Artificial Intelligence in Pediatrics: Learning to Walk Together.

In this era of rapidly advancing technology, artificial intelligence (AI) has emerged as a transformative force, even being called the Fourth Industrial Revolution, along with gene editing and robotics. While it has undoubtedly become an increasingly important part of our daily lives, it must be recognized that it is not an additional tool, but rather a complex concept that poses a variety of challenges. AI, with considerable potential, has found its place in both medical care and clinical research. Within the vast field of pediatrics, it stands out as a particularly promising advancement. As pediatricians, we are indeed witnessing the impactful integration of AI-based applications into our daily clinical practice and research efforts. These tools are being used for simple to more complex tasks such as diagnosing clinically challenging conditions, predicting disease outcomes, creating treatment plans, educating both patients and healthcare professionals, and generating accurate medical records or scientific papers. In conclusion, the multifaceted applications of AI in pediatrics will increase efficiency and improve the quality of healthcare and research. However, there are certain risks and threats accompanying this advancement including the biases that may contribute to health disparities and, inaccuracies. Therefore, it is crucial to recognize and address the technical, ethical, and legal challenges as well as explore the benefits in both clinical and research fields.

The role of S100A12 and Toll-like receptor 4 in assessment of disease activity in familial Mediterranean fever and juvenile idiopathic arthritis.

OBJECTIVE: Our aim was to investigate the possible relationship between the serum S100A12 and Toll-like receptor 4 (TLR4) levels, and the activity of familial Mediterranean fever (FMF) and juvenile idiopathic arthritis (JIA) in accordance with the routine biochemical parameters. Furthermore, the effectiveness of these 2 biomarkers in distinguishing FMF from JIA has been evaluated. METHOD: Sixty-nine children with FMF, 68 children with JIA, and 35 healthy children were included in this study. S100A12 and TLR4 levels were measured by the sandwich enzyme-linked immunosorbent assay technique. RESULTS: In the FMF patient group, serum S100A12 level was found to be significantly higher than in both the JIA and control groups (P = .000 and P = .000, respectively). Although S100A12 levels were higher in the attack period compared to the attack-free period, this increase was not statistically significant (P > .05). TLR4 levels were statistically significantly higher in the attack period compared to the attack-free period in children with FMF (P < .05). Although there was no relationship between S100A12 levels and disease activity, there is a clear correlation between S100A12 and the Auto-Inflammatory Disease Activity Index in attack-free FMF patients (r = 0.612 P = .000). CONCLUSION: Serum S100A12 levels were not found to be a potentially valuable biomarker for assessing disease activity in either FMF or JIA. However, TLR4 levels were found to be a valuable biomarker for assessing disease activity in children with FMF. Further research which includes serial monitoring of S100A12 and TLR4 levels in a large cohort will provide detailed information about accuracy of these 2 potential biomarkers in both patients group.

Assessment of myelin oligodendrocyte glycoprotein antibodies and magnetic resonance spectroscopy in childhood-onset systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterised by the presence of various autoantibodies. Mild cognitive impairment developing in patients without significant neuropsychiatric (NP) symptoms was thought to be the result of immune-mediated myelinopathy. We aimed to determine the role of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in the neurological manifestations of childhood-onset SLE (cSLE) and if there is a correlation between various metabolite peaks in magnetic resonance spectroscopy (MRS) and myelinopathy. METHODS: MOG-Ab levels were studied in all healthy subjects (n=28) and in all patients with (NPSLE=9) and without (non-NPSLE=36) overt neuropsychiatric manifestations. Twenty patients (all had a normal-appearing brain on plain magnetic resonance) in non-NPSLE and 20 subjects in healthy group met the MRS imaging standards for evaluation in which normal appearing brain on plain MR. RESULTS: A total of 45 cSLE (36 non-NPSLE and 9 NPSLE) subjects and 28 healthy children were recruited to the study. The mean age of the SLE patients at study time was 16.22±3.22 years. MOG-Ab was not detected in cSLE or in healthy group. There was no significant difference between the non-NPSLE group and healthy subjects in terms of choline, N-acetyl aspartate (NAA), creatine, NAA/creatine, and choline/creatine. CONCLUSIONS: There was no association of MOG-Ab with cSLE, whether NP manifestations were present or not. A causal relationship between immune-mediated myelinopathy and cognitive impairment could not be suggested, since there has been no patient with positive MOG-Ab and there has been no difference in choline, choline/creatine between groups.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)−(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08−0.16]; FGF23 MD [95% CI]: 12.8 [5.9−19.6]; PTX3 MD [95% CI]: 13.3 [8.9−17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype−phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

The Assessment of Serum Endocan Levels in Children With Juvenile Idiopathic Arthritis.

OBJECTIVES: This study aims to evaluate the levels of serum endocan in children with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: Sixty-seven children with JIA (30 males, 37 females; mean age 10.4±4.9 years; range 2 to 18 years) and a sex- and age- matched healthy control group of 39 children (16 males, 23 females; mean age 9.3±4.1 years; range 1 to 17 years) were recruited. Patients with JIA were divided into two groups as the clinically active JIA group (n=27) and inactive JIA group (n=40). RESULTS: The median serum endocan level in patients with JIA was significantly higher than in the control group (633.75 ng/L vs. 379.76 ng/L, p<0.01). Comparison between patients with active JIA and inactive JIA was not significant in terms of endocan levels (618.70 ng/L vs. 687.36 ng/L, p=0.34). There was a weak negative correlation between Childhood Health Assessment Questionnaire scores of patients with JIA and serum endocan levels. CONCLUSION: The high level of serum endocan highlighted the endothelial damage in patients with JIA.

The Turkish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Turkish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 466 JIA patients (13.7% systemic, 40.6% oligoarticular, 22.5% RF negative poly-arthritis, and 23.2% other categories) and 93 healthy children were enrolled in four centres. The JAMAR components discriminated well-healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Turkish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

New Insights into Cardiac Involvement in Juvenile Scleroderma: A Three-Dimensional Echocardiographic Assessment Unveils Subclinical Ventricle Dysfunction.

Cardiac manifestations in juvenile scleroderma or systemic sclerosis (JSSc) have poor prognosis, begin in early stages of the disease, and remain clinically asymptomatic. New echocardiography modalities, such as 2D/3D speckle tracking (STE, strain analysis for regional and global ventricular functions), can detect cardiac involvement in early stages. We assessed 21 JSSc patients and 19 controls using 2D/3D STE. The left ventricular end diastolic volume, end systolic volume, and ejection fraction of the patient and control groups were significantly different (99.2 ± 23.8 vs. 52 ± 23.8, 40.6 ± 16.0 vs. 20.2 ± 17.4 and 59.2 ± 7.5 vs. 65.6 ± 5.2, respectively). Global longitudinal strain (GLS) and global circumferential strain (GCS) were lower in the patient group (18.4 ± 4.7 vs. 22.4 ± 3.7, 26.4 ± 5.8 vs. 31.4 ± 3.5), as were the peak systolic strain values of the right ventricular longitudinal strain (RVLS) septum and RVLS free wall (18.1 ± 6.8 vs. 24.8 ± 6.0 and 22.8 ± 5.9 vs. 28.0 ± 6.9, respectively). 3D measurements of RVEDV, RVESV, and RVSV were higher in the patient group (88.2 ± 31.3 vs. 50.8 ± 23.5, 43.1 ± 17.6 vs. 19.0 ± 12.2, and 45.0 ± 16.2 vs. 31.7 ± 12.6). RVLS freewall results were lower in the JSSc patients with interstitial lung fibrosis, arthritis, muscle weakness, weight loss, and anti-scl 70 antibodies than in the JSSc patients without these variables. We found that a GCS of <34.5% could identify patients for left ventricular (LV) dysfunction with a sensitivity of 93.3, specificity of 92.9, while an RVEF of <60.7% could identify patients for left ventricular (RV) dysfunction with a sensitivity of 92.9 and specificity of 21.4%. We highlighted key advantages of 3D STE for the tracking of early systolic dysfunction in patients with JSSc who would benefit from medical intervention for cardiac complications.

A novel assessment tool for clinical care of patients with autoinflammatory disease: juvenile autoinflammatory disease multidimensional assessment report.

OBJECTIVES: To develop and test a new multidimensional questionnaire for assessment of children with auto-inflammatory disease (AID) such as FMF, PFAPA, HIDS, TRAPS in standard clinical care. METHODS: The juvenile auto-inflammatory disease multidimensional assessment report (JAIMAR) includes 16 parent or patient-centered measures and four dimensions that assess functional status, pain, therapeutic compliance and health-related quality of life (physical, social, school, emotional status) with disease outcome. It is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 8-18 years for use as a self-report. RESULTS: 250 children with FMF were included in the study. Total of 179 forms were filled up by parents and patients, and 71 forms were filled up by parents having children less than 8 years. Completing and scoring the JAIMAR can be done in 15 minutes. For the JAIMAR's dimensions, the Cronbach's alpha coefficient for internal consistency was between 0.507-0.998. There was a significant and a positive correlation between the test-retest scale scores (ICC=0.607-0.966). Concerning construct validity, all factors loadings were above 0.30. For the criterion validity, the correlation level between each dimension and the related scale ranged from medium (r=0.329, p<0.0001) to large (r=0.894, p<0.0001). The parents' proxy-reported and children's self-reported data were outstandingly concordant (r=0.770-0.989). CONCLUSIONS: The development of the JAIMAR introduces a new and multi-dimensional approach in paediatric rheumatology practice. It is a new tool for children with auto-inflammatory dis-ease and it may help enhance their quality of care.

Economic impact of juvenile idiopathic arthritis and familial Mediterranean fever.

The aim of the study was to determine the economical impact of juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF) in Turkey. A total of 100 patients (69 F/31 M) with JIA and 100 with FMF (68 F/32 F) who were consecutively seen in the outpatient clinic of the pediatric rheumatology department at Cerrahpasa Medical School between August 2008 and January 2009 were studied. Cost data were collected through a questionnaire filled out by the parents. The mean age (JIA: 11 ± 5 years; FMF:12 ± 4 years) and mean disease duration (JIA:5 ± 3 years; FMF: 4 ± 3 years) of the patients were similar. JIA patients were assigned to 5 subtypes (polyarticular: n = 45, oligoarticular: n = 30, systemic onset: n = 13, psoriatic: n = 6, and enthesopathy-related JIA: n = 6). Forty-nine percent of the patients with JIA were treated with anti-TNF drugs and 61% with DMARDs. All patients with FMF were using colchicine. The total annual cost of JIA (3,994 ± 4,101) was considerably higher than that of FMF (162 ± 77) (P < 0.001). Medication fee was the major determinant of total costs in both diseases constituting 85% in JIA and 39% in FMF. Among the subtypes of JIA, total annual costs were the highest among patients with polyarticular type (6,045 ± 4,078). Medications especially anti-TNF drugs were the major contributor among all determinants of costs in JIA. The low costs of health care system and prominent changes in the health care policies for the last 5 years in Turkey might have played role in our findings.

A new set of criteria for the diagnosis of familial Mediterranean fever in childhood.

OBJECTIVES: Several sets of criteria mainly for adults have been proposed for the diagnosis of FMF. The aim of the present study is to validate the most widely used diagnostic 'Tel Hashomer' criteria in children and to establish a new set of criteria for use in childhood. METHODS: The study group consisted of 170 recently diagnosed FMF patients who had mutations at both alleles. They were interviewed about the presence of 35 features and manifestations of FMF at the time of diagnosis. Controls were consecutive patients without FMF (n = 141) who had episodes of fever and clinical features mimicking that of FMF. The diagnostic performance of the candidate features was assessed by multiple logistic regression analysis. RESULTS: The sensitivity and specificity of Tel Hashomer criteria in our study group were 98.8 and 54.6%, respectively. The multiple logistic regression analysis showed that 5 (fever, abdominal pain, chest pain, arthritis and family history of FMF) of the 35 candidate criteria discriminate FMF from controls with a sensitivity and specificity of 88.8 and 92.2%, respectively. The presence of two or more of these five criteria diagnosed FMF with a sensitivity of 86.5% and a specificity of 93.6%. CONCLUSION: It was demonstrated that although the Tel Hashomer criteria were successful in diagnosing the FMF patients in childhood, its specificity was definitely low in children. The new set of criteria has a high sensitivity and specificity for the diagnosis of FMF and is practical to use on an everyday basis.