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Abstract Background Artificial intelligence (AI) has become a popular tool for clinical and research use in the medical field. The aim of this study was to evaluate the accuracy and reliability of a generative AI tool on pediatric familial Mediterranean fever (FMF). Methods Fifteen questions repeated thrice on pediatric FMF were prompted to the popular generative AI tool Microsoft Copilot with Chat-GPT 4.0. Nine pediatric rheumatology experts rated response accuracy with a blinded mechanism using a Likert-like scale with values from 1 to 5. Results Median values for overall responses at the initial assessment ranged from 2.00 to 5.00. During the second assessment, median values spanned from 2.00 to 4.00, while for the third assessment, they ranged from 3.00 to 4.00. Intra-rater variability showed poor to moderate agreement (intraclass correlation coefficient range: -0.151 to 0.534). A diminishing level of agreement among experts over time was documented, as highlighted by Krippendorff’s alpha coefficient values, ranging from 0.136 (at the first response) to 0.132 (at the second response) to 0.089 (at the third response). Lastly, experts displayed varying levels of trust in AI pre- and post-survey. Conclusions AI has promising implications in pediatric rheumatology, including early diagnosis and management optimization, but challenges persist due to uncertain information reliability and the lack of expert validation. Our survey revealed considerable inaccuracies and incompleteness in AI-generated responses regarding FMF, with poor intra- and extra-rater reliability. Human validation remains crucial in managing AI-generated medical information.

Abstract Introduction Recent works in the scientific literature reported the role of C reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as biomarkers of disease activity in rheumatic diseases. Objectives To investigate the role of CAR, PLR and NLR as potential markers of disease activity in children with non-systemic JIA (nsJIA) and their correlation with the risk of persistent disease activity of flare during follow up. Methods Our prospective, cross-sectional study involved 130 nsJIA patients (74 with active disease and 56 with inactive disease according to Wallace criteria) and 62 healthy controls. Demographic, clinical and laboratory data were collected at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3) and 18 months (T4) during follow up. Disease activity was evaluated through Juvenile Arthritis Disease Activity Score (JADAS-27). Results At baseline, CRP and CAR were higher in patients than in controls (p = 0.046), while no differences were found for NLR and PLR. However, there was no positive correlation between CAR, NLR, PLR and JADAS-27 in JIA patients. To better investigate the role of CAR, NLR and PLR as markers of disease activity, we used a generalized estimating equation (GEE) model, applied to all patients either with or without active disease. According to this analysis, CAR and NLR baseline levels were predictive of higher risk of disease activity at 6 months follow up (p

Abstract Background In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. Main body Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. Conclusion Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence.

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions.

Abstract In recent years screening of type 1 diabetes (T1D) in both at risk children and general population has been widely discussed with the aim of increasing awareness of the importance to early detect (and possibly treat) at-risk children in early stages of the chronic autoimmune progression to T1D. In fact, it is well known that first-degree relatives have the highest risk of T1D, but up to 90% of children who develop T1D do not have a family history and belong to the general population. The reasons for screening children well before the clinical onset of T1D include prevention of DKA (still up to 60% children are diagnosed with DKA) and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. There are pros and cons of screening of T1D in children, but recent evidences suggest that it is now time to consider possible a screening for T1D in children. Recently, the European Society for Paediatric Endocrinology (ESPE) has endorsed a Position Statement, discussing the pros and cons of screening for T1D in the general population; ESPE supports national Societies for Paediatric Endocrinology to spread information on this important issue in various countries throughout Europe; the Italian Society for Paediatric Endocrinology and Diabetes (SIEDP-ISPED) and the Italian Society of Paediatrics (SIP) endorse this document with the specific aim of increasing awareness on screening for paediatric T1D in the general population.

The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents. Despite its key role in innate immunity, pyrin has also garnered significant attention due to its association with a range of autoinflammatory diseases (AIDs) including familial Mediterranean fever caused by disruption of the MEFV gene, or in other genes involved in its complex regulation mechanisms. Pyrin activation is strictly dependent on homeostasis-altering molecular processes, mostly consisting of the disruption of the small Ras Homolog Family Member A (RhoA) GTPases by pathogen toxins. The downstream pathways are regulated by the phosphorylation of specific pyrin residues by the kinases PKN1/2 and the binding of the chaperone 14-3-3. Furthermore, a key role in pyrin activation is played by the cytoskeleton and gasdermin D, which is responsible for membrane pores in the context of pyroptosis. In addition, recent evidence has highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The aim of this article is to offer a comprehensive overview of the most recent evidence on the pyrin inflammasome and its molecular pathways to better understand the pathogenesis behind the significant group of pyrin-related AIDs.

Objective: Linear growth is impaired in children with type 1 diabetes (T1D) and poor metabolic control. A good metabolic control is a key therapeutic goal to prevent vascular complications and also to ensure appropriate anthropometric development during childhood. In this study, we aimed to identify and characterize the effects of glycemic variability on linear growth in children with T1D. Methods: Data from 144 prepubertal children with T1D were evaluated. Anthropometric measurements (weight, weight-SDS, height, height-SDS, BMI, BMI-SDS) were collected and glycosylated hemoglobin (HbA1c) was measured at admission and every 4 months over a 2-year period. Glycemic variability indexes (glycemic co efficient of variation (CV), glycemic CV percentage (CV%), and the product between HbA1c-mea n and HbA1c-SDS/100 (M*SDS-HbA1c/100)) were calculated. According to height-SDS changes after 2 years of follow-up, the study population was divided into three tertile groups and differences across groups were investigated for variables of int erest. Results: The three groups were similar in terms of age, gender, and follow-up period. After 2 years, all prepubertal children showed a signifi cant positive trend of anthropometric data. Across the three tertile groups, HbA1c-SDS , CV, CV%, and M*SDSHbA1c significantly decreased from the first to the third tertile of height-SDS. During follow-up, children with lower Δheight-SDS values reported high er values of HbA1c-SDS, CV, CV%, and M*SDS-HbA1c than subjects with higher linear growt h. Conclusions: Glycemic variability correlates with linear growth in children with T1D. Low glycemic variability indexes were reported in higher height-SDS tertiles. Δheight-SDS is inversely correlated with glycemic CV, CV%, and M*SDS-HbA1c.

Ciliopathies are a group of disorders that involve many organs and systems. In this review, we consider the role of the cilium in multiorgan pathology with a focus on endocrinological aspects. Identification of new genes and mutations is the major challenge in development of a tailored and appropriate therapy. It is expected that new mutations will be identified to characterize ciliopathies and promote new therapies.

Abstract Childhood obesity is increasing all over the world. It is associated with a reduction in quality of life and a relevant burden on society costs. This systematic review deals with the cost-effectiveness analysis (CEA) of primary prevention programs on childhood overweight/obesity, in order to benefit from cost-effective interventions. We screened and evaluated all the studies with a cost-effectiveness analysis on childhood obesity primary prevention program by PUBMED and Google Scholar, using inclusion and exclusion criteria. The quality of the studies was assessed by Drummond’s checklist. Ten studies were included. Two of them examined the cost-effectiveness of community-based prevention programs, four focused only on school-based programs while four more studies examined both community-based and school-based programs. The studies were different in terms of study design, target population, health and economic outcomes. Seventy per cent of the works had positive economic results. The majority of the studies showed effective economic outcomes applying primary prevention programs on childhood obesity. It is important to increase homogeneity and consistency among different studies.

This study, conducted by searching keywords such as “maternal lupus”, “neonatal lupus”, and “congenital heart block” in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Background: The SARS-CoV-2 pandemic has significantly affected the pediatric population. Long-term sequelae (Long COVID-19) may particularly involve the central nervous system, with possible effects on psychological well-being and quality of life (QoL), aspects that were already influenced by the restrictive measures and general social impact of the pandemic. Methods: We conducted a cross-sectional survey that aims at investigating the neuropsychological effects and the QoL impairment of SARS-CoV-2 on a cohort of children and adolescents in the Abruzzo region (Italy). A questionnaire was submitted to caregivers with the help of the PEDIATOTEM platform. A control group of healthy subjects was also included to distinguish between the effects of infection from the general influence of the pandemic. Results: A total of 569 subjects responded: 396 COVID-19 patients (99 of whom had Long COVID-19) and 111 controls. After the pandemic, when compared with the COVID-19 group, the controls reported significantly increased appetite, sleeping habits, and time spent remotely with friends and a reduction in physical activity and time spent in person with friends. A significant higher rate of controls asked for psychological/medical support for emotional problems. On the other hand, the Long COVID-19 group showed more fatigue and emotional instability with respect to non-Long-COVID-19 subjects. No differences in QoL results (EuroQOL) were found between the COVID-19 patients and controls, while the Long-COVID-19 subgroup showed significantly higher rates of pain/discomfort and mood instability, as confirmed by the analysis of variation of responses from the pre-COVID-19 to the post-COVID-19 period. Conclusions: Among COVID-19 patients, neuropsychological and QoL impairment was more evident in the Long COVID-19 subgroup, although emotional and relational issues were also reported by uninfected patients, with a growing request for specialist support as a possible consequence of social restriction.

BackgroundHereditary spastic paraplegia (HSP) encompass a variety of neurodegenerative disorders that are characterized by progressive deterioration of walking ability and a high risk for long-term disability. The management of problems associated with HSP, such as stiffness, deformity, muscle contractures, and cramping, requires strict adherence to recommended physiotherapy activity regimes. The aim of this paper is to conduct a critical narrative review of the available evidence focusing exclusively to the therapeutic advantages associated with various forms of physical therapy (PT) in the context of HSP, emphasizing the specific benefit of every distinct approach in relation to muscle relaxation, muscle strength, spasticity reduction, improvement of weakness, enhancement of balance, posture, walking ability, and overall quality of life.MethodsTo conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched.ResultsThe PubMed search returned a total of 230 articles, Scopus returned 218, and DOAJ returned no results. After screening, the final list included 7 papers on PT treatment for HSP patients.ConclusionElectrostimulation, magnetotherapy, hydrotherapy, PT, robot-assisted gait training, and balance rehabilitation have the potential to increase lower extremity strength and decrease spasticity in HSP patients.

Many etiological factors causing short stature have already been identified in humans. In the last few years, the advent of new techniques for the detection of chromosomal and molecular abnormalities has made it possible to better identify patients with genetic causes of growth failure. Some of these factors directly affect the development and growth of the skeleton, since they damage the epiphyseal growth plate, where linear growth occurs, influencing chondrogenesis. In particular, defects in genes involved in the organization and function of the growth plate are responsible for several well-known conditions with short stature. These genes play a pivotal role in various mechanisms involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. In this review, we will discuss the genes involved in extracellular matrix disorders. The identification of genetic defects in linear growth failure is important for clinicians and researchers in order to improve the care of children affected by growth disorders.

This review describes the impact of coronavirus disease 2019 (COVID-19) in children and adolescents, investigating changes in diabetes presentation during the COVID-19 pandemic, possible links between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and diabetes, and mechanisms of pancreatic β-cell destruction. Although glycemic control in individuals with already known diabetes mellitus did not worsen during the pandemic, there was a worrying increase in diabetic ketoacidosis in children with new-onset diabetes, probably due to containment measures and delayed access to emergency departments. Moreover, new evidence suggests that SARS-CoV-2 has the capacity to directly and indirectly induce pancreatic β-cell destruction, and the risk of newly diagnosed diabetes after COVID-19 increased in both children and adults. While long-term studies continue to follow children with SARS-CoV-2 infection, this review discusses available findings on the relationship between COVID-19 and diabetes. It is important to emphasize the need to maintain close links between families of children with chronic conditions and their pediatricians, as well as to promote early access to healthcare services, in order to reduce dangerous delays in diabetes diagnosis and prevent diabetic ketoacidosis.

IntroductionThe health consequences of lactose intolerance remain unclear. We studied the association of lactose intolerance with growth in children.MethodsIn this prospective case–control study, we compared Caucasian prepubertal children with lactose intolerance (LI) [n = 30, median age = 7.87 years (3.00–12.75)] to healthy controls [(n = 75, median age = 2.25 years (2.00–7.25)]. A lactose tolerance test was performed for lactose intolerance diagnosis. The gastrointestinal symptom score was administered at baseline and after a lactose-free diet for a median period of 9.0 months [range 5%–95% (6.0–24.0)]. The anthropometric parameters were measured at baseline and follow-up. All the anthropometric data were converted into standard deviation scores (SDS). A linear regression model was used to investigate the association of lactose intolerance with growth parameters.ResultsWe found no difference in height velocity SDS between the LI and control groups [SDS difference (95% CI): 0.52 (−1.86 to 2.90)]. In addition, we found a significant reduction in the clinical score of the LI group after a lactose-free diet [median (5%–95%): 7.5 (4.0–15.0) and 3 (0.0–8.0); p-value

Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the root cause of T1D development has yet to be determined, enough is known about the natural history of T1D pathogenesis to allow study of interventions that may delay or even prevent the onset of hyperglycemia and clinical T1D. Primary prevention aims to prevent the onset of beta cell autoimmunity in asymptomatic people at high genetic risk for T1D. Secondary prevention strategies aim to preserve functional beta cells once autoimmunity is present, and tertiary prevention aims to initiate and extend partial remission of beta cell destruction after the clinical onset of T1D. The approval of teplizumab in the United States to delay the onset of clinical T1D marks an impressive milestone in diabetes care. This treatment opens the door to a paradigm shift in T1D care. People with T1D risk need to be identified early by measuring T1D related islet autoantibodies. Identifying people with T1D before they have symptoms will facilitate better understanding of pre-symptomatic T1D progression and T1D prevention strategies that may be effective.

There is increasing evidence of a strong association between intrauterine growth and subsequent development of chronic disease in adult life. Birth size and growth trajectory have been demonstrated to have an impact on cardio-metabolic health, both in childhood and adult life. Hence, careful observation of the children’s growth pattern, starting from the intrauterine period and the first years of life, should be emphasized to detect the possible onset of cardio-metabolic sequelae. This allows to intervene on them as soon as they are detected, first of all through lifestyle interventions, whose efficacy seems to be higher when they are started early. Recent papers suggest that prematurity may constitute an independent risk factor for the development of cardiovascular disease and metabolic syndrome, regardless of birth weight. The purpose of the present review is to examine and summarize the available knowledge about the dynamic association between intrauterine and postnatal growth and cardio-metabolic risk, from childhood to adulthood.

Summary: Background: Type 1 diabetes is a complex heterogenous autoimmune disease without therapeutic interventions available to prevent or reverse the disease. This study aimed to identify transcriptional changes associated with the disease progression in patients with recent-onset type 1 diabetes. Methods: Whole-blood samples were collected as part of the INNODIA study at baseline and 12 months after diagnosis of type 1 diabetes. We used linear mixed-effects modelling on RNA-seq data to identify genes associated with age, sex, or disease progression. Cell-type proportions were estimated from the RNA-seq data using computational deconvolution. Associations to clinical variables were estimated using Pearson's or point-biserial correlation for continuous and dichotomous variables, respectively, using only complete pairs of observations. Findings: We found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Significant associations of the gene expression changes were found with ZnT8A autoantibody positivity. Rate of change in the expression of 16 genes between baseline and 12 months was found to predict the decline in C-peptide at 24 months. Interestingly and consistent with earlier reports, increased B cell levels and decreased neutrophil levels were associated with the rapid progression. Interpretation: There is considerable individual variation in the rate of progression from appearance of type 1 diabetes-specific autoantibodies to clinical disease. Patient stratification and prediction of disease progression can help in developing more personalised therapeutic strategies for different disease endotypes. Funding: A full list of funding bodies can be found under Acknowledgments.

Background: Identifying predictive factors of long COVID syndrome (LCS) is essential to preventing and managing this condition. We investigated the prevalence, symptoms, and risk factors of LCS in a cohort of Italian children and adolescents. Methods: We carried out a cross-sectional survey on demographic characteristics and clinical data related to COVID-19 phase and LCS in a cohort of children and adolescents, sending a questionnaire by using the PEDIATOTEM platform. Results: The prevalence of LCS was 25% (99/396). The most frequent symptoms of LCS included nasal congestion, diarrhea, headache, and fatigue. We found no association between demographic data (gender, age, and ethnicity) and LCS. Additionally, we showed that patients with concurrent allergic rhinitis, atopic dermatitis, respiratory disease, gastrointestinal disease, and rheumatologic disease had a higher risk of LCS than patients without those comorbidities. Patients experiencing fatigue, muscle, and abdominal pain in COVID-19 showed a higher risk of LCS than patients complaining of other symptoms. We found no association between vaccination and LCS. Conclusions: Specific comorbidities or symptoms during acute illness were identified as being risk factors for LCS. Understanding which are the risk factors for LCS could yield a clearer picture of its pathogenesis.

Background. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is a rare pediatric disorder consisting of a sudden onset of obsessive–compulsive disorder (OCD) and/or tics after a group A Streptococcus (GAS) infection. Methods. In the period between 2013 and 2023, 61 children presented to our Pediatric Rheumatology unit with a suspicion of PANDAS syndrome. Among these, a retrospective analysis was conducted, and 19 fulfilled the current classification criteria and were included in this study. Results. The male-to-female ratio was 14:5, the median age at onset was 7.0 (2.0–9.5) years, and the median age at diagnosis was 8.0 (3.0–10.4) years. The median follow-up period was 16.0 (6.0–72.0) months. Family and personal history were relevant in 7/19 and 6/19 patients. Tics were present in all patients. Details for motor tics were retrospectively available in 18/19 patients, with the eyes (11/18) and neck/head (10/18) being most often involved. Vocal tics were documented in 8/19, behavioral changes in 10/19, and OCD in 2/19. Regarding the therapeutic response, all patients responded to amoxicillin, 12/13 to benzathine benzylpenicillin, and 7/9 to azithromycin. Conclusions. Our findings partially overlap with previous reports. Larger prospective studies are needed to improve treatment strategies and classification criteria.

McCune-Albright Syndrome (MAS) is a rare mosaic (post-zygotic) genetic disorder presenting with a broad continuum clinical spectrum. MAS arises from somatic, activating mutations in the GNAS gene, which induces a dysregulated Gsα-protein signaling in several tissues and an increased production of intracellular cyclic adenosine monophosphate (cAMP). Overall, MAS is a rare disorder affecting less than 1/100,000 children and, for this reason, data establishing genotype-phenotype correlations remain limited. Affected individuals clinically present with a variable combination of fibrous dysplasia of bone (FD), extra-skeletal manifestations (including cafeí-au-lait spots) and precocious puberty which might also be associated to broad hyperfunctioning endocrinopathies, and also gastrointestinal and cardiological involvement. Central nervous system (CNS) and eye involvement in MAS are among the less frequently described complications and remain largely uncharacterized. These rare complications mainly include neurodevelopmental abnormalities (e.g., delayed motor development, cognitive and language impairment), CNS anomalies (e.g., Chiari malformation type I) and a wide array of ophthalmological abnormalities often associated with vision loss. The pathophysiological mechanisms underlying abnormal neurological development have not been yet fully elucidated. The proposed mechanisms include a deleterious impact of chronically dysregulated Gsα-protein signaling on neurological function, or a secondary (damaging) effect of (antenatal and/or early postnatal) hypercortisolism on early pre- and post-natal CNS development. In this Review, we summarize the main neurological and ophthalmological features eventually associated with the MAS spectrum, also providing a detailed overview of the potential pathophysiological mechanisms underlying these clinical complications.

Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is represented by the growth hormone–insulin-like growth factor axis (GH–IGF), even if several other factors are involved in normal growth. Within the broad spectrum of growth disorders, an increased importance has been placed on growth hormone insensitivity (GHI). GHI was reported for the first time by Laron as a syndrome characterized by short stature due to GH receptor (GHR) mutation. To date, it is recognized that GHI represents a wide diagnostic category, including a broad spectrum of defects. The peculiar characteristic of GHI is the low IGF-1 levels associated with normal or elevated GH levels and the lack of IGF-1 response after GH administration. Recombinant IGF-1 preparations may be used in the treatment of these patients.

IntroductionIncrease in cardiac biomarkers during Coronavirus disease 2019 (COVID-19) was frequent regardless of the presence of myocarditis and multisystem inflammatory syndrome in children (MIS-C). Several studies described MIS-C, but few papers evaluated cardiac manifestations in children with SARS-CoV-2 infection without MIS-C and investigated the role of troponin in absence of electrocardiogram (ECG) and echocardiographic alterations. The aim of this case series is to describe the cardiac manifestations during COVID-19 in children, trying to explain the meaning of laboratory findings during COVID-19, especially of increased troponin.Materials and methodsWe conducted a retrospective case series of children aged

Abstract Background S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns. Methods We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns. Results S100B and LT showed a pattern of concentration characterized by higher levels (P

Abstract Cardiovascular diseases are the main causes of death and health costs in developed countries. Although cardiovascular diseases are thought to affect only adulthood, the underlying process of atherosclerosis begins in the first decade of life. Epidemiological studies show that severity of atherosclerosis depends both on the number and intensity of risk factors. Early detection of cardiovascular risk in childhood is the most powerful tool to prevent cardiovascular accidents in adulthood and possibly reduce its consequent burden for the future. A large amount of cardiovascular risk factors is already detectable in childhood and include non-modifiable elements, among which genetic factors and congenital heart diseases, and modifiable elements, which depend on environmental effects (e.g. lifestyle and nutrition). Regardless of the possibility to intervene on these factors, an early diagnosis is fundamental to ensure an optimal life expectancy in adulthood. The most important cardiovascular risk factors in the paediatric age and adolescence are excess weight, arterial hypertension, glucose metabolism and lipid metabolism alterations. In this review we will discuss the main risk factors strictly correlated with cardiac and vessels diseases, focusing on their pathogenesis, diagnosis, and treatments.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive–compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

The increasing incidence and common specific inflammatory type 2 intracellular pathways have recently allowed for the rise of new biologic therapies in two inflammatory chronic diseases in children: atopic dermatitis (AD) and severe asthma. Such therapies aim at relieving symptoms and reducing inflammation by treating the underlying molecular causes. Dupilumab is a monoclonal antibody indicated in children with moderate–severe AD and severe asthma ineffectively responsive to standard treatments. Here, we report a case series of seven consecutive children with moderate–severe AD, with three of them also affected by asthma and treated with dupilumab. The children experienced a reduction in the extent and severity of lesions and decreased intensity of symptoms, leading to better asthma control, a general improvement in sleep and quality of life (QoL), with a good safety profile. Notwithstanding the observed clinical improvement, further larger prospective studies are needed to better tailor the treatment duration and the potential preventive and long-lasting effects.

Abstract Background The COVID-19 pandemic period is having a strong impact on the management of diabetes as well as other chronic diseases as shown by the most severe clinical presentation at onset. The aim of this study was to evaluate the severity of diabetic ketoacidosis (DKA) in youth with newly diagnosed type 1 diabetes in “Santissima Annunziata Hospital” (Chieti, Italy) during COVID-19 pandemic in comparison to the five previous years. Methods A retrospective population-based incidence study was performed. Data were obtained from hospital records of 172 patients with new onset type 1 diabetes divided into two groups according to the diagnosis: Group I, between January 2015 and February 2020; Group II, between March 2020 and April 2021. Data regarding anthropometric, socio-economic and laboratory test were analyzed. DKA (pH

Obstructive sleep apnea (OSA) is an increasingly recognized disorder in children. Adenotonsillectomy is the primary surgical treatment for OSA in children with adenotonsillar hypertrophy (ATH). We present the case of an obese 4-year-old boy hospitalized for severe desaturation during sleep and severe ATH. Nasal steroid therapy proved ineffective with persistent symptoms. Polygraphy documented severe OSA with an apnea–hypopnea index (AHI) equal to 11. Tonsillectomy resulted in prompt symptom improvement and a substantial reduction of the AHI (2.2). In this case, tonsillectomy alone resulted effective in treating OSA, despite obesity. We concluded that the presence of obesity should not postpone/exclude surgical treatment of preschool children for whom ATH is the most important cause of OSA.

During the year 2020, the COVID-19 pandemic rapidly became a severe health emergency worldwide. In order to contrast the spread of the novel SARS-CoV-2, many countries implemented extraordinary restrictive measures, such as a strict lockdown and school closures. The pandemic had a great impact on children and adolescents’ daily life, leading to a much more sedentary lifestyle, to larger use of electronic devices and to an increase in stress-related symptoms. These conspicuous changes acted as disruptors of children’s normal development. Since the beginning of the pandemic, many studies reported an increase in the number of precocious puberty cases as well as a faster progression rate of puberty itself, if compared to the pre-pandemic years. In this review, our aim was to evaluate the incidence of new cases of early and precocious puberty during the COVID-19 pandemic, analyzing variations in the timing of puberty and in pubertal progression rate, and to investigate the role of environmental and lifestyle factors during the pandemic in modulating the physiopathology of pubertal development. While a direct effect of SARS-CoV-2 infection remains, at the moment, a remote hypothesis, both physical and psychological factors related to the pandemic seem to have a role in triggering GnRH pulsatile secretion leading to earlier pubertal onset. It is indeed important to stress the need to clarify the exact role of COVID-19 in early pubertal onset comparing data from all over the world; long-term comprehensive studies are also pivotal to explain whether this phenomenon will continue while we resume pre-pandemic habits.

BackgroundThere is limited information available on fast and safe bedside tools that could help clinicians establish whether the pathological process underlying cases of wheezing is due to asthmatic exacerbation, asthmatic bronchitis, or pneumonia. The study's aim was to characterize Lung Ultrasound (LUS) in school-aged children with wheezing and evaluate its use for their follow-up treatment.Materials and methodsWe carried out a cross-sectional study involving 68 consecutive outpatients (mean age 9.9 years) with wheezing and suggestive signs of an acute respiratory infection. An expert sonographer, blinded to all subject characteristics, clinical course, and the study pediatrician's diagnosis, performed an LUS after spirometry and before BDT. The severity of acute respiratory symptoms was determined using the Pediatric Respiratory Assessment Measure (PRAM) score.ResultsThe LUS was positive in 38.2% (26/68) of patients [12 (46.1%) with multiple B-lines, 24 (92.3%) with consolidation, and 22 (84.6%) with pleural abnormalities]. In patients with pneumonia, asthmatic bronchitis, and asthma, the percentages of those patients with a positive LUS were 100%, 57.7%, and 0%, respectively. Of note, patients with a positive LUS were associated with an increased need for hospital admission (30.8% vs. 2.4%, p = 0.001), administration of oxygen therapy (14.6% vs. 0%, p = 0.009), oral corticosteroids (84.6% vs. 19.0%, p

Glucose is the most important substrate for proper brain functioning and development, with an increased glucose consumption in relation to the need of creating new brain structures and connections. Therefore, alterations in glucose homeostasis will inevitably be associated with changes in the development of the Nervous System. Several studies demonstrated how the alteration of glucose homeostasis - both hyper and hypoglycemia- may interfere with the development of brain structures and cognitivity, including deficits in intelligence quotient, anomalies in learning and memory, as well as differences in the executive functions. Importantly, differences in brain structure and functionality were found after a single episode of diabetic ketoacidosis suggesting the importance of glycemic control and stressing the need of screening programs for type 1 diabetes to protect children from this dramatic condition. The exciting progresses of the neuroimaging techniques such as diffusion tensor imaging, has helped to improve the understanding of the effects, outcomes and mechanisms underlying brain changes following dysglycemia, and will lead to more insights on the physio-pathological mechanisms and related neurological consequences about hyper and hypoglycemia.

Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases.

In our modern society, where highly palatable and calorie-rich foods are readily available, and sedentary lifestyle is common among children and adolescents, we face the pandemic of obesity, nonalcoholic fatty liver disease, hypertension, atherosclerosis, and T2D. Insulin resistance (IR) is known to be the main underlying mechanism of all these associated health consequences; therefore, the early detection of IR is fundamental for preventing them.A Consensus Statement, internationally supported by all the major scientific societies in pediatric endocrinology, was published in 2010, providing all the most recent reliable evidence to identify the definition of IR in children, its measurement, its risk factors, and the effective strategies to prevent and treat it. However, the 2010 Consensus concluded that further research was necessary to assess some of the discussed points, in particular the best way to measure insulin sensitivity, standardization of insulin measurements, identification of strong surrogate biomarkers of IR, and the effective role of lifestyle intervention and medications in the prevention and treatment of IR.The aim of this review is to update each point of the consensus with the most recent available studies, with the goal of giving a picture of the current state of the scientific literature regarding IR in children, with a particular regard for issues that are not yet fully clarified.

BackgroundThe gold standard to diagnose food allergy (FA) is a double-blind, placebo-controlled food challenge (OFC), even if it shows potential risk of severe allergic reactions for the patient and is time-consuming. Therefore, easier, and less invasive methods are needed to diagnose FA and predict the tolerance, changing the clinical practice.AimThe main aim of this study was to assess whether the total IgE values at the diagnosis of FA were associated with the duration of the tolerance acquisition and thus of the food elimination diet.MethodsWe retrospectively analyzed the medical records of 40 patients allergic to milk or egg who performed an OFC for the reintroduction of the causal food at the Pediatric Allergy and Respiratory Unit of the University of Chieti from January 2018 to December 2020.ResultsWe found a positive association of total serum IgE with the elimination diet duration (β = 0.152; CI, 95% 0.04–0.27) after adjusting for age, sex, and type of allergy (milk or egg). We also showed a significant correlation (r = 0.41 and p-value = 0.007) between the total IgE values and the duration of the elimination diet and a significant correlation between the casein specific IgE values at diagnosis of FA and the severity of the clinical presentation (r = 0.66; p-value 0.009).ConclusionTotal serum IgE at baseline, along with the downward trend of food-specific IgE levels (to milk or egg), may be useful in the prognostication of natural tolerance acquisition.

In children with type 1 diabetes, a healthy lifestyle is important to control postprandial glycemia and to avoid hyperglycemic peaks that worsen the inflammatory state of vessels and tissues. Glycemic index and glycemic load are two important indexes which assess the quality and quantity of foods consumed during meals. The main macronutrients of the diet have a different effect on postprandial blood glucose levels, so it is important that diabetic children consume foods which determine a slower and steadier glycemic peak. In this review, we present the results of the most recent studies carried out in the pediatric population with T1D, whose aim was to analyze the effects of low-glycemic-index foods on glycemic control. The results are promising and demonstrate that diets promoting low-glycemic-index foods guarantee a greater glycemic stability with a reduction in postprandial hyperglycemic peaks. However, one of the main limitations is represented by the poor adherence of children to a healthy diet. In order to obtain satisfactory results, a possibility might be to ensure a balanced intake of low-, moderate- and high-glycemic-index foods, preferring those with a low glycemic index and limiting the consumption of the high- and moderate-glycemic-index types.

Hypoglycemia is due to defects in the metabolic systems involved in the transition from the fed to the fasting state or in the hormone control of these systems. In children, hypoglycemia is considered a metabolic-endocrine emergency, because it may lead to brain injury, permanent neurological sequelae and, in rare cases, death. Symptoms are nonspecific, particularly in infants and young children. Diagnosis is based on laboratory investigations during a hypoglycemic event, but it may also require biochemical tests between episodes, dynamic endocrine tests and molecular genetics. This narrative review presents the age-related definitions of hypoglycemia, its pathophysiology and main causes, and discusses the current diagnostic and modern therapeutic approaches.

Pain is the most common complaint reported by children who access the emergency departments, but despite its frequency and the availability of many international guidelines, it often remains underreported and undertreated. Recently, the American Academy of Pediatrics and the American Pain Society have reiterated the importance of a multidisciplinary approach in order to eliminate pain in children. In all pediatric settings, an adequate assessment is the initial stage in a proper clinical approach to pain, especially in the emergency departments; therefore, an increasing number of age-related tools have been validated. A wide range of analgesic agents are currently available for pain management, and they should be tailored according to the patient’s age, the drug’s pharmacokinetics and the intensity of pain. In order to facilitate the choice of the appropriate drug, a treatment algorithm based on a ladder approach can be used. Moreover, non-pharmacological techniques should be considered to alleviate anxiety and distress in pediatric age. This review aims to offer a simple but intuitive description of the best strategies for pain relief in children, starting with the prompt recognition and quantification of pain through adequate assessment scales, and following with the identification of the most appropriate therapeutic choice among the ones available for pediatric age.

The endocrine and nervous systems reciprocally interact to manage physiological individual functions and homeostasis. The nervous system modulates hormone release through the hypothalamus, the main cerebrally specialized structure of the neuroendocrine system. The hypothalamus is involved in various metabolic processes, administering hormone and neuropeptide release at different levels. This complex activity is affected by the neurons of various cerebral areas, environmental factors, peripheral organs, and mediators through feedback mechanisms. Therefore, neuroendocrine pathways play a key role in metabolic homeostasis control, and their abnormalities are associated with the development of metabolic syndrome (MetS) in children. The impaired functioning of the genes, hormones, and neuropeptides of various neuroendocrine pathways involved in several metabolic processes is related to an increased risk of dyslipidaemia, visceral obesity, insulin resistance, type 2 diabetes mellitus, and hypertension. This review examines the neuroendocrine effects on the risk of MetS in children, identifying and underlying several conditions associated with neuroendocrine pathway disruption. Neuroendocrine systems should be considered in the complex pathophysiology of MetS, and, when genetic or epigenetic mutations in “hot” pathways occur, they could be studied for new potential target therapies in severe and drug-resistant paediatric forms of MetS.

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

Abstract Objective The aim of this study was to evaluate sleep quality and psychological effects on pediatric healthcare workers during the first wave of COVID-19 epidemic in Italy and to evaluate differences between primary and secondary care operators. Pediatric healthcare workers were involved in an online survey to assess sleep quality, stress and anxiety level, self-efficacy and social support in Italian pediatric healthcare workers during COVID-19 pandemic. Results We found that 67.4% of our sample suffered from sleep disturbance and 19.4% of subjects suffered from anxiety. Lower values of anxiety and social support were found in primary care staff compared to secondary care one. The associations between healthcare professional figures (being primary or secondary care operators) and mental health outcomes were not statistically significant. However, sex, age and having a SARS-CoV-2 infected relative/friend had an independent effect on mental health outcomes. It is crucial to provide social and psychological support to pediatric healthcare workers. A tailored psychological screening would be desirable for female healthcare workers and for those who have a SARS-CoV-2 infected relative/friend.

BackgroundDespite recent neonatal care improvements, mechanical ventilation still remains a major cause of lung injury and inflammation. There is growing literature on short- and long-term respiratory outcomes in infants born prematurely in the post-surfactant era, but the exclusive role of mechanical ventilation at birth in lung function impairment is still unclear. The aim of this study was to assess the effect of neonatal mechanical ventilation on lung function parameters in children born ≤ 32 weeks of gestational age at 11 years of age.Materials and MethodsIn total, 55 ex-preterm children born between January 1, 2006 and December 31, 2007 were enrolled at 11 years of age. Neonatal information was obtained from medical records. Information about family and personal clinical history was collected by questionnaires. At 11 years of age, we measured spirometry parameters, lung volumes, diffusing lung capacity, and fractional exhaled nitric oxide. In addition, an allergy evaluation by skin prick test and eosinophil blood count were performed. A multivariable linear or logistic regression analysis was performed to examine the associations of mechanical ventilation with respiratory outcomes, adjusting for confounders (maternal smoking during pregnancy, gestational age, surfactant replacement therapy, and BMI).ResultsNo difference in lung function evaluation between ventilated and unventilated children were found. No association was also found between mechanical ventilation with lung function parameters.ConclusionMechanical ventilation for a short period at birth in preterm children was not associated with lung function impairment at 11 years of age in our study sample. It remains to define if ventilation may have a short-term effect on lung function, not evident at 11 years of age.

Aim/HypothesisTo compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.MethodsForty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019.ResultsOverall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p

Adrenoleukodystrophy is a peroxisomal X-linked recessive disease caused by mutations in the ABCD1 gene, located on the X-chromosome (Xq28). Gene mutations in patient with adrenoleukodystrophy induce metabolic alterations characterized by impaired peroxisomal beta-oxidation and accumulation of very long chain fatty acid (VLCFA) in plasma and in all tissues. Although nutritional intervention associated with a various mixture of oil prevents the accumulation of VLCFA, to date no causal treatment is available. Therefore, haematopoietic stem cell transplantation (HSCT) and gene therapy are allowed only for very early stages of cerebral forms diagnosed during childhood.We reported a case series describing five family members affected by X-linked adrenoleukodystrophy caused by a novel mutation of the ABCD1 gene. Particularly, three brothers were affected while the sister and mother carried the mutation of the ABCD1 gene. In this family, the disease was diagnosed at different ages and with different clinical pictures highlighting the wide range of phenotypes related to this novel mutation. In addition, these characteristics stress the relevant role of early diagnosis to properly set a patient-based follow-up.

Abstract Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2–20 cases per 100,000 and a prevalence of 16–150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10–20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient’s bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.

Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (NMDARe) is the most common cause of nonviral encephalitis, mostly affecting young women and adolescents with a strong female predominance (F/M ratio of around 4:1). NMDARe is characterized by the presence of cerebrospinal fluid (CSF) antibodies against NMDARs, even though its pathophysiological mechanisms have not totally been clarified. The clinical phenotype of NMDARe is composed of both severe neurological and neuropsychiatric symptoms, including generalized seizures with desaturations, behavioral abnormalities, and movement disorders. NMDARe is often a paraneoplastic illness, mainly due to the common presence of concomitant ovarian teratomas in young women. Abdominal ultrasonography (US) is a key imaging technique that should always be performed in suspected patients. The timely use of abdominal US and the peculiar radiological features observed in NMDARe may allow for a quick diagnosis and a good prognosis, with rapid improvement after the resection of the tumor and the correct drug therapy.