Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies.

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.

Paediatric and adult bronchiectasis: Specific management with coexisting asthma, COPD, rheumatological disease and inflammatory bowel disease.

Bronchiectasis, conventionally defined as irreversible dilatation of the bronchial tree, is generally suspected on a clinical basis and confirmed by means of chest high-resolution computed tomography. Clinical manifestations, including chronic productive cough and endobronchial suppuration with persistent chest infection and inflammation, may deeply affect quality of life, both in children/adolescents and adults. Despite many cases being idiopathic or post-infectious, a number of specific aetiologies have been traditionally associated with bronchiectasis, such as cystic fibrosis (CF), primary ciliary dyskinesia or immunodeficiencies. Nevertheless, bronchiectasis may also develop in patients with bronchial asthma; chronic obstructive pulmonary disease; and, less commonly, rheumatological disorders and inflammatory bowel diseases. Available literature on the development of bronchiectasis in these conditions and on its management is limited, particularly in children. However, bronchiectasis may complicate the clinical course of the underlying condition at any age, and appropriate management requires an integration of multiple skills in a team of complementary experts to provide the most appropriate care to affected children and adolescents. The present review aims at summarizing the current knowledge and available evidence on the management of bronchiectasis in the other conditions mentioned and focuses on the new therapeutic strategies that are emerging as promising tools for improving patients' quality of life.

Do Children Just Grow Out of Irritable Bowel Syndrome?

OBJECTIVE: Few data exist on natural history of irritable bowel syndrome (IBS) in children; therefore we investigated symptoms evolution over time in a cohort of children with IBS. STUDY DESIGN: In this observational, single-center study, we prospectively enrolled newly diagnosed children with IBS and reassessed them after 24 months. At both time points, patients completed a symptoms questionnaire, and a score of stool consistency was obtained. The therapeutic strategy adopted was also recorded. RESULTS: Eighty-three children (age 11 years, range, 4-16.6 years; 53 males) completed the study. Forty-seven (56.6%) patients received no medical treatment, whereas polyethylene glycol, probiotics, and trimebutine were prescribed to 9 (10.8%), 24 (28.9%), and 3 (3.6%) subjects, respectively. Twenty-four months after diagnosis, 48 children (57.8%) reported resolution of symptoms (P <.001), without differences between sexes (P = .35) or among IBS subtypes (P = .49). Of these, 30 (62.5%) had been only reassured and 18 (37.5%) had been prescribed medical treatment (P = .26). Despite not being statistically significant, symptoms resolution was more common in patients receiving no medical treatment than in those receiving probiotics (63.8% vs 41.6%, P = .08). Among patients with constipation-IBS, no difference was found in symptoms resolution between patients receiving polyethylene glycol and those receiving no medical treatment (67% and 40%, respectively, P = 1). CONCLUSIONS: Children with IBS are likely to show spontaneous symptoms resolution over a 24-month follow-up, regardless of sex, age, impact of symptoms on daily activities, and IBS subtypes.

A Mixture of 3 Bifidobacteria Decreases Abdominal Pain and Improves the Quality of Life in Children With Irritable Bowel Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

GOALS: We assessed the efficacy of a probiotic mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 in improving abdominal pain (AP) and quality of life (QoL) in children with irritable bowel syndrome (IBS) and functional dyspepsia (FD). BACKGROUND: AP-associated functional gastrointestinal disorders, particularly IBS and FD, are common in pediatrics, and no well-established treatment is currently available. Although probiotics have shown promising results in adults, data in children are heterogeneous. STUDY: Forty-eight children with IBS (median age, 11.2 y; range, 8 to 17.9 y) and 25 with FD (age, 11.6 y; range, 8 to 16.6 y) were randomized to receive either a mixture of 3 Bifidobacteria or a placebo for 6 weeks. After a 2-week "washout" period, each patient was switched to the other group and followed up for further 6 weeks. At baseline and follow-up, patients completed a symptom diary and a QoL questionnaire. AP resolution represented the primary outcome parameter. RESULTS: In IBS, but not in FD, Bifidobacteria determined a complete resolution of AP in a significantly higher proportion of children, when compared with placebo (P=0.006), and significantly improved AP frequency (P=0.02). The proportion of IBS children with an improvement in QoL was significantly higher after probiotics than after placebo (48% vs. 17%, P=0.001), but this finding was not confirmed in FD. CONCLUSIONS: In children with IBS a mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 is associated with improvement in AP and QoL. These findings were not confirmed in FD subjects. Trial identifier: NCT02566876 (http://www.clinicaltrial.gov).

European Society for Pediatric Gastroenterology Hepatology and Nutrition's Educational Offer and the Training Syllabus.

The basic knowledge necessary for a European pediatric gastroenterologist/hepatologist/nutritionist is set-out in the training syllabus (TS) of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). We retrospectively compared the topics covered in ESPGHAN's training events between 2013 and 2016 with the basic knowledge TS items. Thirty-six initiatives including e-learning were identified. Twelve (33%) courses focused on gastroenterology, 9 (25%) on hepatology, and 10 (28%) on nutrition. Five (14%) courses covered >1 field and were classified "General." The initiatives covered 12 of 57 (21%) TS items; 31 of 57 items (54%) were partially covered; and 14 of 57 (25%) not covered. Five of 9 e-learning courses covered gastroenterology topics, whereas none covered hepatology topics. ESPGHAN's 3-year educational offer partially met the training needs listed in the TS. A coordinated educational program covering all TS items would harmonize training within Europe and would provide trainees with a professional portfolio for employment purposes.

Right Ventricular Structure and Function in Idiopathic Pulmonary Fibrosis with or without Pulmonary Hypertension.

AIMS: To elucidate right ventricular (RV) function in patients with idiopathic pulmonary fibrosis (IPF) with and without pulmonary hypertension (PH) and its relation to other features of the disease. METHODS AND RESULTS: Clinical evaluation, standard Doppler echo, Doppler myocardial imaging (DMI), and 2D strain echocardiography (STE) of RV septal and lateral walls were performed in 52 IPF patients (66.5 ± 8.5 years; 27 males) and in 45 age- and sex-comparable controls using a commercial US system (MyLab Alpha, Esaote). Pulmonary artery mean pressure (mPAP) was estimated by standard echo Doppler. RV global longitudinal strain (RV GLS) was calculated by averaging RV local strains. The IPF patients were divided into 2 groups by noninvasive assessment of PH: no PH (mPAP<25 mmHg; 36 pts) and PH (mPAP ≥25 mmHg; 16 pts). Left ventricular diameters and ejection fraction were comparable between controls and IPF, while GLS was impaired in IPF (P < 0.01). RV end-diastolic diameters, wall thickness andmPAP were increased in IPF patients with PH. In addition, pulsed DMI detected in PH IPF impaired myocardial RV early diastolic (Em) peak velocity. Also peak systolic RV strain was reduced in basal and middle RV lateral free walls in IPF, as well as RV GLS (P < 0.0001). The impairment in RV wall strain was more evident when comparing controls with the no PH group than comparing the no PH group with the PH group. By multivariate analysis, independent association of RV strain with both six-minute walking test distance (P < 0.001), mPAP (P < 0.0001), as well as with forced vital capacity (FVC) % (P < 0.005) in IPF patients were observed. CONCLUSIONS: Impaired RV diastolic and systolic myocardial function were present even in IPF patients without PH, which indicates an early impact on RV function and structure in patients with IPF.

Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33.

BACKGROUND: The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored. OBJECTIVE: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. METHODS: Eighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model. RESULTS: Children with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13(+) innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13(+) ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2(-/-) mice lacking a functional receptor for IL-33. CONCLUSION: Pediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.

Mepolizumab in Severe Pediatric Asthma: Certainties and Doubts through a Single-Center Experience and Review of the Literature.

BACKGROUND: Although, in most children with asthma, good symptom control is achieved with a low to moderate dose of inhaled corticosteroids, a small group of patients still experiences frequent symptoms, and even severe exacerbations, impairment of lung function, and reduced quality of life. Some of these subjects with severe asthma require biologic drugs as add-on therapy. In the past decade, numerous monoclonal antibodies have been approved for children or adolescents with severe asthma, in addition to their increasing use in adult asthma. However, the available evidence on how to select the most appropriate biologic based on a single patient's clinical, functional, and laboratory characteristics is still scant, and is insufficient to guide clinicians in the decision-making process of a personalized treatment. MATERIALS AND METHODS: We report a case series of four patients with severe eosinophilic asthma treated with mepolizumab, an anti-interleukin-5 monoclonal antibody, and review the existing literature on this treatment in children and adolescents. RESULTS: Our patients, all with blood eosinophilia and elevated fractional exhaled nitric oxide levels, developed poor symptom control despite prolonged treatment with high-dose inhaled corticosteroids plus a second controller, addressing the addition of a biologic drug. In all of them, a 12-month treatment with subcutaneous mepolizumab showed a reduction in the blood eosinophil count and in asthma exacerbations, as well as an improvement on the Asthma Control Test. The results of the literature search focused on the strengths and limitations of the pediatric use of mepolizumab and highlighted the areas worthy of further research. CONCLUSIONS: Mepolizumab has proven effective in improving symptom control in pediatric patients with severe asthma. Additional well-powered clinical trials will be helpful in developing evidence-based guidelines regarding biologic drugs in the pediatric population.

Changes of intracardiac flow dynamics measured by HyperDoppler in patients with aortic stenosis.

Aims: Assessment of intracardiac flow dynamics has recently acquired significance due to the development of new measurement methods based on echocardiography. Recent studies have demonstrated that cardiac abnormalities are associated with changes in intracardiac vortical flows. Yet, no previous study assessed the impact of aortic stenosis (AS) on intracardiac vortices. This study aims to explore the clinical potential of additional information provided by quantifying intracardiac flow dynamics in patients with AS. Methods and results: One hundred and twenty patients with severe AS, sixty patients with concentric ventricular remodelling (VR), and hundred controls (CTRL) were prospectively included and underwent non-invasive evaluation of intracardiac flow dynamics. In addition to standard echocardiography, fluid dynamics were assessed by means of HyperDoppler. Vortex depth (P < 0.001), vortex length (P = 0.003), vortex intensity (P < 0.001), and vortex area (P = 0.049) were significantly increased in AS compared with CTRL. In addition, mean energy dissipation was significantly higher in AS compared with CTRL (P < 0.001) and VR (P = 0.002). At receiver operating characteristic analysis, vortex depth showed the best discrimination capacity for AS (P < 0.001). Conclusion: Changes in fluid dynamics-based HyperDoppler indices can be reliably assessed in patients with AS. Significant changes in vortex depth and intensity can selectively differentiate AS from both concentric remodelling and healthy CTRLs, suggesting that the assessment of intracardiac flow dynamics may provide complementary information to standard echocardiography to better characterize patients' subsets.

Non invasive assessment of lung disease in ataxia telangiectasia by high-field magnetic resonance imaging.

PURPOSE: A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT. METHODS: Fifteen AT patients (age, 11.3 years; range, 6-31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score. RESULTS: Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p = 0.02). Total or specific MRI scores were not associated with patients' age. Of all scores, only mucous plugging subscore appeared significantly related to FEV1 (r = 0.7, p = 0.04) and FEF25-75% (r = 0.9, p = 0.001). MRI scores from patients with positive (n = 5) or negative (n = 10) sputum culture were not significantly different. CONCLUSIONS: MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.

Flow Dynamic Pattern in Liver and Renal Transplantation under Exercise Prescription Program.

BACKGROUND: Cardiovascular diseases in the context of renal and liver transplants remain the leading cause of morbidity and mortality. Physical exercise at a moderate intensity is allowed to contrast the risk profile. Echocardiographic evaluation is essential to stratifying potential cardiotoxicity by the standard and, more recently, the deformation and dynamic study of the intracardiac vortex. This study aims to investigate the vortex echo parameters of solid-organ-transplanted subjects who are physically active compared to a control group of healthy subjects. METHODS: A group of 33 transplanted subjects (16 kidneys and 17 livers) was studied via a transthoracic echocardiography exam, comprehending the myocardial deformation parameters of global longitudinal strain (GLS), twisting of the left ventricle (LV) chamber, and HyperDoppler image acquisition. RESULTS: The subjects enrolled in this study were 50 in total: there were 33 transplanted and 17 healthy subjects. The transplanted subjects presented higher values of interventricular septum in diastole (IVSd p = 0.001), posterior wall diastolic (PWd p = 0.05), and left ventricle mass index (LVMI p = 0.029); ejection fraction (EF) was found to be higher in athletes (p < 0.001). Transplanted subjects presented mild diastolic dysfunction, emerging only from septal E values (p = 0.001). The 4DStrain (p = 0.018) and GLS2c (p = 0.017) were significantly better in the athletes. All of the geometrical and energetical vortex data were in the normal range and no significant differences were found. An interesting positive correlation was evident for the diastolic parameter, particularly the E/A ratio (p = 0.023) and E' septal value (p = 0.049), along with the vorticity fluctuation. This behavior was present for all subjects, particularly those that were transplanted (p = 0.005). CONCLUSIONS: In the vortex investigation, especially in cases of normal EF, the positive correlation of some diastolic parameters with the flow dynamic patterns corroborates this hypothesis. The HyperDoppler analysis could be helpful to detecting potential damage earlier in the diastolic time before a systolic deficiency.

Incomplete Kawasaki Disease with Peripheral Facial Nerve Palsy and Lung Nodules: A Case Report and Literature Review.

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9-1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment.

Magnetic resonance imaging is an accurate and reliable method to evaluate non-cystic fibrosis paediatric lung disease.

BACKGROUND AND OBJECTIVE: Chest MRI is increasingly used to assess pulmonary diseases, but its utility compared with high-resolution computed tomography (HRCT) has never been evaluated in children using specific performance outcomes. The aim of this study was to assess the accuracy and reliability of MRI compared with HRCT in children with non-cystic fibrosis (CF) chronic lung disease. METHODS: Fifty subjects aged 5.9-20 years, with primary ciliary dyskinesia (n = 17), primary immunodeficiency (n = 17) or recurrent pneumonia (n = 16), underwent chest HRCT and MRI. The prevalence of lung abnormalities on HRCT was evaluated, and sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI versus HRCT were calculated. MRI and HRCT scans were also assessed using a modified Helbich score. RESULTS: Bronchiectasis, mucous plugging, peribronchial wall thickening, consolidation, bullae, abscesses and emphysema were detected by HRCT in 72, 68, 66, 60, 10, 8 and 8% of subjects, respectively. Sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI were good or excellent for most of the changes that were assessed. Median total Helbich scores for HRCT and MRI were 10 (range 0-20) and 10 (range 0-18), respectively. There was good-to-excellent agreement between the two techniques for all scores (r ≥ 0.8). A Bland-Altman plot confirmed this agreement between total scores (bias value: 0.2 ± 1.18; 95% limits of agreement of mean difference: -2.12-2.52). CONCLUSIONS: Chest MRI was equivalent to HRCT to determine the extent of lung disease in children with non-CF lung disease. The findings support the use of chest MRI as an alternative to HRCT in diagnostic pathways for paediatric chronic lung disorders.

Liver and Pancreatic Involvement in Children with Multisystem Inflammatory Syndrome Related to SARS-CoV-2: A Monocentric Study.

Liver and pancreatic involvement in children with Multisystem Inflammatory Syndrome related to SARS-CoV-2 (MIS-C) has been poorly investigated so far. We reviewed a cohort of MIS-C patients to analyze the prevalence of acute liver injury (ALI) and pancreatic injury and their correlation with clinical outcomes. Demographic, clinical, laboratory and imaging features of children with MIS-C at admission and during hospital stay were prospectively collected. Fifty-five patients (mean age 6.5 ± 3.7 years) were included. At admission, 16 patients showed ALI and 5 had increased total serum lipase. During observation, 10 more patients developed ALI and 19 more subjects presented raised pancreatic enzymes. In comparison to those with normal ALT, subjects with ALI were significantly older (p = 0.0004), whereas pancreatic involvement was associated to a longer duration of hospital stay compared with patients with normal pancreatic enzymes (p = 0.004). Time between hospital admission and onset of ALI was shorter compared to the onset of raised pancreatic enzymes (3.2 ± 3.9 versus 5.3 ± 2.7 days, respectively; p = 0.035). Abdominal ultrasound showed liver steatosis in 3/26 (12%) and hepatomegaly in 6/26 (16%) patients with ALI; 2 patients presented enlarged pancreas. Although liver and pancreatic involvement is commonly observed in MIS-C patients, it is mild in most cases with a complete recovery.