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Abstract Background Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection. Methods This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones. Results 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p

Background The COVID-19 pandemic had an important psychological impact on children and their families. This study aims to explore paediatric health services users’ perceptions of quality of care (QOC) and COVID-19-related fears, and their evolution over time in relation to COVID-19 pandemic.Methods In a multicentre cross-sectional study involving 11 public hospitals providing paediatric care across the Italian territory, we collected data from services users through a validated questionnaire. We analysed four indicators—(1) QOC perceived in relation to COVID-19; (2) overall QOC perceived; (3) fear of accessing health services due to COVID-19; (4) fear of contracting COVID-19 in hospital—and calculated Spearman’s correlation indexes (ρ) with the number of COVID-19 new cases over time. Subgroup analyses were conducted by macroregions and single facility.Results Data from 956 services users were analysed. QOC indicators were stable over time at values close to the maximum (range 77–100 and median 100 for COVID-19 QOC, range 74–98 and median 80 for overall QOC), and no correlations were found with the COVID-19 new cases (ρ=−0.073 and −0.016, respectively). Fear of accessing care and fear of contracting the infection varied over time in between 0%–52% and 0%–53%, respectively, but did not correlate directly with number of COVID-19 new cases (ρ=0.101, 0.107 and 0.233, 0.046, respectively). At subgroup analyses, significantly higher frequencies of fear (p values

Background: Urinary tract infections (UTIs) are the most common bacterial infections in children. The high variability in pathogen susceptibility rates leads to the lack of clear guidelines for empiric and targeted therapies. In this view, local microbiological surveillance and locally adapted stewardship interventions need to be implemented. Objective: The study aims to describe the results of a pediatric antimicrobial stewardship program on antibiotic prescriptions for UTIs over 8 years in a pediatric general ward of a tertiary center. Design: This quasi-experimental study was conducted between 2015 and 2022, with two different implementations, one in 2018 and one in 2021. Methods: Demographic, clinical, microbiological, and therapeutic data were retrieved from the electronic clinical records of included patients. The primary outcomes were adherence to local guidelines for empiric therapies and the adequacy of targeted therapy. Secondary outcomes were evaluating antibiotic prescription patterns stratified by antibiotics during hospital stay and at discharge, and assessing the microbiological characteristics of UTI episodes. Results: During the study period, 7038 patients were admitted to the pediatric acute care unit (PACU), and 264 (3.7%) were included in this study. Adherence to local guidelines was highest immediately after the interventions, and it slightly decreased thereafter. Use of cephalosporins remained high throughout the 8 years but the changing microbiological scenario observed led to changing recommendations within the study period. An increase in E. coli strains resistant to co-amoxiclav was observed in the last years. Oral second-line agent consumption remained high but was adequate considering the prevalence of resistant bacteria. Conclusion: The variability of antimicrobial consumption reflects the changing resistance patterns for UTIs pathogens, underlying the importance of locally adapted, persevering antimicrobial stewardship interventions.

Abstract Background Currently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a separate entity. Objectives To describe the clinical characteristics of persistent monoJIA. Methods Patients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview. Results Of 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome. Conclusions MonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives.

BackgroundEuthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C).MethodsA single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney U-test and correlations between different parameters were calculated by Spearman's Rho coefficient.ResultsForty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF

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.

BackgroundDue to the growing evidence of the efficacy of intravenous (IV) cefazolin with an early switch to oral cefalexin in uncomplicated pediatric osteomyelitis (OM) and septic arthritis (SA) in children, we changed our guidelines for empiric antibiotic therapy in these conditions. This study aims at evaluating the impact of the guidelines' implementation in reducing broad-spectrum antibiotic prescriptions, duration of IV antibiotic treatment and hospital stay, treatment failure and recurrence.Materials and methodsThis is a retrospective, observational, quasi-experimental study. The four years pre-intervention were compared to the six years, ten months post-intervention (January 2012, through December 2015; January 2016, through October 31st, 2022). All patients aged 3 months to 18 years with OM or SA were evaluated for inclusion. Each population was divided into three groups: pre-intervention, post-intervention not following the guidelines, and post-intervention following the guidelines. Differences in antibiotic prescriptions such as Days of Therapy (DOT), activity spectrum and Length of Therapy (LOT), length of hospital stay (LOS), broad-spectrum antibiotics duration (bsDOT), treatment failure and relapse at six months were analyzed as outcomes.ResultsOf 87 included patients, 48 were diagnosed with OM (8 pre-intervention, 9 post-intervention not following the guidelines and 31 post-intervention following the guidelines) and 39 with SA (9 pre-intervention, 12 post-intervention not following the guidelines and 18 post-intervention following the guidelines). In OM patients, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group, with also the lowest proportion of patients discharged on IV treatment. Notably, significantly fewer cases required surgery in the post-intervention groups. Considering SA, LOS, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group. The treatment failure rate was comparable among all groups for both OM and SA. There were no relapse cases. The overall adherence was between 72 and 100%.ConclusionsThe implementation of guidelines was effective in decreasing the extensive use of broad-spectrum antibiotics and combination therapy for both OM and SA. Our results show the applicability, safety, and efficacy of a narrow-spectrum IV empirical antibiotic regimen with cefazolin, followed by oral monotherapy with first/second-generation cephalosporins, which was non-inferior to broad-spectrum regimens.

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition triggered by SARS-COV-2 infection, characterized by persistent fever, multiorgan dysfunction, and increased inflammatory markers. It requires hospitalization and prompt treatment, with nearly 60% of the cases needing intensive care and 2% fatality rate. A wide spectrum of clinical characteristics and therapeutic approaches has been reported in MIS-C. We describe a series of four patients with MIS-C, defined according to the current case definitions, with a self-limiting course and no need for immunomodulatory treatment (“self-limiting MIS-C”). Few data about self-limiting MIS-C are available to date and no information on medium- and long-term outcome of this subset of patients has been reported. Although limited in size, our experience provides new insights into the MIS-C syndrome, highlighting an underestimated aspect of the disease that may have significant therapeutic implications.

Kidney involvement has been poorly investigated in SARS-CoV-2 Multisystem Inflammatory Syndrome in Children (MIS-C). To analyze the spectrum of renal involvement in MIS-C, we performed a single-center retrospective observational study including all MIS-C patients diagnosed at our Pediatric Department between April 2020 and May 2022. Demographic, clinical, pediatric intensive care unit (PICU) admission’s need and laboratory data were collected at onset and after 6 months. Among 55 MIS-C patients enrolled in the study, kidney involvement was present in 20 (36.4%): 13 with acute kidney injury (AKI) and 7 with isolated tubular dysfunction (TD). In eight patients, concomitant AKI and TD was present (AKI-TD). AKI patients needed higher levels of intensive care (PICU: 61.5%, p < 0.001; inotropes: 46.2%, p = 0.002; second-line immuno-therapy: 53.8%, p < 0.001) and showed lower levels of HCO3- (p = 0.012), higher inflammatory markers [neutrophils (p = 0.092), PCT (p = 0.04), IL-6 (p = 0.007)] as compared to no-AKI. TD markers showed that isolated TD presented higher levels of HCO3- and lower inflammatory markers than AKI-TD. Our results indicate a combination of both pre-renal and inflammatory damage in the pathogenesis of kidney injury in MIS-C syndrome. We highlight, for the first time, the presence of tubular involvement in MIS-C, providing new insights in the evaluation of kidney involvement and its management in this condition.

Juvenile psoriatic arthritis (JPsA) is a relatively rare condition in childhood as it represents approximately 5% of the whole Juvenile Idiopathic Arthritis (JIA) population. According to International League of Associations of Rheumatology (ILAR) classification, JPsA is defined by the association of arthritis and psoriasis or, in the absence of typical psoriatic lesions, with at least two of the following: dactylitis, nail pitting, onycholysis or family history of psoriasis in a first-degree relative. However, recent studies have shown that this classification system could conceal more homogeneous subgroups of patients differing by age of onset, clinical characteristics and prognosis. Little is known about genetic factors and pathogenetic mechanisms which distinguish JPsA from other JIA subtypes or from isolated psoriasis without joint involvement, especially in the pediatric population. Specific clinical trials testing the efficacy of biological agents are lacking for JPsA, while in recent years novel therapeutic agents are emerging in adults. In this review, we summarize the clinical features and the current evidence on pathogenesis and therapeutic options for JPsA in order to provide a comprehensive overview on the clinical management of this complex and overlapping entity in childhood.

Abstract Background We aimed to test if standardized point-of-care outcome monitoring and clinical decision support (CDS), as compared to standard care, improves disease activity and patient-reported pain in children with enthesitis-related arthritis (ERA). Methods This was a retrospective cohort study of outcomes of children with ERA after phased implementation of I) standardized outcome monitoring with CDS for polyarticular JIA, and II) CDS for ERA, compared to a pre-intervention group of historical controls. We used multivariable mixed-effects models for repeated measures to test whether implementation phase or other disease characteristics were associated with change over time in disease activity, as measured by the clinical juvenile arthritis disease activity score (cJADAS), and pain. Results One hundred fifty-two ERA patients (41% incident cases) were included with a median age of 14.9 years. Implementation of standardized outcome monitoring or ERA-specific CDS did not result in significant differences in cJADAS or pain over time compared to the pre-intervention cohort. Higher cJADAS at the index visit, pain and more tender entheses were significantly associated with higher cJADAS scores over time (all p

Innate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner et al. first introduced the term “autoinflammation” describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-κB-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies.This review aims to provide an overview of the field with the most recent updates (see “Most recent developments in..” paragraphs) and a description of the newly identified AIDs.

Background: There is evidence that obesity could be a risk factor for the severity and response to treatment in adult patients with rheumatoid arthritis (RA) due both to the mechanical effect of overweight and to the potential pro-inflammatory effects of cytokines produced by adipose tissue.Objectives: To evaluate the role of overweight and obesity in a cohort of young patients with juvenile idiopathic arthritis (JIA) in terms of incidence, disease activity, outcome, and response to treatments.Methods: This single-center retrospective cohort study evaluated 110 children affected by JIA under treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents. Body mass index (BMI) categories of 5–84th (normal weight), 85–94th (overweight), and ≥95th (obese) percentile were used. Patients with systemic JIA, uveitis, chronic comorbidities, or under other potentially confounding systemic treatments were excluded. Uni- and multivariate analyses were performed.Results: One hundred and ten JIA patients (polyarticular n = 50, oligoarticular n = 38, psoriatic n = 12, enthesitis-related arthritis n = 8, undifferentiated n = 2) were enrolled in the study, 75% girls and 25% boys. The mean age at treatment onset was 6.09 years. Baseline BMI was ≥5th and ≤84th percentile in 80 patients, 85–94th in 27, and ≥95th in 3.We did not observe a significant association between BMI and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or number of active joints at baseline, while involvement of the joints of lower limbs was significantly greater ( p = 0.025) in overweight/obese patients. However, a trend toward lower remission rates and higher number of relapses, both after DMARDs and biologics, in patients with higher BMI was observed.Conclusion: This study focuses on the relationship between overweight/obesity and JIA. A significant correlation between obesity and a greater involvement of the joints of the lower limbs at baseline was demonstrated. Furthermore, our data suggest that obesity could negatively influence the course of the disease as well as treatment response.