Molecular and cellular pediatrics最新文献

{"title":"Concerted action of gammaherpesvirus infection and moderate hyperoxia on lung structural development including effects on critical lung fibroblast functions in neonatal mice.","authors":"Anne Hilgendorff, Anna M Dmitrieva, Beatrix Steer, Misako Nakayama, Erika Gonzalez, Motaharehsadat Heydarian, Heiko Adler","doi":"10.1186/s40348-026-00256-x","DOIUrl":"10.1186/s40348-026-00256-x","url":null,"abstract":"<p><strong>Background: </strong>The development of chronic lung disease, also known as Bronchopulmonary Dysplasia (BPD), is the most prevalent complication after premature birth. Viral infections are discussed to drive or aggravate lung disease, but only little is known about their role in BPD pathophysiology. We therefore used a preclinical model as well as primary neonatal mouse lung fibroblasts to study the impact of viral infection on disease development in the presence or absence of hyperoxia induced lung injury.</p><p><strong>Methods: </strong>Neonatal C57BL/6 mice (PND 5-7) were infected with murine gammaherpesvirus-68 (MHV-68) by intranasal inoculation with or without pre-exposure to moderate hyperoxia (40%, 24 h). Next to the assessment of infection and replication (lytic and latent phase), lung histology and growth factor signaling were investigated together with indicators of proliferation and apoptosis early and late after infection. In vitro, these experiments were mirrored by exposing hyperoxia challenged and unchallenged primary neonatal mouse lung fibroblasts to MHV-68 (24 h). Analyses included cell function and developmentally relevant signaling.</p><p><strong>Results: </strong>MHV-68 infection in neonatal mice resulted in acute lung inflammation early after infection, followed by histopathologic abnormalities at 5 months of age and altered growth factor signaling in hyperoxia and virus exposed mice. In primary neonatal mouse lung fibroblasts, MHV-68 infection impaired critical developmental functions including migration and proliferation together with a decrease in Pdgfr-α expression that was reproduced in vivo in the lung periphery. Interestingly, in vitro virus-induced effects were only partially augmented by pre-exposure to clinically relevant levels of hyperoxia.</p><p><strong>Conclusions: </strong>The present study highlights the potential of MHV-68 to perturb fibroblast functions with a critical role in structural lung development. These effects are virus-dependent with longer-term effects being partially augmented by oxygen exposure. Our pilot study is the first that combines a relatively mild virus infection with exposure to only moderate levels of oxygen and underscores the importance to identify and better understand early, pathophysiologically relevant insults that impact on the dynamics of lung development and the need to verify these drivers in clinical studies.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715024","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":"Correction: Untargeted metabolomics reveals distinct metabolic profiles in MUT-type methylmalonic acidemia.","authors":"Shuruq Alsuhaymi, Reem H AlMalki, Maha Al Mogren, Ahamd Alodaib, Abdul-Hamid Emwas, Majed Dasouki, Ahmad Alfares, Mariusz Jaremko, Anas M Abdel Rahman","doi":"10.1186/s40348-026-00254-z","DOIUrl":"10.1186/s40348-026-00254-z","url":null,"abstract":"","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674727","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":"MRI paving the way to diagnosis of acute lymphoblastic leukemia in children and adolescents - a retrospective observational study.","authors":"Jan Lipp, Jörg Schaper, Franziska Rummel, Melda Kural, Arndt Borkhardt, Florian Babor, Triantafyllia Brozou","doi":"10.1186/s40348-026-00253-0","DOIUrl":"10.1186/s40348-026-00253-0","url":null,"abstract":"<p><strong>Background: </strong>Prompt diagnosis of childhood acute lymphoblastic leukemia (ALL) remains a clinical challenge, particularly in children presenting with normal blood counts and musculoskeletal symptoms. With the increasing use of magnetic resonance imaging (MRI) in evaluating such complaints, bone marrow signal alterations may be detected before hematologic abnormalities appear. Previous studies have described characteristic MRI patterns in leukemia, suggesting potential for earlier recognition. This study aims to clarify the role of MRI in the diagnostic pathway of pediatric ALL and to define radiological findings that should prompt bone marrow examination. We retrospectively reviewed all patients diagnosed with ALL at our institution between 2006 and 2024 and included those who underwent MRI prior to diagnosis. Clinical data were collected, and all MRI studies were re-evaluated by an experienced pediatric radiologist.</p><p><strong>Results: </strong>Twenty pediatric patients with ALL were included. Due to differing MRI protocols, the cohort was divided into two groups: one group (n = 17) underwent musculoskeletal imaging and one group (n = 3) underwent imaging of the trunk. Overall, MRI-detected bone marrow signal alterations contributed to diagnosis in 20 of 424 (4.7%) newly diagnosed pediatric ALL cases. More than one-third of patients (7/20; 35%) had a completely normal complete blood count (CBC) at presentation. Persistent bone pain was the leading symptom, preceding imaging in 18/20 cases. The mean time from symptom onset to MRI was 20.8 days (range 1-65), while the mean time from MRI to diagnosis was 18.4 days (range 0-180). In the musculoskeletal scans, all patients showed bone marrow signal alterations, predominantly T1-weighted (T1w) hypointensity (17/17) and proton-density-weighted (PDw) or T2-weighted short tau inversion recovery (T2w-STIR) hyperintensity (16/17). In the trunk scans, diffusion-weighted imaging revealed high DWI signal with low ADC values (3/3), and T2-weighted images demonstrated focal lesions (3/3).</p><p><strong>Conclusion: </strong>MRI plays an important role in the diagnostic pathway of pediatric ALL, especially in patients with persistent musculoskeletal pain and normal blood counts. In our cohort, MRI examinations could initiate a rapid diagnostic process leading to ALL confirmation. Diffuse T1w hypointensity and diffusion restriction emerged as key imaging findings. A normal CBC should therefore not delay urgent oncologic assessment when the clinical presentation and MRI pattern are suspicious for leukemia.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671444","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":"Multiple-breath washout at 12 months of age reveals lung function impairments in preterm infants with bronchopulmonary dysplasia.","authors":"Isabell Ricklefs, Elisa Grützner, Hannah Wedman, Mats Ingmar Fortmann, Désirée Lasserre, Nikolas Jakobs, Friederike Pagel, Fumi Sugihara, Wolfgang Göpel, Folke Christina Brinkmann, Matthias Volkmar Kopp, Mirjam Stahl, Christoph Härtel, Julia Pagel","doi":"10.1186/s40348-026-00248-x","DOIUrl":"10.1186/s40348-026-00248-x","url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth and may lead to long-term respiratory morbidity. Early measurements of impaired lung function are needed to guide the development of preventive strategies. This study aimed to evaluate the feasibility and potential utility of MBW-derived parameters for detecting early lung function impairment in preterm infants at a corrected age of 12 months.</p><p><strong>Methods: </strong>We conducted a single-centre study of preterm infants at 12 months' corrected age using sulfur hexafluoride MBW during spontaneous sleep. Tidal Breathing Flow Volume Loops (TBFVL) and MBW were used to assess respiratory parameters including lung clearance index (LCI). This was complemented by parental questionnaires on infant health. The cohort was stratified into three groups based on BPD diagnosis: (I) severe BPD (oxygen requirement at 28 days and respiratory support at 36 weeks' postmenstrual age), (II) mild BPD (oxygen requirement at 28 days but no oxygen or respiratory support at 36 weeks' postmenstrual age ) and (III) no BPD.</p><p><strong>Results: </strong>Reliable TBFVL and MBW measurements during spontaneous sleep were obtained in 45 of 112 infants (40%) including 8 infants with severe BPD and 7 infants with mild BPD. Infants with BPD exhibited higher LCI values (7.0 vs. 6.5, p = 0.018) and lower ratios of tidal volume to functional residual capacity (0.40 vs. 0.51, p = 0.022) compared to infants without BPD. Infants with severe BPD had higher LCI values than those without BPD (7.1 vs. 6.5, p = 0.022). LCI was positively correlated with the duration of continuous positive airway pressure (CPAP) support (Pearson correlation coefficient r = 0.476, p = 0.001), oxygen supplementation (r = 0.444, p = 0.002) and antibiotic treatment (r = 0.435, p = 0.003), respectively. Higher LCI values were also associated with an increased rate of hospital readmissions due to respiratory infections.</p><p><strong>Conclusions: </strong>Despite limited feasibility, MBW measurements obtained during spontaneous sleep at 12 months' corrected age revealed impaired lung function in preterm infants with BPD. LCI correlated with the duration of antibiotic treatment, CPAP support, and oxygen supplementation all of which represent potentially modifiable clinical factors. These findings suggest that LCI may serve as a promising early lung function parameter for long-term respiratory vulnerability.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610892","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":"Gut-brain-immune interactions in neonatal hypoxic-ischemic brain injury.","authors":"Josephine Herz, Ivo Bendix, Frederick Orywal, Christoph Härtel, Ursula Felderhoff-Müser","doi":"10.1186/s40348-026-00252-1","DOIUrl":"10.1186/s40348-026-00252-1","url":null,"abstract":"<p><strong>Background: </strong>Neonatal hypoxia-ischemia (HI) is the leading cause of childhood mortality and neurodevelopmental disability. Despite therapeutic hypothermia as the only clinically established treatment to date, outcomes remain poor for a significant proportion of affected infants. Mechanistic understanding has been brain-oriented in the past, however the gut and immune system are increasingly recognized as active modulators of brain injury, recovery and neurodevelopment.</p><p><strong>Main body: </strong>Gut microbiota regulate microglial maturation, myelination and blood-brain barrier integrity. Neonatal HI induces gut dysbiosis and barrier failure, associated with neuroinflammation. First, faecal microbiota transplantation experiments in animal models suggest a causal relationship. Clinical data corroborate microbial perturbations in HIE infants, though antibiotic exposure and the NICU environment represent potential confounders. At the level of the immune system, dysregulated peripheral innate and adaptive immune responses are well documented in HI-affected neonates, with some alterations persisting into school age. The microbiota dimension of these immune responses remains largely unexplored, despite well-characterized microbiota-immune interactions in models of adult stroke. Therapeutic candidates include probiotics, human milk oligosaccharides and butyrate, each with preliminary preclinical support but no completed clinical trials in HIE.</p><p><strong>Conclusion: </strong>Reframing neonatal HI as a systemic gut-brain-immune disease opens up new possibilities for adjunctive therapy and biomarker discovery. Progress requires longitudinal multi-omic clinical cohorts, sex-stratified and disease-phase-resolved preclinical analyses and rigorous evaluation of microbiome-targeted interventions.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148594979","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":"Subcutaneous infliximab as a maintenance option in pediatric IBD: a real-world cohort including younger and lower-weight children.","authors":"Neele Ridder, Johanna Overberg, Laura Kalveram, Samipa Pudasaini, Caroline Ruppel, Leonie Schumm, Stephan Henning, Philip Bufler","doi":"10.1186/s40348-026-00251-2","DOIUrl":"10.1186/s40348-026-00251-2","url":null,"abstract":"<p><strong>Background: </strong>Subcutaneous infliximab (SC-IFX) offers an alternative to intravenous infliximab (IV-IFX) in adults with inflammatory bowel disease (IBD), but evidence in children is scarce. This study reports treatment persistence, tolerability, and pharmacokinetics in a real-world pediatric IBD cohort following transition from IV-IFX.</p><p><strong>Methods: </strong>We conducted a single center retrospective study including all pediatric IBD patients transitioned from IV-IFX to SC-IFX (120 mg every other week) at our institution between November 2023 and April 2025. Clinical disease activity scores, inflammatory markers, IFX serum concentrations, and anti-IFX antibodies (AIA) were assessed at baseline and during follow-up. The primary outcome was treatment persistence. Secondary outcomes included disease activity, pharmacokinetics, immunogenicity and tolerability.</p><p><strong>Results: </strong>Twenty patients (median age 14.5 years; range 5-17), including six children < 12 years and five weighing < 40 kg, were included. After a median observation period of 44 weeks (IQR 26-60), 16/20 patients (80%) remained on SC-IFX, with no significant difference between Crohn's disease and ulcerative colitis. In a subgroup of four patients who received SC-IFX as a third dose following two intravenous induction doses, 3/4 (75%) maintained treatment over a median observation period of 60 weeks (range 16-64 weeks) and remained in clinical remission during follow-up. IFX serum concentrations increased after switching (median 11.8 µg/mL pre-switch vs. ≥24 µg/mL at follow-up), with most follow-up measurements reaching the assay ceiling. Concentrations were descriptively comparable between weight groups. All patients with detectable AIA prior to switching became antibody-negative during SC-IFX therapy, and no de novo antibodies were observed. Two patients discontinued therapy due to worsening of pre-existing paradoxical psoriasis. No other adverse events were documented.</p><p><strong>Conclusions: </strong>SC-IFX showed high persistence, stable inflammatory markers and good tolerability in this pediatric cohort, including younger and lower-weight children. SC-IFX appears to be a feasible maintenance option in selected pediatric patients, including early use after induction. Prospective studies are warranted to define pediatric-specific pharmacokinetic targets and individualized dosing strategies.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474681","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":"Untargeted metabolomics reveals distinct metabolic profiles in MUT-type methylmalonic acidemia.","authors":"Shuruq Alsuhaymi, Reem H AlMalki, Maha Al Mogren, Ahamd Alodaib, Abdul-Hamid Emwas, Majed Dasouki, Ahmad Alfares, Mariusz Jaremko, Anas M Abdel Rahman","doi":"10.1186/s40348-026-00250-3","DOIUrl":"10.1186/s40348-026-00250-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Methylmalonic acidemia (MMA), the most prevalent type of inherited metabolic disorder, is inherited in an autosomal recessive pattern due to MUT gene mutations that impair methylmalonyl-CoA mutase (MCM) enzyme activity. These mutations lead to the toxic accumulation of methylmalonic acid, which causes mitochondrial dysfunction, metabolic disruptions, and multisystem damage. Newborn screening followed by confirmatory biochemical and genetic tests, such as acylcarnitine analysis and urine organic acid profiling, are widely accepted and routinely used in biochemical genetics laboratories. However, these conventional methods have limited ability to detect novel, clinically relevant biomarkers that may offer deeper insights into the pathophysiology of MMA. This study highlights the importance of untargeted metabolomics to identify candidate biomarkers that could potentially predict long-term prognosis or represent novel therapeutic targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;LC-HRMS was used to analyze serum samples from patients with genetically confirmed MUT-type methylmalonic acidemia (n = 27) and healthy controls (n = 27). Differential metabolite and pathway analyses were performed to identify metabolic alterations associated with MMA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 267 dysregulated metabolites were identified in patients with MMA, including 185 upregulated and 82 downregulated metabolites. Downregulated metabolites included glutamine, isoleucine, and deamido-NAD&lt;sup&gt;+&lt;/sup&gt;, whereas upregulated metabolites included acylcarnitines, succinyladenosine, and leukotriene B4. These dysregulated metabolites were primarily associated with key altered pathways, including arachidonic acid metabolism, nicotinate and nicotinamide metabolism, sphingolipid metabolism, glutathione metabolism, and purine metabolism. Notably, potential biomarkers such as 11,12-epoxyeicosatrienoic acid (AUC = 0.964) and MG (PGF2alpha/0:0/0:0) (AUC = 0.953) are implicated in pathophysiological mechanisms of MMA and its standard treatment through their association with inflammation, oxidative stress, and altered fatty acid metabolism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings identify candidate disease-associated metabolites and provide insight into the metabolic disturbances associated with MMA. However, these results should be considered exploratory and require validation in larger, independent, age-matched, and longitudinal cohorts before clinical application. Methylmalonic acidemia (MMA), the most prevalent type of inherited metabolic disorder, is inherited in an autosomal recessive pattern due to MUT gene mutations that impair methylmalonyl-CoA mutase (MCM) enzyme activity. These mutations lead to the toxic accumulation of methylmalonic acid, which causes mitochondrial dysfunction, metabolic disruptions, and multisystem damage. Newborn screening followed by confirmatory biochemical and genetic tests, such as acylcarnitine analysi","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450722","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":"Diagnostic value of basic and extended procedures in pediatric fever of unknown origin - results of a nation-wide surveillance study.","authors":"Mira Katarina Bienioschek, Alice Lejeune, Gonza Ngoumou, Michael S Urschitz, Stefanie Dollinger, Martina Hagenberg, Kai Lehmberg, Simone Schrauth, Johannes Wolf, Horst von Bernuth, Dirk Foell, Tilmann Kallinich","doi":"10.1186/s40348-026-00249-w","DOIUrl":"10.1186/s40348-026-00249-w","url":null,"abstract":"<p><strong>Background: </strong>Pediatric fever of unknown origin (FUO) remains a major diagnostic challenge encompassing infectious, autoimmune and autoinflammatory as well as malignant diseases. Despite improved diagnostical procedures, no underlying disease can be identified in approximately one third of patients. Current guidelines recommend stepwise diagnostical approaches based on potential diagnostic clues (PDC+). This prospective nation-wide surveillance study aims to evaluate basic and advanced diagnostic procedures in the diagnostic of FUO.</p><p><strong>Methods and results: </strong>Via the German Pediatric Surveillance Unit, children were pseudonymized enrolled based on the following inclusion criteria: fever ≥ 38.5 °C for at least five out of ten consecutive days and no identifiable cause after standard diagnostic workup. The questionnaire collected patient data, symptoms, performed diagnostic workup, and the final diagnosis, if applicable. Among 113 included children, an underlying disease was identified in 72 cases (63.7%). 26 patients (23.1%) had infections, 31 children (27.4%) had systemic onset juvenile idiopathic arthritis/Still's disease (sJIA/SD), and 15 children (13.3%) were classified as \"other diagnoses\" including autoinflammatory diseases, vasculitides, and malignancies. Children with sJIA/SD presented with more clinical symptoms (mean = 4.6, SD = 2.17) compared to those with infections (mean = 2.7, SD = 1.40, p=.002). Basic diagnostic workup revealed at least one PDC + in every case (mean = 6.6). Most PDC+ (mean = 3.1, SD = 1.82) were identified by history taking and physical examination as well as by laboratory testing and blood count (mean = 2.5 PDC+, SD = 1.32). A total of 370 basic imaging investigations, e.g. abdominal ultrasound and echocardiography, provided in total 50 PDCs+ demonstrating their high diagnostical yield. Primarily in children with unclear clinical presentation advanced imaging revealed PDC+. Overall, the number of misleading PDCs (PDC-) was low (mean = 1.0, SD = 1.14) with autoantibody testing being the basic diagnostic procedure accounting for the majority of PDC-.</p><p><strong>Conclusion: </strong>The results of this nation-wide surveillance study highlight the value of basic and advanced diagnostical approaches in the management of pediatric FUO. Careful history taking, physical examination, and targeted basic diagnostic testing can identify multiple PDC+ with only few misleading PDC-, which may contribute to diagnostic accuracy and avoid unnecessary testing. The findings can be introduced into guidelines in order to standardize and improve the diagnostic approaches in children with FUO.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354947","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":"The impact of central venous catheter use on long-term growth and neurobehavioral outcome in preterm children born < 29 weeks of gestation.","authors":"Christine Silwedel, Jana Retzmann, Ingmar Fortmann, Anne Grimm, Anna Häfke, Fabian Kleindiek, Kathrin Hanke, Cornelia Wiechers, Ursula Felderhoff-Müser, Harald Ehrhardt, Jochen Essers, Egbert Herting, Juliane Spiegler, Wolfgang Göpel, Christoph Härtel","doi":"10.1186/s40348-026-00247-y","DOIUrl":"10.1186/s40348-026-00247-y","url":null,"abstract":"<p><strong>Background: </strong>Preterm infants often receive central venous catheters (CVCs) for parenteral nutrition during initial enteral feeding advancement. Whether the use of CVCs promotes growth and neurodevelopmental outcomes is currently unknown.</p><p><strong>Methods: </strong>Using German Neonatal Network data, this retrospective population-based cohort study evaluated long-term outcomes in very low birth weight infants (VLBWI) born < 29 weeks of gestation. Multivariate regression analyses and propensity score matching were applied to assess associations between CVC use, somatic growth, and cognitive outcomes (Wechsler Preschool and Primary Scale III intelligence quotient (IQ), Strengths and Difficulties Questionnaire (SDQ)) at 5-7 years of age.</p><p><strong>Results: </strong>In the follow-up cohort of 2072 infants, 74% had a history of neonatal CVC use. VLBWI with CVCs had a significantly lower mean gestational age (25.97 vs. 26.97 weeks, p < 0.001) and lower somatic parameters at birth (mean weight: 829 vs. 986 g, length: 33.7 vs. 35.7 cm, head circumference: 23.8 vs. 25.1 cm, all: p < 0.001) than those without CVCs. Before risk adjustment, mean weight, head circumference, and body mass index at preschool age were significantly lower in children with prior CVC use. These children additionally exhibited lower IQ and higher SDQ scores. Adjusting for potential confounders, linear regression analyses and propensity score matching indicated that CVC use itself was not associated with differences in weight, length, head circumference, or cognitive outcomes at preschool age. Notably, In infants with CVCs, full enteral feeding was achieved approximately 8 days later than in those without CVCs (21.5 vs. 13.2 d, p < 0.001). Prolonged attainment of full enteral feeding was associated with reduced preschool IQs (β: -0.069, CI: -0.116 to -0.022, p < 0.001).</p><p><strong>Conclusion: </strong>In this study, CVC use was not associated with improved somatic growth or psychomotor outcomes at preschool age. Furthermore, our data suggest that earlier attainment of full enteral feeding is associated with more favorable long-term psychomotor outcomes. Within the limits of an association study, these findings support prioritizing strategies that facilitate early enteral feeding advancement in VLBWI, while avoiding routine CVC insertion whenever clinically appropriate.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304345","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":"Cardiomyopathy and mitochondrial encephalomyopathy in a female child associated with a heterozygous X-linked AIFM1 variant.","authors":"Christoph Sandmann, Swathi Gudapati, Johannes A Mayr, Rami Abou Jamra, Alexander Kovacevic, Steffen Syrbe","doi":"10.1186/s40348-026-00246-z","DOIUrl":"10.1186/s40348-026-00246-z","url":null,"abstract":"<p><strong>Background: </strong>AIFM1 encodes the X-linked oxidoreductase 'apoptosis-inducing factor 1, mitochondrial' that mediates caspase-independent programmed cell death and is involved in redox metabolism. To date, cardiac involvement has been reported in four patients with AIFM1 variants, primarily presenting as ventricular hypertrophy, but its clinical course and prognosis remain not well understood.</p><p><strong>Methods: </strong>We report the first affected female with a heterozygous AIFM1 variant who developed infantile-onset mitochondrial encephalomyopathy and cardiomyopathy with initial ventricular hypertrophy, that progressed to left ventricular dilation and chronic heart failure. In addition, we review the available literature on AIFM1-associated cardiomyopathy to contextualize clinical findings.</p><p><strong>Results: </strong>Genetic testing identified a heterozygous AIFM1 variant, c.506C > T (p.Pro169Leu), with extremely skewed X-inactivation (98:2) in a female. The patient presented with infantile-onset mitochondrial encephalomyopathy. Echocardiography at 8 months revealed marked left ventricular hypertrophy with preserved systolic function. During follow-up, the cardiac phenotype progressively evolved into dilated cardiomyopathy with systolic dysfunction by 2.5 years of age, necessitating initiation of heart failure therapy.</p><p><strong>Conclusions: </strong>A heterozygous AIFM1 variant can result in disease manifestation in females. The phenotypic spectrum of AIFM1-related disease includes cardiomyopathy, typically characterized by early-onset cardiac hypertrophy that may progress to ventricular dilatation and heart failure. This case highlights the importance of early recognition and careful cardiac monitoring in affected individuals, including female variant carriers.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148297649","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}