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Objective: to investigate the trend of autoantibody titers during a 2-year follow-up in pediatric systemic lupus erythematosus (pSLE) and pediatric Sjögren's syndrome (pSS)., Methods: Autoantibodies testing was performed every 3-4 months during 2 years from disease onset in a cohort of children with pSLE and pSS., Results: We enrolled 21 children with pSLE and 22 children with pSS. All pSLE patients at 2 years showed ANA titers significantly lower compared to disease onset. Eleven patients (73%) were still ANA positive at 2 years, while 4 (26%) became ANA negative. At diagnosis, 12 (80%) patients showed a homogeneous pattern, while 3 (20%) patients showed a speckled pattern. The latter remained ANA positive with the same pattern; only 2 patients with a homogenous pattern converted to speckled, 4 patients with a homogeneous pattern became ANA negative. ANA negative pSLE patients showed lower levels of interferon score compared to ANA positive patients. Anti-dsDNA titers declined equally in the two groups. All patients with pSS, at disease onset, were ANA and anti-Ro positive and 14 (66%) were anti-La positive. After 2 years of follow-up, 100% remained ANA positive but showed significant lower titers. During follow-up anti-Ro and anti-La titers remained stable., Conclusion: different patterns in changes of ANA and ENA titers in pSLE and pSS were shown. At 2 years of follow-up, all pSLE patients had a lower ANA titer and 26% became negative; however, all pSS patients remained both ANA and ENA positive. This evidence may be due to different pathogenetic pathways in SLE and pSS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI. Italy has a high prevalence of rare CFTR variants compared to the rest of Europe, potentially leading to significant undertreatment of people with rare CFTR variants. In this study, we used patient-derived intestinal organoids to identify individuals harboring rare CFTR variants who might benefit from ETI modulator therapy. Two CFTR-dependent readouts (steady-state lumen area and forskolin-induced swelling) in intestinal organoids were characterized to assess CFTR function rescue upon ETI incubation. Functional restoration by CFTR modulators was compared to wild type CFTR function, ETI-treated organoids harboring genotypes currently eligible for ETI therapy (F508del/class I) and organoids harboring non-responsive genotypes. Our data showed in vitro response to ETI within or beyond the range of CFTR function associated with F508del-ETI in 19 out of 28 organoids. This suggest that a large percentage of people with rare CFTR variants without access to ETI may benefit from this treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.B. has a patent related to the FIS-assay with royalties paid. C.K.v.d.E. reports a patent (10006904) with royalties paid., (Copyright © 2024. Published by Elsevier B.V.)

Background: The use of mobile applications helps improving self-management in adolescents with asthma. However, no evidence is available for children with preschool wheezing. In addition, we have no data on the reliability of medical history collected at visits. The first aim was to assess the feasibility of a smartphone app in the management of preschool wheezing; secondly we aimed to evaluate the reliability of anamnestic data collected during face-to-face medical interviews., Methods: Children with recurrent wheezing, age between 25 and 72 months, were randomly assigned to the intervention group, provided with a smartphone app for symptoms monitoring and asthma attack treatment, or to the control group, with a written action plan. At follow-up medical history was collected and the asthma control test and a clinical questionnaire were completed. App acceptability was also explored. Respiratory symptoms, medication and utilization of healthcare resources were collected. Plus, medical information obtained from the paper questionnaires was compared with data daily recorded by the app., Results: We enrolled 85 preschool children with recurrent wheezing: 43 assigned to the intervention and 42 to the control group. The average (SD) adherence to e-Diary compilation was 60 (15)%. The acceptance and usability of the intervention was favorable as 70% and 93% of participants in the intervention arm described the app as ''simple and intuitive'' at Visit1 (after 3 months from enrollement) and Visit2 (3 months later than Visit1), respectively and 95% and 98% found it useful in symptoms management. There were no significant differences between the two groups in clinical outcomes. At Visit1, the cACT median score (IQR) was 23,5 (21-25) for the control group (42 patients) and 23 (21-24) for the intervention group (43 patients). At Visit2 (41 controls and 42 in the intervention group) it was 25 (24-25) and 24 (24-25), respectively. Secondary analysis of data from the intervention group showed higher incidence of daily symptoms recorded by the app in comparison with the paper questionnaire, suggesting that collection of retrospective medical history may not be completely reliable., Conclusions: The smartphone app is usable and acceptable by families of preschool wheezers. Future controlled trial are needed to prove an impact on clinical outcomes or its efficacy in a telemedicine program. Finally a daily questionnaire could provide physicians with a more reliable clinical picture as reflected better daily asthma symptoms than the written retrospective questionnaire filled at clinical visit., (© 2024. The Author(s).)

Cystic fibrosis (CF) is a multisystem disorder characterized by progressive respiratory deterioration, significantly impacting both quality of life and survival. Over the years, lung ultrasound (LUS) has emerged as a promising tool in pediatric respiratory due to its safety profile and ease at the bedside. In the era of highly effective CF modulator therapies and improved life expectancy, the use of non-ionizing radiation techniques could become an integral part of CF management, particularly in the pediatric population. The present review explores the potential role of LUS in CF management based on available data, analyzing all publications from January 2015 to January 2024, focusing on two key areas: LUS in CF pulmonary exacerbation and its utility in routine clinical management. Nonetheless, LUS exhibits a robust correlation with computed tomography (CT) scans and serves as an additional, user-friendly imaging modality in CF management, demonstrating high specificity and sensitivity in identification, especially in consolidations and atelectasis in the CF population. Due to its ability, LUS could be an instrument to monitor exacerbations with consolidations and to establish therapy duration and monitor atelectasis over time or their evolution after therapeutic bronchoalveolar lavage. On the basis of our analysis, sufficient data emerged showing a good correlation between LUS score and respiratory function tests. Good sensitivity and specificity of the methodology have been found in rare CF pulmonary complications such as effusion and pneumothorax. Regarding its use in follow-up management, the literature reports a moderate correlation between LUS scores and the type, extent, and CT severity score of bronchiectasis. A future validation of ultrasound scores specifically in CF patients could improve the use of LUS to identify pulmonary exacerbations and monitor disease progression. However, further research is needed to comprehensively establish the role of LUS in the CF population, particularly in elucidating its broader utility and long-term impact on patient care.

Objectives: Paediatric Sjögren's syndrome (pSS) is a rare chronic autoimmune disorder, characterised by inflammation of exocrine glands. B cell hyperactivation plays a central role in adult-onset Sjogren. This study was designed to analyse B cell and T cell phenotype, levels of BAFF, and selection of autoreactive B cells in patients with pSS., Methods: A total of 17 patients diagnosed with pSS and 13 healthy donors (controls) comparable for age were enrolled in the study. B cell and T cell subsets and frequency of autoreactive B cells in peripheral blood were analysed by flow cytometry. Levels of BAFF were analysed by ELISA., Results: The relative frequency of total B cells, transitional, naïve and switched memory B cells was similar between pSS patients and controls. In patients with pSS, we observed a reduction in the frequency of unswitched memory B cells, an increased frequency of atypical memory B cells and an expansion of PD1 hi CXCR5 - T peripheral helper cells. Levels of BAFF were higher in patients with pSS compared with controls and correlated with serum levels of total IgG and titres of anti-Ro antibodies. The frequency of autoreactive B cells in the transitional, unswitched memory and plasmablast compartment was significantly higher in pSS patients than in controls., Conclusions: Our results point to a hyperactivation of B cells in pSS. Current therapies do not seem to affect B cell abnormalities, suggesting that novel therapies targeting specifically B cell hyperactivation need to be implemented for paediatric patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atraumatic limping is a frequent cause of consultation in Pediatric Emergency Departments (PED) and often represents a challenge for pediatricians for its variability in etiology ranging from benign causes to potential crippling conditions. The aims of this research are to illustrate the clinical features of acute limping children (LC) and to identify the possible red flags that could help to make a diagnosis of severe pathologies., Methods: We carried out a retrospective study about non-traumatic limping children referred to the PED of Bambino Gesù Children's Hospital over a 2-year period. We divided the cohort into three groups based on the patient's age: toddlers, children and adolescents. We considered crippling conditions: oncologic etiologies, bone or neurological infections, epiphysiolysis, Perthes disease, Guillain Barrè syndrome and non-accidental injuries., Results: We analyzed 485 patients. At clinical evaluation, 19.5% of the patients presented at least one sign and/or symptom of red flags. Crippling conditions (6.2% of the total population) showed red flags in 36.7%. Transient synovitis of the hip was the most frequent diagnosis. We found crippling conditions in 30 patients, mostly represented by toddlers., Conclusions: Our data suggest that toddlers and patients presenting red flags should be evaluated with particular suspicion because they have an increased risk of underlying severe conditions.

Background: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy., Methods: A single-center study was conducted at CF Unit of Bambino Gesù Children's Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic IV treatment for 14 days. MBW and spirometry were evaluated within 72 h of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated., Results: Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average reduction of -6,99%; 37/57 patients denoted an improvement, 20/57 are stable or worsened in LCI2.5 values and 4/57 (7.02%) had a significant deterioration (> 15%) at end of treatment. On the contrary a significative elevation of FEV1 and FVC were found, respectively of + 7,30% and of + 5,46%. A positive good correlection among LCI 2.5 and Scond (rho = + 0,615, p = 0.000) and LCI 2.5 and Sacin (rho = + 0,649, p = 0.000) and a negative strong correlation between FEV1 and LCI 2.5 were found in post treatment period. A similar modification of LCI 2.5 and FEV1 was noticed in both adult and pediatric population., Conclusions: LCI may have a role in the routine clinical care of both adult and pediatric CF patients as a good tool to assess response to IV antibiotic end-therapy in the same way as FEV1., (© 2024. The Author(s).)

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B., (© 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Background: Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients., Methods: We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV1 <40%), group 2 (FEV1 40-70%), group 3 (FEV1 >70%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods., Results: Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight ( p = 0.018) and BMI ( p = 0.030) among patients with moderate respiratory function compared to patients with compromised respiratory function. During lockdown, patients reported less physical activity, no variation in food amount and composition, more adherence to therapy (43%) and more consistent daily respiratory physiotherapy (47.6%)., Conclusions: Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity.

Peripheral neuropathy is a well described complication in children with cancer. Oncologists are generally well aware of the toxicity of the main agents, but fear the side effects of new drugs. As chemotherapeutic agents have been correlated with the activation of the immune system such as in Chemotherapy Induced Peripheral Neuropathy (CIPN), an abnormal response can lead to Autoimmune Peripheral Neuropathy (APN). Although less frequent but more severe, Radiation Induced Peripheral Neuropathy may be related to irreversible peripheral nervous system (PNS). Pediatric cancer patients also have a higher risk of entering a Pediatric Intensive Care Unit for complications related to therapy and disease. Injury to peripheral nerves is cumulative, and frequently, the additional stress of a malignancy and its therapy can unmask a subclinical neuropathy. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication along with patient factors, namely age and inherited susceptibilities. The recent identification of individual genetic variations has advanced the understanding of physiopathological mechanisms and may direct future treatment approaches. More research is needed on pharmacological agents for the prevention or treatment of the condition as well as rehabilitation interventions, in order to allow for the simultaneous delivery of optimal cancer therapy and the mitigation of toxicity associated with pain and functional impairment. The aim of this paper is to review literature data regarding PNS complications in non-primary pediatric cancer.

Background: Late-presenting congenital diaphragmatic hernia (L-CDH) diagnosis is a challenge for its clinical various presentation. In literature radiologic misdiagnosis is up to 62%. The aim of this study is analyze clinical findings about our cases series in a particular setting of Pediatric Emergency Department (PED) and review of literature., Methods: We retrospectively analyzed the medical records of children older than 1 month, operated for L-CDH from November 2009 to December 2019 presented to PED, with a total of 20 children (5 Morgagni and 15 Bochdaleck)., Results: The median age at diagnosis was 1,48 years. 50% patients had a history of previouses symtptoms with a mean duration of 243,75 days. In 30 % of cases associated anomalies were presented, mainly cardiovascular. 25% of patients had undergone to chest X-ray in past history with misdiagnosis of pneumonia, microganulia and broncovascular thickening. Misdiagnosis are manly among left sided Bochdaleck hernia. Respiratory distress alone or associated with vomiting is commonest acute symptom refered to PED. Respiratory symptoms were more common in younger children, while gastrointestinal ones in older children (not statistically differences p=0,8769). Post-operative recurrence were frequent only in cases of right sided CDH and comparing with left ones, there is a difference statistically significant (p=0.0476)., Conclusions: L-CDH should be suspected in cases of unexplained acute respiratory distress and vomiting, particulary when children are affected to associate cardiovascular malformation. In cases of patients with long previouses symptoms and various accesses to PED is important to emphasize history of respiratory distress, dysphagia and failure to thrive and should be considered a chest X-ray.

Objectives: Acute strabismus (AS) is the most common ocular motility disorder in children. In the emergency setting evaluation, the primary concern is to exclude a potentially dangerous underlying condition, requiring immediate intervention. Our first aim was to describe the epidemiology, clinical features, and underlying causes of AS in a cohort of children presenting to the emergency department (ED). Our second aim was to identify clinical features associated with a significant risk of underlying neurological emergencies (NEs)., Design and Setting: Clinical records of all patients under 18 years presenting for AS to the ED of the Bambino Gesù Children's Hospital over a 10-year period were retrospectively reviewed. A logistic regression model was applied to detect predictive variables associated with a higher risk of NEs., Results: 208 patients (M:F = 1.19) were identified (0.35 cases per 1000 admission). Commonly associated symptoms included diplopia (18.3%), headache (23.1%), nausea or vomit (8.6%). Other ocular or neurological abnormalities were associated in 47.6% of patients. NEs accounted for 24.03% of all cases, mostly represented by brain tumours (8.65%). Ptosis, optic disk blurring, vomit, gait abnormalities and consciousness disorders were found to confer a significantly greater risk of an underlying NE., Conclusions: Potentially severe neurological conditions may affect almost one in four children presenting to the ED for AS. Brain malignancies are the most common dangerous cause. Presence of ptosis, papilledema, vomit, gait disorders, consciousness impairment, pupillary defects and multiple cranial nerves involvement should be considered as red flags., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. No financial or non financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Headache is the world's seventh most significant cause of disability-adjusted-life in people aged between 10 and 14 years. Therapeutic management is based on pharmacological approaches and lifestyle recommendations. Many studies show associations between each migraine-promoting lifestyle, behavioral triggers, frequency, and intensity of headaches. Nevertheless, the overall aspects of this topic lack any definitive evidence. Educational programs advise that pediatric patients who suffer from migraines follow a correct lifestyle and that this is of the utmost importance in childhood, as it will improve quality of life and assist adult patients in avoiding headache chronicity, increasing general well-being. These data are important due to the scarcity of scientific evidence on drug therapy for prophylaxis during the developmental age. The "lifestyle recommendations" described in the literature include a perfect balance between regular sleep and meal, adequate hydration, limited consumption of caffeine, tobacco, and alcohol, regular physical activity to avoid being overweight as well as any other elements causing stress. The ketogenic diet is a possible new therapeutic strategy for the control of headache in adults, however, the possible role of dietary factors requires more specific studies among children and adolescents. Educational programs advise that the improvement of lifestyle as a central element in the management of pediatric headache will be of particular importance in the future to improve the quality of life of these patients and reduce the severity of cephalalgic episodes and increase their well-being in adulthood. The present review highlights how changes in different aspects of daily life may determine significant improvements in the management of headaches in people of developmental age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Raucci, Boni, Evangelisti, Della Vecchia, Velardi, Ursitti, Terrin, Di Nardo, Reale, Villani and Parisi.)