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The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively. Conclusion: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low. What is known: • Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. What is new: • This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events. [ABSTRACT FROM AUTHOR]

Anterior and posterior drooling are prevalent comorbidities in children with neurodevelopmental disabilities. Considering the heterogeneity of the patient population and the multifactorial aetiology of drooling, an interdisciplinary and individualised treatment approach is indispensable. However, no tool for stepwise decision-making in the treatment of paediatric drooling has been developed previously. Within the Radboudumc Amalia Children's Hospital, care for children with anterior and/or posterior drooling secondary to neurodevelopmental disabilities is coordinated by a saliva control team with healthcare professionals from six disciplines. In alignment with international literature, published guidelines, and evidence gained from two decades of experience and research by our team, this paper proposes an algorithm reflecting the assessment and treatment approach applied in our clinic. First, directions are provided to decide on the necessity of saliva control treatment, taking type of drooling, the child's age, and the severity and impact of drooling into account. Second, the algorithm offers guidance on the choice between available treatment options, highlighting the importance of accounting for child characteristics and child and caregiver preferences in clinical (shared) decision-making. Conclusions: With this algorithm, we aim to emphasise the importance of repeated stepwise decision-making in the assessment and treatment of drooling in children during their childhood, encouraging healthcare professionals to apply a holistic approach. What is Known: • Children with anterior or posterior drooling secondary to neurodevelopmental disabilities comprise a heterogeneous group, necessitating an individualised treatment approach. • No stepwise decision-making tool is available for the treatment of paediatric drooling. What is New: • Deciding on the necessity of saliva control treatment should be a conscious process, based on type of drooling, age, and drooling severity and impact. • Type of drooling, age, cognition, oral motor skills, self-awareness, posture, diagnosis, and child/caregiver preferences need to be considered to decide on the optimal treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise‐induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet. Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: • Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. • CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups. Conclusions: The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children. Prospero registration: CRD42020209066. What is known: • Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children. What is new: • BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia. [ABSTRACT FROM AUTHOR]

The number of children eligible for Paediatric Palliative Care has dramatically increased over the years, with few tools that can help with early identification. The Paediatric Palliative Screening Scale is a dedicated German, English, and Portuguese screening tool. We aimed to translate and perform a cultural adaptation to the Italian setting of the Paediatric Palliative Screening Scale. This paper was a descriptive observational cross-sectional study. We carried it out in two consecutive steps: (1) translation and back translation and (2) cultural adaptation through a Delphi process. Twenty Paediatric Palliative Care national experts were invited to judge the content and structure of the translated scale and to assess the appropriateness and clarity of each question. Consensus was defined as 70% or more of experts agreeing with each item's appropriateness and clarity. The Italian version of the Paediatric Palliative Screening Scale was obtained after two rounds of Delphi. After the second round of consultation, a substantial increase in experts' consensus was found, especially for questions 1.1, 3.2 and 3.3 (from 56.3 to 93.8%), and reaching more than 83% for all the revised items. Conclusions: The Paediatric Palliative Screening Scale is a reliable tool that can assist in timely evaluating children who qualify for Paediatric Palliative Care. The tool can be used in Italian healthcare settings with its cultural adaptation. What is Known: • Despite the lack of early diagnosis techniques, there is a significant increase in the number of children entitled to Paediatric Palliative Care. • A specific screening tool called the Paediatric Palliative Screening Scale determines a child's suitability for paediatric palliative treatment. What is New: • The Paediatric Palliative Screening Scale is necessary to assess the psychosocial needs of patients eligible for Paediatric Palliative Care. The Italian scale has good content and face validity ensuring equivalence between the original and target populations. [ABSTRACT FROM AUTHOR]

Purpose: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH. Methods: An anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources. Results: Between September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0–22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia. Conclusions:The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life. What is Known: • Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). • The process of atherosclerosis starts in childhood • Pediatricians play an important role in the detection and treatment of children with FH. What is New: • Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment. • FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood. [ABSTRACT FROM AUTHOR]

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3–5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976. Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges. What is Known? • Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD. • Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD. What is New? • Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group. • Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR. • Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM. [ABSTRACT FROM AUTHOR]

The role of obesity as risk factor for chronic kidney disease (CKD) has been well-recognized. As previously demonstrated in adults, emerging data highlighted the relevant impact of obesity on renal function since childhood. As a matter of fact, obesity also affects renal health through a complex pathogenic mechanism in which insulin resistance (IR) plays a pivotal role. Worthy of note, the vicious interplay among obesity, IR, and renal hemodynamics clinically translates into a plethora of kidney function impairments potentially leading to CKD development. Therefore, renal injury needs to be added to the well-known spectrum of cardiometabolic obesity comorbidities (e.g., type 2 diabetes, IR, metabolic syndrome, cardiovascular disease). Conclusion: Taking this into account, a careful and timely monitoring of kidney function should not be neglected in the global assessment of children with obesity. We aimed to provide a comprehensive overview on the relevance of kidney evaluation in children with obesity by shedding lights on the intriguing relationship of obesity with renal health in this at-risk population. What is Known: • Obesity has been found to be a risk factor for chronic kidney disease. • Unlike adults, pediatric data supporting the association between obesity and renal function are still limited. What is New: • As observed in adults, obesity might affect renal function since childhood. • Kidney function should be carefully evaluated in children with obesity. [ABSTRACT FROM AUTHOR]

Severe obesity defined as BMI value corresponding to an adult > 40 kg/m2 affects 1–5% of children and adolescents in Europe. The purpose of this study was to assess the occurrence of cardiovascular risk factors in children and adolescents with severe obesity. The analysis included 140 patients (75 female) at the mean age of 14 ± 2.1 SD (range 10–18) years (all recruited in 4 regional reference centers in Poland). Severe obesity was defined as BMI > 35 kg/m2 (children 6–14 years), and BMI > 40 kg/m2 (> 14 years). Fasting plasma samples have been obtained in all patients, and OGTT was performed in all patients. The metabolic risk factors were defined as high blood pressure (BP > 90 percentile for height, age, and sex), HDL cholesterol < 1.03 mmol/L, TG ≥ 1.7 mmol/L, and hyperglycemic state (fasting blood glucose > 5.6 mmol/L, or blood glucose 120′ after oral glucose load > 7.8 mmol/L). Additionally, the MetS z-score was calculated using Metabolic Syndrome Severity Calculator. One hundred twenty-four (89%) participants presented with high BP, 117 (84%) with abnormal lipid profile, and 26 with the hyperglycemic. Only 12 (9%) were free of metabolic complications. More than 60% of patients had more than one cardiovascular risk factor. The high BP was significantly associated with the severity of obesity (F = 9.9, p = 0.002). Patients with at least one metabolic complication presented with significantly younger age of the onset of obesity (the mean age of the patients with no overt obesity complications was 10 years, while the mean age of those who presented at least one was 4.7 ± 3.5 SD years (p = 0.002)). A significant positive association between in the value of the Mets BMI z-score with age was observed (R = 0.2, p < 0.05). There were no differences between girls and boys regarding Mets BMI z-score (1.7 ± 0.8 vs 1.7 ± 0.7, p = 0.8). Conclusions: The most common metabolic risk factor in children and adolescents with severe obesity was high BP. The most important factor determining presence of obesity complications, and thus the total metabolic risk, seems to be younger (< 5 years) age of onset of obesity. What is Known? • It is estimated that 1-5% of children and adolescents in Europe suffer from severe obesity corresponding to an adult BMI > 40 kg/m2, and it is the fastest growing subcategory of childhood obesity. • Children with severe obesity face substantial health risk that may persist into adulthood, encompassing chronic conditions, psychological disorders and premature mortality. What is new: • The most common complication is high BP that is significantly associated with the severity of obesity (BMI z-score), contrary to dyslipidemia and hyperglycemic state, which do not depend on BMI z-score value. • The most important factor determining presence of obesity complications, and thus the total metabolic risk, seems to be younger (< 5 years) age of onset of obesity. [ABSTRACT FROM AUTHOR]

As survivors of early cardiac surgery are at high risk of neurodevelopmental impairments, systematic health observations of children with critical congenital heart disease (CCHD) throughout childhood are recommended to enable early diagnosis and offer interventions to optimize neurodevelopment. A qualitative study using thematic analysis was performed to explore parents' concerns, experiences, and needs regarding the development and received developmental care of their child (0–10 years) during hospital admission and beyond. Data were collected using semi-structured online interviews with 20 parents of children with CCHD. Four major themes were identified: (1) "impact of diagnosis and disease on the family-system," (2) "parental concerns from diagnoses and beyond," (3) "the need for information," and (4) "the need for individualized and family-centered care." The main themes can be divided into 13 sub-themes as impact, concerns, and needs are influenced by various impactful moments from diagnosis and afterwards. Conclusion: This study confirms the importance of early identification of neurodevelopmental problems by experienced healthcare professionals, especially in the early years when parental expectations and concerns about their child's neurodevelopment are lower. A tailor-made family-centered follow-up program should be offered, which pays attention to both the neurodevelopment of patients with CCHD as well as the mental wellbeing of the entire family system. Furthermore, an online portal is recommended with a variety of reliable, controlled, understandable information from which parents can obtain the desired information to understand better the consequences of specific heart condition and to provide their child with the best possible guidance. What is Known: • Survivors of early cardiac surgery are at high risk of neurodevelopmental impairments; systematic health observations of children with CCHD throughout childhood are strongly recommended. What is New: • Parents need a tailor-made family-centered follow-up program, which pays attention to both the neurodevelopment of patients with CCHD as well as the mental wellbeing of the entire family system. • An online portal offering diverse, trustworthy information and sources would effectively meet parents' needs by providing accessible insights into the potential consequences of specific heart conditions and guiding them in supporting their child optimally. [ABSTRACT FROM AUTHOR]

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702–0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227–5.144, P = 0.012) for sepsis, 3.109 (1.166–8.290, P = 0.023) for septic shock. Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality. [ABSTRACT FROM AUTHOR]

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018–2019) and covid (2020–2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4–7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42–103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01–1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25–11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00–1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65–100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41–2.89; p = 0.009) even when adjusted for CrP values. Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: •Adenovirus infection is a common cause of fever and respiratory tract infections in children. •Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics. [ABSTRACT FROM AUTHOR]

Torsional disorders of the lower limb are common in childhood, and they are one of the primary reasons parents seek consultation with healthcare providers. While clinical manoeuvres can assess femoral and tibial torsion, their reliability is medium to low. Various imaging-based techniques, including computed tomography, magnetic resonance imaging, fluoroscopy, biplanar radiology and ultrasonography, have been used to evaluate torsional alterations of the lower extremity. Among these, ultrasound assessment offers certain advantages: it is a low-cost, non-irradiating technique, which allows the follow-up of children's torsional development. However, to the best of the authors' knowledge, its validity and reliability have not been summarised in a systematic review. This study aims to analyse the validity and reliability of ultrasonography in determining femoral and tibial torsion in children and adolescents. A search from Medline (via PubMed), Web of Science, Scopus and CINAHL databases were performed from inception to 16 March 2023. No restrictions were placed on the publication year or language. The methodological quality of all eligible studies was independently reviewed by two authors using QUADAS and STARD checklists. Overall, 1546 articles were identified through the searches; 30 were considered eligible for full-text screening; and 8 studies were finally included in this review. The included studies were conducted in Germany, Norway and the UK. Among them, 7 studies analysed the validity of ultrasonography compared with other imaging techniques such as computed tomography, magnetic resonance imaging and biplanar X-ray, and 4 studies assessed intra- and inter-observer reliability. All the studies assessed femoral torsion, but only one of them also included tibial torsion. Conclusion: Ultrasound is a good alternative for routine evaluation and follow-up of femoral torsional alterations in children and adolescents due to its safety, accessibility and immediate results in the clinical examination room. Although ultrasound has good accuracy and reliability for routine evaluations, there is controversy about whether it is sufficient for surgical planning. In cases where greater accuracy is required, magnetic resonance imaging and biplanar radiography are the preferred imaging techniques. What is Known: • Several imaging-based techniques have been described for the assessment of torsional alterations of the lower extremity. • Computed tomography, magnetic resonance imaging, biplanar radiology and ultrasonography are the most used and studied methods. What is New: • Ultrasonography represents a good alternative for the assessment of femoral and tibial torsional alterations in children and adolescents, given its safety, accessibility and immediacy of results in the consultation room. • Its accuracy and reliability are good but not sufficient for surgical planning, in which case MRI and biplanar X-ray will be the preferred choices. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) caused hospitalizations, severe disease, and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LU) in children with COVID-19. We enrolled children between 1 month and 18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection who underwent a LU within 6 h from the first medical evaluation. A total of 213 children were enrolled, 51.6% were male, median age was 2 years and 5 months (interquartile range (IQR) 4 months –11 years and 4 months). One hundred and forty-eight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit. We found an inverse correlation between the lung ultrasound score (LUS) and the oxygen saturation at the first clinical evaluation (r = −0.16; p = 0.019). Moreover, LUS was significantly higher in patients requiring oxygen supplementation (8 (IQR 3–19) vs 2 (IQR 0–4); p = 0.001). Among LU pathological findings, irregular pleural lines, subpleural consolidations, and pleural effusions were significantly more frequent in patients needing oxygen supplementation (p = 0.007, p = 0.006, and p = 0.001, respectively). Conclusion: This multicenter study showed that LU in children with COVID-19 can highlight pleural line irregularities, vertical artifacts, and subpleural consolidation. Notably, children with higher LUS have a higher risk of hospitalization and need for oxygen supplementation, supporting LU as a valid and safe point-of-care first level tool for the clinical evaluation of children with COVID-19. What is Known: • Few children infected with SARS-CoV-2 develop a severe disease and need oxygen therapy. • Lung ultrasound can easily detect low respiratory tract infection during SARS-CoV-2. What is New: • Children with higher lung ultrasound score have a higher risk of need for oxygen supplementation. • Irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequent in patients needing oxygen supplementation. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to assess the effectiveness and safety of colistin used in combination therapy for treating nosocomial bloodstream infections caused by multi-drug resistant gram-negative pathogens in pediatric patients. Patients aged between 1 month and 18 years consecutively hospitalized with healthcare-associated bloodstream infections necessitating the administration of intravenous colistin at Dr. Sami Ulus Training and Research Hospital between January 2015 and January 2020 were included in the study. Patient-specific detailed clinical information, prognoses, and laboratory findings on days 1, 3, and 7 of colistin treatment were obtained from medical records. The study included 45 pediatric patients receiving intravenous colistin; 26 (57.8%) were male and 19 (42.2%) were female, with a median age of 18 months. While the clinical response was observed at 82.2% and microbiological response at 91.1% with colistin treatment, two patients (4.4%) discontinued treatment due to side effects without assessing treatment response. The most common adverse effect associated with the use of colistin was nephrotoxicity, which occurred in eight patients (17.8%). Among these patients, only one had pre-existing chronic kidney failure. Conclusion: Colistin used in combination therapy may be effective and safe for treating nosocomial infections caused by multi-drug resistant gram-negative bacteria in pediatric patients, who often have high mortality rates and limited treatment options. What is Known: • Colistin is an antibacterial agent used in the treatment of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) and is associated with significant adverse effects such as nephrotoxicity. • The increasing prevalence of hospital-acquired infections has led to the expanded use of colistin in clinical practice. What is New: • The study demonstrates a high clinical and microbiological response rate to combination therapy with colistin in the treatment of infections caused by MDR-GNB. • The study highlights the importance of monitoring nephrotoxicity in pediatric patients receiving colistin, showing that these effects can be reversible after treatment cessation. [ABSTRACT FROM AUTHOR]

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25–57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12. [ABSTRACT FROM AUTHOR]

This study aimed to translate, cross-culturally adapt, and validate the CDPQOL questionnaire, a coeliac disease (CD)-specific paediatric health-related quality of life (HRQoL) instrument (CDPQOL), in Spanish children with CD. The CDPQOL questionnaire has two versions for children aged 8–12 and 13–18. Translation and linguistic validation were performed following an international consensus process. Internal consistency was calculated using Cronbach's alpha and McDonald's omega coefficients, and convergent validity was assessed with average variance extracted (AVE). Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA), when necessary, were carried out to assess the construct validity. A total of 235 children were included. In the 8–12 age group, a change in the distribution of items to a new structure of three dimensions (negative emotions, food feelings and social interaction) was required. In this new model, CFA supported the fit of the model (χ2/gl = 1.79, RMSEA = 0.077 (IC 95% 0.05–0.100), CFI = 0.969, TLI 0.960, SRMR = 0.081) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions. In the 13–18 age group, CFA showed that all fit indexes were acceptable (χ2/gl = 1.702, RMSEA = 0.102 (IC 95% 0.077–0.127), p < 0.001, CFI = 0.956, TLI = 0.947, SRMR = 0.103) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions, except for uncertainty dimension. Conclusions: The Spanish version of the CDPQOL questionnaire is a useful instrument to assess quality of life in coeliac children whose native language was Spanish spoken in Spain, with changes in item distribution in the younger age group questionnaire. What is Known: • The first specific questionnaire for coeliac children, Dutch Coeliac Disease Questionnaire (CDDUX), which focuses on diet, was translated into Spanish and validated allowing to evaluate the HRQoL of Spanish coeliac children. • Spanish Children and parents feel the disease had no substantial negative impacts on patient HRQoL using this questionnaire, similar to that observed with other countries. What is New: • The age specific for CD children (CDPQOL) was elaborated in the USA and focuses on other aspects not evaluated by CDDUX such as emotional and social issues related to living with CD. • The CDPQOL was translated into Spanish and validated allowing it to be used to assess Spanish coeliac children's QoL. [ABSTRACT FROM AUTHOR]

The association between breastfeeding and the occurrence of allergic rhinitis (AR) and food allergy (FA) in offspring remains inconclusive. This review aims to comprehensively explore the potential relationships between various patterns and durations of breastfeeding and allergic diseases in offspring. We systematically searched PubMed, EMBASE, Cochrane, WOS databases, and Google Scholar for observational studies published up to March 30, 2023, that investigated the link between breastfeeding and allergies in offspring. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI). Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated employing an appropriate model based on the degree of heterogeneity. A total of 68 studies, encompassing 772,142 children, were ultimately included. The findings indicated that breastfeeding for more than 6 months was associated with a reduced risk of AR (OR = 0.88, 95% CI: 0.79 to 0.98) but posed a risk for FA (OR = 1.69, 95% CI: 1.27 to 2.25). Exclusive breastfeeding exhibited a protective effect against AR (OR = 0.94, 95% CI: 0.90 to 0.97), whereas non-breastfeeding was identified as a risk factor for AR (OR = 1.48; 95% CI: 1.03 to 2.12). No significant association was observed between breastfeeding patterns and FA. Conclusion: Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, large prospective high-quality studies are needed to investigate the potential risk of FA in children with prolonged breastfeeding. What is Known: • The impact of breastfeeding on allergic rhinitis and food allergy in offspring is controversial. • Previous meta-analyses fail to prove the effect of breastfeeding on food allergy in offspring of all ages. What is New: • Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, it potentially elevates the risk of FA in children. Non-breastfeeding is linked to an increased risk of AR in children, but there is no evidence of an association between breastfeeding patterns and FA in children. • The impact of breastfeeding on allergic rhinitis and food allergy in offspring may vary with the time and pattern of breastfeeding. [ABSTRACT FROM AUTHOR]

Henoch-Schönlein purpura nephritis (HSPN) is the most severe manifestation of Henoch-Schönlein purpura (HSP). This study aimed to determine the role of urine metabolomics in predicting HSPN and explore the potential mechanisms of HSP. A liquid chromatography-tandem mass spectrometry-based untargeted metabolomics analysis was performed to investigate the urinary metabolic profiles of 90 participants, comprising 30 healthy children (group CON) and 60 patients with HSP, including 30 HSP patients without renal involvement (group H) and 30 HSPN patients (group HSPN). The differentially expressed metabolites (DEMs) were identified using orthogonal partial least squares discriminant analysis (OPLS-DA), and subsequent bioinformatics analysis was conducted to elucidate the perturbed metabolic pathways. A total of 43 DEMs between H and HSPN groups were analyzed by the Kyoto Encyclopedia of Gene and Genome (KEGG) database, and the result indicates that glycine, serine and threonine metabolism, and cysteine and methionine metabolism were significantly disturbed. A composite model incorporating propionylcarnitine and indophenol sulfate was developed to assess the risk of renal involvement in pediatric patients with HSP. Conclusion: This study reveals the metabolic alterations in healthy children, HSPN patients, and HSP patients without renal involvement. Furthermore, propionylcarnitine and indophenol sulfate may be potential predictive biomarkers of the occurrence of HSPN. What is Known: • HSP is the predominant type of vasculitis observed in children. The long-term prognosis of HSP is contingent upon the extent of renal impairment. In severe nephritis, a delay in appropriate treatment may lead to fibrosis progression and subsequent development of chronic kidney disease (CKD), even leading to renal failure. • The application of metabolomics in investigating diverse renal disorders has been documented. Urine is a robust and sensitive medium for metabolomics detection. What is New: • The metabolic profiles were identified in urine samples of healthy children and those with HSP at the early stage of the disease. Different metabolites were identified between HSP patients without nephritis and those who developed HSPN. • These different metabolites may affect oxidative stress in the progression of HSPN. [ABSTRACT FROM AUTHOR]

Although children wish to be included in their own healthcare, they recognize a gap between their right to be heard and their ability to become involved. Despite adaptation of medical consultation styles which suit a more patient-centered approach, data on the current state of child participation in clinical encounters are missing. We aimed to assess actual child participation in a Dutch pediatric clinic. Children aged 4–18 years visiting a pediatric outpatient clinic for consultation after general practitioner's referral were included. Sixteen consultations of six pediatricians were recorded and transcribed verbatim. Quantitative measurement included word count and speech turn; conversation analysis with qualitative appraisal provided data on participatory behavior. Quantitative child participation equaled parent participation in turns (28% vs 29%, respectively), but remained limited in words (relative contribution 11% for child, 23% for parent and 66% for pediatrician). Children spoke on average six words per speech turn. Child age correlated positively with participation in words (p = 0.022, r = 0.566) and turns (p = < 0.001, r = 0.746). Children were mostly involved during social history taking, introduction, and physical examination but did not actively speak during the decision-making process. Children took an active role by instigating talks. Qualitative facilitators included appropriate language and verbal or non-verbal child allocated turns. Adults involved children by asking them questions and verifying their opinions or plans with the child. Teenagers participated most during the entire consultation, while younger children were more likely to lose their focus by the end of the conversation. Conclusion: Despite increased turn taking, children's verbal participation remains low in pediatric consultations. If pediatricians and parents maintain a triadic conversation style throughout every stage of the medical encounter, child participation may increase. What is Known: • Verbal child participation varies between 4 and 17%, measured in turns, words, speech time, or utterances. • Child participation is limited to social talk, laughter, and providing medical information. What is New: • Child speech turns equal parental speech turns (28%), but average relative word count remains low (11%). • Three percent of the children's turns are defined a "contributing in decision making, giving their opinion or give consent," which equals three turns per consultation. [ABSTRACT FROM AUTHOR]

Sleeping problems are prevalent among children and adolescents, often leading to frequent consultations with pediatricians. While cognitive-behavioral therapy has shown effectiveness, especially in the short term, there is a lack of globally endorsed guidelines for the use of pharmaceuticals or over-the-counter remedies in managing sleep onset insomnia. An expert panel of pediatric sleep specialists and chronobiologists met in October 2023 to develop practical recommendations for pediatricians on the management of sleep onset insomnia in typically developing children. When sleep onset insomnia is present in otherwise healthy children, the management should follow a stepwise approach. Practical sleep hygiene indications and adaptive bedtime routine, followed by behavioral therapies, must be the first step. When these measures are not effective, low-dose melatonin, administered 30–60 min before bedtime, might be helpful in children over 2 years old. Melatonin use should be monitored by pediatricians to evaluate the efficacy as well as the presence of adverse effects. Conclusion: Low-dose melatonin is a useful strategy for managing sleep onset insomnia in healthy children who have not improved or have responded insufficiently to sleep hygiene and behavioral interventions. What is Known: • Pediatric insomnia is a common disorder and impacts children's emotional, behavioral, and cognitive functioning, as well as parents' sleep and daytime functioning. • There is no consensus in Europe on the management of sleep onset insomnia and the use of melatonin in typically developing children. What is New: • A group of European experts has compiled a set of recommendations for the management of insomnia, developing a step-by-step approach. • Sleep hygiene, behavioral strategies, and finally low-dose melatonin represent valid strategies for managing sleep onset insomnia. [ABSTRACT FROM AUTHOR]

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. Conclusions: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment. What is Known: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice. What is New: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections. [ABSTRACT FROM AUTHOR]

Thermal epiglottitis, a non-infectious cause of epiglottitis, is a rare entity that shares some clinical features with infectious epiglottitis. This study presents 16 years of experience in diagnosing and managing thermal epiglottitis. A retrospective descriptive study in a tertiary center in southern Israel included confirmed cases of thermal epiglottitis in children (0–18 years) between 2004 and 2020 by endoscopy. Of approximately 600,000 pediatric ER admissions between 2004 and 2020, seven children were diagnosed by endoscopy with thermal epiglottitis (mean age 24 months, 71% males). Clinical presentation included stridor, respiratory distress, and drooling. Four children had fever and elevated inflammatory markers at presentation and were treated with systemic antibiotics. All were treated with systemic steroids. The median length of stay in the PICU was five days, and four patients required intubations. All fully recovered without experiencing any sequelae. Conclusion: Thermal epiglottitis stands as a potential contributor to acute upper airway obstruction. Although it's rarity, it should be discussed in any child with acute upper airway obstruction. It is essential to inquire directly about the accidental intake of hot beverages, particularly in cases lacking fever or elevated inflammatory markers. What is Known: • Thermal epiglottitis is a rare, non-infectious condition sharing clinical features with infectious epiglottitis. • Common presentations include stridor, respiratory distress, and drooling. What is New: • Thermal epiglottitis is a potential contributor to acute upper airway obstruction, urging consideration even in the absence of fever or elevated markers. • Direct inquiry about hot beverage intake for diagnosis is essential for diagnosis. [ABSTRACT FROM AUTHOR]

While most countries provide safe and effective influenza vaccines for at-risk groups, influenza vaccine coverage among children with rheumatic diseases remains uncertain. This study investigated influenza vaccination rates in children with juvenile idiopathic arthritis (JIA) during the 2019–2020 season and assessed the knowledge and attitudes of caregivers of children with JIA regarding influenza vaccination. The secondary aims were to identify barriers to vaccination and explore strategies to improve vaccination rates. A multi-centre, cross-sectional anonymous survey was conducted in 7 countries during the 2019–2020 influenza season to assess the uptake history of influenza vaccination. Among 287 participants, only 87 (30%) children with JIA received the influenza vaccine during the 2019–2020 season. Children who were more likely to be vaccinated were those with systemic juvenile idiopathic arthritis (sJIA), a history of previous vaccination and those aware of the vaccination recommendations. Conversely, children who previously experienced adverse vaccine-related events reported the lowest uptake. The primary reason for non-vaccination was lack of awareness about the necessity of influenza vaccination. Conclusion: Despite variations among countries, the uptake of influenza vaccines remains low in children with JIA. Improving awareness among families about the importance of influenza vaccination may increase vaccination rates in children with rheumatic diseases. What is Known: • Rheumatic children are at increased risk for influenza infection due to immunosuppressive therapy and immune dysregulation. • Influenza vaccine is formally recommended to children with rheumatic diseases. What is New: • This multicentre study showed that influenza vaccine uptake rates remain suboptimal among children with Juvenile Idiopathic Arthritis despite formal recommendations. • Factors like previous experience with vaccination and information provided by medical professionals via different ways play essential roles in increasing vaccination rates and can contribute to improved health outcomes for these vulnerable children. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage. Conclusion: This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice. What is Known: • Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death. What is New: • This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion. [ABSTRACT FROM AUTHOR]

This study explored the coronavirus disease 2019 (COVID-19) vaccination coverage among children with epilepsy (CwE), factors affecting vaccination coverage, and the effect of COVID-19 vaccines on epilepsy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A questionnaire was administered to CwE and their parents at the Pediatric Neurology Clinic of the Second Affiliated Hospital of Xi'an Jiaotong University between December 12, 2022, and February 28, 2023. Data were analyzed using the t-tests, chi-square tests, and logistic regression. The analysis included 250 CwE who responded to the survey; of these, 152 (60.8%) had been vaccinated against COVID-19. COVID-19 vaccine hesitancy in parents whose CwE were not vaccinated was mostly due to concerns of vaccine-related exacerbation of seizures and of vaccine-related adverse reactions (44.30% and 41.90% of the respondents, respectively). Univariate analysis showed that vaccination and number of doses of vaccine did not affect seizure incidence within 1 month of SARS-CoV-2 infection. Logistic regression analysis showed that CwE below primary school age, and those taking two or more antiseizure medication (ASMs) were less likely to be vaccinated (p = 0.007). Conclusion: The primary reasons for vaccine hesitancy among parents of unvaccinated CwE were concerns regarding seizure exacerbation and adverse reactions following COVID-19 vaccination. CwE who were below primary school age and those who took two or more ASMs were less likely to be vaccinated. Addressing parents' concerns is necessary to build their confidence in COVID-19 vaccines and ensure that CwE are vaccinated. What is Known: • People with epilepsy have a higher risk of severe and fatal COVID-19 than those without epilepsy but, despite this, COVID-19 vaccination coverage is considerably lower in people with epilepsy than in people without epilepsy. What is New: • In unvaccinated children with epilepsy, the foremost reasons for COVID-19 vaccine hesitancy among parents were concerns about seizure exacerbation and vaccine-related adverse reactions. • Vaccination and number of doses of vaccine did not exacerbate seizures in children with epilepsy, those below primary school level and those taking two or more antiseizure medications were less likely to be vaccinated. [ABSTRACT FROM AUTHOR]

Scabies is a human ectoparasitosis caused by Sarcoptes scabei var. hominis. World-wide around 300 million patients are affected. Infants and children have the highest incidence rates. Poverty and overcrowding are social factors contributing to a higher risk of transmission and treatment failure. The leading symptom of the infestation is itch. Complications are bacterial infections that are responsible for mortality. Diagnosis is clinical. Non-invasive imaging technologies like dermoscopy can be used. Polymerase chain reaction (PCR) is less sensitive and specific than microscopy of skin scrapings. Treatment of choice is topical permethrin 5%. Ivermectin is the only oral drug FDA-approved for scabies. It should be used in cases non-responsive to topical therapy and in case of high number of infested patients in addition to topical therapy. Pseudo-resistance to treatment is not uncommon. New drugs are on the horizon. What is Known: • Pruritus is the leading symptom causing sleep disturbances and scratching with the risk of secondary bacterial infections. • Treatment failure is related to inappropriate application of topical drugs and asymptomatic family members. What is New: • COVID-19 pandemic and migration are contributing to an increased incidence of scabies. • New compounds to treat scabies are on the horizon. [ABSTRACT FROM AUTHOR]

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. [ABSTRACT FROM AUTHOR]

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02–1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27–2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01–2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes. Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life. [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe the morbidity and mortality of children during the entire COVID-19 pandemic. Age-disaggregated data of 108,003,741 cases and 560,426 deaths were collected from Canada, France, Germany, and Italy. The number of cases and deaths per million people per week, as well as case fatality rates (CFRs), were calculated for patients aged 0–14 and ≥ 15 years. During the first pandemic period in the four countries, starting from weeks 4 to 11 (in 2020) and ending at week 22 (in 2021), the number of deaths per million people per week and the CFRs in the ≥ 15 years age group were 500 to 2513 and 442 to 1662 times greater, respectively, than those in the 0–14 years age group. The number of deaths per million people per week was significantly lower in the first pandemic period than in the second pandemic period, which started at week 23 (2021) and ended from week 22 to week 25 (2023). During the second pandemic period in the four countries, the disparities between the ≥ 15 years and 0–14 years age groups decreased, and the number of deaths per million people per week in the ≥ 15 years age group was 76 to 180 times greater than it in the 0–14 years age group. Conclusion: Children aged 0–14 years had a far lower mortality risk during the entire COVID-19 pandemic, and the impact of viral variants and/or vaccination on the mortality rate is difficult to distinguish. What is Known: • Although extensive studies have focused on COVID-19-induced mortality, most of them are provisional reports performed during the unfolding of the pandemic and provide imprecise conclusion. What is New: • We described the morbidity and mortality for children aged 0–14 years using complete survey data recorded during the entire COVID-19 pandemic. • The number of deaths per million people per week was far lower in children aged 0–14 years, while the number of deaths per million people per week in children aged 0–14 years was significantly higher in the second period which starting from week 23 (2021) and ending at week 22 to 25 (2023) than in the first period which starting from week 1 to 11 (2020) and ending at week 22 (2021). [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs) are characterized by chronic or recurrent gastrointestinal symptoms (GS) that are not explained by structural or biochemical abnormalities. FGIDs are related to lower quality of life, increased demands on medical resources, and greater somatization and emotional instability. Furthermore, GS appears to be an indicator of dysbiosis in gut-microbiota, affecting the gut-microbiota-brain relationship. To develop and evaluate the psychometric properties of a new instrument called the Gastrointestinal Symptom Severity Scale (GSSS) using a web-based survey in a sample of neurotypical children and adolescents from Spain. Instrument development and validation processes were applied to the GSSS following its administration as part of an online survey. The sample included 1242 neurotypical children and adolescents. The mean age of participants was 13.95 years, with a standard deviation of 1.37 years. Overall, 13.8% suffered infectious diarrhea, 12.6% suffered abdominal pain, 5% suffered dyspepsia and 2.6% suffered gastro-esophageal reflux. A single-factor model produced good fit indices. Furthermore, internal consistency and test-retest reliability outcomes were acceptable. The GSSS was found to have acceptable metric measurement invariance. Significant correlations with other instruments were produced and were of expected direction and magnitude, confirming scale validity for hypothesis testing. Conclusions: The GSSS shows promising psychometric properties for assessing GS in neurotypical Spanish adolescents and children. What is Known: • To the best of our knowledge, instruments assessing the severity of gastrointestinal symptoms in children and adolescents are still too few. What is New: • The GSSS shows promising psychometric properties for assessing GS in neurotypical adolescents and children. The GSSS may help improve understanding of GS involvement in the gut-brain microbiota axis in children and adolescents. [ABSTRACT FROM AUTHOR]

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography. Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults. [ABSTRACT FROM AUTHOR]

Sudden cardiac death in children is a rare event, but of great social significance. Generally, it is related to heart disease with a risk of sudden cardiac death (SCD), which may occur with cardiovascular symptoms and/or electrocardiographic markers; thus, a primary care paediatrician (PCP) could detect them. Therefore, we proposed a study that assesses how to put into practice and conduct a cardiovascular assessment within the routine healthy-child check-ups at six and twelve years of age; that reflects cardiovascular signs and symptoms, as well as the electrocardiographic alterations that children with a risk of SCD in the selected population present; and that assesses the PCP's skill at electrocardiogram (ECG) interpretation. In collaboration with PCPs, primary care nurses, and paediatric cardiologists, an observational, descriptive, multicentre, cross-sectional study was carried out in the Balearic Islands (Spain), from April 2021 to January 2022, inclusive. The PCPs gathered patient data through forms (medical record, electrocardiogram, and physical examination) and sent them to the investigator, together with the informed consent document and electrocardiogram. The investigator passed the electrocardiogram on to the paediatric cardiologists for reading, in an identical form to those the paediatricians had filled in. The variables were collected, and a descriptive analysis performed. Three paediatric cardiologists, twelve PCPs, and nine nurses from seven public health centres took part. They collected the data from 641 patients, but 233 patients did not participate (in 81.11% due to the PCP's workload). Therefore, the study coverage was around 64%, representing the quotient of the total number of patients who participated, divided by the total number of patients who were eligible for the study. We detected 30 patients with electrocardiographic alterations compatible with SCD risk. Nine of these had been examined by a paediatric cardiologist at some time (functional murmur in 8/9), five had reported shortness of breath with exercise, and four had reported a family history of sudden death. The physical examination of all the patients whose ECG was compatible with a risk of SCD was normal. Upon analysing to what extent the ECG results of the PCP and the paediatric cardiologist agreed, the percentage of agreement in the final interpretation (normal/altered) was 91.9%, while Cohen's kappa coefficient was 31.2% (CI 95%: 13.8–48.6%). The sensitivity of the ECG interpretation by the PCP to detect an ECG compatible with a risk of SCD was 29% and the positive predictive value 45%. Conclusions: This study lays the foundations for future SCD risk screening in children, performed by PCPs. However, previously, it would be important to optimise their training in reading and interpreting paediatric ECGs. What is Known: • In Spain at present, there is a programme in place to detect heart disease with a risk of sudden death [1], but it targets only children who are starting on or are doing a physical activity as a federated sport. Implementing such screening programmes has proven effective in several countries [2]. However, several studies showed that the incidence of sudden cardiac death is no higher in children competing in sport activities than in those who do not do any sport [3]. This poses an ethical conflict, because at present, children who do not do any federated sport are excluded from screening. According to the revised literature, so far, only in two studies did they screen the child population at schools, and in both, they successfully detected patients with heart disease associated to the risk of sudden death [4-5]. We have found no studies where the screening of these features was included within the routine healthy-child check-ups by primary care paediatricians. What is New: • We did not know whether—in our setting, at present—the primary care paediatrician could perform a screening method within the routine healthy-child check-ups, in order to detect presumably healthy children at risk of sudden cardiac death, as they present one of the SCD risks. In this regard, we proposed our project: to assess how to put into practice and conduct a cardiovascular assessment via SCD risk screening in the healthy child population by primary care paediatricians and appraise primary care paediatricians' skills in identifying the electrocardiographic alterations associated with SCD risk. The ultimate intention of this pilot study was to make it possible, in the future, to design and justify a study aimed at universalising cardiovascular screening and achieving a long-term decrease in sudden cardiac death events in children. [ABSTRACT FROM AUTHOR]

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases. In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p < 0.001) and serum creatinine levels (Spearman rho −0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort. Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM. [ABSTRACT FROM AUTHOR]

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5–8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556–0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004–1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799–1.000), indicating that these factors can accurately predict a poor prognosis. Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the intracellular and extracellular volume before and after anesthesia in order to ascertain their variations and determine the potential utility of this information in optimizing intraoperative fluid administration practices. A bioimpedance spectroscopy device (body composition monitor, BCM) was used to measure total body fluid volume, extracellular volume, and intracellular volume. BCM measurements were performed before and after general anesthesia in unselected healthy children and adolescents visiting the Pediatric Institute of Southern Switzerland for low-risk surgical procedures hydrated with an isotonic solution. In 100 children and adolescents aged 7.0 (4.8–11) years (median and interquartile range), the average total body water increased perioperatively with a delta value of 182 (0–383) mL/m2 from pre- to postoperatively, as well as the extracellular water content, which had a similar increase with a delta value of 169 (19–307) mL/m2. The changes in total body water and extracellular water content significantly correlated with the amount of fluids administered. The intracellular water content did not significantly change. Conclusion: Intraoperative administration of isotonic solutions results in a significant fluid accumulation in low-risk schoolchildren during general anesthesia. The results suggest that children without major health problems undergoing short procedures do not need any perioperative intravenous fluid therapy, because they are allowed to take clear fluids up to 1 h prior anesthesia. In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy. What is Known: • Most children who undergo common surgical interventions or investigations requiring anesthesia are nowadays hydrated at a rate of 1700 mL/m2/day with an isotonic solution. • The use bioimpedance spectroscopy for the assessment of fluid status in healthy children has already been successfully validated. • The bioimpedance spectroscopy is already currently widely used in various nephrological settings to calculate fluid overload and determine patient's optimal fluid status. What is New: • Routine intraoperative fluid administration results in a significant fluid accumulation during general anesthesia in low-risk surgical procedures. • This observation might be relevant for children and adolescents with conditions predisposing to fluid retention. • In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy. [ABSTRACT FROM AUTHOR]

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1–4 years old have significantly higher anti-N IgG titers compared to children aged 0–1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs. Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1–4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures. [ABSTRACT FROM AUTHOR]

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1–258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1–12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3–258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization. Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6–12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter–Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). Conclusion: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. What is Known: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. What is New: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus. [ABSTRACT FROM AUTHOR]

There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), namely (Crohn's disease (CD) and ulcerative colitis (UC), are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objective of this study was to evaluate the atrial electromechanical properties in children and adolescents with IBD during remission. One hundred IBD patients aged 12–17 years (50 with CD and 50 with UC) in remission state and 100 healthy controls were recruited for the study. Atrial electromechanical properties were measured using transthoracic echocardiography, tissue Doppler imaging, and simultaneous surface ECG recording. Interatrial EMD, left intra-atrial, and right intra-atrial EMD were calculated. IBD patients in remission state have significantly prolonged left and right intra-atrial EMD and interatrial EMD compared to healthy controls (P = 0.03, P = 0.02, and P = 0.01 respectively). No statistical difference was observed between CD and UC in terms of inter- and intra-atrial EMDs. Conclusion: Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD. What is Known: • There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). • Inflammatory bowel diseases are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. • Atrial electromechanical delay (EMD) has been reported as an early marker of AF. What is New: • Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. • Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD. [ABSTRACT FROM AUTHOR]

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p <.001), while the mean eCRPv values did not differ significantly (p =.15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7–17.8], p =.004). Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels. [ABSTRACT FROM AUTHOR]

Assess creatinine levels in French children with Down syndrome (DS) on the basis of the relationship between creatinine levels and age. The study included 279 children with DS aged 0 to 10 years who had been regularly monitored between 2004 and 2021 in a single genetics department and who had had at least one creatinine measurement. The creatinine level curves were established by estimating the median and the quantiles of order 2.5 and 97.5% according to age. A Generalized Additive Model for Location, Scale, and Shape was used. The results showed higher creatinine levels in children with DS than in children from the general population. Conclusion: The present results allow to propose an original chart of creatinine levels according to age in French children with DS, which should help optimize their medical management and improve the early detection of renal diseases. What is Known: • Creatinine is a product of muscle breakdown and depends on muscle mass and children with Down syndrome have muscle and growth characteristics that differ from those of the general paediatric population. • Serum creatinine values in Japanese children with DS are higher than those of children from the general Japanese population. What is New: • Creatinine values in French children with DS are higher than those of children from the general French population. • The proposed original chart for creatinine values according to age, specifically designed for individuals up to 10 years old, should serve for further investigation, prevention, and follow-up of children with DS. [ABSTRACT FROM AUTHOR]

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy. Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30–57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function. [ABSTRACT FROM AUTHOR]

Immunoglobulin A vasculitis(IgAV) is the most common form of systemic vasculitis affecting children. To date, cardiac involvement in pediatric IgAV has not been fully investigated and its prevalence may be underestimated. This study aims to reveal the clinical and laboratory characteristics of cardiac involvement in pediatric IgAV and further determine its risk factors. A total of 1451 children with IgAV were recruited between January 2016 and December 2022. According to the severity of cardiac involvement, the patients were divided into the myocarditis/suspected myocarditis group, cardiac abnormalities group, and non-cardiac involvement group. Demographic, clinical, and laboratory characteristics were retrospectively extracted from the individual data collected in the medical records. Among the 1451 pediatric IgAV patients, 179 (12.3%) were identified with cardiac involvement, including 154 (10.6%) with cardiac abnormalities and 25 (1.7%) with myocarditis/suspected myocarditis. Cardiac involvement in pediatric IgAV mainly manifested as elevated cardiac biomarker levels (n = 162), electrocardiogram abnormalities (n = 46), and echocardiogram/chest X-ray abnormalities (n = 15); however, cardiac-related symptoms were only observed in 15.1% of patients with cardiac involvement. Multivariate analysis demonstrated that interval from disease onset to diagnosis > 7 days (OR, 2.157; 95% CI, 1.523–3.057; p < 0.001), IgAV with multi-organ involvement (OR, 1.806; 95% CI, 1.242–2.627; p = 0.002), and elevated D-dimer levels (OR, 1.939; 95% CI, 1.259–2.985; p < 0.001) were independent risk factors for cardiac involvement in pediatric IgAV. The length of hospital stay was significantly longer in the myocarditis/suspected myocarditis group compared with the other two groups (p < 0.05). Conclusion: This study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. What is Known: • Immunoglobulin A vasculitis (IgAV) is the most common form of systemic vasculitis affecting children and adolescents, which exhibits diverse clinical manifestations. Cases of severe IgAV complicated by cardiac involvement have been anecdotally reported. What is New: • The present study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. [ABSTRACT FROM AUTHOR]

Neurogenic inflammation is involved in the development and progression of respiratory inflammatory diseases. However, its role in community-acquired pneumonia (CAP) remains unclear. We therefore aimed to investigate plasma levels of neurogenic inflammation-related neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and procalcitonin (PCT) in pediatric patients with CAP and to assess their diagnostic value in viral and bacterial/mixed pneumonia. A total of 124 pediatric patients with CAP (1 month-18 years old) and 56 healthy children of similar ages were prospectively enrolled. The patients were classified as viral (n = 99) and bacterial/mixed (n = 25) pneumonia. Plasma levels of the peptides were quantified by ELISA. ROC analysis was performed to evaluate possible diagnostic value of the peptides. While plasma levels of CGRP, VIP and PCT were significantly higher in patients with CAP than in the control group, respectively, NPY levels were significantly lower. Moreover, plasma levels of all neuropeptides and PCT were significantly higher in bacterial pneumonia patients compared to viral pneumonia patients. ROC analysis revealed that CGRP, SP and NPY had a diagnostic value in distinguishing viral and bacterial/mixed pneumonia. Conclusions: Our findings suggest that these neuropeptides may be implicated in pediatric CAP. CGRP, SP and NPY together may be a promising candidate in distinguishing viral and bacterial/mixed pneumonia, however, for this, further studies are needed. What is Known: • Neurogenic inflammation contributes to the development and progression of respiratory inflammatory diseases such as chronic obstructive pulmonary disease and bronchial asthma. What is New: • Plasma levels of neurogenic inflammation related neuropeptides calcitonin gene-related peptide, substance P, vasoactive intestinal peptide and neuropeptide Y are changed in pediatric community-acquired pneumonia. Calcitonin gene-related peptide, substance P and neuropeptide Y are promising candidates in distinguishing viral and bacterial/mixed pneumonia. [ABSTRACT FROM AUTHOR]

Although play has existed in paediatric hospitals for decades, a shared understanding of why and how healthcare professionals use play in clinical practice is lacking. This study aims to reach consensus on a common set of principles and competencies for play interventions and practices in hospitals. We conducted a three-round Delphi study that included healthcare professionals selected by hospital management. The first round comprised open-ended questions on the use of play in clinical practice. Principles and competencies, including learning objectives, were established using content analysis through an iterative process. Participants rated the importance of each principle and learning objective in the second and third rounds. Among the 66 participants, 45 (68%) responded in round 1 and 41 (62%) in rounds 2 and 3. The participants represented ten countries and nine different health professions. After the three rounds, we identified 33 principles and six overall competencies: building trusting relationships; delivering information and increasing understanding; promoting cooperation and participation; reducing procedure-related anxiety and pain; supporting coping and development; and ensuring a professional approach to play, which comprised 20 learning objectives. Conclusion: According to healthcare professionals, play in clinical practice can be used to communicate and build relationships with paediatric patients and thus potentially help provide patient-centred care. Our findings may help guide and prioritize future research initiatives and operationalize play interventions and practices in hospitals. What is Known: • Evidence suggests that using play in clinical practice can help paediatric patients during hospitals stays. • Despite the evidence supporting the use of play, a shared understanding of why and how paediatric healthcare professionals use play is needed. What is New: • This international Delphi study contributes to a shared interprofessional understanding of the principles, competencies and learning objectives for the use of play in clinical practice. • The findings have the potential to aid initiatives in developing training programmes for healthcare professionals in using play to provide care with a patient-centred approach. [ABSTRACT FROM AUTHOR]