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Crohn’s disease (CD) and Takayasu arteritis (TA) are two distinct clinical entities. Τhe likelihood of both diseases coexisting is low, and although CD co-occurs with all types of vasculitis, TA is the most common subtype. Herein, the case of a 15-year-old female, diagnosed with TA following an initial diagnosis of CD, is reported. A review of the literature, including a systemic review of the case reports and case series of children and adolescents up to the age of 21, with both CD and TA, follows the case description. In total, 28 cases of TA and CD were retrieved. The median age of patients was 14.8 years, they were mostly females (72%) and the median time between the two diagnoses was 3.7 years. In the majority of cases, CD was diagnosed first and TA followed. Computed tomography angiography and magnetic resonance angiography were the preferred imaging modalities to assist diagnosis. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults. © The authors 2022.

BACKGROUND: Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. METHODS: NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was -10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT02790996). FINDINGS: Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference -7% [95% CI -15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). INTERPRETATION: In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. FUNDING: EU Seventh Framework Programme for research, technological development and demonstration.

Background and Purpose: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Methods: We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS–CVST versus non-TTS–CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS–CVST compared to non-TTS–CVST; and (4) the dependency or death at discharge among TTS–CVST compared to non-TTS–CVST cases. Results: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS–CVST (OR: 52.34, 95% CI 9.58–285.98). TTS–CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96–44.60) and death or dependency at discharge compared to non-TTS–CVST (OR: 6.70; 95% CI 3.15–14.26). TTS–CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI − 12.64 to − 0.45], affecting younger patients (MD:-9.00 years; 95% CI − 14.02 to − 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26–4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31–9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51–39.98) compared to non-TTS–CVST cases. Conclusions: TTS–CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS–CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS–CVST cases following COVID-19 vaccination. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)–induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma. Aim: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma. Methods: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots. Results: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24–7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48–4.99). Conclusion: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma. © 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background Aiming to the containment of the coronavirus disease 2019 (COVID-19) pandemic, governments worldwide have implemented a series of non-pharmaceutical interventions. Many of them and especially school closures have impacted the circulation of multiple airborne pathogens among children and adolescents. This study investigates the incidence of influenza and invasive meningococcal disease among children aged 0-14 years in Greece during the COVID-19 pandemic. Methods Data regarding the number of influenza-like illness cases, influenza-related paediatric intensive care unit (PICU) admissions and invasive meningococcal disease cases among children 0-14 years old were obtained from the National Public Health Organization. The incidence of the two diseases during the COVID-19 pandemic period (2020/2021) was compared with that of the six preceding seasons (2014-2019). Results A notable decrease was observed in both influenza and invasive meningococcal disease cases during the period 2020/2021 compared with the years 2014-2019. The mean annual rate of influenza-like illness cases and influenza-related PICU admissions in children 0-14 years old has reduced by 66.9% and 100%, respectively, while the mean annual invasive meningococcal disease rate has declined by 70%. Both weekly influenza-like illness and monthly invasive meningococcal disease rates were significantly decreased. Conclusions The activity of influenza and invasive meningococcal disease in the children and adolescents of Greece has decreased during the COVID-19 pandemic period. Reduced transmission is likely related to the public health measures that were implemented to control the pandemic. The value of these measures may have relevance to the future management of influenza or invasive meningococcal disease epidemics. © Author(s) (or their employer(s)) 2022.

BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

OBJECTIVES: Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct-acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high-risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness. METHODS: Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high-risk groups alone were excluded. RESULTS: Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P

BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. Copyright © 2021 Massachusetts Medical Society.

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point-of-care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza-like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0–16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision-making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01–9.82; p =.046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06–20.43; p =.041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs. © 2020 Wiley Periodicals LLC

Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing serious morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV), studies conducted so far conclude that there is limited awareness in both the medical community and public of cCMV infection. The aim of this systematic review was to assess the knowledge and awareness of cCMV among pregnant women and healthcare providers during the last decade. Methods: A literature search was performed in PubMed and Scopus, including studies published between 2011 and 2020. Eligibility criteria included articles focusing on either pregnant women or healthcare providers and reporting data about cCMV awareness. We included cross-sectional and interventional studies. Study quality was assessed using the Study Quality Assessment Tools by National Institute of Health. Results: Overall, 23 studies fulfilled the inclusion criteria, 13 studies referred to pregnant women and 10 to healthcare providers. A total of 6521 pregnant women and 3609 healthcare providers were included. The level of awareness of pregnant women about cCMV was low to moderate. However, pregnant women showed willingness to adopt hygiene strategies following interventional-educational practices. Concurrently, awareness among healthcare providers varied depending on the specialty. Nonetheless, a great proportion admitted feeling inadequate in advising pregnant women for cCMV screening and prevention. Conclusion: The role of healthcare providers in growing awareness among pregnant women is of paramount importance. Due to the lack of an effective vaccine as yet, education of women regarding hygiene measures is currently the best strategy to prevent cCMV disease. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Background: Measles outbreaks pose significant risk for those unvaccinated. Patients and methods: Measles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination. Long term effects were evaluated 12 months post vaccination. Results: Twenty-seven children were vaccinated (36 doses given). Half of parents (51.8%) reported no adverse events following immunization. Adverse events included afebrile seizures (6/36), fever alone (5/36) and febrile seizures (5/36). Two children required hospitalization. Quadrivalent measles-containing vaccine combined with varicella was associated with febrile seizures (p = 0.04). No child needed adjustment of the anti-epileptic treatment or exhibited developmental regression. Conclusion: In a series of children with prior severe neurologic disease, the safety-tolerability profile of vaccines containing a measles vaccine component suggests that vaccination is justified. Main side effect was seizure aggravation in children with known epileptic disease. © 2020 Elsevier Ltd

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants. Copyright © 2021 Abu-Raya, Madhi, Omer, Amirthalingam, Giles, Flanagan, Zimmermann, O’Ryan, Safadi, Papaevangelou, Maertens, Wanlapakorn, Diaz-Brito, Tommelein and Esposito.

Cardiopulmonary resuscitation (CPR) is an emergency lifesaving endeavor, performed in either the hospital or outpatient settings, that significantly improves outcomes and survival rates when performed in a timely fashion. As with any other medical procedure, CPR can bear potential risks not only for the patient but also for the rescuer. Among those risks, transmission of an infectious agent has been one of the most compelling triggers of reluctance to perform CPR among providers. The concern for transmission of an infection from the resuscitated subject may impede prompt initiation and implementation of CPR, compromising survival rates and neurological outcomes of the patients. Infections during CPR can be potentially acquired through airborne, droplet, contact, or hematogenous transmission. However, only a few cases of infection transmission have been actually reported globally. In this review, we present the available epidemiological findings on transmission of different pathogens during CPR and data on reluctance of health care workers to perform CPR. We also outline the levels of personal protective equipment and other protective measures according to potential infectious hazards that providers are potentially exposed to during CPR and summarize current guidelines on protection of CPR providers from international societies and stakeholders. Copyright © 2021 American Society for Microbiology. All Rights Reserved.

Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty Methods: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset

A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the “30–49” year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: The maturation of innate immune responses in health and atopy is still incompletely understood. Methods: We aimed to evaluate age-related trajectories of the TLR3 and TLR7/8 pathways from birth to adulthood and whether these differ between healthy and atopic individuals. Peripheral blood mononuclear cells (PBMCs) were isolated from 39 otherwise healthy, atopic and 39 non-atopic subjects, aged 0–45 years. Selected cytokines involved in antiviral responses were measured by Luminex in culture supernatants of poly(I:C)- and R848-stimulated PBMCs. The non-parametric correlation between age and cytokine expression and differences in developmental trajectories between healthy and atopic subjects were estimated. Patterns of cytokine development were identified with principal component analysis. Results: Normal innate immune maturation entails significant and progressive age-related changes in the production of IL-1β, TNF-α, MIP-1β, MCP-3, IP-10, IL-10, IL-12p70, and IFN-γ upon TLR3 and/or TLR7/8 stimulation. Individual cytokines made small contributions to the observed variability; chemokines MCP-3 and IP-10 were key contributors. The development of these pathways deviated in atopic subjects with significant differences observed in the trajectories of IL-1β, MIP-1β, and IL-10 syntheses. Conclusion: TLR3 and TLR7/8 pathways mature during childhood, while atopy is associated with an abnormal maturation pattern. Suboptimal responses in Th1, inflammatory cytokine, and chemokine production may be implicated in poor antiviral immunity in atopics. Moreover, the deficient maturation of IL-10 synthesis may be implicated in the breaking of tolerance, characterizing the onset of atopic disease. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

As most children infected with SARS-CoV-2 present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and etiology of molecular testing for SARS-CoV-2 in Greek pediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in pediatric departments between March and June 2020. A total of 65 pediatric departments participated to the study, representing 4901 children who were tested for SARS-CoV-2 and 90 (1.8%) were positive. Most pediatric cases were associated with topical outbreaks. Adolescents 11-16 years had the highest positivity rate (3.6%) followed by children 6-10 years (1.9%). However, since testing rate significantly differed between age groups, the modified incidence of SARS-CoV-2 infection per age group was highest in infants 1 year (19.25/105 population). Most children tested presented with fever (70.9%), respiratory (50.1%) or gastrointestinal symptoms (28.1%). Significant differences were detected between public and private hospitals regarding positivity rate (2.34% vs 0.39%, P-value: 0.001). Significant variation in SARS-CoV-2 molecular testing positivity rate and incidence between age groups indicate discrepancies in risk factors among different age groups that shall be considered when ordering molecular testing. © 2021 Cambridge University Press. All rights reserved.

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and-resource intervention to reduce antibiotic use in Greek NICUs implementing a “low-hanging fruit” approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a “low-hanging fruit” approach. In resource-limited settings, similar targeted stewardship interventions can be applied. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.

Group B streptococcus (GBS) is a leading cause of serious neonatal infections. Maternal GBS colonization is associated with early-and late-onset neonatal disease (EOD/LOD). In Greece, a screening-based strategy is recommended, in which concurrent vaginal-rectal cultures should be obtained between 36 0/7 and 37 6/7 weeks’ gestation. We sought to examine the level of adherence to the GBS screening guidelines and estimate the prevalence of GBS colonization among pregnant women. Although in Greece the screening-based strategy is followed, we also examined known EOD risk factors and linked them to GBS colonization. A cross-sectional study of 604 women postpartum in three hospitals and maternity clinics was conducted. Following written informed consent, data were collected via a short self-completed questionnaire and review of patients’ records. In 34.6% of the enrolled pregnant women, no culture had been taken. Of the remaining, 12.8% had proper vaginal-rectal sample collections. The overall maternal colonization rate was 9.6%. At least one risk factor for EOD was identified in 12.6% of participants. The presence of risk factors was associated with positive cultures (p = 0.014). The rate of culture collection did not differ between women with or without an EOD risk factor. Adherence to a universal screening of pregnant women with vaginal-rectal cultures was poor. Despite probable underestimation of GBS carrier status, almost 1 in 10 participants were GBS positive during pregnancy. Screening of women with risk factors for EOD should, at least, be prioritized to achieve prevention and prompt intervention of EOD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: Cytomegalovirus (CMV) is the most common congenital viral infection and is regarded as the leading nongenetic cause of sensorineural hearing loss. Currently, international consensuses discourage prenatal screening of pregnant women. However, in few countries mainly in Southern Europe, screening of pregnant women for CMV infection is common practice. Management of women found with IgG+/IgM + and IgG avidity titers in the grey zone during first trimester causes significant stress to both families and health care workers. Patients and methods: Pregnant women referred to our outpatient clinic with the diagnosis of acute CMV infection (IgM+/IgG+) during early pregnancy (gestational age ≤ 14 weeks) and IgG avidity in the grey zone were prospectively followed. The administration of CMV-HIG was offered and follow-up included fetal U/S, amniocentesis for CMV-DNA detection and MRI when appropriate. All neonates were examined by urine PCR and prospectively followed according to existing recommendations. Results: Ninety women (mean age 30.8 years) were retrospectively analyzed. Most (79.6%) received CMV-HIG. Four women terminated pregnancy (2 unrelated to CMV reasons and 2 because of CMV-positive amniotic fluid). Eighty-seven babies were born asymptomatic. Two newborns were diagnosed with congenital CMV infection. The overall transmission rate was 4.4%; 4.3 versus 5.6% for those receiving or not CMV-HIG. No adverse outcomes were detected during follow-up (median 24 months). Maternal age, parity, detection of maternal CMV-viremia upon diagnosis, delay between diagnosis and consultation, gestational week of first consultation, administration of CMV-HIG and number of doses were not associated with the risk of vertical CMV transmission. Discussions: Vertical transmission of CMV infection in pregnancies with acute CMV-infection and IgG avidity titers in the grey zone during first trimester was 4.4%, higher than that in infants born post nonprimary infection (NPI) during pregnancy. More powered studies are needed to prove a significant reduction in transmission using CMV-HIG. © 2019 Informa UK Limited, trading as Taylor & Francis Group.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit. © 2020 John Wiley & Sons Ltd

Rotor syndrome (RS) is a benign, inherited, commonly misdiagnosed cause of conjugated hyperbilirubinemia whose identification prevents unnecessary invasive investigations. We present the case of a 3-y-old boy with phenotypic and laboratory findings of RS but negative genetic test results, whose diagnosis was confirmed by hepatobiliary scintigraphy. © 2021 Society of Nuclear Medicine Inc.. All rights reserved.

Background: There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children. Methods: We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values. Results: We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants

Background: Congenital cytomegalovirus infection (cCMV) represents the most common viral congenital infection and non-genetic cause of childhood sensorineural hearing loss (SNHL). Newborns with symptomatic cCMV disease are at high risk for long term neurologic sequalae. However, most newborns with cCMV are asymptomatic and have a significantly better prognosis. About 10 % may develop sequalae, mainly SNHL. Objectives: This study aimed to evaluate risk factors associated with the development of sensorineural hearing loss, in children with asymptomatic congenital CMV infection. Study Design: A total of 70 patients with asymptomatic cCMV were retrospectively evaluated. Maternal age, type and trimester of maternal infection, maternal or newborn treatment as well as gestational age and anthropometric measures of newborns were examined as predictors of SNHL. Results: The incidence of SNHL in children with asymptomatic cCMV correlated with low birthweight as well as with both birth weight and head circumference low z-scores adjusted for gestational age. Logistic regression analysis confirmed these results. There was no association between type or trimester of maternal infection and the development of SNHL. Discussion: Study results underscore the need for biomarkers to identify asymptomatic cCMV infants at risk for SNHL development, suggesting that z-scores of birth weight and head circumference adjusted for gestational age may be examined as such in larger cohorts. © 2020 Elsevier B.V.

Loss-of-function mutations of IGSF1 are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69 years for evaluation of obesity. Previous thyroid function evaluation suggested CeH [FT4 0.6 ng/mL, thyroid-stimulating hormone (TSH) 2.2 mIU/L] but his physician took no action. At presentation he was clinically and biochemically euthyroid, prepubertal and obese. Serum prolactin (PRL) was undetectable. Biochemistry was normal except for mild hypercholesterolemia, total cholesterol 198 mg/dL. Subsequently FT4 and TSH levels fluctuated between 0.72-0.95 ng/dL (normal 0.8-2.0) and 1.94-5.77 mIU/L (normal 0.3-5.0), respectively. Sequencing of IGSF1 gene revealed a novel genetic change c.3805C>T in exon 19; substitution of amino acid Arginine at position 1269 with a premature «stop» codon resulting in an altered protein product. The patient additionally presented delayed adrenarche, low height velocity that resolved spontaneously and normal pubertal onset associated with increased FSH levels. At 14 years-of-age, while the patient was at Tanner stage 4, PRL levels became detectable, rising gradually to 2.3 ng/mL at last examination. Thyroxine replacement therapy resulted in decrease in total cholesterol 103 mg/dL. A high index of suspicion for the disorder is needed since several measurements of thyroid function may be required for CeH to be disclosed. The patient’s normal FT4 levels and normal intelligence would have resulted in a missed diagnosis if the serum PRL levels had not been measured. This case highlights the importance of measuring PRL in a boy with low normal FT4 and normal TSH levels. © 2020 by Turkish Pediatric Endocrinology and Diabetes Society.

Objective: To estimate the attributable mortality, length of stay (LOS), and healthcare cost of pediatric and neonatal healthcare-acquired bloodstream infections (HA-BSIs).Design: A systematic review and meta-analysis.Methods: A systematic search (January 2000-September 2018) was conducted in PubMed, Cochrane, and CINAHL databases. Reference lists of selected articles were screened to identify additional studies. Case-control or cohort studies were eligible for inclusion when full text was available in English and data for at least 1 of the following criteria were provided: attributable or excess LOS, healthcare cost, or mortality rate due to HA-BSI. Study quality was evaluated using the Critical Appraisal Skills Programme Tool (CASP). Study selection and quality assessment were conducted by 2 independent researchers, and a third researcher was consulted to resolve any disagreements. Fixed- or random-effect models, as appropriate, were used to synthesize data. Heterogeneity and publication bias were evaluated.Results: In total, 21 studies were included in the systematic review and 13 studies were included in the meta-analysis. Attributable mean LOS ranged between 4 and 27.8 days; healthcare cost ranged between 1,642.16 and 160,804 (2019 USD) per patient with HA-BSI; and mortality rate ranged between 1.43% and 24%. The pooled mean attributable hospital LOS was 16.91 days (95% confidence interval [CI], 13.70-20.11) and the pooled attributable mortality rate was 8% (95% CI, 6-9). A meta-analysis was not conducted for cost due to lack of eligible studies.Conclusions: Pediatric HA-BSIs have a significant impact on mortality, LOS, and healthcare cost, further highlighting the need for implementation of HA-BSI prevention strategies. © 2020 by The Society for Healthcare Epidemiology of America.