Testicular microlithiasis in a boy with X-linked adrenal hypoplasia congenita

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up

Clinical and laboratory markers of the Metabolic Syndrome in children and adolescents with increased body weight

In his Banting Lecture in 1988, Gerald Reaven suggested that three major conditions –type 2 diabetes mellitus (DM2), hypertension and coronary artery disease- must have a common underlying pathomechanism, namely the resistance to insulin-stimulated glucose uptake and the resultant hyperinsulinemia. Since that time, this construct has evolved conceptually and functionally into an entity that many refer to as the Metabolic Syndrome (MS). Several scientific groups have tried to define the MS in adults as well as in children and adolescents. In addition, a vast number of papers have been published in an attempt to clarify the roots of the syndrome, its components and its possible ramifications later in life. Parallel to the obesity pandemic in children and adolescents what became gradually clear was that the MS and its components are already present in obese children since the early years of childhood, predisposing them to DM2 and cardiovascular disease (CVD). Since a universally accepted definition of the syndrome in children and adolescents does not exist and since its pathophysiology and consequences have not been fully elucidated, it is important to seek components of the syndrome in obese children that could help in its early diagnosis. The objective of this study was 3-fold: to detect in obese children and adolescents (through their comparison with lean counterparts) primary and secondary abnormalities identified in adults with the MS; to look for laboratory indices that could help in an early diagnosis of the syndrome in obese children; to determine the prevalence of the MS in obese children and adolescents of northwestern Greece. The present study included 103 obese children and adolescents, 5 to 16 years of age (mean: 11,3±2,9 years), that presented to the University Hospital of Ioannina, Ioannina, Greece, with primary obesity (any cause of secondary obesity was excluded). These children went through a thorough physical examination and blood was drawn for basic labs and more specific lab measurements. In addition, an oral glucose tolerance test (OGTT) was performed for every obese child. Obese children were compared to a control group which comprised 69 healthy children and adolescents for whom, a physical was performed and blood was drawn in the same manner (except for the OGTT). The results of this study show that obese children frequently present the major and some of the secondary components of the MS and thus are at increased risk for its complications. More specifically, regarding the physical measurements, obese children had a statistically significantly higher waist circumference, hip circumference, and waist-to-hip and waist-to-height ratio. In addition, skinfold thickness that was measured in biceps, triceps, subscapular and abdominal areas, showed a statistically significant increase in obese children compared to their lean counterparts. Regarding blood pressure (BP), both systolic and diastolic BP were statistically significantly higher in obese children compared to controls. This statistical difference was more important for systolic BP. In addition, obese boys presented with statistically significantly higher systolic BP compared to obese girls. Glucose handling abnormalities included higher insulin resistance (higher HOMA index) and hyperinsulinemia in obese children compared to controls. There was no statistically significant difference in fasting glucose levels between the two groups. In addition, eight out of the 103 obese children presented with IFG, seven had IGT in OGTT, one had both IFG and IGT and one was diagnosed with DM2. Among the control group, one child had IFG. Regarding lipid metabolism, obese children had statistically significantly lower HDL cholesterol and higher triglycerides compared to controls, while no statistically significant difference in total or LDL cholesterol was found. In addition, obese children had lower levels of the protective apolipoprotein apoAI and higher levels of the atherogenic apoB compared to controls. Regarding the secondary characteristics of the MS, obese children and adolescents presented with a prothrombotic and proinflammatory condition. More specifically, both CRP and ESR were statistically significantly higher in obese children, even if their mean value was within the normal limits. The same was true for fibrinogen. In addition, among the hepatic enzymes that were measured, ALT and GGT were statistically significantly higher in obese children and especially in obese boys. This finding suggests an early liver involvement in obese children with characteristics of the MS. Microalbumin was measured in a first morning spot urine sample but showed no significant difference between the two groups. Finally, uric acid was statistically significantly higher in obese children compared to controls. Special lab parameters measured included leptin, IL-6, adiponectin, visfatin as well as plasma renin activity (PRA) and aldosterone...Το ΜΣ προτάθηκε για πρώτη φορά ως έννοια το 1988 από τον Gerald Reaven, ο οποίος υποστήριξε ότι η ινσουλινική αντίσταση και η επακόλουθη υπερινσουλιναιμία πιθανά να είναι ο παθογενετικός μηχανισμός που συνδέει τη συνύπαρξη πολλαπλών μεταβολικών διαταραχών στον ίδιο ασθενή. Στις δύο δεκαετίες που μεσολάβησαν από τότε προτάθηκαν κριτήρια για τον ορισμό του ΜΣ σε ενηλίκους αλλά και παιδιά κι εφήβους, ενώ σε εξέλιξη είναι η έρευνα σχετικά με την παθοφυσιολογία του και τις πιθανές εκδηλώσεις και επιπλοκές του. Στα χρόνια αυτά, και παράλληλα με την ραγδαία εξάπλωση της παχυσαρκίας στα παιδιά και τους εφήβους, έγινε φανερό ότι το ΜΣ εμφανίζεται ήδη από την πρώτη δεκαετία της ζωής σε παχύσαρκα παιδιά, με αποτέλεσμα την επιδείνωση της υγείας τους και τον κίνδυνο για ανάπτυξη ΣΔ2 και καρδιαγγειακών νοσημάτων στη νεαρή ενήλικη ζωή. Καθώς ευρέως αποδεκτός ορισμός του συνδρόμου στην παιδική ηλικία δεν υπάρχει και καθώς η παθοφυσιολογία του δεν έχει ακόμη πλήρως διαλευκανθεί, είναι πολύ σημαντική η προσπάθεια ανεύρεσης χαρακτηριστικών στα παχύσαρκα παιδιά που συνδέονται με το σύνδρομο και που θα μπορούσαν να βοηθήσουν στην έγκαιρη διάγνωσή του. Στο πλαίσιο αυτό σχεδιάστηκε η παρούσα μελέτη με σκοπό την ανίχνευση, σε παχύσαρκα παιδιά κι εφήβους, χαρακτηριστικών του ΜΣ που έχουν παρατηρηθεί στους ενήλικες, καθώς και τη διερεύνηση πιθανών εργαστηριακών δεικτών που θα μπορούσαν να συμβάλλουν στην διάγνωση του συνδρόμου πριν την πλήρη έκφραση του. Τον πληθυσμό της μελέτης αποτέλεσαν 103 παχύσαρκα παιδιά κι έφηβοι ηλικίας 5-16 χρονών (μέσος όρος 11,3±2,9 έτη), στα οποία αποκλείστηκε κάποιο αίτιο δευτεροπαθούς παχυσαρκίας. Στα παιδιά αυτά, έγινε εκτενής αντικειμενική εξέταση με καταγραφή ειδικών σωματομετρικών παραμέτρων και ΑΠ, και στη συνέχεια έγινε αιμοληψία για γενικό και πιο ειδικό εργαστηριακό έλεγχο και υποβλήθηκαν σε καμπύλη ανοχής γλυκόζης. Τα αποτελέσματα των μετρήσεων αυτών (πλην της καμπύλης ανοχής γλυκόζης) συγκρίθηκαν με ανάλογες μετρήσεις που έγιναν σε 69 υγιή παιδιά κι εφήβους με φυσιολογικό ΒΣ, αντίστοιχης ηλικίας και φύλου (ομάδα ελέγχου). Τα αποτελέσματα της μελέτης δείχνουν ότι τα παχύσαρκα παιδιά εμφανίζουν σε μεγάλη συχνότητα τα κύρια και ορισμένα από τα δευτερεύοντα χαρακτηριστικά του ΜΣ με αποτέλεσμα να διατρέχουν αυξημένο κίνδυνο πρώιμης εμφάνισης των επιπλοκών του. Πιο συγκεκριμένα, όσον αφορά τις σωματομετρικές παραμέτρους, τα παχύσαρκα παιδιά είχαν στατιστικά σημαντικά μεγαλύτερη ΠΜ, ΠΙ καθώς και τους λόγους ΠΜ/ΠΙ και ΠΜ/ΥΣ. Επίσης, το ΠΔΠ που μετρήθηκε στην περιοχή του δικεφάλου, του τρικεφάλου καθώς και στην υποπλάτια και κοιλιακή χώρα ήταν στατιστικά σημαντικά υψηλότερο στα παχύσαρκα παιδιά σε σχέση με τους μάρτυρες. Όσον αφορά την ΑΠ, τόσο η συστολική όσο και η διαστολική ΑΠ ήταν στατιστικά σημαντικά υψηλότερες στα παχύσαρκα παιδιά κι εφήβους σε σχέση με τους μάρτυρες. Η στατιστική αυτή διαφορά ήταν πιο έντονη για τη ΣΑΠ. Επιπλέον, στατιστικά σημαντικά υψηλότερη ήταν η ΣΑΠ στα παχύσαρκα αγόρια έναντι των παχύσαρκων κοριτσιών. Οι διαταραχές στο μεταβολισμό της γλυκόζης και στα επίπεδα ινσουλίνης περιελάμβαναν αυξημένη ινσουλινική αντίσταση στα παχύσαρκα παιδιά (αυξημένος δείκτης HOMA) και υπερινσουλιναιμία συγκριτικά με τους μάρτυρες, ενώ οι τιμές γλυκόζης νήστεως δε διέφεραν στατιστικά σημαντικά μεταξύ των δύο ομάδων παιδιών. Επιπλέον, από τα 103 παχύσαρκα παιδιά, τα 8 είχαν IFG, τα 7 είχαν IGT, ένα είχε ταυτόχρονα IFG και IGT και ένα είχε ΣΔ2. Από την ομάδα ελέγχου, ένα παιδί είχε IFG. Ως προς το μεταβολισμό των λιπιδίων, τα παχύσαρκα παιδιά είχαν στατιστικά σημαντικά χαμηλότερη HDL και υψηλότερα TG σε σχέση με τους μάρτυρες, ενώ η CH και η LDL δεν παρουσίασαν στατιστικά σημαντικές διαφορές. Επίσης, τα παχύσαρκα παιδιά παρουσίασαν μείωση των τιμών της αντι-αθηρωγόνου αποπρωτεΐνης apoAI, ενώ τα επίπεδα της αθηρωγόνου apoB ήταν συγκριτικά αυξημένα. Ως προς τα δευτερεύοντα χαρακτηριστικά του συνδρόμου, τα παχύσαρκα παιδιά εμφάνισαν δείκτες υποκλινικής φλεγμονής και προθρομβωτικής κατάστασης. Συγκεκριμένα, τόσο η CRP όσο και η TKE ήταν στατιστικά σημαντικά υψηλότερες στα παχύσαρκα άτομα, αν και παρέμεναν εντός των φυσιολογικών ορίων. Επίσης, το ινωδογόνο ήταν στατιστικά σημαντικά αυξημένο στα παχύσαρκα παιδιά. Στατιστικά σημαντική αύξηση διαπιστώθηκε και για τα δύο (ALT και γGT) από τα τρία ηπατικά ένζυμα που μετρήθηκαν ως έμμεσοι δείκτες ηπατικής συμμετοχής στο ΜΣ (μη αλκοολική λιπώδης διήθηση του ήπατος). Επιπλέον, τα παχύσαρκα αγόρια είχαν μεγαλύτερη αύξηση σε σχέση με τα παχύσαρκα κορίτσια. Η μικρολευκωματίνη σε πρώτο πρωινό δείγμα ούρων (ως δείκτης πρώιμης νεφρικής δυσλειτουργίας) δεν έδειξε στατιστικά σημαντική διαφορά. Τέλος, το ουρικό οξύ ορού ήταν στατιστικά σημαντικά αυξημένο στα παχύσαρκα παιδιά σε σχέση με τους μάρτυρες..

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S–23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings

Classification and Special Nutritional Needs of SGA Infants and Neonates of Multiple Pregnancies

Data regarding the nutritional management of preterm small for gestational age (SGA) infants are scarce. In the recent report of ESPGHAN, the recommended energy for very preterm infants during hospitalization has been increased, yet this may not fit the needs of all preterm infants. It is important to distinguish fetal growth-restricted (FGR) infants from constitutional SGA infants, as well as preterm SGA from preterm AGA infants, since they may have different nutritional needs. Preterm FGR infants, and specifically infants < 29 weeks’ gestation, accumulate nutrient deficits due to intrauterine malnutrition, prematurity, morbidities, delayed initiation of feeding, and feeding intolerance. Therefore, these infants may need more aggressive nutrition for optimal catch-up growth and neurologic development. However, a balance should be kept between optimal and excessive catch-up growth, since the combination of intrauterine malnutrition and excessive postnatal growth has been linked with later adverse metabolic consequences. Furthermore, multiple gestation is often complicated by FGR and prematurity. There is controversy in the definition of FGR in multiple gestations, and it should be noted that FGR in multiple gestation usually differs etiologically from FGR in singletons. The aim of this review is to summarize existing knowledge regarding the nutritional needs of preterm FGR and FGR infants of multiple gestation

Reintroduction of Legacy Antibiotics in Neonatal Sepsis: The Special Role of Fosfomycin and Colistin

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low- and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics colistin and fosfomycin for the empirical treatment of neonatal sepsis. Based on current knowledge, colistin and fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients

Traditionally a disease of adults, type 2 diabetes (T2D) has been increasingly diagnosed in youth, particularly among adolescents and young adults of minority ethnic groups. Especially, during the recent COVID-19 pandemic, obesity and prediabetes have surged not only in minority ethnic groups but also in the general population, further raising T2D risk. Regarding its pathogenesis, a gradually increasing insulin resistance due to central adiposity combined with a progressively defective β-cell function are the main culprits. Especially in youth-onset T2D, a rapid β-cell activity decline has been observed, leading to higher treatment failure rates, and early complications. In addition, it is well established that both the quantity and quality of food ingested by individuals play a key role in T2D pathogenesis. A chronic imbalance between caloric intake and expenditure together with impaired micronutrient intake can lead to obesity and insulin resistance on one hand, and β-cell failure and defective insulin production on the other. This review summarizes our evolving understanding of the pathophysiological mechanisms involved in defective insulin secretion by the pancreatic islets in youth- and adult-onset T2D and, further, of the role various micronutrients play in these pathomechanisms. This knowledge is essential if we are to curtail the serious long-term complications of T2D both in pediatric and adult populations

Blood Adhesion Molecules as Biomarkers in Children with Chronic Urticaria

Background: The prevailing etiological model of both acute and chronic urticaria implicates specific allergen exposure that triggers the local release of vasoactive factors and inflammatory adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), P-selectin and E-selectin in the superficial dermis. This study focused on the possible role of VCAM-1 and ICAM-1 as biomarkers in children with acute and chronic urticaria. Methods: This study involved 184 children, 40 with acute urticaria, 71 with chronic urticaria, and 73 matched comparison subjects. The serum levels of ICAM-1 and VCAM-1 were determined in venous blood in all the participants on enrollment. Antihistamine treatment was administered to all the patients. In the children with chronic urticaria, the Urticaria Activity Score Questionnaire (UAS7) was completed daily by the parents. In 16 of the patients with acute urticaria and 43 with chronic urticaria, the serum levels of ICAM-1 and VCAM-1 were determined at follow-up after 6–8 weeks of treatment. Results: The mean serum levels of both VCAM-1 and ICAM-1 were higher in both groups of children with urticaria than in the comparison subjects at the start of the study. In the chronic urticaria group, the levels decreased significantly (p = 0.03 and p = 0.01, respectively) following treatment. Similarly, the acute urticaria group exhibited significant reduction in the mean levels of VCAM and ICAM (p < 0.001). In both groups, the mean level of ICAM after treatment was comparable with that of the comparison group. Conclusions: VCAM-1 and ICAM-1 are suggested as promising biomarkers for monitoring both acute and chronic urticaria in children. Future research should explore their utility in larger cohorts and investigate their role in personalized treatment strategies

Serum Fibroblast Growth Factor 21 Levels in Children and Adolescents with Hashimoto&rsquo;s Thyroiditis before and after l-Thyroxin Medication: A Prospective Study

Backgrounds and Objectives: Fibroblast growth factor 21 (FGF-21) is a complex hormone, sharing common sites of action with thyroid hormones. We investigated the association among FGF-21 levels, resting metabolic rate (RMR), and l-thyroxin (LT4) treatment in children and adolescents with Hashimoto&rsquo;s thyroiditis. Materials and Methods: A total of 60 youngsters with chronic autoimmune thyroiditis (AIT) (30 with subclinical hypothyroidism, 30 with euthyroidism) and 30 age and sex-matched healthy participants (5&ndash;18 years old) were enrolled in the study. Anthropometric, biochemical parameters, and RMR levels were assessed in all participants; serum FGF-21 levels were measured in the control group and the group with subclinical hypothyroidism before and six months after medication with LT4. Results: FGF-21 levels were lower in the treatment group compared with the healthy ones, but this difference was not statistically significant (p &gt; 0.05); despite the increase in FGF-21 levels after six months of LT4 treatment, this difference was not statistically significant (p &gt; 0.05). Free thyroxin (FT4) levels correlated well with FGF-21 levels (r = 0.399, p &lt; 0.01), but further analysis revealed no interaction between these two variables. Both patient groups presented elevated triglyceride (TG) levels compared to controls (p &lt; 0.05). LT4 treatment had no impact on RMR and lipid or liver or glycaemic parameters. An increase in fat mass and fat-free mass were reported, independently of FGF-21 levels. Conclusions: In youngsters with subclinical hypothyroidism due to Hashimoto&rsquo;s thyroiditis, the serum FGF-21 levels are not significantly lower than in healthy individuals and increase after treatment with LT4 without a statistical significance. Further studies with a large number of young patients and severe hypothyroidism are recommended to confirm our results

Predictive Factors for Pediatric Craniopharyngioma Recurrence: An Extensive Narrative Review

Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis

Cellular Localization of Orexin 1 Receptor in Human Hypothalamus and Morphological Analysis of Neurons Expressing the Receptor

The orexin system is related to food behavior, energy balance, wakefulness and the reward system. It consists of the neuropeptides orexin A and B, and their receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX1R has selective affinity for orexin A, and is implicated in multiple functions, such as reward, emotions, and autonomic regulation. This study provides information about the OX1R distribution in human hypothalamus. The human hypothalamus, despite its small size, demonstrates a remarkable complexity in terms of cell populations and cellular morphology. Numerous studies have focused on various neurotransmitters and neuropeptides in the hypothalamus, both in animals and humans, however, there is limited experimental data on the morphological characteristics of neurons. The immunohistochemical analysis of the human hypothalamus revealed that OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The rest of the hypothalamic nuclei do not express the receptor, except for a very low number of neurons in the mammillary bodies. After identifying the nuclei and neuronal groups that were immunopositive for OX1R, a morphological and morphometric analysis of those neurons was conducted using the Golgi method. The analysis revealed that the neurons in the lateral hypothalamic area were uniform in terms of their morphological characteristics, often forming small groups of three to four neurons. A high proportion of neurons in this area (over 80%) expressed the OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results were analyzed, and shown to represent, at the cellular level, the distribution of OX1R, and we discuss the regulatory role of orexin A in the intra-hypothalamic areas, such as its special role in the plasticity of neurons, as well as in neuronal networks of the human hypothalamus