Prepubertal Group Research Articles

Pediatric Keloids: A Retrospective, Single-Institution Cohort Analysis in Korea.

There are scant established data on the cause, distribution, treatment options, and recurrence rate of pediatric keloids in Asian populations. We characterized clinical features by comprehensively categorizing pediatric keloid patients into prepubertal and postpubertal groups at a single tertiary center. We searched the database of Kangbuk Samsung Hospital for pediatric patients (< 18 years) with clinically proven keloids who underwent outpatient-based treatment from 2007 to 2021. Clinical features, including demographics, distribution, underlying cause, treatment modality, and recurrence, were analyzed. Of the 93 patients (total 110 keloids), 42 females (45.2%) and 51 males (54.8%), with a mean age of 14.5 ± 4.1 years (range, 1-18 years), were retrospectively analyzed. The mean length of follow-up was 22.0 ± 14.2 months (range, 6-63). Of the 100 keloids with assessable causes, piercing (22%) and acne (19%) were the most common. In the prepubertal group, the lower and upper limbs (n = 7, 28%; n = 6, 24%) were the two most common locations, suggesting that post-traumatic keloids are common during this developmental period. In the postpubertal group, the ear (n = 25, 29.4%) was the most common site, which corresponds to the frequency of cosmetic piercing at this age. No differences were found between the effects of treatment methods on relapse rate. Understanding the clinical features of pediatric keloids is important in the therapeutic considerations for pediatric keloids. Future studies should analyze a larger number of children with keloids over longer observation periods.

Ultrastructural changes in the spermatogenic cells of domestic chicken (Gallus gallus domesticus) observed at different reproductive stages

Spermatogenesis is a complex process. It is the modification of progenitor spermatogonia into mature spermatozoa. The stages are similar in all-male vertebrates, as well as avian species. However, studies on spermatogenesis in birds are fewer compared to mammals. The current study investigated the ultrastructural changes in the spermatogenic cells of domestic chickens in different reproductive stages. Thirty (30) male birds, ten (10) in each of the three reproductive stages: pre-pubertal, pubertal, and adult were used in the study. Testicular tissues from all age groups were processed for transmission electron microscopy (TEM). TEM results showed spermatogonia and primary spermatocytes in the pre-pubertal testis, and the seminiferous tubule lumen was wide and empty. Also, the nuclei of spermatogonia at this stage did not contain condensed chromatin material at the center nor scattered at the periphery of the nuclear membrane. There were slight differences between the spermatogenic cells in the pubertal and adult age groups. The spermatogonia, primary and secondary spermatocytes, and round spermatids with scanty chromatin material were observed in both age groups. In the adult age group, round and elongated spermatids with condensed chromatin materials were observed besides the other spermatogenic cells. Also, the seminiferous tubule lumen was filled with sperm cells and cellular debris, unlike in the pre-pubertal and pubertal age groups where they were wide and empty. The presence of numerous oval mitochondria were observed in all age groups. This signifies the active process of spermatogenesis in pre-pubertal, pubertal, and adult male domestic chickens.

Hormonal and inflammatory responses in prepubertal vs. pubertal male children following an acute free-weight resistance training session.

Examine the acute hormonal and cytokine responses to free-weight resistance training in trained prepubertal and pubertal male children. Prepubertal (n = 21; age 11.4 ± 1.1years; Tanner I-II) and pubertal male children (n = 20; age 15.8 ± 0.7years; Tanner III-V) conducted a moderate-intensity free-weight resistance training program to failure with venous blood sampling before (pre), immediately after (post) and during the recovery phase of the program (post-15,-30min). Growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, testosterone, IL-6, and TNF-α were analyzed in serum samples. Biological maturation was assessed according to the stages of the Tanner scale. There was a significant time-by-group interaction in IGF-I response (p = 0.044; η2 = 0.209) and testosterone (p < 0.001; η2 = 0.508), indicating a greater change in the pubertal group compared to the prepubertal group. Both groups significantly increased post-exercise GH levels (p < 0.05). Only the prepuberal group significantly increased levels of IL-6 at all post-exercise time points (p < 0.05). Both groups showed a significant (p < 0.05) increase in TNF-α levels compared to resting levels. These data suggest that acute testosterone and IGF-I response following resistance training differ between trained prepubertal and pubertal male children. Moderate-intensity resistance training performed to failure may thus have different effects in trained prepubertal and pubertal male children, which should be considered when giving training advice. Clinical trials number: NCT05022992.

Morphometric, immunohistochemical and ultrastructural examination of age-related structural alterations in optic nerve

Aims: As individuals age, there is a known decline in visual function attributed to a reduction in the optic nerve fibers and myelin sheath degeneration. Studies present conflicting findings on whether aging affects axonal integrity in the human optic nerve. This study aims to investigate degenerative changes in the aging rat optic nerve. Methods: The investigation involved 36 Wistar albino rats. The rats were divided into six groups: the newborn, prepubertal, pubertal, junior, adult, and elderly groups. This study investigated optic nerve axon counts, axon diameters, levels of glial fibrillary acidic protein immunoreactivity (GFAP-IR) and nerve growth factor immunoreactivity (NGF-IR), as well as findings from light microscopy (LM) and electron microscopy (EM) in these groups. Results: This study observed age-related alterations in rat optic nerves, including increased diameter, irregular axon count fluctuations (both increases and decreases), elevated astrocyte count, and a simultaneous decline in oligodendrocyte count. Additionally, it was observed that NGF-IR was predominantly at the membrane level in newborns and moderately in the cytoplasm, whereas in older ages, it was evident at both cellular and axonal levels furthermore, it was observed that GFAP-IR increased with age. However, in LM and EM examinations, axonal loss and rarefaction, accumulation of osmiophilic substances, splitting of the myelin sheath, vacuolization, axonal retraction were observed. Conclusion: In this study, it was found that one of the causes of age-related vision loss is the advanced degenerative changes in the optic nerve and it was concluded that the remaining small-diameter myelinated nerve fibers may partially compensate for the sense of vision. Our study reveals that age-related degenerative changes in the central nervous system resemble those in multiple sclerosis (MS), suggesting a potential contribution to MS pathogenesis.

Paediatric idiopathic intracranial hypertension: Epidemiology, clinical features and treatment outcomes in a tertiary care centre in Western Australia.

This retrospective study aims to analyse the epidemiology, clinical and neuroimaging features, treatment modalities, and outcomes of paediatric idiopathic intracranial hypertension (IIH) in a tertiary care centre in Australia. Using the International Classification of Diseases Diagnostic Criteria for IIH, we identified and analysed a cohort of children diagnosed with IIH over a 5-year period (2017-2022). Data on patient demographics, symptomatology, examination findings, investigative results, treatments and outcomes were collected from medical records and electronic health records. A total of 45 cases were analysed. The pre-pubertal group saw a male predominance and the post-pubertal a female one. Increased body mass index was an associated comorbidity in majority of patients. Headaches (89%) and visual symptoms (56%) were the most common symptoms, with tinnitus also seen in 20% of patients. Papilledema was detected in 91% of the cases examined. The commonest neuroimaging features were optic nerve sheath distention (78%) and empty sella (49%). Acetazolamide was the primary treatment, with most patients responding well. Only a minority required surgical intervention. Long-term resolution of headaches was achieved in 89% of patients. The incidence of paediatric IIH in the West Australian population appears relatively high. It presents with subtle symptoms, emphasising the need for increased awareness among health-care providers. Younger children may represent a distinct subgroup with unique clinical features. Timely diagnosis and aggressive medical management lead to favourable outcomes. However, weight loss interventions showed limited effectiveness. This study underscores the importance of early recognition and management of paediatric IIH to optimise patient outcomes.

Pediatric sex estimation using AI-enabled ECG analysis: influence of pubertal development

AI-enabled ECGs have previously been shown to accurately predict patient sex in adults and correlate with sex hormone levels. We aimed to test the ability of AI-enabled ECGs to predict sex in the pediatric population and study the influence of pubertal development. AI-enabled ECG models were created using a convolutional neural network trained on pediatric 10-second, 12-lead ECGs. The first model was trained de novo using pediatric data. The second model used transfer learning from a previously validated adult data-derived algorithm. We analyzed the first ECG from 90,133 unique pediatric patients (aged ≤18 years) recorded between 1987–2022, and divided the cohort into training, validation, and testing datasets. Subgroup analysis was performed on prepubertal (0–7 years), peripubertal (8–14 years), and postpubertal (15–18 years) patients. The cohort was 46.7% male, with 21,678 prepubertal, 26,740 peripubertal, and 41,715 postpubertal children. The de novo pediatric model demonstrated 81% accuracy and an area under the curve (AUC) of 0.91. Model sensitivity was 0.79, specificity was 0.83, positive predicted value was 0.84, and the negative predicted value was 0.78, for the entire test cohort. The model’s discriminatory ability was highest in postpubertal (AUC = 0.98), lower in the peripubertal age group (AUC = 0.91), and poor in the prepubertal age group (AUC = 0.67). There was no significant performance difference observed between the transfer learning and de novo models. AI-enabled interpretation of ECG can estimate sex in peripubertal and postpubertal children with high accuracy.

Deregulation of oxidative phosphorylation pathways in embryos derived in vitro from prepubertal and pubertal heifers based on whole-transcriptome sequencing

BackgroundAlthough, oocytes from prepubertal donors are known to be less developmentally competent than those from adult donors it does not restrain their ability to produce full-term pregnancies. The transcriptomic profile of embryos could be used as a predictor for embryo’s individual developmental competence. The aim of the study was to compare transcriptomic profile of blastocysts derived from prepubertal and pubertal heifers oocytes. Bovine cumulus-oocyte complexes (COCs) were obtained by ovum pick- up method from prepubertal and pubertal heifers. After in vitro maturation COCs were fertilized and cultured to the blastocyst stage. Total RNA was isolated from both groups of blastocysts and RNA-seq was performed. Gene ontology analysis was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery).ResultsA higher average blastocyst rate was obtained in the pubertal than in the pre-pubertal group. There were no differences in the quality of blastocysts between the examined groups. We identified 436 differentially expressed genes (DEGs) between blastocysts derived from researched groups, of which 247 DEGs were downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes, and 189 DEGs were upregulated. The genes involved in mitochondrial function, including oxidative phosphorylation (OXPHOS) were found to be different in studied groups using Kyoto Encyclopedia of Genes (KEGG) pathway analysis and 8 of those DEGs were upregulated and 1 was downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes. DEGs associated with mitochondrial function were found: ATP synthases (ATP5MF-ATP synthase membrane subunit f, ATP5PD- ATP synthase peripheral stalk subunit d, ATP12A- ATPase H+/K + transporting non-gastric alpha2 subunit), NADH dehydrogenases (NDUFS3- NADH: ubiquinone oxidoreductase subunit core subunit S3, NDUFA13- NADH: ubiquinone oxidoreductase subunit A13, NDUFA3- NADH: ubiquinone oxidoreductase subunit A3), cytochrome c oxidase (COX17), cytochrome c somatic (CYCS) and ubiquinol cytochrome c reductase core protein 1 (UQCRC1). We found lower number of apoptotic cells in blastocysts derived from oocytes collected from prepubertal than those obtained from pubertal donors.ConclusionsDespite decreased expression of genes associated with OXPHOS pathway in blastocysts from prepubertal heifers oocytes, the increased level of ATP12A together with the lower number of apoptotic cells in these blastocysts might support their survival after transfer.

Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view.

Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.

Malignant Leydig Cell Tumor of Testis: Case Report

Testicular tumors accounts for % of the tumors in men. 5% of which are the sex cord stromal tumors and the remaining are of germ cell origin. Leydig cell are the common subtype of Sex cord stromal tumors and accounts for 1%-2% of all the testicular tumors. Tumor arises from the leydig cells that normally reside in the interstitium of testicles and secrete testosterone in the presence of leutenizing hormone. They show a bimodal distribution with peaks in the prepubertal age group and between 30-60yrs of age. Leydig cell tumor being a hormonally active tumor often presents with precocious puberty, breast tenderness and gynaecomastia. Histopathology reveals a well circumscribed mass .Cut surface shows golden brown homogenous appearance. Microscopically, tumor cells are large to polygonal with round to oval nucleus with deeply granular cytoplasm. Cytoplasm shows characteristics rod sghaped crystals referred to as “ crystalloids of Reinke”. Leydig cell tumors are mostly follow a benign course but approximately 5-10% of these have malignant potential. Regional lymph nodes, lungs , liver and bones are the commonest sites of metastsis. Due to aggressive difficult to treat nature of metastatic disease it is essential to differentiate benign leydig cell tumor from its malignant counterpart in order to guide its initial surgical and radiological management. Assessment of the clinicopathological features of Leydig cell tumor allows for its optimal management.

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24h; u24LH = 0.035 or 0.08 IU/24h). The combination of u24FSH > 1.1 IU/24h and u24LH > 0.08 IU/24h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. No specific funding was used. All authors declared no conflict of interest. In-house #23-5214 registered study.

(246) Age Dependent Effect on Contralateral Testicular Compensation Following Testicular Loss

Abstract Introduction The human testicle is susceptible to loss from events like torsion, trauma, cancer, or cryptorchidism. Most paired organs are known to undergo compensatory hypertrophy following unilateral organ loss. The testicle is physiologically distinct in that it is thought to undergo a period of quiescence in childhood. Previous work has demonstrated testicular hypertrophy occurs if the loss of the contralateral testis occurs before puberty. However, it is unknown if compensatory physiology and growth differs by age of pre-pubertal loss. Objective This study aimed to investigate compensatory changes in testicular growth and the hormonal axis following unilateral orchiectomy in a neonatal, pre-pubertal and pubertal/adult murine model. Methods C57BL/6 mice were divided into experimental groups: neonatal (days of life 2-4), pre-pubescent (days of life 12-21), and post-pubescent (days of life 42-44) to undergo unilateral orchiectomy. A control group that did not undergo orchiectomy was utilized. Mice were sacrificed at maturity (over 80 days of life), blood samples were drawn, and the remaining testis was removed. Body and testis weight and testicular length in the long axis were measured in blinded fashion. Similarly, testosterone, luteinizing hormone (LH), and Follicle stimulating hormone (FSH) were assessed and expressed as a median and an interquartile range. Results Contralateral testes from neonatal and pre-pubertal mice who underwent orchiectomy weighed more (110.5, 12.2 and 103.0, 7.2 mg respectively. Figure 1.) (p &amp;lt; 0.05) than the control mice (91, 11.9 mg, respectively). There was no difference between post-pubertal group and control group. The degree of compensatory hypertrophy was greater in the neonatal group but not the pre-pubertal group when compared to the post-pubertal group. When examining the ratio of testicular weight to body weight, only the neonatal group was significantly higher than that of the control. Differences in FSH and testosterone were not statistically significant between experimental and control arms (p &amp;gt; 0.05). LH was significantly elevated in all experimental groups as compared to the control (p &amp;lt; 0.05). Conclusions This is the first study to assess testicular compensatory hypertrophy following contralateral testicular loss using a neonatal mouse survival surgery model. Testicular hypertrophy occurs when unilateral loss occurs prior to puberty, but not in adulthood in mice. Earlier testis loss may contribute to a greater degree of growth. Functionally, the unilateral testis can maintain eugonadal testosterone levels, but higher levels of LH are required following hemicastration to sustain eugonadal testosterone levels. Future studies are warranted to identify testicular transcriptomics in this model to evaluate for candidate genes potentially responsible for this phenotypic change. Disclosure No.

Exploring the link between pediatric headaches and environmental noise exposure

BackgroundHeadaches are the most common neurologic symptoms in the pediatric population. Most primary headache in children and adolescents focuses on associated factors, including noise. Auditory discomfort is related to recognizing the pain. We aimed to analyze the headache profile of pediatric populations and the connection between noise exposure and head pain in children and adolescents.MethodsWe reviewed retrospectively medical records of the pediatric population with headaches in Gyeongsang National University Changwon Hospital from January 2022 to April 2023. Personal headache profiling from self-questionnaires and environmental noise data from the National Noise Information System (NNIS) were used to analyze each variable, and chi-square tests and linear regression models by SAS were used to analyze the statistical correlation.ResultsOf the 224 participants, 125 were clinically diagnosed with headaches. Of the 104 pubertal subjects, 56.7% were diagnosed with headaches, compared to 60% in the prepubertal group. Both daytime and nighttime noise was significantly higher in the diagnosed headache group than in the non-diagnosed group. Headache duration increased by daytime and nighttime noise with statistical significance in age-adjusted models.ConclusionWe found that noise exposure is correlated to headaches in children and adolescents. Daytime and nighttime environmental noise exposure was significantly associated with the duration of headaches through our data. Therefore, we assume that noise exposure is vitally relevant to prolonged headaches in the pediatric population. Further research is needed to improve our data.

Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

Pediatric intracranial hypertension: A review of presenting symptoms, quality of life, and secondary causes

AbstractOur understanding of primary (idiopathic) intracranial hypertension has evolved in recent years. There have been efforts to rename the disorder as pseudotumor cerebri syndrome or primary intracranial hypertension. Some studies have suggested a higher threshold opening pressure to define intracranial hypertension. The reported annual incidence varies from 0.6 to 0.9 per 100 000 children around the world. Patients are typically divided into prepubertal and pubertal groups, with pubertal patients having the same risk factors as adults. Prepubertal patients do not share these risk factors. They are more likely to be asymptomatic, have equal gender distributions, and are less likely to be obese. Headache is the most common presenting complaint, followed by vision changes and nausea/vomiting. A newer concept of fulminant intracranial hypertension has emerged, defined as acute onset with rapid progression of visual deficits or papilledema. Quick insertion of a temporary lumbar drain as a bridge while medical management reaches effectiveness improves visual outcomes and helps avoid permanent shunt placement. Headache is typically the first symptom to resolve with treatment, and papilledema resolves in five to six months. Recurrence rates in children and adolescents range from 28.5% to 36.4%, with higher rates after puberty.

Evaluation of an objective staging system for assessment of cervical vertebral maturation

BackgroundThe aim of this study was to evaluate an objective method for Cervical Vertebral Maturation (CVM) staging.MethodsAn initial sample of 647 Lateral Cephalometric Radiographs (LCR) were staged according to the CVM (Baccetti et al.) by 4 examiners. The final sample (n = 394) included LCR on which the staging of the 4 investigators matched. The objective staging was performed by a single operator. The sample was divided according to the maturational stages into pre-pubertal, pubertal and post-pubertal groups. Measurements were performed on the cervical vertebrae (C2, C3 and C4). The angle between posterior and superior borders for C3 and C4 was the Superior Wall Inclination Angle (SWIA). Concavity Depth (CD) for C2, C3 and C4, and Body Shape (BS) (ratio of width to height of C3 and C4). Measurements of the 3 groups were compared.ResultsReliability of subjective staging was high (intra-observer reliability, 0.948; inter-observer reliability, 0.967). Good agreement was observed for the outcomes measured. Intra-observer reliability was good (0.918, 0.885 and 0.722 for CD, BS and SWIA, respectively). The same was for the inter-observer reliability results (0.902, 0.889 and 0.728 for CD, BS and SWIA, respectively). Significant differences were observed for mean values of SWIA and BS and median values of CD within maturational stage. Similar findings were observed when the outcomes were compared at different phases (P < 0.001).ConclusionsA standardized, objective staging system using linear, angular measurements and ratios was applied for the determination of cervical vertebral maturation.

Reference intervals for serum 11-oxygenated androgens in children.

Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens. Reference interval study for serum 11-oxygenated androgens in children. We developed and validated a sensitive LC-MS/MS assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal (n=133; 94 boys, 39 girls) and pubertal (n=123; 52 boys, 71 girls)) to compute reference intervals (2.5th - 97.5th percentiles). In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not. We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism.

Clinicopathological Evaluation of Extragonadal Germ Cell Tumors - A Retrospective Study from a Regional Cancer Center in India

Introduction: Extragonadal germ cell tumors (EGGCTs) are tumors arising at extragonadal ana-tomical locations. The biological behavior and prognosis of these tumors differ from their gonadal counterparts. Our study aims to analyze their histological subtypes, the outcome, and the prognosis of these lesions at various age groups.Material and Methods: We carried out a retrospective analysis of all patients with EGGCTs diag-nosed from January 2017 to December 2019. Results: Our study included 61 cases of EGGCTs. These cases were divided into neonatal (birth to six months), prepubertal (more than six months to 12 years), and post-pubertal group (&gt;12 years). The most frequently affected group was prepubertal (44.2%). The age ranged from birth to 45 years with a male-to-female ratio of 1:1.03. The frequently involved site was sacrococcyx (36%) followed by mediastinum (31.1%). The common histologic subtype was mature teratoma (39.3%), followed by yolk sac tumor (YST) (18%), mixed germ cell tumor (18%), immature teratoma (14.7%), and germinoma (9.8%). Four cases of teratoma had somatic malignancies. There were 48 stage I, 8 stage II, and 2 stage III tumors. Statistical analysis revealed a significant association of age group concerning primary site (p=0.004), histological type (p=0.002), and clinical stage (p=0.034). In a median follow-up of 30 months, an Overall Survival (OS) of 93.2% and Event Free Survival (EFS) of 90.4% were noted across all age groups. OS of 100% (neon tal), 96% (prepubertal) and 88.0% (post-pubertal) revealing a declining trend (p=0.324) with increasing age was noted. The important prognostic factors include histological subtype (mixed germ cell tumors and teratomas with somatic malignancies had reduced overall survival) and stage (I vs II and III) for OS and stage alone for EFS (P&lt;0.0001). Conclusion: Our study highlights the clinicopathological characteristics, prognostic parameters, and the outcome of GCTs occurring at extragonadal sites and emphasizes the role of pathologists in the detailed reporting of these lesions.&#x0D;

Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (-0.3 SD vs. -1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was -0.2 SD in the cyclical menstruation group and -2.3 SD in the HRT group (p = 0.016). Spearman's rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

Prepubertal ve Pubertal Hastalarda Hashimoto Tiroiditi’nin Dağılımı, Klinik Özellikleri ve Laboratuvar Bulguları

Aims:Hashimoto's thyroiditis (HT) is the most common cause of acquired hypothyroidism in childhood. This disease, which develops on an autoimmune basis, often appears in adolescence. However, in recent years, However, in recent years, cases diagnosed with this disease in prepubertal and infant period have been reported. This is considered to regarding early exposure to environmental factors that disrupt the endocrine system and trigger autoimmunity. We aimed to evaluate the distribution, clinical features, and laboratory findings of our patients diagnosed with Hashimoto's thyroiditis in our clinic in prepubertal and pubertal periods. Material and Method:In the study, the cases diagnosed with Hashimoto's Thyroiditis in Ankara City Hospital Pediatric Endocrinology 5th outpatient clinic between August 2019 and May 2022 were divided into two groups prepubertal (Tanner stage 1) and pubertal (Tanner stage 2-3-4-5). The two groups were compared retrospectively in terms of clinical, laboratory, and ultrasound findings. Results: The mean±SDS of 134 patients diagnosed with HT was 12.4±3.4 years. While 25% (n:33) of the cases were prepubertal, 75% (n:101) were pubertal. The cases' female/male ratio (F/M) was 4.1/1, F/M: 2.3/1 in the prepubertal period, and F/M: 5.3/1 in the pubertal period. The euthyroid phase was detected most frequently in all cases at diagnosis. While the rate of euthyroid and subclinical hypothyroidism was the same in the prepubertal group, it was most detected in these two phases. In the pubertal group, it was mostly detected in the euthyroid phase. When we compared the prepubertal and pubertal groups, it was seen that subclinical hypothyroidism and hypothyroidism were most common in the prepubertal group. In contrast, subclinical hyperthyroidism and hyperthyroidism were more common in the pubertal group. Conclusion:In our study, HT is more prevalent in boys at the prepubertal stage than in the pubertal stage. While the patients in the prepubertal period applied in the hypothyroid phase, it was remarkable that the pubertal group had hyperthyroidism in their admissions.

Comparisons of soft tissue changes after Herbst appliance treatment in three different growth phases

This study aimed to compare the soft tissue effects of Herbst appliance in Class II malocclusion patients treated in three different craniofacial growth phases: prepubertal (PRE), circumpubertal (CIR), and postpubertal (POS). In total, 95 patients with Class II Division 1 malocclusion previously treated with a Herbst appliance were analyzed. Through the cervical vertebral maturation stages method, patients were allocated into three groups depending on the growth craniofacial phase at the beginning of treatment: PRE, CIR, and POS. Seventeen cephalometric measures were evaluated from each lateral radiograph before and after Herbst therapy using the Radiocef 2 software (Radio Memory, Belo Horizonte). Intragroup and intergroup treatment changes were compared statistically using a paired t test and MANOVA test, respectively. Soft tissue thickness changes were related only to mandible; all three mandibular measurements (L1_LL, B_B', and Pog_Pog') showed thickening for the PRE group ranging from 0.92 mm (Pog_Pog') to 2.02 mm (B_B'), and only lower lip thickened overtime for the POS group (L1_LL = 0.99 mm). Soft and hard tissue pogonion displaced anteriorly, but only the soft tissue showed differences among groups; PRE group presented more anterior displacement than POS group (3.61 mm and 1.39 mm, respectively). Hard and soft tissue facial convexity decreased more in the PRE and CIR groups than in the POS group. Mentolabial sulcus depth reduced more in the PRE (1.07 mm) and CIR (1.29 mm) groups than in the POS (0.55 mm) group. Horizontal movement of the skeletal and soft pogonion presented a moderate-high positive correlation (r = 0.783), and hard and soft facial convexity showed a moderate-low positive correlation (r = 0.403). Herbst appliance therapy produces soft tissue improvements in the three phases of craniofacial growth, being greater in patients in the PRE and CIR phases.