sex. CONCLUSIONS: Smoking habits delay sputum conversion in patients with pulmonary tuberculosis not associated with HIV and non-resistant bacilli. According to these results it is necessary to assist smoking cessation in patients who are receiving antituberculous treatment.

Tabaquismo y negativización bacteriológica del esputo en la tuberculosis pulmonar / Tobacco smoking and sputum smear conversion in pulmonary tuberculosis

FUNDAMENTO Y OBJETIVO: Analizar si el consumo de tabaco retrasa la negativización microbiológicaen la tuberculosis pulmonar.PACIENTES Y MÉTODO: Se incluyó a 98 pacientes diagnosticados de tuberculosis pulmonar, sin inmunodepresióncausada por el virus de la inmunodeficiencia humana (VIH) ni resistencia farmacológica.Eran fumadores 64, con un índice medio (desviación estándar) de 33,69 (23,12)paquetes/año. Se consideró conversión bacteriológica retardada (CR) a la persistencia de 2 cultivospositivos al segundo mes del inicio del tratamiento antituberculoso, y se relacionó con lassiguientes variables en 2 grupos: a) general (que englobaba a todos los pacientes): edad, sexo,tabaquismo, factores de riesgo (consumo de alcohol, diabetes mellitus, inmunodepresión, adiccióna drogas, desnutrición), tiempo de evolución de los síntomas, presentación radiológica ycarga bacilar, y b) fumadores: edad, sexo, índice paquetes/año, factores de riesgo, tiempo deevolución de los síntomas, presentación radiológica y carga bacilar. En cuanto al estudio estadístico,se realizaron los siguientes análisis: distribución de la χ2, prueba de la t de Student yregresión logística paso a paso hacia adelante, considerando como variable dependiente la CR.RESULTADOS: En el grupo general presentaron CR 17 pacientes (17,3%), de los que 16 referíanantecedentes de tabaquismo, y en el estudio univariado la CR se relacionó con el consumo dealcohol, el tiempo de evolución de los síntomas, la presentación radiológica cavitaria bilateral yel tabaquismo. En el análisis de regresión logística mantenían la relación el tabaquismo (oddsratio = 9,80; p = 0,03) y la cavitación bilateral (odds ratio = 3,61; p = 0,02). En el grupo defumadores, la CR se asoció en el análisis univariado únicamente con sexo femenino.CONCLUSIONES: El tabaquismo retrasa la CR en pacientes diagnosticados de tuberculosis pulmonarno ligada al VIH y con aislamientos sensibles. Dada la trascendencia de este hallazgo, espreciso reforzar su abandono durante el tratamiento antituberculoso

BACKGROUND AND OBJECTIVE: To analyze if cigarette smoking delays the sputum smear conversionin pulmonary tuberculosis.PATIENTS AND METHOD: Ninety eight patients were diagnosed with pulmonary tuberculosis. Patientswere all not immunosuppressed, infected by human immunodeficiecy virus (HIV) or drugresistant. Sixty four of them were smokers with a pack-year index (standard deviation) of 33.69(23.12). Delayed sputum smear conversion (DC) was considered when 2 positive sputum cultureresults were obtained in the second month of anti-tuberculous treatment and was associatedwith the following variables in 2 groups: a) total group (in which all the patients were included):age, sex, smoking habits, risk factors (alcohol consumption, diabetes mellitus, immunosuppression,drug addicion, malnutrition), time with symptoms, radiologic presentation andbacterial load, and b) smokers: age, sex, risk factors, time with symptoms, radiologic presentation,bacterial load and pack-year index. For the statistical analysis, χ2 test, Student t test andlogistic regression model were used, considering the dependant variable DC.RESULTS: In the total group, 17 patients (17.3%) had DC, 16 of them had a history of smokingand in the univariate analysis it was associated with: alcohol consumption, time with symptoms,radiologic presentation as bilateral cavitary infiltrates and smoking habits. The logistic regressionanalysis showed an association with smoking habits (odds ratio = 9.8; p = 0.03) andbilateral cavitary infiltrates (odds ratio = 3.61; p = 0.02). In the group of smokers, DC was associatedin the univariate analysis with the female sex.CONCLUSIONS: Smoking habits delay sputum conversion in patients with pulmonary tuberculosisnot associated with HIV and non-resistant bacilli. According to these results it is necessary toassist smoking cessation in patients who are receiving antituberculous treatment

[Treatment and course of community-acquired pneumonia caused by atypical pathogens]. / Neumonía adquirida en la comunidad por gérmenes atípicos: tratamiento y evolución.

OBJECTIVE: To study the course of disease and outcomes in a group of patients with community-acquired pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella species ,Coxiella burnetii, and Chlamydophila pneumoniae) according to the empiric treatment received. PATIENTS AND METHODS: Of a total of 390 patients admitted to our hospital with pneumonia between January 1996 and February 2001, the causative microorganism was an atypical pathogen in 89 cases. Patients were divided retrospectively into 2 groups according to the empiric treatment they received: group A, who had received an antibiotic regime (quinolones or macrolides) that provided coverage for atypical pathogens; and group B, who had received treatment that did not provide such coverage. Clinical course was assessed in terms of the differences between the 2 groups in length of hospital stay, radiographic resolution, readmission at 30 days after discharge, and mortality. RESULTS: A total of 89 patients with pneumonia caused by atypical pathogens (39 in group A and 50 in group B) were studied. No significant between-group differences in the variables were found. CONCLUSIONS: In this group of patients hospitalized for community-acquired pneumonia, antibiotic regimens providing coverage for atypical pathogens did not improve either clinical or radiographic evolution.

Neumonía adquirida en la comunidad por gérmenes atípicos: tratamiento y evolución / Treatment and course of community-acquired pneumonia caused by atypical pathogens

Objetivo: Estudiar la evolución de un grupo de neumonías extrahospitalarias causadas por gérmenes atípicos (Mycoplasma pneumoniae, Legionella spp. ,Coxiella burnetii y Chlamydophila pneumoniae) en función del tratamiento empírico recibido. Pacientes y métodos: Entre enero de 1996 y febrero de 2001 ingresaron en nuestra unidad 390 casos de neumonía, de los que 89 estaban causados por gérmenes atípicos. Los pacientes se dividieron retrospectivamente en 2 grupos según el tratamiento empírico pautado: grupo A, al que se había proporcionado cobertura frente a gérmenes atípicos (quinolonas o macrólidos), y grupo B, al que no se había proporcionado dicha cobertura. Se estudió la evolución según las diferencias entre ambos grupos en la estancia hospitalaria, la resolución radiológica, el reingreso en el primer mes tras el alta y la mortalidad. Resultados: El grupo de estudio lo constituyeron 89 pacientes con neumonía causada por gérmenes atípicos (39 en el grupo A y 50 en el B). Las variables estudiadas no mostraron diferencias significativas entre ambos grupos. Conclusiones: En nuestra serie de neumonías extrahospitalarias la cobertura antibiótica frente a gérmenes atípicos no mejoró la evolución clínica y radiológica de los pacientes

Objective: To study the course of disease and outcomes in a group of patients with community-acquired pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella species ,Coxiella burnetii, and Chlamydophila pneumoniae) according to the empiric treatment received. Patients and methods: Of a total of 390 patients admitted to our hospital with pneumonia between January 1996 and February 2001, the causative microorganism was an atypical pathogen in 89 cases. Patients were divided retrospectively into 2 groups according to the empiric treatment they received: group A, who had received an antibiotic regime (quinolones or macrolides) that provided coverage for atypical pathogens; and group B, who had received treatment that did not provide such coverage. Clinical course was assessed in terms of the differences between the 2 groups in length of hospital stay, radiographic resolution, readmission at 30 days after discharge, and mortality. Results: A total of 89 patients with pneumonia caused by atypical pathogens (39 in group A and 50 in group B) were studied. No significant between-group differences in the variables were found. Conclusions: In this group of patients hospitalized for community-acquired pneumonia, antibiotic regimens providing coverage for atypical pathogens did not improve either clinical or radiographic evolution

[Chemotherapy and survival in advanced non-small cell lung carcinoma: is pneumologists' skepticism justified?]. / Quimioterapia y supervivencia en el carcinoma broncogénico no microcítico en estadios avanzados: 'está justificado el nihilismo de los neumólogos?

OBJECTIVE: Few studies have assessed whether the advantage chemotherapy has been shown to have in treating advanced non-small lung carcinoma in clinical trials is transferrable to normal health care activity. This could explain the skepticism of a large number of pneumologists towards this treatment. The objective of our study was to analyze prognostic factors related to survival and to see whether cytostatic treatment was an independent predictor. PATIENTS AND METHODS: Patients enrolled in the study had been diagnosed with non-small cell carcinoma in stages IV or IIIB with pleural or N2-N3 involvement and with a performance status of 2 or below according to the Eastern Cooperative Oncology Group (ECOG). Survival was analyzed with regard to the following variables: age, sex, comorbidity, weight loss, laboratory test results, histological type, ECOG score, TNM staging, and treatment. The Student t test, the chi(2) test, the Kaplan-Meier method, the log-rank test, and Cox regression analysis were used in the statistical analysis. RESULTS: We enrolled 190 patients (157 men and 33 women) with a mean (SD) age of 61.75 (10.85) years (range, 33-85 years). Of these patients, 144 received cytostatic treatment and 46 palliative treatment. The median survival was 31 weeks and was related to absence of weight loss (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.26-2.39; P=.001), cytostatic treatment (HR, 1.85; 95% CI, 1.25-2.76; P=.002), and ECOG score of 0 to 1 (HR, 2.84; 95% CI, 1.62-5.00; P=.0001). In patients with ECOG scores of 0 to 1, weight loss and treatment were significant prognostic factors. Survival in the ECOG 2 group was 15 weeks for patients undergoing cytostatic treatment and 11 weeks for patients with symptomatic treatment. CONCLUSIONS: In normal clinical practice, chemotherapy significantly prolongs survival in patients with performance status of less than 2, more time being gained if there is no associated weight loss. We conclude that the reluctance shown by many pneumologists toward using this treatment is not entirely justified.

Quimioterapia y supervivencia en el carcinoma broncogénico no microcítico en estadios avanzados: ¿está justificado el nihilismo de los neumólogos? / Chemotherapy and survival in advanced non-small cell lung carcinoma: is pneumologists' skepticism justified?

Objetivo: Pocas series han valorado si el beneficio que en los ensayos clínicos muestra la quimioterapia en el carcinoma broncogénico no microcítico en estadios avanzados es trasladable a la actividad asistencial habitual, lo que podría explicar el escepticismo de gran parte de los neumólogos. En este contexto, el objetivo de nuestro trabajo es analizar factores pronósticos relacionados con la supervivencia y si el tratamiento citostático influye de manera independiente. Pacientes y métodos: Se incluyó a pacientes diagnosticados de carcinoma no microcítico en estadios IV y IIIb con afectación pleural o N2-N3 y grado de actividad, según el Eastern Cooperative Oncology Group (ECOG), menor o igual a 2. Se relacionaron con la supervivencia las siguientes variables: edad, sexo, comorbilidad, pérdida de peso, parámetros analíticos, tipo histológico, ECOG, TNM y tratamiento. Para el análisis estadístico se emplearon las pruebas de la t de Student, de la χ2, el método de Kaplan-Meier, el test de rangos logarítmicos y el modelo de regresión de Cox. Resultados: Se incluyó en el estudio a 190 enfermos (157 varones y 33 mujeres), con una edad media (± desviación estándar) de 61,75 ± 10,85 años (rango: 33-85), de los cuales 144 recibieron tratamiento citostático y 46 paliativo. La mediana de supervivencia fue de 31 semanas y se relacionó con: ausencia de pérdida de peso (razón de probabilidad [HR] = 1,73; intervalo de confianza [IC] del 95%, 1,26-2,39; p = 0,001), tratamiento citostático (HR = 1,85; IC del 95%, 1,25-2,76; p = 0,002) y ECOG 0-1 (HR = 2,84; IC del 95%, 1,62-5,00; p = 0,0001). En el grupo ECOG 0-1 mostraban significado pronóstico la pérdida de peso y el tratamiento. La supervivencia en ECOG 2 fue de 15 semanas en los pacientes con tratamiento citostático y de 11 semanas en aquellos con tratamiento sintomático. Conclusiones: En la práctica clínica habitual la quimioterapia prolonga la supervivencia significativamente en los pacientes con grado de actividad inferior a 2 y esta ganancia es mayor si no existe pérdida de peso asociada. Por tanto, creemos que la opinión poco favorable que muestra gran parte de los neumólogos acerca de este tratamiento no parece plenamente justificada

Objective: Few studies have assessed whether the advantage chemotherapy has been shown to have in treating advanced non-small lung carcinoma in clinical trials is transferrable to normal health care activity. This could explain the skepticism of a large number of pneumologists towards this treatment. The objective of our study was to analyze prognostic factors related to survival and to see whether cytostatic treatment was an independent predictor. Patients and methods: Patients enrolled in the study had been diagnosed with non-small cell carcinoma in stages IV or IIIB with pleural or N2-N3 involvement and with a performance status of 2 or below according to the Eastern Cooperative Oncology Group (ECOG). Survival was analyzed with regard to the following variables: age, sex, comorbidity, weight loss, laboratory test results, histological type, ECOG score, TNM staging, and treatment. The Student t test, the χ2 test, the Kaplan-Meier method, the log-rank test, and Cox regression analysis were used in the statistical analysis. Results: We enrolled 190 patients (157 men and 33 women) with a mean (SD) age of 61.75 (10.85) years (range, 33-85 years). Of these patients, 144 received cytostatic treatment and 46 palliative treatment. The median survival was 31 weeks and was related to absence of weight loss (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.26-2.39; P=.001), cytostatic treatment (HR, 1.85; 95% CI, 1.25-2.76; P=.002), and ECOG score of 0 to 1 (HR, 2.84; 95% CI, 1.62-5.00; P=.0001). In patients with ECOG scores of 0 to 1, weight loss and treatment were significant prognostic factors. Survival in the ECOG 2 group was 15 weeks for patients undergoing cytostatic treatment and 11 weeks for patients with symptomatic treatment. Conclusions: In normal clinical practice, chemotherapy significantly prolongs survival in patients with performance status of less than 2, more time being gained if there is no associated weight loss. We conclude that the reluctance shown by many pneumologists toward using this treatment is not entirely justified