Effectiveness of pharmacological procedural sedation in children with autism spectrum disorder: A systematic review and meta-analysis.

AIM: Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD. METHODS: We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD. RESULTS: Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone. CONCLUSION: Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

Successful treatment of cortical visual impairment in children using anti-amblyopia treatment despite the absence of amblyopia: a case report.

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.

An ecological study shows increased prevalence of autism spectrum disorder in children living in a heavily polluted area.

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.

Lung transplant list withdrawal in a liver transplant patient thanks to elexacaftor-tezacaftor-ivacaftor: a case report.

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.

Administration of bicarbonates through percutaneous gastrostomy with continuous nocturnal infusion in a patient with Kearns-Sayre disease: a life changing therapeutical paradigm.

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.

Continuous Infusion of Dexmedetomidine for Maintenance of Sedation in an Aggressive Adolescent with Autism Spectrum Disorder in the Emergency Department.

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.

Recommendations for cardiovascular magnetic resonance and computed tomography in congenital heart disease: a consensus paper from the CMR/CCT Working Group of the Italian Society of Pediatric Cardiology and the Italian College of Cardiac Radiology endorsed by the Italian Society of Medical and Interventional Radiology (Part II).

Cardiovascular magnetic resonance (CMR) and computed tomography (CCT) are advanced imaging modalities that recently revolutionized the conventional diagnostic approach to congenital heart diseases (CHD), supporting echocardiography and often replacing cardiac catheterization. This is the second of two complementary documents, endorsed by experts from the Working Group of the Italian Society of Pediatric Cardiology and the Italian College of Cardiac Radiology of the Italian Society of Medical and Interventional Radiology, aimed at giving updated indications on the appropriate use of CMR and CCT in different clinical CHD settings, in both pediatrics and adults. In this article, support is also given to radiologists, pediatricians, cardiologists, and cardiac surgeons for indications and appropriateness criteria for CMR and CCT in the most referred CHD, following the proposed new criteria presented and discussed in the first document. This second document also examines the impact of devices and prostheses for CMR and CCT in CHD and additionally presents some indications for CMR and CCT exams when sedation or narcosis is needed.

School Absenteeism Longer Than Two Weeks Is a Red Flag of Somatic Symptom and Related Disorders in Hospitalised Children and Adolescents: A Matched Cohort Study.

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 in Children and Adolescents: A General Overview.

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). ß-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.

Adolescent gender dysphoria management: position paper from the Italian Academy of Pediatrics, the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, the Italian Society of Adolescent Medicine and the Italian Society of Child and Adolescent Neuropsychiatry.

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.

Clinical and laboratory characteristics but not response to treatment can distinguish children with definite growth hormone deficiency from short stature unresponsive to stimulation tests.

Introduction: It 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. Methods: Retrospective 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%). Results: At 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 <-2 SDS) (56% vs 51%, p=0.45). IGF-1 SDS were significantly lower in dGHD (-2.0 vs -1.3, p<0.01). After 1 year of treatment, the prevalence of short stature was significantly reduced in both groups (31% in dGHD vs. 21% in SUS, p<0.01) without any significant differences between groups (p=0.19), while the increase in IGF-1 SDS for bone age was greater in the dGHD category (+1.9 vs. +1.5, p<0.01), with no further difference in IGF-1 SDS between groups. At the last available follow-up, 59 patients had reached the near adult height (NAH) and underwent retesting for GHD. No differences in NAH were found (-0.3 vs. -0.4 SDS, 0% vs. 4% of short stature). The prevalence of pathological retesting was higher in dGHD (60% vs. 10%, p<0.01) as well as of overweight and obesity (67% vs. 26%). Conclusion: Stimulation tests and the equivalent benefit from rhGH therapy, cannot distinguish between dGHD and SUS populations. In addition, lower IGF-1 concentrations at baseline and their higher increase during treatment in dGHD patients, and the lack of pathological retesting upon reaching NAH in SUS patients, are facts that suggest that deficient GH secretion may not be the cause of short stature in the SUS studied population.

Brugada Syndrome: Focus for the General Pediatrician.

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.

The Risks of Phosphate Enemas in Toddlers: A Life-Threatening Unawareness.

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.

Timeline of diagnosed pain causes in children with severe neurological impairment.

Objective: Pain'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. Methods: We 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). Results: Eighty 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 < 0.001). Conclusions: Some causes of pain are more frequent in children with severe neurological impairment in defined age-related periods. Specific age-related pain frequencies may help physicians in the diagnostic approach.

Decrease in Mycophenolate Mofetil Plasma Concentration in the Presence of Antibiotics: A Case Report in a Cystic Fibrosis Patient with Lung Transplant.

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.

Food Behaviour and Metabolic Characteristics of Children and Adolescents with Type 1 Diabetes: Relationship to Glycaemic Control.

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.

Increased bronchiolitis burden and severity after the pandemic: a national multicentric study.

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 < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021-2022, 0 in 2020-2021, 11 (2%) in 2019-2020 and 6 (1%) in 2018-2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021-2022, 1 (33%) in 2020-2021, 68 (23%) in 2019-2020, 61 (28%) in 2018-2019 (p = 0.001). CONCLUSIONS: This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years.

Nonpharmacological treatment of rumination syndrome in childhood: A systematic review of the literature.

Rumination syndrome (RS) is a complex functional disorder characterized by recurrent, repetitive regurgitation of recently swallowed food. RS may have medical and psychosocial implications, compromising the quality of life and causing high rates of school absenteeism. Pediatric RS has been poorly studied and little evidence regarding its treatment is available. This systematic review aims to evaluate the literature on the nonpharmacological treatment of RS in childhood. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, from 2000 to 2023. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different designs of study, and the risk of bias was evaluated with the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). Five hundred ninety-six studies were screened, and 7 studies were included in the review. Diaphragmatic breathing was the most used nonpharmacological treatment, and it was always combined with other therapeutic strategies. The vast heterogeneity of the physical or mental comorbidities and the methodology adopted in the publications did not allow a comparative analysis of the different treatments. Regardless of the type of treatment, high-intensity therapeutic programs and specific operators' training emerged as the most influencing factors for patients' outcomes. According to the available evidence, there is not enough high-quality evidence to suggest a defined therapeutic strategy. Large observational studies on selected patients accounting for possible confounders, with adequate follow-up times, and with clearly defined treatment regimens are needed to identify the best therapeutic approach.