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Abstract Background Elexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking. Case presentation We report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects. Conclusions This case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.

Abstract Background Mitochondrial diseases (MDs) are systemic disorders that can affect multiple organs. Renal manifestations, including renal tubular acidosis, are common because kidneys are particularly vulnerable to energy deprivation. Treatment of MDs is often complex and electrolyte replacement can be difficult especially in pediatric patients, because large and repeated amounts of oral supplements are needed but are not well tolerated. Case presentation We describe the case of a girl affected by Kearns-Sayre disease with severe renal tubular acidosis. The management of her metabolic acidosis was challenging because she showed persistent low levels of serum bicarbonates despite a progressive incrementation of oral bicarbonates. Furthermore, as a result to the ingestion of large amounts of alkali, the girl developed an aversion to oral supplementation. After positioning a percutaneous gastrostomy (PEG) and starting enteral administration of bicarbonates (with daily boluses and continuous nocturnal infusion), she finally obtained an adequate electrolyte control, with a significant increase in her quality of life. Conclusions In MDs, the combination of nocturnal continuous enteral administration of alkali plus diurnal boluses may represent a valid solution to correct metabolic acidosis. It can also result in an improved patients’ quality of life, particularly in pediatric settings, where compliance to oral therapy is often lacking due to the large and repeated amounts of unpalatable bicarbonates solutions required.

Abstract The burden of autism spectrum disorder (ASD) is increasing worldwide with genetic, epigenetic, and environmental factors being possibly responsible for the observed epidemiological figures. In the setting of environmental exposure, the city of Taranto, in Southern Italy, represents an interesting case study as it hosts well inside the city one of the biggest steel plants in Europe. This is a cross-sectional ecological study carried out in the year 2020 in the province of Taranto designed to estimate the burden of ASD in the municipalities of Taranto and Statte, classified as high environmental risk areas (Contaminated Site of National Interest—SIN), compared to the other 27 municipalities of the same province. Differences have been evaluated using the Chi Square Test. Children aged 6–11 years identified in SIN municipalities had a statistically significant higher prevalence of ASD than children of other municipalities (9.58 vs. 6.66/1000 respectively, p = 0.002). No statistically significant difference was observed for the 12–18 years group (3.41 vs. 2.54/1000, p = 0.12). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

Abstract Background Cortical visual impairment (CVI) is a verifiable visual dysfunction that cannot be attributed to disorders of the anterior visual pathways or any potentially co-occurring ocular impairment. Given the limited knowledge on the most effective interventions for visual impairment resulting from CVI, this case report provides valuable insights into an example of successful implementation of anti-amblyopia therapy in a patient with CVI. Case presentation This case report presents a 5-year-old girl with CVI secondary to hypoxic-ischemic injury, resulting in visual impairment, dyspraxia, and abnormal visual evoked potential testing. The girl did not suffer from amblyopia, there was no evidence of relevant refractive errors or strabismus, so visual pathway damage was the cause of her visual deficit. Nevertheless, the patient underwent anti-amblyopia therapy and showed significant improvement in visual acuity after 12 months of treatment. The improvement, resulting from visual stimulation, was due to a good functional recovery by a better usage of the damaged visual pathways. The therapy included prescribing corrective glasses and implementing secondary occlusion of the better eye for 4 months, which was protracted for another 4 months, leading to further improvements in visual acuity. Conclusions The case report shows that addressing even minor refractive errors and implementing anti-amblyopia therapy can significantly improve vision in children with CVI, even without co-existing amblyopia. It also highlights the importance of early intervention and multidisciplinary rehabilitation in children with CVI, focusing on motor and cognitive skills. Additionally, it emphasizes the need for further research to establish evidence-based practice standards for improving vision in children with CVI.

Background Despite evidence showing that the intranasal and sublingual routes are safe and effective in providing analgesia, no data are available about their day-to-day use in the emergency department (ED). The aim of this study was to assess the frequency of the use of the intranasal and sublingual routes, and the clinical characteristics of the patients receiving analgesia through these routes.Methods A multicentre study was performed in the EDs participating in the Pain in Paediatric Emergency Room research group. It included a survey and a retrospective data collection in which the medical records of all patients who received analgesia from 1 April 2022 to 31 May 2022 were collected.Results 48 centres (91%) answered the survey. The intranasal and sublingual routes were used in 25 centres (52%). 13 centres (27%) used both routes, 9 centres (19%) used only the sublingual and 3 centres (6%) used only the intranasal route.12 centres (48%) participated in the retrospective study. Data about 3409 patients, median age 9 years (IQR 5–12), were collected. Among them, 337 patients (9.6%) received sublingual analgesia, and 87 patients (2.5%) received intranasal analgesia. The intranasal route was employed for injuries in 79 (90.8%) cases, and fentanyl was the drug delivered in 85 (97.7%) cases. The sublingual route was used mainly for injuries (57.3%), but also for abdominal pain (15.4%), musculoskeletal pain (14.5%) and headache (10.7%). Paracetamol, ketorolac and tramadol were administered through this route.Conclusions The use of the intranasal and sublingual routes for analgesia in the paediatric ED is still limited.

BackgroundBrain magnetic resonance imaging (MRI) is mandatory or highly recommended in many pediatric endocrinological conditions to detect causative anatomic anomalies and rule out neoplastic lesions. However, MRI can also show findings associated with the underlying clinical condition, as well as unrelated “incidentalomas”. These latter findings are often abnormalities with a high incidence in the general population for which there is no clear literature regarding their management, especially in pediatric patients. The present study aimed to evaluate the number of unnecessary performed MRIs in pediatric endocrinology.MethodsRetrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty).ResultsThe MRI scans were completely normal in 67% of the individuals, and the prevalence of individuals who underwent more than one MRI was 18%, with no significant differences among the groups. The overall prevalence of incidentalomas was 17%. Among 170 repeated MRI scans, 147 (86%) were not required according to a dedicated protocol. Only five patients (four GHD, one Noonan) correctly repeated the MRI. All the repeated MRI scans did not reveal any progression in the findings. If we include the MRIs performed in cases of OCSS other than Noonan syndrome (n=32) and girls with CPP older than 6 years (n=89), an additional 121 MRIs could have been avoided, leading to a total number of unnecessary MRIs to 268 (46%).ConclusionsOnly a few specific neuroimaging findings in endocrinologic pediatric patients warrant further investigation, while too often repeated imaging is carried out unnecessarily. We advocate the importance of guidelines to reduce costs for both the healthcare system and patients’ families, as well as to alleviate physical and psychological distress for patients and caregivers.

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.

Abstract Oral immunotherapy is proposed as the only active intervention to modify allergies and decrease the risk of severe reactions. However, it is crucial to note that oral immunotherapy still presents a notable failure rate and potential for severe, life-threatening outcomes. Notably, patients who discontinue oral immunotherapy may face an increased risk of fatal reactions. Omalizumab could be a viable option for patients with failed oral immunotherapy.

Abstract Background The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020–2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology. Methods We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law. Results Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021–2022, 34 in 2020–2021, 395 in 2019–2020 and 483 in 2018–2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022–2023), compared to 5.7 ± 4 in 2021–2022, 5.3 ± 4 in 2020–2021, 6.4 ± 5 in 2019–2020 and 5.5 ± 4 in 2018–2019 (p

ObjectivePain's causes in children with severe cognitive impairment may be challenging to diagnose. This study aimed to investigate if there is a relationship between pain causes and the age of children.MethodsWe conducted a multicenter retrospective study in three Italian Pediatric Units. Eligible subjects were patients from 1 to 18 years with severe neurological impairment. We collected data regarding diagnoses, pain causes and medical or surgical procedures. The timing of pain episodes was categorized into age-related periods: infants and toddlers (0–24 months), preschool children (3–5 years), schoolchildren (6–12 years), and adolescents (13–17 years).ResultsEighty children with severe neurological impairment were enrolled. The mean age was 11 years (±5.8). Gastroenterological pain was most common in the first years of life (p = 0.004), while orthopaedic and tooth pain was the most typical in schoolchildren and adolescents (p = 0.001 and p = 0.02). Concerning surgical procedures, PEG placement and gastric fundoplication were significantly more common in the first 5 years of age (p = 0.03), and heart surgery was typical of infants (p = 0.04). Orthopaedic surgery was more commonly reported in older children and adolescents (p

IntroductionIt has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Only children with a monogenic cause of GHD or an identifiable combined hormonal deficiency or anatomical anomaly in the hypothalamic-pituitary axis should be considered definite GHD (dGHD). The remaining patients can be defined as a separate group of patients, “short stature unresponsive to stimulation tests” (SUS). The aim of this proof-of-concept study, was to assess whether SUS patients treated with rhGH exhibit any differences compared to GHD patients undergoing the same treatment.MethodsRetrospective analysis on 153 consecutive patients with short stature and pathological response to two GH stimulation tests. Patients with dGHD were defined as those with a clear genetic or anatomical hypothalamic-pituitary anomaly, as well as those with combined pituitary hormone deficiencies and those with a known insult to the hypothalamic-pituitary axis (i.e. total brain irradiation) (n=38, 25%); those without any of the previous anomalies were defined as SUS (n=115, 75%).ResultsAt diagnosis, dGHD and SUS populations did not differ significantly in sex (F 32% vs 28%, p=0.68), age (11.9 vs 12.1, p=0.45), height SDS at diagnosis (-2.2 vs. -2.0, p=0.35) and prevalence of short stature (height

Abstract Background Neuroblastoma is the most frequent extracranial solid tumor occurring in childhood, representing approximately 28% of all cancers diagnosed in infants. Signs and symptoms of neuroblastoma vary with the site of development of the tumor and can mimic other diseases due to its extreme clinical variability. However, torticollis is not reported in the medical literature as a leading symptom of neuroblastoma. Case presentation Here we report the case of a 3 years-old girl with fever and neck stiffness. Blood tests revealed a mild anemia and a rise in inflammatory markers. CT-scan showed a solid, heterogeneous, predominantly hypodense surrenal mass with eccentric calcification and extensive inhomogeneity of the vertebral metamers. Blood tests revealed raised serum levels of Neuron-Specific Enolase. At the 24-hours urine collection urinary catecholamines were greatly increased. A course of chemotherapy for neuroblastoma was promptly started with immediate clinical improvement. Conclusions This case shows that the presence of torticollis could be a chief complaint of neuroblastoma. To our knowledge, neuroblastoma is not mentioned among life-threatening underlying conditions of torticollis in most recent literature reviews.

Abstract Background Beckwith-Wiedemann syndrome (BWS, OMIM #130,650) is a pediatric overgrowth disorder involving a predisposition to tumor development. Although the clinical management of affected patients is well established, it is less clear how to handle with the cases of siblings of affected patients, since the prevalence of the condition in twins (1:1000) is ten times higher than in singletones (1:10000). Case presentation We report the case of a premature twin patient who during her follow-up develops a clinical phenotype compatible with BWS, genetically confirmed in blood. However, the methylation alteration characteristic of the condition was also found in the almost phenotypically normal sibling, making it challening her management. Conclusion Through our case report we highlight how the diagnosis of BWS can be made without any prenatal suspicion and we propose a review of the literature on how to manage siblings of affected patients in twinning situation.

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

Background: The treatment of aggressive behavior and agitation in pediatric patients with autism spectrum disorder (ASD) in the emergency department is topical and challenging. Case Presentation: We described an adolescent with autism spectrum disorder treated ten times in the pediatric emergency department for severe episodes of aggressiveness and agitation. After resolving the acute phase of these behavioural crises, sedation was maintained with a continuous infusion of dexmedetomidine to prevent the resurgence of agitation and to organize discharge properly, considering the family’s needs. The continuous infusion of dexmedetomidine allowed the patient to remain asleep most of the time during his stay at the emergency department. No adverse events were recorded. Conclusions: The continuous infusion of dexmedetomidine could represent a safe and valuable tool to facilitate the permanence of the patient in the PED.

Abstract The prevalence of children with medical complexity is increasing, therefore drug formulations must be updated in accordance with their needs. Furthermore, a different drug formulation may be also needed for patients who require a very low dosage which is not easily reachable with those of the industrial products or for those following a ketogenic diet. Galenic (or compounded) drugs have been recently pointed out as effective in treating children. Nonetheless, their knowledge among healthcare providers is limited. We investigated how much did pediatricians know about galenic compounds by a short questionnaire administered to family and hospital pediatricians and pediatric residents in Friuli Venezia Giulia, Italy. We collected answers from 65 family pediatricians (57,5%), 39 hospital pediatricians (36,1%), and 47 pediatric residents (41,2%). Overall, both family and hospital pediatricians substantially know what is a galenic compound and the indications to its use. Of note, most of pediatricians ignore which is the legislation that allows the galenic compounds’ preparation and use, and which is the correct procedure to prescribe them. Moreover, half of the hospital pediatricians and one-third of the family ones erroneously stated that galenic formulations cost more or like the industrial products, and around the 15% of both categories affirmed that galenic compounds are less safe than the commercial product. In conclusion, the use of galenic drug may significantly improve children’s and caregivers’ quality of life. We believe that all pediatricians should be updated on this quite new and interesting topic.

Abstract Background Mild hyponatremia is frequently encountered in the pediatric emergency department (PED). Although usually of little clinical concern, its prognostic meaning as a possible marker of more severe disease has not yet been well established. Methods We retrospectively analyzed data from children and adolescents who performed a blood sample with plasmatic sodium measurement on admission to the PED of IRCCS “Burlo Garofolo” Pediatric Hospital in Trieste, Italy, in 2019. We compared the rate, length of admissions and laboratory characteristics of patients with hyponatremia to those with normal sodium. Results Among 807 subjects, hyponatremia (sodium 5 days (aOR 1.99; 95%CI 1.03–3.85). When considering only subjects with mild hyponatremia, we found similar results. Conclusion Hyponatremia and mild hyponatremia in the PED are associated with an increased admission rate and extended hospital stays. Mild hyponatremia should be considered a warning sign for a possibly more serious condition.

IntroductionGirls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as “thelarche variant” (TV), characterized by an FSH-predominant response, although a univocal definition is lacking.MethodsRetrospective analysis on 91 girls with early thelarche (5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm3). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02).ConclusionUsing laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a “precocious prepuberty” in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls’ age).

Chronic school absenteeism is a common problem in childhood and adolescence, and it is frequently observed in patients with somatic symptom and related disorders (SSRDs). This study aimed to determine whether and to what extent the presence of school absenteeism may be a risk factor for the diagnosis of SSRDs in hospitalised patients. This matched cohort study included children and adolescents aged between 8 and 17 years, admitted to the paediatric ward of the IRCCS Burlo Garofolo in Trieste from 2021 to 2023, who were divided into two groups, the first including children with at least 15 days of absence from school for medical reasons and the second including children with regular school attendance, matched to the former group by age and sex. We consecutively enrolled 70 patients, 35 in the absentee group and 35 in the control group. In the absentee group, 30/35 (85.7%) patients were diagnosed with an SSRD, while in the control group, 1/35 (2.9%) was diagnosed with an SSRD. The absentee group had a 30-fold higher risk of being diagnosed with SSRDs than the control group (RR = 30 [95% CI = 4.3–208]; p < 0.001). This study shows that in hospitalised children, a history of school absenteeism of more than two weeks is an important risk factor for the diagnosis of SSRDs.

Congenital long QT syndrome (LQTS) represents a disorder of myocardial repolarization characterized by a prolongation of QTc interval on ECG, which can degenerate into fast polymorphic ventricular arrhythmias. The typical symptoms of LQTS are syncope and palpitations, mainly triggered by adrenergic stimuli, but it can also manifest with cardiac arrest. At least 17 genotypes have been associated with LQTS, with a specific genotype–phenotype relationship described for the three most common subtypes (LQTS1, -2, and -3). β-Blockers are the first-line therapy for LQTS, even if the choice of the appropriate patients needing to be treated may be challenging. In specific cases, interventional measures, such as an implantable cardioverter-defibrillator (ICD) or left cardiac sympathetic denervation (LCSD), are useful. The aim of this review is to highlight the current state-of-the-art knowledge on LQTS, providing an updated picture of possible diagnostic algorithms and therapeutic management.

Background: While oral laxatives represent the first-line treatment of fecal impaction, enemas are frequently used in clinical practice in pediatric emergency departments (PEDs) and by family pediatricians (FPs). Objectives: Phosphate-containing enemas (PcEs) are commonly employed, even causing the risk of rare but lethal toxicity. We investigated pediatricians’ awareness of PcE risks. Methods: We conducted an online survey by sending a multiple-choice questionnaire to the referents of 51 PEDs and 101 FPs. We collected and compared the answers with recommendations reported by the Italian Drug Agency (AIFA) and the available literature about PcE administration. Results: Of the institutions and pediatricians receiving the questionnaire, 23 PEDs (45%) and 63 FP (62.3%) participated in the survey. Of PEDs, 95% and 33.0% of FPs treated fecal impaction with PcE. Moreover, 54% of PEDs and 86.0% of FPs did not provide treatment according to the AIFA recommendations for the daily dose. Conclusions: This study shows limited pediatricians’ awareness of the potential risks related to PcE.

This case report describes two cases of unilateral limbal Vernal keratoconjunctivitis (VKC) in the same family. To our knowledge, these are the first two reported cases of unilateral limbal VKC. VKC is a chronic inflammatory disease that typically affects both eyes, with unilateral cases being rare and previously only reported in the tarsal form. Our first case involved a 12-year-old girl with a history of allergic asthma, who had been experiencing conjunctivitis in her right eye since the age of 7. Upon examination, she was diagnosed with unilateral limbal VKC and treated with 1% cyclosporine eye drops with a significant improvement observed at the one and three-month follow-ups. Her 7-year-old brother was also examined and found to have unilateral limbal VKC in his right eye, although it was milder and not associated with allergic pathogenesis. Therefore, in this case, a treatment with hydrocortisone eye drops was started leading to an immediate reduction of the itching. In both cases an IgE-mediated mechanism is less likely because of the monolateral eye involvement, the complete absence of nasal symptoms, the lack of correlation between symptoms and any pollen season, and the negative prick skin test in one of the two siblings. Both cases suggest that unilateral VKC may occur even in the limbal form and that genetic mechanisms may contribute to the inflammatory reaction in VKC. This report highlights the need for further studies to explain the occurrence of unilateral VKC cases and reminds clinicians to consider the possibility of unilateral limbal VKC in pediatric patients.

Abstract To date, pain and anxiety are the most common symptoms reported by children who refer to pediatric emergency department. Despite it is well known that the undertreatment of this condition has some negative consequences in a short term and long term of time, gaps in the management of pain in this setting still persist. This subgroup analysis aims to describe the current state of art of pediatric sedation and analgesia in Italian emergency departments and to identify existing gaps to solve. This is a subgroup analysis of a cross-sectional European survey of pediatric emergency departments sedation and analgesia practice undertaken between November 2019 and March 2020. The survey proposed a case vignette and questions addressing several domains, like the management of pain, availability of medications, protocols and safety aspects, staff training and availability of human resources around procedural sedation and analgesia. Italian sites responding to the survey were identified and their data were isolated and checked for completeness. Eighteen Italian sites participated to the study, the 66% of which was represented University Hospitals and/or Tertiary Care Centers. The most concerning results were an inadequate sedation to 27% of patients, lack of availability of certain medications like nitrous oxide, the lack of use of intranasal fentanyl and topical anesthetics at the triage, the rare use of safety protocols and preprocedural checklists, lack of staff training and lack of space. Furthermore, the unavailability of Child Life Specialists and hypnosis emerged. Despite procedural sedation and analgesia in Italian pediatric emergency departments is progressively more used than previously, several aspects still require an implementation. Our subgroup analysis could be a starter point for further studies and to improve and make the current Italian recommendations more homogeneous.

Abstract Background Noonan syndrome (NS) is a clinically and genetically heterogeneous disorder. Since its clinical phenotype is often mild and difficult to differentiate from other syndromes, its diagnosis can be challenging and its prevalence in the pediatric population is most certainly underestimated. The difficulty in identifying Noonan syndrome is also increased by the fact that genetic tests are currently not able to detect an underlying mutation in around 10% of the cases. Methods This is a retrospective, observational study conducted at the Institute for Maternal and Child “Burlo Garofolo” in Trieste, Italy. We recruited all the patients with clinical and/or genetic diagnosis of NS who were evaluated at the Department of Pediatrics between October 2015 and October 2020. Statistical analyses were performed with IBM SPSS Statistics software. The association between discrete variables has been evaluated through chi-squared test, indicating statistically significant p with Pearson test or Fischer test for variables less than 5. Results We recruited a total of 35 patients affected by Noonan syndrome. In 24 patients (75%) we identified an underlying genetic substrate: 17 patients had a mutation on PTPN11 (61%), 2 in SOS1, KRAS and SHOC2 (7% each) and only 1 in RAF1 (4%). 25% of the subjects did not receive a genetic confirm. As for the phenotype of the syndrome, our study identified the presence of some clinical features which were previously unrelated or poorly related to NS. For example, renal and central nervous system abnormalities were found at a higher rate compared to the current literature. On the contrary, some features that are considered very suggestive of NS (such as lymphatic abnormalities and the classical facial features) were not frequently found in our population. Conclusions In our analysis, we focused on the main phenotypic features of NS, identifying various clinical manifestation that were not associated with this genetic condition before. This could be helpful in raising the knowledge of NS’s clinical spectrum, facilitating its diagnosis.

Abstract Background COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. Case presentation We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists’ ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. Conclusions In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.

Brugada Syndrome is an “inherited” channelopathy characterized by a predisposition to syncope and sudden death. It typically presents in young adults but is also known to affect the pediatric population, even if the prevalence is low compared to the adult population. The diagnostic ECG pattern shows coved-type ST-segment elevation in the right precordial leads, occurring spontaneously or after provocative drug tests with IV administration of Class I antiarrhythmic drugs. However, the electrocardiographic findings may vary, and transient or concealed forms of the syndrome further complicate diagnosis, necessitating thorough evaluation and close clinical follow-up. The clinical presentation of Brugada Syndrome may range from asymptomatic individuals to patients who have experienced syncope or sudden cardiac arrest. The syndrome remains underdiagnosed due to its elusive symptoms and the absence of abnormal findings between episodes. Additionally, specific triggers such as fever, certain medications and alcohol consumption may unmask the electrocardiographic changes and provoke arrhythmias in susceptible individuals. Given its elusive nature, early diagnosis and risk stratification are crucial in identifying individuals who may benefit from an implantable cardioverter defibrillator, the mainstay of treatment for high-risk patients, or pharmacological interventions.

Diet is an essential element of treating and managing type 1 diabetes (T1D). However, limited research has examined food behaviour in children and adolescents with T1D and their relationship to glycaemic control. This study evaluated food behaviour, metabolic characteristics and their impact on the glycaemic control of children and adolescents with T1D. Two hundred and fifty-eight participants with T1D (6–15 years, duration of diabetes >1 year) were recruited. Demographic, anthropometric and clinical data were collected. Questionnaires on food neophobia and food preferences were administered. The Child Food Questionnaire (CFQ) also assessed parental feeding practices. An analysis of food behaviour showed that food neophobia was inversely associated with the liking of vegetables, fruits, fish, sweets and carbohydrates. Moreover, by analysing parental feeding practices, an inverse association of “Pressure to eat”, “Monitoring” and “Restriction” with liking for vegetables and carbohydrates emerged. Considering glycaemic control, increased food neophobia and the parent practices “Restriction”, “Pressure to eat” and “Concern about weight” were found in participants with glycated haemoglobin (HbA1c) values >8.5%. Finally, higher body mass index (BMI) and total cholesterol values were observed in subjects with HbA1c values >8.5%. These findings contribute to a better understanding of eating behaviour, metabolic status and their complex relationship with glycaemic control.

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug–drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.

Aim: The loosening of social distancing measures over the past two years has led to a resurgence of seasonal epidemics associated with respiratory viral infections in children. We aim to describe the impact of such infections through urgent hospitalizations in a pediatric emergency department. Methods: We performed a retrospective review of medical records of all children and adolescents with a positive nasal swab admitted at the children’s hospital IRCCS Burlo Garofolo of Trieste, in Italy, from September 2021 to March 2022, and September 2022 to March 2023. Results: Respiratory Syncytial Virus and Influenza viruses accounted for up to 55% of hospitalizations for respiratory infections during the study periods. During the last season, the number of hospitalizations related to the Influenza virus was five times higher than those related to SARS-CoV-2 (25% vs. 5%). Respiratory Syncytial Virus was associated with a greater need for respiratory support, mostly HFNC (High Flow Nasal Cannula). Conclusions: Respiratory Syncytial Virus and Influenza virus had a more significant impact on urgent hospitalizations during the past wintery seasons than SARS-CoV-2.

Background and Objectives: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard method for diagnosing central precocious puberty (CPP), although it requires multiple blood samplings over 120 min. This study aimed to evaluate if a shorter test may have an equivalent diagnostic accuracy. Materials and Methods: We retrospectively reviewed the GnRH tests of 188 consecutive pediatric patients (169 females) referred for signs of early pubertal development. The diagnostic accuracy of the hormonal levels was evaluated at different time points (15, 0, 60, 90, and 120 min after the GnRH stimulus). Results: A diagnosis of CPP was made in 130 cases (69%), with 111 (85%) being female. Sensitivity and specificity ratings higher than 99% for the diagnosis of CPP were achieved for LH levels ≥4.7 mU/mL at 30 and 60 min after the stimulus (area under the ROC curve (AUC) = 1), with no further increase in the diagnostic accuracy in the remaining time points. No sex differences in diagnostic accuracy were found. The LH/FSH ratio at 30 min showed a sensitivity of 94.9%, with an AUC of 0.997 and a value ≥0.76. Conclusions: A short-duration GnRH test of 60 min provided optimal results for the diagnosis of CPP. Extending the test for an extra hour is therefore unnecessary and inadvisable.

Abstract According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy. The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging. Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.

Abstract To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown. This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies. We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers. The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group. The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013). Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group.

Abstract Background Wolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures. Nevertheless, great phenotypic variability exists due to the variable extent of the responsible 4p deletion. In addition, exome sequencing analyses, recently identified two genes, namely NSD2 and NELFA, whose loss-of-function variants contribute to a clinical spectrum consistent with atypical or partial WHS. The observation of patients exhibiting clinical features resembling WHS, with only mild developmental delay and without the typical dysmorphic features, carrying microdeletions sparing NSD2, has lead to the hypothesis that NSD2 is responsible for the intellectual disability and the facial gestalt of WHS. While presenting some of the typical findings of WHS (intellectual disability, facial gestalt, microcephaly, growth restriction and congenital heart defects), NSD2-deleted children tend to display a milder spectrum of skeletal abnormalities, usually consisting of clinodactyly, and do not exhibit seizures. We describe the clinical picture of a child with WHS due to a de novo mutation of NSD2 and discuss the clinical and diagnostic implications. Case presentation A 6-year-old boy was evaluated for a history of intrauterine growth restriction, low birth weight, neonatal hypotonia, and psychomotor delay. No episodes of seizure were reported. At physical examination, he displayed marphanoid habitus, muscle hypotrophy and facial dysmorphisms consisting in high frontal hairline, upslanting palpebral fissures and full lips with bifid ugula. Cryptorchidism, shawl scrotum, mild clinodactyly of the right little finger and bilateral syndactyly of the II and III toes with sandal gap were also noted. The radiographic essay demonstrated delayed bone age and echocardiography showed mild mitral prolapse. Whole genome sequencing analysis revealed a heterozygous de novo variant of NSD2 (c.2523delG). Conclusions Full WHS phenotype likely arises from the cumulative effect of the combined haploinsufficiency of several causative genes mapping within the 4p16.3 region, as a contiguous genes syndrome, with slightly different phenotypes depending on the specific genes involved in the deletion. When evaluating children with pictures resembling WHS, in absence of seizures, clinicians should consider this differential diagnosis.

Abstract Background While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics. Methods Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center. Results Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (− 10% tests; − 8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (− 35%), while LHRH tests increased (+ 22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females. Conclusion This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children’s growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children’s anxiety as possible triggers of CPP.

Abstract Background Attention Deficit and Hyperactivity Disorder (ADHD) is a multi-factorial condition, with inheritance playing a major role. Recognizing parents’ ADHD represents a clue not only for an earlier diagnosis of the disease in their children, but also to optimize psycho-educational therapy outcomes, by addressing the impairment of parenting related to untreated ADHD. This study aimed to assess the frequency of features suggestive of ADHD during childhood among parents of affected children, and the presence of school and emotional impairment. Methods We administered the Wender Utah Rating Scale-25, a self-assessment tool for the retrospective identification of symptoms consistent with ADHD during childhood, to a cohort of 120 parents of 60 children with ADHD, and to a consistent number of “controls”. Results The WURS-25 proved positive in 49.1% of fathers and 30.0% of mothers of ADHD patients, compared to 1.7% of fathers and 1.7% of mothers of non-ADHD patients (p

Recipients of HSCT have a high risk of infective and non-infective pulmonary diseases. Most patients with pulmonary involvement present multiple pathogenetic mechanisms simultaneously with complex interactions. Therefore, it can be difficult to distinguish the contributions of each one and to perform studies on this subject. In this opinion article, we discuss only chronic pulmonary manifestations, focusing on LONIPCs (late-onset non-infectious pulmonary complications). This term embraces drug-related toxicity, allergies, and chronic pulmonary graft versus host disease (GvHD) in all its recently identified clinical variants. Among LONIPCs, GvHD represents the most critical in terms of morbidity and mortality, despite the rapid development of new treatment options. A recently emerging perspective suggests that pulmonary lung rejection in transplant patients shares striking similarities with the pathogenesis of GvHD. In a pulmonary transplant, the donor organ is damaged by the host immune system, whereas in GvHD, the donor immune system damages the host organs. It constitutes the most significant breakthrough in recent years and is highly promising for both hematologists and thoracic transplant surgeons. The number of patients with LONIPCs is scarce, with heterogenous clinical characteristics often involving several pathogenetic mechanisms, making it challenging to conduct randomized controlled trials. Therefore, the body of evidence in this field is scarce and generally of low quality, leading to jeopardized choices in terms of immunosuppressive treatment. Moreover, it risks being outdated by common practice due to the quick evolution of knowledge about the diagnosis and treatment of LONIPCs. The literature is even more pitiful for children with pulmonary involvement related to HSCT.

Abstract Background Some studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt. Methods Single‐center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8–24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8‐week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re‐evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL). Results During OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all. Conclusion In this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

Abstract Background Non-painful diagnostic procedures require an inactive state for a prolonged time, so that sedation is often needed in younger children to perform the procedures. Our standard of care in this setting consists of the association between oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (4 mcg/kg). One of the limits of this approach is that the onset of action is quite delayed (up to 55 min) and poorly predictable. We chose to compare this association with intranasal-ketamine and intranasal-dexmedetomidine. Methods This is a “pre-post” study. The study population included the first forty children receiving sedation with the “new” combination intranasal ketamine (3 mg/kg) and intranasal dexmedetomidine (4 mcg/kg) compared to a historical cohort including the last forty children receiving sedation with our standard of care combination of intranasal dexmedetomidine (4mcg/kg) and oral midazolam (0,5 mg/kg). Results The association intranasal dexmedetomidine and intranasal ketamine allowed for a significantly shorter sedation induction time than the combination intranasal dexmedetomidine and oral midazolam (13,5 min versus 35 min). Both group’s cumulative data showed a correlation between age and sedation effectiveness, with younger children presenting a higher success rate and shorter induction time (p 0,001). Conclusions: This study suggests that the ketamine and dexmedetomidine intranasal association may have a shorter onset of action when compared to intranasal dexmedetomidine and oral midazolam.

Abstract Background Italy was the first European country to experience a massive outbreak of Sars-coV-2 in March 2020. Severe measures were introduced to face the pandemic, significantly impacting all healthcare services, including pediatric palliative care (PPC) networks. We investigated how the Covid-19 pandemic modified the provision of PPC services in Friuli Venezia Giulia, Italy. Both the acute and long-term impacts on the families were addressed. Methods We administered a retrospective three-sections online questionnaire to the eligible families assisted by our regional PPC network. Inclusion criteria were: child needing specialistic PPC, adequate knowledge of the Italian language, being in charge of the PPC regional network of Friuli Venezia Giulia from February 1, 2020. The three sections examined the same issues in different periods: the pre-covid period (until February 29, 2020), the lockdown period (March 1, 2020, to April 30, 2020), and the post-lockdown period (May 2021). Results Twelve patients were included. During the lockdown period, 54.6% of children had to stop physiotherapy sessions, while, among those who continued, 80.0% experienced a reduction in the sessions’ frequency. In the post-lockdown period, 45.5% of children did not have physiotherapy as often as before the pandemic onset. Overall, the access to medical visits during the lockdown and after its end was significantly reduced (p = 0.01). The level of support perceived by the families descended from grade 3 (intermediate) in the pre-covid period to 2 (low) during the lockdown (p

AimWe compared adolescents’ visits to a tertiary-level paediatric emergency department (PED) in Italy during the pre-pandemic year and the first and second years of the COVID-19 pandemic, focusing on mental health presentations.MethodsThis was a retrospective study. We collected the number of visits, the demographical features, triage codes, discharge diagnoses, and outcomes of adolescents 13–17 years old who accessed the PED from 1 March 2019 to 28 February 2022.ResultsDuring the study period, 13,410 adolescents accessed the PED. The number of visits related to mental health problems was 304 (6.4%) in the second year of the pandemic and 306 (5.6%) in the pre-pandemic year, p = 0.07. In the same periods, females’ prevalence was higher, 220 (72.4%) vs. 197 (64.4%), p = 0.03. The absolute number of subjects needing admission increased, 44 vs. 34, p = 0.21, and more urgent psychiatric consultations were needed, 161 vs. 114, p

BackgroundFatigue is a common, nonspecific complaint commonly used to describe various conditions, ranging from a vague, subjective sense of weariness to muscular weakness, fatigability, exercise intolerance or excessive daytime somnolence. Despite its high frequency in the general population, literature addressing the approach to the child with fatigue from a general pediatrician perspective is poor. We herein propose a review of the available evidence on the topic, providing a practical framework to assist physicians in dealing with the issue.MethodsData were identified by searches of MEDLINE, UpToDate, Google Scholar and references from relevant articles. Articles published between 1990 and 2021 were considered, prioritizing systematic reviews and meta-analyses. Then, an empirically-based model of approaching the tired child was proposed according to our center experience.ResultsTo correctly characterize the meaning of fatigue reporting, specific clues from history and physical examination should be emphasized. Duration, severity, and the age at onset are to be considered. Then, specific queries about everyday activities, sleep hygiene and social domain could be useful in reaching a specific diagnosis and offering an appropriate treatment.ConclusionsWe suggest a pragmatic approach to fatigue in children based on age assessment, targeted questions, physical examination clues, and some laboratory first-level tests. This could provide pediatricians with a useful tool to discriminate the broad etiology of such a complaint, disentangling between psychological and organic causes. Further studies are needed to investigate the predictive value, specificity and sensitivity of this diagnostic workflow in managing the child with fatigue.

Abstract Background Describe the efficacy of a galenic glycopyrrolate formulation and its impact on patients with sialorrhea Quality of Life (QoL), including costs analysis. Methods We performed a retrospective observational study on 21 patients who received a custom-formulated galenic glycopyrrolate syrup for sialorrhea for an average period of 14.3 months. We analyzed the telephone interviews with elaborated and validated questionnaires and the therapy costs comparing the brand marketed drug with the galenic formulation. Results Overall, 16 out of 21 patients (76.2%) reported a significant improvement in sialorrhea and QoL. In 14 subjects (66.7%), there was a remarkable decrease in the drooling severity; 10 individuals (47.6%) reported a reduction in drooling frequency. Nine patients experienced at least one adverse effect of glycopyrrolate therapy, and three of them stopped the treatment. No severe side effects were observed. The galenic drug significantly reduced costs for patients. Conclusions An oral glycopyrrolate solution easily administered to children with brain injuries is not commercially available in many European countries. This study demonstrates the efficacy of a compounded glycopyrrolate syrup on drooling severity, frequency and ensures a better QoL in patients and their caregivers.