Introduction: Diabetes mellitus is associated with systemic complications, including the development of pulmonary injury, characterized mainly by excessive accumulation of extracellular matrix components and

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.

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.

Introduction: Newborn screening (NBS) is a system of organized search in the entire neonatal population for specific diseases. In Bosnia and Herzegovina, two diseases are included in NBS, congenital hypothyroidism (CH), and phenylketonuria. The screening for CH is based on determination of thyroid stimulating hormone (TSH) levels in blood obtained by heel prick method. The aim of this study is to evaluate the effectiveness of NBS program for CH based on TSH and establish the mean age of diagnosis of CH.Methods: TSH was measured by time-resolved fluoroimmunoassay (DELFIA Neonatal hTSH kit). The TSH cutoff value was 9 μU/mL. Neonates with TSH < 9 μU/mL had a negative NBS result. Neonates with TSH ≥ 9 μU/mL were recalled for a confirmation test and thyroid hormones were determined from venous blood to establish diagnosis of CH.Results: A total of 24,351 neonates were subjected to NBS in our institution. A total of 164 newborns with TSH ≥ 9 μU/ml were sent to additional testing (mean recall rate of 0.68%) at a mean age of 11.4 ± 0.5 days of life. In this group, diagnosis of CH was confirmed in 22 neonates (13.41%). The mean rate of false positive results of NBS was 0.59%. The incidence of CH in Sarajevo Canton ranged from 1/2477 in 2018 to 1/641 in 2020. The mean incidence of CH over a 5-year period was 1/1085, while the mean age at the time of diagnosis was 16.5 ± 1.2 days.Conclusion: The analysis of NBS on congenital hypothyroidism data showed the satisfactory recall and false positive rate and indicated well selected TSH cutoff value. The mean age at the time of diagnosis assures early treatment and good neurological outcome in neonates with CH.

Background Altered levels of many hematological parameters have been directly associated with diabetes in adults, while studies on children with type 1 diabetes mellitus are lacking. The aim of this study was to determine hematological indices in diabetic Bosnian children in comparison to healthy controls as well as to correlate their levels to blood glucose and hemoglobin A1c. Methods 100 healthy and 100 children with type 1 diabetes mellitus (age 1-18) were included in this study. Complete blood count, hemoglobin A1c, and glucose were tested. Results were analysed by IBM SPSS Statistics version 23. Results Significant differences (p<0.05) between healthy and diabetic children were found in relation to HbA1c, glucose, mean platelet volume, the number of white blood cells and erythrocytes, hematocrit, hemoglobin and MCH values. No gender differences or significant age differences were seen for hemoglobin, hematocrit, and MCV, while platelets, MPV, and MCH differed by age only in healthy children. When diabetic children were classified according to HbA1c levels, significant differences were seen for erythrocyte count and hematocrit value (p=0.013 and 0.019, respectively). The number of erythrocytes and white blood cells correlated significantly with HbA1c (p=0.037 and 0.027, respectively). Conclusions Lower levels of erythrocytes, hematocrit, and hemoglobin in diabetic compared to healthy children indicate possible development of anemia, while higher MCV, MCH, and MPV values indicate an alteration in erythrocyte morphology. Hematological indices could be a useful inexpensive tool in the diagnosis and follow up of type 1 diabetes in children.

7 ES P E Poster presented at: LATE REFERRAL OF SIBILINGS WITH COMBINED PITUITARY HORMONE DEFICIENCY (PROP1) Snijezana Hasanbegovic, Amila Kljucic Division for Childrens' Health, Pediatric Clinic 1 Clinical Center University of Sarajevo Bosnia and Herzegovina PROP1 (Prophet of POUF1) mutations are the most frequent genetic cause of combined anterior pituitary hormone deficiency. The PROP1 gene encodes a transcription factor of synthesis: somatotrophs, lactotrophs, thyreotrops and gonadothrops. These mutations are characterized by great clinical variability, including time of onset of hormonal deficiencies, hypophyseal dimensions and secretion of cortisol. INTRODUCTION

Introduction Insulin therapy of pediatric patients with type 1 diabetes mellitus (T1DM) is highly demanding due to their dynamic growth, development and different daily life activities. Goal To determine the optimal insulin delivery method for the prevention of hypoglycemia recorded by continuous monitoring of glucose in patients with insulin pump and PEN. Material and Methods The study included patients up to 18 years of age with diagnosed T1DM and treated with insulin pump and by insulin therapy with PEN at the Pediatric Clinic of the Clinical Center in Sarajevo. The study involved 149 patients, and lasted for 3 years. Patients were divided into two groups: group of patients on insulin pump therapy and group on insulin PEN. Results There were 73 patients (49.6%) on insulin pump therapy and 79 patients (52.4%) on the insulin PEN therapy. There was no significant difference in the age between genders nor groups with different insulin application methods. There were no significant differences in the number of anamnestic hypoglycemia in patients with a different mode of insulin application (83.56% vs. 81.58%, p=0.114, F=2.533 < Fk=3.919). The number of hypoglycemia episodes in history is higher with the PEN therapy than in the insulin pump group. Conclusion The number of anamnesis hypoglycemia as well as hypoglycemia from CGM records did not differ significantly in patients with IP and PEN therapy. The CGM record was significantly more valuable in the presentation of hypoglycemia compared to the history of hypoglycemia in all patients studied. Continuous monitoring of glycemia due to the ability to show glycemia variability and unrecognized hypoglycemia as well as predictive options for long-term metabolic control should be performed for all T1DM patients at least once a year.

Introduction: Thyroid gland diseases in children are in second place by frequency among all endocrine disorders. When interpreting the results of the thyroid function assessment it should be taken into account the significant differences in the concentrations of TSH, thyroid hormones, thyroid binding proteins and calcitonin among children of different ages. Goal: To present the age and sex structure of the patients diagnosed with hypothyroidism, evaluate diagnostic methods for making diagnosis, evaluation of etiology of hypothyroidism, with special review of the therapeutic modality. Patients and methods: The study have retrospective character and includes all patients who have the diagnosis of hypothyroidism, but at the moment of data collection were aged 0-18 years. Results: Distribution of patients on the basis of gender, revealed more significant representation of female (65.93%), and without significant difference in the presence of the disease in relation to age (p>0.05). Physical examination of the struma was not verified in the majority of cases (74; 81.32%, p<0.05) suffering from hypothyroidism. Ultrasound review in 22 (50%) cases confirmed the struma. Ultrasound findings in most cases 14 (31.81%) demonstrated diffuse struma and Hashimoto thyroiditis together. In relation to the etiology of hypothyroidism most patients belong to a group where hypothyroidism is associated with other diseases and conditions (27; 29.67%), but the least with congenital hypothyroidism with 18 (19.78%) cases. The average dose of L-thyroxine in the age of 0-1 months was 50 mg, 1 month–10 years 37.5 mcg, and the group of patients over 10 years 65 mcg. Conclusion: Congenital hypothyroidism has about one-fifth of patients. Physical examination revealed in about one fifth of patients the struma of the thyroid gland; TSH levels is critical for the diagnosis and correction of therapy in pediatric patients with hypothyroidism. Congenital hypothyroidism is diagnosed on average at the age of 12 days, which is optimal for period for therapeutic response; Substitution treatment is carried out with L-thyroxine which is relatively reduced in doses from neonatal age onwards.

Introduction: Thyroid gland diseases in children are in second place by frequency among all endocrine disorders. When interpreting the results of the thyroid function assessment it should be taken into account the significant differences in the concentrations of TSH, thyroid hormones, thyroid binding proteins and calcitonin among children of different ages. Goal: To present the age and sex structure of the patients diagnosed with hypothyroidism, evaluate diagnostic methods for making diagnosis, evaluation of etiology of hypothyroidism, with special review of the therapeutic modality. Patients and methods: The study have retrospective character and includes all patients who have the diagnosis of hypothyroidism, but at the moment of data collection were aged 0-18 years. Results: Distribution of patients on the basis of gender, revealed more significant representation of female (65.93%), and without significant difference in the presence of the disease in relation to age (p>0.05). Physical examination of the struma was not verified in the majority of cases (74; 81.32%, p