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Sniježana Hasanbegović

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<p><strong>Aim</strong> To determine whether demographic data, clinical features, and laboratory variables at disease onset can predict the response to methotrexate in juvenile idiopathic arthritis (JIA) patients.&nbsp;<br /><strong>Methods</strong> A cohort of 143 newly diagnosed JIA patients initially treated with methotrexate was enrolled in this study. Demographic, clinical, and laboratory parameters were analysed using univariate and multivariate logistic regression to identify predictors of response to methotrexate. The variables included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelets, IgA, IgG, the number of active joints and age at disease onset. Treatment response was assessed at six months, with patients classified as responders (those who achieved clinically inactive disease according to the American College of Rheumatology - ACR criteria) or non-responders.&nbsp;<br /><strong>Results</strong> Poor response to methotrexate was associated with the number of active joints (p=0.0001; OR=2.7), baseline levels of CRP (p=0.044; OR=1.138), IgA (p =0.004; OR=2.159), and platelet count (p=0.01; OR=1.05). IgG level (P=0.236) did not correlate with the treatment response.&nbsp;<br /><strong>Conclusion</strong> We identified widely available and clinically acceptable biomarkers that can be utilized as predictive indicators of response to methotrexate in JIA patients.</p>

Introduction: Diabetes mellitus is associated with systemic complications, including the development of pulmonary injury, characterized mainly by excessive accumulation of extracellular matrix components and inflammatory cell infiltration in lung tissue. This process is driven by oxidative stress and chronic inflammation, both caused and exacerbated by hyperglycemia. N-acetylcysteine (NAC) and glycine, known for their antioxidant and anti-inflammatory effects, offer potential therapeutic benefits in mitigating diabetes-induced lung injury. Objective: The study aimed to investigate the effects of supplementation by either NAC or glycine or their combination on reducing lung injury in rats with type 1 diabetes Materials and methods: The study used 30 adult Wistar albino rats (10 weeks old, weighing between 180 g and 380 g). Six of them were used as controls, while 24 adult rats (10 weeks old, 180-380 g) with type 1 diabetes, induced through a single intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg, were randomly assigned to four experimental groups: control (CTL), diabetic (Db), NAC treatment (diabetic+NAC), glycine treatment (diabetic+glycine), and combined NAC and glycine treatment (diabetic+NAC+glycine). NAC (100 mg/kg) and glycine (250 mg/kg) were administered orally for 12 weeks. At the end of the study, lung tissues were collected for histopathological examination. Qualitative, semi-quantitative, and stereological histological analysis was used to analyze structural changes in the lung tissue. Semi-quantitative scoring was carried out to evaluate the extent of inflammation, while stereological analysis was performed to determine the volume density of alveolar spaces and septal connective tissue. The semi-quantitative scoring included scores ranging from 0 (absent), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe). Results: Qualitative histological analysis revealed pronounced inflammation and fibrosis in the lungs of untreated diabetic rats, characterized by thickened alveolar septa and immune cell infiltration. Both treatments with NAC and glycine individually reduced inflammation and fibrosis compared to untreated diabetic rats. The greatest improvement was observed in the NAC+glycine group, where the alveolar structure appeared almost normal, with minimal inflammation. Semiquantitative analysis showed statistically significant differences in peribronchial and peribrochiolar infiltrates between the diabetic group (2.16±0.47) and the control group (0.33±0.21, p=0.026). The combination of NAC and glycine significantly reduced peribronchial and peribronchiolar infiltrates (0.33±0.33, p=0.026) compared to the diabetic group. Similarly, septal inflammatory infiltrates were significantly lower in the NAC+glycine group (1±0.36) compared to diabetic rats (3.33±0.33, p=0.004). Total airway inflammatory infiltration was also significantly reduced in the NAC+glycine group (1.33±0.33, p=0.002) compared to the diabetic group (5.5±0.5). Conclusion: As the combination of NAC and glycine demonstrated protective effects against lung inflammation and fibrosis in diabetic rats, a synergistic effect of NAC and glycine in mitigating pulmonary complications associated with type 1 diabetes may be suggested. These findings warrant further exploration of the combination for managing diabetic lung disease and potentially other fibrotic conditions.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

Bushra Ali Sherazi, Stephanie Läer, S. Hasanbegovic, Emina Obarcanin

Background Type 1 diabetes mellitus (T1DM) management in children and adolescents requires intensive supervision and monitoring to prevent acute and late diabetes complications and to improve quality of life. Digital health interventions, in particular diabetes mobile health apps (mHealth apps) can facilitate specialized T1DM care in this population. This study evaluated the initial usability of and satisfaction with the m-Health intervention Diabetes: M app, and the ease of use of various app features in supporting T1DM care in rural and remote areas of Bosnia-Herzegovina with limited access to specialized diabetes care. Methods This cross-sectional study, performed in February–March 2023, evaluated T1DM pediatric patients who used the Diabetes: M app in a 3-month mHealth-based T1DM management program, along with their parents and healthcare providers (HCPs). All participants completed self-administered online questionnaires at the end of the 3-month period. Data were analyzed by descriptive statistics. Results The study population included 50 T1DM patients (children/parents and adolescents) and nine HCPs. The mean ± SD age of the T1DM patients was 14 ± 4.54 years, with 26 (52%) being female. The mean ± SD age of the HCPs was 43.4 ± 7.76 years; all (100%) were women, with a mean ± SD professional experience of 17.8 ± 8.81 years. The app was reported usable in the domains of ease-of-use and satisfaction by the T1DM children/parents (5.82/7.0), T1DM adolescents/young adults (5.68/7.0), and HCPs (5.22/7.0). Various app features, as well as the overall app experience, were rated positively by the participants. Conclusion The results strongly support the usability of mHealth-based interventions in T1DM care, especially in overcoming care shortage and improving diabetes management and communications between HCPs and patients. Further studies are needed to compare the effectiveness of apps used to support T1DM management with routine care.

Background: Diabetes mellitus type 1 (T1D) is an autoimmune organ-specific disease with a wide range of clinical manifestations, in which the β cells of the pancreatic islets of Langerhans are destroyed by the action of autoreactive T lymphocytes and the formation of autoantibodies against β cell components. Among used serological markers of T1D, anti-glutamic acid decarboxylase antibodies (GAD65), anti-tyrosine phosphatase antibodies (IA2), islet cell antibodies (ICA), insulin autoantibodies (IAA) and anti-zinc transporter antibodies (Zn-T8) are of great significance. Objective: This study aimed to analyze presence of type 1 diabetes-related autoantibodies (GAD65, IA2, ICA, IAA and Zn-T8 and effects of age and gender on their occurrence in pediatric population. Methods: Sixty seven (N=67) T1D pediatric patients were included in the study. The levels of immunological parameters such as anti-glutamic acid decarboxylase antibodies (GAD-Ab), anti-tyrosine phosphatase antibodies (IA2-Ab), islet cell antibodies (ICA) and insulin autoantibodies (IAA) were determined by chemiluminescence immunoassay (CLIA) and anti-zinc transporter antibodies (Zn-T8-Ab) were determined by enzyme-linked immunosorbent assay (ELISA). For statistical analysis, we used SPSS statistical program. Results: Our study revealed that among 67 patients with T1D (40 male and 27 female), with an average age of 12,1±3,9 years. The average age of diabetes diagnosis was 6,15±3,29 years. 24 (35,8%) cases were positive for GAD65, 15 (22,4%) for ICA, 34 (50,7%) for IAA, 16 (23,9%) for IA2 and 36 (53,7%) for Zn-T8. The largest number of patients had single positive antibody, the most dominated among them was IAA dominated (40,9%), then Zn-T8 (31,8%). According to Spearman correlation test Zn-transporter shows a significant positive correlation with age of the participants (p=0.027) and disease duration (p=0.006). Anti IA2 shows significant negative correlation with HbA1c (p=0.043). Zn-transporter is associated with patients age and duration of T1D. Conclusion: In most cases, patients with T1D are positive for at least one of the specific autoantibodies. Zn-T8 is the most frequently detected and is an important serological marker of type 1 diabetes mellitus. Gender effects on autoantibodies seems to be insignificant, while age alongside disease duration shows important effects.

Aim To analyse the association of human leukocyte antigen B27 with clinical and laboratory parameters in patients with juvenile idiopathic arthritis (JIA) at the disease onset. Methods A retrospective review of medical records of 25 HLAB27 positive and 25 HLA-B27 negative JIA patients was performed. The diagnosis of JIA was based on the 1997-2001 International League Against Rheumatism (ILAR) criteria. Collected data: age, sex, HLA- B27 antigen presence, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid-factor (RF), antinuclear antibody (ANA), fever, rash, uveitis, enthesitis, inflamed joints and subtype of JIA. Results HLA- B27 positive study group had more boys (p=0.01), higher erythrocyte sedimentation rate (p=0.038), higher presence of fever (p= 0.025) and enthesitis (p=0.024). Any significant difference in age of the disease onset, CRP, ANA, RF, rash, uveitis, inflamed joint and dactylitis was not noticed. The most common subtype of JIA in the HLA-B27 positive patients was ERA (60%). Conclusion This study showed that the presence of HLA- B27 antigen plays a significant role in determining the presenting clinical and laboratory characteristics in JIA patients.

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