Search Results (74)

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization in infancy. Reliable biomarkers reflecting host antiviral responses and disease dynamics are still lacking. Methods: We evaluated the expression of the interferon-stimulated genes IFI44L, IFI27, and RSAD2 in peripheral blood of infants hospitalized with RSV bronchiolitis at admission and discharge, and in healthy controls, using multiplex RT-qPCR. A composite interferon-based Viral Score was derived from coordinated ISG expression. Results: All three ISGs and the Viral Score were markedly elevated during acute RSV infection at hospital admission compared with discharge and healthy controls. Following clinical recovery, ISG expression and Viral Score declined significantly and approached baseline levels. The Viral Score clearly discriminated acute infection from recovery and healthy states, reflecting dynamic systemic interferon activation. Conclusions: A Viral Score based on IFI44L, IFI27, and RSAD2 captures systemic antiviral immune responses in infants with RSV bronchiolitis and declines with disease resolution. This interferon-based host-response signature represents a promising biomarker for defining viral infection status and monitoring disease dynamics in pediatric respiratory infections. Full article

Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m² every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m² every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into various connective tissue cell types. Adipose tissue provides a rich source of MSCs (ADSCs), which can differentiate into osteoblasts, adipocytes, and chondroblasts. Pluripotency factors such as SOX2, NANOG, and OCT4 maintain MSC stemness, whereas human endogenous retroviruses (HERVs) and their epigenetic regulators TRIM28 and SETDB1 have been implicated in transcriptional regulation and cell fate decisions. This study investigated the transcriptional expression of HERV-H, -K, and -W, TRIM28, SETDB1, and pluripotency markers (NANOG, OCT4, SOX2) during chondrogenic differentiation of ADSCs using Real-Time PCR. Chondrogenesis was confirmed by aggrecan (ACAN) upregulation and aggrecan immunostaining. Although no statistically significant differences were observed for HERV-H, HERV-K, or HERV-W, HERV-K and HERV-W showed a trend toward decreased expression in differentiated cells, consistent with the overall shift in transcriptional profile during lineage commitment. TRIM28 expression was significantly reduced, while SETDB1 showed a decreasing trend. Among pluripotency markers, OCT4 was significantly downregulated, whereas NANOG and SOX2 remained stable. Correlation analyses revealed that in differentiated ADSCs, HERV-W expression correlated negatively with TRIM28 and positively with SETDB1, while no correlations were found for HERV-H or HERV-K. These findings suggest that specific HERV families and their epigenetic regulators may undergo coordinated modulation during chondrogenic differentiation, supporting a complex and family-specific interplay between retroelement regulation, pluripotency factors, and MSC lineage commitment. Full article

Background and Objectives: Type I interferon (IFN-I) transcriptional signatures are widely utilised as readouts of innate immunity. We evaluated whether age and sex affect single interferon-stimulated genes (ISGs) and the composite IFN-I score, with implications for control selection and assay calibration. Materials and Methods: Ninety-five healthy individuals (53 males, 42 females; 18 days to 89 years) were studied. Whole-blood expressions of IFI27, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC1 was quantified by RT-qPCR, normalised to GAPDH and calibrated to a paediatric reference. Age associations used Spearman’s rho; sex differences, two-sided Mann–Whitney U tests. Results: Age effects were modest and gene-specific: IFI44L declined and IFI27 increased with age (significant overall and in females), whereas in males only IFI44L decreased; other ISGs were null (|r| ≤ 0.36). The composite IFN-I score showed no association with age or sex, indicating that aggregation mitigates small gene-level variation and that demographic influences on baseline IFN-I readouts appear minimal within this six-gene whole-blood qPCR panel in our cohort. Conclusions: Methodologically, a single primary cut-off within homogeneous pipelines is appropriate. Although best practice favours age-, sex- and matrix-matched healthy controls, our data show no significant age- or sex-related differences in the composite IFN-I score; matching therefore primarily supports comparability and clinical governance rather than correction of demographic shifts. Full article

Background/Objectives: Thiopurines remain a cornerstone in the management of inflammatory bowel disease (IBD) and gastrointestinal immune diseases but are associated with significant interindividual variability in efficacy and toxicity, mainly influenced by polymorphisms in Thiopurine S-methyltransferase TPMT and Nudix Hydrolase 15 NUDT15. This study aimed to assess the frequency of TPMT and NUDT15 variants in a pediatric cohort and evaluate their clinical impact to support a pharmacogenetic-guided approach to thiopurine therapy. Methods: Eighty-three pediatric patients with IBD and other autoimmune diseases were genotyped for clinically relevant TPMT and NUDT15 variants using two HRM-PCR assays and were confirmed with sequencing. Variant frequencies were compared to expected population data, and clinical records were reviewed to assess thiopurine dosing, tolerance, and adverse events. Results: Among the cohort, six carried heterozygous TPMT variants *1/*3A, while 2 carried the NUDT15 *1/*9 diplotype, with frequencies higher than expected. Among patients with TPMT variant alleles, some needed dose reductions or treatment discontinuation due to adverse effects, while others tolerated standard dosing without significant issues. Notably, no significant differences in adverse reactions were observed between NUDT15 *1/*9 carriers and wild-type patients. Conclusions: Our results confirm the clinical relevance of TPMT and NUDT15 genotyping to personalize thiopurine therapy in pediatric IBD. Routine implementation of rapid genetic testing, combined with therapeutic drug monitoring and a structured management algorithm, may optimize treatment outcomes and minimize preventable toxicity. Full article

Pediatric inflammatory bowel disease (PIBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is associated with inflammation that extends beyond the gastrointestinal tract. Among the most significant extraintestinal complications are anemia and thrombosis, both of which can impact disease severity, quality of life, and long-term outcomes. This review aims to explore the intertwined pathophysiology of anemia and thrombosis, clinical implications of these two complications, and management strategies for anemia and thrombosis in PIBD. Anemia is the most common systemic complication in PIBD, with multifactorial etiologies, including iron deficiency, chronic inflammation, and nutritional deficiencies. Despite its high prevalence, it remains underdiagnosed and undertreated. Thrombosis, although less frequent, poses significant risk, particularly during disease flares, hospitalizations, and in the presence of central venous catheters or corticosteroid therapy. The proinflammatory and hypercoagulable state in inflammatory bowel disease (IBD) increases thrombotic risk, necessitating early identification and, in high-risk cases, consideration of thromboprophylaxis. Anemia and thrombosis represent significant yet often overlooked complications in PIBD. Proactive screening, individualized risk stratification, and integrated management approaches are critical to improving outcomes. Further pediatric-specific research is needed to develop tailored prevention and treatment strategies. Full article

Background: Some patients with juvenile idiopathic arthritis (JIA) can successfully undergo withdrawal of treatment with anti-tumor necrosis factor alpha (anti-TNF-α) therapy, which may reduce economic and treatment-related burdens and the potential morbidity of treatment for at least 6 months. Currently, no guidelines exist on the appropriate withdrawal of anti-TNF-α therapy once clinically inactive disease (CID) has been achieved. This study aimed to assess the possibility of withdrawing anti-TNF-α therapy in children with non-systemic JIA after achieving long-term clinical remission. Methods: This single-center retrospective cohort study included data from 137 non-systemic JIA patients treated with anti-TNF-α therapy (etanercept or adalimumab) and having maintained CID for at least 24 months during treatment. Demographic, laboratory, and treatment data were collected at JIA onset, at the initiation of anti-TNF-α therapy, every 6 months during therapy, and at the time of disease flare. Anti-TNF-α therapy was discontinued abruptly after discussing it with the patients and their families in each case. Outcomes were assessed using standard criteria for remission in JIA (ACRpedi and Wallace criteria). Results: Following withdrawal of TNF-α inhibitors, 93/137 patients (67.9%) experienced a disease flare, with a median time to flare of 7 months (3; 14). Thirty-two percent of patients remained in remission for a median of 63 months. Absence of flare during the first 22 months after discontinuation was associated with prolonged biologic-free remission (odds ratio 682; 95% CI 38.6–12,062; p < 0.0001), with 83% sensitivity and 100% specificity (area under the ROC curve 0.967). Most flares involved arthritis (76%) and/or uveitis (24%), primarily affecting knees, ankles, and wrists. Inflammatory markers were generally lower at flare compared to baseline. Biological therapy was resumed in 84/93 patients (90.3%), achieving at least a 50% improvement according to ACRpedi criteria within 3 months and remission according to Wallace criteria within 6 months. Conclusion: Over two-thirds of patients with non-systemic JIA who achieve CID experience a flare within seven months of anti-TNF-α discontinuation. Re-initiation of biologic therapy is effective in restoring remission. These results indicate that prolonged biologic-free remission is possible in a subset of patients, highlighting the need for individualized withdrawal strategies and careful post-discontinuation monitoring. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Background: Child poverty is a critical issue that affects millions of children worldwide and represents a global issue. This article focuses on exploring the risk of child poverty and social exclusion across Europe, with Serbia being in a comparable position with respect to other countries with different levels of development. Methods: This is an epidemiological, retrospective, and descriptive study based on data on the national populations of the European countries within our research interest. The data analyzed in this study was taken from publicly available datasets from Eurostat. The indicators of interest were the ones considering the social inclusion of children in the time period between 2014 and 2023 for all European countries available in the datasets. Results: The indicator of the risk of poverty and social exclusion showed a decreasing trend in the majority of countries; but still, seven countries showed an increase during the observation period of one decade. The highest percentage was in Romania and the lowest in Slovenia. The indicator of the risk of poverty exhibited a significant difference in terms of gender (being mostly higher among females) in Bulgaria, Lithuania, Portugal, Sweden, Switzerland, Montenegro, Albania, and Turkey. The indicator of children living in households with very low work intensity exhibited a significant difference in terms of gender (being mostly higher among males) in Bulgaria, Lithuania, Malta, the Netherlands, Finland, Sweden, Switzerland, and Albania. The indicator of severe social and material deprivation exhibited a significant difference in terms of gender (being mostly higher among females) in Bulgaria, Denmark, Estonia, Lithuania, Montenegro, Albania, and Turkey. Serbia did not show a significant gender difference, but the male gender had higher values than the female for all indicators. Conclusions: Child poverty is a multifaceted issue that affects various aspects of children’s lives, including health, education, and social inclusion. Addressing this issue requires a comprehensive approach that includes social protection, access to quality services, and efforts to combat discrimination. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies of the biliary tract, often originating from chronic inflammation associated with gallstones and cholecystitis. Persistent inflammation plays a pivotal role in the development of preneoplastic changes, such as metaplasia, which may progress to malignancy. Despite its relatively low incidence, GBC is characterized by a poor prognosis due to late-stage diagnosis, highlighting the urgent need for improved early detection strategies. This study aimed to assess the diagnostic and prognostic significance of CA 19-9 and CEA levels in patients with gallbladder lesions, while also evaluating systemic inflammation and hemostatic dysregulation. A retrospective analysis was conducted on patients diagnosed with gallbladder lesions, with histopathological confirmation of adenocarcinoma and metaplasia. Laboratory assessments included serum levels of tumour markers, inflammatory markers such as CRP, and key hemostatic parameters, including thrombocyte count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen levels. A predictive scoring model was developed using the cutoff values of CA 19-9 and CEA to assess their combined diagnostic potential. Among the patients studied, 48.9% had an initial diagnosis of chronic cholecystitis, while 32.2% presented with acute cholecystitis. Adenocarcinoma was identified in 6.7% of cases after histopathological examination, predominantly in females over 65 years old with acute cholecystitis. Metaplasia was detected in 7.8% of cases, primarily in elderly females with chronic cholecystitis. Laboratory findings revealed significantly elevated levels of CA 19-9, CEA, AFP, and CA-125 in patients with adenocarcinoma. Additionally, abnormalities in hemostatic parameters, including increased fibrinogen levels and alterations in thrombocyte count, were observed in patients with malignancy. A combined predictive score using CA 19-9 and CEA demonstrated strong potential for detecting adenocarcinoma and metaplasia, improving diagnostic accuracy. Our findings emphasize the clinical importance of integrating tumour markers, inflammatory biomarkers, and hemostatic parameters in the evaluation of gallbladder lesions associated with chronic inflammation. The combined assessment of these factors enhances early detection, facilitates malignancy risk stratification, and improves prognostic evaluation, particularly in patients with metabolic and cardiovascular comorbidities. Full article

Background/Objectives: Childhood obesity is a significant health concern also capable of impacting ocular health. This study evaluates the effects of childhood obesity on corneal morphology, anterior chamber parameters, intraocular pressure (IOP), and corneal endothelial cell morphology. Understanding these relationships may contribute to early diagnosis and management strategies. Methods: This prospective, cross-sectional study was conducted at the Harran University Faculty of Medicine between January and December, 2024. Ninety children aged 7–17 years were included, with only the right eyes being analyzed. The participants were categorized into three groups based on body mass index (BMI) percentiles: normal weight (≤85th percentile), overweight (86–94th percentiles), and obese (≥95th percentile). All participants underwent comprehensive ophthalmological examinations, including IOP measurement with a non-contact tonometer, corneal topography assessment using a Scheimpflug camera, and endothelial cell morphology evaluation via specular microscopy. Results: IOP was significantly higher in the overweight and obese groups (p < 0.001). Central corneal thickness (CCT) also increased significantly in these groups (p < 0.05). Positive correlations were determined between BMI and IOP (r = 0.493, p < 0.001) and CCT (r = 0.345, p < 0.001). Additionally, waist circumference exhibited a strong correlation with BMI (r = 0.905, p < 0.001) and a significant association with IOP (r = 0.463, p < 0.001). No significant differences were observed among the groups in terms of other anterior chamber or endothelial parameters. Conclusions: Childhood obesity is associated with increased IOP and CCT, suggesting potential alterations in corneal biomechanics and ocular physiology. These findings highlight the importance of routine ophthalmological evaluation in obese children to detect early ocular changes and prevent long-term complications. Full article

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The review discusses the molecular and cellular mechanisms underlying platelet dysfunction, including aberrations in platelet activation, aggregation, and secretion. It also highlights the interplay between platelets and other components of the coagulation cascade, such as fibrinogen and clotting factors, in maintaining vascular integrity. Moreover, the review examines clinical implications, including how platelet dysfunction can be a contributing factor in conditions like deep vein thrombosis, stroke, and disseminated intravascular coagulation (DIC). Finally, current therapeutic approaches targeting platelet dysfunctions, including antiplatelet agents and emerging therapies, are reviewed to provide insights into potential strategies for managing fluid-coagulation system imbalances. This review underscores the importance of a comprehensive understanding of platelet dysfunction to improve diagnosis and treatment of hemostatic disorders. Full article

Background/Objectives: Cervical spine arthritis (CSA) in children with juvenile idiopathic arthritis (JIA) can lead to clinically significant and irreversible functional impairment. Our study aimed to evaluate the features of the JIA disease course in children with CSA. Methods: In the retrospective cohort study, the data from medical charts of children with JIA (n = 753) who corresponded to the ILAR criteria and were treated from 2007 to 2016 were included. CSA was diagnosed by clinical manifestations (pain and limited range of motion) with radiological confirmation in the available cases. Results: CSA had 101 JIA patients (13.4%), predominantly with polyarticular (48%, OR = 1.8 (1.2; 2.7), p < 0.001) and systemic (18.9%, OR = 3.6 [2.0; 6.6], p < 0.001) JIA categories. CSA was associated with longer disease duration, higher inflammatory activity, a higher number of active joints, a lower probability of achieving remission (HR = 1.33 (95% CI: 1.01; 1.76, p = 0.04)), and a higher probability of being treated with biologics (HR = 1.78 (95% CI: 1.22; 2.59, p = 0.002)). Patients with temporomandibular arthritis (OR = 10.4 [5.4; 19.8], p < 0.001) and shoulder arthritis (OR = 14.1 [7.5; 26.3], p < 0.001) had the highest risk of having CSA. Conclusions: CSA was an independent predictor of treatment with biologics and failure to achieve remission. Identified predictors can help to find the group of patients with higher suspicion for whom the functional tests and MRI are required to not miss the CSA. A radiology assessment of CSA should be performed as far as possible in children, unless there are risks of general anesthesia for younger patients. Full article