Search Results (32,124)

Background: Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below 18 years of age and carries a boxed warning for excess mortality that is most pronounced in hospital-acquired and ventilator-associated pneumonia. Its role, if any, in preterm infants with VAP is undefined. Objectives: To systematically identify and appraise all human evidence on the efficacy (clinical cure, microbiological eradication, survival) and safety (adverse events, mortality) of tigecycline used to treat VAP or nosocomial pneumonia during mechanical ventilation in preterm infants and neonates. Methods: A PRISMA 2020 structured search of PubMed/MEDLINE, Cochrane CENTRAL, Scopus, trial registries, regulatory documents, Google Scholar and reference lists was designed without language or date restrictions. Eligible reports described tigecycline treatment of pneumonia/VAP in neonates or young infants; pediatric case series and syntheses were retained as contextual evidence. Because only case reports and small non-comparative series were anticipated, a narrative synthesis was pre-specified; JBI tools and GRADE were planned for appraisal and certainty. Results: No randomized controlled trial, controlled observational study, or study dedicated to tigecycline for VAP in preterm infants was identified. Direct evidence meeting the full eligibility criteria (preterm neonate, VAP specifically, separately extractable outcomes) was limited to two case reports of extremely preterm neonates with VAP successfully weaned after tigecycline-based salvage combination therapy. Six further neonatal/young-infant reports initially considered were, on full-text re-review, reclassified as contextual (not index) evidence because they described non-VAP infections (sepsis, or CNS infections such as ventriculitis/meningitis), non-preterm ages, or mixed-infection series without separable VAP data. Reported outcomes were generally favorable in published cases but are subject to severe selection and publication bias; thrombocytopenia, hypofibrinogenemia and hepatic enzyme elevation were the principal adverse signals, against a class-level mortality signal concentrated in VAP. Quantitative pooling was not appropriate. The overall certainty of evidence was very low. Conclusions: There is no direct, credible efficacy or safety evidence supporting tigecycline for VAP in preterm infants. Available data neither establish benefit nor exclude harm. Based on this very-low-certainty evidence and on regulatory/class-level safety data rather than on demonstrated efficacy, tigecycline warrants consideration only as a last-resort, combination salvage option for culture-confirmed pan- or extensively drug-resistant pathogens when no safer alternative exists, with intensive monitoring and, ideally, within a registry or trial. Adequately designed neonatal pharmacokinetic and comparative safety studies are urgently needed. Registration: PROSPERO CRD420261450972 (registered 14 July 2026). Full article

Micro- and nanoplastics (MNPs) are widely detected in food, drinking water, food-contact materials, and human biological samples. This narrative review evaluates whether experimental evidence supports a role for MNPs as modifiers of food-allergen digestion, intestinal-barrier function, microbiota composition, and immune tolerance. In vitro studies indicate that protein-corona formation can alter allergen conformation, epitope accessibility, and proteolysis, although effects vary by polymer, particle size, dose, and digestive model. Rodent studies provide evidence that MNP exposure can disrupt epithelial integrity, induce oxidative and inflammatory signaling, and modify microbiota-dependent immune regulation. More direct food-allergy models have reported exacerbation of ovalbumin- and cow’s-milk-allergic responses, including Th2 polarization and changes in dendritic cell and regulatory T-cell compartments. Infants may represent a susceptible and highly exposed population because of immature digestive and barrier function and the use of plastic feeding equipment; however, the available pediatric evidence is limited to exposure studies and simulated digestion. The effect of MNP exposure on the incidence of food allergies, reaction thresholds, or clinical severity in humans has not yet been studied. Accordingly, current findings support biological plausibility and identify research priorities, but they do not establish causality in humans. Full article

Lower respiratory tract infections (LRTIs) are a leading infectious cause of death in children worldwide. Complete blood count (CBC)-derived inflammatory ratios are low-cost and widely available, yet their reported performance varies. We reviewed 46 PubMed-indexed studies (2016–2026) in children aged 0–18 years with viral, bacterial, or mycobacterial LRTI. The findings were mapped across diagnosis, etiological differentiation, severity, and outcome prediction. The neutrophil-to-lymphocyte ratio (NLR) was the most investigated marker, with the broadest evidence base for severity assessment and for separating bacterial from viral disease, although its performance remained pathogen-, population-, and endpoint-dependent; it was elevated in severe pertussis, tuberculosis, Mycoplasma pneumoniae, Streptococcus pneumoniae, and SARS-CoV-2 infection, whereas findings in respiratory syncytial virus infection were conflicting. The platelet-to-lymphocyte ratio had the next broadest evidence base for severity, and the systemic immune-inflammation index was consistently elevated in Mycoplasma pneumoniae and SARS-CoV-2 infection. No single ratio performed consistently across all etiologies. Ratios governed by one dominant immunopathogenic mechanism behaved predictably; those whose numerator and denominator respond to the same process did not. Cut-offs were neither standardized, age-specific, nor externally validated, and most estimates derived from retrospective cohorts in few countries; reported values therefore represent association and discrimination rather than validated prediction. Standardized, age-specific thresholds are needed before these markers can support routine risk stratification. Full article

Background: Type 1 diabetes (T1D) incidence is rising at 3–5% per year. Autoantibody (AAB) screening identifies at-risk children pre-symptomatically, yet the clinical significance of single AAB positivity and its short-term trajectory remain incompletely characterized. Methods: Five T1D-associated AABs (anti-GAD65, anti-IA2, anti-ZnT8, ICA, IAA) were measured in 210 Bulgarian children (160 with first-degree T1D relatives, 50 controls). Seven single-AAB-positive children received lifestyle counseling (low-glycemic-index diet, physical activity ≥ 60 min/day) and were reassessed at 3 or 6 months with repeat AAB panels, HbA_1c, blood glucose and C-peptide. Results: Anti-GAD65 was the most frequent single AAB (n = 3), followed by anti-ZnT8 (n = 2), anti-IA2 (n = 1) and IAA (n = 1). None developed a second AAB or metabolic abnormalities. Titer dynamics were heterogeneous: two children showed apparent seroreversion (in one, substantially confounded by concurrent immunosuppressive therapy for an unrelated condition), one showed a ~15-fold titer reduction while remaining seropositive, one showed a minimal titer decrease, and three displayed mildly increasing titers. None progressed to multiple autoantibody positivity, and all maintained normal metabolic profiles. Conclusions: Favorable short-term outcomes were observed during follow-up of children with single autoantibody positivity. These findings suggest that single AAB positivity may follow a non-progressive course in some children. However, this study design cannot distinguish the contribution of lifestyle counseling from natural variability. Prospective controlled studies with larger cohorts, HLA stratification and longer follow-up are needed to determine whether lifestyle interventions can independently alter autoantibody dynamics and delay T1D progression. Full article

Objective: This prospective study evaluated systolic and diastolic cardiac functions in pediatric cirrhosis using conventional and tissue Doppler imaging (TDI), and explored their correlation with liver severity scores. Methods: Conducted at Inonu University, we enrolled 75 pediatric cirrhotic patients (44 compensated, 31 decompensated) from Pediatric Gastroenterology and 61 controls of similar age and sex without structural/functional heart disease from Pediatric Cardiology outpatients. All underwent clinical, laboratory, and echocardiographic assessments. To address multiple testing, Bonferroni correction was applied. Adjustments for age, sex, and disease severity were integrated into the correlation matrices to control for confounding parameters. Results: The cirrhosis cohort exhibited significantly higher heart rates, ejection fractions, and aortic/pulmonary velocity-time integrals than controls (p < 0.05). Conversely, growth-independent diastolic indices revealed distinct relaxation impairment: transmitral E/A and annular e′/a′ ratios were significantly lower, while Mitral E/e′ was elevated (p < 0.05). Deceleration time, isovolumetric relaxation time, and Myocardial Performance Index (MPI) were significantly prolonged (p < 0.01). Decompensated patients demonstrated significantly higher left ventricular filling pressures (Mitral E/e′) than compensated patients and controls (p = 0.002). After adjusting for age and sex, the Pediatric End-Stage Liver Disease (PELD) score maintained significant positive correlations with heart rate (r = 0.408) and Mitral E/e′ (r = 0.433) (p ≤ 0.002). FIB-4 and APRI scores showed positive correlations with VTI and TAPSE, markers of right ventricular volume overload (p < 0.05). Conclusions: Hyperdynamic circulation appears to mask resting systolic metrics in pediatric cirrhosis. However, prolonged diastolic phases and increased MPI suggest presence of subclinical myocardial dysfunction, especially during clinical decompensation. Routine non-invasive liver staging scores show potential clinical utility as ancillary screening tools for early cardiovascular risk evaluation. Full article

In the post-pandemic era, identifying children who are most susceptible to severe illness and COVID-19-related mortality is essential for guiding public health policies. This study examined the risk factors for COVID-19-related severe illness and mortality from 2023 to mid-2025. We conducted a population-based cohort study using nationwide Brazilian data from patients aged <18 years with laboratory-confirmed SARS-CoV-2 infection between January 2023 and June 2025. The primary outcomes were COVID-19-related severity and death. Separate binary multivariable logistic regression models were developed for each of the outcomes. Among 465,689 children, 1.3% (n = 5963) developed severe illness, and 0.18% (n = 847) died. Factors associated with an increased risk of severe illness included age < 2 years, presence of comorbidities, Indigenous ethnicity, and lack of vaccination. Neurological disorders conferred the highest risk among the clinical conditions (adjusted odds ratio [aOR] = 34.1; 95% CI: 27.9–41.8). Regional differences were also observed; the North and Northeast regions showed higher mortality (aOR = 2.3; 95% CI: 1.8–3.0) than the Central-West region. Compared with White ethnicity, non-White ethnicities had higher mortality: Indigenous (aOR = 23.5; 95% CI: 13.5–39.3), Black (aOR = 1.95; 95% CI: 1.29–2.92), and Brown (aOR = 1.43; 95% CI: 1.18–1.73) ethnicities. Lack of any vaccine dose was associated with a significantly increased risk of severe illness (aOR = 1.39; 95% CI: 1.15–1.67. p < 0.001) and death (aOR = 2.1; 95% CI: 1.3–3.5; p < 0.001). In the post-pandemic era, younger age, comorbidities, sociodemographic disparities, and lack of vaccination were associated with an increased risk of severe illness and COVID-19-related death in the pediatric population. Full article

Objectives: Robot-assisted stereoelectroencephalography (SEEG) is increasingly used for invasive presurgical evaluation in drug-resistant epilepsy. Feasibility and accuracy data for robotic alignment systems remain limited. We analyzed our initial institutional experience and compared the results with the contemporary literature. Methods: We retrospectively analyzed nine consecutive patients who underwent SEEG depth electrode implantation using the Brainlab Cirq robotic alignment system and intraoperative MRI for registration. Demographic and operative variables were extracted from institutional records. Implantation accuracy was measured on fused postoperative imaging as Euclidean entry point error (EPE) and target point error (TPE). A PubMed-focused literature screen was performed to identify studies reporting robotic SEEG implantation accuracy and/or efficiency metrics for comparison. Results: Nine patients underwent implantation of 69 SEEG electrodes. Mean age was 21.7 ± 11.4 years. A mean of 7.7 ± 2.1 electrodes was implanted per patient. Mean operative time was 120.2 ± 31.9 min, corresponding to 16.0 ± 3.4 min per electrode. Mean EPE was 1.36 ± 0.60 mm and mean TPE was 1.79 ± 0.69 mm. Moreover, the maximum projected skull-entry angle was not independently associated with either EPE or TPE. In comparison with published robotic SEEG series and meta-analyses, our accuracy results fall within the established high-precision range and compare favorably with the most recent robotic-arm-specific data. Conclusions: In this initial consecutive series, our robotic arm alignment system enabled accurate SEEG implantation with sub-2-mm mean target error. These findings support robotic arm systems as effective robotic alignment platforms for invasive epilepsy monitoring, while larger multicenter studies remain necessary to define comparative accuracy, learning curve effects, and complication profiles. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the most common chronic liver disease in childhood, paralleling the global increase in pediatric obesity and metabolic dysfunction. Once considered a benign condition, pediatric MASLD is now recognized as a heterogeneous and potentially progressive disease that may advance from simple steatosis to steatohepatitis, fibrosis, and, rarely, cirrhosis, with lifelong hepatic and cardiometabolic consequences. Its pathogenesis is multifactorial, involving insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, genetic and epigenetic susceptibility, environmental factors, and alterations in the gut microbiome. Most affected children are asymptomatic, and diagnosis is often prompted by elevated liver enzymes or incidental imaging findings. Noninvasive tools, including ultrasonography, elastography, serum biomarkers, and emerging multi-omics approaches, are improving disease detection and risk stratification, although liver biopsy remains the reference standard in selected cases. Lifestyle modification, including dietary optimization, increased physical activity, and gradual weight reduction, remains the cornerstone of management, while pharmacological therapies are still under investigation in pediatric populations. The marked variability in disease susceptibility; progression; and treatment response underscores the need for a personalized medicine approach. Integrating clinical characteristics with genomic, epigenomic, metabolomic, and microbiome data may enable early identification of high-risk children, more accurate prognostic assessment, and individualized preventive and therapeutic strategies. Early detection and multidisciplinary care involving pediatricians, hepatologists, endocrinologists, dietitians, and families may help reduce disease progression and the risk of long-term hepatic and cardiometabolic complications. This review summarizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pediatric MASLD, with a particular emphasis on precision diagnostics, biomarker discovery, and personalized therapeutic approaches. It also discusses current challenges and future directions for implementing personalized medicine to improve outcomes and reduce the lifelong burden of pediatric MASLD. Full article

Psoriasis is a chronic, relapsing skin disease driven by failed immune tolerance toward self-antigens and sustained IL-23/IL-17 signaling. Systemic drugs and biologics control disease in many patients, yet they do not restore lasting tolerance, and most patients relapse after treatment withdrawal. Tolerogenic vaccines aim to re-educate the cutaneous immune system: when administered under non-inflammatory conditions, they push antigen-presenting cells toward tolerogenic dendritic cells (tDCs) and regulatory T cells (Tregs) instead of pathogenic effectors. Because the hyperkeratotic stratum corneum of psoriatic plaques blocks macromolecular vaccines, microneedle (MN) arrays can deposit nanocarriers directly into the dermal-epidermal junction. The narrative review asks whether MN-delivered tolerogenic nanovaccines can advance psoriasis therapy beyond broad immunosuppression. We first define tolerogenic vaccination and explicitly distinguish antigen-specific tolerogenic vaccines, antigen-independent immune-reprogramming nanocarriers, and conventional local drug delivery, then survey MN engineering and nanocarrier architectures, the immunomodulatory pathways involved, and translational barriers spanning manufacturing, safety, and regulation. Because most evidence is preclinical, the level of evidence is reported for each platform, and the unresolved autoantigen problem, the limitations of imiquimod-based models, and the need for human-relevant validation are emphasized. Full article

Osteogenesis imperfecta (OI) is the most common heritable bone-fragility disorder, with type I (non-deforming OI) representing its mildest classical phenotype (historically referred to as Lobstein disease). Intramedullary (IM) rodding is essential for managing recurrent long-bone fractures and progressive deformities, with the Fassier–Duval (FD) telescopic rod now being the standard choice. This narrative review, based on a structured search from the seminal 1959 description of IM rodding to 2026, synthesizes the design principles, the minimally invasive technique and the comparative outcomes of FD rodding of the lower limb, with explicit attention to type I disease. Across cohort studies, comparative series and a recent systematic review, telescopic rods consistently achieve lower revision rates and longer implant survival than static or non-telescopic devices, reducing reoperation odds by roughly three-quarters. Overall complication rates nonetheless remain high (commonly 33–55%) and are dominated by implant migration and failure of telescoping. Younger age and eccentric epiphyseal positioning after incomplete deformity correction increase migration risk. Type-I-specific evidence remains limited. A report published under the “Lobstein” designation involved a Sillence type IV patient and therefore does not constitute type-I-specific evidence. Retrospective data nevertheless suggest favorable implant survival with telescopic fixation, but definitive conclusions cannot yet be drawn. Proper technique, adjunctive bisphosphonate therapy and multidisciplinary care remain decisive. Phenotype-stratified prospective data are the principal unmet need. Full article

Background: The diagnosis of infectious diseases currently relies predominantly on polymerase chain reaction (PCR) assays. However, the range of pathogens that can be detected simultaneously using these methods is limited, and their effective use depends on an a priori etiological hypothesis. Multiplex PCR-based targeted next-generation sequencing (mp-tNGS) is considered a promising complementary approach for expanded viral testing. This study aimed to develop an in-house mp-tNGS method, perform an initial evaluation of its analytical sensitivity, and explore its performance using clinical respiratory specimens. Methods: The method comprised a panel targeting 28 viruses and bioinformatics pipelines for mp-tNGS data processing. Analytical sensitivity was evaluated using positive control samples (PCSs) containing encapsulated RNA or DNA. Performance with clinical specimens was explored using 910 nasopharyngeal and oropharyngeal swab specimens, which were divided into three groups based on the results of prior PCR testing. Results: Of the 28 viral targets, 23 underwent experimental analytical evaluation, whereas five were assessed in silico only. For 19 of the 23 PCSs tested, the estimated limit of detection (LoD) ranged from 6.3 × 10² to 9.4 × 10³ copies/mL. In the group of 216 PCR-positive specimens, PCR and mp-tNGS results were fully concordant in 139 cases; in 28 specimens, mp-tNGS additionally detected other viruses. Among 394 PCR-negative specimens, mp-tNGS detected viruses in 81. In the group of 300 hospital-derived specimens, mp-tNGS detected at least one viral target in 131 specimens, including additional viral detections and coinfections not identified during the initial testing. A substantial proportion of the additional findings involved Epstein–Barr virus (EBV) and cytomegalovirus (CMV), warranting cautious clinical interpretation. Conclusions: The developed mp-tNGS approach demonstrated the potential to simultaneously detect a broad range of known viruses, provide viral typing, and identify coinfections. The method may be used as an adjunctive tool to broaden the laboratory diagnosis of respiratory infections; however, further optimization, validation, and standardization of criteria for result interpretation are required. Full article

Canine degenerative myelopathy (DM) is a progressive, adult-onset neurodegenerative disease, with similarities to superoxide dismutase 1 (SOD1)-associated ALS. Clinical signs of DM begin with asymmetric pelvic limb general proprioceptive ataxia and spastic paresis that progresses to flaccid tetraplegia and respiratory failure. Although pelvic limb muscle atrophy and peripheral neuropathy have been reported in DM, intramuscular SOD1 accumulation and muscle spindle pathology remain incompletely characterized. This study evaluated pathological changes in the tibialis cranialis muscle of Pembroke Welsh Corgis with early- and late-stage DM and age-matched unaffected controls. Histologic stains and immunohistochemistry were used to evaluate myofiber morphology, fiber type distribution, muscle spindle integrity, and SOD1 immunoreactivity. Compared to unaffected dogs, DM-affected dogs exhibited increased SOD1 immunolabeling, greater variability in myofiber size, altered myofiber shape and packing, and fibrosis. A progressive reduction in the percentage of type I myofibers was observed without evidence of fiber type grouping. These changes were evident during early disease and became more pronounced with disease progression. Muscle spindles exhibited late-stage disruption of intrafusal myofiber organization and marked increase in SOD1 immunoreactivty. The observed alterations suggest that the muscle pathology was, at least in part, intrinsic to the muscle, rather than being secondary to neurodegeneration. Our findings demonstrate early and progressive pathological changes in the tibialis cranialis muscle, expanding our understanding of skeletal muscle involvement in DM. Full article

Severe dengue remains an important cause of pediatric hospitalization, morbidity, and mortality in tropical and subtropical regions, particularly where rapid triage and pediatric critical-care capacity are limited. This structured narrative review synthesizes evidence on the epidemiology, pathogenesis, early recognition, diagnosis, management, and prevention of severe dengue in children. Severe disease reflects interactions among viral factors, pre-existing immunity, dysregulated host responses, and microvascular endothelial injury. Antibody-dependent enhancement, inflammatory mediators, dengue nonstructural protein 1, and endothelial glycocalyx disruption contribute to vascular hyperpermeability, plasma leakage, shock, severe bleeding, and organ impairment. Because deterioration often occurs abruptly around defervescence, serial clinical assessment, hematocrit trends, urine-output monitoring, and timely recognition of warning signs are central to risk stratification. Molecular assays and NS1 antigen testing are most useful during the early febrile phase, although diagnostic performance varies with illness timing and immune status. Carefully titrated isotonic crystalloid therapy remains the cornerstone of treatment; both delayed resuscitation and excessive fluid administration may worsen outcomes. Reducing mortality requires integrated clinical and public-health strategies combining standardized pediatric management, accessible diagnostics, effective referral systems, vaccination where appropriate, surveillance, and vector control. Full article

Background/Objectives: Skeletal maturity assessment is essential for timing orthodontic growth-modification treatment. The cervical vertebral maturation (CVM) method is widely used, but manual staging is subjective and prone to inter-observer variability, and artificial intelligence (AI) may improve its consistency and accuracy. The aim of this study was to develop and externally validate a fully automated deep-learning pipeline for CVM assessment and to determine its diagnostic accuracy for three-phase and six-stage classification against calibrated expert staging. Methods: A cross-sectional three-stage deep-learning pipeline was trained and internally cross-validated on 523 cephalometric radiographs from King Abdulaziz University. Images were CLAHE-enhanced; YOLOv8 detected the C2–C4 region; a ResNet-50 classifier assigned the growth phase (Early, Peak, Late); and phase-specific binary classifiers assigned CVM stages (CS1–CS6). External validation used the independent ‘Aariz dataset (n = 150). Results: The detector achieved mAP@0.5 = 0.9939 and mean IoU = 0.8884. On external validation, the three-phase classifier reached 96.0% accuracy, macro-F1 0.919, weighted κ 0.951 and ROC-AUC 0.998, whereas the end-to-end six-stage cascade reached 79.3% accuracy, macro-F1 0.735, weighted κ 0.910 and ROC-AUC 0.923. Most errors occurred between adjacent stages, with 98.7% of predictions within ±1 stage of the reference standard. Conclusions: The automated pipeline showed promising performance for three-phase CVM classification and moderate performance for six-stage classification on one independent external benchmark. Further multicenter prospective validation is required to establish its generalizability and clinical utility. Full article

Introduction: Determining the prognosis and probable evolution of dilated cardiomyopathy (DCM) in pediatric patients has been an area of interest in the literature over the years. The aim of this study was to investigate baseline clinical, laboratory, and echocardiographic parameters associated with early ventricular recovery during hospitalization in children with dilated cardiomyopathy. Materials and methods: A retrospective, observational, single-center study was conducted including 56 pediatric patients diagnosed with DCM between 2015 and 2025. Baseline clinical and paraclinical variables were collected at admission. Changes in the left ventricular ejection fraction were assessed during hospitalization, and patients were categorized into recovery and non-recovery groups. Statistical analysis was performed to identify independent predictors of early ventricular recovery. Results: Early ventricular recovery occurred in 25 (44.64%) patients. In multivariate logistic analysis, Ross functional class was the only independent marker associated with early ventricular recovery (OR 2.547, 95% CI 1.179–5.501; p = 0.017). Bootstrap validation confirmed the robustness of the association. Troponin, NT-proBNP, mitral regurgitation and treatment strategy were not independently associated with recovery. ROC analysis demonstrated a modest discriminatory performance for the Ross functional class. Discussion: In this cohort of children with DCM, symptom severity was the only baseline variable consistently associated with early ventricular recovery. Clinical assessment was more useful than laboratory biomarkers and echocardiographic parameters in predicting short-term improvement in ventricular function. Conclusions: The Ross functional class was the only baseline variable independently associated with early ventricular recovery. These findings support the use of the Ross functional classification as a simple bedside tool, useful in early prognostic stratification in children with dilated cardiomyopathy, although its discriminatory performance was modest. Full article