Human nasal microbiota shifts in healthy and chronic respiratory disease conditions.

BACKGROUND: An increasing number of studies investigate various human microbiotas and their roles in the development of diseases, maintenance of health states, and balanced signaling towards the brain. Current data demonstrate that the nasal microbiota contains a unique and highly variable array of commensal bacteria and opportunistic pathogens. However, we need to understand how to harness current knowledge, enrich nasal microbiota with beneficial microorganisms, and prevent pathogenic developments. RESULTS: In this study, we have obtained nasal, nasopharyngeal, and bronchoalveolar lavage fluid samples from healthy volunteers and patients suffering from chronic respiratory tract diseases for full-length 16 S rRNA sequencing analysis using Oxford Nanopore Technologies. Demographic and clinical data were collected simultaneously. The microbiome analysis of 97 people from Lithuania suffering from chronic inflammatory respiratory tract disease and healthy volunteers revealed that the human nasal microbiome represents the microbiome of the upper airways well. CONCLUSIONS: The nasal microbiota of patients was enriched with opportunistic pathogens, which could be used as indicators of respiratory tract conditions. In addition, we observed that a healthy human nasal microbiome contained several plant- and bee-associated species, suggesting the possibility of enriching human nasal microbiota via such exposures when needed. These candidate probiotics should be investigated for their modulating effects on airway and lung epithelia, immunogenic properties, neurotransmitter content, and roles in maintaining respiratory health and nose-brain interrelationships.

Latent Tuberculosis Infection and Associated Risk Factors among People Living with HIV and HIV-Uninfected Individuals in Lithuania.

BACKGROUND: People living with HIV (PLHIV) with latent tuberculosis infection (LTBI) are at increased risk of tuberculosis (TB) reactivation compared to the HIV-negative population. Lithuania belongs to the 18 high-priority TB countries in the European region. The aim of this study was to compare the prevalence of LTBI and LTBI-related risk factors between PLHIV and HIV-uninfected populations. METHODS: A cross-sectional study was conducted in three Lithuanian Infectious Diseases centres from August 2018 to May 2022 using the interferon gamma release assay (IGRA) and tuberculin skin test (TST) in Vilnius, and IGRA only in Siauliai and Klaipeda. Cohen's kappa was used to assess IGRA and TST agreement. A structured questionnaire was completed by the study participants. LTBI-related risk factors were identified using a multivariable logistic regression model. RESULTS: In total, 391 PLHIV and 443 HIV-uninfected individuals enrolled, with a median age of 41 (IQR 36-48) and 43 (IQR 36-50), consisting of 69.8% and 65.5% male, respectively. The prevalence of LTBI defined by positive IGRA and/or TST among PLHIV was higher compared to that in the HIV-uninfected population (20.5% vs. 15.3%; OR 1.42; 95% CI 1.02-2.03; p = 0.04). The concordance between IGRA and TST was fair: kappa = 0.23 (95% CI 0.09-0.34). In multivariable analyses, association with injecting drug use (IDU) (ORa 2.25, 95% CI 1.27-3.99, p = 0.01) and imprisonment (ORa 1.99, 95% CI 1.13-3.52, p = 0.02) in all participants, IDU (ORa 2.37, 95% CI 1.09-5.15; p = 0.029) in PLHIV and a history of contact with an active TB patient (ORa 3.33, 95% CI 1.53-7.24; p = 0.002) in HIV-uninfected individuals were significant associations evidenced by LTBI. CONCLUSIONS: The prevalence of LTBI among PLHIV in Lithuania is higher compared to that in the HIV-uninfected population and the European average. The association with IDU in PLHIV emphasizes the need for integrated HIV, TB and substance abuse treatment to provide patient-centred care.

Lymphocyte Subsets and Pulmonary Nodules to Predict the Progression of Sarcoidosis.

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes)-blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

The socio-demographic, clinical characteristics and outcomes of tuberculosis among HIV infected adults in Lithuania: A thirteen-year analysis.

BACKGROUND: Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania. METHODS: A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression. RESULTS: The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome. CONCLUSIONS: In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.

Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study.

OBJECTIVES: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.

Human airway and lung microbiome at the crossroad of health and disease (Review).

The evolving field of the microbiome and microbiota has become a popular research topic. The human microbiome is defined as a new organ and is considered a living community of commensal, symbiotic and pathogenic microorganisms within a certain body space. The term 'microbiome' is used to define the entire genome of the microbiota. Bacteria, archaea, fungi, algae and small protists are all members of the microbiota, followed by phages, viruses, plasmids and mobile genetic elements. The composition, heterogeneity and dynamics of microbiomes in time and space, their stability and resistance, essential characteristics and key participants, as well as interactions within the microbiome and with the host, are crucial lines of investigation for the development of successful future diagnostics and therapies. Standardization of microbiome studies and harmonized comparable methodologies are required for the transfer of knowledge from fundamental science into the clinic. Human health is dependent on microbiomes and achieved by nurturing beneficial resident microorganisms and their interplay with the host. The present study reviewed scientific knowledge on the major components of the human respiratory microbiome, i.e. bacteria, viruses and fungi, their symbiotic and parasitic roles, and, also, major diseases of the human respiratory tract and their microbial etiology. Bidirectional relationships regulate microbial ecosystems and host susceptibility. Moreover, environmental insults render host tissues and microbiota disease-prone. The human respiratory microbiome reflects the ambient air microbiome. By understanding the human respiratory microbiome, potential therapeutic strategies may be proposed.

Predictors of Noninvasive Respiratory Support Failure in COVID-19 Patients: A Prospective Observational Study.

Background and Objective: Respiratory assistance tactic that is best for COVID-19-associated acute hypoxemic respiratory failure (AHRF) individuals has yet to be determined. Patients with AHRF may benefit from the use of a high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The goals of this prospective observational research were to estimate predictive factors for HFNC and NIV failure in COVID-19-related AHRF subjects. Materials and Methods: The research enlisted the participation of 124 patients. A stepwise treatment approach was used. HFNC and NIV were used on 124 (100%) and 64 (51.6%) patients, respectively. Thirty (24.2%) of 124 patients were intubated and received invasive mechanical ventilation. Results: 85 (68.5%) patients were managed successfully. Patients who required NIV exhibited a higher prevalence of treatment failure (70.3% vs. 51.6%, p = 0.019) and had higher mortality (59.4% vs. 31.5%, p = 0.001) than patients who received HFNC. Using logistic regression, the respiratory rate oxygenation (ROX) index at 24 h (odds ratio (OR) = 0.74, p = 0.018) and the Charlson Comorbidity Index (CCI) (OR = 1.60, p = 0.003) were found to be predictors of HFNC efficacy. It was the ROX index at 24 h and the CCI optimum cut-off values for HFNC outcome that were 6.1 (area under the curve (AUC) = 0.73) and 2.5 (AUC = 0.68), respectively. Serum ferritin level (OR = 0.23, p = 0.041) and lymphocyte count (OR = 1.03, p = 0.01) were confirmed as predictors of NIV failure. Serum ferritin level at a cut-off value of 456.2 ng/mL (AUC = 0.67) and lymphocyte count lower than 0.70 per mm3, (AUC = 0.70) were associated with NIV failure with 70.5% sensitivity, 68.7% specificity and sensitivity of 84.1%, specificity of 56.2%, respectively. Conclusion: The ROX index at 24 h, CCI, as well as serum ferritin level, and lymphocyte count can be used as markers for HFNC and NIV failure, respectively, in SARS-CoV-2-induced AHRF patients.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study.

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Age as a Risk Factor in the Occurrence of Complications during or after Bronchoscopic Lung Biopsy.

INTRODUCTION: Bronchoscopic lung biopsy (BLB) is a widely used procedure. As the world's population is ageing, more BLBs are performed for older people with comorbidities. The aim of the study was to investigate if an older age is a risk factor for BLB related complications. MATERIALS AND METHODS: A prospective study at the Centre of Pulmonology and Allergology of Vilnius University Hospital Santaros klinikos was conducted. Seven hundred and eighty-six patients (male 60.6%), mean age 57 ± 16, who underwent BLB, were included. The complications that occurred due to BLB were evaluated. Bleeding and pneumothorax were classified into I° or II° grades depending on their severity. Potential determinants, which may increase the risk of complications, emphasizing on age, were analyzed. RESULTS: Fifty-seven (7.2%) BLB-related complications occurred. There were 27 (3.4%) pneumothoraxes, and 19 (70%) of them required thoracic drainage. Thirty (3.8%) bleeding complications occurred, and four (16%) of them were severe. Higher rates of bleeding were found in the age group ≥65 years, p = 0.001. The risk of bleeding in older patients was 3.2 times higher (95% CI 1.51-6.87). CONCLUSIONS: Older age is related to a higher incidence of mild bleeding during BLB. However, the risk of life-threatening complications is low despite the age, and older age should not be considered as a contraindication for the procedure if needed.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) Comorbidities in Lithuanian National Database: A Cluster Analysis.

Various comorbidities and multimorbidity frequently occur in chronic obstructive pulmonary disease (COPD), leading to the overload of health care systems and increased mortality. We aimed to assess the impact of COPD on the probability and clustering of comorbidities. The cross-sectional analysis of the nationwide Lithuanian database was performed based on the entries of the codes of chronic diseases. COPD was defined on the code J44.8 entry and six-month consumption of bronchodilators. Descriptive statistics and odds ratios (ORs) for associations and agglomerative hierarchical clustering were carried out. 321,297 patients aged 40-79 years were included; 4834 of them had COPD. A significantly higher prevalence of cardiovascular diseases (CVD), lung cancer, kidney diseases, and the association of COPD with six-fold higher odds of lung cancer (OR 6.66; p < 0.0001), a two-fold of heart failure (OR 2.61; p < 0.0001), and CVD (OR 1.83; p < 0.0001) was found. Six clusters in COPD males and five in females were pointed out, in patients without COPD-five and four clusters accordingly. The most prevalent cardiovascular cluster had no significant difference according to sex or COPD presence, but a different linkage of dyslipidemia was found. The study raises the need to elaborate adjusted multimorbidity case management and screening tools enabling better outcomes.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study / Medidas de confinamento específicas de cada país em resposta à pandemia de COVID-19 e seu impacto no controle da tuberculose: um estudo global

ABSTRACT The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

RESUMO O objetivo deste estudo foi descrever as medidas de confinamento específicas de cada país e os indicadores de tuberculose coletados durante o primeiro ano da pandemia de COVID-19. Dados referentes a confinamento/restrições sociais (uso obrigatório de máscaras faciais e higiene obrigatória das mãos; restrições a viagens internacionais e locais; restrições a visitas familiares e fechamento das escolas) foram coletados de 24 países em cinco continentes. A maioria dos países implantou múltiplos confinamentos, com reabertura parcial ou total. Houve uma redução geral dos casos de tuberculose ativa, tuberculose resistente e tuberculose latente. Embora os confinamentos nacionais tenham sido eficazes na contenção dos casos de COVID-19, vários indicadores de tuberculose foram afetados durante a pandemia.

Risk factors for complicated community-acquired pneumonia course in patients treated with ß-lactam monotherapy.

INTRODUCTION: We aimed to investigate community-acquired pneumonia (CAP) requiring hospitalisation, empirically treated with b-lactam monotherapy, with 30-day mortality and risk factors predicting its complicated course. MATERIAL AND METHODS: A prospective observational study was conducted at the Pulmonology and Allergology Department in a tertiary care university hospital. 253 consecutive patients diagnosed with CAP requiring hospitalisation were enrolled. Hospital admission was based on PSI or CRB-65 scores, severe comorbidities, signs of intoxication, aspiration risk, social risk consider-ations, ineffective prior antibiotic treatment. RESULTS: Fourty seven percent of the subjects had complications on admission, 13% developed new CAP complications during inpatient treatment. Overall, 53% of individuals had a complicated CAP course. 30-day mortality rate was 5.9%. The factors predicting a complicated CAP course were as follows: neuromuscular disease, multilobar opacities on chest X-ray (or computed tomography), and clinically unstable condition as evaluated using Halm's criteria. CONCLUSIONS: The mortality rate in CAP patients treated with b-lactam monotherapy is low. Neuromuscular disease, multilobar opacities, and clinically unstable condition as evaluated using Halm's criteria predict a complicated CAP course.

Systemic Inflammatory Response to Different Sclerosing Agents as a Predictor of Pleurodesis Outcome.

BACKGROUND/AIM: The objectives of this study were to evaluate systemic inflammation using different sclerosing agents and to estimate the prediction of systemic inflammation for the efficacy of pleurodesis. PATIENTS AND METHODS: Ninety-six patients with recurrent and symptomatic malignant pleural effusion were enrolled in this retrospective study. We used serum C-reactive protein (CRP) levels, serum leukocyte counts and neutrophil-to-lymphocyte ratios (NLRs) as parameters of systemic inflammatory reactions. Evaluations of these parameters were performed before and 24 h after pleurodesis. RESULTS: Pleurodesis was successful in 81 (84.4%) patients. The non-graded talc induced the highest changes in serum CRP levels, total white blood cell and neutrophil counts compared to other agents, while mitoxantrone induced the lowest. Graded talc and bleomycin induced the same levels of changes in serum CRP levels and serum leukocyte counts. The change in serum NLR was the same for all agent groups. Logistic regression confirmed that a change in serum CRP levels [odds ratio (OR)=0.92, p=0.002] and previous chemotherapy (OR=3.31, p=0.012) were independent predictors of pleurodesis efficacy. CONCLUSION: Pleurodesis agents induced a systemic inflammatory response at different levels. The change in serum CRP levels could be useful for predicting the success of pleurodesis.

CD31+, CD38+, CD44+, and CD103+ lymphocytes in peripheral blood, bronchoalveolar lavage fluid and lung biopsy tissue in sarcoid patients and controls.

BACKGROUND: The mechanisms driving the transition from inflammation to fibrosis in sarcoidosis patients are poorly understood; prognostic features are lacking. Immune cell profiling may provide insights into pathogenesis and prognostic factors of the disease. This study aimed to establish associations in simultaneous of lymphocyte subset profiles in the blood, bronchoalveolar lavage fluid (BALF), and lung biopsy tissue in the patients with newly diagnosed sarcoidosis. METHODS: A total of 71 sarcoid patients (SPs) and 20 healthy controls (HCs) were enrolled into the study. CD31, CD38, CD44, CD103 positive T lymphocytes in blood and BALF were analysed. Additionally, the densities of CD4, CD8, CD38, CD44, CD103 positive cells in lung tissue biopsies were estimated by digital image analysis. RESULTS: Main findings: (I) increase of percentage of CD3+CD4+CD38+ in BALF and blood, and increase of percentage of CD3+CD4+CD44+ in BALF in Löfgren syndrome patients comparing with patients without Löfgren syndrome, (II) increase of percentage of CD3+CD4+103+ in BALF and in blood in patients without Löfgren syndrome (comparing with Löfgren syndrome patients) and increase of percentage of CD3+CD4+103+ in BALF and in blood in more advanced sarcoidosis stage. (III) Increasing percentage of BALF CD3+CD4+CD31+ in sarcoidosis patients when comparing with controls independently of presence of Löfgren syndrome, smoking status or stage of sarcoidosis. Several significant correlations were found. CONCLUSIONS: Lymphocyte subpopulations in blood, BALF, and lung tissue were substantially different in SPs at the time of diagnosis compared to HCs. CD3+CD4+CD31+ in BALF might be a potential supporting marker for the diagnosis of sarcoidosis. CD3+CD4+CD38+ in BALF and blood and CD3+CD4+CD44+ in BALF may be markers of the acute immune response in sarcoidosis patients. CD4+CD103+ T-cells in BALF and in blood are markers of the persistent immune response in sarcoidosis patients and are potential prognostic features of the chronic course of this disease.

Evaluation of Obstructive Sleep Apnea Phenotypes Treatment Effectiveness.

Background and Objective: Obstructive sleep apnea (OSA) is a heterogeneous chronic sleep associated disorder. A common apnea-hypopnea index (AHI)-focused approach to OSA severity evaluation is not sufficient enough to capture the extent of OSA related risks, it limits our understanding of disease pathogenesis and may contribute to a modest response to conventional treatment. In order to resolve the heterogeneity issue, OSA patients can be divided into more homogenous therapeutically and prognostically significant groups-phenotypes. An improved understanding of OSA phenotype relationship to treatment effectiveness is required. Thus, in this study several clinical OSA phenotypes are identified and compared by their treatment effectiveness. Methods and materials: Retrospective data analysis of 233 adult patients with OSA treated with continuous positive airway pressure (CPAP) was performed. Statistical analysis of data relating to demographic and anthropometric characteristics, symptoms, arterial blood gas test results, polysomnografic and respiratory polygraphic tests and treatment, treatment results was performed. Results: 3 phenotypes have been identified: "Position dependent (supine) OSA" (Positional OSA), "Severe OSA in obese patients" (Severe OSA) and "OSA and periodic limb movements (PLM)" (OSA and PLM). The highest count of responders to treatment with CPAP was in the OSA and PLM phenotype, followed by the Positional OSA phenotype. Treatment with CPAP, despite the highest mean pressure administered was the least effective among Severe OSA phenotype. Conclusions: Different OSA phenotypes vary significantly and lead to differences in response to treatment. Thus, treatment effectiveness depends on OSA phenotypes and treatment techniques other than CPAP may be needed. This emphasizes the importance of a more individualized approach when treating OSA.

Case of Severe Treatment-Resistant Cryptogenic Organizing Pneumonia.

Cryptogenic organizing pneumonia is a rare interstitial lung disease with different onset of symptoms, which responds rapidly to glucocorticoid treatment. We present a case of cryptogenic organizing pneumonia which manifested as a progressive 3-year dyspnea that ultimately has led to acute respiratory failure. Moreover, treatment with prednisone for this patient exhibited slow onset of the effect.

Incidence of Tuberculosis in Inflammatory Rheumatic Diseases: Results from a Lithuanian Retrospective Cohort Study.

Background and objective: With an increase in survival rates among rheumatic patients, comorbidities and infections, in particular, have gained more importance, especially after the introduction of biologicals to the treatment algorithms. Tuberculosis (TB) infection has always been given a special attention in patients with rheumatic diseases (RD). Although Lithuanian population has one of the highest TB incidence rates among European countries, the incidence of TB in the rheumatic patients' population is still unknown. The aim of this study was to assess the incidence rate of TB in an inflammatory RD retrospective cohort and to compare that rate with a rate in a general population. Methods: Patients with the first-time diagnosis of inflammatory RD during the period between 1 January 2012 and 31 December 2017 were identified from the Lithuanian Compulsory Health Insurance Information System database SVEIDRA. All cases were cross-checked with Health Information center at the Institute of Hygiene, for the vital status of these patients and date of death if the fact of death was documented, and with Tuberculosis Register operated by Vilnius University Hospital Santaros Klinikos, for the confirmation of TB cases. Sex and age standardized incidence ratios (SIR) were calculated by dividing the observed numbers of TB among rheumatic patients by the expected number of cases, calculated using national rates from Lithuanian Department of Statistics Official Statistics website. Results: Overall, 8779 patients with newly diagnosed RD were identified during the 2013-2017 period, these included 458 patients who used biological disease modifying drugs (bDMARDs). The mean duration of the follow-up period was 2.71 years. The cohort consisted mainly of women (70%) and a half of the cohort were rheumatoid arthritis (RA) patients (53%). Mean age of patients at the time of RD diagnosis was 56 years (range = 18-97 years). There were 9 TB cases identified during 23,800 person years of follow-up: 2 cases among them were treated with bDMARDs. The mean calculated annual TB incidence in RD cohort was 37.81 per 100,000 person years, which is consistent with the incidence rate predicted by national estimates, with a resultant SIR of 0.90 (0.41-1.70). The unadjusted hazard ratio for bDMARD use versus no bDMARD use was 4.54 (0.94; 21.87) in a total cohort and very similar in rheumatoid arthritis cohort; in both cohorts, it was not a statistically significant risk. Conclusions: Here, we present the first nationwide cohort study to assess the incidence of TB in a broad spectrum of inflammatory RD. Although limited by short follow-up period, this study shows that TB incidence in RD cohort does not exceed TB incidence in the general Lithuanian population.

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer.

We evaluated the effect of antihyperglycemic therapy on the survival of patients with lung cancer (LC). The analysis included patients with LC and concomitant type 2 diabetes. 15,929 patients were classified into five groups: metformin users, insulin users, metformin and insulin users, sulphonylurea users and non-diabetic group. A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72-92 for metformin and HR 0.65, 95% CI 0.44-95 for insulin). When deaths from all causes were considered, only metformin exposure was associated with a significantly lower risk of death (HR 0.82, 95% CI 0.73-0.92). Users of sulphonylurea were at a higher risk of LC-specific and overall mortality (HRs 1.19, 95% CI 0.99-1.43 and 1.22, 95% CI 1.03-1.45). Our study shows a positive effect of metformin on the survival of patients with LC. Moreover, our results show that exposure to insulin was associated with a lower risk of LC-specific mortality, but not with deaths from all causes. The study results suggested that users of sulphonylurea may be at a higher risk of LC-specific and overall mortality.