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result(s) for
"Popevic, Spasoje"
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Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study
2021
To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
Case-control study.
We collected data from international participants via an online survey.
In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7).
COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
Journal Article
The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity
by
Gompelmann, Daniela
,
Djurdjevic, Natasa
,
Milivojevic, Ivan
in
Airflow limitation
,
Analysis
,
Biomarkers
2023
Background
Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations.
Methods
In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed.
Results
COPD patients (
n
= 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (
n
= 47) (
p
≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all
p
< 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV
1,
FEV
1
/FVC, VC, and IC (all
p
< 0.05). For MMP-9, a positive correlation was found with RV/TLC% (
p
= 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (
p
= 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (
p
≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found.
Conclusions
COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.
Journal Article
Utility of neutrophil to lymphocyte ratio in the prediction of inflammation and COPD mortality
by
Golubovic, Aleksa
,
Milivojevic, Ivan
,
Popevic, Spasoje
in
Aged
,
Aged, 80 and over
,
Biomarkers - blood
2025
Introduction: The Neutrophil-to-Lymphocyte Ratio (NLR) has been utilized to predict clinical outcomes in cardiovascular diseases, infectious diseases, and solid tumors and it has a potential association with the severity of Chronic Obstructive Pulmonary Disease (COPD). This study aimed to determine whether NLR is a possible predictor of inflammation severity and mortality in COPD. Methodology: A prospective analysis of NLR in 70 COPD patients, and its relation with biochemical, lung function parameters, and mortality was assessed. Results: NLR was negatively associated with oxygen saturation (p < 0.05) and positively related to C-reactive protein (CRP) (p < 0.05), matrix metalloproteinase-9 (MMP-9) (p ≤ 0.001), tissue inhibitor of metalloproteinase-1 (TIMP-1) (p < 0.05), MMP-9/TIMP-1 ratio (p < 0.05), and the modified Medical Research Council dyspnea scale (mMRC) score (p < 0.05). Deceased patients had significantly higher NLR (p < 0.05). Older age and lower levels of saturation were independently associated with higher mortality in COPD patients (p < 0.05). Conclusions: NLR in COPD correlates with inflammation and protease/antiprotease balance, with elevated NLR detected in deceased patients. These findings suggest that NLR can be a helpful clinical marker in COPD.
Journal Article
Early Functional Impairment in Smokers with CT-Detected Emphysema: Spirometry Provides Complementary Physiological Information in Lung Cancer Screening
by
Vukoja, Marija
,
Djurdjevic, Natasa
,
Stosic-Markovic, Kristina
in
airflow limitation
,
Bronchodilators
,
Cancer
2026
Background: Low-dose computed tomography (LDCT) lung cancer screening (LCS) frequently identifies emphysema in high-risk smokers. However, the extent to which CT-detected emphysema reflects underlying physiological impairment remains uncertain. We evaluated whether spirometry can detect functional abnormalities in this population beyond structural imaging findings. Methods: This cross-sectional study included 323 individuals with LDCT- detected emphysema and no lung cancer or prior chronic respiratory diseases within a screening cohort (n = 3076). Participants underwent pre-bronchodilator spirometry and symptom assessments (COPD Assessment test (CAT) and Modified Medical Research Council (mMRC) Dyspnea Scale). Pre-bronchodilator airflow limitation was defined as forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) < 0.70. Small airways dysfunction was defined by ≥2 reduced mid-expiratory flow parameters (<60% predicted). Flow–volume curve morphology was assessed qualitatively. Results: Pre-bronchodilator airflow limitation was observed in 45.2% of participants, predominantly mild. Small-airway dysfunction was present in 52%, and an abnormal flow–volume curve morphology in 67.5%. Notably, functional abnormalities were frequently observed despite preserved FEV1. Symptom burden was low, with only 7.7% of participants reporting clinically significant symptoms. Functional impairments often overlapped and were common in minimally symptomatic individuals. Conclusions: In a lung cancer screening (LCS) cohort with CT-detected emphysema, functional abnormalities are frequently observed, including in individuals with preserved FEV1 and minimal symptoms. Spirometry provides additional physiological insight beyond structural imaging; however, these findings are descriptive and should not be interpreted as diagnostic of COPD. Further studies are needed to determine their clinical relevance.
Journal Article
Clinical Characteristics and Survival of Patients with Idiopathic Pulmonary Fibrosis: Analysis of the Serbian Cohort from the EMPIRE Registry
by
Stosic, Kristina
,
Milivojevic, Ivan
,
Popevic, Spasoje
in
antifibrotic treatment
,
Carbon monoxide
,
Care and treatment
2025
Background/Objectives: Idiopathic pulmonary fibrosis (IPF) registries are established to enhance understanding of its natural history. Methods: Serbia (RS) participated in the EMPIRE (European Multi-Partner IPF Registry) from June 2015 to October 2022, involving four centers. The registry included patients over 18 diagnosed with IPF based on the 2011 international criteria. We aimed to gather key clinical, functional, and survival data, along with treatment information for IPF patients in RS, using a centralized electronic case report for consistency. Results: 188 RS patients participated (median age at diagnosis 65, 63.8% male, 51% smoking history, 56% radiological usual interstitial pneumonia (UIP) pattern). At the diagnosis, median forced vital capacity (FVC) was 73.7% and diffusion capacity for carbon monoxide (DLCO) was 38%. At initiation of antifibrotic therapy, median FVC was 73.2% (71.5% for deceased, 75.8% for survivors (p = 0.455), and DLCO was 33.8% (19.9% for deceased, and 35.6% for survivors (p = 0.046)). The median long-term survival from diagnosis was 29.4 months (95% CI: 22.6–36.2 months), and 9.4 months (95% CI: 5.9–12.9 months) from the initiation of therapy, with no difference in the duration of antifibrotic treatment between survivors and deceased (p = 0.598). Conclusions: The RS EMPIRE cohort represents a younger, less comorbid population with fewer smokers and more probable UIP, factors linked to a favorable prognosis. Nevertheless, survival was poorer than expected, mainly due to advanced disease severity at the time of antifibrotic initiation, as indicated by lower DLCO. These findings highlight the importance of earlier diagnosis and treatment before significant physiological decline to improve outcomes.
Journal Article
Hyperglycemia and Lung Cancer—A Possible Relationship
2025
Glucose is the main source of energy in human cells. Elevated levels of glucose are one of the most common metabolic disorders, and it has been shown to have a significant, mostly negative, effect on multiple chronic and acute diseases. Lung cancer remains one of the biggest challenges for treatment in modern medicine, with a high prevalence, incidence and mortality. Hyperglycemia is not uncommon in patients with lung cancer; however, it is usually overlooked. Patients with unregulated glycemia and lung cancer have been shown to have worse outcomes, reduced therapeutic effect and more complications during treatment. Studies have identified multiple molecular pathways common in both hyperglycemia and lung cancer; however, no clear correlation has been identified. By understanding these signaling pathways, we can influence the outcome therapeutically and thereby improve the survival of patients with lung cancer.
Journal Article
Can Galectin-3 Be Used as a Predictor of Obstructive Sleep Apnea Severity: Insights from High-Volume Patient Single Center
2025
Background/Objectives: Obstructive sleep apnea (OSA) is a condition characterized by intermittent airway obstructions, leading to reduced oxygen levels and increased sympathetic nervous system activity. OSA can cause a range of health problems, including an increased risk of cardiovascular diseases and mortality. Galectin-3, a member of the galectin family, plays a significant role in inflammation and fibrosis, and studies show that it is elevated in various conditions, including heart and lung diseases. The aim of this study was to determine whether galectin-3 levels are related to the severity of sleep apnea. Methods: A total of 191 participants from the University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, between January 2023 and May 2024, were included in the analyses. All patients were hospitalized under suspicion of OSA, and they all underwent a polysomnography test. Various demographic, respiratory, laboratory, and clinical parameters were obtained. Correlations between numerical variables and galectin-3 were assessed by the Pearson or Spearman correlation coefficients. Univariate and multivariate linear regression models were used to assess the predictors of galectin-3 values. In all analyses, the significance level was set at 0.05. Results: The mean age of the study participants was 56.2 years, mostly male (68.9%). Of the comorbidities, two-thirds of patients had hypertension (66.1%), 46.8% had hyperlipoproteinemia, and 21.1% had diabetes mellitus. Patients who had an AHI of more than fifteen events per hour more often had higher values of galectin-3. OSA severity had a significant positive correlation with galectin-3 (p = 0.014). In multivariate linear regression analysis, significant independent predictors of higher galectin-3 values were older age, presence of coronary disease, hypoventilation syndrome, higher BMI, NTproBNP, lactate, creatinine, lower LDL, and lower FEV1 (p < 0.05). Conclusions: The present study demonstrated that galectin-3 is linked to the severity of OSA and plays a crucial role in inflammation induced by intermittent hypoxia in OSA. Further screening and interventions targeting galectin-3 could aid in preventing inflammatory diseases related to sleep disturbances.
Journal Article
Contemporary Diagnostics of Cardiac Sarcoidosis: The Importance of Multimodality Imaging
by
Klasnja, Andrea
,
Radojevic, Aleksandra
,
Milivojevic, Ivan
in
Algorithms
,
Asymptomatic
,
Autopsies
2024
Sarcoidosis is an inflammatory condition that can affect multiple organ systems and is characterized by the formation of non-caseating granulomas in various organs, including the heart. Due to suboptimal diagnostic rates, the true prevalence and incidence of cardiac sarcoidosis (CS) remain to be determined. In patients with suspected CS, an initial examination should include 12-lead ECG or ambulatory ECG monitoring, and echocardiography with the estimation of LV, RV function, and strain rate. In patients with confirmed extracardiac sarcoidosis and with high clinical suspicion for CS, sophisticated imaging modalities, including cardiac MRI and PET, are indicated. Typical inflammation patterns and myocardial scarring should pose a high suspicion for CS. In patients without diagnosed extracardiac sarcoidosis and high clinical suspicion, although with low diagnostic probability, an endomyocardial biopsy should be considered to establish the diagnosis of definite isolated cardiac sarcoidosis. Timely diagnosis enables the initiation of therapy and close monitoring of adverse cardiac events that can be life-threatening, including sudden cardiac death, ventricular tachycardia, high-degree AV block, and heart failure. Implementing biomarkers in correlation to cardiac imaging can determine the disease’s severity and progression but can also be helpful in following the treatment response. The formation of larger global registries can be helpful in the identification of independent predictors of adverse clinical events and the development of specific diagnostic algorithms to reduce the overall risk of this serious condition.
Journal Article
Utility of angiotensin-converting enzyme activity in aqueous humor in the diagnosis of ocular sarcoidosis
by
Popevic, Spasoje
,
Stanojevic-Paovic, Anka
,
Aleksic, Andjelka
in
ACE inhibitors
,
Analysis
,
Anesthesia
2017
Purpose:
Many studies include elevated activity of angiotensin-converting enzyme (ACE) in serum in sarcoidosis and in ocular sarcoidosis as well, but there are only a few analyzing ACE activities in aqueous humor. The aim of this study is to illuminate the diagnostic value of ACE in aqueous humor in patients with ocular sarcoidosis.
Methods:
We analyzed twenty patients with ocular sarcoidosis and 18 patients with nonocular involvement. All patients have biopsy-positive sarcoidosis of the lungs and/or mediastinal lymph nodes. Blood samples for ACE serum levels were obtained from all patients. Aqueous humor samples were taken by paracentesis with a 25-gauge needle in local anesthesia. With appropriate statistical tests, we compared ACE activity in serum and aqueous humor in patients with and without ocular sarcoidosis.
Results:
The majority of our patients with ocular sarcoidosis were female (12/20), also in the group with systemic sarcoidosis and without ocular involvement (12/6). Mean age of the whole analyzed group of sarcoidosis patients was 45 ± 6 years. There is no statistically significant difference in ACE activity in serum between two groups of patients (with and without ocular sarcoidosis). There is statistically significant difference in ACE activity in aqueous humor among patients with ocular and nonocular sarcoidosis. ACE activity in aqueous humor is significantly higher in patients with ocular sarcoidosis.
Conclusion:
Increased ACE activity in aqueous humor can point to a diagnosis of ocular sarcoidosis, without the need for ocular biopsy.
Journal Article
Review of lung sealant technologies for lung volume reduction in pulmonary disease
by
Popevic, Spasoje
,
Milenkovic, Branislava
,
Dimic Janjic, Sanja
in
Adhesives
,
Analysis
,
Atelectasis
2018
Emphysema is an incurable and underdiagnosed disease with obstructive ventilatory impairment of lung function. Despite decades of research, medical treatments available so far did not significantly improve the survival benefits. Different bronchoscopic methods for lung volume reduction (LVR) in emphysema were used in the past 2 decades aiming to close the airways serving the hyperinflated lung regions and to allow the gas in the more distal bullas to be absorbed. Sealants and adhesives can be natural/biological, synthetic and semisynthetic. In lung surgery, lung sealants are used to treat prolonged air leak, which is the most common complication. Sealants can also be applied in bronchoscopic lung volume reduction (BLVR) as they administer into the peripheral airways where they polymerize and act as tissue glue on the surface of the lung to seal the target area to cause durable permanent absorption atelectasis. Initial studies analyzed the efficacy of bronchoscopic instillation of a fibrinogen-thrombin complex solution in advanced emphysema. Future studies will analyze the effects of adding chondroitin sulfate and poly-L-lysine to thrombin-fibrinogen complex thus promoting fibroblast attachment, proliferation and scarring, causing bronchial fibrostenosis and preventing ventilation of the affected part of the lung. Modifications of these methods were later developed, and the efficacy of BLVR with other sealants was analyzed in clinical studies. Results from current studies using this treatment method are promising showing that it is effective in improving exercise tolerance and quality of life in patients with advanced emphysema. It seems that subjective benefits in dyspnea scores and quality of life are more marked than improvements in lung function tests. The safety profile of sealant techniques in BLVR was mostly acceptable in clinical studies. The definite conclusions about the effectiveness of sealant in BLVR could be difficult because only a small population was involved in the current studies. More randomized large controlled studies are needed in establishing the definite role of biological BLVR in the bronchoscopic treatment of emphysema.
Journal Article