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

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

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

Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections

11 páginas, 5 figuras, 1 tablaPolyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples.The authors were supported by projects SAF2016-77346-R and PID2019-104477RB-I00 awarded to IC and the grant BES-2017-079656 awarded to MM by the Spanish Ministry of Economy and Competitiveness and Ministry of Science, the ERC project 638553-TBACCELERATE awarded to IC, Spanish Government-FEDER Funds through CV contract CPII18/00031 and grant PI16/01511, and Generalitat Valencia Grant to I.C. (code PROMETEO/2020/012). The grant providers played no part in study design, data collection, and analysis, or the preparation of the manuscript.Peer reviewe

Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development

Nyaditum resae (NR) is a galenic preparation of heat-killed Mycobacterium manresensis (hkMn). This is a new species that belongs to the Mycobacterium fortuitum complex, and it is present in drinking water—thus, regulatorily speaking, it is considered a food supplement. Preclinical studies in the murine model of active tuberculosis (TB) in the C3HeB/FeJ strain have demonstrated that daily administration of NR containing 103–106 hkMn for 14 days was able to stop the progression toward active TB [1]. The mechanism of action was linked to the induction of low dose tolerance and was related to the increase of Tuberculin Purified Protein Derivative (PPD) memory-specific Tregs (CD4+CD25+CD39+ cells) after ex vivo incubation of splenocytes for 7 days. This increase of Tregs was related to the increase of interleukin (IL)-10 in the spleen and in the reduction of IL-17 in the lungs, where there was also a reduction in bacillary load and the pathology caused by a reduction of neutrophiles' infiltration [2]. Two randomized, double-blind placebo-controlled clinical trials (CTs) have been conducted in humans. The NYADATREG study (Clinicaltrials.gov identifier NCT02076139; 2013–2014) was aimed to evaluate the safety and the immunogenicity of two concentrations of NR (containing 104 hkMn and 105 hkMn) versus placebo (all administered orally everyday for 14 days) in tuberculin-positive and tuberculin-negative volunteers (total n = 51). The results demonstrated an excellent safety record, with no differences between groups in terms of adverse effects. A significant increase in PPD-specific memory regulatory T cells was also detected in both NR groups [3]. The NYADAPETRICS study (Clinicaltrials.gov identifier NCT02581579) is evaluating the safety and immunogenicity of NR 105 hkMn (capsule format, orally) in the pediatric population. Currently, an efficacy study (randomized, double-blinded, placebo-controlled CT) is being conducted in Georgia. This NYADAGEORG trial includes close contacts of active TB cases with positive sputum not tributaries of chemoprophylaxis (<5-year-old children and HIV-positive individuals), which will receive NR (containing 105 hkMn) or placebo (orally, every day for 14 days). A total of 3300 participants will be recruited in four medical centers around Tbilissi. The participants are monitored by telephone for up to 2 years to evaluate the incidence of active TB. The hypothesis is that the NR group will exhibit a 40% reduction in expected TB incidence. Thus, the anticipated TB incidence will be 3% in the NR group versus 5% in the placebo group. The CT is projected to end by 2021 (Clinicaltrials.gov identifier NCT02897180). The administration of the food supplement NR appears to be a new, easy, safe, and reliable method for reducing the risk of developing active TB, and new CTs must be encouraged to discern the particular efficacy power according to different population characteristics

High percentage of mixed infections in a high MDR-TB country identified from lung surgery samples

Trabajo presentado en Applied Bioinformatics and Public Health Microbiology Cambridge, UK, 5-7 June 201

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

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

Hepatitis C virus co-infection increases the risk of anti-tuberculosis drug-induced hepatotoxicity among patients with pulmonary tuberculosis.

The country of Georgia has a high prevalence of tuberculosis (TB) and hepatitis C virus (HCV) infection.To determine whether HCV co-infection increases the risk of incident drug-induced hepatitis among patients on first-line anti-TB drug therapy.Prospective cohort study; HCV serology was obtained on all study subjects at the time of TB diagnosis; hepatic enzyme tests (serum alanine aminotransferase [ALT] activity) were obtained at baseline and monthly during treatment.Among 326 study patients with culture-confirmed TB, 68 (21%) were HCV co-infected, 14 (4.3%) had chronic hepatitis B virus (HBV) infection (hepatitis B virus surface antigen positive [HBsAg+]), and 6 (1.8%) were HIV co-infected. Overall, 19% of TB patients developed mild to moderate incident hepatotoxicity. In multi-variable analysis, HCV co-infection (adjusted Hazards Ratio [aHR]=3.2, 95% CI=1.6-6.5) was found to be an independent risk factor for incident anti-TB drug-induced hepatotoxicity. Survival analysis showed that HCV co-infected patients developed hepatitis more quickly compared to HCV seronegative patients with TB.A high prevalence of HCV co-infection was found among patients with TB in Georgia. Drug-induced hepatotoxicity was significantly associated with HCV co-infection but severe drug-induced hepatotoxicity (WHO grade III or IV) was rare

Pulmonary function and respiratory health after successful treatment of drug-resistant tuberculosis

Background: Post-treatment morbidity among subjects with drug-resistant tuberculosis (DR-TB) is unclear. Methods: This was a cross-sectional study of patients from Tbilisi, Georgia with cavitary DR-TB and an outcome of cure. Participants had a chest X-ray (CXR), St. George Respiratory Quality (SGRQ) survey, and pulmonary function tests (PFTs) performed. Correlations between SGRQ and PFT results and factors associated with pulmonary impairment were examined. Results: Among 58 subjects (median age 31 years), 40% used tobacco, 59% had prior TB, and 47% underwent adjunctive surgical resection. The median follow-up time was 41 months. Follow-up CXR revealed fibrosis in 30 subjects (52%) and bronchiectasis in seven (12%). The median forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio was 0.72, with 24 subjects (41%) having a ratio of ≤0.70. Significant correlations existed between PFT measures and overall and component SGRQ scores. In linear regression, age, prior TB, and CXR fibrosis or bronchiectasis were significantly associated with decreased pulmonary function. Adjunctive surgery was significantly associated with a higher percent predicted FEV1 and FVC. Conclusions: A high proportion of DR-TB subjects had residual pulmonary impairment, particularly with recurrent TB and severe radiological disease. The association of surgical resection with improved lung function deserves further study. PFTs and SGRQ may both be useful to evaluate lung health. Keywords: St. George Respiratory Quality survey, Lung health, Tuberculosis, Impairment, Pulmonary function, Surger

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

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