A Real-World Data-Based Analysis of Prognostic Indices as Part of Trial Eligibility Criteria in Diffuse Large B-Cell Lymphoma Patients.

OBJECTIVES: Recent front-line clinical trials used the International Prognostic Index (IPI) to identify trial-eligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, many IPI-like variants with improved accuracy have been developed over the years for rituximab-treated patients. METHODS: We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low-risk IPI patients based on POLARIX/EPCORE DLBCL-2 trial criteria. RESULTS: We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0-1 scores were included. IPI and NCCN-IPI assigned 33.3% and 11.9% of patients to the low-risk group, respectively. Shorter 5-year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low-risk IPI group compared with low-risk NCCN-IPI group. Analyzed models failed to identify true high-risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL-2 trial eligibility criteria. CONCLUSION: True low-risk patients are more optimal identified by NCCN-IPI and should be excluded from front-line clinical trials due to their excellent prognosis. However, additional high-risk factors besides clinical prognostic models need to be considered when selecting trial-eligible patients.

A real-world analysis of pharmacotherapy adherence and the factors influencing it in Serbia: a nationwide, population-based, cross-sectional study.

Introduction: Monitoring the pharmacotherapy adherence in society is crucial for identifying occurance and causes of potential inadequate use of drugs and inform providers about the need for better customer counceling. It is necessary component of the strategic planning of the quality of healthcare services. This population- based study aimed to assess the medication intake adherence in the Republic of Serbia and the individual factors and health system variables influencing its pattern. Methods: We applied a cross-sectional approach to study medication intake adherence using a secondary analysis of the latest 2019 Serbian National Health Survey data. The statistical modeling of the pharmacotherapy adherence incorporated sociodemographic data, self-reported disease, and lifestyle behavior. Results: In 2019, in the representative sample of 12,066 adults in Serbia, requiring prescribed medicine, 49.8% did comply with the prescribed drugs, and 50.2% do not. Participants who adhered to prescribed medication were significantly (p < 0.001) older (62.4 ± 14 years), predominantly female (55.3%), had secondary education (48.5%), resided in southern and eastern parts of Serbia (55.5%), and belonged to the lowest income quintile (21.4%). The participants most often take prescribed drugs for hypertension (64.1%) and lower back pain (30.5%), while around 20% take medication for coronary disease, diabetes mellitus, and high blood cholesterol. About 85-92% of participants with financial or general difficulties using prescribed medication. Conclusion: There is poor medication intake adherence to prescribed medication in Serbia. Gender, age, and region determine the adherence. Also, health-related and healthcare system-related factors impact the use of prescribed medication. Study findings can inform planning the counceling interventions in the target groups where improving medication adherence is necessary, as well as to enhance training of healthcare providers about pharmacotherapy adherence.

Can pharmacogenetics impact the therapeutic effect of cytarabine and anthracyclines in adult acute myeloid leukaemia patients?: A Serbian experience.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients' genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients. Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test. Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome. Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population.

Anticoagulation Monitoring Using Activated Clotting Time in Patients Receiving Extracorporeal Membrane Oxygenation: A Meta-Analysis of Correlation Coefficients.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe hemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool; however, the evidence of its correlation with unfractionated heparin (UFH) infusion dose is limited. Here we aimed to analyze the correlation between ACT and UFH infusion during ECMO. DESIGN: Systematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024). PROSPERO: CRD42023448888 SETTING: All retrospective and prospective studies PARTICIPANTS: Patients receiving ECMO support INTERVENTION: Anticoagulation monitoring during ECMO support MEASUREMENTS AND MAIN RESULTS: Nineteen studies were included in the analysis, and the meta-analysis encompassed 16 studies. The vast majority of studies (n = 15) found a weak correlation, and no study reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12,625 samples) identified a weak correlation, with a pooled estimate of correlation coefficients of 0.132 (95% confidence interval 0.03-0.23). The most common adverse events were hemorrhage (pooled incidence, 45%) and thrombosis (30%), and 47% of the patients died during their hospital stay. CONCLUSIONS: Even though ACT is a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are needed to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support.

Anti-Xa-guided Anticoagulation With Unfractionated Heparin and Thrombosis During Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-analysis.

OBJECTIVE: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support. DESIGN: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023). SETTING: All retrospective and prospective studies. PARTICIPANTS: Patients receiving ECMO support. INTERVENTION: Anticoagulation monitoring during ECMO support. MEASUREMENTS AND MAIN RESULTS: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%). CONCLUSIONS: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support.

Revisiting beta-2 microglobulin as a prognostic marker in diffuse large B-cell lymphoma.

BACKGROUND: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (ß2M). However, the role of ß2M in DLBCL patients is not fully understood. METHODS: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. RESULTS: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with ß2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of ß2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (ß2M-NCCN-IPI) by adding ß2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. CONCLUSION: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. ß2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL.

Using machine learning algorithms and techniques for defining the impact of affective temperament types, content search and activities on the internet on the development of problematic internet use in adolescents' population.

Background: By using algorithms and Machine Learning - ML techniques, the aim of this research was to determine the impact of the following factors on the development of Problematic Internet Use (PIU): sociodemographic factors, the intensity of using the Internet, different contents accessed on the Internet by adolescents, adolescents' online activities, life habits and different affective temperament types. Methods: Sample included 2,113 adolescents. The following instruments were used: questionnaire about: socio-demographic characteristics, intensity of the Internet use, content categories and online activities on the Internet; Facebook (FB) usage and life habits; The Internet Use Disorder Scale (IUDS). Based on their scores on the scale, subjects were divided into two groups - with or without PIU; Temperament Evaluation of Memphis, Pisa, Paris, and San Diego scale for adolescents (A-TEMPS-A). Results: Various ML classification models on our data set were trained. Binary classification models were created (class-label attribute was PIU value). Models hyperparameters were optimized using grid search method and models were validated using k-fold cross-validation technique. Random forest was the model with the best overall results and the time spent on FB and the cyclothymic temperament were variables of highest importance for these model. We also applied the ML techniques Lasso and ElasticNet. The three most important variables for the development of PIU with both techniques were: cyclothymic temperament, the longer use of the Internet and the desire to use the Internet more than at present time. Group of variables having a protective effect (regarding the prevention of the development of PIU) was found with both techniques. The three most important were: achievement, search for contents related to art and culture and hyperthymic temperament. Next, 34 important variables that explain 0.76% of variance were detected using the genetic algorithms. Finally, the binary classification model (with or without PIU) with the best characteristics was trained using artificial neural network. Conclusion: Variables related to the temporal determinants of Internet usage, cyclothymic temperament, the desire for increased Internet usage, anxious and irritable temperament, on line gaming, pornography, and some variables related to FB usage consistently appear as important variables for the development of PIU.

Trends in oesophageal cancer mortality in Montenegro, 1990-2018.

BACKGROUND: Oesophageal cancer (OC) is a significant public health issue, despite the decreasing trends in OC mortality rates observed globally in the past decades. The objective of our study is to analyze the pattern of OC mortality in Montenegro between 1990 and 2018 and contribute to the development of a national long-term strategy for the prevention and control of this malignancy. METHODS: The data on OC death cases in Montenegro between 1990 and 2018 were collected. The mortality rates were standardized according to the World Standard Population. The Joinpoint, Linear and Poisson regressions were applied to analyze the OC mortality trend. RESULTS: Joinpoint regression analysis showed an increase in death rates for men and the overall level which were not statistically significant. However, the number of cases increases significantly with an average annual percentage change (AAPC) increase of 2.6% for the overall level [AAPC (95% CI)=2.6 (1.0-4.2); P = 0.002] at the expense of the increase in men, which on average was 2.6% annually [AAPC (95%CI) = 2.6 (1.2-4.1); P = 0.001]. The age groups 55-64 and 65-74 have the highest percentage of deaths cases from OC with 30.6% and 31.4%, respectively. CONCLUSION: Montenegro has witnessed a recent increase in the number of deaths from OC, although the mortality rates remain stable. National strategies to further reduce mortality rates for OC are necessary. Individuals aged 55-64 and 65-74 need specific attention during the ongoing monitoring of this cancer.

Association of anti-factor Xa-guided anticoagulation with hemorrhage during ECMO support: A systematic review and meta-analysis.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the ECMO system, but this comes with an increased risk of bleeding. Evidence on the use of anti-Xa-guided monitoring to prevent bleeding during ECMO support is limited. Therefore, we aimed to analyze the association between anti-factor Xa-guided anticoagulation and hemorrhage during ECMO. METHODS: A systematic review and meta-analysis was performed (up to August 2023). PROSPERO: CRD42023448888. RESULTS: Twenty-six studies comprising 2293 patients were included in the analysis, with six works being part of the meta-analysis. The mean anti-Xa values did not show a significant difference between patients with and without hemorrhage (standardized mean difference -0.05; 95% confidence interval [CI]: -0.19; 0.28, p = .69). We found a positive correlation between anti-Xa levels and unfractionated heparin dose (UFH; pooled estimate of correlation coefficients 0.44; 95% CI: 0.33; 0.55, p < .001). The most frequent complications were any type of hemorrhage (pooled 36%) and thrombosis (33%). Nearly half of the critically ill patients did not survive to hospital discharge (47%). CONCLUSIONS: The most appropriate tool for anticoagulation monitoring in ECMO patients is uncertain. Our analysis did not reveal a significant difference in anti-Xa levels in patients with and without hemorrhagic events. However, we found a moderate correlation between anti-Xa and the UFH dose, supporting its utilization in monitoring UFH anticoagulation. Given the limitations of time-guided monitoring methods, the role of anti-Xa is promising and further research is warranted.

Immediate and long-term effects of COVID-19 on antibiotic dispensing: increasing use of Watch antibiotics.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic affected antibiotic usage worldwide. However, there is limited data from Serbia. Dispensing of oral antibiotics in Serbian pharmacies was analyzed to calculate monthly and yearly changes between 2018-2021, and to explore immediate and long-term effects of COVID-19 on antibiotic dispensing during this period. METHODOLOGY: The number of antibiotic packages dispensed from pharmacies during the study period was analyzed with a Chi-square test to assess the average change in annual dispensing, and an interrupted time-series analysis was used to evaluate the impact of the pandemic on antibiotic dispensing. The data from 2018-2021 were retrieved from the database of a large community pharmacy chain in Serbia. RESULTS: The average number of antibiotic packages dispensed per day and per pharmacy was higher in 2021 compared to 2018 by one package. However, the dispensing of macrolides increased significantly; 17.7% (2018) vs. 22.5% (2021) (p < 0.05). In general, an increase in antibiotic dispensing was detected during COVID-19 for total antibiotics (16.4%), Watch antibiotics (44.8%), third-generation cephalosporins (80.4%), macrolides (45.5%) and azithromycin (83.7%). However, the immediate effect of COVID-19 was a decrease in the dispensing of Watch antibiotics, penicillin, and third-generation cephalosporins (p < 0.05); and a notable long-term COVID-19 effect was an increase in the dispensing of azithromycin (p < 0.05). CONCLUSIONS: In spite of a relatively stable trend of total antibiotic dispensing before and during COVID-19 pandemic, the use of Watch antibiotics, third-generation cephalosporins, and macrolides (particularly azithromycin) showed an increasing trend in dispensing that should be optimized.

Venous thromboembolism in patients with acute myeloid leukemia: development of a predictive model.

BACKGROUND: Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. OBJECTIVES: This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. RESULTS: Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077-2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4-4.96), international normalized ratio (OR 0.21, 95% CI: 0.05-0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53-0.94), and intensive therapy (OR 2.05, 95% CI: 1.07-3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. CONCLUSION: We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Predisposition and Working Conditions for the Occurrence of Lumbar Syndrome in Medical Workers of the Clinical Center of Montenegro during the COVID-19 Pandemic.

Background: Lumbar pain is a condition of discomfort in the lower back caused by numerous factors, lasting for short or longer periods of time. Healthcare professionals, regardless of the type of care they are engaged in, are at risk of lumbar pain. This is the first study that deals with the problem of lumbar syndrome in health workers in Montenegro. Methods: This cross-sectional study included full-time health workers employed in the Clinical Center of Montenegro who were involved in the treatment of COVID-19 patients during 2020 and 2021. The survey consisted of general questions for collecting socio-demographic and COVID-19 engagement data; the Modified Nordic questionnaire was used for the analysis of musculoskeletal symptoms, and the EQ-5D-questionnaire was used to measure the quality of life associated with health. Results: The one-year prevalence of lumbar pain was 68.1%. Factors associated with lumbar pain were as follows: a higher degree of physical inactivity (each subject with a higher degree of physical inactivity had a 24% higher chance of occurrence of lumbar pain); a higher degree of load and over-engagement during the COVID-19 pandemic (each subject with a higher degree of workload had a nearly 50% higher chance of occurrence of lumbar pain); duration of engagement during the COVID-19 pandemic (subjects engaged up to a month were 4 times more likely to develop lumbar pain, and subjects engaged for 1-3 months were 3.5 times more likely to develop lumbar pain compared to those who were not engaged in COVID-19 treatment). This study also confirms that lumbar syndrome affects the quality of life of health workers. Conclusions: Lumbar syndrome is highly prevalent among healthcare professionals in the Clinical Center of Montenegro, especially in the population of nurses, where evidence-based preventive measures are needed.

Nurses' Perception of Tension, Stress, and Pressure before and during the COVID-19 Pandemic: A Multicenter Serbian Study.

The mental health of healthcare workers, especially the nursing staff in intensive care units, is crucial for the optimal functioning of healthcare systems during medical emergencies. This study implements a cross-sectional design to investigate the associations between nurses' personal characteristics, workplace challenges, and job satisfaction with the increased perception of tension, stress, and pressure at the workplace (TSPW) before and during the COVID-19 pandemic. In 2021, we surveyed 4210 nurses from 19 intensive healthcare facilities in the capital of Serbia, Belgrade, and, at that time, collected data about their perceived TSPW before and during the COVID-19 pandemic. Our study identified six predictors of the increase in TSPW, as perceived by nurses: their work in COVID-19 infectious zones (OR = 1.446), exhaustion due to work under protective equipment (OR = 1.413), uncertainty and fear of infection (OR = 1.481), a high degree of superiors' appreciation and respect (OR = 1.147), a high degree of patients' attitudes (OR = 1.111), and a low degree of work autonomy (OR = 0.889). The study's findings suggest that a solution to this issue is necessary to ensure that nurses are safe and able to alleviate the physical and mental strain that comes with prolonged use of protective equipment. Nurses on the frontline of the pandemic require better health protection, better conditions, and respect for their role. Strategies to promote mental health would help reduce nurses' stress and increase job satisfaction.

Should we use nomograms for risk predictions in diffuse large B cell lymphoma patients? A systematic review.

Models based on risk stratification are increasingly reported for Diffuse large B cell lymphoma (DLBCL). Due to a rising interest in nomograms for cancer patients, we aimed to review and critically appraise prognostic models based on nomograms in DLBCL patients. A literature search in PubMed/Embase identified 59 articles that proposed prognostic models for DLBCL by combining parameters of interest (e.g., clinical, laboratory, immunohistochemical, and genetic) between January 2000 and 2024. Of them, 40 studies proposed different gene expression signatures and incorporated them into nomogram-based prognostic models. Although most studies assessed discrimination and calibration when developing the model, many lacked external validation. Current nomogram-based models for DLBCL are mainly developed from publicly available databases, lack external validation, and have no applicability in clinical practice. However, they may be helpful in individual patient counseling, although careful considerations should be made regarding model development due to possible limitations when choosing nomograms for prognostication.

Trends in gastric cancer mortality in Montenegro, 1990 - 2018: joinpoint regression.

Background Gastric cancer (GC) remains a significant global public health problem, despite the decreasing trends in GC mortality rates in the last five decades. Our study aimed to examine the pattern of GC mortality in Montenegro between 1990 and 2018 and to contribute to the future designing a national long-term strategy for the control and prevention of GC. Methods Gastric cancer mortality data in Montenegro from 1990 to 2018 were collected. Mortality rates were age-standardized to the World Standard Population for estimating both the overall and gender-specific trends. The joinpoint regression model was used to assess GC mortality and identified significant changes in the linear time trend. Linear and Poisson regressions were also applied for additional trend analyses. Results Joinpoint regression reveals a statistically significant decrease in the age-standardized rate for the overall level, on average by 1.4% per year (AAPC (95% IP)= -1.4 (-2.4)-(-0.4); P= 0.007), which was due to a decrease in the age-standardized rate in men with an average annual change of -1.8% (AAPC (95% IP)= -1.8 (-2.9)-(-0.6); P=0.003), while in women the rates were stable (p=0.565). The results for age groups indicate that a decline was registered at the overall level, and among men, as a consequence of the trend of decreasing age-specific rates for the age group 55-64 on average annually by 2% among men (AAPC (95% IP)= -2 ((-3.8)-(-0.1)); P=0.035), and for the overall level (AAPC (95% IP)= -2 ((-3.7)-(-0.3)); P=0.026). Conclusions Our findings indicate a noteworthy decline in age-standardized overall GC mortality rates among men in Montenegro, while rates for women have remained constant. National strategies to further reduce mortality rates for GC are necessary.

The Comparative Effects of Myo-Inositol and Metformin Therapy on the Clinical and Biochemical Parameters of Women of Normal Weight Suffering from Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a multisystem reproductive-metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to determine the influence of myo-inositol (MI) on insulin resistance (IR), menstrual cycle regularity, and hyperandrogenism in women suffering from PCOS with normal BMI and diagnosed IR. METHODS: We performed a prospective randomized controlled trial (RCT) that included 60 participants with PCOS who had IR and a normal BMI. Two groups were formed. A group of thirty patients received MI, and thirty patients in the control group received metformin (MET). RESULTS: A statistically significant reduction in the area under the curve (AUC) of insulin values during the oral glucose tolerance test (OGTT) was recorded in both examined groups after the applied therapy with MI and MET. The regularity of the menstrual cycle in both groups was improved in >90% of patients. A statistically significant decrease in androgenic hormones (testosterone, SHBG, free androgen index-FAI, androstenedione) was recorded in both groups and did not differ between the groups. CONCLUSIONS: Both MI and MET can be considered very effective in the regulation of IR, menstrual cycle irregularities, and hyperandrogenism in women with PCOS.

Diagnostic and prognostic value of 99mTc-Tektrotyd scintigraphy and 18F-FDG PET/CT in a single-center cohort of neuroendocrine tumors.

Introduction: The aim was to assess the diagnostic value of 99mTc-Tektrotyd scintigraphy (TCT) and positron emission tomography/computed tomography using F-18 fluorodeoxyglucose (18F-FDG PET/CT) in the detection and follow-up of neuroendocrine tumors (NETs), and their predictive value for disease progression. Material and methods: In this retrospective cohort, TCT and 18F-FDG PET/CT were performed in 90 patients (37 men, 53 women, mean age 52.7 ±15.1), with NET. Correlation of Ki67 and tumor grade versus Krenning score and SUVmax was assessed, Kaplan-Meier analysis was used for progression-free survival (PFS), and Cox regression analysis was performed to identify the association between progression-related factors and PFS. Results: Out of 90, true positive TCT was detected in 56 (62.2%) patients, true negative in 19 (21.1%), false positive in 4 (4.4%), false negative in 11 (12.2%), while 18F-FDG PET/CT was true positive in 69 (76.7%) patients, true negative in 10 (11.1%), false positive in 5 (5.5%), false negative in 6 (6.7%). Mean 18F-FDG PET/CT SUVmax was 6.8 ±6.2. Diagnostic sensitivity of TCT was 83.6%, specificity 82.6%, accuracy 83.3% vs. 18F-FDG PET/CT sensitivity was 92.0%, specificity 66.7%, accuracy 87.8%. A significant correlation between Ki67 and SUVmax was found in positive 18F-FDG PET/CT findings, unlike the correlation between Ki67 and Krenning score. Median PFS was 25 months (95% CI: 18.2-31.8), in 18F-FDG PET/CT positive patients 23 months (95% CI: 16.3-29.7) and 18F-FDG PET/CT negative 26 months (p = 0.279). Progression-free survival predictors were SUVmax and Krenning score. Conclusions: In our study, TCT and 18F-FDG PET/CT have high diagnostic accuracy in detection of NET. Higher Krenning score on TCT and SUVmax in positive 18F-FDG PET/CT findings are predictors of disease progression. 99mTc-Tektrotyd scintigraphy and 18F-FDG PET/CT can be useful complementary tools in management of patients with NETs and in predicting patients' outcome.

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19.

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.

Knowledge, attitudes, and practices regarding antibiotic use among the population of the Republic of Serbia - A cross-sectional study.

BACKGROUND: Antimicrobial resistance presents one of the most significant threats to public health. This study aimed to examine antibiotic usage within the general population in the Republic of Serbia and their knowledge, attitudes, and behavior concerning this topic. METHODS: We conducted an online cross-sectional study over two weeks in December 2022, on a sample of 1014 respondents, representative of the Republic of Serbia's population. Predictors of the Antibiotic Knowledge Score (composed of four questions) were analyzed by multivariate ordinal logistic regression. RESULTS: In 2022, 76.8% of the participants from the Serbian population had taken antibiotics, mostly upon a medical prescription, with the most common reasons being upper respiratory tract infections. Only 31.3% of all respondents received any kind of advice about the rational use of antibiotics and half of them changed their opinions on using antibiotics after receiving this information. The average Antibiotic Knowledge Score was 2.6 out of 4, with 32.5% of respondents answering all knowledge questions correctly. The multivariate ordinal logistic regression analysis showed that female gender, higher education level, and the willingness to change opinions regarding the usage of antibiotics after receiving information about the rational use of antibiotics from any available source were significant predictors of better knowledge about antibiotics use. Respondents who were open to changing their opinion after receiving information about the rational use of antibiotics had 28% higher odds of higher antibiotic knowledge scores. CONCLUSION: This is the first population-level study on public knowledge, attitudes, and practices about antibiotic use in Serbia and therefore the baseline for future research and measuring the impact of potential interventions. Our findings underline the importance of taking into account specific population characteristics, knowledge levels, and attitudes when designing educational and intervention strategies for antibiotic use. Policymakers can leverage these findings to target specific groups and enhance the population's knowledge and practices regarding rational antibiotic usage.

Prognostic indices in diffuse large B-cell lymphoma: a population-based comparison and validation study of multiple models.

Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available.