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Background/Objectives: MTHFR gene polymorphisms (677C>T and 1298A>C) correlate with various types of cancer across all age groups; however, a small number of studies have included solely children and adolescents. The aim of this systematic review and meta-analysis was to present and synthesize all the available evidence on the association between MTHFR gene polymorphisms and the incidence of all types of cancer in children and adolescences. Methods: After a systematic search of all of the available data, original case–control studies involving children or adolescents with a confirmed diagnosis of any type of cancer and a molecular genetic test of MTHFR gene polymorphisms were included. Results: A total of 53 original studies in children and adolescents with cancer were included in the systematic review. Among these, 40 studies reviewed children and adolescents with Acute Lymphoblastic Leukemia (ALL), 4 those with Acute Myeloblastic Leukemia (AML), 8 those with central nervous system (CNS) tumors and 3 those with other types of cancer. Children and adolescents with ALL had less frequent T allele sequences (CT and TT variations) of the 677C>T polymorphism compared to a healthy population (OR: 0.85; CI: 0.80–0.91; p < 0.00001). Concerning the 1298A>C polymorphism, the C allele sequences (AC and CC) did not present a statistically significant difference in frequency compared to a healthy population (OR: 1.01; CI: 0.95–1.08; p = 0.69). Conclusions: Children and adolescents with ALL appeared to have the T allele sequences of the 677C>T polymorphism of the MTHFR gene less frequently compared to a healthy population. [ABSTRACT FROM AUTHOR]

Background: Despite the progress achieved regarding survival rates in childhood acute lymphoblastic leukemia (ALL), relapsed or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved by the Food and Drug Administration for adults and pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. Case presentation: Herein, we present the case of a 23-month-old girl with high-risk B-ALL who experienced very early isolated medullary relapse; following the failure of conventional chemotherapy according to the ALL-IC REL 2016 protocol, she went on to receive the bispecific T-cell engager (BiTE) blinatumomab and subsequently, due to refractory disease, the combination of fludarabine, cytarabine, and the proteasome inhibitor bortezomib without achieving remission. Given the high CD22 expression by the lymphoblasts, off-label use of inotuzumab ozogamicin (InO) was chosen and administrated in a 28-day cycle as a salvage treatment. The minimal residual disease (MRD) was 0.08% on day 28, and InO was continued, thus achieving MRD negativity; the patient successfully underwent an allogeneic stem cell transplantation from a matched family donor. Conclusions: Our case highlights the efficacy and safety of InO as a salvage treatment in the setting of relapsed B-ALL refractory not only to conventional chemotherapy but also to novel treatments, such as blinatumomab and bortezomib. [ABSTRACT FROM AUTHOR]

Background: Adolescent overweight and obesity are a public health problem with an epidemic trend. There is growing evidence that sleep quality correlates to body weight. The aim of this study was to investigate, sleep quality in adolescents with obesity/overweight. Methods: A total of 100 adolescents with overweight/obesity aged 12–18 years were enrolled. Anthropometric parameters were recorded and a laboratory investigation in the fasting state [glucose, insulin, cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, uric acid and glycated hemoglobin (HbA1c)] was performed. Insulin resistance was calculated by the Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR). Sleep quality was assessed with the Adolescent Sleep Hygiene Scale (ASHS) questionnaire. Results: According to ASHS, 93% of the participants were classified as "Good Sleepers" (GSs) (score > 3.8) and 7% as "Poor Sleepers" (PSs) (score < 3.8). PSs had a statistically higher body mass index (BMI) compared to GSs (p = 0.026). Increased body mass index (BMI) (r = −0.306, p = 0.002), fast insulin (r = −0.224, p = 0.027), and HOMA-IR (r = −0.260, p = 0.010) exerted a negative effect on sleep quality. Controlling for lipids and uric acid, only TC levels appeared to have a statistically significant and specifically positive correlation with the ASHS score (r = 0.202, p = 0.045). HbA1c values and waist circumference tended to be negatively correlated, but not significant to adolescent sleep quality [(r = −0.101, p = 0.330), (r = −0.095, p = 0.359), respectively]. The influence of central obesity on the ASHS score was also explored, but no correlation was found (p = 0.566). Conclusions: Sleep quality, as reflected by the ASHS score, was associated negatively with BMI, fasting insulin levels, and insulin resistance. Furthermore, a gender difference was observed, as adolescent males were found to achieve a higher overall ASHS score compared to females. [ABSTRACT FROM AUTHOR]

Monogenic defects of beta cell function refer to a group of rare disorders that are characterized by early-onset diabetes mellitus due to a single gene mutation affecting insulin secretion. It accounts for up to 5% of all pediatric diabetes cases and includes transient or permanent neonatal diabetes, maturity-onset diabetes of the young (MODY), and various syndromes associated with diabetes. Causative mutations have been identified in genes regulating the development or function of the pancreatic beta cells responsible for normal insulin production and/or release. To date, more than 40 monogenic diabetes subtypes have been described, with those caused by mutations in HNF1A and GCK genes being the most prevalent. Despite being caused by a single gene mutation, each type of monogenic diabetes, especially MODY, can appear with various clinical phenotypes, even among members of the same family. This clinical heterogeneity, its rarity, and the fact that it shares some features with more common types of diabetes, can make the clinical diagnosis of monogenic diabetes rather challenging. Indeed, several cases of MODY or syndromic diabetes are accurately diagnosed in adulthood, after having been mislabeled as type 1 or type 2 diabetes. The recent widespread use of more reliable sequencing techniques has improved monogenic diabetes diagnosis, which is important to guide appropriate treatment and genetic counselling. The current review aims to summarize the latest knowledge on the clinical presentation, genetic confirmation, and therapeutic approach of the various forms of monogenic defects of beta cell function, using three imaginary clinical scenarios and highlighting clinical and laboratory features that can guide the clinician in reaching the correct diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to report on the menarcheal age in girls of Greek origin and assess its potential associations with their demographic and perinatal data, as well as their maternal menarcheal age. Methods: In this case–control study, adolescent girls were recruited between September 2021 and September 2022 from two Pediatric Endocrinology Units, Aristotle University of Thessaloniki, Greece. Eligible participants included Greek girls up to the age of 18 years, with menarche and the absence of chronic disease or chronic medication use. Participants were divided into two groups, the early menarche group and the control group (menarche before or after 11 years of age, respectively). Data included participants' maternal menarcheal age, their chronological age, place of residence, anthropometric data (at recruitment) and perinatal data (birth order, gestational age, type of delivery, birth weight/length). Results: A total of 100 girls aged 7–17 years (mean age ± SD 12.51 ± 2.59 years) were included in this study. The mean ± SD menarcheal age of the total sample was 11.47 ± 1.55 years (median 11.20 years; range 7.50–16.25 years); 43% had early menarche (median menarcheal age 10.50 years; range 7.50–10.91 years), and 57% had menarche after age 11 (median menarcheal age 12.08 years; range 11.00–16.25 years). The caesarean section rate was significantly (p < 0.001) higher in girls with early menarche (83.7%) than controls, whereas other variables did not differ significantly between groups. Conclusions: This Greek sample demonstrated a relatively young age at menarche with a significant proportion of girls with early menarche; in the latter group, the rate of caesarian sections was significantly higher than controls. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]