Browsing by Author "Rankovic, Ivan (57192091879)"

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer’s disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation. Copyright © 2024 Miskovic, Ljubicic, Bonaci-Nikolic, Petkovic, Markovic, Rankovic, Djordjevic, Stankovic, Klaassen, Pavlovic and Stojanovic.

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer’s disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation. Copyright © 2024 Miskovic, Ljubicic, Bonaci-Nikolic, Petkovic, Markovic, Rankovic, Djordjevic, Stankovic, Klaassen, Pavlovic and Stojanovic.

[No abstract available]

Background: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia. Methods: An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked. Results: Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%. Conclusions: Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options. © 2023 S. Karger AG. All rights reserved.

Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of non-invasive scores in predicting the presence of EV in patients with liver cirrhosis, and to determine the value of these scores in predicting the outcome of patients with cirrhosis presenting with acute variceal bleeding. Materials and Methods: A total of 386 patients with liver cirrhosis were included. The model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), fibrosis-4-index (FIB-4), fibrosis index (FI), King’s Score, albumin-bilirubin (ALBI) score, and platelet-albumin-bilirubin (PALBI) score were calculated. The discriminatory capacities of the examined scores in predicting the presence of esophageal varices were tested using receiver operating characteristic (ROC) curves. Results: The ROC curve analysis showed (area under the curve) AUC values of ALBI and PALBI of 0.603, and 0.606, respectively, for the prediction of EV. APRI, MELD, PALBI, King’s, FIB-4, and ALBI scores showed statistically significant correlation with EV bleeding (p < 0.05). AUC of APRI and MELD for predicting EV bleeding were 0.662 and 0.637, respectively. The AUC value of MELD in short-term mortality was 0.761. Conclusions: ALBI and PALBI scores had modest diagnostic accuracy of EVs in liver cirrhosis. APRI and MELD can be used as a reference index for the EV bleeding, and MELD score is best associated with short-term outcome in cirrhotic patients. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background: The purpose of this review is to take a deep dive into general problems and challenges of diagnosis and treatment of patients with symptoms of dyspepsia in primary care practice. Summary: Primary care physicians become acquainted with a broad range of clinical problems and therefore require a wide span of knowledge in taking care of patients from their first medical examination within the health care system. Dyspepsia and Helicobacter pylori infection are two of the most frequent reasons of digestive-related health care issues, despite that in primary care practice, current recommendations for diagnosis and differential therapy are often not implemented. The "test-and-treat"strategy is the initial management of the condition, reserving gastroscopy for patients refractory to symptomatic treatment and for patients presenting with any of the following alarm signs: age of above 55, dysphagia, anemia, weight loss, frequent vomiting, family history of GI malignancy, or a physical examination with key pathological findings. Key Messages: Examination and treatment of dyspepsia symptoms is the diagnostic and therapeutic challenge dictated by organizational and economic potentials of the health system, professional resources, and primary health care capabilities to accept and treat patients with dyspepsia and to properly refer those with alarm symptoms and findings indicative of organic disease to a gastroenterologist. © 2021 S. Karger AG, Basel. Copyright: All rights reserved.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus–host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death. © The Author(s) 2022.

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus–host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death. © The Author(s) 2022.

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. © 2024 by the authors.

Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. © 2024 by the authors.

Cirrhotic cardiomyopathy (CCM) is a diagnostic entity defined as cardiac dysfunction (diastolic and/or systolic) in patients with liver cirrhosis, in the absence of overt cardiac disorder. Pathogenically, CCM stems from a combination of systemic and local hepatic factors that, through hemodynamic and neurohormonal changes, affect the balance of cardiac function and lead to its remodeling. Vascular changes in cirrhosis, mostly driven by portal hypertension, splanchnic vasodilatation, and increased cardiac output alongside maladaptively upregulated feedback systems, lead to fluid accumulation, venostasis, and cardiac dysfunction. Autocrine and endocrine proinflammatory cytokines (TNF-alpha, IL-6), as well as systemic endotoxemia stemming from impaired intestinal permeability, contribute to myocardial remodeling and fibrosis, which further compromise the contractility and relaxation of the heart. Additionally, relative adrenal insufficiency is often present in cirrhosis, further potentiating cardiac dysfunction, ultimately leading to the development of CCM. Considering its subclinical course, CCM diagnosis remains challenging. It relies mostly on stress echocardiography or advanced imaging techniques such as speckle-tracking echocardiography. Currently, there is no specific treatment for CCM, as it vastly overlaps with the treatment of heart failure. Diuretics play a central role. The role of non-selective beta-blockers in treating portal hypertension is established; however, their role in CCM remains somewhat controversial as their effect on prognosis is unclear. However, our group still advocates them as essential tools in optimizing the neurohumoral pathologic axis that perpetuates CCM. Other targeted therapies with direct anti-inflammatory and antioxidative effects still lack sufficient evidence for wide approval. This is not only a review but also a comprehensive distillation of the insights from practicing clinical hepatologists and other specialties engaged in advanced approaches to treating liver disease and its sequelae. © 2024 by the authors.

[No abstract available]

Background and Objectives: Forceps delivery is a crucial obstetrical technique that has become increasingly underutilized in favor of cesarean delivery, despite the numerous complications related to cesarean sections. The major concerns with regard to assisted vaginal birth (AVB) are safety and long-term consequences. We aimed to investigate a neurological outcome of neonates and children at the age of 7 who were born via forceps delivery. This would greatly improve informed decision making for both mothers and obstetricians. Materials and Methods: A single-arm cohort study was conducted from January 2012 to December 2016 among 49 women and their children born via forceps delivery at the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The Sarnat and Sarnat classification was used to evaluate the neurological status of neonates, and logistic regression analysis was employed to explore the association with perinatal factors. Long-term neurological outcomes were assessed using the Griffiths Mental Development Scale and a questionnaire for parents based on the Motor and Social Development (MSD) scale, which was derived from the Bayley-III Scale. Results: The main indication for forceps delivery was maternal exhaustion (79.6%), followed by fetal distress (20.4%). A pathological neurological status was observed in 16.3% of newborns, with pathological ultrasound of the CNS in 3%. A statistically significant association was observed with the Apgar score, with an odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, with an odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, these associations were unlikely to be related to the mode of delivery. Long-term adverse neurological outcomes were seen in three cases, which accounts for 6.4%. These included mild disorders such as delayed milestone, speech delay, and motor clumsiness. Conclusions: The present study highlights the safety of forceps delivery regarding children’s neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide. © 2024 by the authors.

BACKGROUND Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course. AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients. METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014-2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient's demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated. RESULTS Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05). CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection. © 2020, Baishideng Publishing Group Co.

Background: Non-ST-segment elevation acute myocardial infarction (NSTEMI) represents a heterogeneous patient population with varying risks of adverse outcomes. The RISK-PCI score, initially developed for ST-segment elevation myocardial infarction (STEMI) patients, was evaluated for its prognostic value in NSTEMI patients undergoing percutaneous coronary intervention (PCI). Methods: A retrospective observational study of 242 NSTEMI patients treated with PCI at the Clinical Center of Serbia from June 2011 to June 2016 was conducted. The RISK-PCI score, incorporating clinical, echocardiographic, and angiographic variables, was calculated for each patient. The primary outcome was 30-day major adverse cardiovascular events (MACE). Secondary outcomes included individual components of MACE. Statistical analyses were performed to assess the predictive value of the RISK-PCI score. Results: The primary outcome of 30-day MACE occurred in 9.9% of patients. Independent predictors of 30-day MACE included age > 75 years, glucose ≥ 6.6 mmol/L, creatinine clearance < 60 mL/min, and post-procedural TIMI flow < 3. The RISK-PCI score demonstrated good discrimination for 30-day MACE (AUC = 0.725). Patients stratified into the very high-risk group (RISK-PCI score ≥ 7) had significantly higher risks of 30-day MACE (29.4%). Conclusions: The RISK-PCI score effectively stratifies NSTEMI patients by their risk of 30-day MACE, identifying a very high-risk subgroup that may benefit from closer monitoring and tailored interventions. External validation on larger cohorts is recommended to confirm these findings. © 2025 by the authors.