Early Developmental Intervention and Enriched Environment in CDKL5 Developmental and Epileptic Encephalopathy: A Case Report.

Objectives: CDKL5 developmental and epileptic encephalopathy (CDKL5-DEE) is a rare X-linked dominant genetic disorder. Family-centered Early Intervention (EI) programs, which promote axonal plasticity and synaptic reorganization through exposure to an enriched environment, should be integrated into clinical practice. However, there is presently a dearth of dedicated EI protocols for patients with CDKL5-DEE and cerebral visual impairment (CVI). Methods: We present a girl with a deletion of the CDKL5 gene (MIM*300203). At the age of 2 months, the child presented with severe epilepsy. The neurologic examination was abnormal, and she had severe CVI. At the first assessment, at 5 months old, her Developmental Quotient (DQ) on the Griffiths Mental Developmental Scales III (GMDS-III) was equivalent to 3-month-old skills (95% CI). The child was enrolled in an EI program for 6 months. Results: At 12 months of age, the DQ score was 91. There has been improvement in the neurovisual functions. The findings from the scales show a gradual improvement in neuromotor and psychomotor development, which is in contrast to the expected outcome of the disease. Discussion: The case study shows that a family-centered EI and prompt assessment of CVI can promote and enhance neurodevelopment.

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.

Present and future are getting confused: are we equipped to face the technological revolution?

BACKGROUND: This is a commentary reporting the outcome of a workshop promoted by the Department of Woman's and Child's Health of the University of Padua (Italy) focused on the emerging issue of what seems to be the increasing agemone role of technology. MAIN BODY: Over the centuries, technology has always been at the service of science, with theoretical insights anticipating experimental proofs. Over the last decades, however, the situation has radically changed, due to several factors. Technology seems to be playing an agemone role. The present and notably the future generation of scientists have major challenges to face. They have to deal with the forces generated by the infosphera; to dominate the technology and to maintain the capacity of generating inquisitive, creative, ethical and spiritual thoughts capable of addressing new scientific hypotheses and projects directed to the individual and collective good. However, in this scenario, what seems more relevant is to focus all our efforts in preparing ourselves, first, and then the new generations to face these challenges. From this point of view, the academic institutions and the scientific societies, have a major responsibility to deal with. CONCLUSIONS: The academic ecosystem traditionally used to educate the new generation of professionals as well as, and most importantly, the cultural, the professional pathways presently used to form them need to be extensively revised. The time is running short and the stakes are high. The debate is open.

Surgeons' perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey.

BACKGROUND: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons' knowledge and perception of using AI-based tools in clinical decision-making processes. METHODS: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society's website and Twitter profile. RESULTS: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons' preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. DISCUSSION: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI.

Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis.

BACKGROUND: Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. OBJECTIVE: The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. METHODS: The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. RESULTS: The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. CONCLUSIONS: Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.

Serum Aspergillus-specific IgE, IgG and IgG4 immunoglobulins assessment in the work-up of invasive pulmonary aspergillosis: a prospective cohort study.

BACKGROUND: Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG4, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy). METHODS: We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG4 specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patients. RESULTS: Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG4 showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM. CONCLUSIONS: In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

Eligibility criteria for pediatric patients who may benefit from anti SARS-CoV-2 monoclonal antibody therapy administration: an Italian inter-society consensus statement.

The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts' agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

ARIA-ITALY multidisciplinary consensus on nasal polyposis and biological treatments.

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Agreements and controversies of national guidelines for bronchiolitis: Results from an Italian survey.

INTRODUCTION: Significant variations in the management of bronchiolitis are often recorded, and, in parallel, to recommend a univocal clinical approach is challenging and still questioned. This study is aimed to evaluate the diagnostic and therapeutic management of bronchiolitis in children adopted by Italian pediatricians following the national guidelines. MATERIAL AND METHODS: A survey study was designed and carried out by sending an email an open-ended questionnaire developed by an expert panel of the Scientific Board of the Italian Society of Pediatric Allergology and Immunology (SIAIP). Questions were designed according to the national intersociety consensus document on treatment and prevention of bronchiolitis in newborns and infants. RESULTS: Overall, 234 pediatricians were taking part in the study. When diagnosing bronchiolitis, only 44.01% (103/234) of participants correctly followed the national guidelines. All participants (100%) would perform laboratory tests and/or radiological exams. 44.01% administered oxygen (O2 ) when O2 saturation was minor than 92%. About the therapeutic regimen, marked discrepancies between national guidelines and recorded answers were reported. Indications for hospital admission and discharge criteria were in line with the national guidelines. CONCLUSIONS: There is a significant practice variation in the management of acute bronchiolitis among Italian physicians. Some wrong attitudes need to be further discouraged, such use of diagnostic procedures and therapeutic approaches. Further research is urgently required to define the best management of patients with bronchiolitis and implement strategies to standardize care and improve the quality of care.

COVID vaccination and asthma exacerbation: might there be a link?

INTRODUCTION: There is ongoing debate regarding the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of coronavirus disease 2019 (COVID-19) vaccination on asthma is entirely unexplored. CASE STUDY: This study examined a challenging case of severe asthma exacerbation in a 28-year-old female following two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at IRCCS Policlinico San Matteo in Pavia, Italy. The patient, a fourth-year resident at the hospital, was vaccinated in early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She tested negative for SARS-CoV-2 on several molecular swabs and serology tests. RESULTS: After receiving the second dose of vaccine, the patient started to experience worsening of respiratory symptoms. Following several episodes and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug (interleukin-5) antagonist monoclonal antibody. CONCLUSION: This single case study is insufficient to draw conclusions about the association between asthma exacerbation and the COVID-19 vaccine. While the cause-effect link between vaccination against SARS-CoV-2 and worsening of asthmatic disease might only be suggested at present, this case is a valuable prompt for further investigation. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe.

The relevance of symptom perception in the management of severe asthma in adolescents.

BACKGROUND: Severe asthma in adolescents is a demanding challenge that deserves adequate management, including thorough work-up and rigorous follow-up. METHODS: We evaluated a group of adolescents with severe asthma to investigate the change over time of clinical, functional, and biological parameters. RESULTS: Most of adolescents treated with standard therapy improved, but some did not achieve an optimal asthma control and FeNO values increased. CONCLUSIONS: Despite guidelines-based therapy and clinical-functional improvement, type 2 inflammation could be not completely controlled. Biologics option could be considered if biomarkers suggest potential asthma relapse.

Impact that the COVID-19 pandemic on routine childhood vaccinations and challenges ahead: A narrative review.

AIM: To document the decline in vaccination coverage in the first months of 2020 as an indirect effect of the COVID-19 pandemic. METHODS: We performed a literature review in medical databases. Overall, 143 articles were initially retrieved, out of which 48 were selected and included in the review. RESULTS: Our review retrieved similar data in many countries worldwide, and, globally, preliminary data from the first 4 months of 2020 indicate a decline in diphtheria-tetanus-pertussis coverage, generally considered the marker of vaccination coverage across countries. World Health Organization recommends maintaining vaccination services, prioritising primary series vaccinations especially for measles-rubella or poliomyelitis, but it also lets each country decide whether to maintain the immunisation services evaluating the current epidemiology of vaccine-preventable diseases and the COVID-19 local transmission scenario. Successively, recovering of vaccinations should be planned. Moreover, during the pandemic, influenza vaccination should be promoted as a central public health measure. CONCLUSION: Future challenges will be to maintain the vaccination programmes, especially in children younger than 2 years old and adolescents, to plan the recovery of vaccinations for subjects who postponed them during the lockdown, and to early identify any vaccine-preventable disease outbreak.

Eosinophilic colitis in children: a new and elusive enemy?

PURPOSE: Eosinophilic gastrointestinal disorders are rare in children and present with a broad spectrum of non-specific symptoms. To date, no guidelines for diagnosis, therapy and follow-up are validated. Aim of our study is to focus on eosinophilic colitis (EC), to determine a possible correlation between associated disorders, macroscopic findings and treatment/follow up. METHODS: Retrospective study from 2015 to 2019 including all colonoscopies performed at our Institution. Eosinophilic colitis was defined according to the threshold identified by Collins: > 100 Eo/Hpf: right colon, > 84 Eo/Hpf transverse and left colon, > 64 Eo/Hpf sigma and rectum. We excluded colonoscopy in patients with IBD or other diseases causing hypereosinophilia (i.e., parasite infection, GVHD). RESULTS: Among 399 colonoscopies performed in 355 patients, we made 50 diagnosis of EC, 36 males, 14 females, median age 8.5 (3-17). Symptoms leading to endoscopy were recurrent abdominal pain (66%), chronic diarrhea (64%), and chronic constipation (8%). Two patients presented with GI bleeding and one with weight loss. Macroscopic findings were mostly normal or lymphoid nodular hypertrophy presenting different endoscopic features. In seven children (14%) we found history of allergy and atopy. 22 children present a diagnosis of autistic spectrum disorder (ASD) with a prevalence higher than in the overall population (44% vs 28.5%, p = 0.03). According to symptoms, treatment consist variably of steroids, six food elimination diet, mesalamine. For patients with available follow-up, we found histological persistence of Eosinophils in 75%, even in patients with symptoms relief. CONCLUSION: This study focus attention on EC as a new challenging pathology. Multicentric randomized clinical trials are needed to understand physiopathological mechanisms to validate a possible endoscopic score and related histological threshold, and to standardize therapy according to clinical features and instrumental findings. The high prevalence of EC in ASD need further specific research.

Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis.

non-IgE and mixed gastrointestinal food allergies present various specific, well-characterized clinical pictures such as food protein-induced allergic proctocolitis, food protein-induced enterocolitis and food protein-induced enteropathy syndrome as well as eosinophilic gastrointestinal disorders such as eosinophilic esophagitis, allergic eosinophilic gastroenteritis and eosinophilic colitis. The aim of this article is to provide an updated review of their different clinical presentations, to suggest a correct approach to their diagnosis and to discuss the usefulness of both old and new diagnostic tools, including fecal biomarkers, atopy patch tests, endoscopy, specific IgG and IgG4 testing, allergen-specific lymphocyte stimulation test (ALST) and clinical score (CoMiss).

Abdominal pain as first manifestation of lyme neuroborreliosis in children, case report and review of literature.

BACKGROUND: Lyme neuroborreliosis can cause a variety of neurological manifestations. European children usually present facial nerve palsy, other cranial nerve palsies and aseptic meningitis. CASE PRESENTATION: We hereby report a case of Lyme neuroborreliosis in a 9-year-old boy with abdominal pain as first symptom and subsequent onset of attention deficit and ataxia. Diagnosis was made by detection of specific antibody in both serum and cerebrospinal fluid with neuro-radiological images suggestive for this infectious disease. A 12-months follow-up was performed during which no relevant neurological sequelae were revealed. CONCLUSION: This case report shows that abdominal radiculitis, although extremely rare, could be the first manifestation of early Lyme neuroborreliosis in pediatric patients. Pediatricians must consider Lyme disease in the differential diagnosis of abdominal pain of unknown origin in children, especially in countries where the infection is endemic.

The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999-2019).

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data collected from the IPINet registry after 20 years of activity. A total of 3352 pediatric and adult patients affected with PIDs are registered in the database. In Italy, a regional distribution trend of PID diagnosis was observed. Based on the updated IUIS classification of 2019, PID distribution in Italy showed that predominantly antibody deficiencies account for the majority of cases (63%), followed by combined immunodeficiencies with associated or syndromic features (22.5%). The overall age at diagnosis was younger for male patients. The minimal prevalence of PIDs in Italy resulted in 5.1 per 100.000 habitants. Mortality was similar to other European registries (4.2%). Immunoglobulin replacement treatment was prescribed to less than one third of the patient cohort. Collectively, this is the first comprehensive description of the PID epidemiology in Italy.

Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical.

Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis.

Lertal®, a multicomponent nutraceutical, could reduce the use of antihistamines in children with allergic rhinoconjunctivitis.

Antihistamines are the cornerstone treatment of allergic rhinitis (AR). To quantify the antihistaminic consume is particularly relevant in clinical practice, since a remarkable use is usually associated with severe symptoms. The aim of the study was to measure the use of antihistamines in two groups of children suffering from AR. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). Both groups took antihistamines on demand. The children were visited at baseline and after 1 year. The number of days of antihistaminic use was the primary outcome. Children in AG had a significant reduced number of antihistamines use in comparison with CG (p=0.008). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the use of symptomatic antihistamines in children with allergic rhinoconjuncti- vitis.

Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal(R).

Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed: Lertal®. It contains quercetin, perilla extract, and vitamin D3. These agents exert anti-allergic and anti-inflammatory activities. This article reports and discusses the results of four clinical studies conducted in adult and paediatric patients suffering from AR. Outcomes provided evidence that Lertal® may significantly prevent clinical worsening when prescribed as add-on to continuous antihistaminic treatment and also prevent clinical exacerbations, such as the need of rescue medication, when used alone as preventive strategy in AR patients.