In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD, due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive cure available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cells-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to higher-risk subpopulations of premature infants. Hence the need for easy-to-use noninvasive tools for a standardized, precise and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic but can result in a fatal outcome, therefore, prediction of the disease severity is important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single nucleotide polymor-phisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case-control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS -C) and 15 healthy who did not have COVID-19 infection (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe course COVID-19 infection, and MIS-C in 85.6% of cases. The World Health Organization reported new COVID-19 variants may cause previously unseen symptoms in chil-dren. Although the study has limitation due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.

Introduction: Determination of radiological bone age (BA) is a diagnostic method that consists of estimating chronological age (CA) from the bone maturation of children. Although environmental and hormonal factors can interfere with bone ossification, the process is essentially dependent on ancestral inheritance. These ethnic backgrounds are not usually considered, which can lead to biased interpretations and inadequate decision-making by pediatricians or forensic experts. The objective of this study was to determine the precision and accuracy of these radiological procedures among different ethnic groups. Methods: A qualitative systematic review carried out following MOOSE statement and previously registered in the International Prospective Registry of Systematic Reviews PROSPERO (CRD42023449512). Search was performed in MEDLINE (PubMed) (n=561), Cochrane Library (n=261), CINAHL (n=103), Web of Science (WOS) (n=181) and public institutional repositories (n=37) from inception to 31st December 2022 using Mesh as “Diagnostic Techniques and Procedures”, “Diagnostic imaging”, “Radiography”, “Age Determination by Skeleton” and free terms combining with booleans “AND” and “OR”. PEDro scale, and Risk of Bias in non-randomized Studies of Exposure (ROBINS-E) were used to assess methodological quality and risk of bias of included studies respectively. Results: 51 articles (n=19,531) were included according to the inclusion criteria previously established. There was a good to moderate methodological quality and a high to very high risk of bias. Skeletal methods for determining BA were precised in terms of intra-observer and inter-observer reliability in all ethnic groups. Regarding to accuracy of Skeletal methods in Caucasians and Hispanic children, GPA was accurate at all ages, but in youths, TW3 RUS could be a consistent alternative. In Asian and Arab, GPA and TW3 overestimated BA in adolescents near adulthood. In African youths, GPA overestimated BA while TW3 was more accurate in estimating CA. Dental and Cervical radiographic methods are equally precise but lesser accurate than Skeletal BA determination. Conclusion: Skeletal radiographic methods GPA and TW3 are both precise for BA determination among all ethnical groups, but their accuracy in estimating CA can be altered by racial bias.

Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Acute myeloid leukemia (AML) is the second common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes the childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management and prognosis prediction is much more important than before. The WHO classification of myeloid neoplasms and the European LeukemiaNet (ELN) classification were both revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different, therefore, in this review we emphasize in well-known genetic subtypes in childhood AML, including Core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotypes AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML and acute promyelocytic leukemia (APL). Current risk group classification, management algorithm in childhood AML and novel treatment modalities, such as targeted therapy, immune therapy, chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.

Kinetic estimation of glomerular filtration rate (KeGFR) proved its utility in predicting acute kidney injury (AKI) in both adults and children. Our objective is to assess the clinical utility of KeGFR in predicting AKI severity and progression to acute kidney disease (AKD) in patients already diagnosed with AKI and to examine major adverse kidney events at 30 days (MAKE30). We retrospectively calculated the KeGFR in the first 24 hours of identified AKI (KeGFR1) and in the 24 hours prior to AKD (KeGFR2) in all admitted children under 18 years old. The cohort consisted of 803 patients with AKI. We proposed a new classification of KeGFR stages, from 1 to 5, and assessed the predictive value of KeGFR stages for AKD development and MAKE30. AKI severity was associated with lower KeGFRs. KeGFR1 and KeGFR2 predicted AKD with AUC values between 0.777 and 0.841 respectively, p<0.001. KeGFR2 had the best performance in predicting MAKE30 (AUC of 0.819) with a sensitivity of 66.67% and specificity 87.7%. KeGFR1 stage 3, 4 and 5 increased the risk of AKD by 3.07, 6.56 and 28.07 times respectively while KeGFR2 stage 2, 3, 4 and 5 increased the risk of AKD 2.79, 3.58, 32.75 and 80.14 times fold. Stage 5 KeGFR1 and KeGFR2 stages 3, 4 and 5 increased the risk of MAKE30 by 7.77, 4.23. 5.89 and 69.42 times in the adjusted models. KeGFR proved to be a useful tool in AKI settings. KeGFR dynamics can predict AKI severity, duration and outcomes.

Successful implementation of antibiotic stewardship programs (ASP) requires a well-structured approach involving all stakeholders. Despite embracing key responsibilities, nurses’ role remains poorly defined, preventing consistent engagement. We conducted a scoping survey to assess knowledge, attitude and perception of nurses towards nurse-led initial sepsis risk evaluation using the sepsis risk calculator (SRC) of newborns admitted to the mother-baby unit. Single-center, cross-sectional study. Study link was sent to all full-time nurses in mother-baby unit. Survey centered around knowledge of unit’s ASP and attitude and perception towards nurse-led initial sepsis risk evaluation. 89% response rate. 100% agreed that SRC reduced antibiotic use and 66% felt nurse-led sepsis risk evaluation will enhance nurse involvement, but this was offset by extra burden of work (66%) and low confidence in differentiating stable from clinically unstable infants (46%). Other facilitating factors included greater nurse/patient ratio (100%), targeted education (89%) and incorporation of the SRC into EMR (78%). Only 11% were willing to serve as champions for it. There was no significant correlation to age or experience however, greater number of fresh grads were interested in championing this effort. Our study identifies a need for strong foundation of knowledge and greater nurse/patient ratio as two main factors for improving nurse-led use of the SRC. Multi-site studies scoping barriers to nursing involvement for successful implementation of ASPs are necessary.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

This study aimed evaluating 7 years’ outcome in 118 very preterm newborn (VPN, gestational age=26±1.4wks) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS) requiring ventilation for 14±2 days post-natal age (PNA). Repeated instillation of 200mg/kg Poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but SURF infants needed less re-hospitalization than controls for respiratory problem at 1- and 2-years PNA. There was no growth difference at 7.1±0.3 years for 41 SURF vs. 36 controls (80% eligible children); 7.9% SURF vs. 28.6% controls presented asthma (p=0.021). Children underwent cogni-tive assessment (WISC IV) and pulmonary function testing (PFT) measuring spirometry, lung volumes and airway resistance. Spirometry showed differences (p<0.05) between SURF and con-trols (mean±standard deviation (median z-score)) for FEV1 (L/s) (1.188±0.690(-0.803) vs. 1.080±0.243(-1.446)); FEV1 after betamimetics (1.244±0.183(-0.525) vs. 1.091±0.209(-1.342)); FVC (L) (1.402±0.217 (-0.406) vs. 1.265±0.267(-1.141)), and FVC after betamimetics 1.452±0.237 (-0.241) vs. 1.279±0.264(-1.020)). PFT showed no difference in volumes or airway resistance. Global IQ median [Inter-quartile Range] was 89[82:99] vs. 89[76:98] with 61% children >85 in both groups. Former VPN presenting severe neonatal RDS treated with repeated Surfactant have improved lung function and less asthma at 7 years PNA. There were no differences in neurodevelopmental outcome

The 2022-2023 influenza season in Romania was characterized by high pediatric hospitalization rates, predominated by influenza A subtypes H1N1 and H3N2. Lowered population immunity to influenza after the SARS-CoV-2 pandemic and subsequent stoppage of influenza circulation, particularly in children who had limited pre-pandemic exposures, influenced hospitalization among children immunosuppressed, and patients with concurrent medical conditions who are at increased risk for developing severe forms of influenza. This study focused on the characteristics of influenza issues among paediatric patients, as well as the relationship between different influenza virus types and viral and bacterial coinfections and illness severity in the 2022-2023 season after the SARS-CoV-2 pandemic. We conducted a retrospective clinical analysis on 301 cases of influenza in pediatric inpatients (age ≤ 18 years), hospitalized at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" IX Pediatric Infectious Diseases Clinical Section between October 2022 and February 2023. The most significant age group was 57.8% representing children between one to four years old and female. The average clinical forms were found in 61.7%, whereas severe versions represented 18.2% of cases. Most of the complications were respiratory (acute interstitial pneumonia, 76.1%), hematological (72.1%), represented by intra-infectious and deficiency anemia, leukopenia, thrombocytopenia), 33.6% were digestive, such as diarrheal disease, liver cytolysis syndrome, and the acute dehydration syndrome associated with electrolyte imbalance (71.4%). Severe complications were associated with a risk of unfavorable evolution: acute respiratory failure and neurological complications (convulsions, encephalitis). No deaths were reported. We noticed that the flu season 2022-2023 was characterized by the association of co-infections (viral, bacterial, fungal and parasitic) more frequent than in previous years (26.2% vs. 16%), which evolved more severely, with prolonged hospitalization and more complications (p<0.05), and time of use of oxygen therapy was statistically significant (p > 0.05); influenza vaccination in this group was zero. In conclusion, coinfections with respiratory viruses increase the severity of the pediatric population's immunity to influenza, especially among young children who are more vulnerable to developing a serious illness. All people above the age of six months should get vaccinated against influenza to prevent the illness and its severe complications.

Three-quarters of a million babies are born extremely preterm (< 28 weeks’ gestation) world-wide with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopul-monary dysplasia (BPD) and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal pe-riod. In newborn animal models, pioglitazone is shown to be protective against BPD, necrotising en-terocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelop-ment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema seen rarely in adults may be avoided with a short treatment course. Other effects of pioglitazone including improved glycaemic control and lipid metabolism may provide added benefit in prematurity. Currently, there is no formulation of pioglitazone suited for administration to preterm babies A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.

Background. Human Milk (HM) is a dynamic nourishment: its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important evaluate the impact that gestational diseases have on HM components and if their presence, as source of oxidative stress in the mother, influence milk’s redox homeostasis. To assess Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) effect on milk’s total oxidative load, we chose to investigate both oxidative and antioxidant aspects, with respectively Lipid hydrop-eroxides (LOOHs) and Glutathione (GSH)). Methods. GSH and LOOHs were quantified using an ELISA test. To investigate the effect of pathology on redox homeostasis, mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were re-cruited. The GSH concentration results significant lower in GDM women than in healthy only in colostrum (p<0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the anti-oxidant composition of HM mainly in colostrum, but in case of PE, the composition of HM milk is preserved.

Sleep-disordered breathing is a significant problem affecting the pediatric population. These conditions can affect sleep quality and significantly affect children's overall health and well-being. Difficulties in social interaction, communication, and repetitive behavioral patterns characterize autism spectrum disorder. Sleep disturbances are common in children with ASD. This literature review aims to gather and analyze available studies on the relationship between SDB and children with autism spectrum disorder. We comprehensively searched the literature using major search engines (PubMed, Scopus, and Web of Science). After removing duplicates, we extracted a total of 96 records. We selected 19 studies for inclusion after a thorough title and abstract screening process. A total of 7 articles were ultimately included. This review has analyzed the relationship between autism spectrum disorder and sleep-disordered breathing, particularly Obstructive Sleep Apnea, highlighting an intriguing web of complex associations. Some studies involving children have demonstrated a significant association between autism spectrum disorder and the presence of Obstructive Sleep Apnea. Furthermore, a heightened risk of developing sleep disturbances, including sleep-disordered breathing, has emerged in children with autism. The risk and prevalence of obesity are increasing in pediatric subjects with autism spectrum disorder. Obesity has been identified as a predictive factor for Sleep-disordered breathing, and Body Mass Index can directly correlate with Obstructive Sleep Apnea in these children. Adenotonsillectomy has proven to be pivotal in improving behavioral issues in autism spectrum disorder children with obstructive Sleep Apnea. In conclusion, this review underscores the complexity of the interplay between autism spectrum disorder and sleep-disordered breathing, emphasizing the importance of further research to understand underlying mechanisms and develop optimal therapeutic and preventative approaches to enhance sleep quality and overall health in children with autism spectrum disorder.

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

Lipofibromatous hamartoma, first reported in 1953, is a rare, slowly-progressive soft tissue tumor, characteristics of which include enlargement of the affected nerve by epineurial and perineurial proliferation of adipose and fibrous tissues. Out of previously reported 200 cases of lipofibromatous hamartoma of the median nerve, there have been approximately 40 pediatric cases under the age of 18. Herein, we report a case of lipofibromatous hamatoma of the median nerve in a 3-year-old female patient, who was surgically decompressed by carpal tunnel release only and histologically confirmed. The patient was followed-up on outpatient clinic basis annually along with ultrasonography, and the postoperative 10th year follow-up did not show recurrence or any deficits in motor and sensory functions

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency. In this study we assess the prevalence of restless sleep disorder, as well as that of periodic leg movements during sleep (PLMS) in these children. Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery or tracheostomy were included. Three groups were compared, children with PLMS index&gt;5, children with restless sleep disorder (RSD), and children with neither elevated PLMS index nor RSD. During the study, 2,577 sleep studies were conducted. Ninety-two studies fit our criteria and were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; after polysomnography 18% were found to have PLMS index &gt;5/hour, 14% fit the criteria for RSD. There were no statistically significant differences in polysomnographic parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). There was elevated frequency of RSD and elevated PLMS in children with history of prematurity that might be linked to the increased risk of iron deficiency in premature infants. These new results add new knowledge on the prevalence of RSD in these children.

To learn what mothers know on newborn bloodspot screening (NBS), the procedure, and sources used, a pilot study was performed. An online questionnaire was developed, with a first part fo-cused on characteristics and the NBS procedure, a second on knowledge, information sources, and health care providers (HCP). This questionnaire was accessible until 200 answers were received. Characteristics of respondents were representative for the population. Mothers recalled verbal consent in 69.5%, 12.5% did not, 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, 5 multiple-choice questions on sources, and assessment (5-point Likert) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory and post-analysis sample handling were poorly known. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was pro-vided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 (clarity, timing ap-propriateness, sufficiency, usefulness). The knowledge level and consent practices were reasonable well. Key HCP were midwives and nurses, leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

Standardized protocols were specifically designed and developed for clinical information collection and obtaining trio genomic information from infants affected with congenital anomalies (CA) and their parents, as well as securing human biological resources. Two large areas of these protocols include clinical and genomic information collection on CA which were difficult to diagnose using pre-existing screening methods. The following are three essential items for the clinical information collection protocol: establishment of a consent system for collecting and utilizing research resources, establishment of criteria for target patient selection, and collection of clinical and epidemiological information. A total of 138 cases consisting of 45 families of infants with CA and their parent trios have provided human-derived resources and genomic information. Whole genome sequencing data have been generated for all participants, and standardized protocols for resource collection and manufacturing have been developed. Phenotype information according to the Human Phenotype Ontology term and major test findings were recorded. It is important to keep updating and recording clinical symptoms and genetic diagnosis that are newly added or changed over time. The unique significance of this study is to develop a protocol that enables long-term tracking by adding growth and development tests that reflect important characteristics of newborns. By using these clinical and genetic information collection protocols for CA, it will be possible to establish an essential platform for early genetic diagnosis and diagnostic research, and further present new genetic diagnostic guidelines in the near future.

product transfusions, but clinical practices vary widely. Many very low birth weight (VLBW) infants receive packed red blood cell (RBC) or platelet transfusions during their initial NICU stay, with incidence inversely proportional to gestational age at birth ^1,2. Many critically ill infants are also transfused with plasma or cryoprecipitate to promote coagulation ^3,4. These blood product transfusions are most often prophylactic, with clinical decisions made in response to numerical blood count values, as opposed to therapeutic transfusions in the context of active bleeding.Emerging evidence has shown that some transfusion practices are harmful for certain NICU patients, such as platelet transfusions in preterm infants ^5,6. More broadly, transfusion reactions can occur with virtually all blood products ⁷ and these reactions are likely under-diagnosed, under-estimated, and under-reported in pediatric patients ³. Our intention was to establish optimal transfusion guidelines for our division and neonatal network, including 19 hospitals, based on a review of currently available literature.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

Introduction: congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of urinary collecting system, known as hydronephrosis or ureterohy-dronephrosis. Mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin 11 and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate expression of fibrosis related genes in obstructive and normal ureteral tissue. Material and methods: it is a monocentric study in which nineteen patients were selected prospec-tively. 17 patients of which underwent Hynes-Anderson pyeloplasty due to the PUJO, 2 patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO) and 6 patients were chosen for control group: 5 underwent nephrectomies due to the kidney tumor and 1- upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR to evaluate the relative expres-sion of Tgfb1, Mmp1, Timp1, Pai1, Ctgf and Vegfa was performed. Expression levels of Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and Wilcoxon rank-sum test was performed to determine statistical significance of the differences. Results: significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, Pai1 was found. Discussion and conclusions: These findings suggest that tissue fibrosis similar to other tissues and organs is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF ex-pression is indicative of developmental origin of obstruction.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

Since first described by Dr. Tomisaku Kawasaki in 1967, the clinical diagnosis of Kawasaki disease (KD) has remained relatively unchanged. However, studies since then have suggested that diagnoses using only that original clinical criteria may lead to underdiagnosis. In this review, updated KD diagnostic methods, diagnostic methods for “atypical” KD, diagnostic pitfalls, and other differential diagnoses are discussed. Peripheral blood eosinophil showed important in distinguishing KD from febrile children. We review herein the current literature regarding new biomarkers, scoring systems, and microRNA panels that may aid in the diagnosis of KD, the importance of eosinophil and treatment updates.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

Abstract: Accurately predicting a fetus's gestational age (GA) is of utmost importance in prenatal care. This study aimed to develop an artificial intelligence (AI) model that can automatically predict GA using biometric measurements derived from fetal brain mag-netic resonance imaging (MRI). Additionally, we aimed to assess the significance of con-sidering different references when interpreting GA predictions. To achieve this, we obtained measurements such as Biparietal Diameter (BPD), Fron-to-occipital Diameter (FOD), and Head Circumference (HC) from a dataset comprising 52 normal fetal MRI cases with T2 Haste sequences from Rush University. Both manual and AI-based methods were utilized to acquire these measurements. We also employed three reference papers (Garel, Freq, and Bio) for comparison purposes. The results demonstrated a strong correlation between manual and AI measure-ments, indicating consistency between the two methods. The AI-based measurement of HC exhibited a higher correlation with actual values compared to BPD, FOD, and correct-ed BPD (BPDC). When comparing these measurements with GA in the Picture Archiving and Communication System (PACS), the differences varied depending on the reference used. Specifically, the differences ranged from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Furthermore, the Pearson correlation coeffi-cient analysis revealed that all correlation coefficients between PACS records and GA pre-dictions using different references were greater than 0.97. In conclusion, the AI model based on fetal brain MRI accurately predicts GA by uti-lizing BPD, FOD, and HC measurements. The AI approach, which involves combining line segments to calculate fetal head circumference, offers improved accuracy and con-venience compared to manual estimation. This study underscores the potential of AI models in accurately estimating gestational age and highlights their utility in prenatal care. By integrating AI as a valuable tool in prenatal care, we can enhance the accuracy, ef-ficiency, and decision-making involved in assessing fetal development and monitoring pregnancies using MRI measurements.

The influence of diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration, and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Background: The role of NFATC genes expression in BAV progression is not fully understood. Aim of study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. Methods: In 47 children with BAV the standard Doppler echocar-digraphic characteristics were detected and the expression of the NFATC1 and NFATC4 genes was studied. Results: PWTd, AoPPG, in BAV patients were significantly higher compared to healthy controls (PWTd median(min-max) 9 (7-10) mm vs 7 (6-8) mm), AoPPG median (min-max) 7,79 (2,98-15,09) mm Hg vs 2,94 (2,42-3,72) mm Hg. Expression of NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min-max) 70,88 (8,79-106,51) e.u. vs 7,72 (1,74-22,67) e.u., respectively p<0,05). Significant correlation of NFATC1 expression with Ao found (R=+0,53, p<0,05). In BAV patients with PWTd > 8 mm and Ao> 21 mm the NFATC1 expression was significantly higher compare to those with PWTd< =8 mm and Ao<=21 mm NFATC1 median (min-max) 45,49 (5,01-101,52) e.u. vs 15,53 (2,36-44,40) e.u., p<0.05 and 81.11 (20.27-101.10) e.u. mm vs 12.16 (2,40-45.49) e.u., p<0.05, respectively) Conclusion: in children with BAV the high expression of the NFATC1 calcineurin signalling pathway gene is associated with elevated PWTd and Ao.

Background: Wilms' tumor (or nephroblastoma) is a malignant and solid neoplasm that derives from the primitive renal bud. It represents the most frequent primary tumor of the urogenital tract in childhood, and treatment consists of surgery and chemo-radiotherapy. However, concerning the quality of life, the new therapeutic frontier is exploring other safer and potentially more effective options, such as minimally invasive surgery and biological drugs. Method: Literature (Pubmed) from January 2013 to March 2023 was reviewed. Results: One hundred five articles were included in the review. Conclusion: In addition to the therapeutic strategies already identified, such as classic surgery and pharmacological therapies, recent studies focus attention on the new frontiers of minimally invasive surgery, such as diagnostics using biomarkers and immunotherapy, which could represent a new therapeutic option and possibly less risky than in the past, contributing in fact to the current knowledge of the scientific panorama in terms of "tumor microenvironment" and systemic implications deriving from oncological disease.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by food selectivity in a significant portion of the population. The nature of this selectivity remains unclear, with hypotheses suggesting associations with sensory disorders or stereotypical and repetitive patterns of activity and interests. This study aimed to determine the prevalence and nature of food selectivity traits in individuals with ASD compared to the neurotypical population. The study involved 219 participants, with 115 diagnosed with autism and 92 without. 12 children undergoing diagnosis were excluded from the analyses. Findings revealed that food selectivity traits are more common in individuals with ASD, with differences in preferences mainly involving structure, color, taste, and serving method. Children with ASD had more food selectivity traits than those without, and certain food characteristics could alter intake as they grow. Selectivity occurred for both sensory and stereotypical reasons, but stereotypical features significantly differentiated neurotypical individuals from those with ASD.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

Embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present study, umbilical venous and arterial oxygen levels, fetal oxygen extraction, oxygen content, CO2, and lactate were evaluated in a cohort of healthy newborns with gestational age &lt; 37 weeks. A progressive decrease in pO2 levels associated with a concomitant increase in pCO2 and reduction of pH has been observed starting from the 23rd week until approximately the 33-34th week of gestation. Over this period, despite the increased hypoxemia, oxygen content remains stable thanks to increasing hemoglobin concentration, which allows the fetus to becoming more hypoxemic, but not more hypoxic. Starting from the 33-34th week, fetal oxygenation increases and ideally continues following the trend recently described in term fetuses. The present study confirms that oxygenation during intrauterine life continues to vary even after placenta development, showing a clear biphasic trend. Fetuses, in fact, from mid-gestation to near-term become progressively more hypoxemic. However, starting from the 33-34th week, oxygenation progressively increases until birth. In this regard, our data suggest that the placenta is the hub that ensures this variable oxygen availability to the fetus, and we speculate that this biphasic trend is functional to the promotion, in specific tissues and at specific timing, of stemness and intrauterine differentiation.

Originating in the 1970s, Magnetic Compression Anastomosis (MCA) has lately been revisited with a focus on minimal invasive surgery (MIS). The aim of this report is to reappraise our earlier experience with MCA with the intention of facilitating future MCA advancement. A retrospective review was conducted regarding preclinical experiments and clinical trials at a single institution from 1980 through 1995. The reviewed information was compiled and appraised to generate proposals for future MCA use. The experimental studies, including 250 MCA cases in gastrointestinal and urinary tract animal models, demonstrated the technical versatility of MCA as well as the superior biomechanical characteristics in comparison to hand-sewn anastomoses. Clinical trials encompassed 87 MCA procedures in 86 children, 2 to 10 years of age, involving the following techniques: non-operative esophageal recanalization (n=15), non-operative ileostomy undiversion (n=46), Swenson pull-through (n=10), non-operative urethral recanalization (n=5), and extravesical ureterocystoneostomy (n=11). Clinical MCA was found to be successful in over 87% of cases. MCA limitations concerning anastomotic failure and scarring were thought to be mostly due to inadequate magnetic compression. Based on our historic experience, we propose further research on the technical aspects of MCA, along with the biologic aspects of anastomotic tissue remodeling. Magnets should be designed and manufactured for a wide spectrum of pediatric surgical indications, particularly in combination with novel MIS techniques.

Bibliometric studies on inherited metabolic diseases(IMDs) didn't exist in the literature.Our research aims to conduct a bibliometric study to determine the current status,trending topics,and missing points of publications on IMDs.Between 1968-2023, we conducted a literature search with keyword "inherited metabolic disease" in the SCOPUS-database.We included research articles in medicine written in English,published in the final section.We created our data pool using VoSviewer, SciMAT, and Rstudio software programs for bibliometric parameters of the articles that met the inclusion criteria.We performed bibliometric analysis of the data with R-package "bibliometrix" and BibExcel programs.We included 2702 research articles published on IMDs.Top three countries that have written the most articles in this field are; USA(n= 501), United Kingdom(n=182), and China(n= 172).The most preferred keywords by the authors were;newborn screening(n=54), mutation(n=43), phenylketonuria(n=42), children(n=35), genetics(n= 34) and maple syrup urine disease(n=32).Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective showing that molecular and genetic studies in inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

Ascites is a term that describes a pathological accumulation of fluid in a peritoneal cavity. It is generally a rare occurrence in a pediatric population and is most commonly associated with liver failure and cirrhosis. In that case, a diuretic treatment is usually implemented to relieve the ascites as it forms in the mechanism of water retention and water leakage from the portal venous system due to portal hypertension. It is important to note however that many other issues may cause ascites in children. Those require a catered approach suited to the pathomechanism of ascites formation in those underlying conditions. That is why a complex diagnostic process ought to be run in pediatric patients with ascites to correctly identify a condition causing it and provide the patient with adequate and thorough care.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9 – 8 years), including 50 M and 26 F, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, F showed significantly better scores than M in grammatical production (p=.002), and M showed better active negative sentences comprehension (p=.035). Moreover, comparing the language profiles between M and F with receptive disorder, F had significantly worse grammatical comprehension and better grammatical production than M. Even among children without receptive disorder, F had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in F than M, can partially contribute to the delayed ASD diagnosis or underdiagnosis of F without intellectual disability. Finally, our results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

BACKGROUND: It has been known for decades that breastfeeding leads to a lower risk of asthma, respiratory infections, or metabolic syndrome at school age. In addition, evidence is now accumulating on the influence of breast milk on the shape, volume, or function of the heart and lungs. Within this field of research into the effects of breast milk on the structure of the heart and lungs, we have set out to analyze the differential electrocardiographic characteristics of schoolchildren who were once breastfed. METHOD: Observational cross-sectional study including 138 children aged 6 or 12 consecutively presenting to a well-child clinic between May and December 2022. Inclusion criteria: the ability to perform reproducible ECG records, the feasibility of weighing and measuring patient, and breastfeeding data collected from birth. RESULTS: Using the 40º cut-off value for the mean P-wave axis among schoolchildren, 76% of never breastfed children in our sample have a P-wave axis in a more vertical position than the mean as compared to 58% of ever-breastfed children (OR:2.25;95%CI:3.13-1.36); there was no other significant difference between infant feeding groups in somatometric characteristics or ECG parameters, CONCLUSION: We found a significant difference of the mean values of the P-wave axis between never and ever breastfed children. Although this report should be approached cautiously, these findings add to the renewed interest in discerning developmental interventions to improve cardiovascular health.

A high prevalence of childhood obesity has been observed in the last years. Ultrasound of adi-pose tissue is technique validated in adults in order to detect risk of comorbidity as NAFLD and NASH, but no studies at pediatric population. The main objective is to assess measurement of preperitoneal fat by nutritional ultrasound as a screening method for non-alcoholic fatty liver disease (NAFLD) in obese children. Patients and methods: Prospective longitudinal study. A study of somatometry, bioelectrical impedancemetry and nutritional ultrasound has been car-ried out. Results : 102 patients were included, with a mean BMI (SDS) of 2.58. A linear and direct correlation was observed between the fat mass measured by bioelectrical impedancemetry and the total subcutaneous abdominal fat measured by nutritional ultrasound. We also observed a correlation between preperitoneal fat measured by nutritional ultrasound and NASH, with a cut-off point of 0.93 cm of preperitoneal fat (sensitivity 96% and specificity 94%).Conclusions: Measurement of preperitoneal fat by nutritional ultrasound is a good screening method for NASH in obese children.

Congenital cytomegalovirus (cCMV) infection resulting from non-primary maternal infection or reactivation during pregnancy can cause serious fetal-neonatal sequelae. We describe a male newborn born at term, with signs of perinatal asphyxia, and intractable acute provoked seizures, in the context of severe cCMV infection. The newborn was delivered in a referral hospital by emergency caesarean section due to fetal distress. Due to signs of asphyxia at birth and clinical moderate encephalopathy (Sarnat 2), he was transferred to our center for therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 hours, however, soon after rewarming, he presented refractory status epilepticus. Cranial ultrasonography revealed bilateral ventricular and intraparenchymal hemorrhage. Routine infectious screen-ing on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions revealed positive CMV DNA Polymer-ase Chain Reaction (PCR) on all samples. The CMV DNA performed on the bloodspot (Guthrie) card taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. Maternal non-primary CMV infection in pregnancy is transmitted to the fetus in 0.5-2% of cases. When transmitted, it may cause serious fetal abnormalities, complications in the immediate neonatal period, and se-vere sequelae later in childhood. During pregnancy, it is useful to monitor maternal serology for CMV, even in previously immunized mothers, to identify signs of new infection or viral reactivation and implement measures to prevent neonatal sequelae. The possible advantages of standardized CMV screening of all newborns are a pertinent discussion point, as this may enable us to identify affected neonates timeously and prevent long term disabilities.

Neonatal apnoea has been treated with caffeine, affecting the central nervous and the cardiovascular system. Heart rate variability (HRV) reflects the activity of the autonomic nervous system (ANS) and might be used as a measure of ANS maturation in newborns. We aimed to establish the effect of caffeine on HRV in newborns and sought for a potential correlation between HRV and the postmenstrual age. In 25 newborns hospitalized due to apnoea and treated with caffeine (2.5 mg/kg), we assessed breathing frequency, arterial oxygen saturation, body temperature, and the heart rate, while they were sleeping. We assessed HRV by spectral analysis using fast Fourier transformation. The same protocol was reapplied 100 hours after caffeine withdrawal to assess control parameters. Caffeine increased breathing frequency (p=0.023) but did not affect any other parameter assessed including HRV. We established a positive correlation between postmenstrual age and HRV during treatment with caffeine as well as after caffeine had been withdrawn (total power: p=0.044; low-frequency band: p=0.039). Apparently, the maintenance dose of caffeine is too low to affect the heart rate and the HRV. A positive correlation between postmenstrual age and HRV might reflect maturation of ANS, irrespective of caffeine treatment.

Introduction The increase in survival of extremely preterm infants has led to increased rates of bronchopulmonary dysplasia (BPD). Therefore, a potential role of human milk feeding in protecting against this condition has been suggested. Material and methods Retrospective descriptive study based on data about morbidity in the population of infants born from 22+0 to 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and who were alive at discharge. The primary outcome was moderate-severe BPD. In addition, associated conditions were studied, including breastfeeding at discharge. The temporal trends of BPD and breastfeeding rates at discharge were also studied. Results In the study population of 4341 infants who survived to discharge, the rate of moderate-severe BPD was 43,7% and increased over the period to a rate >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were male sex, high-frequency oscillatory ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding at discharge and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901, and OR 0.714, 95% CI 0.602-0.847, respectively). The rates of human milk at discharge in infants with moderate-severe BPD increased over the period. In the last years, more than one-third of extremely preterm infants were discharged on exclusive human milk feeds, and about two-thirds of them on any amount of human milk feeding. Conclusions
The results of the present study strongly support the role of any amount of human milk in preventing BDP in extremely preterm infants.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Appropriate nutrition during pregnancy and the post-partum period is vital to both the parent and their offspring. Both under- and over-nourished status may have important microbial implications on the parental and infant gut microbiomes. Alterations to the microbiome can have implications for a person’s risk of obesity and metabolic diseases. In this review, we examine alterations in the parental gut, vaginal, placental, and milk microbiomes in the context of pre-pregnancy BMI, gestational weight gain, body composition, gestational diabetes, and parental diet. We also investigate how the infant gut microbiome may be altered by these different parameters. Many of the microbial changes seen in under- and over-nourished states in birthing parents may result in long-term implications to the health of offspring. Differences in diet appear to be a major driver of the parental, and subsequently milk and offspring microbiomes. Further prospective longitudinal cohort studies are needed examining nutrition and the microbiome to better understand its implications. Additionally, trials involving dietary interventions in child-bearing age adults should be explored to improve the parent and child’s risks for metabolic diseases.

Background: Children with anorectal malformation (ARM) require long-term follow-up, especially for fecal continence and main predictors of longer-term success are the type of ARM, associated anomalies and sacral integrity. Three-Dimensional High Resolution Anorectal Manometry (3D-HRAM) provides an image of the pressure profile of anal sphincter complex. Aim of study was to evaluate the anal sphincter function in ARM patients with 3D HRAM correlating this analysis to clinical outcome and to associated malformations. Methods: Forty ARM patients, were submitted to 3D HRAM: manometric, anatomical and clinical score were correlated to response to bowel management (BM). Results: A positive correlation between all scores and type of ARM was found: in high ARM and in patients with spinal anomalies (regardless to ARM type) lower scores were reported and even after BM they do not achieve good continence. Conclusions: 3D-HRAM provides information on the functional anatomy of the sphincter complex. Our study shows good correlation between the manometric results and clinical outcome, confirming spinal malformations and ARM type as most important prognostic risk factors for poor outcome. Specific sphincteric defects can be explored with manometry, allowing for tailored bowel management strategies.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P &lt; 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P&lt;0.01) and CRP was increased (P&lt;0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g. ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam), although old antibiotics such as colistin, tigecyclin and fosfomycin are also encombassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarse, with few clinical trials enrolling neonates for the evaluation of efficacy, safety and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population.

Prediction of survival in very preterm infants is very important in terms of clinical medicine and parent counseling. In this prospective study involving 96 very preterm infants, we evaluated whether metabolomic analysis of gastric fluid and urine samples obtained soon after birth could predict survival on days of life (DOL) 3 and 15 as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used. Uni- and multivariate statistical analyses were carried out to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time-points of the study. Binary logistic regression showed that certain metabolites in the gastric fluid including arabitol as well as succinic, erythronic and threonic acids was associated with DOL 15 and overall survival. Gastric glyceric acid was also associated with DOL 15 survival. Urine glyceric acid could predict survival on DOL 3 and overall survival. In conclusion, non-surviving preterm infants showed a different metabolic profile compared survivors showing a significant discrimination with the use of GC-MS-based gastric fluid and urine analysis. Results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants.

Mothers’ own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for the effects on the outcome in the short and long term, especially the neurological one. We studied the use of the MOM for WLBWs over a 5-year period. Statistical comparisons concerned data on feeding with the MOM during stay in NICU and at discharge with respect to maternal and neonatal variables (gestational age, birth weight, type of pregnancy if single or twin, maternal age) and to feeding data (timing of the start of the Minimal Enteral Feeding and the availability of the MOM, the achievement of the Full Enteral Feeding, the type of nutrition at discharge). We observed an increase, between 2017 and 2021, of MOM use (p=0.003). The availability of the MOM occurred on average on the fourth day of life and improved over the years. Start of MEF with human milk averaged 1.78 days and 54.3% of VLBWs received MEF with donor milk on the first day of life (50% within the first 6 hours). The average MOM at discharge was 47.6% with 36.1% exclusive MOM (EMOM) and an increase from 45.8% in 2017 (EMOM 33.3%) to 58.82% (EMOM 41.18%) in 2021. The mean average daily growth of the weight improved (p<0.001) during this period. There is no statistical difference between infants fed with MOM and those fed with bank milk. The maternal age, the start day of the MOM feeding and gestational age have a significant impact on the type of feeding at discharge.

(1) Birth asphyxia is the major cause for delivery room resuscitation. Subsequent organ failure and hypoxic-ischemic encephalopathy (HIE) account for 25% of all early postnatal deaths. The neonatal Sequential Organ Failure Assessment (nSOFA) considers platelet count, respiratory and cardiovascular dysfunction in neonates with sepsis. To evaluate whether nSOFA is also a useful predictor for in-hospital mortality in neonates (≥ 36+0 weeks of gestation (GA)) following asphyxia with HIE and therapeutic hypothermia (TH), (2) nSOFA was documented at ≤ 6 hours of life. (3) 65 infants fulfilled inclusion criteria for TH. All but one infant received cardiopulmonary resuscitation and/or respiratory support at birth. nSOFA was lower in survivors (median 0 [IQR 0-2]; n = 56, median GA 39+3, female n = 28 (50%)) than in non-survivors (median 10 [4-12], p < 0.001; n = 9, median GA 38+6, n = 4 (44.4%)). This was also observed for the respiratory (p < 0.001), cardiovascular (p < 0.001), and hematologic sub scores (p = 0.003). The odds ratio for mortality was 1.6 [95% CI = 1.2 – 2.1] per one-point increase in nSOFA. The optimal cut-off value of nSOFA to predict mortality was 3.5 (sensitivity 100.0%, specificity 83.9%). (4) Since early accurate prognosis following asphyxia with HIE and TH is essential to guide end-of-life decisions, nSOFA (≤ 6 hours of life) offers the potential to identify infants at risk of mortality.

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects, most frequently conotruncal cardiac anomalies, thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of the 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers, environmental factors as well as the impact of hemizygosity on the remaining allele contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach.

Kawasaki disease is a form of acute febrile multisystem vasculitis. In Japan, the Kobayashi score is used to predict intravenous immunoglobulin resistance and subsequent complications, including coronary artery abnormalities, in children with Kawasaki disease. If the score is high, it is standard practice to use steroids in the initial treatment of the disease. In this study, we describe a pediatric case of coronary artery abnormality formation after acute steroid treatment for Kawasaki disease, despite the lack of an inflammatory response and Kawasaki disease symptoms. The use of steroids with acute Kawasaki disease patients can mask laboratory findings and clinical symptoms. Echocardiogram should be considered an equivalent technique to physical examination.

Background: In healthy children, the frequency of anomalous persistence of primitive reflexes (PRs) and craniosacral blocks (CBs) are unknown, as well as their impact on neurodevelopment, behaviour disorders and related consequences. We aim to know the prevalence of anomalous PRs and CBs in apparently healthy children and its relationships with behavior and neurodevelopment anomalies. Methods: Participants (n=120) were evaluated through physical examination to detect PRs and CBs, an ad hoc parent survey to collect perinatal events, and children behavior assessment by teachers using Battelle score. Results: PRs were present in 89.5%. Moro (70.8%), cervical asymmetric (78.3%) and cervical symmetric PRs (67.5%) were the most frequent observed PRs. CBs were found in 83.2%, and the most frequent CBs were dura mater (77.5%) and sphenoid bone (70%) blocks. Moro, cervical asymmetric and cervical symmetric active primitive reflexes are significantly associated to cranial blocks of dura mater, parietal zones, and sphenoid bone sway. Gestational disorders or perinatal complications were associated to a higher frequency of PRs and CBs. The presence of PRs and CBs were associated with abnormal Battelle scores and neurobehavioral problems. Conclusion: Presence of PRs and CBs in children without diagnosed diseases are frequent and related with disturbances in childhood neurodevelopment.

Since 2000, caffeine is used as citrate salt of caffeine for treatment of apnea of prematurity. However, it remained elusive if caffeine citrate has a direct function in the respiratory epithelium, potentially as modulator for ciliary beat frequency (CBF) regulation in human respiratory cells (hRECs). Here, we studied the mechanism of action of caffeine citrate on the respiratory epithelium on hRECs derived from healthy donors and individuals with cystic fibrosis (CF) cultured under air-liquid-interface (ALI) conditions. CBF analyses of hRECs were performed by high-speed video microscopy. In the presence of caffeine, hRECs show a significant increase in CBF over ciliary base frequency (CBFb), demonstrating a direct influence of caffeine on ciliary function. We also demonstrate a specific action of caffeine at ryanodine receptor (RYR) channels, mediating calcium efflux from intracellular stores to increase CBF. We describe a novel pharmacological effect of caffeine citrate - direct increase of CBF of primary hRECs cultured at ALI. Caffeine citrate has certain advantages over other methylxanthines: it was shown to have stable plasma concentration, longer half-life, and is better tolerated than e.g. theophylline. We conclude that caffeine citrate therapy might be suitable strategy to treat respiratory diseases with compromised mucociliary clearance.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician’s toolbox. Several formularies exist worldwide, but they have never been fully mapped nor compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence.Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates.Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding.Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems in pregnancy and birth, and maternal health. It is clinically useful to be able to screen for developmental delay so that healthcare interventions can be considered. The present research used machine learning (random forest) to create an algorithm predicting psychomotor delay in 9-month-old infants using information ascertainable at birth and in early infancy. The dataset was the UK longitudinal Millennium Cohort study. Fifty-two predictors measuring socioeconomic indicators, paternal, family and social support for the mother, beliefs about good parenting, maternal health, pregnancy and birth were included in the initial algorithm. Feature reduction showed that of the 52 variables, birthweight, family income and parents’ ages had the highest feature importance scores and could alone correctly predict developmental delay with over 99% sensitivity and 100% specificity. The relationships between delay and some of the predictors, particularly income, were nonlinear and complex. The results suggest that the risk of psychomotor developmental delay can be identified in early infancy using machine learning, and that the best predictors are factors present prior to birth. Surprisingly, the most important factors included in the present study did not include illnesses during pregnancy such as eclampsia and infections.

Objective: This study aimed to determine impact of eHealth literacy on health promotion activities and preventive health practice among adolescents. Methods: This cross-sectional study was conducted between March and May 2022 with 706 adolescents in Çorum, Turkey. A face to face questionnaire form including socio demographic characteristics, preventive health practices, eHealth Literacy scale and Adolescent Health Promotion Scale were used. The data of the research were analyzed with the SPSS 22.0 program. Percentage, mean, Pearson Correlation analysis and multiple regression analysis were used in the analyzes. The p<0.05 value was considered statistically significant in the evaluations. Results: In the study, 55.8% were female and the mean age of the whole group was 16.09±2.63 years. The mean score of eHealth Literacy scale was 29.40±6.29. The mean of the total scores obtained from the Adolescent Health Promotion Scale was 137.97±21.87. Among the adolescents 96.0% didn’t use alcohol and 81% didn’t smoke. The rate of annual weight measure was 68.8%. Measurements of annual blood pressure, annual blood iron, annual cholesterol, annual dental examination and regular exercise rate were below 50%. There was a significant positive correlation between eHealth literacy and the Adolescent Health Promotion Scale (p<0.001). Multiple linear regression analysis was performed to predict eHealth literacy using the variables of Adolescent Health Promotion and preventive health practices. eHealth literacy was positively and significantly predicts health promotion behaviors (β= 0.27, t (695)= 7.54, p<0.001). eHealth literacy increased annual weight measurement by more than 0.13 (β=0.13), the annual blood iron measurement by more than 0.16 (β=0.16), annual dental examination by more than 0.11 (β=0.11). Conclusions: Adolescents ehealth literacy was high and effected via health promotion activities and preventive health practices. Developing eHealth litracy interventions will be important for environments with a high concentration of adolescents (schools, courses). Also, primary health care services should be entegrated with school environment.

Background & Objective. Perinatal hypoxia acutely triggers the release of cytokines and chemokines from neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, with the production of proinflammatory molecules. The brain damage extension seems to be related with both the severity of hypoxia and the balance between pro and anti-inflammatory host response. Methods: In this preliminary study we compared in 10 neonates with hypoxic ischemic encephalopathy (HIE), during therapeutic hypothermia (TH), plasmatic cytokines and other inflammatory molecules levels: monocytic chemotactic-protein-1 (CCL2/MCP-1), CXCL8, glial fibrillary acidic protein (GFAP), Interferon gamma (IFN y), Interleukin 10 (IL-10), IL-18, IL-6, CCL3, ENOLASE2, Colony Stimulating Factor(GM-CSF), IL-1b, IL-12p70, IL-33, Tumor Necrosis Factor alpha(TNF), collected at four different time points during TH (24 hours, 25-48 hours, 49-72 hours) , and after the rewarming (7-10 days from birth). Five of enrolled babies had pathological brain MRI (“cases”) and 5 had a normal examination (“controls”). Cytokines were measured by Magnetic Luminex Assay (Luminex SV 013-17 (14), instrument Biorad Bio-Plex 100 s.n. LX 10005039304). MRI images were classified according to the Barkovich score. Results: Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups of patients. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. After rewarming, some molecules showed an upward trend. At T4, levels tended to be close again (with the exception of IL-6, IL10 and IL18). Infants with worse MRI showed plasmatic GFAP levels higher than those with normal MRI, while their IL-18 was lower. Mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both the groups of neonates. Conclusion. In children with worse brain MRI we found high levels of GFAP and of IL-10 at T4, considered respectively an early biomarker of brain damage and a predictor of adverse outcome, according to the literature, and a trend towards low IL-18 levels. We found the greatest, although not significant, difference between molecules levels in cases and controls at time points T2 and T3, during TH. With the rewarming some molecules showed an upward trend. We cannot exclude that the small sample size may prevent significance in the differences from being achieved.

Abstract: Introduction: Covid-19 lockdown has caused important changes in children's routines, especially in terms of nutrition, physical activity, screen time, social activity, and school time. Regarding these changes, recent studies show that Covid-19 lockdown was associated with higher levels of anxiety and depression in children. The objective of this study was to assess changes in sleep quality in Spanish children during lockdown decreed by the Spanish government between March and June 2020. Methodology: We compared the BEAR score of 478 participants in the SENDO project at the periods before, during and after lockdown. We used hierarchical models with two levels of clustering to account for the intra-cluster correlation between siblings. Interaction of time with and a set of a priori selected variables was assessed by introducing the interaction term into the model and calculating the likelihood ratio test. Results: Mean scores in the BEAR questionnaire referred to the periods before, during, and after lockdown were 0.52 (sd 1.25), 1.43 (sd 1.99) and 1.07 (sd 1.55), respectively, showing a worsening of sleep quality as a result of confinement. Parental level of education was found to be an effect modifier (p for interaction=0.004). Children whose parents had higher education (university graduates or higher) showed a smaller worsening than those without. Conclusion: We found that the mean score in the BEAR questionnaire significantly worsened during lockdown and significantly improved after it. However, it did not reach the initial level. The mean score in the BEAR questionnaire referred to the period after lockdown was significantly higher than before.

Children under two years old are at risk for anemia because young children have an increased need for iron for their physical growth and brain development. The purpose of this study was designed to evaluate the effects of a caregiver potential support program on anemia prevention in children six months to two years old attending the subdistrict health-promoting hospital in Thasala District, Nakhon Si Thammarat Province. This study was quasi-experimental. The sample included children aged six months to two years old and their caregivers, who were selected by random sampling and allocated to either the experimental or control group, with 40 pairs per group. The experimental group received a potential support program, while the control group received regular care. Both groups were followed for 12 weeks. The instruments used were the potential caregiver assessment, children’s anemia assessment, and a program to support the potential of primary caregivers. Descriptive statistics, chi-square, and t-tests were used to analyze the data. The results revealed that 11.4% of the children had anemia, and a hematocrit count of less than 33% (range = 30-40, M = 34.89, SD = 1.97). The mean scores of knowledge about anemia and iron supplementation after using the program in the experimental group and control group were significantly different (p < 0.001). The mean scores of knowledge about anemia in the experimental and control group were 15.75, SD = 0.54, and 13.28, SD = 1.43 respectively. The mean scores of knowledge about iron supplementation in the experimental and control group were 10.75, SD = 0.49, and 8.15, SD = 1.54 respectively. It was found that the experimental group had a higher mean score on food care behaviors than the control group for 6-11 months and 1-2 years, with statistical significance. The experimental group also had a higher mean score of care behaviors concerning children’s consumption of medicine than the control group (M = 58.20, SD = 4.05; M = 45.78, SD = 9.66, respectively), (p < 0.001). The mean score of the hematocrit level for the experimental group was found to be higher than the control group after receiving the program (M = 35.80, SD = 1.55; M = 34.83, SD = 2.14, respectively), (p < 0.05). Therefore, healthcare providers should support caregivers' capacity to provide continued care for children to prevent anemia.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires comprehensively address the adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable for assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their well-being is affected and to identify children at risk.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

This study analysed through the perspective of networks the association between physical activity (PA), sedentary behaviour (SB), and cardiovascular risk factors in overweight low-income schoolchildren from the perspective of complex systems. Methods: The sample consisted of 41 overweight children between 6 and 10 years old (56% girls). PA and SB were analysed by accelerometer, and the measures of cardiovascular factor risk were: anthropometric and hemodynamic measurements, body fat, lipid profile and glucose, cardiorespiratory fitness (CRF), left ven-tricular mass (LVM), and Sokolov-Lyon. Network analysis with Boot-strap-1000 was performed to analyze the association between PA, SB and the cardiovascular risk factors. Results: Moderate to vigorous PA was positive related with Waist circumference (WC; 0.499), HDL-C (0.307), and CRF (0.276), and negatively associated with BMI (-0.251) and Fat (-0.341). For SB, positive associations were seen with WC (0.326), CRF (0.296), LVM (0.250) and Sokolov (0.215). Adicionalment, the centrality indicators highlighted WC as the most important variable in the network. Conclu-sion: Interventions that aim to mitigate the harmful effects of obesity on cardiovascular risk factors in overweight children should consider WC as an important variable in of system.

Novel treatment strategies are emerging for rare, genetic diseases, resulting in clinical trials that require adequate biomarkers for the assessment of the treatment effect. For enzyme defects, biomarkers that can be assessed from patient serum, such as enzyme activity, are highly useful, but the activity assays need to be properly validated to ensure a precise, quantitative measurement. Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by the deficiency of the lysosomal hydrolase aspartylglucosaminidase (AGA). We have here established and validated a fluorometric AGA activity assay for human serum samples from healthy volunteers and AGU patients. We show that the validated AGA activity assay is suitable for the assessment of AGA activity in the serum of healthy controls and AGU patients, and it can be used for diagnostics of AGU and, potentially, for following a treatment effect.

Introduction: The aim of this study was to prospectively evaluate parents’/guardians’ late recall of surgical procedures and risks of elective surgery after pre-operative interview with surgeons. Materials and Methods: All parents/guardians of patients <18 years of age undergoing elective procedures from January 15th to September 1st, 2022, were prospectively enrolled in the study. Before discharge, parents/guardians were asked to complete a questionnaire regarding the duration of the consent procedure, duration of the interview, quality of the informative handouts, and their ability to recall the type of disease, type of surgical procedure, and surgical risks. Answers were graded from 1 to 4. Results: One hundred and two questionnaires were returned. In all cases, informed consent was obtained between 24 and 72 hours prior to surgery. The following responses were collected: 98/102 (96%) parents/guardians reported that the duration of the consent process was adequate; 95/102 (93%) reported that the handouts were fully informative, and 7/102 (7%) reported that they were partially informative regarding explanation of the disease and surgical procedure; regarding complications, 93/102 (91%) perceived the handouts to be fully/partially informative, while 4/102 (4%) perceived the handouts to be poorly/non-informative, and 5/102 (5%) did not provide a response; 94/102 (92%) stated that they remembered the pathology, but only 87/94 (93%) recalled it correctly; 90/102 (88%) stated that they remembered the type of procedure, but only 76/90 (84%) recalled it correctly; and 53/102 (52%) stated that they remembered the surgical risks, but only 20/53 (38%) could recall more than one complication. Conclusions: Late recall of surgical complications by parents was poor despite the high perceived quality of the surgical risk handouts and medical interview.

Worldwide, diarrhoea in children under-five years of age is the second leading cause of death. Despite having high morbidity and mortality, diarrhoeal diseases can be averted by simple and cost-effective interventions. The Integrated Management of Childhood Illness (IMCI) has proposed the use of Oral Rehydration Salt (ORS) and zinc together with adequate food and fluid intake for the management of acute non-dysenteric watery diarrhoea in children. In the past, few studies examined the determinants of adherence to diarrhoea case management. Therefore, this study measured the determinants of therapeutic and dietary adherence to diarrhoea case management using the third and fourth wave of Pakistan Demographics & Health Surveys (PDHS) datasets. Data from 4,068 children between 0 to 59.9 months with positive history of diarrhoea were included, while data on children with dysentery, severe dehydration, and co-morbid condition was excluded. This study reported therapeutic adherence in less than 10% of children in Pakistan, while dietary adherence was reported in 39.2% of children (37.7% in 2012-2013 ~ 40.7% in 2017-2018). A significant improvement in therapeutic (0.8% in 2012-2013 ~ 8.1% in 2017-2018) and dietary adherence (37.7% in 2012-2013 ~ 40.7% in 2017-2018) was reported in the 2017-2018 survey, compared to the 2012-2013 survey. In general, children over the age of one year (compared to children <1 year) and of the richer/richest socioeconomic class (compared to poorest/poorer socioeconomic class) have showed higher therapeutic and dietary adherence. Therapeutic and dietary adherence among diarrhoeal children can be improved by increasing the awareness and accessibility of ORS, zinc, and essential foods.

Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.

Introduction: In the marginalised countries most neglected health issue is Newborn mortality. A study was undertaken to assess the influence of factors and newborn care practices influencing newborn health in the rural area of Bareilly district. Methodology: The Descriptive cross-sectional study was organized in the rural areas of Bareilly. Study participants were selected based on the mothers who gave birth to a baby during the last six months. The mothers who delivered in that area within six months were included, and using the semi-structured questionnaire, data was collected. Data analyzed using Microsoft Excel and SPSS 2021 version for windows. Results: Mothers initiating early breastfeeding were more commonly 78 (52.3%) observed in the younger mothers at 24-29 years, followed by 48(32.3%) at 30-35 years, the difference was statistically significant (p<0.05). Delayed bathing was observed in nearly 125 (70.1%) three fourth in the age of 24-29 years, followed by 29 (16.8%) in the age period 30-35 years. It was observed that unsafe cord care practices were observed more among 8(53.4%) nuclear families than 7(46.6%) joint families, and it was found to be statistically insignificant. Conclusion: The practice of essential newborn care still needs to improve in Bareilly; there is a need to create awareness to the mothers and family members on newborn and early neonatal care aspects, such as promoting exclusive and early initiation of breastfeeding and delayed bathing practices.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of functional impairments on altered muscle growth remains unclear. This prospective longitudinal study modelled the morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III=47/22/18). Repeated ultrasound assessments were performed during 2-year (y) follow-up with an interval of minimal 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I versus GMFCS-II&amp;III. MV and CSA growth trajectories showed piecewise model with 2 breakpoints, with the highest growth before 2y and negative growth rates after 6-9y. Before 2y, children with GMFCS-II&amp;III already showed lower growth rates compared to GMFCS-I. From 2-9y, the growth rates did not differ between GMFCS-levels. After 9y, a more pronounced reduction in normalized CSA was observed in GMFCS-II&amp;III. Different trajectories in ML growth were shown between the GMFCS-level subgroups. These longitudinal trajectories could be used to monitor the SCP muscle pathology during childhood and to optimize treatment planning and goals aiming to stimulate muscle growth

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.

Alloys based on TiNi are widely used in various fields of technology and medicine. In the present work, we report on preparation of TiNi-alloy based wire with the shape memory effect, which was used for compression clips for surgery. Composition and structure of the wire, and its martensitic and physical-chemical properties were studied using SEM, TEM, optic microscopy, profilometry, mechanical tests, etc. The TiNi alloy was found to consist of B2 and B19' and secondary-phase particles of Ti2Ni, TiNi3 and Ti3Ni4. Its matrix was slightly enriched in Ni (50.3 at. % of Ni). Homogeneous grain structure was revealed (an average grain size of 19±0.3 μm) with equal quantities of grain boundaries of special and general types. Surface oxide layer provide improved biocompatibility and promote adhesion of protein molecules. Overall, the obtained TiNi wire was concluded to exhibit martensitic, physical and mechanical properties suitable for its use as an implant material. The wire was then used for manufacturing compression clips with the shape memory effect and applied in surgery. The medical experiment that involved 46 children demonstrated that the use of such clips in children with double-barreled enterostomies permitted to improve the results of surgical treatment.

Background: The coexistence of a high IgE level and transient hypogammaglobulinemia of infancy ( THI ) with atopic dermatitis (AD) is well known, but the coexistence with a marked serum IgE level ≥ 1000 IU/mL is a rare finding. Literature is scarce regarding IgE levels in patients with THI and AD after treatment with immunoglobulin (Ig). The present article is the first to describe a finding of marked IgE elevation (> 1000 IU/mL) after treatment with intravenous immunoglobulin (IVIG). This paper also reviews previous related reports and series. Case presentation and review: We reported on a female infant 8 months old, with THI and severe AD. She was treated with IVIG infusion after the failure of conventional therapy. Initially, serum levels of IgE were high, and serum levels of IgG were low. After 4 weeks of treatment with IVIG, the patient showed clinically improved AD in parallel with elevated IgG level but increased IgE level to a higher level. We also review previous results of IgE levels reported in cases with THI and AD before and after Ig therapy. The mean increment in IgE levels was 227.5 IU/mL (SD = 164.2). The review showed that the IgG is directly related to IgA and IgM in addition to IgE. Results also showed that IgA and IgM also have a direct relation with IgE. Conclusion: We report a case of marked IgE level in a THI patient with AD after IVIG treatment. Also, there were increased levels of IgA and IgM. A similar finding was observed in other reviewed cases.

Background: The first few minutes after birth are the most dangerous for the survival of an infant. Babies in neonatal intensive care units are either under heated or overheated, and hypothermic infants remain hypothermic or develop a fever. As a result, special attention must be paid to monitoring and maintaining the time of recovery from hypothermia states. Despite numerous studies, only a few have examined the transition from neonatal hypothermia and associated risk factors in depth. Method: A retrospective observational study was conducted to track axillary temperatures taken at the time of neonatal intensive care unit admission, which were then tracked every 30 minutes until the newborn's temperature stabilized. All hypothermic neonates admitted to the neonatal intensive care unit between January 2018 and December 2020 was included in the study. Temperature data were available at birth and within the first three hours of admission for 391 eligible hypothermic neonates. The effect of factors on the transition rate in different states of hypothermia was estimated using a multi-state Markov model. Result: The likelihood of progressing from mild to severe hypothermia was 5%, while the likelihood of progressing to normal was 34%. The average time spent in a severe hypothermia state was 48, 35, and 24 minutes for three different levels of birth weight, and 53, 41, and 31 minutes for low, moderate, and normal Apgar scores, respectively. Furthermore, the mean sojourn time in a severe hypothermia state was 48, 39, and 31 minutes for three different levels of high, normal, and low pulse rate, respectively. Conclusion: For hypothermic survivors within the first three hours of life, very low birth weight, low Apgar, and high pulse rate had the strongest association with hypothermia and took the longest time to improve/recover. As a result, there is an urgent need to train all levels of staff dealing with maintaining the time of recovery from neonatal hypothermia.

The standard of care for nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. Methods: In our single-center retrospective study, we reviewed 46 pediatric patients who underwent nonoperative management of perforated appendicitis with Interventional Radiology (IR) percutaneous drainage. We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data. Results. Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38 [100%]), Bacteroides spp (33 [87%]) and Escherichia coli (27 [71%]). All patients who grew Pseudomonas aeruginosa had an oral antibiotic as a treatment option; similarly with 93% (25/27) of E. coli, 81% (13/16) of α-hemolytic Streptococcus spp, and 76% (29/38) of Enterococcus faecalis.  Conclusions:  Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Background. To improve maternal and child health, it is essential to adhere to health-promoting and preventive measures. However, reliable information as well as effective tools are not easy to identify in this field. Our cross-sectional study investigated the needs and expectations of expectant and new mothers and fathers -primary users of an app supporting the first 1000 days of life. Methods. Between May and August 2022, we recruited expectant and new parents by administering a 71-item 5-point Likert scale questionnaire related to content, functionalities, and technical features of a hypothetical app. We stratified responses by sociodemographic characteristics and then performed ward hierarchical clustering. Results. The 94 women and 69 men involved in our study generally agreed with the proposed content, but expressed low interest in certain app functionalities, especially those related to interaction mechanism and interactivity. Women were generally more demanding than men, and family income declined as the needs and expectations increased. Conclusions. Our findings, resulting from the engagement of end-users, may be useful for designers and technology providers to implement mHealth solutions that, in addition to conveying reliable information, are tailored to the needs and preferences of end-users in the first 1000 days of life.

It is already well known that infants and children infected with COVID-19 develop mild to mod-erate forms of the disease, with fever and oropharyngeal congestion being the most common symptoms. Nevertheless, there are cases in which the patients accuse respiratory symptoms. These cases need lung evaluation, which can be done using lung ultrasound (LUS), because it is a non-irradiating and repeatable imaging technique. 19 children with COVID-19 pneumonia were eval-uated using LUS. The LUS score (LUSS) for each patient varied between 1 to 8 points from a max-imum of 36 points. The arithmetic mean was 4.47 ± 2.36 (S.D), while 95% CI for the Arithmetic mean was 3.33 to 5.61. The lung changes were correlated with their biomarkers, specifically in-flammatory markers. The correlation between LUSS and LDH, D-dimers and IL-6 was a strong positive one with r=0.66 (p=0.01, 95% CI 0.147 to 0.896) between the LUSS and LDH level at symptomatic infants and children (with cough present) and r=0.66 (p=0.01, 95% CI 0.140 to 0.895) between LUSS and D-dimers level at symptomatic infants and children (with cough pre-sent). The results suggest that LUS could be a good imaging technique that can be used both in ini-tial evaluation of children with respiratory diseases, and, also in their follow-up, correlated with symptoms and biomarkers.

Background: Health inequity (HI) remains a major challenge in public health. Improving the health of children with low socioeconomic status (SES) can help to reduce overall HI in children. Childhood obesity is a global problem, entailing several adverse health effects. It is crucial to assess influencing factors for adoption, implementation and sustainment of interventions. This review aims to identify articles reporting about influencing factors for the implementation of school-based interventions promoting obesity prevention behaviors in children with low SES. It aims to critically appraise the articles’ quality, assess influencing factors, categorize and evaluate them, and to discuss possible implications. Methods: A systematic search was conducted in 7 databases with the following main inclusion criteria: 1) school-based interventions and 2) target group aged 5–14 years. The Consolidated Framework for Implementation Research, its five domains (intervention characteristics, inner setting, outer setting, characteristics of individuals, process) along with 39 constructs within these domains were used to deductively analyze the data. We grouped the articles with regard to the characteristics of the interventions in simple and complex interventions. For each domain, and for the groups of simple and complex interventions, the most commonly reported influencing factors are identified. Results: 6452 articles were screened, and 16 met all eligibility criteria. Included articles applied mixed methods (n=10), qualitative (n=5) and quantitative design (n=1). Of these, five were considered to report simple interventions and eleven were considered to report complex interventions. In total, 295 influencing factors were assessed. Aspects of the inner setting were reported in every study, aspects of the outer setting were the least reported domain, and in the group of simple interventions not reported at all. In the inner setting, most reported influencing factors were time (n=7), scheduling (n=6) and communication (n=6). Conclusion: This review found a wide range of influencing factors for implementation. Most important influencing factors need to be assessed for every setting. Including all stakeholders involved in the implementation process enhances the prioritization of the most important influencing factors for the specific setting. More empirical research and practical guidance are needed to promote obesity prevention behaviors among children with low SES.

In Kawasaki disease (KD), convulsions are rare and mostly attributed to latent and coexisting encephalitis/encephalopathy due to KD itself. Therefore, we retrospectively investigated concomitant viral infections in patients with KD. Between January 2012 and December 2020, among 523 patients with KD, 7 (1.53%), 1 (0.19%), 6 and 1 (1.15% and 0.19%) were positive for adenovirus (AdV-Ag), respiratory syncytial virus (RSV-Ag), and influenza A or B (Flu A-Ag or Flu B-Ag) antigens, respectively. Among them, two were positive for both AdV-Ag and FluA-Ag. Seven patients with KD (1.3%) presented febrile convulsions, and only one was diagnosed with encephalitis/encephalopathy. Between January 2021 and August 2022, 57 patients with KD were newly diagnosed among whom FilmArray® respiratory panel (FARP) was applied on 24 patients, and 14 (58.3%) were positive for at least one virus. During the same period, 32 out of 45 patients (71.1%) with febrile convulsions examined using the FARP were positive for at least one virus. The trend of viruses in patients with KD and febrile convulsion reflected the regional epidemic viral infection. Respiratory virus detected at a much higher rate using the FARP suggests that most convulsions in patients with KD might be related to concomitant viral infection. The possible involvement and association of concomitant respiratory viral infections in patients with KD with prognosis or encephalopathy/encephalitis remain to be investigated.

Rabies is a life-threatening and vaccine-preventable infectious disease and is triggered by an RNA virus, part of the Rhabdoviridae family, Lyssavirus genus. It is transmitted from infected saliva due to biting, but also from contact with infected blood or organs from rabid animals to humans. Children are at high risk due to their inability to defend themselves from infected animals and most deaths occur with a particularly high incidence in this category (under the age of 15 years). Postexposure prophylaxis (PEP) is standard and life-saving if given early after exposure. We are reporting the case of a ten-year-old female child, who was bitten by an unvaccinated cat ten days before admission to the Paediatric Intensive Care Unit at National Institute for Infectious Diseases „Prof. Dr Matei Bals”, Bucharest. The child had category III cat bites and did not receive PEP. Suggestive clinical manifestations such as an altered general state, psychomotor agitation, auditory and visual hallucinations, and hypersomnia followed by aerophobia and hydrophobia were present. Despite the maximal treatment introduced from early admission (Human Rabies Immunoglobulin, anti-rabies vaccination, orotracheal intubation plus mechanical ventilation, vital functions’ support, parenteral feeding, symptomatic drugs) the evolution of the patient was unfavourable, namely death two months after admission. The diagnosis was established in both pre-mortem by identifying the rabies virus in the cerebrospinal fluid based on reverse transcription-polymerase chain reaction (RT-PCR) and post-mortem by a histopathological examination (which reveals the presence of Babes-Negri bodies in the hippocampus). The objective is to understand the mechanism of infection and mortality from rabies virus in children. Conclusion: The most effective prevention methods are early administration of specific prophylaxis (immunoglobulin and vaccination) and, most importantly, early elimination of animal rabies outbreaks, while rapid diagnosis is helpful in the management of human rabies in humans. The rate of human exposure may be significantly decreased by controlling rabies through pet immunization programs.

It appears that up to 80% of females with autistic spectrum disorder (ASD) have not been diagnosed by 18 years of age. This translates to a prevalence of about 5-6%, and if true has serious implications for female mental health. One way of finding the true value is to use Bayes’ Theorem with a comorbid condition as a more easily recognizable flag. An obvious choice is anorexia nervosa (AN), but it transpires that the proportion of women with ASD who develop AN is unknown. This study uses published data in novel ways to provide two methods of estimating a range for this variable, and gives a median value of 8.3% for AN in ASD and with four other methods a median prevalence of 6% for female ASD. The clinical implications for diagnosis and management of ASD and comorbidities are discussed and a solution is provided for the rate of ASD in generalized joint hypermobility.

Care coordination (CC) for children with special healthcare needs and medical complexity (CSHCN-CMC) is challenging, and medication management is especially difficult for providers, parents/caregivers, and patients alike. While numerous strategies for CC have been suggested and implemented, barriers to medication optimization remain. The report describes the creation of a pediatric clinical pharmacotherapy practice, related standard operating procedures to assure consistent application of screening tools and care provision through comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy delegation, monitoring, and modification. The methodology of a prospective case series is also presented to highlight drug therapy problems and their resolution in CSHCN-CMC. Future opportunities to expand the practice for engagement in population health management as well as prior authorization activities on behalf of physicians will be discussed.

Ankyloglossia is a condition of limited tongue mobility caused by a short lingual frenulum. The diagnosis and treatment of ankyloglossia are still controversial. The main clinical problem encountered during breastfeeding is difficulty in sucking and its clinical reflections. This study aims to evaluate the newborn population born regarding ankyloglossia and to determine the results of frenotomy. We conducted an observational, cross-sectional study among newborns born in a tertiary hospital. We included all newborns born between January 1 and June 30, 2022. The study algorithm was determined before the defined dates and data were recorded during the screening period. The recorded data were retrospectively collected from the files. Within six months, 705 babies were born. Due to additional problems and other conditions that prevent breastfeeding, evaluable data of 207 (29.3%) infants could not be provided. Of the remaining 498 infants, 234 (33.2%) had ankyloglossia. Breastfeeding was unsuccessful before frenotomy in 12 Coryllos type-1 patients, and all had difficulty in sucking. Frenotomy was performed within the three-months follow-up period in all patients with complaints of inability to firmly grasp the breast, nipple slipping from the mouth, and nipple biting during the first 24 hours. In terms of breastfeeding problems, regardless of the anatomical typology, frenotomy can be performed safely in the early life with successful results. If deficiencies or difficulties in nursing is noticed in ankyloglossia patients even at the first control, frenotomy should be recommended in clinical conditions.

There is disagreement on the associations between chorioamnionitis and pneumonia/sepsis, respiratory distress syndrome (RDS), and bronchopulmonary (BPD)dysplasia, three pulmonary outcomes of concern for preterm newborns. Determining clear correlations is challenging due to the intricacy of the prenatal, postnatal, and therapeutic practices that affect the diagnosis of RDS, pneumonia/sepsis, and BPD, two long-term outcomes, as well as their short- and long-term consequences. Owing to the interconnected nature of the variables, the vaguely defined fetal exposures, and the imprecise identification of disorders like RDS and BPD, multivariant studies of huge data sets are unreliable methods for defining associations. On the other hand, research using animal models offers reliable data regarding the effects of exploratory chorioamnionitis on the fetal lung. Understanding the clinical intricacy and the experimental consequences of chorioamnionitis together will help us understand on the impact on the fetal lung .

Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been in the past associated with adverse effects on human health among which belong also respiratory diseases. Our study is focused on the evaluation of PAH exposure by measuring the concentrations of their monohydroxylated metabolites (OH-PAHs) in urine and comparing their concentrations with the incidence of respiratory diseases in 2-year-old children from two locations of the Czech Republic – a control locality Ceske Budejovice and a previously highly contaminated mining district Most. Methods: The total number of 248 participants were sampled for urine samples that were analysed for the presence of 11 OH-PAHs using liquid-liquid extraction with ethyl acetate and clean-up employing dispersive solid phase extraction with a sorbent Z-Sep. Separation, identification and quantification of the target compounds was achieved by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The incidence of respiratory diseases was evaluated according to the questionnaires provided by the paediatricians. Results and discussion: The concentrations of measured OH-PAHs were higher in the urine samples collected from 2-year-old children living in Most compared to 2-year-old children from Ceske Budejovice. The same trend was observed also when the urine samples were analysed when these children were studied as newborns in our previous study. From all of the monitored respiratory diseases, only influenza due to unidentified influenza virus showed a difference between tested locations where the 2-year-old children living in Most were more frequently diagnosed with this disease. Conclusion: Even though the air pollution and lifestyle in both cities is very similar, we have observed higher incidence of respiratory diseases as well as higher concentration of OH-PAHs in urine of the 2-year-old children from Most. Therefore, we hypothesize that the population living in this previously highly contaminated location (in 1970s and 1980s) can carry some long-term health burden.

Background: The robustness of sero-surveillence has delineated the high burden of SARS-CoV-2 infection in children; however, these existing data showed wide variation. This study aimed to identify the serostatus of antibodies against SARS-CoV-2 and associated factors among children following the fourth pandemic wave in Vietnam. Methods: A cross-sectional study was conducted at Vietnam National Children’s Hospital (VNCH) between March 13 and April 3, 2022. 4,032 eligible children seeking medical care for any medical condition not related to acute Covid-19 infections was tested for IgG SARS-CoV-2 Antibodies by ADVIA Centaur® SARS-CoV-2 IgG (sCOVG) assay using the residuals of routine blood samples. Results: The median age of enrolled children was 39 (IQR=14-82) months. The overall seropositive prevalence was 59.2%, and the median antibody titer was 4.78 [IQR 2.38-9.57] UI/mL. The risk of seropositivity and the median antibody titer was not related to gender (58.6% versus 60.1%, 4.9 versus 4.6 UI/mL, all p&gt;0.05). Among age groups, the highest seroprevalence was reported in the children aged 13 to &lt;36 months old. Children aged ≤12 months were likely to be seropositive compared to children aged 36 to &lt;60 months (59.2% versus 57.5%, p=0.49) and those aged ≥144 months (59.2% versus 65.5%, p=0.16). Children aged ≥144 months exhibited a significantly higher titer of protective COVID-19 antibodies than other age groups (p &lt;0.001). In multivariate logistic regression, we observed independent factors associated with SARS-CoV-2 seropositivity, including the age 13 to &lt;36 months (OR=1.29, 95%CI=1.06-1.56, p=0.01), 60 to &lt;144 months (OR=79, 95%CI=0.67-0.95, p=0.01), ≥144 months (OR=1.84, 95%CI=1.21-2.8, p=0.005), the presence of infected household members (OR=2.36, 95%CI=2.06–2.70, p&lt;0.001), participants from Hanoi (OR=1.54, 95%CI=1.34-1.77, p&lt;0.001), underlying conditions (OR=0.71, 95%CI=0.60-0.85, p&lt;=0.001), and using corticosteroids or immunosuppressants (OR=0.64, 95%CI=0.48-0.86, p=0.003). Conclusions: This study highlights a high seroprevalence of antibodies against SARS-CoV-2 among children seeking medical care for non-COVID-19-related conditions in a tertiary children’s hospital in Hanoi, Vietnam. In the context of reopening in-person schools and future emerged COVID-19 variants, this point will also be a key message about the necessity of “rush-out” immunization coverage for children, especially those under the age of three years.

Anemia is a significant public health problem among children, especially school-age children because their body quickly produces red blood cells to provide sufficient blood volume with plasma expansion to maintain blood concentration. This research aimed to study the anemia situation, knowledge about anemia, food consumption behaviors, and the association between knowledge, food consumption behaviors, and hematocrit level among school-age children in primary school, in Thasala district, Nakhon Si Thammarat Province. This is a descriptive study among 408 students, Grades 4 to 6, aged 9-12 years. Research instruments included the demographic data of the children and their knowledge about anemia, food consumption behaviors, and hematocrit assessment. Data were analyzed using descriptive, Spearman’s rank correlation coefficient, and logistic regression statistics. The results revealed that 23.2% of the samples had anemia, whereas 22.22% had mild anemia and 0.98% had moderate anemia. The children knew about anemia, where the mean score was at a moderate level (Mean= 6.63; SD= 2.51) out of 10. The mean score on food consumption behaviors was in the moderate level (Mean= 17.49; SD= 3.68) out of 24. There were significantly positive correlations between the knowledge about anemia and the hematocrit level at a moderate level (r= 0.45, p< 0.001). Correlation analysis revealed moderate food consumption behaviors with the hematocrit level (r= 0.40, p< 0.001). When confirm with Logistic regression found that knowledge about anemia (OR = 9.15, 95% CI: 4.57-18.34), and food consumption behaviors (OR = 19.09, 95% CI: 9.71-37.53) were significantly associated with the hematocrit level. Conclusions: This study showed that knowledge and appropriate food consumption behaviors are associated with hematocrit levels. Enhancing knowledge about anemia and food consumption behaviors may be reduced the prevalence of anemia in school-age children. The health care providers in primary care should be encouraged children to have health education and eat sufficient food.

Abstract: Objective: To assess both individual and interactive effects of prenatal medical conditions depression and Diabetes, and health behaviors including smoking during pregnancy on infant birth defects. Methods: The data for this research study were collected by the Pregnancy Risk Assessment Monitoring System (PRAMS) in 2018. Birth certificate records were used in each participating jurisdiction to select a sample representative of all women who delivered a live-born infant. Complex sampling weights were used to analyze the data with a weighted sample size of 4,536,867. Descriptive statistics were performed to explore frequencies of the independent and dependent variables. Bivariate and multivariable analyses were conducted to examine associations among the independent and dependent variables. Results: The results indicate and significant interaction between the variables smoking and Depression and Depression and Diabetes (OR= 3.17; p-value <0.001 and OR= 3.13; p-value <0.001 respectively). Depression during pregnancy was found to be strongly associated with delivering an infant with a birth defect (OR= 1.31, P-value < 0.001). Conclusion: Depression during pregnancy and its interaction with smoking and Diabetes are vital in determining birth defects in infants. The results indicate that birth defects in the United States can be lowering Depression in pregnant women.

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern, with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neo-nates. Further research in this age category is needed to improve primary screening practices, earlier detection of risk factors and precision pharmacovigilance.

Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms generally referred as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared sleep behavior at three different time points: pre-COVID-19, post-COVID-19 at initial presentation and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients, whilst 11% experienced moderate disease. Initial presentation occurred at a median of 20.4 weeks (6 weeks - 14 months) after infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82+8.7 points) to post-COVID-19 (49.40+8.3 points; p=&lt;0.01). The score then normalized at re-presentation (46.98+7.8; p=0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data show that children and adolescents with long COVID often suffer from sleep disturbance. For most children and adolescents these sleep disorders decreased over time without further medical intervention, aside from a basic sleep consultation.

Introduction Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI) is a validated metric in adult surgery for the analysis of complication and morbidity in surgical patients. We aimed to analyze the CCI for the first time in BA infants and to corelate its association with the outcome. Material and Methods Retrospective review of medical records of infants with type III BA undergoing Kasai procedure between January 2011 and December 2021 at our institution. All unexpected events were ranked according to the Clavien-Dindo classification and the CCI per patient was subsequently calculated. Clavien-Dindo grades, individual events, the CCI and the total event number per patient were correlated with the one- and two-year outcome post Kasai. Results 131 events were identified in 101 patients (range 0 – 11 per patient). Forty-four Grade I (33.6%), 67 Grade II (51.1%), 18 Grade III (13.7%) and two sentinel events [> Grade IV] (1.5%) were documented according to Clavien-Dindo, including one death in a cardiac-associated BA patient. None of the complications correlated significantly with a poor outcome. Sixty-three (62.4%) CCI were calculated (range 0 – 100). The mean CCI during the in-patient treatment post Kasai, was significantly higher in patients with a poorer outcome compared to patients with native liver survival at one- and two-year follow-up (22.7 21.7 vs 13.2 18.1; p=0.02). Conclusion Not the severity of complications, but the accumulation of numerous events related to Kasai procedure are associated with a poorer outcome. Therefore, the CCI is an excellent instrument for the postoperative morbidity assessment of BA patients.

This study aimed to evaluate the role of chest radiographs and electrocardiograms in predicting the hemodynamics of congenital heart disease (CHD). This retrospective study included 50 patients with a diagnosis of CHD who had undergone any form of cardiac intervention, either surgical or nonsurgical between September 2019 and September 2020. Chest radiographs and electrocardiograms were evaluated and compared with the diagnostic gold standard echocardiography. Chest radiographs had the highest sensitivity, specificity, and accuracy, with all being 100%, in detecting situs and cardiac position. There was a very good agreement between chest radiographs and echocardiography in the detection of both situs and cardiac position (κ = 1.00, p &lt; 0.001), while moderate agreement was observed for the detection of cardiomegaly, position of aortic knuckle, main pulmonary artery dilation, and right pulmonary artery dilation. Electrocardiograms had a high sensitivity (100.00%), but modest specificity and accuracy for the detection of left ventricle pressure overload. For the detection of left atrial enlargement and left ventricle volume overload, electrocardiograms had high specificity (94.12% and 94.29%, respectively) but low sensitivity and modest accuracy. There was a moderate agreement between electrocardiograms and echocardiography in the detection of right ventricle pressure overload (κ = 0.43, p = 0.002) and left ventricle volume overload (κ = 0.46, p &lt; 0.001). The study findings indicate that chest radiographs and electrocardiograms alone are not adequate for the assessment of hemodynamics of CHD and reinstates the recommendation that in addition to routine chest radiographs and electrocardiograms, echocardiography should be performed.