The effect of near-infrared Photobiomodulation therapy on the ion content of 50B11 sensory neurons measured through XRF analysis.

Photobiomodulation therapy (PBMT) is a form of treatment commonly used for routine clinical applications, such as wound healing of the skin and reduction of inflammation. Additionally, PBMT has been explored for its potential in pain relief. In this work, we investigated the effect of PBMT on ion content within the 50B11 sensory neurons cell line in vitro using X-Ray fluorescence (XRF) and atomic force microscope (AFM) analysis. Two irradiation protocols were selected utilizing near-infrared laser lights at 800 and 970 nm, with cell fixation immediately following irradiation. Results showed a decrease in Calcium content after irradiation with both protocols, and with lidocaine, used as an analgesic control. Furthermore, a reduction in Potassium content was observed, particularly evident when normalized to cellular volume. These findings provide valuable insights into the molecular impact of PBMT within 50B11 sensory neurons under normal conditions. Such understanding may contribute to the wider adoption of PBMT as a therapeutic approach.

Use of intranasal and sublingual analgesia in children and adolescents in the paediatric emergency department.

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.

Minimizing unnecessary brain magnetic resonance imaging in pediatric endocrinology: a retrospective cohort analysis.

Background: Brain 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. Methods: Retrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty). Results: The 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%). Conclusions: Only 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.

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.

Neuron-Derived Extracellular Vesicles miRNA Profiles Identify Children Who Experience Adverse Events after Ketamine Administration for Procedural Sedation.

Ketamine provides the highest safety profile among sedatives for procedural sedation and analgesia in the pediatric emergency setting. However, it can cause vomiting and recovery agitation. No studies have examined epigenetic factors, such as microRNAs, for predicting the occurrence of these adverse events. Neuronal-derived extracellular vesicle microRNA profiles were studied to predict the occurrence of ketamine-induced vomiting and recovery agitation in children. For this aim, a single-center prospective pharmacoepigenetic study was performed and 50 children who underwent procedural sedation with intravenous ketamine as the only sedative drug were enrolled between October 2019 and November 2022. MiRNA profiling in plasma neural-derived extracellular vesicles was analyzed through next-generation sequencing and measured before treatment with ketamine. Twenty-two patients experienced vomiting or recovery agitation. Among the 16 differentially expressed microRNAs, the upregulated miR-15a-5p and miR-484 targeted genes related to N-methyl-D-aspartate (NMDA) receptor activity, including glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A). Preliminary data confirmed lower GRIN2A levels in patients who developed these events. Downregulated miR-126-3p and miR-24-3p targeted AMPA receptor-associated genes. Functional analyses of gene targets revealed the enrichment of glutamatergic and neurotrophins signaling. Recovery agitation was associated with this network. Vomiting was related to dopaminergic and cholinergic systems. Three miRNAs (miR-18a-3p, miR-484, and miR-548az-5p) were identified as predictive biomarkers (AUC 0.814; 95% CI: 0.632-0.956) for ketamine-induced vomiting and recovery agitation. MicroRNA profiles can predict the development of ketamine-induced vomiting or recovery agitation in children. This study contributes to the understanding of the mechanisms underlying ketamine-induced adverse events.

Implementation of the WHO standards to assess quality of care for children with acute pain in EDs: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is little experience on the use of the WHO Standards for improving the quality of care (QOC) for children. We describe the use of four prioritised WHO Standard-based Quality Measures to assess the provision of care for children with pain in emergency departments (EDs). METHODS: In a multicentre observational study in 10 EDs with different characteristics in Italy, we collected data on 3355 children accessing the EDs between January 2019 and December 2020. The association between children and facility characteristics and quality measures was analysed through multivariate analyses. RESULTS: The proportion of children whose pain was measured was 68.7% (n=2305), with extreme variations across different centres (from 0.0% to 99.8%, p<0.001). The proportion of children treated for pain was 28.9% (n=970) again with a wide range (5.3%-56.3%, p<0.001). The difference between the frequency of children with pain measured and pain treated varied widely between the facilities (ranging from -24.3 to 82). Children with moderate and severe pain were more frequently treated (48.9% and 62.9% of cases, respectively), although with large variations across centres (ranges: 0%-74.8% and 0%-100% respectively, p<0.001). After correction for children's characteristics, the variable more strongly associated with analysed outcomes was the facility which the child accessed for care. Being a facility in Northern Italy was associated with a higher rate of pain measurement (67.3%-95% CI: 39.9% to 94.6%, p<0.001) compared with facilities in South Italy (-22.1% lower (95% CI: -41.7% to -2.50%, p=0.03). CONCLUSIONS: The use of few WHO Standard-based measures related to pain can help identifying priority gaps in QOC for children and in monitoring it over time. There is a need for more implementation research to establish which are the most sustainable and effective interventions to improve the QOC for acute pain in children.

Evaluation of the WHO standards to assess quality of care for children with acute respiratory infections: findings of a baseline multicentre assessment (CHOICE) in Italy.

BACKGROUND: Experience is lacking on the implementation of the WHO standards for improving the quality of care (QOC) for children at facility level. We describe the use of 10 prioritised WHO standard-based quality measures to assess provision of care for children with acute respiratory infections (ARI) in Italy. METHODS: In a multicentre observational study across 11 emergency departments with different characteristics, we collected 10 WHO standard-based quality measures related to case management of children with ARI and no emergency/priority signs. Univariate and multivariate analyses were conducted. RESULTS: Data from 3145 children were collected. Major differences in QOC across facilities were observed: documentation of saturation level and respiratory rate varied from 34.3% to 100% and from 10.7% to 62.7%, respectively (p<0.001); antibiotic prescription rates ranged from 22.6% to 80.0% (p<0.001), with significant differences in the pattern of prescribed antibiotic; hospitalisations rates ranged between 2.3% and 30.6% (p<0.001). When corrected for children's individual sociodemographic and clinical characteristics, the variable more consistently associated with each analysed outcome was the individual facility where the child was managed. Higher rates of antibiotics prescription (+33.1%, p<0.001) and hospitalisation (+24.7%, p<0.001) were observed for facilities in Southern Italy, while university centres were associated with lower hospitalisation rates (-13.1%, p<0.001), independently from children's characteristics. CONCLUSIONS: The use of 10 WHO standard-based measures can help quickly assess QOC for children with ARI. There is an urgent need to invest more in implementation research to identify sustainable and effective interventions to ensure that all children receive high QOC.

Implementation of the WHO Standards to assess the quality of paediatric care using health workers as source of data: findings of a multicentre study (CHOICE) in Italy.

OBJECTIVES: There is little experience in implementing the WHO Standards for improving the quality of care (QOC) for children. We describe the use of 75 WHO-Standard based Quality Measures to assess paediatric QOC, using health workers (HWs) as data sources. DESIGN: Cross-sectional study. SETTING: 12 Italian hospitals. PARTICIPANTS: The minimum target of 75% of HWs was reached in all facilities; answers from 598 HWs were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: 75 prioritised WHO Quality Measures were collected using a validated, and Italian-language questionnaire exploring views of HWs providing care to children. A QOC index was also calculated based on the assessed Quality Measures. RESULTS: In both the domain of resources and work organisation, most Quality Measures showed a high overall frequency of reported 'need for improvement', with high variability across hospitals. Key needs for improvement included: availability of clear and complete protocols (eg, on paediatric emergencies: 44.6%; range 10.6%-92.6%); clear hospitalisation criteria for diarrhoea (50.5%; range 30.3%-71.7%); number of hand-washing stations (13.2%; range 3.4%-37.0%); equipped working rooms with computers for HWs (66.1%; range: 32.1%-97.0%); training (eg, on pain management: 43.5%; range 17.9%-76.7%), periodic discussion of clinical cases (43.5%; range 8.1%-83.7%) audits (48.8%; range 29.7%-76.7%); and all indicators related to system to improve QOC. Factors significantly associated with a lower QOC Index included HWs working in facilities in Southern Italy (p=0.001) and absence of a paediatric emergency department (p=0.011). CONCLUSIONS: The use of the 75 prioritised Quality Measures, specific to HWs provide valuable data on paediatric QOC, which can be used to drive a quality improvement process.

Long-Term Stability of Glycopyrrolate Oral Solution Galenic Compound at Different Storage Conditions.

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.

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.

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.

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.

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.