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The autoantibody profile associated with known autoimmune diseases in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that adults with COVID-19 had a moderate prevalence of autoantibodies against the lung antigen KCNRG, and SLE-associated Smith autoantigen. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin(IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoringin vivodecay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Together these findings demonstrate that administration of high-dose IVIG is responsible for the detection of several autoantibodies in MIS-C and KD. Further studies are needed to investigate autoantibody production in MIS-C patients, independently from IVIG administration.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs. Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs. Supplementary Information The online version contains supplementary material available at 10.1186/s13052-021-01150-0.

Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, a multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in children with COVID-19 (n=105) and MIS-C (n=76). pCOVID-19 was characterized by enhanced type I IFN responses, and MIS-C by type II IFN- and NF-κB dependent responses, matrisome activation, and increased levels of Spike protein. Reduced levels of IL-33 in pCOVID-19, and of CCL22 in MIS-C suggested suppression of Th2 responses. Expansion of TRBV11-2 T-cell clonotypes in MIS-C was associated with inflammation and signatures of T-cell activation, and was reversed by glucocorticoids. The association of MIS-C with the combination of HLA A*02, B*35, C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load. Use of IVIG was identified as a confounding factor in the interpretation of autoantibody levels.

Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions.Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period.Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0–6.2, range 0.1–17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days.Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.

Thanks to the advances in antiretroviral therapies (ART) and early diagnosis, pediatric HIV has turned into a chronic infection that requires the collaboration of all pediatric subspecialists for holistic patient management. Gastrointestinal complaints are a frequent reason for seeking access to medical care in all pediatric patients worldwide. Intestinal involvement is present in virtually all children with HIV infections. In high-prevalence settings, up to 25% of children accessing the hospital for diarrhea are diagnosed with HIV. More than half of patients with advanced disease present with gastrointestinal symptoms, from mild infectious diarrhea to severe gastrointestinal impairment, malabsorption and failure to thrive. Gastrointestinal disorders do not spare children on ART, particularly in the initial months of therapy. ART-associated pancreatitis and hepatitis are rare but potentially severe adverse events, whereas lower abdominal symptoms have been reported in more than a third of patients. The latter are usually mild and transient, but may limit ART adherence; a correct framing of the problem is necessary to minimize therapy switches while optimizing the quality of life of children on ART. This review aims to provide state-of-the-art guidance for the initial approach to gastrointestinal diseases in children living with HIV.

We report two cases of neonatal measles (one congenital and one post natal infection) admitted to our neonatal intensive care unit and discuss the management. This report intend to keep alert against measles and point out the risk for susceptible pregnant women and their offspring in countries with reduction of coverage from anti measles vaccine.

Background: Worldwide medical authorities recommend vitamin A supplementation for severe measles requiring hospitalization; however, evidence supporting its use in high-income countries is lacking. A nationwide vitamin A shortage reported in concomitance with a recent measles outbreak in Italy provided an opportunity to test the effectiveness of vitamin A in a high-income setting, simulating a random allocation to treatment. Methods: We conducted a prospective controlled cohort study involving children admitted to a tertiary-care hospital in Southern Italy. The primary outcome was the duration of fever· Secondary outcomes included the length of hospitalization, rate of complications, need for antibiotic treatment, and body temperature. The study has been registered to the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance ( EU PAS 31805). Findings: A total of 108 inpatient children (36% females, median age 16·3 months) were enrolled; 36 received two doses of oil-based vitamin A according to age, and 72 matched controls received standard care. There were no significant differences between the study groups in the duration of fever (7·03±2·67 vs· 6·82±3·27, p=0·74), length of hospitalization (median, 5·5 vs· 5·0 days, p=0·36), maximum body temperature (median, 39°C in both groups, p=0·90), rate of organ (69·4% vs· 63·9%, p=0·56) and hematological complications (41·7% vs· 59·7%, p=0·07), or the need for antibiotic treatment (66·7% vs· 61·1%, p=0·57). Overall, vitamin A supplementation did not reduce the risk of any complications (relative risk, 1·33; 95% confidence intervals 0·59 to 2·96). Sub-group analysis in children with chronic conditions, weight-for-age

Background Multisystem inflammatory syndrome in children (MIS-C) is a rare life-threatening clinical condition that can develop in patients younger than 21 years of age with a history of infection/exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cardiovascular system is a main target of the inflammatory process that frequently causes myocardial dysfunction, myopericarditis, coronary artery dilation, hypotension, and shock. Multisystem inflammatory syndrome in children-associated myocarditis is usually characterized by fever, tachycardia, non-specific electrocardiogram abnormalities, and left ventricular dysfunction, but serious tachyarrhythmias may also occur. We report two cases of patients with MIS-C-associated myocarditis who developed severe bradycardia. Case summary Two female adolescents with recent history of coronavirus disease 2019 (COVID-19) were initially hospitalized for long-lasting high-grade fever and severe gastrointestinal symptoms. Both patients were diagnosed with MIS-C-associated myocarditis for elevation of markers of myocardial injury (mean highly-sensitive cardiac troponin 2663 pg/mL, mean N-terminal-pro-brain natriuretic peptide 5097 pg/mL) and left ventricular dysfunction, which was subsequently confirmed by cardiac magnetic resonance. Both patients developed a severe sinus bradycardia (lowest heart rate 36 and 42, respectively), which appeared refractory to the treatment with intravenous Methylprednisolone and Immunoglobulins, despite a clinical and biochemical improvement. The use of Anakinra (a recombinant interleukin-1 receptor antagonist), was associated with a rapid improvement of cardiac rhythm and excellent clinical outcome at 6 months of follow-up. Discussion In patients with MIS-C-associated myocarditis, a continuous cardiac monitoring is mandatory to promptly identify potential conduction abnormalities. Adolescents may present bradycardia as a rhythm complication. We experienced a rapid recovery after treatment with Anakinra, to be considered as add-on therapy in cases refractory to standard anti-inflammatory treatment.

Background Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient’s age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. Methods A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. Results Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. Conclusions The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

OBJECTIVES: The paucity of symptoms and the difficulties in wearing personal protective equipment make children a potential source of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for health care workers (HCWs). Previous experience in pediatric settings reported high rate of intrahospital SARS-CoV-2 transmission in HCWs caring for children. We aimed at investigating the rate and determinants of SARS-CoV-2 infection among HCWs working in a regional reference center in the Southern Italy. METHODS: A prospective observational study was conducted to monitor the occurrence of SARS-CoV-2 infections among HCWs and investigate the relation between the infection rate and hours of exposure or number and characteristics of procedures, including nasopharyngeal swab, high-flow oxygen delivery, suctioning of airway secretions, sputum induction, and nebulizer administration. RESULTS: After 5 months of monitoring, 425.6 hours of SARS-CoV-2 exposure (18.5 hours per person), and 920 hospital procedures, no case of nosocomial transmission was reported among the 23 HCWs enrolled in the study. CONCLUSIONS: The application of stringent preventive measures, also outside the area dedicated to patients’ care, can effectively control infection spreading also in pediatric settings.

Diagnosis of systemic cat scratch disease may be challenging. Here, we describe a case of an immunocompetent girl exhibiting fever and multifocal hepatosplenic abscesses. Diagnostic tests for Bartonella henselae infection (enzyme immunoassay and polymerase chain reaction) were found steadily negative and the diagnosis, suspected on the basis of the Margilet's criteria, was finally confirmed by indirect immunofluorescent antibodies.

Background In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. Result Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2–9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5–19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. Conclusion An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.

A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.

During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics' market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics' efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics' strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.

Background: In comparison with adults, severe acute respiratory syndrome (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods: We designed a hub-and-spoke system involving a Hub Centre to provide relevant healthcare information, based on the use of telemedicine and stringent admission criteria. Result: Between March and April 2020, the Hub Centre managed a total of 119 children (62 males, 52%; median age, 5.5 years; interquartile range [IQR], 2; 10) with suspected or confirmed COVID-19. Of the 119 children, 90 were managed in cooperation with family paediatricians and 29 with hospital-based physicians. In total, 8 (6.7%) children were hospitalised, with a median length of hospital stay of 10 days (IQR, 8.5 days; range, 4–22 days). Conclusion: case-by-case management allows a global evaluation in which the clinical condition is one determinant in medical decision-making along with the use of isolation to prevent the spread of COVID-19 among family members and cohabitants, and biocontainment measures. Large centres could coordinate paediatric COVID-19 cases through telemedicine, taking advantage of the generally milder presentation in children but also considering their dependence on adults and risk of infection spreading.

During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics’ market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics’ efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics’ strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.

Objective: Clinical and psychological HIV-related problems peak during adolescence, which coincides with transition of children and adolescents infected from mothers from pediatric to adult reference centers for HIV infection. Transition often is done without specific programs. We wanted to explore transition as an opportunity to increase the efficacy of care and the psychological well-being through a specific program. Methods: Thirteen vertically infected patients aged 13-20 years were followed up for 24 months by pediatricians, infectious disease specialists, a psychologist, and a nurse. Interventions consisted in joint clinic, simplification of therapy, patient group discussions, HIV infection explanations, and psychological support, lasting 12 months. Efficacy was measured by viro-immunological outcomes and adherence to therapy and psychological tests. Clinical, viro-immunological, and psychological evaluations were performed at 0 (T0) and 12 months (T12) and 6 months after transition to an adult center (T18). Psychological outcomes were assessed using standardized questionnaires for quality of life and self-esteem. Results: In 11/13 participants, pills administrations/day were significantly reduced. Patients with undetectable viral load and CD4+ >25% increased from 61 to 77% and from 61 to 74%, respectively. Six months after transition, all patients exhibited an undetectable viral load. Adolescents' awareness of the severity of the disease and the risk of sexual transmission was generally poor. Patients classified with "severe" psychological distress according to the quality of life index decreased from 38 to 15% and well-being increased. Similar results were observed 6 months after the transition to adult care. No effect was observed on self-esteem index. Conclusions: Specific protocols for transition should be developed to optimize resilience and psychological well-being, including routine psychological support for adolescents with HIV infection transiting from pediatric to adult centers for HIV infection.

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

The role of Plasmodium in the etiology of acute diarrhea in developing countries remains controversial, and gastrointestinal (GI) symptoms are inconsistently reported in malaria. In this observational case–control study, we investigated the prevalence and risk factors for GI symptoms in hospitalized malarious children aged 1 month to 5 years in northern Uganda. Children with a diagnosis of Plasmodium falciparum malaria were enrolled as cases, and feverish children in whom malaria was excluded were enrolled as controls. Among 451 malarious children, 46.1% had GI symptoms at admission. Compared with controls, the frequency of diarrhea (24.8% versus 11.2%, P < 0.001) and vomiting (35.5% versus 17.5%, P < 0.001) was significantly higher in children with malaria, who had a higher chance of showing either vomiting (odds ratio [OR]: 3.22; 95% CI: 2.14–4.91) or diarrhea (OR: 3.14; 95% CI: 1.99–5.07) at hospital admission. A subgroup analysis performed in children with severe malaria, severe anemia, or high-grade fever confirmed these results. Diarrhea was more frequent in infants and children younger than 3 years than in older children. The analysis of 71 malarious children with diarrhea who received intravenous artesunate showed that the symptom resolved within the first 24 hours since the beginning of the treatment in 85.9% of cases. The 3-fold higher prevalence of diarrhea and vomiting in malarious children compared with febrile controls may provide rationale for incorporating malaria testing in the symptom-guided diagnostic approach of the young child with diarrhea and vomiting in malaria-endemic settings.

Background: Italy is classified as a low tuberculosis (TB) incidence country (rate 6.5/100,000 inhabitants). However, the Campania Region Pediatric Reference Centre (CRRC) observed an increase in TB, contemporarily with a rise in migration.Our aim was to investigate trends in TB notification rates, association with migration, and changes in clinical outcomes of children living in Campania. Methods: We conducted a prospective cohort study (January 1, 2009-December 31, 2018), including children

BackgroundMeasles is a highly communicable infection with potentially severe complications. It is rarely reported in high-income countries and the limited awareness and experience of pediatricians may result in misdiagnosis. The present study aimed at investigating physician’s ability and timing to reach diagnosis during a recent outbreak in Italy.MethodsThe Italian Society for Pediatric Infectious Diseases conducted a retrospective, multicenter study in children hospitalized for measles between 1 January 2016 and 30 August 2017 in secondary and tertiary care hospitals. The appropriateness of diagnosis at admission, the time to reach clinical diagnosis, and serological confirmation of measles were recorded.ResultsAt hospital admission, measles was misdiagnosed in 101 (40.5%) of the 249 children (median age, 14.5 months) enrolled. The appropriate diagnosis increased from 30% to 72.5% during the period of observation (P < .001). A greater chance of receiving an appropriate diagnosis was demonstrated in children who reported a contact with measles (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.0–9.2) or in those seen in institutions that managed more cases (OR, 7.39; 95% CI, 3.22–16.9; P = .0001). In contrast, children with underlying chronic conditions had a higher risk of misdiagnosis (appropriate diagnosis OR, 0.19; 95% CI, 0.10–0.33). The mean time from the onset of symptoms to clinical diagnosis was 4.55 ± 2.2 days and to serological confirmation was 7.0 ± 3.4 days.ConclusionsMeasles is frequently misdiagnosed in low-prevalence settings. Specific measures to increase pediatricians’ awareness about vaccine-preventable infections need to be implemented.

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

Background Ascites can develop as a consequence of a number of diseases in childhood. Despite chronic liver disease is the most common cause, several conditions can lead to ascites also in the absence of liver dysfunction. As non-cirrhotic ascites shows a high degree of overlapping sign and symptoms it is still a challenge for physicians. Case presentation A 8-year-old Caucasian girl was referred for fever, vomit and diarrhea occurred over the past few weeks. Physical examination showed timpanitic distension of the abdomen with marked tenderness and increased abdominal wall rigidity. Abdominal imaging showed diffuse ascites and thickened omentum and bowel wall. Blood tests showed increased C- reactive protein levels and decreased lymphocyte count. Specific treatment for inflammatory bowel disease was started. Persisting of ascites required additional investigations. Positive tuberculin skin test and Interferon Gamma release assay (IGRA) as well as increased Ca125 serum concentrations were found. Computed tomography scan showed mediastinal and mesenteric adenopathies and diffuse smooth thickening of the omentum with significant enhancement (omental cake-like). Ascitic fluid analysis revealed high leucocytes and protein levels. Presumptive diagnosis of peritoneal tuberculosis (PTB) was made. Antituberculous treatment resulted in the resolution of ascites and normalization of lymphocyte count and Ca125 serum concentrations. Conclusions PTB is still possible in low-prevalence countries. As it is a great mimicker of other abdominal pathology whose treatment might worsen tuberculosis progression, clinical suspicion and adequate screening are required to avoid unnecessary interventions and delayed treatment. Ca125 is a non-specific marker of peritoneal inflammation but it might be helpful in monitoring the treatment response.

Measles outbreaks were recently reported in Europe due to low immunization rates. In this scenario, identifying the reasons of no vaccination is crucial to set up strategies to improve immunization rate. A cross-sectional study was conducted to investigate the determinants of missed vaccination in children living in Southern Italy, during the 2016 outbreak. A standardized face-to-face questionnaire was used to record demographic data, immunization status, and reasons for missed vaccination. A total of 1141 children (median age 86months, male 47.2%) was enrolled, 77.8% of the children were adequately vaccinated for age, 6.3% were incompletely vaccinated for age, and 15.9% did not receive any vaccine dose. Vaccination rate and reasons for not vaccinating significantly varied according to age, with children ≤ 24months showing the lowest rate (67.8%). Reasons for not vaccinating included fear for side effects (51%), presence of underlying chronic conditions (12.2%), skip scheduled appointment (12.2%), refusal of vaccination (10.3%), acute illnesses (7.2%), and allergy to eggs (4.6%). The presence of underlying condition was a risk factor for inadequate immunization (p < 0.0001). Only 4.7% of conditions were true contraindications to vaccine administration. Conclusion: We reported inadequate measles immunization rate in Southern Italy, with lowest rates in children ≤ 2years or with underlying conditions. Only a minority had true contraindications to vaccine uptake. Implementation strategies addressed to health-care professionals and families should focus on the reported determinants to increase measles vaccination coverage.What is Known:• Measles is a viral, highly communicable disease, preventable by vaccine.• Measles elimination in Europe failed as demonstrated by outbreaks in several countries, due to low immunization rates.What is New:• Inadequate measles immunization rate due to false contraindications in Southern Italy, with lowest rates in children ≤ 2years.• The presence of underlying disease is a risk factor for inadequate immunization.

Objective: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries. The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. Methods: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. Results: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%–96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%–95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. Conclusions: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners’ compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.

Children have tended to have milder symptoms during the COVID-19 pandemic than adults and multisystem inflammatory syndrome has been a rare complication. However, restrictions implemented to reduce transmission have directly affected children, as most countries closed schools during the first wave, despite a lack of strong evidence. Europe is now facing a rising of new cases and this will be a challenge for health systems as temperatures drop and influenza and bronchiolitis rise.

Acute infectious diarrhea (AID) is one of the most common diseases in pediatric age with relevant burden both in high- and in low-income countries.Thanks to their direct action on enterocyte functions and indirect actions on mucosal and systemic immune system and intestinal microenvironment, probiotics are an ideal intervention to manage AID in childhood. However, their efficacy is strictly related to strains and indications, and practitioners should take this information into account in clinical practice.This chapter summarizes the main mechanisms of action of probiotics in AID, with a focus on proof of efficacy supporting their use in prevention and treatment of infant AID.The use of selected strains in appropriate doses is strongly recommended by guidelines of AID, based on large and consistent proofs of efficacy and safety. At present, therapy with probiotics of AID is arguably the strongest indication for probiotics in medicine. Future research should investigate probiotic efficacy in at-risk populations and settings where the evidence is missing.Their role in prevention of AID is however questionable in healthy population, whereas it should be considered in at-risk population. Evidence for prevention of diarrhea in day-care centers and communities is lacking, but consistent evidence supports efficacy in prevention of hospital acquired diarrhea.Overall, AID is the most convincing area for probiotic use in children, and effective strains should be used early after onset of symptoms.

Acute/subacute haematogenous osteomyelitis (AHOM/SAHOM) are potentially devastating diseases. Updated information about the epidemiology, management and outcome of AHOM/SAHOM is needed to minimize the risk of complications and sequelae. METHODS: A multicenter study was performed to evaluate retrospectively the management and outcome of AHOM/SAHOM in Italy. Data from children aged >1 month, and hospitalized between 2010 and 2016, in 19 pediatric centers, were analyzed. RESULTS: 300 children with AHOM and 98 with SAHOM were included. Median age was 6.0 years (IQR: 2.0-11.0). No clinical difference was observed with the exception of fever at onset (63.0% vs. 42.9%; P < 0.0001), and a more common spinal involvement in SAHOM (6.7% vs 20.4%; P < 0.001). Fifty-Eight Staphylococcus aureus strains were isolated; 5 (8.6%) were MRSA. No Kingella kingae infection was documented. No different risk for complication/sequela was observed between AHOM and SAHOM (38.3% vs. 34.7%; OR:0.85; 95%CI: 0.53-1.38; P = 0.518). Duration and type of antibiotic therapy were not associated with risk of complication/sequelae. CONCLUSION: AHOM and SAHOM displayed some differences, however occurrence and risk factors for complications and sequelae are similar, and the same empiric treatment might be recommended.

BACKGROUND AND OBJECTIVES: A 2007 meta-analysis showed probiotics, specifically Lactobacillus rhamnosus GG (LGG), shorten diarrhea from acute gastroenteritis (AGE) by 24 hours and decrease risk of progression beyond 7 days. In 2005, our institution published a guideline recommending consideration of probiotics for patients with AGE, but only 1% of inpatients with AGE were prescribed LGG. The objective of this study was to increase inpatient prescribing of LGG at admission to >90%, for children hospitalized with AGE, within 120 days. METHODS: This quality improvement study included patients aged 2 months to 18 years admitted to general pediatrics with AGE with diarrhea. Diarrhea was defined as looser or ≥3 stools in the preceding 24 hours. Patients with complex medical conditions or with presumed bacterial gastroenteritis were excluded. Admitting and supervising clinicians were educated on the evidence. We ensured LGG was adequately stocked in our pharmacies and updated an AGE-specific computerized order set to include a default LGG order. Failure identification and mitigation were conducted via daily electronic chart review and e-mail communication. Primary outcome was the percentage of included patients prescribed LGG within 18 hours of admission. Intervention impact was assessed with run charts tracking our primary outcome over time. RESULTS: The prescribing rate increased to 100% within 6 weeks and has been sustained for 7 months. CONCLUSIONS: Keys to success were pharmacy collaboration, use of an electronic medical record for a standardized order set, and rapid identification and mitigation of failures. Rapid implementation of evidence-based practices is possible using improvement science methods.

AIM: Implementing international guidelines guarantees high standards of clinical care. A group of experts developed an algorithm to drive the management of common gastrointestinal symptoms in infancyby paediatricians and general practitioners. METHODS: The algorithm started from the evidence-based recommendations of the European Society of Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Infectious Diseases and an updated review of the literature. We used the structured quantitative method of nominal group technique to reach a consensus. RESULTS: A practical algorithm for the management of infants with acute diarrhoea was designed based on theconsensus reached for each statement. The management of an infant with acute diarrhoeashould include a sequence of actions: 1) a semi-quantitative estimate of infant dehydration through validated clinical scores, 2) rehydration therapy and early re-feedingwith breast milk or regular formula and 3) effective agents to reduce the severity and duration of the diarrhoea. Finally, in children with prolonged diarrhoea, the search for aetiology should include persistent infections or reinfections, cows' milk protein allergy and celiac diseases. Lactose should always be withdrawn. CONCLUSION: This algorithm provides an evidence-based sequence of interventions to optimisethe management of infants with acute diarrhoea. This article is protected by copyright. All rights reserved.

Objective: Acute gastroenteritis (AGE) is a major cause of child mortality and morbidity. This study aimed at systematically reviewing clinical practice guidelines (CPGs) on AGE to compare recommendations and provide the basis for developing single universal guidelines.Methods: CPGs were identified by searching MEDLINE, Cochrane-Library, National Guideline Clearinghouse and Web sites of relevant societies/organizations producing and/or endorsing CPGs.Results: The definition of AGE varies among the 15 CPGs identified. The parameters most frequently recommended to assess dehydration are skin turgor and sunken eyes (11/15, 73.3%), general appearance (11/15, 66.6%), capillary refill time, and mucous membranes appearance (9/15, 60%). Oral rehydration solution is universally recognized as first-line treatment. The majority of CPGs recommend hypo-osmolar (Na+ 45–60 mmol/L, 11/15, 66.6 %) or low-osmolality (Na+ 75 mmol/L, 9/15, 60%) solutions. In children who fail oral rehydration, most CPGs suggest intravenous rehydration (66.6%). However, nasogastric tube insertion for fluid administration is preferred according by 5/15 CPGs (33.3%). Changes in diet and withdrawal of food are discouraged by all CPGs, and early refeeding is strongly recommended in 13 of 15 (86.7%). Zinc is recommended as an adjunct to ORS by 10 of 15 (66.6%) CPGs, most of them from low-income countries. Probiotics are considered by 9 of 15 (60%) CPGs, 5 from high-income countries. Antiemetics are not recommended in 9 of 15 (60%) CPGs. Routine use of antibiotics is discouraged.Conclusions: Key recommendations for the management of AGE in children are similar in CPGs. Together with accurate review of evidence-base this may represent a starting point for developing universal recommendations for the management of children with AGE worldwide.

Background Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children's hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions. Methods A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8: 00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected. Results The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% -53.8%). We describe antibiotic prescriptions separately in neonates ( = 30 days to

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

SummaryA case of visceral disseminated infection by Mycobacterium sherrisii in an African HIV-infected adolescent with multiple abdominal abscesses is reported. Despite multiple drug resistance to first-line antibiotics in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with appropriate antiretroviral treatment, resulted in clinical and radiological cure after 19 months of therapy and follow-up.

The stimulating role that the gut microbiota exerts on human life and its potential involvement in the pathophysiology of several diseases. The human microbiota exerts important immune, metabolic, trophic, and protective functions that are now interpreted with a model of symbiosis between the host and intestinal microbes. The gut microbiota may be seen as a "dynamic hidden organ" whose structure varies according to many factors including genetic factors, age, nutrition, disease and related treatments. In contrast, the adult microbiota is complex, but relatively stable and similar among individuals. Intestinal colonization begins at birth with amniotic membrane rupture or perhaps even before, according to a very recent experimental hypothesis. Irritable bowel syndrome (IBS) is a common gastrointestinal complaint in adults and children. This chapter introduces the concept of fecal microbiota transplantation (FMT) for the treatment of subjects with the metabolic syndrome. FMT is the major barrier to the large dissemination of the treatment for intestinal diseases.

INTRODUCTION: Tuberculosis is a major problem in children depending on their families for management and a re-emerging disease in low incidence countries, where foreign-born cases account for a large proportion of cases. METHODS: We investigated socioeconomic features of families and their impact on management and outcome of children with tuberculosis disease seen at a tertiary care centre for paediatric infectious diseases in Italy. RESULTS: Forty-nine Italian and 30 foreign-origin children were included. Children from foreign families had more complicated diseases (20 % vs 0 %; P = 0.002), harbored more drug resistant strains (20 % vs 2 %; P = 0.011), showed longer hospital stay (12 ± 13.1 vs 5.1 ± 6.5 days; P = 0.012) and higher proportion of missed medical visits (15.7 ± 16 vs 8.6 ± 9.6; P ≤ 0.042) than those from Italian families. Harboring drug resistant strains was an independent risk factor for complicated disease course (OR: 72.98; 95 %CI: 1.54–3468.58; P = 0.029), and this risk is higher in children from Eastern Europe (OR: 10.16; 95 %CI: 1.7–61.9; P = 0.012). CONCLUSIONS: Children from immigrant families showed an increased risk of complicated course of tuberculosis due to a higher rate of resistant strains and raise problems in clinical management. Specific protocols are needed to support these populations ensuring easy access to health services and monitoring.

Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. This document describes the recommendations of a group of scientific societies on the therapeutic approach to pediatric MDR- and XDR-TB. On the basis of a systematic literature review and their personal clinical experience, the experts recommend that children with active TB caused by a drug-resistant strain of Mycobacterium tuberculosis should always be referred to a specialised centre because of the complexity of patient management, the paucity of pediatric data, and the high incidence of adverse events due to second-line anti-TB treatment.

BACKGROUND: The spread of carbapenem-resistant Enterobacteriaceae (CRE) is a health problem of major concern. CRE-related infections have significant morbidity and mortality, but data on CRE infection in pediatric population are limited. The aim of this study was to analyze epidemiologic and clinical characteristics, risk factors, therapeutic options and outcome of CRE infections in children in Italy. METHODS: We performed a retrospective, multicenter, observational study of children with confirmed CRE infection or colonization admitted between January 1, 2011, and March 1, 2014, to 7 Italian pediatric centers. RESULTS: Sixty-nine patients presenting 74 CRE infections and/or colonization were included. The most frequently isolated strain was Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Children with CRE infections had longer length of stay in hospital (P < 0.001), duration of disease (P = 0.001) and antimicrobial treatment (P < 0.001) than colonized children. Oncologic/immunosuppressive conditions are one of the factors significantly associated with a fatal outcome among children with CRE infections. CONCLUSIONS: Our study confirms that CRE infections affect mostly children with oncologic diseases and immunosuppression. Controlled studies in large cohorts are needed to evaluate the best therapeutic options and to assess further risk factors influencing outcomes and the survival of pediatric patients with infections caused by CRE.

Tuberculosis (TB) is a re-emerging health problem in developed countries. This paper is part of large guidelines on the global management of TB in children, by a group of scientific societies. It describes the indications to hospitalization of children with suspected or diagnosed TB, the isolation measures, hospital discharge, and re-admission into the community. Using the Consensus Conference method, relevant publications in English were identified by means of a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Available data on indications to hospitalization were mainly indirect and largely derived from observational studies. They include: (1) host-related risk factors, the main being age

OBJECTIVE: To assess the quality of guidelines, consensus statements and systematic reviews on flu and pneumococcal immunisations in HIV-infected children. METHOD: The authors screened PubMed and Embase databases until the year 2009 for guidelines, consensus statements and systematic reviews on flu and pneumococcal immunisations in HIV-infected patients. The authors also explored relevant websites of agencies/institutions involved with HIV infection, immunisation or guidelines. The Appraisal of Guidelines for Research and Evaluation instrument and the checklists of the Scottish Intercollegiate Guidelines Network were used to evaluate the scientific quality of guidelines and systematic reviews. RESULTS: Eighteen articles were identified. Only one guideline was of good overall quality. Generally the weakest domains were 'Applicability' and 'Editorial Independence.' Although of poor methodological quality, the main recommendations on flu and pneumococcus vaccinations were similar. There were minor differences in the type of pneumococcal vaccines in relation to patient's age, namely based on the settings in which recommendations were produced. CONCLUSIONS: Although guidelines and systematic reviews on flu and pneumococcal vaccination in HIV-infected children came from authoritative institutions, their overall quality is poor, with the weakest fields being the methodological domains.

AIM: The aim of the study was to assess the quality of clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, a validated international tool. MATERIALS AND METHODS: CPGs were identified by searching MEDLINE (1966-January 2009) and Embase (1988-January 2009), CPG databases, and relevant Web sites of agencies and organizations that produce and/or endorse guidelines. Included in the study were CPGs in English that addressed the management of acute gastroenteritis in children. Retrieved CPGs were evaluated with the AGREE instrument for quality assessment by 6 independent reviewers. AGREE consists of 6 domains for a total of 23 items. RESULTS: Nine CPGs were identified. Four were evidence based (EB) and 2 of these included tables of evidence. Eight CPGs (88%) scored