Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

The Role of Electroencephalography in Children with Acute Altered Mental Status of Unknown Etiology: A Prospective Study.

INTRODUCTION: Acute altered mental status (AAMS) is often a challenge for clinicians, since the underlying etiologies cannot always easily be inferred based on the patient's clinical presentation, medical history, or early examinations. The aim of this study is to evaluate the role of electroencephalogram (EEG) as a diagnostic tool in AAMS of unknown etiology in children. MATERIALS AND METHODS: We conducted a prospective study involving EEG assessments on children presenting with AAMS between May 2017 and October 2019. Inclusion criteria were age 1 month to 18 years and acute (<1 week) and persistent (>5 minutes) altered mental status. Patients with a known etiology of AAMS were excluded. A literature review was also performed. RESULTS: Twenty patients (median age: 7.7 years, range: 0.5-15.4) were enrolled. EEG contributed to the diagnosis in 14/20 cases, and was classified as diagnostic in 9/20 and informative in 5/20. Specifically, EEG was able to identify nonconvulsive status epilepticus (NCSE) in five children and psychogenic events in four. EEG proved to be a poorly informative diagnostic tool at AAMS onset in six children; however, in five of them, it proved useful during follow-up. CONCLUSIONS: Limited data exist regarding the role of EEG in children with AAMS of unknown etiology. In our population, EEG proved to be valuable tool, and was especially useful in the prompt identification of NCSE and psychogenic events.

Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

Parents' and nurses' affective perception of a pictorial intervention in a pediatric hospital environment: Quasi-experimental design pre-post-testing.

BACKGROUND/AIM: The humanization of the hospital environment of pediatric departments represents an area of research and intervention on improving the quality of life for hospitalized patients, but also that one of relatives and health professionals. The aim of the study was to test, in a sample of nurses and hospitalized children's parents, whether the pictorial intervention impacted the perceptions of affective qualities of hospital environment. METHODS: This quasi-experimental design study investigated the effects of a pictorial humanization intervention which consisted of some naturalistic and colorful illustrations in the corridor of two pediatric wards of an Italian hospital. A total of 425 parents of hospitalized children and 80 nurses were asked to complete the Italian version of the "Scale of measurement of the affective qualities of places" in two different moments: 1) before the pictorial intervention and 2) three months after its implementation. RESULTS: For all participants (parents and nurses), results showed a significant effect of pictorial intervention with the four positive dimensions investigated (Relaxing, Exciting, Pleasant, and Stimulating) reporting higher scores after being performed it, and with the four negative dimensions (Distressing, Gloomy, Unpleasant, Sleepy) showing lower scores. CONCLUSIONS: Data suggest that the pictorial intervention could be particularly useful to create more welcoming hospital environments, reducing distress levels from hospitalized patients, but also of relatives and healthcare professionals. IMPLICATIONS TO PRACTICE: Pictorial interventions improve the emotional atmosphere in pediatric healthcare settings. Integrating visual elements related to care and healing enhances user experience, creating a more welcoming environment.

Measles virus and cytomegalovirus co-infection, in a child with recent SARS-CoV-2 infection, during COVID-19 pandemic: a case report.

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.

Clinical and psychopathological profiles of children with somatic symptom disorders in a pediatric emergency unit: an observational study before and during the SARS-CoV-2 pandemic.

Somatic symptom disorders (SSDs) are a group of clinical conditions characterized by heterogeneous physical symptoms, not directly supported by a demonstrable organic process. Despite representing a growing problem in the pediatric age, the literature lacks studies assessing the psychopathological and clinical features of subjects with SSD, particularly during the SARS-CoV-2 pandemic. This is a retrospective, observational study, involving two historical cohorts of children admitted to a tertiary referral Italian hospital over the 2 years preceding and following the start of the SARS-CoV-2 pandemic. Demographic, clinical, socio-economical, and psychological variables were investigated. Standardized tests for the developmental age were administered to assess psychopathological variables. Overall rates and trends of accesses for SSD, as compared to the total accesses for any cause at the Pediatric Emergency Room during the same periods, were reported as well. Fifty-one (pre-pandemic, 29; pandemic, 22) children with SSD were enrolled (age, 11.4 ± 2.4 years, F = 66.7%). Subjects in the pandemic historical cohort reported more frequently fever (p < 0.001), headache (p = 0.032), and asthenia (p < 0.001), as well as more chronic conditions in personal and family history, and fewer previous hospital accesses, as compared to the pre-pandemic cohort. Depressed mood and anxious traits were documented in both samples. None of them had an ongoing or a previously reported SARS-CoV-2 infection. During the pandemic, a clinical psychologist was more frequently consulted before the hospital discharge to mental health services, to support the diagnosis.  Conclusion: This study showed the significant burden of SSD in children, highlighting the need to implement pediatricians' education to optimize the management of these patients. Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features. Future studies, conducted on longitudinal and controlled samples, are indicated to further investigate children with these conditions. What is Known:    â€¢ Somatic symptoms disorders (SSDs) are frequent in the pediatric age, especially in early adolescence.    â€¢ Evidence remains scarce on the impact of the SARS-CoV-2 pandemic on SSDs in children. What is New:    â€¢ Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features.    â€¢ The implementation of pediatricians' education and a multidisciplinary approach are needed to optimize the management of SSDs.

Kawasaki disease, multisystem inflammatory syndrome in children, and adenoviral infection: a scoring system to guide differential diagnosis.

Children with Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), and Adenovirus infections (AI) of the upper respiratory tract show overlapping features. This study aims to develop a scoring system based on clinical or laboratory parameters to differentiate KD or MIS-C from AI patients. Ninety pediatric patients diagnosed with KD (n = 30), MIS-C (n = 26), and AI (n = 34) admitted to the Pediatric Emergency Unit of S.Orsola University Hospital in Bologna, Italy, from April 2018 to December 2021 were enrolled. Demographic, clinical, and laboratory data were recorded. A multivariable logistic regression analysis was performed, and a scoring system was subsequently developed. A simple model (clinical score), including five clinical parameters, and a complex model (clinic-lab score), resulting from the addition of one laboratory parameter, were developed and yielded 100% sensitivity and 80% specificity with a score ≥2 and 98.3% sensitivity and 83.3% specificity with a score ≥3, respectively, for MIS-C and KD diagnosis, as compared to AI. CONCLUSION: This scoring system, intended for both outpatients and inpatients, might limit overtesting, contribute to a more effective use of resources, and help the clinician not underestimate the true risk of KD or MIS-C among patients with an incidental Adenovirus detection. WHAT IS KNOWN: • Kawasaki Disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C) and adenoviral infections share overlapping clinical presentation in persistently febrile children, making differential diagnosis challenging. • Scoring systems have been developed to identify high-risk KD patients and discriminate KD from MIS-C patients. WHAT IS NEW: • This is the first scoring model based on clinical criteria to distinguish adenoviral infection from KD and MIS-C. • The score might be used by general pediatricians before referring febrile children to the emergency department.

Frequency and type of domestic injuries among children during COVID-19 lockdown: what changes from the past? An Italian multicentre cohort study.

Accidents are the main cause of injury in children, more than half events happen at home. Aims of this study were to assess if SARS-CoV-2 lockdown influence emergency department (ED) visits due to children domestic accident (DAs) and to identify factors associated with hospitalization. This was a multicentre, observational, and retrospective cohort study involving 16 EDs in Italy and enrolling children (3-13 years) receiving a visit in ED during March-June 2019 and March-June 2020. Risk factors for hospitalization were identified by logistic regression models. In total, 8860 ED visits due to domestic accidents in children occurred before (4380) and during (4480) lockdown, with a mean incidence of DA of 5.6% in 2019 and 17.9% in 2020 (p < 0.001) (IRR: 3.16; p < 0.001). The risk of hospitalization was influenced by the type of occurred accident, with fourfold higher for poisoning and twofold lower risk for stab-wound ones. In addition, a higher risk was reported for lockdown period vs 2019 (OR: 1.9; p < 0.001), males (OR: 1.4; p < 0.001), and it increased with age (OR: 1.1; p < 0.001).    Conclusions: The main limitation of this study is the retrospective collection of data, available only for patients who presented at the hospital. This does highlight possible differences in the total number of incidents that truly occurred. In any case, the COVID-19 lockdown had a high impact on the frequency of DAs and on hospitalization. A public health campaign aimed at caregivers would be necessary to minimize possible risks at home. What is Known: • In Italy, domestic accidents are the second leading cause of paediatric mortality after cancer. • During the first SARS-CoV-2 lockdown in 2020, a sharp decrease in the total number of Emergency Departments visits for all causes was observed, both in children and in adults. What is New: • During the first SARS-CoV-2 lockdown in 2020, domestic accidents involving children increased threefold from the previous year. • Higher risk of hospitalization was showed in minors accessing during 2020 vs 2019, in males than in females and it increased with advancing age. Considering the type of injury, a significant higher risk of hospitalization for poisoning was observed.

The effects of an active breaks intervention on physical and cognitive performance: results from the I-MOVE study.

BACKGROUND: The present quasi-experimental study aimed to evaluate the effects of active breaks intervention (ABs) to promote physical and cognitive improvement in primary school. METHODS: The active breaks group (ABsG) performed 10 min of ABs three times per school day and the control group (CG) did normal lessons. The baseline and follow-up evaluation was conducted respectively in October 2019 and in May 2021. Cognitive performance was assessed using working memory test, physical performance was analyzed with ActiGraph accelerometers and physical fitness tests, quality of life was monitored using the Paediatric Quality of Life questionnaire (PedsQL) and classroom behavior was collected with an ad hoc questionnaire. RESULTS: We enrolled 153 children (age: 7.61 ± 1.41, 54.2% males). Working memory significantly increased in the ABsG (ΔWM: 1.30 ± 1.17) than in CG (ΔWM: 0.96 ± 1.20). The 6 min Cooper test increased in the ABsG (Δ: 1.77 ± 136.03) but not in CG (Δ: -156.42 ± 187.53), P < 0.05. The weekly physical activity levels increased in both groups; however, the sedentary behavior significantly increased both in ABsG and CG. Children reported improvements in their quality of school life including feeling better in class and in school when using ABs; moreover, children improved their time on task behaviors in ABsG. CONCLUSION: The present study has proven to be effective on children's physical and cognitive performance.

Outdoor Air Pollution and Childhood Respiratory Disease: The Role of Oxidative Stress.

The leading mechanisms through which air pollutants exert their damaging effects are the promotion of oxidative stress, the induction of an inflammatory response, and the deregulation of the immune system by reducing its ability to limit infectious agents' spreading. This influence starts in the prenatal age and continues during childhood, the most susceptible period of life, due to a lower efficiency of oxidative damage detoxification, a higher metabolic and breathing rate, and enhanced oxygen consumption per unit of body mass. Air pollution is involved in acute disorders like asthma exacerbations and upper and lower respiratory infections, including bronchiolitis, tuberculosis, and pneumoniae. Pollutants can also contribute to the onset of chronic asthma, and they can lead to a deficit in lung function and growth, long-term respiratory damage, and eventually chronic respiratory illness. Air pollution abatement policies, applied in the last decades, are contributing to mitigating air quality issues, but more efforts should be encouraged to improve acute childhood respiratory disease with possible positive long-term effects on lung function. This narrative review aims to summarize the most recent studies on the links between air pollution and childhood respiratory illness.

Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

Epidemiology and clinical evolution of non-multisystem inflammatory syndrome (MIS-C) dermatological lesions in pediatric patients affected by SARS-CoV-2 infection: A systematic review of the literature.

COVID-19 can present with a range of skin manifestations, some of which specific of the pediatric age. The aim of this systematic literature review was to determine the type, prevalence, time of onset, and evolution of cutaneous manifestations associated with COVID-19 in newborns, children, and adolescents, after excluding multisystem inflammatory syndrome in children (MIS-C). PubMed, Tripdatabase, ClinicalTrials, and Cochrane Library databases were searched using an ad hoc string for case reports/series and observational studies, published between December 2019 and February 2022. Study quality was assessed using the STROBE and CARE tools. Seventy-three (49 case reports/series and 24 studies) out of 26,545 identified articles were included in the analysis. Dermatological lesions were highly heterogeneous for clinical presentation, time of onset, and association with other COVID-19 manifestations. Overall, they mainly affected the acral portions, and typically presented a favorable outcome. Pseudo-chilblains were the most common. CONCLUSIONS: Mucocutaneous manifestations could be the only/predominant and early manifestation of COVID-19 that could precede other more severe manifestations by days or weeks. Therefore, physicians of all disciplines should be familiar with them. WHAT IS KNOWN: • A variety of cutaneous manifestations have been reported in association with COVID-19. • Urticaria, maculopapular, or vesicular rashes can occur at any age, while chilblains and erythema multiforme are more common in children and young patients. WHAT IS NEW: • Skin lesions related to SARS-CoV-2 infection often show a peculiar acral distribution. • Mucocutaneous lesions of various type may be the only/predominant manifestation of COVID-19; they could present in paucisymptomatic and severely ill patients and occur at different stages of the disease.

Midazolam premedication in ileocolic intussusception: a retrospective multicenter study.

Ileocolic intussusception is a common cause of bowel obstruction. When spontaneous reduction does not occur, non-operative management through enema reduction is necessary. Despite the evidence indicating that sedatives favor success in the reduction, their use is still not a common practice. To determine if midazolam (MDZ) before enema improves the rate of procedure success, we retrospectively reviewed charts of patients admitted to two Italian pediatric emergency departments. Outcome measures were the success rate of the enema, recurrence, and need for surgery. Patients were grouped according to the use of MDZ or not, before hydrostatic reduction attempt. We included 69 and 37 patients in the MDZ and non-MDZ groups, respectively. The two groups did not differ in demographics, clinical characteristics, and ultrasound findings. Intussusception reduction after the first enema attempt occurred in 75% (MDZ group) and 32.4% (non-MDZ group) of patients (P < .001); 27.9% (MDZ group) and 77.8% (non-MDZ group) of patients underwent surgery (P < .001). Among them, spontaneous reduction of intussusception during the induction of general anesthesia occurred in 31.6% and 42.9% of patients, respectively (P .43). Multivariate logistic regression analysis showed that only MDZ had a positive effect on the result of the enema (OR 7.602, 95%CI 2.669-21.652, P < .001). CONCLUSION: Procedural sedation with MDZ for enema reduction of intussusception can increase the success rate and lead to a better management of patients. WHAT IS KNOWN: • Despite the evidence of the usefulness of sedatives in the reduction of intussusception, their use is still not a common practice. WHAT IS NEW: • Midazolam during enema reduction of intussusception can increase the success rate and consequently lead to better management of patients.

The impact of COVID-19 on physical activity behaviour in Italian primary school children: a comparison before and during pandemic considering gender differences.

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.

Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice.

AIM: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. METHODS: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. RESULTS: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. CONCLUSION: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits.

Psoriasis and Cardiovascular Risk in Children: The Usefulness of Carotid Intima-Media Thickness.

Psoriasis is a skin disorder which mostly affects adults, beginning in childhood in almost one-third of patients. In adults it is associated with increased risk for cardiovascular diseases (CVD), while this association is still debated at younger age. Our aim was to evaluate the association between psoriasis and metabolic markers and cardiovascular findings in this age group. Twenty consecutive patients previously diagnosed with psoriasis (group A) were enrolled and compared with healthy non- psoriatic age- and sex-matched subjects (group B). The severity of the disease, CV risk factors, including anthropometric data with adiposity and its distribution, blood pressure (BP), laboratory metabolic tests, echocardiography and vascular ultrasound (transcranial echo-Doppler and carotid artery echo-Doppler with carotid intima-media thickness, cIMT) were performed for each subject. Personal history for CV risk, BP, anthropometric data were similar between the two groups, while familiar history for psoriasis was more frequent in group A (p < 0.02). C-IMT was significantly higher in group A compared to B (right, p = 0.001; left, p = 0.002). In addition, c-IMT was positively correlated with disease duration, triglycerides and triglycerides/glucose. Cerebral flow velocities, cardiac measurements, systo-diastolic function, ventricle geometry and mass were normal and comparable between the two groups, and did not correlate with CV risk factors. In childhood psoriasis c-IMT could represent a marker of pre-clinical cardiovascular involvement and contribute to start a personalized management, while cardiac findings seem to be normal in the early stage of disease. Longitudinal studies can clarify the progression of CV involvement in paediatric-onset psoriasis.

Circulating Endothelial Cells: A New Possible Marker of Endothelial Damage in Kawasaki Disease, Multisystem Inflammatory Syndrome in Children and Acute SARS-CoV-2 Infection.

BACKGROUND: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are pediatric diseases characterized by systemic inflammation and vascular injury, potentially leading to coronary artery lesions (CALs). Data on vascular injury occurring during acute COVID-19 (AC19) in children are still lacking. The aim of our study was to investigate endothelial injury in KD-, MIS-C- and AC19-dosing circulating endothelial cells (CECs). METHODS: We conducted a multicenter prospective study. CECs were enumerated by CellSearch technology through the immunomagnetic capture of CD146-positive cells from whole blood. RESULTS: We enrolled 9 KD, 20 MIS-C and 10 AC19. During the acute stage, the AC19 and KD patients had higher CECs levels than the MIS-C patients. From the acute to subacute phase, a significant CEC increase was observed in the KD patients, while a mild decrease was detected in the MIS-C patients. Cellular clusters/syncytia were more common in the KD patients. No correlation between CECs and CALs were found in the MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation. CONCLUSIONS: Our study suggests a possible role of CECs as biomarkers of systemic inflammation and endothelial dysfunction in KD and MIS-C and different mechanisms of vascular injury in these diseases. Further larger studies are needed.

Mucosal and Histologic Healing in Children With Inflammatory Bowel Disease Treated With Antitumor Necrosis Factor-Alpha.

OBJECTIVES: Mucosal healing (MH) and histological healing (HH) have been recently proposed as a novel treatment target for inflammatory bowel disease (IBD). The aim of the present study was to evaluate real-life achievement of such outcomes in a cohort of pediatric patients with IBD treated with anti-TNF-alpha (ATA) agents. METHODS: A retrospective analysis was performed on patients affected by IBD who received ATA and were followed up at two referral centers. Incidence and cumulative rates for MH and HH for each group were calculated. RESULTS: Of 170 (105 Crohn's disease [CD] and 65 ulcerative colitis [UC]) patients, 78 with CD and 56 with UC underwent endoscopic re-assessment during the study period. MH was achieved by 32 CD (41%) and 30 UC (53.6%) patients; 26 CD (33.3%) and 22 UC (39.3%) patients achieved HH. MH incidence rate was 19.1/1000 and 47/1000 person-months, whereas HH incidence rate was 15.5/1000 and 34.7/1000 person-months for CD and UC, respectively. Remission at the end of induction was associated with higher MH and HH rates (HR: 2.43, P = 0.049 and HR: 2.94, P = 0.046, respectively) in CD. In UC, adalimumab was associated with lower MH and HH rates (HR: 0.16, P = 0.004 and HR: 0.07, P = 0.003). CONCLUSIONS: We reported a real-life experience arising from a large cohort of pediatric IBD who received ATA scheduled treatment. Less than half of patients with CD and only a little >50% of UC patients achieved MH. Microscopical inflammation was observed in 18.8% CD and 26.7% UC patients who achieved MH. Overall, MH and HH rates appear lower compared to previously published data.

Viral rashes mimicking drug reaction with eosinophilia and systemic symptoms syndrome in children after ß-lactams intake: a diagnostic challenge.

In cases of skin eruptions over the course of antibiotic therapy and concomitant viral infection, differential diagnosis is often challenging. Confirming or ruling out drug hypersensitivity is not always a clear-cut question. Drug reaction with eosinophilia and systemic symptoms (DRESS) cases, for example, is classified as severe cutaneous adverse reactions due to drugs, but frequently the clinical manifestations do not completely fit into the diagnosis of DRESS. The aim of the present paper is to highlight similarities and differences among DRESS syndrome and DRESS-like rashes during viral infections and amoxicillin intake in children, in order to highlight those aspects that can help clinicians in early detection. We describe the dermatological, clinical, and laboratory characteristics of five patients hospitalized for DRESS-like skin rashes appearing roughly 1 week since the start of an amoxicillina course for upper respiratory tract infection (URTI) symptoms. The data are compared with those of 3 patients with early-onset DRESS syndrome. The absence of eosinophilia might be an initial marker to help identifying DRESS-like rashes; a quick clinical improvement and the confirmation of a viral infection able to explain the symptoms can help to finally rule out DRESS syndrome. Conclusion: A rapid, correct diagnosis of such DRESS-like rashes during viral infections allows more appropriate management and avoids unnecessary, life-long exclusion of useful and effective antibiotics because of a falsely "amoxicillin-allergy" labelling. What is Known: • Viral infections are common causes of skin rashes in children during antibiotic intake and may require differential diagnosis with drug reactions. • Early-onset DRESS syndrome is usually induced by antibiotics and appears ≤15 days after drug intake. What is New: • Prominent midface edema, maculopapular rash, and mild-to-moderate systemic symptoms may appear in children during viral illnesses treated with amoxicillin few days after drug intake, and may require differential diagnosis with early-onset DRESS. • In such cases, absence of eosinophilia, low (2-3) RegiSCAR score, confirmation of viral etiology, and a rapid resolution of the rash (2-5 days) might help to rule out DRESS; conversely, at an early stage, the presence of eosinophilia should suggest a diagnosis of DRESS.

The Role of the Noradrenergic System in Eating Disorders: A Systematic Review.

Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.