ABSTRACT Importance Elevated microvessel density (MVD) and lymphatic vessel density (LVD) have been linked to poor outcomes in several malignancies. However, their prognostic significance in neuroblastoma (NB) remains unclear. Objective To evaluate the prognostic value of MVD and LVD in NB and construct an optimized prognostic model. Methods Sixty patients with NB were included. MVD and LVD were quantified using immunohistochemical staining for CD31 and D2‐40, respectively. Cox regression‐based prognostic models combining these markers with the International Neuroblastoma Risk Group (INRG) classification were compared with the standard INRG‐based model using receiver operating characteristic curves, the concordance index (C‐index), decision curve analysis (DCA), net reclassification improvement, and integrated discrimination improvement. Model robustness was assessed using bootstrap with 1000 resamples. Results The median MVD and LVD were 24.0/mm 2 and 7.16/mm 2 , respectively. High MVD (area under the curve [AUC] = 0.788) and high LVD (AUC = 0.693) were significantly associated with lower 5‐year event‐free survival (22.2% vs. 78.2% for MVD; 44.8% vs. 81.5% for LVD; both P < 0.05). In the multivariable Cox regression analysis, both LVD (hazard ratio [HR] = 1.088, P = 0.010) and INRG classification (HR = 5.594, P = 0.008) showed statistically significant associations with prognosis in the model incorporating LVD into the INRG classification. The model also enhanced the C‐index (0.747 vs. 0.696 for the original model), AUC, and DCA, with consistent results in internal validation. Interpretation Both MVD and LVD were associated with adverse outcomes in NB, while incorporation of LVD provided additional prognostic information beyond the INRG classification. Integrating LVD may improve the predictive performance of INRG‐based models and help identify biologically aggressive tumors among clinically non‐high‐risk patients, providing a foundation for more precise treatment planning.
Importance:Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by dysregulated lipid metabolism, inflammation, and mitochondrial dysfunction. Given the rising burden of MASLD in children and adolescents, identifying experimentally tractable mechanisms relevant to pediatric diseases is of considerable interest. Tryptophan hydroxylase-1 (TPH1), the rate-limiting enzyme for peripheral serotonin synthesis, has been implicated in metabolic disorders, but its hepatic role in MASLD remains unclear. Objective:To investigate whether Tph1 suppression alleviates lipid accumulation, mitochondrial dysfunction, and hepatocyte injury through changes associated with Parkin-mediated mitophagy. Methods:MASLD was induced in young adult male C57BL/6J mice by a 12-week high-fat diet (HFD). At HFD onset, mice received a single tail-vein injection of liver-tropic AAV8-shTph1 or the control AAV8. The HFD feeding was continued for 12 weeks until the end of the experiment. Hepatic histology, serum biochemistry, oxidative stress, inflammatory responses, apoptosis, and mitochondrial function were also evaluated. Mechanistic studies were conducted in palmitic acid/oleic acid-treated AML12 hepatocytes using siRNA targeting Tph1 and Parkin. Results:Hepatic TPH1 expression was elevated in MASLD mice. Tph1 knockdown alleviated diet-induced steatosis, reduced serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and transaminase levels, suppressed oxidative stress, and attenuated inflammatory and fibrotic markers. Tph1 silencing decreased hepatocyte apoptosis and restored mitochondrial function. Transmission electron microscopy and fractionated Western blotting analyses revealed increased Parkin-associated mitophagy. In AML12 cells, siTph1 reduced lipid accumulation and apoptosis, whereas co-silencing Parkin partially reversed these effects. Interpretation:Hepatic TPH1 is associated with MASLD progression and impaired Parkin-mediated mitophagy. Tph1 suppression may represent a potential therapeutic strategy for experimental MASLD, with possible translational relevance to pediatric MASLD, though direct clinical validation is still needed.
Atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur in children and adolescents, increasing the disease burden and clinical complexity. Accumulating evidence suggests that children with AD have a higher risk of incident ADHD, a risk that is particularly pronounced in those with early-onset, severe AD, or significant sleep disturbances. The underlying mechanisms are hypothesized to involve the dysregulation of the "inflammation-itching-neurobehavioral" axis. This narrative review synthesizes current evidence regarding the epidemiology, potential mechanisms, and clinical management of this comorbidity. We propose that proactive screening and aggressive control of skin inflammation and pruritus are key to disrupting this vicious cycle.
Early autism identification in children aged 0-5 years is often discussed in terms of screening accuracy, yet consequential delay frequently occurs across the pathway from first concern to referral, diagnostic assessment, and support. This critical narrative review examines early autism identification as a pathway problem rather than as a single testing event. It synthesizes evidence on developmental surveillance, autism-specific screening, parental and clinician concern, referral conversion, diagnostic waiting, service capacity, inequity, family burden, and pre-diagnostic support. Screening tools can identify an elevated likelihood of autism and may accelerate diagnosis for some screen-positive children, but they cannot confirm diagnosis or safely exclude autism when concern persists, and they do not compensate for failures in follow-up, referral, assessment capacity, or support initiation. Recent evidence supports a cautious interpretation of universal autism screening because diagnostic stability, screening accuracy, and intervention benefit in screen-detected children remain uncertain. Comparative evidence on the Modified Checklist for Autism in Toddlers, Revised with Follow-Up suggests context-dependent performance, including variable sensitivity, low or inconsistent positive predictive value, and age-dependent accuracy. Multicultural surveillance and implementation studies indicate that adding tools without aligning workflow, language support, follow-up systems, and service capacity may not improve pathway performance. The review argues that early autism identification should be evaluated through linked quality measures: response to concern, repeated surveillance following negative or ambiguous screening, referral completion, time to diagnostic assessment, support initiation before diagnostic closure, and equity of access. The clinical priority is not a perfect screening instrument in isolation, but faster, more coherent, and more equitable local pathways that translate concern into timely action.
