8 research outputs found

    Impact of adjuvant therapeutic surgery on the health-related quality of life of pulmonary tuberculosis patients

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    Altres ajuts: This study was funded by the Spanish Government-FEDER Funds through CV contracts CP13/00174, CPII14/00021 and PI16/01511 grant; the "CIBER Enfermedades Respiratorias" Network (CIBERES); the "Spanish Society of Pneumology and Thoracic Surgery" (SEPAR) through grant 16/023; and the "Agència de Gestió d'Ajuts Universitaris i de Recerca" (AGAUR) through AD contract (2017 FI_B_00797).This study aimed to determine the health-related quality of life (HRQoL) of patients with pulmonary tuberculosis (TB) and to assess its change after a therapeutic surgical procedure. In this scenario, the purpose was to elucidate and quantify the effect of various demographic, epidemiological, clinical, surgical and psychosocial details on this variable. A prospective cohort of 40 patients undergoing therapeutic surgery for pulmonary TB (Study of Human Tuberculosis Lesions (SH-TBL) cohort) was recruited in Tbilisi, Georgia, between 2016 and 2018. HRQoL was assessed by administering the St George's Respiratory Questionnaire (SGRQ) and a novel psychosocial questionnaire, the BCN-Q, both at baseline and at 6 months post-surgery. A statistically and clinically significant improvement in the SGRQ total score was observed at follow-up, although it did not reach the values found for the healthy population. The differences between time points were statistically significant for the following groups: women, age <40 years, body mass index ≥20 kg·m −2, nonsmokers, drug-susceptible and drug-resistant participants, both new and relapsed patients, early culture negativisation, cases with a single lesion, either lesions <35 mm or ≥35 mm, and lesion, lobe and lung resections. The analysis of BCN-Q together with the SGRQ showed that several of its items, such as marital status, living conditions, nutrition, employment, external support, certain attitudes towards the healthcare system, emotional burden and sleep troubles, can impact HRQoL. These results highlight the benefit of adjuvant therapeutic surgery for pulmonary TB in selected patients in terms of HRQoL and suggest that a comprehensive approach including demographic, epidemiological, clinical and psychosocial variables may more accurately predict TB evolution and prognosis. Adjuvant therapeutic surgery in selected pulmonary TB patients improves their health-related quality of life. Impact of psychosocial variables on HRQoL may be assessed using a newly developed questionnaire, namely BCN-Q

    Retrospective study of clinical and lesion characteristics of patients undergoing surgical treatment for Pulmonary Tuberculosis in Georgia

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    Altres ajuts: This work was supported by CIBER Enfermedades Respiratorias (CB06/06/0031); and the SEPAR trough Project 2016/023.Our aim was to retrospectively compare clinical data and characteristics of removed lesions of the cohort of patients undergoing therapeutical surgery for their tuberculosis. Demographic and epidemiological details, clinical data, data on the surgery performed, macroscopic characteristics of the TB lesions removed, and outcome were recorded retrospectively from the 137 patients who underwent therapeutical surgery for their TB in Tbilisi, Georgia during 2014 and 2015. Men represented 70% of the included patients, presented more comorbidities and underwent operation earlier in terms of days between diagnostic and surgery. Women underwent operation at younger ages, and in MDR/XDR-TB cases, showed higher percentages of sputum conversion at >2 months and of fresh necrosis in the surgical specimens, suggesting a worse evolution. Half of cases were MDR/XDR-TB cases. In spite of being considered microbiologically cured according to WHO, a non despricable percentage of cases showed viable bacilli in the surgical specimen. Even if no causality could be statistically demonstrated, differences could be encountered according to gender and drug susceptibility of the responsible strains. According to our results, host factors such as gender, type of necrosis found in the lesions, size of lesions and presence of viable bacilli in the surgical specimen, should be included in future studies on therapeutical surgery of TB. As most of studies are done in MDR/XDR-TB, more data on DS-TB operated cases are needed. Our results also highlight that, in spite of achieving the microbiologically cured status, sterilization might not occur, and thus new biomarkers and new methods to evaluate the healing process of TB patients are urgently needed and radiological assays should be taken into account

    The Study of Human Tuberculosis Lesions : circulant and transcriptional biomarkers in a cohort of tuberculosis patients undergoing therapeutic surgery

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    La tuberculosi (TB), és la major causant de morts associades a malalties infeccioses al món. La cirurgia terapèutica segueix sent una eina essencial en els casos més complicats de TB, per exemple, si el pacient mostra persistència de lesions cavitàries malgrat bona adherència als antibiòtics. Avui dia, la recerca en TB està centrada en identificar factors clínics-epidemiològics que condueixen al pacient a evolucionar negativament durant el tractament i identificar biomarcadors que puguin predir l'estat de salut i una mala prognosi. Aquestes estratègies no reflecteixen la malaltia pulmonar in situ, i per tant, la resposta local de l'hostatger al patogen no està representada. En aquesta tesi doctoral vàrem hipotetizar que l'estudi de la resposta immunològica local i sistèmica de pacients que rebran cirurgia terapèutica per la seva TB pulmonar podria ajudar a determinar nous biomarcadors així com informació essencial respecte els mecanismes de resposta de l'hostatger en la generació de les lesions tuberculoses. Es van analitzar retrospectivament dades clínic-epidemiològiques considerant les característiques macroscòpiques de les lesions obtingudes en una cohort de 137 pacients tuberculosos sotmesos a cirurgia. En una nova cohort de 40 pacients sotmesos a cirurgia terapèutica, vam avaluar els nivells de marcadors immunològics circulants i vam realitzar RNA-seq en biòpsies fresques de granuloma tuberculós humà, per ser correlacionades amb el perfil fisiopatològic dels participants juntament amb les característiques macroscòpiques de les lesions extirpades. Vam detectar persistència del Mycobacterium tuberculosis en biòpsies de lesions malgrat negativitat microbiològica en cultiu. El sexe i hàbits tòxics son factors importants que podrien determinar l'evolució de la TB. Biomarcadors circulants correlacionen amb la mida de la lesió, formes multi-resistents i factors considerats de mal pronòstic. Es va detectar un efecte immunosupressor induït per la presència de les lesions, suggerit per marcadors immunològics i el transcriptoma de la lesió tuberculosa. Vam generar una signatura de 6056 gens del granuloma tuberculós humà i una llista de gens d'interès que aglomeren l'expressió gènica de les característiques fisiopatològiques de la cohort. La plataforma de biomarcadors circulants i els gens haurien de ser validats i avaluats en altres pacients amb TB i confirmar la seva potencial utilitat com a eina de prognosi.La tuberculosis (TB), es la mayor causante de muertes asociadas a enfermedades infecciosas en el mundo. La cirugía terapéutica sigue siendo una herramienta esencial en los casos más complicados de TB, por ejemplo, si el paciente muestra persistencia de lesiones cavitarias a pesar de probar una buena adherencia a los antibióticos. Hoy en día, la investigación en TB está centrada en identificar factores clínicos-epidemiológicos que conducen al paciente a evolucionar negativamente durante el tratamiento e identificar biomarcadores que puedan predecir el estado de salud y un mal pronóstico. Estas estrategias no reflejan la enfermedad pulmonar in situ y, por tanto, la respuesta local del huésped al patógeno no está representada. En esta tesis doctoral hipotetizamos que el estudio de la respuesta inmunológica local y sistémica de pacientes que recibirán cirugía terapéutica por su TB pulmonar podría ayudar a determinar nuevos biomarcadores así como información esencial respecto a los mecanismos de respuesta del huésped en la generación de las lesiones tuberculosas. Se analizaron retrospectivamente datos clínico-epidemiológicos considerando las características macroscópicas de las lesiones obtenidas en una cohorte de 137 pacientes tuberculosos sometidos a cirugía. En una nueva cohorte de 40 pacientes sometidos a cirugía terapéutica, evaluamos los niveles de marcadores inmunológicos circulantes y realizamos RNA-seq en biopsias frescas de granuloma tuberculoso humano, para ser correlacionadas con el perfil fisiopatológico de los participantes junto con las características macroscópicas de las lesiones extirpadas. Detectamos persistencia de Mycobacterium tuberculosis en biopsias de lesiones a pesar de mostrar negatividad microbiológica en cultivo. El sexo y los hábitos tóxicos son factores importantes que podrían determinar la evolución de la TB. Biomarcadores circulantes correlacionan con el tamaño de la lesión, formas multi-resistentes y factores considerados de mal pronóstico. Se detectó un efecto inmunosupresor inducido por la presencia de las lesiones, sugerido por marcadores inmunológicos y el transcriptoma de la lesión tuberculosa. Generamos una firma de 6056 genes del granuloma tuberculoso humano y una lista de genes de interés que aglomeran la expresión génica de las características fisiopatológicas de la cohorte. La plataforma de biomarcadores circulantes y los genes deberían ser validados y evaluados en otros pacientes con TB y confirmar su potencial utilidad como herramienta de prognosis de los pacientes con TB.Tuberculosis (TB) is the worldwide leading cause of death among infectious diseases. Therapeutic surgery is still an invaluable tool to resolve the most complicated TB cases, for instance, if the patient is experiencing persistent lung cavities despite good adherence to chemotherapy. Scientific efforts are focused on identifying which clinical-epidemiological factors lead a patient to evolve poorly during treatment and to identify biomarkers that can predict the treatment response, health status, and fatal outcomes. Nonetheless, these strategies are not reflecting the in situ lung pathology, and therefore, the local host-to-pathogen response is misrepresented. We hypothesized that the study of the local and systemic immune responses from patients undergoing therapeutic surgery for their pulmonary TB could help us to identify potential TB biomarkers and essential information regarding the role of the host in the mechanisms associated to the generation of the TB lesions. Clinical-epidemiological data of a cohort of 137 patients undergoing therapeutic surgery for pulmonary TB were retrospectively analyzed according to the macroscopic features of the removed TB lesions. Next, in a new cohort of 40 patients also receiving therapeutic surgery, we assessed the levels of circulating immune markers and we performed RNA-seq upon the fresh human TB granuloma biopsies, to be correlated with the pathophysiological phenotype of the participants together with the macroscopic lesions' characteristics. We found the persistence of Mycobacterium tuberculosis in surgical TB cavitary biopsies despite microbiological clearance in culture. Sex and toxic habits are important factors that may determine the evolution of the disease. Circulant biomarkers correlated with the size of the lesion, with multi-drug resistant forms, and factors considered to indicate the worst disease outcomes. We noted an immunosuppressive effect exerted by the presence of the TB lesions, suggested by the immune-markers and the human TB granuloma transcriptome. Finally, we generated a 6056-gene signature of the human TB granuloma and a list of genes of interest gathering the total-RNA expression of the main pathophysiological traits of the cohort. The proposed platform of circulant biomarkers and its genes should be further validated and assessed in other active TB patients to confirm the potential use as a prognostic tool

    The Study of Human Tuberculosis Lesions: circulant and transcriptional biomarkers in a cohort of tuberculosis patients undergoing therapeutic surgery

    No full text
    La tuberculosi (TB), és la major causant de morts associades a malalties infeccioses al món. La cirurgia terapèutica segueix sent una eina essencial en els casos més complicats de TB, per exemple, si el pacient mostra persistència de lesions cavitàries malgrat bona adherència als antibiòtics. Avui dia, la recerca en TB està centrada en identificar factors clínics-epidemiològics que condueixen al pacient a evolucionar negativament durant el tractament i identificar biomarcadors que puguin predir l’estat de salut i una mala prognosi. Aquestes estratègies no reflecteixen la malaltia pulmonar in situ, i per tant, la resposta local de l’hostatger al patogen no està representada. En aquesta tesi doctoral vàrem hipotetizar que l’estudi de la resposta immunològica local i sistèmica de pacients que rebran cirurgia terapèutica per la seva TB pulmonar podria ajudar a determinar nous biomarcadors així com informació essencial respecte els mecanismes de resposta de l’hostatger en la generació de les lesions tuberculoses. Es van analitzar retrospectivament dades clínic-epidemiològiques considerant les característiques macroscòpiques de les lesions obtingudes en una cohort de 137 pacients tuberculosos sotmesos a cirurgia. En una nova cohort de 40 pacients sotmesos a cirurgia terapèutica, vam avaluar els nivells de marcadors immunològics circulants i vam realitzar RNA-seq en biòpsies fresques de granuloma tuberculós humà, per ser correlacionades amb el perfil fisiopatològic dels participants juntament amb les característiques macroscòpiques de les lesions extirpades. Vam detectar persistència del Mycobacterium tuberculosis en biòpsies de lesions malgrat negativitat microbiològica en cultiu. El sexe i hàbits tòxics son factors importants que podrien determinar l’evolució de la TB. Biomarcadors circulants correlacionen amb la mida de la lesió, formes multi-resistents i factors considerats de mal pronòstic. Es va detectar un efecte immunosupressor induït per la presència de les lesions, suggerit per marcadors immunològics i el transcriptoma de la lesió tuberculosa. Vam generar una signatura de 6056 gens del granuloma tuberculós humà i una llista de gens d’interès que aglomeren l’expressió gènica de les característiques fisiopatològiques de la cohort. La plataforma de biomarcadors circulants i els gens haurien de ser validats i avaluats en altres pacients amb TB i confirmar la seva potencial utilitat com a eina de prognosi.La tuberculosis (TB), es la mayor causante de muertes asociadas a enfermedades infecciosas en el mundo. La cirugía terapéutica sigue siendo una herramienta esencial en los casos más complicados de TB, por ejemplo, si el paciente muestra persistencia de lesiones cavitarias a pesar de probar una buena adherencia a los antibióticos. Hoy en día, la investigación en TB está centrada en identificar factores clínicos-epidemiológicos que conducen al paciente a evolucionar negativamente durante el tratamiento e identificar biomarcadores que puedan predecir el estado de salud y un mal pronóstico. Estas estrategias no reflejan la enfermedad pulmonar in situ y, por tanto, la respuesta local del huésped al patógeno no está representada. En esta tesis doctoral hipotetizamos que el estudio de la respuesta inmunológica local y sistémica de pacientes que recibirán cirugía terapéutica por su TB pulmonar podría ayudar a determinar nuevos biomarcadores así como información esencial respecto a los mecanismos de respuesta del huésped en la generación de las lesiones tuberculosas. Se analizaron retrospectivamente datos clínico-epidemiológicos considerando las características macroscópicas de las lesiones obtenidas en una cohorte de 137 pacientes tuberculosos sometidos a cirugía. En una nueva cohorte de 40 pacientes sometidos a cirugía terapéutica, evaluamos los niveles de marcadores inmunológicos circulantes y realizamos RNA-seq en biopsias frescas de granuloma tuberculoso humano, para ser correlacionadas con el perfil fisiopatológico de los participantes junto con las características macroscópicas de las lesiones extirpadas. Detectamos persistencia de Mycobacterium tuberculosis en biopsias de lesiones a pesar de mostrar negatividad microbiológica en cultivo. El sexo y los hábitos tóxicos son factores importantes que podrían determinar la evolución de la TB. Biomarcadores circulantes correlacionan con el tamaño de la lesión, formas multi-resistentes y factores considerados de mal pronóstico. Se detectó un efecto inmunosupresor inducido por la presencia de las lesiones, sugerido por marcadores inmunológicos y el transcriptoma de la lesión tuberculosa. Generamos una firma de 6056 genes del granuloma tuberculoso humano y una lista de genes de interés que aglomeran la expresión génica de las características fisiopatológicas de la cohorte. La plataforma de biomarcadores circulantes y los genes deberían ser validados y evaluados en otros pacientes con TB y confirmar su potencial utilidad como herramienta de prognosis de los pacientes con TB.Tuberculosis (TB) is the worldwide leading cause of death among infectious diseases. Therapeutic surgery is still an invaluable tool to resolve the most complicated TB cases, for instance, if the patient is experiencing persistent lung cavities despite good adherence to chemotherapy. Scientific efforts are focused on identifying which clinical-epidemiological factors lead a patient to evolve poorly during treatment and to identify biomarkers that can predict the treatment response, health status, and fatal outcomes. Nonetheless, these strategies are not reflecting the in situ lung pathology, and therefore, the local host-to-pathogen response is misrepresented. We hypothesized that the study of the local and systemic immune responses from patients undergoing therapeutic surgery for their pulmonary TB could help us to identify potential TB biomarkers and essential information regarding the role of the host in the mechanisms associated to the generation of the TB lesions. Clinical-epidemiological data of a cohort of 137 patients undergoing therapeutic surgery for pulmonary TB were retrospectively analyzed according to the macroscopic features of the removed TB lesions. Next, in a new cohort of 40 patients also receiving therapeutic surgery, we assessed the levels of circulating immune markers and we performed RNA-seq upon the fresh human TB granuloma biopsies, to be correlated with the pathophysiological phenotype of the participants together with the macroscopic lesions&#8217; characteristics. We found the persistence of Mycobacterium tuberculosis in surgical TB cavitary biopsies despite microbiological clearance in culture. Sex and toxic habits are important factors that may determine the evolution of the disease. Circulant biomarkers correlated with the size of the lesion, with multi-drug resistant forms, and factors considered to indicate the worst disease outcomes. We noted an immunosuppressive effect exerted by the presence of the TB lesions, suggested by the immune-markers and the human TB granuloma transcriptome. Finally, we generated a 6056-gene signature of the human TB granuloma and a list of genes of interest gathering the total-RNA expression of the main pathophysiological traits of the cohort. The proposed platform of circulant biomarkers and its genes should be further validated and assessed in other active TB patients to confirm the potential use as a prognostic tool.Universitat Autònoma de Barcelona. Programa de Doctorat en Microbiologi

    Impact of adjuvant therapeutic surgery on the health-related quality of life of pulmonary tuberculosis patients

    No full text
    Altres ajuts: This study was funded by the Spanish Government-FEDER Funds through CV contracts CP13/00174, CPII14/00021 and PI16/01511 grant; the "CIBER Enfermedades Respiratorias" Network (CIBERES); the "Spanish Society of Pneumology and Thoracic Surgery" (SEPAR) through grant 16/023; and the "Agència de Gestió d'Ajuts Universitaris i de Recerca" (AGAUR) through AD contract (2017 FI_B_00797).This study aimed to determine the health-related quality of life (HRQoL) of patients with pulmonary tuberculosis (TB) and to assess its change after a therapeutic surgical procedure. In this scenario, the purpose was to elucidate and quantify the effect of various demographic, epidemiological, clinical, surgical and psychosocial details on this variable. A prospective cohort of 40 patients undergoing therapeutic surgery for pulmonary TB (Study of Human Tuberculosis Lesions (SH-TBL) cohort) was recruited in Tbilisi, Georgia, between 2016 and 2018. HRQoL was assessed by administering the St George's Respiratory Questionnaire (SGRQ) and a novel psychosocial questionnaire, the BCN-Q, both at baseline and at 6 months post-surgery. A statistically and clinically significant improvement in the SGRQ total score was observed at follow-up, although it did not reach the values found for the healthy population. The differences between time points were statistically significant for the following groups: women, age <40 years, body mass index ≥20 kg·m −2, nonsmokers, drug-susceptible and drug-resistant participants, both new and relapsed patients, early culture negativisation, cases with a single lesion, either lesions <35 mm or ≥35 mm, and lesion, lobe and lung resections. The analysis of BCN-Q together with the SGRQ showed that several of its items, such as marital status, living conditions, nutrition, employment, external support, certain attitudes towards the healthcare system, emotional burden and sleep troubles, can impact HRQoL. These results highlight the benefit of adjuvant therapeutic surgery for pulmonary TB in selected patients in terms of HRQoL and suggest that a comprehensive approach including demographic, epidemiological, clinical and psychosocial variables may more accurately predict TB evolution and prognosis. Adjuvant therapeutic surgery in selected pulmonary TB patients improves their health-related quality of life. Impact of psychosocial variables on HRQoL may be assessed using a newly developed questionnaire, namely BCN-Q

    Retrospective study of clinical and lesion characteristics of patients undergoing surgical treatment for Pulmonary Tuberculosis in Georgia

    No full text
    Objectives: Our aim was to retrospectively compare clinical data and characteristics of removed lesions of the cohort of patients undergoing therapeutical surgery for their tuberculosis. Design and methods: Demographic and epidemiological details, clinical data, data on the surgery performed, macroscopic characteristics of the TB lesions removed, and outcome were recorded retrospectively from the 137 patients who underwent therapeutical surgery for their TB in Tbilisi, Georgia during 2014 and 2015. Results: Men represented 70% of the included patients, presented more comorbidities and underwent operation earlier in terms of days between diagnostic and surgery. Women underwent operation at younger ages, and in MDR/XDR-TB cases, showed higher percentages of sputum conversion at >2 months and of fresh necrosis in the surgical specimens, suggesting a worse evolution. Half of cases were MDR/XDR-TB cases. In spite of being considered microbiologically cured according to WHO, a non despricable percentage of cases showed viable bacilli in the surgical specimen. Even if no causality could be statistically demonstrated, differences could be encountered according to gender and drug susceptibility of the responsible strains. Conclusions: According to our results, host factors such as gender, type of necrosis found in the lesions, size of lesions and presence of viable bacilli in the surgical specimen, should be included in future studies on therapeutical surgery of TB. As most of studies are done in MDR/XDR-TB, more data on DS-TB operated cases are needed. Our results also highlight that, in spite of achieving the microbiologically cured status, sterilization might not occur, and thus new biomarkers and new methods to evaluate the healing process of TB patients are urgently needed and radiological assays should be taken into account

    Retrospective study of clinical and lesion characteristics of patients undergoing surgical treatment for Pulmonary Tuberculosis in Georgia

    No full text
    Altres ajuts: This work was supported by CIBER Enfermedades Respiratorias (CB06/06/0031); and the SEPAR trough Project 2016/023.Our aim was to retrospectively compare clinical data and characteristics of removed lesions of the cohort of patients undergoing therapeutical surgery for their tuberculosis. Demographic and epidemiological details, clinical data, data on the surgery performed, macroscopic characteristics of the TB lesions removed, and outcome were recorded retrospectively from the 137 patients who underwent therapeutical surgery for their TB in Tbilisi, Georgia during 2014 and 2015. Men represented 70% of the included patients, presented more comorbidities and underwent operation earlier in terms of days between diagnostic and surgery. Women underwent operation at younger ages, and in MDR/XDR-TB cases, showed higher percentages of sputum conversion at >2 months and of fresh necrosis in the surgical specimens, suggesting a worse evolution. Half of cases were MDR/XDR-TB cases. In spite of being considered microbiologically cured according to WHO, a non despricable percentage of cases showed viable bacilli in the surgical specimen. Even if no causality could be statistically demonstrated, differences could be encountered according to gender and drug susceptibility of the responsible strains. According to our results, host factors such as gender, type of necrosis found in the lesions, size of lesions and presence of viable bacilli in the surgical specimen, should be included in future studies on therapeutical surgery of TB. As most of studies are done in MDR/XDR-TB, more data on DS-TB operated cases are needed. Our results also highlight that, in spite of achieving the microbiologically cured status, sterilization might not occur, and thus new biomarkers and new methods to evaluate the healing process of TB patients are urgently needed and radiological assays should be taken into account
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