The need of biomarkers predicting the course of MTB infection, and the necessity of specific therapy, is well recognized. We measured the induced expression of effector and regulatory cytokines ...IFN-γ, TNF-α, IL-2, IL-17, IL-6, IL-10 in relation to the lipid mediators PGE2 and LXA4 in: active TB infection (ATB, n=15) before and after therapy (ATB-T, n=6); established latent infection (LTBI, n=22), recent contacts of ATB (RC, n=12); and healthy controls (n=11) A flow cytometry microarray (CBA, BD Biosciences) and quantitative ELISA (SunRed Tech.) were employed. RC were characterized by a high potential for IL-17 and Th1 cytokine secretion, combined with low IL-6 expression, while ATB donors had a partially preserved TNF-α potential, and higher IL-6 expression. PGE2 /LXA4 ratio discriminated between situations with high bacterial load (ATB), and contained infection (LTBI, ATB-T), and defined clearly-cut subgroups among RC and ATB donors. Our results propose that increased PGE2/LXA4 ratio coupled with high induced IL-10 level indicates infection after a recent contact. In the settings of ATB, increased ratio and low TNF-α level point to inefficient granuloma formation in the settings of ATB.
Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An underlying lung disease or immune ...deficiency is a prerequisite for clinical manifestation. However, disseminated MAC disease primarily manifests in people living with human immunodeficiency virus (HIV) in the severe immunodeficiency stage with a whole host of clinical symptoms. We present two cases of disseminated M. avium infection in people living with HIV in the stage of severe immunodeficiency. Both patients exhibited distinct disease progression, with the absence of pulmonary symptoms being a common characteristic. The first patient predominantly experienced high fever, accompanied by diarrhea and severe anemia. The normothermia in the second patient was incongruent with the presence of marked cachexia, severe abdominal pain, and magnetic resonance imaging evidence of abdominal lymph node involvement. The causative agent was isolated from both sputum and stools. The patients underwent treatment that comprised aminoglycoside, macrolide, ethambutol, and rifampicin. Although both patients achieved optimal viral suppression of HIV, the immunologic response to antiretroviral therapy was suboptimal. The first patient died in the setting of severe immunodeficiency due to the development of decompensated liver cirrhosis, while the second patient demonstrated a slight reverse course of the disease.
Isoniazid (H; INH) is an important first-line drug for the treatment of active tuberculosis (TB) and latent TB infection because of its potent early bactericidal activity against Мycobacterium ...tuberculosis. Currently, TB resistant to INH, alone or in combination with other drugs, is the most common type of drug-resistant TB. Epidemiology of INH-resistant TB, the molecular mechanisms of drug resistance, current methods for diagnosis and therapeutic regimens of this TB form are presented. Studies in the last years have shown that resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other important first-line drugs. Based on the most recent meta-analyses, the last WHO recommendations for treatment of INH-resistant TB are to include rifampicin (RIF), ethambutol, pyrazinamide and levofloxacin for 6 months, and not to add streptomycin or other injectable agents to the drug regimen. The guideline emphasizes the importance of excluding resistance to RIF before starting the regimen for INH-resistant TB because of the risk for development of multidrug-resistant TB during the treatment course. The WHO recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty in the estimates of effect. Therefore, further work is needed to optimize the treatment and control of INH-resistant TB.
In recent years, there has been a revolution in the genomic profiling and molecular typing of lung cancer. A key oncogene is the epidermal growth factor receptor (EGFR). The gold standard for ...determining EGFR mutation status is tissue biopsy, where a histological specimen is taken by a bronchoscopic or surgical method (transbronchial biopsy, forceps biopsy, etc.). However, in clinical practice the tissue sample is often insufficient for morphological and molecular analysis. Bronchoalveolar lavage is a validated diagnostic method for pathogenic infections in the lower respiratory tract, yet its diagnostic value for oncogenic mutation testing in lung cancer has not been extensively investigated. This study aims to compare the prevalence of EGFR mutation status in bronchoalveolar lavage and peripheral blood referring to the gold standard - tissue biopsy in patients with primary lung adenocarcinoma.
Twenty-six patients with adenocarcinoma were examined for EGFR mutation from tissue biopsy, peripheral blood sample and bronchoalveolar lavage.
Thirteen patients had wild type EGFR and the other 13 had EGFR mutation. EGFR mutation from a peripheral blood sample was identified in 38.5% (5/13) of patients, whereas EGFR mutation obtained from bronchoalveolar lavage (BAL) was identified in 92.3% (12/13). This study demonstrates that a liquid biopsy sample for EGFR status from BAL has a higher sensitivity compared to a venous blood sample.
Background: Each year, approximately two million adolescents and young adults in the world become infected with tuberculosis (TB). The problem is that the classification of the disease includes ...children in the age group 0−14 years and young adults aged 15 and over. The present study aims to analyze and compare the epidemiology and clinical presentation of TB in Bulgaria in the different age subgroups of childhood. Methods: A retrospective study was undertaken of the newly diagnosed children (n = 80) with TB treated onsite from January 2018 to December 2020 at the Multiprofile Hospital for Active Treatment of Pulmonary Diseases (“St. Sofia”). They were distributed into three age groups: aged 8−11 (prepuberty), aged 12−14 (younger adolescents), and aged above 15 (older adolescents). Results: A clear finding of the research indicated that adolescent children develop TB both as primary and secondary infections. In a large number of cases with the children under our care, we found enlarged intrathoracic lymph nodes as well as infiltrative changes in the lungs, i.e., we observed transitional forms. There were statistically significant differences between the age group >15 years old and each of the other two younger groups for diagnosis, the severity of intoxication, and BK spreading status. Conclusion: The course of tuberculosis in adolescence has its own specifics and differences between the three age groups in the current study.
Tuberculosis has a greater impact on morbidity and mortality in HIV-1-infected individuals than the rest of the opportunistic infections. We report a case of 57-year-old HIV-infected patient ...co-infected with multidrug- resistant tuberculosis (MDR-TB). The patient`s leading clinical syndromes were fever, diarrhoea and weight loss. The meticulously performed laboratory investigations revealed severe immune suppression and high HIV viral load. Microbiological and parasitological tests confirmed the presence of two AIDS-defining conditions: disseminated candidiasis and cryptosporidiosis. Sputum smear microscopy for acid-fast bacilli was negative but sputum culture showed positive result for Mycobacterium tuberculosis. Drug susceptibility testing determined resistance to isoniazid and rifampicin (MDR-TB). The diagnosis was confirmed with Xpert-MTB/RIF PCR test. Treatment continued with second-line anti-TB drugs, together with antiretroviral therapy. Culture conversion was recorded in the first month. The outcome was reported as „cured“ after 16 months` therapy. This case shows yet again that the clinical manifestation of tuberculosis in HIV-infected patients is very atypical. Multidrug-resistant tuberculosis requires prolonged treatment and represents therapeutic challenge because of the possibility of adverse drug reactions.
Abstract Objective To analyze determinants of success and death in multidrug-resistant tuberculosis patients (MDR-TB; resistance to, at least, isoniazid and rifampicin) placed on treatment in ...Bulgaria during the period September 2009 to March 2010 using logistic regression. Results Fifty MDR-TB patients started treatment. Male:Female ratio was 2.3:1; mean age 43 years (range: 18–77); 19 patients (38%) were new; median duration of disease before treatment was 5 years (range: 1–13). All patients tested negative for HIV. Eight cases had XDR-TB (MDR-TB plus resistance to any fluoroquinolone and any second-line injectable). Twenty-four months after starting treatment, 24 patients (48%) had a successful outcome, in 6 (12%) treatment failed, 19 (38%) died, and one (2%) interrupted treatment. XDR-TB cases experienced higher mortality than others (75% vs. 30.9%, respectively, P < 0.05). Sputum smear positivity at start of treatment and weight loss or no weight gain were positively associated with death (adjusted Odds ratio: 5.16; 95% confidence interval: 1.16–22.84 and 5.61; 1.48–21.20, respectively) and negatively with success (0.13; 0.02–0.94 and 0.02; 0.00–0.19). No previous TB treatment increased likelihood of success (7.82; 1.09–56.15). Discussion and conclusions Most MDR-TB patients in this first treatment cohort using WHO-recommended norms had advanced disease explaining the high mortality and low success. Early, adequate treatment of MDR-TB patients can improve outcomes and avert transmission.
Last generation IFN gamma – based assays (IGRAs) evaluate bulk CD4 and CD8 T cell responses, and do not discriminate between latent and active Micobacterium tuberculosis (MTB) infection. The ...identification of biomarkers predicting the clinical course and specific therapy effect in latent MTB infection (LTBI) is a major contemporary challenge. Using multicolor flow cytometry, we compared the levels of circulating CD8 and CD4 effector subsets, in relation to the levels of phenotypically defined regulatory subsets, in two groups of age- and sex-matched MTB-infected individuals: clinically and microbiologically confirmed ATB (n=15), and QFT+ stable LTBI (n=15). As compared to LTBI subjects, ATB patients are characterized with decreased proportions of CD4 and CD8 CD45RO+CCR7- effectors (14.6% vs. 24%, and 28% vs. 40%, p <0.05 for both), decreased Th1 (10% vs. 16,5 %) and Th1/Th17 (12,5% vs. 21,5%) effector subsets. These changes are accompanied by a significantly increased share of induced (CD39+) FoxP3+CD4Treg (46% vs. 22.6%, p<0.05). The difference affected mostly the Th17-specific (CD39+CCR6+Treg) subset (10.5% vs 4.8%, p<0.05), which correlated inversely with the level of Th1/Th17 effectors (R= -0.5, p<0.05). In conclusion, we describe a clear-cut distinction between the effector/ regulatory T subset balance in ATB and LTBI. The combined evaluation of Th17Treg and Th1/Th17 effectors in peripheral blood can be employed for MTB-infection monitoring. ACKNOWLEDGMENTS: This work was supported by the Bulgarian National Science Fund (Research Grant ДН 13/1; 14.12.2017)
Smoking as a cause of cancer development has been the subject of research by the International Agency for Research on Cancer (IARC) 1, 2. The highest rates are for lung (up to 90% of cases), oral ...cavity (92%) and larynx (87%) cases 3. Smoking is one of the most important causes in the etiology of lung cancer 3, 4.
The purpose of the study was to determine whether smoking had an effect on the morphological type of lung cancer. One hundred and fifty patients with histologically proven lung cancer by gender, age, smoking experience, and morphology of lung cancer were studied.
The number of men is twice that of women; the highest number of patients is between 40 and 60 years of age. 76.6% of patients are active smokers, 88.6% of them have used cigarettes for more than 10 years, and 59% have smoked more than 20 cigarettes daily. Of the nonsmoking patients, 48.6% are passive smokers.
The distribution by morphological type of lung cancer in smokers indicates that the ratio of squamous type of cancer (59%) is the highest, followed by adenocarcinoma (29.5%), and small cellular cancer (11.3%).
The aim of this study was to analyse temporal changes in treatments for and outcomes of multidrug-resistant (MDR)/rifampin-resistant (RR)-tuberculosis (TB) in the context of national economic ...status.We analysed data collected by the Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB Treatment on MDR/RR-TB patients from 37 countries. The data were stratified by three national income levels (low-/lower-middle, upper-middle and high) and grouped by time of treatment initiation (2001-2003, 2004-2006, 2007-2009, 2010-2012 and 2013-2015). Temporal trends over the study period were analysed. The probability of treatment success in different income groups over time was calculated using generalised linear mixed models with random effects.In total, 9036 patients were included in the analysis. Over the study period, use of group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid) recommended by the World Health Organization increased and treatment outcomes improved in all income groups. Between 2001-2003 and 2013-2015, treatment success rates increased from 60% to 78% in low-/lower-middle-income countries, from 40% to 67% in upper-middle-income countries, and from 73% to 81% in high-income countries. In earlier years, the probability of treatment success in upper-middle-income countries was lower than that in low-/lower-middle-income countries, but no difference was observed after 2010. However, high-income countries had persistently higher probability of treatment success compared to upper-middle income countries.Improved treatment outcomes and greater uptake of group A drugs were observed over time for patients with MDR/RR-TB at all income levels. However, treatment outcomes are still unsatisfactory, especially in upper-middle-income countries.
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