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Victor Daniel Miron,1 Oana Săndulescu,1,2 Mihai Craiu1,3 1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 2National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania; 3National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Bucharest, RomaniaCorrespondence: Victor Daniel Miron, Carol Davila University of Medicine and Pharmacy, 127, Lacul Tei Street, Second District, Bucharest, 020382, Romania, Email victor.miron@drd.umfcd.ro

Allergic severe asthma is rare disease among young children. Most of these patients should be evaluated by an expert and treatment has to be tailored according to evolutive phenotype. One option for adult patients with such a condition is adding omalizumab [anti-IgE antibodies] to step IV GINA medication. Authors present a small pediatric series of severe uncontrolled asthmatic patients treated with an average 12 months course of omalizumab. Demographics, clinical features and comorbid conditions are documented. Due to safety issues all patients were monitored during and after omalizumab injection in the resuscitation module of the Emergency Department from a tertiary referral pediatric hospital. Monitoring and protocol are presented. All children had a positive outcome, three with partial control and one with complete control. No serious side effects were observed. Low grade fever was easily controlled with trivial antipyretics. Conclusion: anti-IgE monoclonal antibodies in severe allergic asthma patients are efficacious also in children and represent a safe and solid alternative for long-term oral corticosteroid treatment. [ABSTRACT FROM AUTHOR]

WHO data are still documenting high mortality rate due to acute gastroenteritis in children, worldwide. In the last two decades in Romania there were significant improvements in therapeutic management of the most severe cases, with a 10-fold decrease in mortality rate inflicted by acute hypovolemic shock. The present paper is a practical approach of major emergencies related to acute dehydration, according to PALS (Pediatric Advanced Life Support) and RANP (Reanimation Avancee Neonatale et Pediatrique) guidelines. Pathogenetic mechanisms of acute dehydration are discussed and clinical correlations are presented for hyponatremic, izonatremic and hypernatremic dehydration. Vascular access aspects, amount and nature of fluids used during vascular expansion and infusion rates are briefly summarized. [ABSTRACT FROM AUTHOR]

Introduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs., Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023. We estimated rVE of the second versus first COVID-19 vaccine booster dose against SARS-CoV-2 infection, overall, by time since second booster and restricted to the bivalent vaccines only. Using Cox regression, we calculated the rVE as (1-hazard ratio)*100, adjusting for hospital, age, sex, prior SARS-CoV-2 infection and at least one underlying condition., Results: Among the 979 included HCWs eligible for a second booster vaccination, 392 (40 %) received it and 192 (20 %) presented an infection during the study period. The rVE of the second versus first booster dose was -5 % (95 %CI: -46; 25) overall, 3 % (-46; 36) in the 7-89 days after receiving the second booster dose. The rVE was 11 % (-43; 45) when restricted to the use of bivalent vaccines only., Conclusion: The bivalent COVID-19 could have reduced the risk of SARS-CoV-2 infection among HCWs by 11 %. However, we note the limitation of imprecise rVE estimates due to the proportion of monovalent vaccine used in the study, the small sample size and the study being conducted during the predominant circulation of XBB.1.5 sub-lineage. COVID-19 vaccine effectiveness studies in HCWs can provide important evidence to inform the optimal timing and the use of updated COVID-19 vaccines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: APU reported payment under EMA DARWIN EU project outside of the submitted work. MLM, AM, LCC reported additional support received from ISIDORe (EATRIS) Network for carrying out the local SARS-CoV-2 sequencing. CPP reported speaker fees from Pfizer and MSD. SAF reported speaker fees from and participation in Advisory board of Pfizer, MSD and Gilead. CMA reported speaker fees from MSD, Pfizer and Sanofi. JS reported support for attending ESID conference 2022 from Takeda Pharmaceutical. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May-6 September 2021), Delta (7 September-14 December 2021), and Omicron (15 December 2021-2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: -25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7-90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs.

Background: Acute viral respiratory tract infections constitute a significant challenge in pediatric healthcare globally, with rhinovirus representing one of the primary etiological agents. In this context, we conducted a study with the objective of identifying the clinical characteristics and outcomes of rhinovirus infection in comparison with other respiratory viruses in children hospitalized in one of the largest pediatric hospitals in the capital of Romania., Methods: We conducted a retrospective study among children hospitalized for influenza-like illness symptoms and who were tested by multiplex RT-PCR with a nasopharyngeal swab between May 2020 and December 2021., Results: A total of 496 children were eligible for inclusion in the study, and the positivity rate for at least one virus was 58.5%. The rhinovirus was identified in 138 patients (median age 12.5 months), representing 27.8% of all children tested and 49.3% of all positive samples. Although the clinical features of children with rhinovirus were dominated by cough (63.7%) and dyspnea (51.6%), no symptoms were identified that were strongly associated with rhinovirus infection in comparison to other respiratory viruses. The probability of receiving an antibiotic prescription was 1.92 times lower ( p = 0.011) in children who tested positive for rhinovirus compared to children with negative RT-PCR results. The incidence of acute bronchiolitis or acute bronchitis, acute respiratory failure, and acute otitis media was higher among rhinovirus-positive children than among those who tested negative via RT-PCR. However, the incidence of these conditions was similar among children who tested positive for other respiratory viruses., Conclusions: Rhinovirus was the most prevalent virus identified in children hospitalized with influenza-like illness symptoms. The utilization of multiplex RT-PCR molecular tests is instrumental in elucidating etiology with precision and implementation of these advanced diagnostic methods, which can bring significant benefits in practice. A positive result for rhinovirus helps to reduce the unnecessary administration of antibiotics and optimizes patient management, thus decreasing the risk of severe complications such as acute respiratory failure and acute otitis media.

Background: Our study aimed to explore the way artificial intelligence (AI) utilization is perceived in pediatric medicine, examining its acceptance among patients (in this case represented by their adult parents), and identify the challenges it presents in order to understand the factors influencing its adoption in clinical settings., Methods: A structured questionnaire was applied to caregivers (parents or grandparents) of children who presented in tertiary pediatric clinics., Results: The most significant differentiations were identified in relation to the level of education (e.g., aversion to AI involvement was 22.2% among those with postgraduate degrees, 43.9% among those with university degrees, and 54.5% among those who only completed high school). The greatest fear among respondents regarding the medical use of AI was related to the possibility of errors occurring (70.1%)., Conclusions: The general attitude toward the use of AI can be considered positive, provided that it remains human-supervised, and that the technology used is explained in detail by the physician. However, there were large differences among groups (mainly defined by education level) in the way AI is perceived and accepted.

Infants are a unique pediatric group due to their high hospitalization rates and unfavorable outcomes from acute infectious diseases. Understanding the clinical differences and aftereffects of SARS-CoV-2 in comparison to other prevalent viruses in this age group, like RSV, is crucial for effective management. We conducted a retrospective case-control study of infants hospitalized with SARS-CoV-2 or respiratory syncytial virus (RSV) infection in one year, in a tertiary pediatric hospital in Bucharest, Romania. A total of 188 infants were included in the analysis in a 1:1 ratio (94 with SARS-CoV-2 infection and 94 with RSV infection). Infants with COVID-19 were 10.2 times more likely to have fever ( p < 0.001) and 2.4 times more likely to have diarrhea ( p = 0.016). Conversely, infants with RSV were 2.5 times more likely to have a cough ( p < 0.001), 3.0 times more likely to have nasal congestion ( p < 0.001), and 14.7 times more likely to present with dyspnea ( p < 0.001). Increased lymphocyte count was more common in infants with RSV ( p = 0.008), while lymphopenia was more frequent in infants with SARS-CoV-2 ( p = 0.011). The median length of hospital stay was one day longer in infants with RSV infection (5 days vs. 4 days). Overall, infants with RSV infection had a 27.3-fold increased risk of developing respiratory failure ( p < 0.001), while infants with COVID-19 had a 5.8-fold increased risk of laryngitis ( p = 0.003). Our findings suggest that infants with SARS-CoV-2 infection may present with polymorphic symptoms, mostly dominated by fever, whereas infants with RSV often present with respiratory symptoms. Laboratory differentiation between the two infections is challenging; therefore, the use of rapid antigen or molecular diagnostic tests is crucial for accurate diagnosis, epidemiologically appropriate measures, and effective management. Continued surveillance of both viruses in infants, and beyond, and the implementation of specific control measures are needed to mitigate their impact on this vulnerable pediatric group.

Background and Objectives: Childhood obesity has been increasing at a worrisome pace and emerging as a non-infectious pandemic in the pediatric population in recent years. Raising awareness on this problem is of utmost importance, in order to take action to control body weight from an early age. Materials and Methods: We performed a retrospective study among overweight or obese children evaluated on an outpatient basis in the Department of Pediatric Endocrinology of a tertiary care hospital in Bucharest Romania in 2021 in order to identify laboratory changes occurring according to age and sex. Results: A total of 268 children were included in the analysis, with a median age of 10.9 years (IQR: 8.3, 13.3 years); 61.8% were obese and 38.2% overweight. We identified a subclinical pro-inflammatory status characterized by increased neutrophil count (12.7%) and increased C-reactive protein (16.4%). Biochemically, we identified the highest increases for uric acid (35.4%). More than half of the children included in the study had dyslipidemia-specific changes: high low-density lipoprotein cholesterol (LDL) (50.0%), low high-density lipoprotein cholesterol (HDL) (58.9%) and increased triglyceride levels (12.7%), especially children with a body mass-index (BMI) percentile above 95%. Increased thyroid stimulating hormone (TSH) was identified in 20.3% and low thyroxine (T4) level in 13.4%, especially in females. Conclusions: Early measures to control excess body weight are needed since preventing obesity is easier than treating it. However, this is often difficult to do in our country because parents frequently do not recognize the problem until it is advanced. Furthermore, doctors are not always adequately prepared and sometimes they do not have the support of the health systems to provide children in need with the adequate care. Educational strategies and awareness of issue should be revisited in current post-pandemic context that facilitates increase of obesity prevalence in children. Increase of efficient communication could be achieved by pointing to these objective findings.

Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein-Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients.

This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.

The COVID-19 pandemic, through the restrictions and the non-pharmaceutical interventions implemented, has importantly impacted the circulation and epidemiology of respiratory viruses. Specifically, the 2020/21 season was entirely dominated by SARS-CoV-2, while influenza activity reached an all-time low, despite initial warnings that a double concurrent epidemic could be possible. The current season, 2021/22, started with the shift of circulating SARS-CoV-2 variants from delta to omicron, which then rapidly spread globally, as most countries, including Romania, removed all restrictions and compulsory non-pharmaceutical interventions. In this report we present the clinical reality observed in March 2022 in a tertiary paediatric hospital in Bucharest, Romania, where we observed a sudden surge in influenza cases, after two consecutive years (March 2020 to March 2022) when influenza had stopped circulating in our country. Thus, in March 2022 the positivity rate of rapid influenza antigen tests unexpectedly increased to 33.5%, paralleled by a decrease to 7.5% in the positivity rate of rapid SARS-CoV-2 antigen tests. This significant increase in the influenza attack rate was observed from the first week (14.9% positivity rate), through the fourth week of March (42.1% positivity rate, p < 0.001), while the COVID-19 attack rate displayed a significant decreasing trend (from 11.2% to 4.8%, p < 0.001). These data serve as a warning about relaxing restrictions in a precipitous approach with minimised vigilance. The evolution of these observations needs to be followed very carefully in all countries, particularly in settings where epidemiological interactions and non-pharmaceutical interventions have so far led to the extensive circulation of only one of these viruses, and we should now be prepared to perform a correct differential diagnosis between influenza and COVID-19, in order to ensure the best quality of care and personalized management of each case of respiratory infection. The results of active influenza surveillance studies for the whole 2021/22 season are awaited, in order to quantify the joint influenza—COVID-19 burden among children.

The COVID-19 pandemic has had a significant impact on the pediatric population, particularly on their access to health services. We conducted a retrospective study to assess the influence that the pandemic, and its related containment and mitigation public health measures, had on pediatric emergencies and hospitalizations in a major tertiary pediatric hospital in Bucharest, Romania, during the first six months of the pandemic, March−August 2020, compared to the same period in 2019. In these first 6 months of the COVID-19 pandemic, the number of pediatric emergencies decreased 2.8-fold compared to the same period in 2019, but the proportion of major emergencies increased significantly (p < 0.001). The number of admissions also decreased 3.3-fold in 2020, compared to 2019, but the risk of admission for lower respiratory tract infections and respiratory failure increased 1.3- and 2.3-fold, respectively. In conclusion, the restrictions imposed by the pandemic containment and mitigation plan not only had a significant impact on reducing emergency department presentations, but also on pediatric admissions in Romania. These data highlight the importance of maintaining optimal access to child health services when confronted with a public health threat, such as the COVID-19 pandemic. Active communication with parents, involving general practitioners, pediatricians, and authorities, is essential for managing children with acute signs of illness in the case of future restrictions or lockdown measures.

Vaccination is one of the most useful medical interventions for controlling certain infectious diseases. The aim of current research is to identify some of the drivers of vaccine hesitancy or acceptance in a rather skeptical European population by addressing parental perception on optional vaccination (OV) perception. Novel tools, delivered by social media, were used in our research attempt. A validated questionnaire was distributed online among parents. Parental knowledge, attitudes and perceptions of OV were analyzed. The majority of parent respondents (55.1%) showed very good knowledge about vaccination and vaccine-preventable diseases, and 76.0% stated that they had given at least one optional vaccine to at least one of their children. The most common optional vaccine administered was the rotavirus vaccine. The level of knowledge appeared to be related to compliance with OV. Concurrently, the rate of vaccine acceptance in the NIP (National Immunization Program) was not correlated with the level of parental knowledge. In total, a high percentage of parents (77.6%) believed that OV can bring an additional health safety benefit to their children. This study shows the need to involve the medical community in a steady dialogue with parents about OV. Raising awareness by presenting clear and understandable information could be a game-changing intervention in mitigating the public health impact of OV-preventable diseases.

Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant condition characterized by cutaneous, cerebral, and other multiorgan involvement. Aneurysms due to TSC pathogenic mechanism are rarely present, mainly aortic, renal, or intracranial and very few associated with peripheral circulation. A TSC patient, aged 31 years, who developed brachial and subclavian arteries aneurysms is presented. The question of a random association of the aneurysms with TSC versus aneurysms within pathogenic released mammalian target of rapamycin (mTOR) pathway effect was raised., Case Presentation: Patient's file, available from the age of six months, was analyzed for demonstration of the TSC diagnosis. Patient was examined, and cerebral magnetic resonance imaging (MRI) was repeated. Surgery and angiographic reports and images were reviewed. Pathology of the aneurysmal wall available from surgery was reexamined and special stainings and immunohistochemistry markers were applied. Genetic characterization of the patient was performed. Definite TSC was diagnosed based on major criteria [ungual fibromas, shagreen patch, cortical tubers, subependymal nodules (SENs), subependymal giant cell astrocytoma (SEGA)], minor criteria (confetti skin lesions, dental enamel pits, gingival fibromas), genetic result showing heterozygous variant in exon 8 of TSC1 gene (c.733C>T-p.Arg245*). Pathology analysis revealed markedly thickened aneurysmal wall due to smooth muscle cells (SMCs) proliferation in media and neoformation vessels with similar characteristics in the aneurysmal wall., Discussions and Conclusions: This is a rare case with aneurysms related to TSC, with an exceptional peripheral localization. Pathology exam is the key investigation in demonstrating the TSC-related pathogenic mechanism. A literature review showed 73 TSC cases presenting aneurysms published until now.

Introduction: Urinary tract infections (UTIs) are among the most common bacterial diseases of childhood with an increased frequency in infants and young children., Methods: We conducted a retrospective study of children diagnosed with UTI in the Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania between January 2017 and December 2019. We evaluated the patients' clinical characteristics, laboratory parameters and the resistance profile of the identified uropathogens., Results: A total of 264 children were included in the analysis. Females (71.6%, n=186) and infants (52.7%, n=139) were more commonly affected. The recurrence rate was 27.7% and was positively associated with the presence of renal malformations. Age under 1-year, increased leukocyte and neutrophil counts, and elevated C-reactive protein were associated with hospitalization. E. coli (80.3%, n=212) was the main etiological agent isolated, followed by Proteus mirabilis (9.8%, n=26) and Klebsiella spp. (6.4%, n=17). We identified increased resistance for all germs to common antibiotics used in pediatrics: ampicillin, amoxicillin/clavulanate, cefuroxime, ceftriaxone, and trimethoprim/sulfamethoxazole., Conclusions: We identified an increased resistance of uropathogens to antimicrobials commonly used in children. Reporting antimicrobial resistance from real-world clinical practice is necessary for accurate mapping and continuous updating of initial treatment recommendations until antibiogram results are received. In Romania and other countries, extensive studies are needed to follow up uropathogen resistance in both children and adults., Competing Interests: Conflicts of interest: All authors – none to declare., (GERMS.)

Introduction: The most common clinical manifestation of mango allergy is contact dermatitis, which can be localized or systemic. The sensitising substances that have long been suspected are alk(en)yl catechols and/or alk(en)yl resorcinols., Methods: We reviewed the original articles published on Pubmed, Embase and Cochrane Library before 15 September 2021, on the topic of contact allergy induced by mango and we synthesized the key data., Results: We found 12 case reports and four case series, with a total of 37 patients. Only seven of these cases were reported in patients from mango-cultivating countries, the other 30 were from countries where mango cultivation does not occur, and 26 were also from countries where poison ivy/oak are commonly found. We found that contact dermatitis may occur on the first exposure to mango due to previous sensitisation to urushiol-containing plants. The diagnosis was confirmed by patch testing in some of the cases. There was great heterogeneity between the reagents used., Conclusion: Mango fruit is frequently consumed, but mango induced contact dermatitis, the main hypersensitivity reaction induced by mango, is rare. Further data is necessary for a better understanding of sensitising substances and, consecutively, standardization of patch test reagents.

Competing Interests: There are no conflicts of interest.

Introduction: Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe., Methods: Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data., Results: We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals., Conclusion: Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident., Competing Interests: Conflict of interest: E. Santos-Valente has nothing to disclose. Conflict of interest: H. Buntrock-Döpke has nothing to disclose. Conflict of interest: R. Abou Taam has nothing to disclose. Conflict of interest: S. Arasi has nothing to disclose. Conflict of interest: A. Bakirtas has nothing to disclose. Conflict of interest: J. Lozano Blasco reports personal fees from Novartis and GSK outside the submitted work. Conflict of interest: K. Bønnelykke has nothing to disclose. Conflict of interest: M. Craiu reports a speaker fee for a scientific meeting regarding 5 years of Xolair in Romania (9 May 2018) from Novartis Romania outside the submitted work. Conflict of interest: R. Cutrera has nothing to disclose. Conflict of interest: A. Deschildre reports personal fees and other support from Novartis, GSK and Sanofi outside the submitted work. Conflict of interest: B. Elnazir has nothing to disclose. Conflict of interest: L. Fleming reports grants from Asthma UK, and speakers fees or fees for expert consultation from Teva, Astra Zeneca, Sanofi, Respiri, Novartis; all fees paid direct to her institution and outside the submitted work. Conflict of interest: U. Frey has nothing to disclose. Conflict of interest: M. Gappa reports personal fees from Boehringer Ingelheim, GSK, Novartis and Sanofi outside the submitted work. Conflict of interest: A. Nieto García reports grants for clinical studies and advisory boards membership, as well as lecture fees from Novartis, GSK and MSD. Conflict of interest: K. Skamstrup Hansen has nothing to disclose. Conflict of interest: L. Hanssens has nothing to disclose. Conflict of interest: K. Jahnz-Rozyk received lecture and advisory board fees from AstraZeneca, Novartis, GSK, and Sanofi Aventis, outside the submitted work. Conflict of interest: M. Jesenak has nothing to disclose. Conflict of interest: S. Kerzel reports a speaker fee from Novartis for a lecture that has no topical overlap at all with the current manuscript. Conflict of interest: M. V. Kopp reports personal fees from ALK-Abello GmbH, Chiesi GmbH, Infectopharm GmbH, Novartis GmbH, Sanofi Aventis HmbH and Vertex GmbH, and grants and personal fees from Allergopharma GmbH, outside the submitted work. Conflict of interest: G.H. Koppelman reports grants from Lung Foundation Netherlands, TETRI Foudation, Ubbo Emmius Foundation, Vertex, Teva the Netherlands, GSK, European Union, outside the submitted work; and he participated in advisory board meetings to GSK and Pure IMS (money to institution). Conflict of interest: U. Krivec has nothing to disclose. Conflict of interest: K.A. MacLeod has nothing to disclose. Conflict of interest: M. Mäkelä has nothing to disclose. Conflict of interest: E. Melén reports personal fees from AstraZeneca, Chiesi, Novartis and Sanofi (advisory board fees), outside the submitted work. Conflict of interest: G. Mezei reports a travel grant from LOFARMA outside the submitted work. Conflict of interest: A. Moeller has nothing to disclose. Conflict of interest: A. Moreira has nothing to disclose. Conflict of interest: P. Pohunek reports personal fees for advisory board membership from Novartis and GlaxoSmithKline, and for consultation from Chiesi and AstraZeneca, outside the submitted work. Conflict of interest: P. Minić has nothing to disclose. Conflict of interest: N.W.P. Rutjes reports personal fees from GSK (advisory board on mepolizumab) and Sanofi (advisory board on dupilumab) outside the submitted work. Conflict of interest: P. Sammut has nothing to disclose. Conflict of interest: N. Schwerk reports lecture and advisory board fees from Novartis, Sanofi and Allergopharma; advisory board fees from Boehringer Ingelheim; and lecture fees from Abvie and Infectopharm, all outside the submitted work. Conflict of interest: Z. Szépfalusi has nothing to disclose. Conflict of interest: M. Turkalj has nothing to disclose. Conflict of interest: I. Tzotcheva has nothing to disclose. Conflict of interest: A. Ulmeanu has nothing to disclose. Conflict of interest: S. Verhulst reports grants from GSK during the conduct of the study. Conflict of interest: P. Xepapadaki reports personal fees for advisory services from Uriach, Novartis, Nestle and Nutricia outside the submitted work. Conflict of interest: J. Niggel has nothing to disclose. Conflict of interest: S. Vijverberg reports grants from ZonMW during the conduct of the study. Conflict of interest: A-H. Maitland van der Zee has received research grants outside the submitted work from GSK, Boehringer Ingelheim and Vertex; she is the principal investigator of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD and Novartis); and she has served in advisory boards for AstraZeneca, GSK and Boehringer Ingelheim, with money paid to her institution. Conflict of interest: U. Potocnik was funded by the Ministry of Education, Science and Sport of the Republic of Slovenia, grant PERMEABLE (contract number C3330-19-252012), during the conduct of the study. Conflict of interest: S. M. Reinartz has nothing to disclose. Conflict of interest: C. M. van Drunen has nothing to disclose. Conflict of interest: M. Kabesch reports grants to his institution from the European Union, the German Ministry of Education and Research, and the German Research Foundation, during the conduct of the study; and consultancy fees from Bionorica, Sanofi, Novartis and Bencard, payments for lectures form the ERS, EAACI, ATS, Novartis, Glaxo, Nutricia, Hipp and Allergopharma, and a patent for a method for testing a subject thought to have or be disposed to asthma (European patent application 5 EP070301 135.5), outside the submitted work., (Copyright ©The authors 2021.)

Background: Little is known about the incidence and dynamics of occult bacteremia (OB) among infants/young children following the introduction of pneumococcal conjugate vaccines (PCVs) into the national immunization program in Israel in 2009-2010. The aim of this study was to characterize the epidemiologic and microbiologic picture of OB among febrile infants/children aged 3-36 months in southern Israel, before and after PCVs introduction., Methods: Retrospective study enrolling all infants/young children attending the emergency room of a tertiary medical center in southern Israel with fever without source, discharged, and reported with a positive blood culture., Results: Of 453 true bacteremias, 89 (19.6%) were defined as OB. OB rate was 0.22%; a significant decrease was recorded in OB rates, with the highest rate during 2005 (0.34%) and the lowest during 2011 (0.15%). OB cases decreased in post-PCV (2010-2012) versus prevaccination period (2005-2009) from 66/22,256 cases (0.3%) to 23/13,213 cases (0.17%; p = 0.03). Most frequent single OB pathogens were Streptococcus pneumoniae, Streptococcus viridans spp., and Kingella kingae (39.3%, 10.1%, and 9.0%, respectively); Enterobacteriaceae spp. were isolated in 10 cases (11.2%). No changes were recorded in S. pneumoniae-OB cases; K. kingae-OB decreased significantly (p = 0.047). None of the S. pneumoniae serotypes isolated during 2011-2012 belonged to 13-valent PCV (PCV13). An increase in non PCV13 serotypes was recorded during 2011-2012 (3/3, 100% vs. 7/32, 21.9%, p = 0.01)., Conclusion: OB rates decreased significantly following the introduction of PCVs. S. pneumoniae was the most frequent isolated pathogen in OB, but in lower percentages compared with the medical literature. No PCV13 serotypes were detected as a cause of OB during 2011-2012., (Copyright © 2015. Published by Elsevier B.V.)

Background: Data on the various aspects of brucellosis in children living in southern Israel are missing., Objectives: Our aim was to study the epidemiological, microbiological, diagnostic, clinical, therapeutic and outcome features of brucellosis in children <19 years of age in southern Israel during 2005-2011., Patients and Methods: The study population included all patients hospitalized with a diagnosis of brucellosis, established according to a clinical presentation compatible with brucellosis+presence of Brucella bacteremia (BB)., Results: A total of 128 (50.8%) of 252 patients admitted with a diagnosis of brucellosis had BB (all with Brucella melitensis). All patients were of Muslim Bedouin ethnicity. The mean incidence of BB in southern Israel was 16 cases/100,000 Bedouin, with no significant changes during the study period. Overall duration of symptoms before diagnosis was 10.1±10.9 days. Fever at diagnosis was recorded in <20% of the patients. The most frequent symptoms were arthralgia (61.7%), weakness (32.8%), gastrointestinal disturbances (27.3%), myalgia (25%), and headache (18.8%). The main clinical findings included monoarthritis (36.7%), hepatosplenomegaly (25%), lymphadenopathy (17.2%), heart murmur (11.7%), and skin rash (9.4%), respectively. Anemia, leukopenia, thrombocytopenia, and pancytopenia were reported in 17.6%, 29.6%, 12.8%, and 2.3% of the patients, respectively. Twenty-nine (30.5%) patients with BB had serum agglutinin titers ≤1/160 (13, 13.7%%, had titers <1/160). Twenty-seven (93%) of the 29 patients aged 0-4 years were treated with gentamicin and trimethoprim-sulfamethoxazole; a total of 77 (60.2%) patients received gentamicin and doxycycline., Conclusions: Childhood brucellosis remains an important public health problem in southern Israel. BB was diagnosed in >50% of the children with brucellosis, and B. melitensis was identified in all cases. Arthralgia, weakness, and gastrointestinal complaints were the most common symptoms, and monoarthritis, hepatosplenomegaly, and lymphadenopathy were the most common clinical findings. A considerable number of patients with BB had undetectable/low serum agglutinin titers, suggesting insufficient reliability on serology alone in diagnosis of brucellosis.

Background: We present clinical and molecular findings of a patient with ceroid-lipofuscinosis CLN7, with a compound heterozygous mutation of the MFSD8 gene, with Rett syndrome clinical signs onset and a later development of full picture of vLINCL., Case Presentation: A 7 years-old female patient with normal development until the age 12 months, developed Rett like clinical picture (psychomotor regression, microcephaly, stereotypic hands movements in the midline, hyperventilation episodes) present at the onset of her condition (age 18 months), features still present at the initial evaluation in our clinic at age 5 years., Results: MECP2 (methyl CpG binding protein 2) gene mutation was negative. At age 6 years she was readmitted for severe ataxia and blindness, seizures, and severe developmental regression leading to NCL (neuronal ceroid lipofuscinosis) suspicion. EEG showed slow background with IRDA (intermittent rhythmic delta activity). A conjunctive biopsy showed abnormal curvilinear and fingerprint lysosomal deposits, and genetic analysis revealed two heterozygous mutations of MFSD8 gene (c.881C > A p.Thr294Lys and c.754 + 2T > A) each inherited from carrier parents and a heterozygous variant (c.470A>C p.Asp157Ala) of CLN5 gene., Conclusion: NCL should be suspected and MFSD8 genetic testing should also be considered in patients with Rett like phenotype at onset and negative MECP2 mutation. Such cases should be carefully and frequently re-evaluated in order to avoid delayed diagnosis and offer proper genetic advice to the family. In our knowledge, this might be the first case of CLN7 disease with Rett like onset described in the literature, which developed typical vLINCL clinical phenotype after age 5.5 years. A short review of the literature showing NCL onset modalities is presented., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

We report the case of a male patient with a normal development in the first three months of life, presenting for global regression, central axial hypotonic syndrome, pyramidal syndrome, focal epileptic seizures, and a particular aspect of the hair - almost absent, short, sparse, lightly colored, at age of five months, becoming coarse, twisted (kinky hair) by the age of 21 months. Different diseases associate similar neurological and macroscopic aspect of the hair (biotinidase deficiency, argininosuccinic aciduria, aminoaciduria, giant axonal neuropathy, trichothiodistrophy and Menkes syndrome). The microscopic aspect of the patient's hair showing normal hair, silver colored hair, hair shafts twisting 1800, trichoclasis, and trichoptilosis, was highly characteristic for Menkes disease. Diagnosis was further supported by the low concentration of serum copper and ceruloplasmin and exclusion of other metabolic disorders with similar macroscopic aspect of the hair. Molecular genetic testing by multiplex PCR indicated deletion of exon 22 in the ATP7A gene situated in Xq21.1 region, consistent with the clinical and biochemical phenotype. Physicians should use microscopic evaluation of the hair more often when suspicion of Menkes disease is raised, aiming a narrow further diagnostic workup and early positive diagnosis and genetic advice for the affected families.

Asthma is the most frequent chronic disease of childhood. In spite of significant improvement of treatment options and diagnostic tools, asthma remains in many patients uncontrolled. The term of "severe asthma" seems to be rather a large umbrella for a heterogeneous group of diseases. This paper is presenting our experience in two respiratory disease clinics that evaluate asthmatic children. Current study was designed to test an algorithm for daily practice in a special group of patients: children with previously diagnosed asthma or recurrent-wheezing, evaluated by family physician or pediatrician as severe disease ("Asthma Decalogue in Children"). Out of 313 referrals (during a six months inclusion time) we had 202 children completing study per-protocol. 49 (22.69%) had severe disease, but only 8 had severe asthma (3.7% of total patients and 18.6% of severe patients). They were older, with less male predominance and with more frequent rhino-conjunctivitis and D vitamin deficiency than other asthmatic children with less severe disease. Asthma Decalogue in Children seems to be an efficient tool to differentiate severe asthma from the rest of children with reactive airway diseases.

Cystic fibrosis ormucoviscidosis (CF) is the most frequent monogenic genetic disease with autosomal dominant transmision in caucasians. Currently, the typical approach is referring the CF patient to specialized centers with multidisciplinary teams. The inherent questions appear: which is then the role of the general practitioner (GP)? Should the GP be confined to the pasive role of exchanging medical letters with the specialist, or should he take active part in monitoring the disease? Is it ethicallyand professionally correct for the GP to simply copy the treatment of a patient that hedidn't actually see for years, or to assume the palliative care in final stages of a patient who was actually taken care of only by the specialist? What are the families' expectations and what is the level of competence they expect from the GP? These are some of the questions we will try to answer, considering the expertise we accumulated in the regional center in "Alfred Rusescu" lnstitute for Protection of Mother and Child, where 16.22% (60 out of 370) of CF patients in Romania are monitored, and based on a questionnaire addressed to the CF patient's families.

Unlabelled: The objective of this study was to investigate the percent of infections with adenovirus (ADV) in children who had pneumonia, acute bronchiolitis or viral respiratory infections and were admitted to two pediatrics hospitals in Bucharest (Grigore Alexandrescu Hospital and Alfred Rusescu Hospital)., Subjects: 70 children aged one month - five years, admitted to the above mentioned pediatrics hospitals in Bucharest, who were negative for the Respiratory Syncytial Virus (RSV) and the human Metapneumovirus (hMPV) by Reverse Transcription -Polymerase Chain Reaction (RT-PCR). 48 of them presented pneumonia upon admission to hospital, 6--acute bronchiolitis and 16 respiratory viral infections. Samples (nasal swabs) were taken from patients and introduced in viral transport medium., Diagnostic Methods: RT-PCR for RSV and hMPV, Multiplex PCR by seeplex multi-detection system with Seeplex RV/PB 18 ASE Detection for detection of 5 pneumonial bacteria and Real-Time PCR, Duplica Real Time Adenovirus Detection for ADV., Results: Of the total 70 patients negative for RSV, hMPV and 5 pneumonial bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila), 10 were ADV positive; none of the children < 6 months (N = 16) presented ADV infection. In the 6 months - 2 years group (N = 35), 6 were ADV positive. In the 2 - 5 years group (N = 19), 4 were ADV positive., Conclusions: The percent of ADV infections in children hospitalized with acute respiratory infections (ARI) caused by neither RSV or hMPV is 14.2%. ADV is most frequently encountered in the 6 months - 2 years and then 2 - 5 years groups, but the most severe pneumonia forms can be seen in the 6 months - 2 years group. In children < 6 months with acute bronchiolitis ADV was not found to be an etiologic agent.