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BackgroundThe use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important.MethodsThis is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation.ResultsIn the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. “Symptoms, signs and Ill-defined conditions,” “Injury and poisoning” and “Diseases of the Respiratory System” accounted for 74% of the reduction. A different pattern was instead seen for “Mental Disorders,” which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12–0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13–1.33), with the sharpest decline (−94%) and rise (+36%) observed in the “Diseases of the Respiratory System” category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM.ConclusionNPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Background: Pediatric dermatology represents one of the most underserved subspecialties in pediatrics. Artificial intelligence (AI) and telemedicine have become considerable in dermatology, reaching diagnostic accuracy comparable to or exceeding that of in-person visits. This work aims to review the current state of telemedicine and AI in pediatric dermatology, suggesting potential ways to address existing issues and challenges. Methods: We conducted a literature review including only articles published in the last 15 years. A total of 458 studies were identified, of which only 76 were included. Results: Most of the studies on telemedicine evaluate accuracy focused on concordance, which ranges from 70% to 89% for the most common pediatric skin diseases. Telemedicine showed the potential to manage chronic dermatological conditions in children, as well as decrease waiting times, and represents the chance for unprivileged populations to overcome barriers limiting access to medical care. The main limitations of telemedicine consist of the language barrier and the need for adequate technologies and acceptable image-quality video, which can be overcome by AI. AI-driven apps and platforms can facilitate remote consultations between pediatric dermatologists and patients or their caregivers. However, the integration of AI into clinical practice faces some challenges ranging from technical to ethical and regulatory. It is crucial to ensure that the development, deployment, and utilization of AI systems conform to the seven fundamental requirements for trustworthy AI. Conclusion: This study supplies a detailed discussion of open challenges with a particular focus on equity and ethical considerations and defining possible concrete directions.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs.MethodsThis is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends.ResultsOverall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for “Respiratory Diseases,” whereas the “Mental Disorders” category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08–0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30–0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98–1.69).ConclusionOur findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort.

Background/Objectives: Levothyroxine (L-T4) is available for use in congenital hypothyroidism (CH) in three formulations: tablets, drops, and oral solution. This study aims to compare the efficacy and safety of all three L-T4 formulations. Methods: We enrolled 63 children born between January 2019 and April 2023 in the Emilia-Romagna Region (Italy) and diagnosed with CH by newborn screening. They were divided according to the L-T4 formulation used: drops (Group D), oral solution (Group S), and tablets (Group T). Clinical and laboratory data were collected up to 3 years after the start of replacement therapy. Results: Serum-free thyroxine (sFT4) and thyroid stimulating hormone (sTSH) normalization occurred within the first month of treatment in most patients of all groups. No negative effects on growth and cognitive development were observed. At 7–15 days we found higher median sTSH levels (p = 0.031) and a greater percentage of patients with sTSH > 5 µU/mL (p = 0.011) in Group S than in Group T, but comparable sFT4 levels. At 12 months, a greater percentage of patients of Group D showed sFT4 values below the normal range than Group S (p = 0.011) and Group T (p = 0.038); Conclusions: Overall, our study reported an equal efficacy of the L-T4 oral solution compared to drops and tablets in CH treatment. A larger series of patients and a long-term follow-up are needed.

(1) Background: The impact of inflammation on voriconazole exposure in oncohematological pediatric patients represents a debated issue. We aimed to investigate the impact of serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels on voriconazole exposure in oncohematological pediatric patients requiring allogeneic hematopoietic stem cell transplantation (HCT). (2) Methods: Pediatric patients undergoing allogeneic HCT and receiving therapeutic drug monitoring (TDM)-guided voriconazole as primary antifungal prophylaxis between January 2021 and December 2023 were included. The ratio between concentration and dose (C/D) of voriconazole was used as a surrogate marker of total clearance. A receiving operating characteristic curve analysis was performed by using CRP, PCT, or IL-6 values as the test variable and voriconazole C/D ratio > 0.188 or >0.375 (corresponding to a trough concentration value [Cmin] of 3 mg/L normalized to the maintenance dose of 16 mg/kg/day in patients of age < 12 years and of 8 mg/kg/day in those ≥12 years, respectively) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. (3) Results: Overall, 39 patients were included. The median (IQR) voriconazole Cmin was 1.7 (0.7–3.0) mg/L. A CRP value > 8.49 mg/dL (AUC = 0.72; 95%CI 0.68–0.76; p < 0.0001), a PCT value > 2.6 ng/mL (AUC = 0.71; 95%CI 0.63–0.77; p < 0.0001), and an IL-6 value > 27.9 pg/mL (AUC = 0.80; 95%CI 0.71–0.88; p < 0.0001) were significantly associated with voriconazole overexposure. Consistent results were found in patients aged

Kawasaki disease (KD) is an acute vasculitis that mainly affects children under 5 years of age, leading to coronary artery alterations (CAAs) in 25% of untreated patients. Macrophage activation syndrome (MAS) is a secondary hemophagocytic lymphohistiocytosis (HLH) that can complicate the acute, subacute, and chronic phases of KD. We retrospectively reviewed three cases of children affected by KD complicated with MAS hospitalized in two pediatric units in Emilia Romagna, a northern region of Italy. Case 1: a previously healthy 23-month-old female with full clinical criteria of KD and a hemorrhagic rash due to MAS during the acute phase of the illness. This patient responded promptly to a high dose of intravenous immune globulin (IVIG) and three pulses of high doses of methylprednisolone (MPD) with improvement in clinical signs and laboratory tests without the development of CAA at any phase of illness. Case 2: a previously healthy 10-month-old female with incomplete KD with persistent fever and maculopapular rash. This patient did not respond to IVIG and developed MAS during the subacute phase, characterized by persistent fever, hypertransaminasemia, hyperferritinemia, and hypofibrinogenemia after two high doses of IVIG and boluses of MPD. The patient responded to the addition of IL-1 blocker and anakinra and did not present CAA alterations during any phase of the illness. Case 3: a previously healthy 26-month-old male with incomplete KD with fever, maculopapular rash, cheilitis, and hyperemic conjunctivitis. This patient developed gallbladder hydrops and CAA in the acute phase and did not respond to two high doses of IVIG and a high dose of MPD. In the subacute phase, this patient was complicated with MAS and responded to intravenous anakinra. During the subacute phase, the patient developed transient aneurysms that regressed during the chronic phase. These cases reiterate that prompt diagnosis and aggressive immunomodulatory treatment can limit the most severe complications of MAS complicating KD. High doses of IVIG and MPD may result in a favorable outcome or more aggressive adjunctive treatment may be needed. Anakinra, cyclosporine, monoclonal antibodies, and plasmapheresis can be used as adjunctive treatment in the case of unresponsive MAS in KD. Notably, MAS, present during the subacute phase in cases 2 and 3, promptly responded to anakinra, an IL-1 blocker, without the use of cyclosporine. Our experience confirms that the IL-1 blocker can be considered an optimal choice after non-response to IVIG and MPD in KD complicating with MAS, avoiding over-treatment with cytotoxic drugs.

Abstract Measles virus (MV) and cytomegalovirus (CMV) may cause pediatric infection. We report the first described case of MV and CMV co-infection in an unvaccinated 13-mo-old girl, with a recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, occurred during coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic context, combined with patient’s complex clinical scenario, presenting symptoms as persistent fever, diarrhea, vomiting, maculopapular rash and edema, in addition to high level of inflammatory markers, led to a suspicion of multisystemic inflammatory syndrome in children (MIS-C). The final diagnosis and the successfully management of the case, discharged after resolution of symptoms, was achieved by a proper virological diagnosis and a close two-way cooperation between pediatricians and clinical microbiologists. The report mainly highlights that awareness about measles should be raised in unvaccinated patients with consistent symptoms, even in the COVID-19 era.

Abstract Febrile neutropenia (FN) represents one of the main complications of pediatric patients with oncological and hematological diseases. In these patients, it is crucial to identify bacterial infections. The aim of this study is to evaluate presepsin as an early biomarker of bacterial infections during FN. We compared patients with oncological and hematological diseases and a 2:1 age-matched healthy control group. In the FN group, we evaluated 4 biomarkers, namely, C reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL6) and presepsin at the onset of fever (T0) and 48 h after T0 (T1). In the control group, we only evaluated presepsin. We enrolled a total of 41 children with oncological and hematological diseases disease experiencing 50 FN episodes and 100 healthy patients in the control group. In patients with FN, we found that presepsin was significantly higher than in the control group (p

Children, adolescents, and young adult cancer survivors (CAYAs) constitute a growing population requiring a customized approach to mitigate the incidence of severe complications throughout their lifetimes. During cancer treatment, CAYAs cancer survivors undergo significant disruptions in their nutritional status, elevating the risks of mortality, morbidity, and cardiovascular events. The assessment of nutritional status during cancer treatment involves anthropometric and dietary evaluations, emphasizing the necessity for regular assessments and the timely identification of risk factors. Proactive nutritional interventions, addressing both undernutrition and overnutrition, should be tailored to specific age groups and incorporate a family-centered approach. Despite encouraging interventions, a notable evidence gap persists. The goal of this review is to comprehensively examine the existing evidence on potential nutritional interventions for CAYAs cancer survivors. We explore the evidence so far collected on the nutritional intervention strategies elaborated for CAYAs cancer survivors that should target both undernutrition and overnutrition, being age-specific and involving a family-based approach. Furthermore, we suggest harnessing artificial intelligence (AI) to anticipate and prevent malnutrition in CAYAs cancer survivors, contributing to the identification of novel risk factors and promoting proactive, personalized healthcare.

Abstract Background Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia. Methods An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn. Results The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management. Conclusions The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.

Abstract Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

IntroductionRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once.MethodsHere, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing.ResultsInterestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals.DiscussionMonitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.

Despite being rare, the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a serious, possibly fatal condition that may affect both adults and children who may be also burdened by delayed sequelae. It is an adverse drug reaction characterized by widespread skin involvement, fever, lymphadenopathy, visceral involvement, and laboratory abnormalities (eosinophilia, mononucleosis-like atypical lymphocytes). It is more frequently triggered by anticonvulsants, sulphonamides, or antibiotics, the latter being responsible for up to 30% of pediatric cases. The disease typically develops 2–8 weeks after exposure to the culprit medication, with fever and widespread skin eruption; mild viral prodromes are possible. Unfortunately, diagnosis is challenging due to the absence of a reliable test; however, a score by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) allows to classify suspect patients into no, possible, probable, or definite DRESS cases. Moreover, rapid-onset DRESS syndrome has been described in recent years. It affects children more often than adults and differs from the most common form because it appears ≤15 days vs. >15 days after starting the drug, it is usually triggered by antibiotics or iodinated contrast media rather than by anticonvulsants and has a higher presence of lymphadenopathy. Differential diagnosis between rapid-onset antibiotic-driven DRESS syndrome, viral exanthems, or other drug eruptions may be challenging, but it is mandatory to define it as early as possible to start adequate treatment and monitor possible complications. The present review reports the latest evidence about the diagnosis and treatment of pediatric DRESS syndrome.

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03–0.07), receiving respiratory support (OR 0.19, 95% CI 0.06–0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22–0.56) and developing complications (OR 0.27, 95% CI 0.14–0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.

During the SARS-CoV-2 pandemic, the pediatric emergency department (ED) of Bologna, Emilia-Romagna, Italy faced a reorganization to better deal with the new clinical needs. We herein describe the main changes in the organization and in the attendances to our pediatric ED. From the 1 March 2020 to the 31 January 2022, 796 children positive for SARS-CoV-2 presented to our pediatric ED, but only 26 required hospitalizations, of which only 9 for COVID-19 related reasons. During this period, we also registered a temporal correlation between multisystem inflammatory syndrome in children (MIS-C) admissions and the peaks of SARS-CoV-2 infection in the Italian population. Respiratory syncytial virus (RSV) remained during last year the viral infection with the highest hospitalization rate. The analysis and description of the changes in the activity of the pediatric ED during the SARS-CoV-2 pandemic may help to better understand the routinary activity and be prepared for any possible new challenge.

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard.

Abstract Kawasaki Disease (KD) is systemic vasculitis involving medium-sized vessels in children. The aim of our study is to determine if fecal calprotectin (FC) could be useful in predicting the development or persistence of coronary artery lesions (CALs) in KD. We conducted a prospective monocentric study including all consecutive diagnoses of. Clinical, laboratory, echocardiographic data were recorded during the acute and subacute phase, including FC. Correlations among laboratory values, FC, clinical manifestations, IVIG-responsiveness and CALs development were investigated. We enrolled 26 children (76.9% boys; median age 34.5 months). The combination of FC > 250 microg/g and z-score > 2 during the acute phase was associated with the persistence of CALs (p = 0.022). A z-score > 2 alone during the acute phase was not related to CALs during the subacute stage (p > 0.05). A neutrophil percentage > 70% and WBC > 15,000/mmc during the acute phase significantly correlated with the presence of CALs during the subacute phase (p = 0.008). C-reactive protein (CRP) > 13 mg/dL at KD onset was significantly associated with the presence of CALs during the acute (p = 0.017) and subacute phase (p = 0.001). The combination of FC > 250 microg/g and a z-score > 2 during the acute phase of KD may be used as a predictor of CALs persistence. It can be useful especially in children with an initial CRP

Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. Implications: In the light of the current imbalance between gammaglobulins’ demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.

Abstract Background The World Health Organization stated an average of 60 min of Moderate to Vigorous Physical Activity (MVPA) that children should accumulate every day. Nevertheless physical inactivity is growing and, due to restrictions imposed during pandemic, PA levels of children might be more negatively affected. The study aimed to analyse the impact of COVID-19 on the PA of an Italian sample of primary school children by comparing it before and during COVID-19 considering gender differences. Methods A pre-post analysis (October 2019–January 2021) was conducted using a randomized sample (N = 77) from the I-MOVE study settled in an Italian primary school. Both objective (Actigraph accelerometers) and self-reported (PAQ-c questionnaires) assessments of PA were performed. Changes were compared using T-Student and Chi-Square test. Gender differences were calculated using Anova. Results Weekly and daily minutes time spent in MVPA significantly decreased respectively by − 30.59 ± 120.87 and − 15.32 ± 16.21 from before to during pandemic while the weekly time spent in sedentary behaviour increased (+ 1196.01 ± 381.49). PAQ-c scores followed the same negative trend (− 0.87 ± 0.72). Boys seem to have suffered more than girls from the imposed restrictions. Conclusion These findings outline the need for strategies to promote PA and reduce sedentary behaviours in children to prevent COVID-19 restriction long-term effects.

Abstract 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.

Pericardial effusion is rare in pediatric patients and is characterized by a variable clinical presentation. Mild symptoms may be present despite severe effusion. We here report the case of a patient with massive pericardial effusion with mild clinical presentation. Our case points out the need not to exclude this diagnosis in patients with mild general impairment. This clinical suspicion can be lifesaving.

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) represents a potentially curative strategy for many oncological, hematological, metabolic, and immunological diseases in children. The continuous effort in ameliorating supportive care represents one of the cornerstones in the improvement of outcome in these patients. Nowadays, more than ever nutritional support can be considered a key feature. Oral feeding in the early post-transplant period is severely impaired because of mucositis due to conditioning regimen, characterized by, mainly by vomiting, anorexia, and diarrhea. Gastrointestinal acute graft-versus-host-disease (GvHD), infections and associated treatments, and other medications, such as opioids and calcineurin inhibitors, have also been correlated with decreased oral intake. The consequent reduction in caloric intake combined with the catabolic effect of therapies and transplantation-related complications with consequent extended immobilization, results in a rapid deterioration of nutritional status, which is associated with decreased overall survival and higher complication rates during treatment. Thus, nutritional support during the early post-transplantation period becomes an essential and challenging issue for allo-HSCT recipients. In this context, the role of nutrition in the modulation of the intestinal flora is also emerging as a key player in the pathophysiology of the main complications of HSCT. The pediatric setting is characterized by less evidence, considering the challenge of addressing nutritional needs in this specific population, and many questions are still unanswered. Thus, we perform a narrative review regarding all aspects of nutritional support in pediatric allo-HSCT recipients, addressing the assessment of nutritional status, the relationship between nutritional status and clinical outcomes and the evaluation of the nutritional support, ranging from specific diets to artificial feeding.

Abstract Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

IntroductionThe high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures.MethodsA global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management.ResultsNinety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision.ConclusionSeven key actions for improving RSV prevention and management in LMICs are proposed.

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy.MethodsWe retrospectively collected the clinical features and histological findings of three previously healthy children who underwent appendectomy for clinical suspicion of acute appendicitis but were later diagnosed with MIS-C.FindingsThe three children presented with prominent abdominal manifestations and fever leading to the suspicion of acute abdomen. Histological findings showed transmural and perivascular inflammation. Notably, CD68+ macrophages were predominant in the child with milder abdominal symptoms without cardiac injury, while CD3+ lymphocytes in the patient presented with more severe abdominal pain and cardiovascular involvement at admission.InterpretationGastrointestinal symptoms of children with MIS-C improve after proper immunomodulatory therapy, conversely showing inadequate response to surgical appendectomy. Histological findings revealed different inflammatory cell infiltration that primarily involved perivisceral fat and vessels, and subsequently mucosal tissue, in contrast to other forms of acute appendicitis. Our findings suggest that this kind of peri-appendicitis in MIS-C could represent a focal sign of systemic inflammation, with different histological patterns compared to other forms of acute appendicitis.

Background: Lower respiratory tract infections (LRTIs) and community-acquired pneumonia (CAP) are among the most frequent reasons for referrals to the pediatric emergency department (PED). The aim of this study is to describe the management of antibiotic prescription in febrile children with LRTI or CAP admitted to a third-level PED and to investigate the different variables that can guide physicians in this decision-making. Methods: This is an observational, retrospective, monocentric study including patients < 14 years old who were presented to the PED for a febrile LRTI or CAP during the first six months of the year 2017. Demographic and clinical data, PED examinations, recommended therapy, and discharge modality were considered. Two multivariate logistic regression analyses were performed on patients with complete profiles to investigate the impact of demographic, laboratory, and clinical variables on antibiotic prescription and hospital admission. Results: This study included 584 patients with LRTI (n = 368) or CAP (n = 216). One hundred and sixty-eight individuals (28.7%) were admitted to the hospital. Lower age, higher heart rate, and lower SpO2 were associated with an increased risk of hospitalization. Antibiotics were prescribed to 495 (84.8%) patients. According to the multivariate logistic regression, the diagnosis and duration of fever were substantially linked with antibiotic prescription. Conclusions: The present study reports real-life data about our PED experience. A high rate of antibiotic prescription was noted. In the future, it is necessary to improve antibiotic stewardship programs to increase clinical adherence to guidelines.

Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change.

Abstract Background Measures to contain the Covid-19 pandemic led to significant lifestyle changes for children and adolescents mainly related to the closure of schools and recreational activities, reduced social interaction, and increased family concerns. Methods A cross-sectional online survey of 78 questions investigating social determinants of health, mood changes, symptoms of anxiety, increase in sleep disorders and unusual repetitive movements was offered to parents living in Italy with children ≤18 years; including families of children with disabilities, autism spectrum disorders, chronic diseases, and specific learning disabilities. The survey was conducted on the Qualtrics platform 6 months after the beginning of the pandemic and distributed in hospitals and paediatricians’ waiting rooms as well as through social networks. The primary outcomes were the increase in sleep disorders among children and adolescents. Possible risk factors were investigated through multivariable regression. Results Six thousand two hundred ten volunteer parents responded to the questions concerning mood changes, sleep disorders and unusual repetitive movements, and were included in the present study. The majority were female (91.8%) and Italian (97.0%). 72.7% answered that their children had become more nervous, worried, or sad (80.2% in children with learning disabilities); 77.6% reported feelings of loneliness and 69.3% more difficulties in children falling asleep, 30.2% in staying asleep, and 18.7% an increase in nightmares and/or sleep terrors. Statistical analysis identified socioeconomic status, parent’s job loss, food insecurity, family attitude toward the pandemic, and children’s mood swing, feelings of loneliness, or missing outdoor activities, as major risk factors for sleep disorders. Conclusion The first Covid-19 lockdown impacted children’s and adolescents’ health through an increase in sleep disorders. In the following phases of the pandemic, this evidence may be useful to investigate and treat these disorders as well as make decisions about containment health policies concerning this age group.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Respiratory Syncytial Virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. The role of RSV load in disease severity is still debated. We present the interim results of a prospective monocentric study enrolling previously healthy infants hospitalized for RSV bronchiolitis, collecting nasopharyngeal aspirates every 48 h from admission to discharge, and evaluating RSV load dynamics in relation to clinical outcome measures of bronchiolitis severity, including: need, type and duration of oxygen therapy, length of hospitalization, and the bronchiolitis clinical score calculated at admission. The results showed that the highest viral replication occurs within the first 48 hours after admission, with a significant decrease at subsequent time points (p < 0.0001). Moreover, higher RSV-RNA values were associated with the need for oxygen therapy (p = 0.03), particularly high-flow nasal cannula type (p = 0.04), and longer duration of respiratory support (p = 0.04). Finally, higher RSV load values were correlated with lower white blood cells, especially lymphocyte counts and C-reactive protein levels (p = 0.03, p = 0.04, and p = 0.01, respectively), as well as with patients of a younger age (p = 0.02). These data suggest that RSV may actively contribute to the clinical severity of bronchiolitis, together with other potential non-viral factors.

Abstract A 6‐year‐old African boy with multi‐viral infection including parvovirus B19 and severe acute respiratory syndrome coronavirus 2 was admitted for persistent fever associated with respiratory distress and myocarditis complicated by cardiogenic shock needing ventilatory and inotropic support. Coronary aneurysms were also documented in the acute phase. Blood tests were suggestive of macrophage activation syndrome. He was treated with intravenous immunoglobulins, aspirin, diuretics, dexamethasone, hydroxychloroquine, and prophylactic low molecular weight heparin. Normalization of cardiac performance and coronary diameters was noticed within the first days. Cardiac magnetic resonance imaging, performed 20 days after the hospitalization, evidenced mild myocardial interstitial oedema with no focal necrosis, suggesting a mechanism of cardiac stunning related to cytokines storm rather than direct viral injury of cardiomyocytes.

Background: The thymus gland is a lymphoid organ normally located in the anterior mediastinum. Location abnormalities of the thymus, such as ectopic thymus or the superior herniation of a mediastinal thymus, could be responsible for the occurrence of cervical masses in pediatric patients, raising concerns among clinicians. The knowledge of these conditions is essential for a thorough differential diagnosis and for preventing unnecessary invasive procedures. Methods: Descriptive retrospective series of three patients with a cervical mass, that was later diagnosed as ectopic thymic tissue. Results: The thymus has a unique and distinctive ultrasound appearance that is the keystone to detecting thymic parenchyma in locations other than anterior mediastinum. In selected patients, an accurate ultrasound could be conclusive for the diagnosis, with no need for further and potentially risky procedures. Conclusions: This case series supports the use of ultrasound in both diagnosis and follow-up of thymus location abnormalities, advocating a minimal invasive and conservative approach.

Minor head trauma (MHT) is very frequent in children and post-traumatic headache (PTH) is one of its most common complications; however, its management is still a challenge. We aimed to assess the incidence and clinical characteristics of, and risk factors for, PTH among children referred to our pediatric emergency department (PED) for MHT. A total of 193 patients aged 3–14 years evaluated for MTH were enrolled and followed up for 6 months through phone calls and/or visits. PTH occurred in 25/193 patients (13%). PTH prevalence was significantly higher in school-aged (≥6 years) than in pre-school-aged children (21.6% vs. 4.9%, respectively, p < 0.009). Females were found to be more affected. The median time of onset was 4.6 days after MHT; resolution occurred in a median of 7 weeks. In 83.3% of patients, PTH subsided in

Bronchiolitis is the main cause of hospitalization in infants. Diagnosis is clinical, and treatment is based on hydration and oxygen therapy. Nevertheless, unnecessary diagnostic tests and pharmacological treatments are still very common. This retrospective study aimed to evaluate whether the setting of bronchiolitis care influences diagnostic and therapeutic choices. The management of 3201 infants, referred to our Italian Tertiary Care Center for bronchiolitis between 2010 and 2020, was analyzed by comparing children discharged from the pediatric emergency department (PEDd group) undergoing short-stay observation (SSO group) and hospitalization. Antibiotic use in PEDd, SSO, and ward was 59.3% vs. 51.6% vs. 49.7%, respectively (p < 0.001); inhaled salbutamol was mainly administered in PEDd and during SSO (76.1% and 82.2% vs. 38.3% in ward; p < 0.001); the use of corticosteroids was higher during SSO and hospitalization (59.6% and 49.1% vs. 39.0% in PEDd; p < 0.001); inhaled adrenaline was administered mostly in hospitalized infants (53.5% vs. 2.5% in SSO and 0.2% in PEDd; p < 0.001); chest X-ray use in PEDd, SSO, and ward was 30.3% vs. 49.0% vs. 70.5%, respectively (p < 0.001). In a multivariate analysis, undergoing SSO was found to be an independent risk factor for the use of systemic corticosteroid and salbutamol; being discharged at home was found to be a risk factor for antibiotic prescription; undergoing SSO and hospitalization resulted as independent risk factors for the use of CXR. Our study highlights that different pediatric acute care settings could influence the management of bronchiolitis. Factors influencing practice may include a high turnover of PED medical staff, personal reassurance, and parental pressure.

Introduction: Anaphylaxis is one of the most frequent and misdiagnosed emergencies in the pediatric emergency department (PED). We aimed to assess which factors play a major role for a correct diagnosis and an appropriate therapy. Methods: We reviewed the records of children discharged with a diagnosis of anaphylaxis or an allergic reaction over 11 years from 3 hospitals in the Bologna city area. Results: One hundred and sixteen cases matched the criteria (0.03% of the total admittances) and were divided according to the patients’ symptoms at arrival: active acute patients [AP], n = 50, or non-acute patients ([NAP], n = 66). At the patients’ discharge, anaphylaxis was diagnosed in 39 patients (33.6%). Some features seemed to favor a correct diagnosis: active symptoms at arrival (AP vs. NAP, p < 0.01), high-priority triage code (p < 0.01), and upper airway involvement (p < 0.01). Only 14 patients (12.1%), all in the AP group, received epinephrine, that was more likely administered to patients recognized to have anaphylaxis (p < 0.01) and with cardiovascular, respiratory, or persistent gastrointestinal symptoms (p < 0.02), as confirmed by logistic regression analysis. Conclusions: Anaphylaxis is still under-recognized and under-treated. Correct triage coding and a proper diagnosis seem to foster an appropriate treatment. Physicians often prefer third-line interventions. Specific training for nurses and physicians might improve the management of this disease.

High Flow Nasal Cannula (HFNC) is a noninvasive technique for respiratory support increasingly used in the pediatric wards for the management of respiratory failure. Few data are reported about the safety of HFNC. We describe the case of a 3-months-old infant admitted for acute bronchiolitis Respiratory Syncyctial Virus-related and treated with HFNC for severe respiratory distress. 12 hours after the beginning of HFNC a subcutaneous swelling of the neck, attributable to subcutaneous emphysema, became clinically evident. Radiological imaging showed pneumomediastinum with air leaking up to the neck. Patient was moved to PICU where he further worsened due to a mediastinal shift requiring drainage and mechanical ventilation. He was then progressively weaned from ventilation and was discharged from the hospital. Pneumomediastinum may occur during HFNC, particularly in moderate-severe cases of acute bronchiolitis. Patients undergoing HFNC should be strictly monitored in order to promptly recognize this complication and treat the child appropriately.

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings.Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, 48 h).Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases.Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios.

Abstract The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school’s closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school’s closure.

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00–0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00–0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02–0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease.Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020.Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5–9 years and lymphopenia were statistically related to ICU admission (p < 0.05).Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

The aim of this study was to understand the epidemiology, disease severity, and microbiology of bronchiolitis in Italy during the 2021–2022 cold season, outside of lockdowns. Before COVID-19, the usual bronchiolitis season in Italy would begin in November and end in April, peaking in February. We performed a prospective observational study in four referral pediatric centers located in different geographical areas in Italy (two in the north, one in the center and one in the south). From 1 July 2021 to 31 January 2022, we collected all new clinical diagnoses of bronchiolitis in children younger than two years of age recording demographic, clinical and microbiological data. A total of 657 children with a clinical diagnosis of bronchiolitis were enrolled; 56% children were admitted and 5.9% required PICU admission. The first cases were detected during the summer, peaking in November 2021 and declining into December 2021 with only a few cases detected in January 2022. RSV was the commonest etiological agent, while SARS-CoV-2 was rarely detected and only since the end of December 2021. Disease severity was similar in children with RSV vs. non-RSV bronchiolitis, and in those with a single infectious agent detected compared with children with co-infections. The 2021–2022 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons, but had a shorter duration. Importantly, the current bronchiolitis season was not more severe when data were compared with Italian published data, and SARS-CoV-2 was rarely a cause of bronchiolitis in children younger than 24 months of age.

In most children, coronavirus disease 2019 (COVID-19) is a mild or moderate disease. Moreover, in a relevant number of cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains totally asymptomatic. All these findings seem to suggest that otherwise healthy children with suspected COVID-19 might be managed in the community in most cases, thus avoiding hospital admission and closely related medical, social and economic problems, including overwhelming hospitals. Unfortunately, home management of children with suspected COVID-19 rarely occurs, and many children with suspected or laboratory-confirmed SARS-CoV-2 infection are frequently hospitalized irrespective of the severity of disease. To evaluate the role of community health houses (CHHs) in the management of children with COVID-19, 1,009 children with suspected SARS-CoV-2 infection were studied in Emilia-Romagna Region, Italy. Among them, 194 (19.2%) resulted positive for SARS-CoV-2. The majority (583, 58%) were tested at home by CHHs, while 426 (42%) were brought to the hospital for testing. The patients who were managed in the hospital had a significantly lower median age than those who were managed at home (2 vs. 12 years, p < 0.001). Exposure to SARS-CoV-2 cases within the family was significantly more frequent among those who were managed at home (82 vs. 46%, p < 0.05). The clinical findings were similar between the children who were managed at home and those who were managed in the hospital. Only one of the children managed at home (0.7%) required hospitalization; in comparison, 26 (48%) of those whose swab samples were taken at the hospital were hospitalized. Our research shows for the first time the importance of CHHs in the management of COVID-19 in children; because of the high frequency of mild to moderate cases, management by CHHs can reduce the care load in hospitals, providing enormous advantages on the familial, medical, social, and economic levels. These findings could be useful for suggesting a territorial rather than hospital-based strategy in pediatrics in the case of a new wave of the epidemic.

The Emilia Romagna (ER) region, Italy, in March 2020 has seen one of the largest and most serious clusters of COVID-19 in the world. In the period of 30 January to 31 May 2020, the number of paediatric emergency department presentations in Bologna, ER, decreased by 50% compared with the same period of 2019. Visits declined for every age group, with a decrease of 35%, 55% and 46% for the three age groups 0–2, 2–10 and 10–14 years, respectively. The admission rate increased from 5% to 13%. Fewer non-urgent attendances, alongside a decrease in seasonal infections due to the lockdown, appear to be the main reasons.

Abstract Background Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. Methods We enrolled children admitted to our hospital in 2016–2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient’s clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. Results Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen’s kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). Conclusions This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. Trial registration Identifier: NCT03280732. Registered 12 September 2017 (retrospectively registered).

Abstract Background Acute mastoiditis is the main suppurative complication of acute otitis media. Its incidence ranges from 1.2 to 4.2/100.000 children/year and a rise has been reported in the last years. There are controversial data regarding risk factors for mastoiditis and its complications. Aim of the study: to evaluate demographics and clinical characteristics of children with acute mastoiditis and to identify possible risk factors for complications. Methods We retrospectively reviewed medical charts of all the children aged 1 month-14 years admitted to our Paediatric Emergency Department from January 2002 to December 2016. Results One hundred forty-seven cases (97 males and 50 females) were included in the analysis, mean age was 4.8 ± 3.6 years and 28.2% of the patients were younger than 2 years. We found an increasing number of mastoiditis per year during the last 3 years of the study. Children younger than 2 years were less treated with antibiotics for acute otitis media or treated for a shorter period (p

Mycoplasma pneumoniae (MP) is one of the main causes of both upper and lower respiratory infections in school-aged children, accounting for up to 40% of community-acquired pneumonia. Younger children are also affected, and extrapulmonary manifestations have been recently reported in the pediatric population. We carried out a retrospective analysis of MP-positive patients admitted to the Pediatric Emergency Unit of S. Orsola Malpighi University Hospital in Bologna, the largest tertiary pediatric referral center in the Emilia–Romagna region, Northern Italy, between 2012 and 2020. We identified 145 patients with MP infection (82 males and 63 females), 27% of which were younger than 2 years; the median age was 5 years (interquartile range 1–9). The clinical presentation partially differed between age groups. School-aged children were more likely to have a chest X-ray-confirmed pneumonia (p = 0.013), while younger children required oxygen therapy more often (p = 0.048). Seventy-four children (51%) showed extrapulmonary manifestations, mainly gastrointestinal (30%) and dermatological (14%). Neurological symptoms were more frequent in children older than 6 years (p = 0.006). The rate of other extrapulmonary manifestations did not differ significantly between age groups. This study shows that MP infection is a frequent cause of pediatric hospitalization, including of children younger than 2 years. Clinicians should be aware of the variable clinical expressions of MP, including extrapulmonary manifestations, to achieve a correct diagnosis and determine appropriate treatment.