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BACKGROUND: Previous studies have developed the Migraine Aura Complexity Score (MACS) system. MACS shows great potential in studying the complexity of migraine with aura (MwA) pathophysiology especially when implemented in neuroimaging studies. The use of sophisticated machine learning (ML) algorithms, together with deep profiling of MwA, could bring new knowledge in this field. We aimed to test several ML algorithms to study the potential of structural cortical features for predicting the MACS and therefore gain a better insight into MwA pathophysiology. METHODS: The data set used in this research consists of 340 MRI features collected from 40 MwA patients. Average MACS score was obtained for each subject. Feature selection for ML models was performed using several approaches, including a correlation test and a wrapper feature selection methodology. Regression was performed with the Support Vector Machine (SVM), Linear Regression, and Radial Basis Function network. RESULTS: SVM achieved a 0.89 coefficient of determination score with a wrapper feature selection. The results suggest a set of cortical features, located mostly in the parietal and temporal lobes, that show changes in MwA patients depending on aura complexity. CONCLUSIONS: The SVM algorithm demonstrated the best potential in average MACS prediction when using a wrapper feature selection methodology. The proposed method achieved promising results in determining MwA complexity, which can provide a basis for future MwA studies and the development of MwA diagnosis and treatment.
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Epilepsia , Migraña con Aura , Humanos , Migraña con Aura/diagnóstico por imagen , Imagen por Resonancia Magnética , Neuroimagen , Aprendizaje AutomáticoRESUMEN
Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: ⢠Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). ⢠Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: ⢠Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. ⢠Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.
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Hiperinsulinismo Congénito , Hiperinsulinismo , Niño , Preescolar , Hiperinsulinismo Congénito/genética , Consanguinidad , Humanos , Lactante , Recién Nacido , Mutación , Estudios Retrospectivos , Serbia/epidemiología , Receptores de Sulfonilureas/genéticaRESUMEN
Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in Central Serbia from 1983 to 2013. Newborn screening for CH was based on measuring neonatal thyroid-stimulating hormone (TSH) using a 30 mU/l cutoff (CO) until 12/1987 (P1), 15 mU/l until 12/1997 (P2), 10 mU/l until 12/2006 (P3), and 9 mU/l thereafter (P4). During the study period, there were 1,547,122 live births screened for CH. Primary CH was detected in 434 newborns, with incidence of 1:3728. With gradual lowering of the CO, the incidences of CH increased from 1:5943 in P1 to 1:1872 in P4 (p < 0.001). Incidence of CH with ectopic and enlarged gland doubled (p < 0.001), while prevalence of athyreosis remained relatively constant. The most prominent finding was the increase in the transient CH from none in P1 to 35 % of all CH patients in P4. CONCLUSION: The overall incidence of CH in Central Serbia during study period nearly tripled, with a significant increase in almost all etiological categories, and was associated with lowering TSH cutoffs as well as other yet unidentified factors. Further studies are needed to identify other factors associated with increasing incidence of CH. WHAT IS KNOWN: Congenital hypothyroidism (CH) is the main cause of preventable mental retardation. Recent reports have indicated a progressive increase in the incidence of primary CH throughout the world, partially explained by lowering of the TSH cutoff values. WHAT IS NEW: During the study period associated with lowering of the TSH cutoffs, the overall incidence of CH in Serbia tripled, including transient CH, ectopy, and dyshormonogenesis, while prevalence of athyreosis remained stable during 30 years. Significant increase in the incidence of both permanent and transient CH was observed, associated with lowering of TSH cutoffs as well as other yet unidentified factors.
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Hipotiroidismo Congénito/epidemiología , Hipotiroidismo Congénito/etiología , Tamizaje Neonatal/métodos , Tirotropina/sangre , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Estudios Retrospectivos , Serbia/epidemiologíaRESUMEN
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.
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Arteriosclerosis/genética , Síndromes de Inmunodeficiencia/genética , Síndrome Nefrótico/genética , Osteocondrodisplasias/genética , Embolia Pulmonar/genética , Receptores de Interleucina-7/genética , Linfocitos T/metabolismo , Adolescente , Adulto , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Células Cultivadas , Niño , Preescolar , ADN Helicasas/genética , Metilación de ADN , Citometría de Flujo , Expresión Génica , Humanos , Inmunohistoquímica , Síndromes de Inmunodeficiencia/metabolismo , Síndromes de Inmunodeficiencia/patología , Interleucina-17/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Mutación , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patología , Enfermedades de Inmunodeficiencia Primaria , Regiones Promotoras Genéticas/genética , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patología , Receptores de Interleucina-7/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (≥2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13-2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA-IR cutoff point of ≥2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion. CONCLUSION: Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children. WHAT IS KNOWN: ⢠Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. ⢠Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children. WHAT IS NEW: ⢠Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. ⢠Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in order to maintain glucose homeostasis.
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Resistencia a la Insulina , Síndrome Metabólico/diagnóstico , Obesidad Infantil/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Síndrome Metabólico/fisiopatología , Obesidad Infantil/fisiopatología , Fenotipo , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: Most of what is known about the metabolically healthy obese phenomenon is derived from studies in the adult population and no standardized criteria to identify these individuals exist to date. The aim of this study was to determine if the preserved insulin sensitivity evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) index is associated with favorable metabolic profile in the obese children. We studied a group of 248 children and adolescents (150 female, 98 male), aged 5.9-18.9 years with diet-induced obesity (BMI >95th percentile). The entire cohort was divided into quartiles based on levels of insulin resistance determined by HOMA-IR index. Subjects in the lower quartile of HOMA-IR were classified as insulin-sensitive group (ISG), whereas children in the upper quartile were categorized as insulin-resistant group (IRG). The ISG subjects had values of HOMA-IR ≤2.75 while the children from the IRG group had HOMA-IR ≥6.16. Subjects from ISG group had lower basal ß-cell activity and were less likely to have impaired fasting glucose or impaired glucose tolerance. Concentrations of LDL and total cholesterol, triglycerides, and transaminases were lower and HDL cholesterol levels were higher in ISG subjects. Findings obtained by the use of Matsuda index correlated well with the findings obtained by the use of HOMA-IR. CONCLUSION: Lower HOMA-IR values were significantly associated with favorable metabolic profile in studied children, which correlates with findings in the adult population and emphasizes the need for further, longitudinal studies of insulin resistance development in childhood obesity.
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Resistencia a la Insulina/fisiología , Obesidad/sangre , Obesidad/fisiopatología , Adolescente , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Indicadores de Salud , Humanos , MasculinoRESUMEN
OBJECTIVE: The present study assessed changes of craniofacial complex in Turner syndrome (TS) patients treated with growth hormone (GH) during development. The objective was to examine the growth rate and pattern of craniofacial structures and to establish effects of GH on craniofacial development. MATERIALS AND METHODS: The study population consisted of 15 TS patients treated with GH aged 5-18.5 years (13.3 ± 4.4) and corresponding control group of 45 females aged 6.8-18.7 (11.4 ± 2.6). According to the stage of cervical vertebral maturation, subjects were categorized into pre-growth (5 TS and 15 controls) and growth (10 TS and 30 controls) subgroups. The cephalometric analysis comprised angular and linear variables, measured on lateral cephalometric radiographs. RESULTS: The mandibular corpus/anterior cranial base ratio increased significantly only in controls during development. In growth period, ramus/corpus ratio was significantly larger in TS group. SNA and SNB angles were significantly smaller in TS growth subgroup compared to corresponding controls. Among other variables, no statistically significant differences were revealed. CONCLUSIONS: In TS patients treated with GH, growth capacities of cranial base and maxilla are adequate which can be attributed to GH treatment. Shape of mandible is altered due to decreased growth of corpus and overdeveloped ramus. Both maxillary and mandibular retrognathism are becoming more expressed during development. CLINICAL RELEVANCE: Favorable influence of GH on craniofacial complex growth rate and altered growth pattern revealed in this study should be considered while planning both orthodontic treatment and retention.
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Huesos Faciales/crecimiento & desarrollo , Hormona de Crecimiento Humana/uso terapéutico , Desarrollo Maxilofacial/efectos de los fármacos , Cráneo/crecimiento & desarrollo , Síndrome de Turner/tratamiento farmacológico , Adolescente , Determinación de la Edad por el Esqueleto , Cefalometría/métodos , Vértebras Cervicales/crecimiento & desarrollo , Niño , Preescolar , Huesos Faciales/efectos de los fármacos , Femenino , Humanos , Mandíbula/efectos de los fármacos , Mandíbula/crecimiento & desarrollo , Maxilar/efectos de los fármacos , Maxilar/crecimiento & desarrollo , Hueso Nasal/efectos de los fármacos , Hueso Nasal/crecimiento & desarrollo , Retrognatismo/fisiopatología , Silla Turca/efectos de los fármacos , Silla Turca/crecimiento & desarrollo , Cráneo/efectos de los fármacos , Base del Cráneo/efectos de los fármacos , Base del Cráneo/crecimiento & desarrolloRESUMEN
Introduction: Migraine with aura (MwA) is a neurological condition manifested in moderate to severe headaches associated with transient visual and somatosensory symptoms, as well as higher cortical dysfunctions. Considering that about 5% of the world's population suffers from this condition and manifestation could be abundant and characterized by various symptoms, it is of great importance to focus on finding new and advanced techniques for the detection of different phenotypes, which in turn, can allow better diagnosis, classification, and biomarker validation, resulting in tailored treatments of MwA patients. Methods: This research aimed to test different machine learning techniques to distinguish healthy people from those suffering from MwA, as well as people with simple MwA and those experiencing complex MwA. Magnetic resonance imaging (MRI) post-processed data (cortical thickness, cortical surface area, cortical volume, cortical mean Gaussian curvature, and cortical folding index) was collected from 78 subjects [46 MwA patients (22 simple MwA and 24 complex MwA) and 32 healthy controls] with 340 different features used for the algorithm training. Results: The results show that an algorithm based on post-processed MRI data yields a high classification accuracy (97%) of MwA patients and precise distinction between simple MwA and complex MwA with an accuracy of 98%. Additionally, the sets of features relevant to the classification were identified. The feature importance ranking indicates the thickness of the left temporal pole, right lingual gyrus, and left pars opercularis as the most prominent markers for MwA classification, while the thickness of left pericalcarine gyrus and left pars opercularis are proposed as the two most important features for the simple and complex MwA classification. Discussion: This method shows significant potential in the validation of MwA diagnosis and subtype classification, which can tackle and challenge the current treatments of MwA.
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PURPOSE: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test. METHODS: A prospective, case-control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis. RESULTS: Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model. CONCLUSIONS: Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche.
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Pubertad Precoz , Pamoato de Triptorelina , Femenino , Hormona Folículo Estimulante , Hormona Liberadora de Gonadotropina , Humanos , Hormona Luteinizante , Estudios Prospectivos , Pubertad Precoz/diagnóstico , Pubertad Precoz/tratamiento farmacológicoRESUMEN
OBJECTIVE: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). DESIGN: Single- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16-25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. RESULTS: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). CONCLUSION: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.
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We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 1/complicaciones , Cetoacidosis Diabética/epidemiología , Índice de Severidad de la Enfermedad , Glucemia/análisis , Niño , Preescolar , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/etiología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Serbia/epidemiologíaRESUMEN
Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and neurodegeneration. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Over the period 1977-2008 we evaluated ten subjects with the clinical diagnosis of triple A syndrome. Molecular analysis was performed in seven patients and revealed that all except one are compound heterozygotes for two mutations in the AAAS gene. Two novel mutations were detected: c.123+2T>C resulted in splice defect while c.1261_1262insG mutation resulted in a truncated protein (p.V421fs), which most probably is not functional. Genotype-phenotype correlation could not be established. In all our patients, except one sibling of previously diagnosed brother and sister, genetic analysis was performed when at least two symptoms were present, usually alacrima and achalasia. Based on our experience, we recommend that in case of the presence of alacrima and at least one more symptom of triple A syndrome, adrenal function testing and molecular analysis should be performed. In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted.
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ADN/genética , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas de Complejo Poro Nuclear/genética , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/genética , Insuficiencia Suprarrenal/metabolismo , Niño , Preescolar , Cromosomas Humanos Par 12 , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/genética , Acalasia del Esófago/metabolismo , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Lactante , Masculino , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Estudios Retrospectivos , Factores de TiempoRESUMEN
Background Oxidative stress is implicated in both, the onset and the progression of type 1 diabetes mellitus (T1DM). There is accumulated evidence of increased biomarkers of oxidative stress in newly diagnosed, T1DM patients without complications, and in those with advanced disease. In this cross-sectional study, we investigated factors affecting oxidative stress status in pediatric patients with T1DM. Methods Advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), total sulfhydryl (SH) groups, and superoxide dismutase (SOD) activity were determined in 170 children and adolescents with T1DM. Principal component analysis was used to investigate clustering of clinical and laboratory variables associated with elevated oxidative stress and reduced antioxidative defense biomarkers. Results Factor analysis extracted five factors, interpreted as (1) "weight status factor" including age, BMI, waist and hip circumferences; (2) "proatherogenic factor" that included LDL-cholesterol, non-HDL-cholesterol, and triglycerides; (3) "metabolic control factor" including glucose and HbA1c; (4) "renal marker factor" with positive loading of urinary albumin excretion rate and negative loading of GFR; and (5) "antiatherogenic factor" that included HDL-cholesterol. High AOPP levels were independently predicted by "proatherogenic" (OR: 2.32; 95% CI: 1.44-3.71; p < 0.001), "metabolic control" (OR: 2.24; 95% CI: 1.35-3.73; p < 0.01), and "renal marker" (OR: 1.65; 95% CI: 1.03-2.65; p < 0.05) factors. "Renal marker factor" was a significant predictor of PAB (OR: 0.52; 95% CI: 0.34-0.81; p < 0.01). Regarding antioxidative defense markers, reduced SH groups were predicted by "proatherogenic factor" (OR: 0.56; 95% CI: 0.34-0.94; p < 0.05), while "weight status factor" predicted lower SOD activity (OR: 1.66; 95% CI: 1.03-2.67; p < 0.05). Conclusions Cardiometabolic risk factors and renal function are associated with oxidative stress in pediatric T1DM patients.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Estrés Oxidativo/fisiología , Adolescente , Biomarcadores/sangre , Niño , Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Triglicéridos/sangreRESUMEN
Milenkovic T, Vukovic R, Radojicic B, Mitrovic K, Todorovic S, Zatezalo L. Thirty years of the newborn screening program in Central Serbia: the missed cases of congenital hypothyroidism. Turk J Pediatr 2019; 61: 319- 324. Newborn Screening (NS) program for congenital hypothyroidism (CH) has completely changed the natural history of this devastating disorder for the vast majority of children with CH. However, cases of missed CH do happen, and it is important to keep this possibility in mind during every day clinical practice. The objective of this study was to analyze the recognized cases of undiagnosed CH by the NS program in Central Serbia in order to evaluate the reasons for such omissions. Data regarding the recognized missed cases of CH between the years of 1983 and 2013 were collected and analyzed. During 30 years of the NS program for CH on the territory of Central Serbia, 1,547,122 newborns were screened, and during this period, 14 children with CH were missed by the NS. Five missed cases were children with athyreosis (35.8%), 8 had ectopic thyroid gland (57.1%) and one child had dyshormonogenesis (7.1%). The median age at diagnosis of CH in these missed cases was 1.12 years (range 0.08-13.5 years). In the group of children with missed diagnosis of CH, 71.4% were missed due to errors during sample collection, and 28.6% of patients were missed due to false negative screening results. Continuous education of neonatologists as well as nurses in neonatal units of maternity hospital are necessary to avoid errors in sample collection. It is of high importance to notice in a discharge list if a child is referred to the hospital before the sample is taken in a maternity hospital. On the other hand, the maternity hospital has to inform the screening laboratory about any child who was referred to another hospital if the blood samples for screening are not taken. Parents should be better informed that each child has to be included in the NS which is obligatory in Serbia. In addition, awareness amongst pediatricians in primary care should be raised regarding the possibility of missed cases of CH.
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Hipotiroidismo Congénito/diagnóstico , Diagnóstico Erróneo/estadística & datos numéricos , Tamizaje Neonatal , Adolescente , Niño , Preescolar , Hipotiroidismo Congénito/epidemiología , Reacciones Falso Negativas , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Errores Médicos , Estudios Retrospectivos , Serbia/epidemiología , Manejo de Especímenes/efectos adversosRESUMEN
BACKGROUND AND AIMS: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. METHODS: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9⯱â¯3.0 years and treated by intensive insulin therapy. RESULTS: Plasma PCSK9 levels significantly increased with worsening of glycemic control (pâ¯<â¯0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (pâ¯<â¯0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (pâ¯<â¯0.001), but negatively with HDL size (pâ¯<â¯0.05). CONCLUSIONS: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Lipoproteínas LDL/metabolismo , Proproteína Convertasa 9/sangre , Adolescente , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Niño , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Dislipidemias/sangre , Femenino , Humanos , Insulina/uso terapéutico , Lipoproteínas HDL/metabolismo , Masculino , Análisis MultivarianteRESUMEN
Ostojic S, Vukovic R, Milenkovic T, Mitrovic K, Djuric M, Nikolic L. Alpha coma in an adolescent with diabetic ketoacidosis. Turk J Pediatr 2017; 59: 318-321. This is the first report of alpha coma (AC) caused by brain edema in a patient with diabetic ketoacidosis (DKA). A previously healthy 15-year-old girl was admitted to the intensive care unit due to altered state of consciousness during the course of treatment for DKA. Patient was in a coma, intubated and had tachycardia with poor peripheral perfusion. Results of laboratory analyses indicated severe DKA and computed tomography scan indicated diffuse brain edema. The EEG pattern showed uniform alpha activity. Treatment with intravenous fluids, insulin and mannitol was started. Patient`s state of consciousness gradually improved and on the third day she was extubated. On the fifth day, her neurologic status and EEG findings were completely normal with no residual neurological deficits. In conclusion, although AC is associated with a high fatality rate, favorable outcome can be achieved with prompt recognition and treatment of cerebral edema in pediatric patients with DKA.
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Edema Encefálico/complicaciones , Coma/etiología , Cetoacidosis Diabética/complicaciones , Adolescente , Edema Encefálico/diagnóstico , Edema Encefálico/terapia , Coma/terapia , Cetoacidosis Diabética/terapia , Electroencefalografía , Femenino , Fluidoterapia/métodos , Humanos , Insulina/uso terapéutico , Unidades de Cuidados Intensivos , Manitol/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
This seven-year retrospective study analysed the live birth rate (LBR) for women undergoing IVF treatment with various antral follicle counts (AFC). The LBR decreased with lower AFC ratings, and in 290 treatment cycles for women in the poorest AFC category, ≤4 follicles (group E), the LBR was the lowest at 10.7%. The pregnancy loss rate (PLR) significantly increased with poorer AFC categories, from 21.8% in AFC group A (≥20 follicles), to 54.4% in AFC group E (p<0.0001). This trend was repeated with advancing age, from 21.6% for younger women (<35years), to 32.9, 48.5 and 100% for ages 35-39, 40-44 and ≥45 years, respectively (p<0.0001). However, LBR within the specific AFC group E cohort was also age-dependent and decreased significantly from 30.0% for <35 years old, to 13.3, 3.9 and 0% for patients aged 35-39, 40-44 and ≥45 years, respectively. Most, importantly, LBR rates within these age groups were not dependent on the number of IVF attempts (1st, 2nd, 3rd or ≥4 cycles), which indicated that cycle number should not be the primary deciding factor for cessation of IVF treatment in responding women <45years old.
Asunto(s)
Mantenimiento del Cuerpo Lúteo/efectos de los fármacos , Técnicas de Cultivo de Embriones , Transferencia de Embrión , Fertilización In Vitro , Infertilidad Femenina/terapia , Reserva Ovárica , Inducción de la Ovulación , Adulto , Tasa de Natalidad , Gonadotropina Coriónica/farmacología , Estudios de Cohortes , Pérdida del Embrión/epidemiología , Femenino , Fármacos para la Fertilidad Femenina/farmacología , Humanos , Infertilidad Femenina/diagnóstico , Nacimiento Vivo , Edad Materna , Persona de Mediana Edad , Embarazo , Pronóstico , Estudios Retrospectivos , Australia Occidental/epidemiologíaRESUMEN
BACKGROUND: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". CASE PRESENTATION: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. CONCLUSIONS: This is the first described case of a child with PHH following esophageal reconstruction.
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Atresia Esofágica/cirugía , Derivación Gástrica/efectos adversos , Hiperinsulinismo/etiología , Hipoglucemia/etiología , Obesidad Mórbida/cirugía , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias , Niño , Femenino , Humanos , Hiperinsulinismo/patología , Hipoglucemia/patología , Obesidad Mórbida/complicaciones , Periodo Posprandial , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: The dichotomous nature of the current definition of metabolic syndrome (MS) in youth results in loss of information. On the other hand, the calculation of continuous MS scores using standardized residuals in linear regression (Z scores) or factor scores of principal component analysis (PCA) is highly impractical for clinical use. Recently, a novel, easily calculated continuous MS score called siMS score was developed based on the IDF MS criteria for the adult population. OBJECTIVE: To develop a Pediatric siMS score (PsiMS), a modified continuous MS score for use in the obese youth, based on the original siMS score, while keeping the score as simple as possible and retaining high correlation with more complex scores. SUBJECTS AND METHODS: The database consisted of clinical data on 153 obese (BMI ≥95th percentile) children and adolescents. Continuous MS scores were calculated using Z scores and PCA, as well as the original siMS score. Four variants of PsiMS score were developed in accordance with IDF criteria for MS in youth and correlation of these scores with PCA and Z score derived MS continuous scores was assessed. RESULTS: PsiMS score calculated using formula: (2xWaist/Height) + (Glucose(mmol/l)/5.6) + (triglycerides(mmol/l)/1.7) + (Systolic BP/130)-(HDL(mmol/l)/1.02) showed the highest correlation with most of the complex continuous scores (0.792-0.901). The original siMS score also showed high correlation with continuous MS scores. CONCLUSION: PsiMS score represents a practical and accurate score for the evaluation of MS in the obese youth. The original siMS score should be used when evaluating large cohorts consisting of both adults and children.
Asunto(s)
Síndrome Metabólico/metabolismo , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Análisis de Componente PrincipalRESUMEN
Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy.