Molecular and cellular pediatrics最新文献

{"title":"Post-intensive care sequelae after severe bacterial infections in previously healthy children.","authors":"S C Goretzki, C Held, S Tschirner, C Pentek, H Kölbel, A Della Marina, A Gangfuß, H Reusch, N Schlaghecke, S Benson, U Schara-Schmidt, U Felderhoff-Müser, C Dohna-Schwake, N Bruns","doi":"10.1186/s40348-026-00245-0","DOIUrl":"10.1186/s40348-026-00245-0","url":null,"abstract":"<p><strong>Background: </strong>Severe complications of common community-acquired infections can necessitate pediatric intensive care even in previously healthy children. While survival after pediatric intensive care has improved, data on long-term physical, cognitive, and psychosocial outcomes in this population remain limited. This study evaluated 12-month outcomes in previously healthy children admitted to the pediatric intensive care unit for severe infectious complications and describes the implementation of a structured post-intensive care follow-up program at a tertiary care center in Germany.</p><p><strong>Methods: </strong>We conducted a retrospective single-center study including previously healthy children admitted to the PICU in 2023 due to severe complications of community-acquired infections. Patients participated in a structured multidisciplinary follow-up program with standardized neurological, physical, cognitive, and psychosocial assessments performed up to 12 months after discharge.</p><p><strong>Results: </strong>Thirty-seven previously healthy children admitted in 2023 were included. The largest subgroup of the study population consisted of children with intracranial abscess or meningitis (43%), orbital abscess (27%), septic shock (14%), osteomyelitis (11%), and necrotizing fasciitis (5%). Despite appropriate acute management and survival of all patients, 25 children (68%) developed persistent neurological, somatic, or psychosocial impairments during follow-up. Common sequelae included motor deficits, neurocognitive dysfunction, sensory impairment, anxiety, and reduced physical endurance. Importantly, many complications were not apparent early after discharge and emerged several months later, with a median time to identification of approximately five months. Recovery trajectories varied considerably, reflecting the multidimensional nature of pediatric post-intensive care morbidity.</p><p><strong>Conclusions: </strong>A substantial proportion of previously healthy children experience clinically relevant, multidimensional morbidity after severe infections requiring intensive care. These findings highlight the importance of structured, multidisciplinary post-intensive care follow-up to enable early recognition of delayed sequelae and timely intervention, with the potential to reduce long-term morbidity and improve quality of life for affected children and their families.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13226762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersectionality of early developmental risks and resilience after preterm birth.","authors":"Julia Jäkel, Janika Ludwig, Britta Hüning, Ursula Felderhoff-Müser, Christoph Härtel","doi":"10.1186/s40348-026-00242-3","DOIUrl":"10.1186/s40348-026-00242-3","url":null,"abstract":"<p><p>The period from conception through preschool age represents a critical developmental window for both microbiome and brain. During this time, several modifiable factors may influence development via the gut-brain axis, including the mode of delivery, exposure to antibiotics, maternal nutrition, breastfeeding, and sensitive, emotionally responsive caregiving. Infants born preterm (<37 weeks gestation) face numerous challenges that can perturb their developing gut microbiome as well as neurobehavioral trajectories. Biological and medical risks are exacerbated by stressful social context conditions. Understanding the complex mechanisms shaping the gut-brain axis and identifying modifiable protective factors is key to help define specific target groups and critical windows for individualized prevention of adverse outcomes after preterm birth. Today, a large knowledge gap exists on (a) how gut, brain, and behavioral development interact over time, and (b) which social and modifiable factors are key drivers of this interaction that could be harnessed for treatment and intervention. Translational research on the gut-brain axis after preterm birth is critically needed. Future studies should consider intentional sampling for variation in social factors such as level of education and immigrant background to identify populations that are susceptible to microbiome modifications and provide more evidence of how interventions might optimize long-term outcomes.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priming innate immunity and long-term outcome.","authors":"Victoria Pradler, Clyde J Wright, Nazanin Kazemi-Butterfield, Kirsten Glaser","doi":"10.1186/s40348-026-00244-1","DOIUrl":"10.1186/s40348-026-00244-1","url":null,"abstract":"<p><strong>Background: </strong>While advancements in neonatal intensive care have significantly improved the survival of preterm infants, inflammation-related complications continue to be a major factor in short- and long-term morbidity, especially in the most immature babies. Profound evidence indicates that prenatal and postnatal inflammatory exposures, interacting in a multi-hit sequence, significantly affect both immune responses and long-term organ development.</p><p><strong>Content: </strong>While preterm birth frequently represents the initial trigger of an adverse cascade of inflammation, various postnatal environmental factors, such as respiratory support, oxygen therapy, and neonatal infections, contribute to this process, with each event serving as an inflammatory stressor independently associating with inflammation-driven tissue damage. The preterm innate immune system seems particularly susceptible not only to infection, but to pro-inflammatory immune responses and sustained immune activation. Mechanistically, several processes have been implicated, including disturbed homeostasis of inflammatory mediators, antioxidant enzymes, and proteases, as well as altered pathogen recognition, and particularities in the resolution of inflammation. In addition, trained immunity, immune tolerance, epigenetic and metabolic reprogramming, and interactions between altered gut microbiota and the developing immune system may further shape these responses. Subsequently altered, often increased or sustained inflammation has been recognized as a central mechanism linking early-life exposures to impaired lung, brain, gut, and retinal development, and adverse long-term outcomes. The frequency of episodes of inflammation seems to significantly impact the latter.</p><p><strong>Conclusions: </strong>A better understanding and greater awareness may enable improved risk stratification and avoidance of inflammatory exposures, and promote the development of more targeted strategies to prevent adverse inflammation during a vulnerable period.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the long-term tolerability of BNT162b2 in children and adolescents.","authors":"Jeanne Moor, Vivien Grieshaber, Nicole Toepfner, Sarah Holzwarth, Matthias B Moor, Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao","doi":"10.1186/s40348-026-00243-2","DOIUrl":"10.1186/s40348-026-00243-2","url":null,"abstract":"<p><strong>Background: </strong>Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the sex differences in the tolerability of BNT162b2 in children younger than 18 years in Germany.</p><p><strong>Methods: </strong>A post-hoc analysis of retrospectively collected tolerability data, collected through an authentication-based survey of legal guardians of children vaccinated with BNT162b2 under the age of 18 years (CoVacU18-study). Primary outcome was the frequency of the four most common post-vaccination symptom categories (local, general, musculoskeletal symptoms, fever) reported after the 1st-4th doses. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interactions between sex and age group effects on post-vaccination symptoms were assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines.</p><p><strong>Results: </strong>Three thousand two hundred twenty-eight participants (median age 5.7 years, male 49.6%). In logistic regression, female sex was associated with higher odds of local symptoms (OR = 1.28 [95% CI: 1.17-1.40], p < 0.05), general symptoms (OR = 1.27 [1.13-1.44], p < 0.05), and musculoskeletal symptoms (OR = 1.27 [1.03-1.56], p < 0.05). Interactions between sex and age groups existed for post-vaccination local symptoms. Following non-BNT162b2 childhood vaccinations, female sex was not associated with odds of any post-vaccination symptoms. No relevant interaction existed between vaccine types (BNT162b2 vs non-BNT162b2) and sex for the association with post-vaccination symptoms.</p><p><strong>Conclusion: </strong>Sex differences exist in post-vaccination symptoms after BNT162b2 administration in young children and adolescents. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LEF1 gene mutation impairs the intestinal barrier and causes diarrhea.","authors":"Jianan Jie, Mengling Qiu, Xing Liu, Qingqing Zhang, Jing Xie, Lanlan Geng, Sitang Gong, Yang Cheng","doi":"10.1186/s40348-026-00240-5","DOIUrl":"10.1186/s40348-026-00240-5","url":null,"abstract":"<p><p>Whole-exome sequencing identified a novel de novo heterozygous LEF1 variant (c.880 C > T; p.Pro294Ser) in a male pediatric patient who presented with intractable chronic yellow-green watery diarrhea with onset at 18 months of age. The condition persisted for 4 years and was complicated by protein-energy malnutrition and growth failure refractory to standard therapy. Gastrointestinal endoscopy showed mucosal edema accompanied by mild chronic inflammation, and this variant was not present in public population genomic databases. Functional validation was performed in Lef1 (c.876 C > G; p.Pro292Ser) knock-in mice (the murine ortholog of the human LEF1 p.Pro294Ser variant), and revealed increased susceptibility to dextran sulfate sodium (DSS)-induced diarrhea, intrinsic intestinal structural abnormalities, and impaired intestinal barrier integrity. Molecular and proteomic analyses revealed downregulated expression of tight junction proteins and aquaporin - 4 in both mutant mice and patient-derived intestinal tissues, concomitant with dysregulated ion transport, and aberrant inflammatory pathways. Mechanistically, the LEF1 variant enhances its own expression and nuclear accumulation, driving Epithelial-Mesenchymal Transition (EMT) and subsequent intestinal barrier disruption. Collectively, these findings establish LEF1 variant as a pathogenic driver of pediatric chronic diarrhea, broaden the functional role of LEF1 in intestinal homeostasis, and identifies its potential utility as a diagnostic biomarker and therapeutic target for this disorder.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive application of lung growth factors and lack of attenuation of phenotype disruption of lung resident MSC from preterm infants by hyperoxia.","authors":"Lena Holzfurtner, Judith Behnke, Pauline Korte, Maurizio J Goetz, Jutta Petzinger, Anita C Windhorst, Tayyab Shahzad, Stefano Rivetti, Ying Dong, Saverio Bellusci, Harald Ehrhardt","doi":"10.1186/s40348-026-00241-4","DOIUrl":"10.1186/s40348-026-00241-4","url":null,"abstract":"<p><strong>Background: </strong>Phenotype disruption of lung resident mesenchymal stem cells (MSC) is a key event in the pathogenesis of bronchopulmonary dysplasia (BPD). Hyperoxia (HOX) constitutes one major harmful factor resulting in growth arrest and changes of functional properties including downregulation of PDGFRα. FGF-10, HGF, IGF-1 and PDGF-AA constitute promising cytokines to preserve lung growth. We studied their preventive application before HOX exposure of MSC cultures.</p><p><strong>Results: </strong>As described before, HOX inhibited spontaneous proliferation of MSC and induced cell death. Growth inhibition was larger at HOX80% than at HOX40%. The one-time preventive application of FGF-10, HGF, IGF-1 or PDGF-AA in therapeutic dosage or the repetitive application during HOX (40% or 80%) did not attenuate the growth inhibition and cell death induction by HOX even during the milder HOX40% exposure. Furthermore, the phenotype disruption with downregulation of PDGFRα as critical hallmark event remained unchanged.</p><p><strong>Conclusion: </strong>Our data indicate that the deleterious effects of HOX to lung resident MSC are that pronounced that single lung growth promoting cytokines cannot attenuate their phenotype disruption, growth inhibition and cell death by HOX. The results demand focus on MSC functionality when the therapeutic potential of lung growth promoting factors and other therapeutics intended to prevent BPD is studied.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-hospital rotavirus vaccination in premature and medically ill infants: a systematic review of uptake and safety.","authors":"Janna-Lina Kerth, Calvin Kurz, Jonas Obitz, Tim Vogel, Ertan Mayatepek, Mark Dzietko","doi":"10.1186/s40348-026-00238-z","DOIUrl":"10.1186/s40348-026-00238-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rotavirus vaccination is widely recommended in infancy and has substantially reduced morbidity from severe gastroenteritis. In premature and medically ill infants, prolonged hospitalization often interferes with timely vaccination. Despite recommendations to vaccinate clinically stable hospitalized infants according to chronological age, concerns regarding adverse events, apnea-bradycardia episodes, and nosocomial transmission continue to limit uptake in neonatal intensive care units (NICUs). Delayed vaccination may result in missed opportunities, as initiation after 24 weeks of age is contraindicated. The objective of this review was to systematically assess the evidence on the administration of rotavirus vaccines to premature and medically ill infants during their in-hospital stay (e.g., neonatal intensive care units or postnatal wards), and to evaluate the occurrence, type, and frequency of adverse events following such vaccination.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This systematic review was conducted in accordance with PRISMA guidelines. Medline, Embase, and Web of Science were searched without restrictions on publication year or language. Eligible studies included premature or medically ill infants who received rotavirus vaccination during hospitalization. Randomized controlled trials, cohort studies, case-control studies, and case series with at least five infants were considered. Data were extracted on vaccination uptake, adverse events, viral shedding, and nosocomial infection. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools, and certainty of evidence was evaluated using the GRADE approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fifteen observational studies including a total number of 5,443 infants met inclusion criteria; no randomized controlled trials were identified. Vaccination uptake varied widely and was generally low in routine clinical practice. Reported adverse events were predominantly mild and transient, with gastrointestinal symptoms being most common. Fever occurred in up to 10% of vaccinated infants. No cases of intussusception or volvulus were reported. Apnea-bradycardia episodes were inconsistently documented; where assessed, their frequency was comparable to baseline rates or to those observed after routine two-month vaccinations. Viral shedding of vaccine-strain rotavirus was frequently detected, particularly after the first dose; however, nosocomial transmission to unvaccinated infants was rare and not associated with symptomatic gastroenteritis. Overall certainty of evidence was low due to heterogeneity and moderate to high risk of bias.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Available evidence suggests that in-hospital rotavirus vaccination in clinically stable premature and medically ill infants is generally safe and not associated with relevant nosocomial infection. Nevertheless, uptake remains inconsistent. Standardized protocols, provider education, and impleme","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeine citrate increases ciliary beat frequency in human respiratory epithelial cells.","authors":"Sandra Cindrić, Laura Bodenbeck, Rim Hjeij, Niki Tomas Loges, Christine Edelbusch, Sebastian George, Petra Pennekamp, Esther Rieger-Fackeldey, Heymut Omran","doi":"10.1186/s40348-026-00239-y","DOIUrl":"10.1186/s40348-026-00239-y","url":null,"abstract":"<p><strong>Background: </strong>Caffeine citrate is the gold-standard pharmacological treatment for apnea of prematurity, improving survival and long-term respiratory outcomes in preterm infants. Beyond its established central nervous system effects, emerging evidence suggests broader benefits in reducing extubation failure, lowering bronchopulmonary dysplasia rates, and decreasing the need for mechanical ventilation-but its direct actions on the respiratory epithelium remain largely unknown. Caffeine is a methylxanthine with multiple molecular targets, including adenosine receptor antagonism, phosphodiesterase inhibition, and stimulation of calcium (Ca²⁺) release from intracellular stores-mechanisms also linked to the regulation of ciliary beat frequency (CBF), a critical determinant of mucociliary clearance. Since impaired CBF is a hallmark of several chronic airway diseases, understanding whether caffeine citrate can directly modulate this function could broaden its therapeutic relevance. We hypothesized that caffeine citrate directly enhances CBF in human respiratory epithelial cells (hRECs), thereby supporting airway defense mechanisms in health and disease.</p><p><strong>Results: </strong>CBF was quantified by high-speed video microscopy in hRECs derived from healthy donors and individuals with cystic fibrosis (CF) cultured under air-liquid interface conditions. Caffeine citrate significantly increased CBF above baseline (CBF_b) in both healthy and CF-derived cells, indicating a robust and reproducible stimulatory effect. Mechanistic experiments identified ryanodine receptor (RYR)-mediated Ca²⁺ efflux from intracellular stores as the key pathway, as pharmacological blockade of RYR abolished the caffeine-induced CBF enhancement.</p><p><strong>Conclusions: </strong>This study reveals a novel pharmacological effect of caffeine citrate-direct stimulation of CBF in primary hRECs through RYR-dependent Ca²⁺ signaling. By improving mucociliary clearance, caffeine citrate may offer peripheral airway benefits in addition to its central actions for apnea prevention. Given its favorable pharmacokinetic profile, long half-life, and good tolerability compared to other methylxanthines, caffeine citrate warrants further evaluation as a dual-action therapy for respiratory diseases with compromised clearance, including CF and bronchopulmonary dysplasia. These findings expand the mechanistic understanding of caffeine's actions and highlight new translational opportunities in respiratory care.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world impact of nirsevimab on RSV hospitalizations in children under 2 years of age: retrospective monocentric study in a large German tertiary pedatric center.","authors":"Moritz Bauer, Anke Wendt, Marcus A Mall, Horst von Bernuth, Stephanie Thee","doi":"10.1186/s40348-026-00232-5","DOIUrl":"10.1186/s40348-026-00232-5","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants and young children. Broad immunization with the monoclonal antibody nirsevimab represents a promising preventive strategy. However, real-world data on its impact at the population level remain limited, particularly in routine clinical settings.</p><p><strong>Methods: </strong>This retrospective single-center study evaluated a cohort of 261 children under two years of age hospitalized with RSV across three seasons (2018-2019, 2023-2024, 2024-2025) at a Berlin tertiary care hospital.</p><p><strong>Results: </strong>We analyzed admissions and clinical courses of RSV-associated hospitalizations in children < 2 years of age at a large tertiary care center in Germany between 2018 and 2025. Following the nationwide introduction of nirsevimab in 2024, the number of RSV-related hospitalizations in our center decreased by 51% compared to the previous season. During the 2024/2025 season 90.2% of hospitalized patients had not received nirsevimab immunization.</p><p><strong>Conclusion: </strong>The introduction of nirsevimab was associated with a substantial reduction in RSV-related hospitalizations in infants and young children in a real-world clinical setting. These findings support a beneficial role of passive immunization with nirsevimab and highlight its potential to reduce RSV-related disease burden.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13153340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenocopies of 22q11.2DS: revealing genetic diversity in clinically suspected 22q11.2 deletion syndrome.","authors":"Fanni Szumutku, Anna Lengyel, Éva Pinti, Ilona Kun, Krisztina Németh, Tünde Abonyi, Fanni Gál, Seung Woo Ryu, Yongjun Song, Anikó Ujfalusi, Krisztina Kádár, Eszter Jávorszky, Kálmán Tory, Éva Kis, Vera Goda, Gergely Kriván, Árpád Ferenc Kovács, Irén Haltrich","doi":"10.1186/s40348-026-00236-1","DOIUrl":"10.1186/s40348-026-00236-1","url":null,"abstract":"<p><strong>Background: </strong>Although 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, a substantial proportion of patients with clinically suspected 22q11.2DS (clin22q11.2) remain without a definitive diagnosis. While CNVs other than the typical 22q11.2 deletion have been identified in patients with clin22q11.2 (defined here as phenocopies of 22q11.2DS, or phen22q11.2), SNVs associated with phen22q11.2 are less well defined.</p><p><strong>Results: </strong>We aimed to investigate genetic variants associated with phen22q11.2 to achieve definitive diagnoses and improve clinical management in the clin22q11.2 cohort, while also comparing the phenotypic features of 22q11.2DS and phen22q11.2 to guide optimal diagnostic approaches. We assessed 336 consecutive pediatric patients from three centers presenting with clin22q11.2 according to Tobias criteria. Diagnostic testing included fluorescence in situ hybridization or multiplex ligation-dependent probe amplification in all patients. In subsets of patients, additional investigations were performed as clinically indicated, including but not limited to karyotyping, chromosomal microarray analysis, and/or exome sequencing (ES) with CNV detection. To identify phenotypic differences, Fisher's exact test and Chi-squared test were performed. Genetic abnormalities were identified in 127 patients, including 88 patients diagnosed with 22q11.2DS. Phen22q11.2 was identified in 39 patients, including de novo variants in 12 patients. Several SNVs were detected, including variants in recurrently affected genes, such as CHD7 (n = 4), TBX1 (n = 2), JAG1 (n = 2), as well as variants in genes implicated in rare and ultra-rare diseases. We also described several rare and previously unreported clinical features associated with variants linked to phen22q11.2. No statistically significant phenotypic differences were observed between patients with phen22q11.2 and those with 22q11.2DS.</p><p><strong>Conclusions: </strong>Phen22q11.2 is genetically and phenotypically heterogeneous. The results support the use of ES with CNV analysis as a first-tier, high-throughput diagnostic approach in clin22q11.2, as comprehensive genomic testing is essential for improving diagnostic accuracy and optimizing both genetic counseling and clinical management in this population.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}