Browsing by Author "Stjepanović, Mihailo (55052044500)"

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients. © 2016 Sociedade Brasileira de Pneumologia e Tisiologia.

Introduction: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. Methodology: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. Results: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Conclusions: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB. © 2022 Journal of Infection in Developing Countries. All rights reserved.

Introduction: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. Methodology: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. Results: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Conclusions: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB. © 2022 Journal of Infection in Developing Countries. All rights reserved.

Background/Aim. Thymoma is the most common mediastinal tumor. The treatment procedures are based on the results from the research of retrospective studies because they are not frequent tumors. The aim of this work was to define common clinical features, therapeutic aspects, survival and recurrence free survival. Methods. This study was performed in the Clinic for Pulmonology, Clinical Centre of Serbia, Belgrade from January 1993 to December 2013. We analyzed 62 patients with histopathologically proven thymoma. The results were obtaind from medical history, physical exam, chest X-ray and/or computed tomography and operational findings or diagnostic procedure reports. Thymomas were clasiffied according to the World Health Organization classifying system, based on histopathological findings, and staged according to the Masaoka-Koga staging system. Results. There were more female (54.8%) patients. Patients were mostly in the seventh decade of life. One third (29%) of the patients were asymptomatic. Cough was the dominant symptom. Myasthenia gravis was the most common paraneoplastic syndrome (12.9%). Solitary tumor was the most common in our patients (61.3%), as well as the tumors larger than 5 cm (52.5%), and noninvasive thymomas (52.5%). The majority of patients (40%) were in the stage I of the disease. The operative approach was conducted in most of the patients (88.7%). A statistically significant difference in survival was in women, patients with solitary tumor, non-invasive thymomas, patients in the stage I of the disease, and those who were operated. The dimension of the tumor mass approached the conventional level of significance. Conclusion. In patients with thymomas, statistically significant survival rate predictors are gender, presence of solitary tumor mass, tumor invasiveness, clinical stage and surgical treatment of the disease. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction: Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. Methodology: This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Results: Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Conclusions: Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity. Copyright © 2024 Belic et al.

Introduction: Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. Methodology: This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Results: Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Conclusions: Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity. Copyright © 2024 Belic et al.

Background and Objectives: Advanced lung cancer is usually manifested by endoluminal tumor propagation, resulting in central airway obstruction. The objective of this study is to compare the high dose rate brachytherapy treatment outcomes in non-small-cell lung cancer (NSCLC) depending on the treatment planning pattern—two-dimension (2D) or three-dimension (3D) treatment planning. Materials and Methods: The study was retrospective and two groups of patients were compared in it (a group of 101 patients who underwent 2D planned high-dose-rate endobronchial brachytherapy (HDR-EBBT) in 2017/18 and a group of 83 patients who underwent 3D planned HDR-EBBT between January 2021 and June 2023). Results: In the group of 3D planned brachytherapy patients, there was a significant improvement in terms of loss of symptoms of bronchial obstruction (p = 0.038), but no improvement in terms of ECOG PS (European Cooperative Oncology Group Performance Status) of the patient (p = 0.847) and loss of lung atelectasis (if there was any at the beginning of the disease) (p = 0.781). Two-year overall survival and time-to-progression periods were similar for both groups of patients (p = 0.110 and 0.154). Fewer treatment complications were observed, and 91.4% were in 3D planned brachytherapy (BT) patients. Conclusions: Three-dimensionally planned HDR-EBBT is a suggestive, effective palliative method for the disobstruction of large airways caused by endobronchial lung tumor growth. Independent or more often combined with other types of specific oncological treatment, it certainly leads to the loss of symptoms caused by bronchial obstruction and the improvement of the quality of life of patients with advanced NSCLC. Complications of the procedure with 3D planning are less compared to 2D planned HDR-EBBT. © 2024 by the authors.

Immune checkpoint inhibitors (ICIs) like atezolizumab have improved outcomes in advanced non-small cell lung cancer (NSCLC) patients, especially in the second-line setting after progression on platinum-based chemotherapy. However, access to ICIs remains limited in many developing nations. This study evaluated the efficacy of atezolizumab as a second-line versus later-line treatment for advanced NSCLC patients in Serbia. Methods: This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. Results: The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0–1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Conclusions: Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions. © 2024 by the authors.

Immune checkpoint inhibitors (ICIs) like atezolizumab have improved outcomes in advanced non-small cell lung cancer (NSCLC) patients, especially in the second-line setting after progression on platinum-based chemotherapy. However, access to ICIs remains limited in many developing nations. This study evaluated the efficacy of atezolizumab as a second-line versus later-line treatment for advanced NSCLC patients in Serbia. Methods: This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. Results: The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0–1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Conclusions: Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions. © 2024 by the authors.

Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients’ treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era. © 2023 by the authors.

Introduction: This is a presentation of a 61-year-old female patient. Since 44 years have passed from the onset of her first symptoms until the final diagnosis of sarcoidosis, this was the reason of our decision to publish the case. Case Outline: During the follow-up period of 44 years the patient had ocassional polymorphic complains, such as adynamia, nausea, abdominal pains, myalgia, arthralgia, body weight loss (8-10 kg) etc. The clinical course was predominated by splenomegaly, hepatitis and arthralgia, and later chronic renal failure also developed. Laboratory findings snowed elevated markers of acute inflammation and autoantibodies. The patient was hospitalized in different university internal hospitals (gastroenterology, allergology, rheumatology, nephrology and pulmology). Liver biopsy was performed three times, rectum and kidney biopsy once each and finally bronchoscopy and pulmonary biopsy was done. At last, about 40 years from the onset of the first symptoms, in 2006 the diagnosis of lung sarcoidosis was established. Conclusion: The final diagnosis of spleen sarcoidosis was confirmed by pathologically verified sarcoidosis of the lungs. This case is particularly interesting because of the presence of familial sarcoidosis (the patient's son also had recurrent pulmonary sarcoidosis).

Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly one-half of patients, and depend on the location in the central nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement. © 2021, Serbia Medical Society. All rights reserved.

[No abstract available]

Introduction Surgery of the primary tumor following extended course of chemoimmunotherapy has only recently been recognized as a feasible and safe option for selected groups of patients with initially unresectable non-small cell lung cancer. Case outline Here we report a case of a 49-year-old female patient, who never smoked, that was diagnosed with metastatic non-small cell lung cancer. Lesions were evident in both lungs and the brain. She underwent stereotactic radiosurgery for brain metastases and combination therapy of chemotherapy, atezolizumab and bevacizumab. Response to therapy was both remarkable and durable. Ten cycles into treatment, magnetic resonance imaging of the brain revealed no metastatic lesions. Positron emission tomography / computed tomography revealed a single lesion in the right upper lobe 22 × 23 mm in diameter. The patient underwent a right upper lobectomy. Pathohistological evaluation of the specimen revealed complete pathologic response. The patient recovered from surgery and continued chemoimmunotherapy. Four months post-surgery she is disease free and of excellent performance status. Conclusion Primary tumor surgery following extensive chemoimmunotherapy regiment is feasible and could be considered as a treatment option. Further research is warranted to define a patient population that stands to benefit the most from this modality. © 2024, Serbia Medical Society. All rights reserved.

Currently, topical are studies that examine different reasons for delay of tuberculosis (TB) diagnosis and its impact on disease prognosis. The aim was to examine three time periods associated with treatment delay: patient related, health system related and total delay. This retrospec-tive-prospective study included 100 consecutive patients hospitalized at Department of Pulmonology, Clinical Center of Serbia, in the period from March to December 2015. Study results showed median patient delay to be 92.5 days. Total delay was affected by patient related delay. Median healthcare delay was 18.5 days. Patients that reported excessive alcohol consumption were more likely to have prolonged time to seek medical help. Years of alcohol consumption yielded moderate positive correlation with patient related delay (r=0.362, p<0.001). Correlation between the number of cigarettes and patient delay was moderate, positive and statistically significant (r=0.314, p=0.001). Delay in seeking medical help was more likely in patients with negative family history of TB. There was no difference in the effect of the presence of symptoms on patient related delay (p>0.05). Clinical characteristics such as patient TB category and chest radiograph abnormalities were not associated with prolonged patient related delay (p>0.05). Study results point to the importance of health education and/or health intervention in the population group at a high risk of TB. © 2018, Klinicka Bolnica Sestre Milosrdnice. All rights reserved.

[No abstract available]

Introduction COVID-19 pneumonia does not have a characteristic course and prognosis. Many facts still remain hidden, mainly why certain patients develop complications with serious tissue damage and whether it causes a permanent organ impairment. If and when will fibrosis develop in COVID-19 pneumonia requires further research, but a link between the amount of tissue afflicted and the development of fibrosis exists. Case outline A previously healthy, non-smoker, woman with minor symptoms on admission had suddenly developed a serious respiratory insufficiency and whose radiographic finding on computed tomography scan had shown a serious progression with the development of fibrosis in a matter of days. The exact mechanism and correlation of this clinical course remains unknown; however, it is clear that the pulmonary fibrosis is caused by COVID-19 pneumonia. Follow-up computed tomography scan, performed 50 days after initial symptoms, had shown a partial regression of consolidations and post-inflammatory fibrosis. Conclusion Pulmonary fibrosis is the most severe complication of COVID-19 infection on the respiratory system. Who, when or if a patient will develop any complication is still unclear, as well as whether these changes are reversible? Also, the number of recovered patients who later develop some chronic complications remains to be seen. © 2021, Serbia Medical Society. All rights reserved.

Background: Pembrolizumab monotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC) patients whose tumors express a PD-L1 tumor proportion score (TPS) of ≥50%. However, real-world data regarding its effectiveness outside of clinical trials, particularly in Eastern European populations, are limited. Methods: We conducted a retrospective, multicenter study including 225 patients with metastatic NSCLC and PD-L1 TPS ≥ 50% who received first-line pembrolizumab monotherapy in Serbia between 2019 and 2022. Patient demographics, clinical characteristics, and treatment outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression was performed to identify predictors of outcomes. Results: The median PFS was 9.7 months (95% CI: 7.979–11.421), and the median OS was 17.0 months (95% CI: 12.813–20.187) at a median follow-up of 18.1 months. The overall response rate (ORR) was 36.4%, and the disease control rate (DCR) was 73.4%. Multivariable analysis identified good performance status (ECOG PS 0–1), PD-L1 TPS ≥ 90%, and the occurrence of immune-related adverse events (irAEs) as independent predictors of improved PFS and OS. Conclusions: Our study highlights the efficacy and safety of first-line pembrolizumab monotherapy in a real-world Serbian population with metastatic NSCLC and high PD-L1 expression. Furthermore, it confirms the prognostic value of ECOG PS, high PD-L1 expression, and the development of irAEs in predicting favorable clinical outcomes. © 2025 by the authors.

Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy. © 2019 Buha et al.

Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy. © 2019 Buha et al.