Medicine and Pharmacology

Abstract: Antimicrobial resistance is a growing threat in neonatal intensive care units (NICUs) worldwide, challenging the management of neonatal sepsis for decades. The aim of this narrative review is to compare the epidemiology and resistance patterns of neonatal sepsis in NICUs between two periods, 2000-2005 and 2020-2025, and to identify key insights that may inform future practices to limit the emergence and dissemination of antimicrobial resistance in NICUs. During the early 2000s, resistant pathogens, including extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative Staphylococcus (CoNS), were increasingly reported in NICUs. The increasing prevalence of antibiotic-resistant strains was associated with the widespread use of broad-spectrum antibiotics, exerting selective pressure that contributed to the emergence of multidrug-resistant pathogens in the 2020s, including carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Acinetobacter baumanni, and to the further dissemination of resistant strains in NICUs. The evolution of antimicrobial resistance over the past twenty years highlights that preserving the effectiveness of antibiotics, through rational antibiotic use, is a key strategy to limit the emergence of resistant pathogens. This is of particular importance for the neonatal population due to the limited therapeutic options. Although antimicrobial stewardship programs have been implemented in numerous NICUs with encouraging results, optimization of antibiotic use requires the identification of biomarkers that can promptly and accurately diagnose sepsis and the development of new effective antimicrobial agents against multidrug-resistant pathogens. Future studies are expected to further enhance diagnostic precision, therapeutic options, and stewardship strategies to limit the spread of antibiotic resistance.

Abstract: Objective: Neonatal sepsis is a major cause of morbidity and mortality. Vitamin D modulates immune responses and influences the risk and outcomes of neonatal sepsis. Therefore, we aimed to systematically outline the role of vitamin D in neonatal sepsis, including its effects on incidence, severity, treatment outcomes, and underlying mechanisms. Methods: A systematic search was conducted in the MEDLINE and EMBASE databases with English language restrictions and no date limit. Eligible sources included experimental, observational, and descriptive studies as well as reviews addressing vitamin D status, supplementation, and mechanisms in neonatal sepsis. This review followed the PRISMA Extension for Scoping Reviews guidelines. Results: Forty-five studies were selected and analyzed. Vitamin D deficiency was globally prominent among neonates and may be correlated with an increased risk or severity of sepsis. Most studies were observational, primarily case-control or cross-sectional, and conducted in South Asia and the Middle East, with increasing research activity after 2018. The number of term infants were higher than that of preterm infants. Recently, innate immune mechanisms, including antimicrobial peptides and toll-like receptor signaling, were highlighted. However, comparisons across studies were limited by inconsistencies in design, vitamin D cut-offs, timing of blood sampling, and sepsis definitions. Only six studies included patients with culture-proven sepsis, whereas others included clinically suspected cases. Few studies assessed the long-term outcomes, immune maturation, or neurodevelopmental consequences. Conclusions: Vitamin D deficiency may be associated with neonatal sepsis; however, the findings remain inconsistent because of methodological variability. Therefore, high-quality, standardized, multicenter studies are needed.

Abstract: Paenibacillus is abundant in nature and environmental samples, and generally does not contain invasion factors. Therefore, Paenibacillus growth in blood is generally considered a contamination. However, it can lead to infection in children and adults, particularly in at-risk groups. In many of these cases, it may not be clear whether Paenibacillus is the true cause of the infection. The literature reports a limited number of cases of Paenibacillus urinalis in adults. However, there is no information available regarding P. urinalis infection in children and infants. This retrospective study aimed to clinically evaluate P. urinalis growth in blood cultures of children in a tertiary referral hospital over a 5.5-year period. A total of 170 hospitalized children showed P. urinalis growth in blood cultures (blood; 162, catheter; 7, CSF; 1). Identification was performed using the MALDI-TOF MS method. Forty percent of all P. urinalis growths occurred in only three wards (neonatal intensive care unit, hematology, oncology). Of 170 cultures, 5 (2.9%) showed P. urinalis growth again in control cultures, which was considered significant. In cases with a second culture, the average culture growth time was 24+7 hours (mean + SD, min-max; 17-33 hours). No mortality was observed in any case. Evaluations were conducted under the responsibility of the Hospital Infection Control Committee to determine the source of P. urinalis contamination. P. urinalis growth was detected in 33% of samples taken from clean, packaged linens before use, 53% of ambient air cultures, and 65% of skin swabs of the hospitalized patients. In conclusion, P. urinalis blood culture growths are primarily considered contamination. However, these growths should be carefully evaluated in risk groups. In hospitalized patients, clustered growths may be influenced by environmental and skin colonization.

Abstract: Background/Objectives: Children with sickle cell disease (SCD) experience gastrointes-tinal symptoms; the contribution of disorders of gut–brain interaction (DGBIs) to this symptom burden remains underrecognized, particularly in low-middle-income coun-tries. This study aimed to determine the prevalence of DGBIs and associated factors in children with SCD. Methods: Descriptive cross-sectional study conducted in two pediatric centers in Cali, Colombia. Children aged 4-18 years with confirmed SCD were included. DGBIs were identified using the Questionnaire for Pediatric Gastrointestinal Symptoms–Rome IV. Sociodemographic/familial/clinical variables were obtained. Quality of Life was assessed using the Pediatric Quality of Life Inventory. Uni-bivariate, and multivariable logistic regression analyses were performed. Results A total of 103 patients were included. Prevalence of DGBIs was 11.7%. The most common functional constipation (7.8%), fol-lowed by functional dyspepsia (3.9%). Overlap was observed in 1.0%. Quality of life was impaired in 34.9%. This was reflected in 66.7% school absenteeism of patients with DGBIs compared of those without (38.5%) (OR=3.20; 95%CI=0.77-15.45; p=0.062). In the bivariate analysis, living with both parents, asthma, positive sickling test, and history of hema-tologic replacement therapy showed a trend toward association with DGBI. In the mul-tivariable analysis, asthma and history of transfusion also showed a trend toward asso-ciation, statistical significance was not reached. Conclusions: DGBIs are present in a clinically relevant proportion of children with SCD and represent a potentially under-diagnosed comorbidity. Quality of life was impaired. The incorporation of systematic screening using standardized Rome Criteria may improve the identification of DGBIs and strengthen the comprehensive management of these children.

Abstract: Background: Interfacility neonatal transport is essential for regionalized perinatal care, yet its effects on systemic immune responses remain poorly characterized. This study evaluated longitudinal changes in hematologic and inflammatory biomarkers during neonatal transport and investigated the influence of transport modality on these responses. Methods: In this prospective observational study, 161 neonates undergoing air or ground transport to Level III/IV neonatal intensive care units were evaluated at three time points: before transport (T0), immediately after transport (T1), and 12 hours after admission (T2). Physiological stability parameters, complete blood count variables, and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and mean corpuscular volume-to-lymphocyte ratio (MCVL), were analyzed using repeated-measures and mixed-effects models adjusted for transport duration, sedation, and physiological stability. Results: Physiological stability was maintained throughout transport, with no significant changes in heart rate, oxygen saturation, or body temperature. In contrast, significant longitudinal changes were observed in leukocyte populations and inflammatory indices. Total leukocyte and neutrophil counts decreased over time, whereas lymphocyte counts increased. Mixed-effects analyses identified significant effects of time, transport modality, and Time × Transport interaction for WBC, neutrophils, lymphocytes, NLR, SII, and SIRI. These associations remained significant after adjustment for clinical and physiological confounders. MCVL also demonstrated significant effects of time, transport modality, and their interaction, emerging as a potential novel marker of transport-related immune adaptation. Conclusions: Neonatal transport is associated with significant hematologic and immune adaptations despite preserved physiological stability. Air and ground transport induce distinct patterns of leukocyte redistribution and inflammatory responses. MCVL may represent a promising biomarker of transport-related immune adaptation and warrants further investigation in neonatal transport medicine.

Abstract: Telemedicine is increasingly transforming pediatric cardiology by expanding access to specialized care, supporting early diagnosis, and improving longitudinal monitoring of children with cardiovascular disease. This narrative review summarizes current applications of digital health in pediatric cardiology, with emphasis on congenital heart disease, pediatric hypertension, and arrhythmia management. Tele-echocardiography represents one of the most established telehealth tools, enabling remote interpretation of fetal, neonatal, and pediatric echocardiographic images and improving referral appropriateness, particularly in peripheral or resource-limited settings. In infants with complex congenital heart disease, especially those with single-ventricle physiology during the interstage period, home monitoring programs using mobile applications, pulse oximeters, digital scales, and structured caregiver reporting may facilitate early recognition of clinical deterioration and reduce avoidable transfers. In non-congenital cardiovascular disease, home blood pressure monitoring can improve diagnostic accuracy by reducing white-coat effects and supporting repeated measurements in real-life settings. Smartphone-enabled electrocardiographic devices and wearable technologies may enhance detection of intermittent arrhythmias and strengthen outpatient management. Despite these advantages, challenges remain, including data fragmentation, limited pediatric validation of consumer devices, interoperability issues, privacy concerns, and socioeconomic disparities in technology access. Properly integrated telemedicine may promote more timely, equitable, and patient-centered pediatric cardiovascular care.

Abstract: Background: Pediatric transfers to tertiary hospitals may reflect disparities in regional healthcare capacity and impose substantial healthcare costs. However, data regarding pediatric transfer pathways, tertiary-care utilization, and transport-related expenditure in Greece remain limited. Methods: We conducted a retrospective observational study of children aged 0–16 years transferred to a tertiary children's hospital in Athens, Greece, during 2022–2023. Transfers were classified as prehospital emergency medical service (EMS) transports or interfacility transfers. Post-transfer outcomes were analysed using a predefined binary endpoint: ED/short-stay discharge versus tertiary hospital-level care/admission. Potentially avoidable transfers were identified using conservative predefined resource-utilization criteria. Transport costs were analysed descriptively according to transport modality and geographic region. Results: A total of 423 pediatric transfers were analysed, including 216/423 (51.1%) prehospital EMS transports and 207/423 (48.9%) interfacility transfers. Overall, 224/423 children (53.0%) required tertiary hospital-level care/admission, whereas 199/423 (47.0%) were managed as ED/short-stay discharges. Importantly, only 54/199 ED/short-stay discharge cases met the stricter criteria for potential avoidability, representing 54/423 (12.8%) of all transfers. Ground ambulance accounted for most transfers, whereas air and sea transport accounted for only 12.1% of transfers, but 97.0% of transport-related expenditure. Interfacility transfers were substantially more likely than prehospital EMS transports to require tertiary hospital-level care/admission (OR 3.72, 95% CI 2.49–5.57; p < 0.001) and accounted for 93.8% of total transport costs. Conclusions: Most pediatric transfers were associated with clinically meaningful tertiary-level care, and only a minority met predefined criteria for potential avoidability. Interfacility transfers demonstrated substantially higher tertiary-care utilization and disproportionately concentrated transport expenditure, highlighting the importance of strengthening regional pediatric capacity and optimizing referral networks to improve the efficiency of pediatric transfer systems.

Abstract: Objectives: This study investigated the effects of augmented reality motor training (ARMT) on gait and balance in children with cerebral palsy (CP). Methods: Thirty five children with spastic uni- and bilateral CP, aged 7–12, years were randomly assigned to two groups. One group (n = 20) underwent ARMT while wearing a VR headset, with five 30-min. sessions per week as part of their 4-week conventional rehabilitation. The control group (n = 15) participated in a 4-week conventional rehabilitation without AR exercises. Before and after rehabilitation all children performed a 10-meter walking test with a G-walk sensor, a one-leg balance task from the MABC-2 test, and the Pediatric Balance Scale (PBS). Results: The ARMT group demonstrated a significant decrease in the coefficient of variability (%) for three variables of the stride cycle, an improvement in total PBS score, longer duration of left-leg stance, and longer duration of stance on the less affected side, as compared to the control group. Conclusions: The study suggested that after just 4 weeks, movement training with balance and gait exercises performed in AR could lead to stabilization of gait patterns, accompanied by improved balance.

Abstract: Background/Objectives: Although cow’s milk allergy is the most common food allergy in infants, its diagnosis remains challenging. Conventional allergy tests, including skin prick testing and serum-specific IgE, can support the diagnosis in cases with a clear clinical history; however, neither positive nor negative results are sufficient for a definitive diagnosis without confirmation via an oral food challenge or reintroduction. The basophil activation test has emerged as a promising adjunctive tool in this context. Methods. We searched in the electronic databases PubMed and Google Scholar combinations of the following keywords: “basophil activation test”, “BAT”, “cow’s milk allergy”, “CMA”. Results. While its widespread use is currently limited by the lack of standardized protocols, the need for fresh blood samples, and restricted availability outside specialized centers, the basophil activation test has the potential to improve diagnostic accuracy and support clinical decision-making in IgE-mediated cow’s milk allergy. Importantly, basophil activation test may also reduce the need for oral food challenge by providing a safe, functional assessment of allergen reactivity, thereby minimizing patient risk and the burden of invasive testing. Conclusion. Further studies and validation are needed before the basophil activation test can be implemented as a routine diagnostic tool.

Abstract: Ebstein anomaly is a rare congenital cardiac malformation with a highly variable prenatal course, ranging from stable physiology to progressive fetal heart failure and perinatal death. Predicting outcome remains difficult because anatomical severity alone does not reliably reflect physiological burden, ventricular performance, or disease progression. Therefore, fetal echocardiography plays a central role in both diagnosis and risk stratification. This review summarises the current approaches to fetal echocardiographic assessment of Ebstein anomaly, focusing on anatomical, functional, and Doppler-derived markers associated with adverse outcomes, including severe tricuspid regurgitation, cardiomegaly, right and left ventricular dysfunction, abnormal pulmonary and ductal flow patterns, and circular shunt physiology. Established prognostic scoring systems were reviewed, highlighting their contributions to risk stratification. Emerging functional parameters and serial assessment strategies have been discussed as complementary tools to better capture the dynamic nature of the disease.

Abstract: Background/Objectives: Long-term psychosocial/neurocognitive sequelae are frequently observed in survivors of pedi-atric cancer and adversely affect quality of life in adulthood. Although clinical predictors are well established, the con-tribution of familial, cultural, and socio-economic factors has received less attention. Methods: Between November 2022-January 2023, 93 survivors parents of pediatric patients with solid tumors including 38 individuals with central nervous system (CNS) tumors, completed a specifically designed 60-item questionnaire. Outcomes were evaluated across four domains—psychological, neurocognitive, academic, and social—along with a broad range of potential pre-dictors encompassing demographic, clinical, family-related, cultural, socio-economic, and premorbid characteristics. Statistical analyses included Fisher’s exact test and non-parametric methods. Results: New-onset or aggravated inter-nalizing symptoms were reported in 53% of survivors, externalizing behaviors in 32%, neurocognitive impairments in 45%. Academic difficulties were identified in 32%, with 25% requiring an Individualized-Education-Plan. Social chal-lenges affected 30% of participants and were more prevalent among CNS tumor survivors, who also demonstrated greater functional losses and rehabilitation needs. Lower parental educational attainment was associated with exter-nalizing symptoms (p = 0.039), whereas household income, parental occupation, and residential setting were not. Premorbid psychological or learning difficulties were strong predictors of adverse outcomes (all p < 0.01). Older paternal age was protective for relational and academic functioning, while having more siblings was linked to increased cogni-tive risk. Conclusions: Psychosocial and neurocognitive late effects remain common among pediatric cancer survivors. Educational background and premorbid vulnerabilities appear more influential than economic factors, supporting the need for targeted neuropsychological surveillance and family-centered screening strategies.

Abstract: Background/Objectives: Advanced maternal age (≥35 years) significantly increases the risk of fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13. Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) in maternal plasma has substantially improved the accuracy and safety of prenatal screening. Methods: We previously developed and clinically validated a multiplex droplet digital PCR (ddPCR)-based NIPT assay for detecting fetal trisomies 21, 18, and 13 in Mongolia. The assay targeted specific loci on chromosomes 21, 18, and 13, using chromosome 1 as an internal reference. A Z-score threshold >3 indicated high risk, and all positive results were confirmed by invasive karyotyping. Results: In this study we collected 74 pregnant women of advanced maternal age and samples were successfully analyzed, with high technical performance (mean >100,000 accepted droplets per reaction and clear signal separation). Ten high-risk pregnancy cases were identified (8 trisomy 21 and 2 trisomy 18), all of which showed complete concordance with confirmatory karyotyping. Complete concordance with available reference standard results were observed in this limited cohort. No trisomy 13 cases were detected. Conclusions: This ddPCR-based NIPT assay exhibited excellent diagnostic accuracy and reproducibility in a Mongolian cohort of advanced maternal age pregnancies. Its technical simplicity, relatively low cost, and minimal infrastructure requirements make it a promising tool for implementation in resource-limited settings. However, the small sample size limits generalizability, and larger multicenter studies are needed to confirm clinical utility across broader populations, including low-risk pregnancies.

Abstract: Background/Objectives: Antimicrobial resistance in pediatric infections presents a worsening global public-health challenge, with antimicrobial resistance (AMR) accounting for more than one million deaths annually and disproportionately affecting children younger than 5 years of age. Neonates and critically ill children face heightened risk owing to immature immunity, frequent healthcare exposures, and limited therapeutic options. This review synthesizes evidence on the epidemiology, mechanisms of resistance, clinical outcomes, and management of AMR across the full pediatric age range.Methods: PubMed/MEDLINE and Google Scholar were searched for literature from 2014 to 2026 using terms covering antibiotic resistance, pediatric populations, and key pathogens. Approximately 1,840 records were screened; 64 sources met all inclusion criteria. A narrative synthesis approach was used, given heterogeneity across study designs and outcomes.Results: Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant pathogens, and methicillin-resistant Staphylococcus aureus drive substantial morbidity and mortality in children. Approximately one in five pediatric Gram-negative bloodstream isolates are resistant to third-generation cephalosporins, a phenotype independently associated with a roughly three-fold increase in adjusted mortality. Carbapenem-resistant Klebsiella pneumoniae bacteremia carries a 30-day mortality approaching 40%, and isolates in low- and middle-income countries (LMICs) frequently harbor multiple resistance genes. Pneumococcal conjugate vaccine implementation was associated with absolute reductions of 7–11% in the proportion of pediatric pneumococcal isolates that were penicillin-non-susceptible or penicillin-resistant, largely by preventing infections caused by resistant serotypes and by reducing antibiotic selection pressure, rather than through a direct effect on resistance mechanisms; global AMR mortality in children younger than 5 years of age fell by more than 50% between 1990 and 2021.Conclusions: Pediatric AMR reflects intersecting microbiological, clinical, and health-system challenges. Priority actions include scaling antimicrobial stewardship programs, expanding access to rapid molecular diagnostics, integrating whole-genome sequencing into surveillance, conducting pediatric-inclusive randomized trials, and deploying vaccines as primary prevention tools, with particular emphasis on LMICs where the burden is greatest.

Abstract: Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have im-proved outcomes but remain limited by treatment-related toxicity, donor availability, and incom-plete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfu-sion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical tri-als, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particu-larly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clin-ical studies have shown encouraging outcomes, including transfusion independence in many pa-tients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclu-sion: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access.

Abstract: Background: Moderate-to-severe preterm brain injury (PBI), including intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), remains an important cause of adverse neurodevelopmental outcomes in preterm infants. Early risk stratifi-cation using routinely collected clinical data may help prioritize surveillance in vul-nerable infants. Methods: We retrospectively included 318 preterm infants admitted between 2015 and 2024 as the development cohort. Thirty-three candidate predictors derived from perinatal factors, first laboratory tests within 24 h of admission, and se-lected early hospitalization variables were evaluated. Seven machine-learning algo-rithms were developed using stratified 10 × 5 nested cross-validation with prespecified preprocessing, class-balancing, and feature-selection procedures. Candidate models were compared primarily using the mean fold-level area under the receiver operating characteristic curve (AUROC). After model selection, the finalized LightGBM model was calibrated using Platt scaling, and its pooled out-of-fold (OOF) performance was summarized. Two prespecified thresholds (Youden and high-sensitivity) were used for risk stratification. A small independent temporal cohort of 35 infants was used for preliminary external validation. Results: PBI occurred in 62/318 infants (19.5%) in the development cohort and 6/35 infants (17.1%) in the temporal external cohort. During candidate-model comparison, LightGBM achieved the highest mean fold-level AU-ROC (0.768, 95% CI 0.708–0.825). The finalized 14-feature LightGBM model, evaluated using pooled OOF predictions after Platt calibration, yielded an AUROC of 0.747 (95% CI 0.679–0.811), a PR-AUC of 0.392, and a Brier score of 0.136. At the Youden threshold (0.18), sensitivity was approximately 0.70 and specificity approximately 0.85; at the high-sensitivity threshold (0.10), sensitivity was approximately 0.95 and specificity approximately 0.50. Key predictors included ventilation status and early physiologic and laboratory indicators. In the small temporal external cohort, the AUROC was 0.897 (95% CI 0.672–1.000), but the confidence interval was wide and calibration was suboptimal, indicating that this external assessment should be considered preliminary. Conclusions: We developed an interpretable LightGBM model using routinely avail-able early postnatal and early hospitalization data to support risk stratification for PBI in preterm infants. The model showed moderate internal discrimination and a positive net benefit across clinically relevant thresholds. Preliminary temporal external valida-tion yielded highly uncertain estimates; larger multicenter cohorts are needed to con-firm generalizability, refine calibration, and determine the appropriate role of the model in early PBI risk assessment before clinical use.

Abstract: The widespread implementation of next-generation sequencing (NGS) has revolution-ized clinical genetics, yet the identification of variants of uncertain significance (VUS) frequently hinders definitive diagnoses. Here, we report the molecular and functional characterization of a novel BTD missense variant to resolve a complex six-year diagnostic odyssey in a patient with suspected partial biotinidase (BTD) deficiency missed by newborn screening. The patient, presenting with moderate developmental delay, hypo-tonia, and motor impairment, was found to harbor two compound heterozygous variants in the BTD gene: the well-known hypomorphic pathogenic variant p.(Asp424His) and a novel VUS, p.(Thr459Met). To determine the precise molecular impact of the VUS, we combined in silico structural predictions with in vitro functional assays. Site-directed mutagenesis, followed by expression in recombinant HEK-293T cells, revealed that the p.(Thr459Met) variant dramatically impairs protein secretion and significantly reduces both intracellular and extracellular biotinidase enzymatic activity, comparable to other established pathogenic mutations. Further in vivo validation in patient plasma confirmed a partial reduction in overall BTD activity. These findings reclassify the p.(Thr459Met) variant as a likely pathogenic hypomorphic allele. This study highlights the critical ne-cessity of functional molecular validation to accurately interpret VUS, overcome the limitations of newborn screening, and achieve precision medicine in metabolic disorders.

Abstract: Background/Objectives: Acute bronchiolitis is one of the leading respiratory infections in infants and represents a substantial burden on healthcare services. Parents’ knowledge, attitudes and practices are key to its prevention and home management. The aim of this study was to analyze parents’ knowledge, attitudes, and practices regarding the prevention and home management of bronchiolitis in infants in Gran Canaria, Spain. Methods: A cross-sectional observational study was conducted. The Bronchiolitis Knowledge, Attitudes and Practices Questionnaire was used, comprising 26 items grouped into four dimensions: risk factors, signs and symptoms, prevention, and care/pharmacological support. Data were collected using an online questionnaire. Descriptive analyses, nonparametric tests, and multiple linear regression were performed. Statistical analysis was conducted using Jamovi (version 2.4.12). Statistical significance was set at p &lt; 0.05. Results: A total of 162 parents were included. The mean normalized total score was −22.84 (SD = 10.12), indicating a low overall level of knowledge and practices. The prevention dimension showed the lowest scores, whereas the signs and symptoms and care/pharmacological support dimension presented higher scores (p &lt; 0.001). Significant associations were identified with educational level (β = −4.96; p = 0.023), history of bronchiolitis in the current child (β = −4.61; p = 0.012), and previous experience with bronchiolitis (β = 4.24; p = 0.043). The model explained 15.1% of the variance. Conclusions: Parents showed insufficient knowledge, attitudes and practices, particularly in relation to prevention. Targeted educational interventions are needed to improve the home management of bronchiolitis and help reduce healthcare burden.

Abstract: Syphilis remains a global health concern despite the well-known nature of its symptoms, the availability of diagnostic methods, and the existence of effective therapy. The infection can be transmitted vertically from mother to fetus during pregnancy, and a global increase in the number of reported cases has been observed. Congenital syphilis continues to be one of the leading causes of spontaneous abortion, preterm birth, neonatal mortality and severe long-term sequelae in affected individuals. The disease may present with a wide spectrum of clinical manifestations, ranging from mild symptoms that mimic other neonatal conditions to severe systemic disease. Asymptomatic infants are also reported, further emphasizing the necessity for prompt and accurate diagnosis, as well as adequate and comprehensive treatment. We present a case of a premature newborn with early congenital syphilis and severe multiorgan involvement, high-lighting the complexity of clinical presentation, diagnostic challenges, and the need for multidisciplinary management. Furthermore, this case underscores the critical importance of antenatal screening, early identification of infected preg-nant women, and their timely treatment.

Abstract: Pain and stress are frequent and clinically relevant challenges in neonatal intensive care, particularly among preterm and critically ill newborns exposed to repeated invasive procedures, mechanical ventilation, surgery, and advanced life-support interventions. Effective analgosedation is essential to reduce discomfort, attenuate physiological instability, improve tolerance of intensive care procedures, and potentially limit adverse neurodevelopmental consequences. However, neonatal pain and sedation management remain complex because of developmental immaturity, pharmacokinetic and pharmacodynamic variability, and the need to balance adequate analgesia against treatment-related complications. This narrative review summarizes current evidence on analgosedation in the Neonatal Intensive Care Unit, focusing on clinical indications, pharmacological agents, non-pharmacological strategies, monitoring tools, adverse effects, and future perspectives. Opioids, benzodiazepines, dexmedetomidine, and ketamine each have specific potential benefits and limitations, requiring individualized selection, careful titration, and continuous reassessment. Non-pharmacological interventions, including oral sucrose, non-nutritive sucking, facilitated tucking, breastfeeding, skin-to-skin care, and environmental modulation, should be integrated into multimodal pain-management protocols. Validated instruments such as COMFORTneo, N-PASS, and PIPP-R support standardized assessment and guide therapeutic decisions. Future advances may derive from objective monitoring technologies, artificial intelligence, developmental pharmacology, and precision-medicine approaches. A multidisciplinary, protocol-driven, and family-centered strategy is essential to optimize neonatal comfort while minimizing avoidable drug exposure.

Abstract: Objective: This multicenter retrospective real-world data study aimed to determine whether a preparation containing polyphenol, vitamin D3, vitamin C, and zinc added to antiviral therapy accelerates clinical recovery in children diagnosed with influenza by evaluating its effects on symptom duration and severity, time to fever resolution, and functional recovery. Materials and Methods: This was a five-center, multicenter, retrospective, comparative real-world data analysis. A total of 128 patients aged 4-10 years with a clinical diagnosis of influenza were classified into a control group receiving antiviral therapy alone (n=64) and a combined polyphenol group receiving, in addition to antiviral therapy, a preparation containing polyphenol, vitamin D3, vitamin C, and zinc (n=64). Clinical data were obtained from electronic patient records and parent-reported information. Symptom severity (0-3 ordinal score), recovery time, and functional outcomes were assessed on Days 0, 3, 5, and 7. Continuous variables were compared using the independent-samples t test, categorical variables using the chi-square or Fisher exact test, and changes over time using a repeated-measures general linear model. Statistical significance was accepted as a two-sided p value of < 0.05. Results: In this study including 128 pediatric patients, there were no significant differences between the combined polyphenol and control groups in demographic or baseline clinical characteristics (p>0.05). During follow-up, all symptom scores improved more rapidly and markedly in the combined polyphenol group than in the control group. By Day 3, significant differences were observed between groups in fever, cough, rhinorrhea, sore throat, fatigue, general condition, and physical activity scores (p< 0.001 for all parameters). By Day 5, almost complete resolution of symptoms (score 0) was observed in the combined polyphenol group, whereas symptoms persisted to a substantial extent in the control group (p< 0.001). The time to fever resolution was significantly shorter in the combined polyphenol group (1.84±0.72 days vs 4.5±1.36 days; p< 0.001). Similarly, time to return to school (3.21±0.9 days vs 5.8±1.91 days; p< 0.001) and time for parents to return to work were significantly shorter in the combined polyphenol group (p< 0.001). The need for additional healthcare visits and antipyretic use was markedly lower in the combined polyphenol group (Day 3: 20.3% vs. 53.1%; Day 5: 0% vs. 15.6%; p< 0.001 for both comparisons). Repeated-measures analyses showed a significant time-by-group interaction, indicating that the reduction in symptom scores occurred more rapidly and prominently in the combined polyphenol group (p< 0.001). Treatment was generally well tolerated in the combined polyphenol group; no serious adverse events were reported, and parent-reported tolerability was high (9.39±0.7). Conclusion: This multicenter retrospective real-world data study shows that the preparation containing polyphenol, vitamin D3, vitamin C, and zinc added to antiviral therapy significantly reduces symptom duration and severity, accelerates clinical recovery, and markedly decreases healthcare utilization in children diagnosed with influenza. These findings suggest that this combination may represent an effective and well-tolerated adjuvant treatment option in the management of pediatric influenza.