Djordje Kralj

Dr. Djordje Kralj

orcid

Research Focus & Metrics

Academic Career Length

4Years (2023-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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14 May 2024 in Antioxidants
Verified
Journal Article
Open access
PDF file
Marija BrankovićMarija Branković
Marija Branković
Tijana GmizićTijana Gmizić
Tijana Gmizić
MDMarija Dukić
Marija Dukić
MZMarija Zdravković
Marija Zdravković
BDBranislava Vojislav Daskalovic
Branislava Vojislav Daskalovic
Zoran TodorovicZoran Todorovic
Zoran Todorovic
Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA’s effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.

Verified
Journal Article
Open access
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MMMladen Maksic
Mladen Maksic
Irfan CorovicIrfan Corovic
Irfan Corovic
TVTijana Veljkovic
Tijana Veljkovic
JZJelena Zivic
Jelena Zivic
MZMilos Z Zivic
Milos Z Zivic
Miloš NikolićMiloš Nikolić
Miloš Nikolić
The emergence of anti-TNF agents has revolutionized the management of inflammatory bowel disease, yet a significant proportion of patients experience primary non-response or secondary loss of response due to immunogenicity. As the field of precision medicine advances, genetic predictors such as human leukocyte antigen (HLA) variants are gaining increasing attention. This review provides a comprehensive synthesis of current evidence on the role of HLA genotypes in inflammatory bowel disease susceptibility and disease behavior, with a focus on their mechanistic and clinical relevance in anti-TNF therapy. Special emphasis is placed on HLA-DQA1*05, a validated predictor of anti-drug antibody formation and reduced therapeutic durability. We explore the immunological basis of HLA-mediated immunogenicity, summarize pharmacogenetic and biomarker findings, and discuss how HLA typing may be integrated into treatment algorithms to improve patient stratification and long-term outcomes. As immunogenetics continues to inform clinical decision-making, understanding the interplay between HLA polymorphisms and therapeutic response offers new opportunities for biomarker-guided, personalized care in inflammatory bowel disease.

23 December 2024 in Pharmaceutics
Verified
Journal Article
Open access
PDF file
SMSrdjan Markovic
Srdjan Markovic
DKDjordje Kralj
Djordje Kralj
PSPetar Svorcan
Petar Svorcan
TITamara Knezevic Ivanovski
Tamara Knezevic Ivanovski
OGOlga Golubovic
Olga Golubovic
Katarina M VučićevićKatarina M Vučićević
Katarina M Vučićević
Background/Objectives: Vedolizumab (VDZ) is approved in the treatment of patients with moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). VDZ exhibits considerable variability in its pharmacokinetic (PK) profile, and its exposure-response relationship is not yet fully understood. The aim was to investigate the variability in VDZ trough levels and PK parameters, to assess the relationship between VDZ PK and biochemical response, as well as clinical and endoscopic outcomes. Methods: We included 61 UC and 45 CD patients. Patients’ data and trough VDZ concentrations were retrospectively obtained. Population PK analysis was performed using non-linear mixed-effects modelling with NONMEM (version 7.5). Graphs and statistical analyses were performed using R (version 4.1.3). Results: In total, 116 trough VDZ concentrations from 106 patients were described by a two-compartment model. For a typical patient, clearance (CL) was estimated at 0.159 L/day, while in patients previously treated with anti-TNFα agents, VDZ CL increased by 26.4% on average. In univariate binary logistic regression, VDZ trough concentration was not statistically significant predictor of remission, whereas CL was. Moreover, combined CL and faecal calprotectin (FCP) were a statistically significant predictors of remission. The hazard ratio (HR) for CL above 0.1886 L/day was 0.35 (p = 0.05) and for FCP below 250 µg/g was 2.66 (p = 0.02) in a time-to-event analysis. Conclusions: Our population PK model incorporates the effect of prior anti-TNFα agents on CL, suggesting its association with more severe forms of IBD. VDZ CL emerged as a more robust and clinically relevant predictor of remission in IBD patients than trough concentration.

14 February 2025 in Medicina
Verified
Journal Article
Open access
PDF file
SMSrdjan Markovic
Srdjan Markovic
DKDjordje Kralj
Djordje Kralj
TITamara Knezevic Ivanovski
Tamara Knezevic Ivanovski
PSPetar Svorcan
Petar Svorcan
Background and Objectives: On 11 March 2020, our hospital adapted to the COVID-19 pandemic by becoming a temporary COVID-19 facility, leading to the suspension or delegation of non-COVID-19 services. Among the international IBD community, there were significant concerns regarding the neglect of immunocompromised IBD patients and their increased vulnerability to COVID-19. To address these challenges, the COVID-19 ECCO Taskforce recommended the implementation of telehealth. Following this recommendation, our hospital’s IT department integrated audiovisual hardware and software solutions to facilitate virtual consultations. This approach enabled patients and their local physicians to receive formal reports comparable to those issued during standard in-person care. Materials and Methods: We retrospectively analyzed data from patients diagnosed with Crohn’s disease and ulcerative colitis who participated in telemedicine consultations. Average distances and time saved were calculated using Google Maps, while carbon emissions and carbon footprint reductions were determined. Results: Between 11 August 2021 and 15 June 2023, 107 telehealth consultations were completed. Patients benefited from reduced travel distances, with an average saving of 168.28 km per consultation and a total reduction of 18,006 km. Travel time savings averaged 2 h and 22 min per consultation, amounting to a total of 252 h saved. The reduction in carbon emissions was calculated at 3.26 tons, equivalent to the annual absorption capacity of 109 fully grown trees, considering that an individual tree absorbs approximately 21.77 kg of CO2 annually. These findings underscore telemedicine’s role in reducing environmental impact while enhancing patient convenience. Conclusions: The adoption of telehealth successfully optimized outpatient clinic operations, maintaining high-quality patient outcomes while contributing to environmental sustainability.

30 September 2024
Verified
Book Chapter
Open access
PDF file
Irfan CorovicIrfan Corovic
Irfan Corovic
MMMladen Maksic
Mladen Maksic
DRDušan Radojević
Dušan Radojević
Samir Alija VuceljSamir Alija Vucelj
Samir Alija Vucelj
SSSabir Sagdati
Sabir Sagdati
MJMarina Jovanovic
Marina Jovanovic
Esophageal motility disorders are common conditions that impede the normal movement of food and liquids from the esophagus to the stomach, frequently manifesting as dysphagia, chest pain, and regurgitation. These disorders arise from a variety of etiological factors and can greatly diminish patients’ quality of life. If left untreated, esophageal motility disorders may lead to severe complications, including malnutrition, weight loss, and aspiration pneumonia. This chapter offers an in-depth examination of the etiology and pathogenesis of both primary and secondary EMDs. It thoroughly investigates the clinical manifestations and diagnostic methods, highlighting the critical role of differential diagnosis in the accurate identification of these conditions. Additionally, the chapter reviews current treatment options, including pharmacological interventions, endoscopic procedures, and surgical techniques, and discusses the potential of novel therapies and future research directions. Through a detailed analysis of these aspects, the chapter aims to provide a comprehensive understanding of esophageal motility disorders and to guide effective clinical management and innovative therapeutic approaches.

28 July 2025 in Pharmaceuticals
Verified
Journal Article
Open access
PDF file
BMBojana Milasinovic
Bojana Milasinovic
SKSandra Vezmar Kovačević
Sandra Vezmar Kovačević
SMSrdjan Markovic
Srdjan Markovic
Marija JovanovicMarija Jovanovic
Marija Jovanovic
TITamara Knezevic Ivanovski
Tamara Knezevic Ivanovski
Katarina M VučićevićKatarina M Vučićević
Katarina M Vučićević
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations.