Search Results (8,389)

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes. Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance. Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values >5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine <5 mg/dL; n = 10) and high-risk groups (creatinine >5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury. Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted. Full article

Postoperative delirium (POD) is a frequent and serious complication among elderly surgical patients. Despite its clinical relevance, reliable biomarkers for early identification and pathophysiological insight remain limited. Recent evidence implicates systemic immune activation and complements dysregulation as contributors to cognitive decline after surgery. This study investigated the association between perioperative levels of selected complement pathway proteins and both the incidence and severity of POD. Methods: We performed a secondary analysis of 22 patients aged ≥ 60 years from the prospective CONFESS cohort undergoing elective spine surgery. Complement proteins (C1q, C2, C4), mannose-binding lectin (MBL), Factor D [FD], Factor B [FB], Factor I [FI] were quantified from blood samples collected at baseline, preoperatively, and on postoperative days 1 and 2. POD was assessed using the Nursing Delirium Screening Scale (Nu-DESC) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium severity was rated with the Confusion Assessment Method–Severity (CAM-S) scale. Associations were tested using univariate and multivariate regression analyses. Preoperative levels of FD and C2 were significantly elevated in patients who developed POD (FD: p = 0.023; C2: p = 0.044), while C4 levels trended lower. FD remained an independent predictor of POD in multivariate regression (p = 0.049), although cognitive performance was the only significant predictor when adjusted for surgery duration. Delirium severity was associated with perioperative reductions in C1q, FI, and FB and with increased MBL levels, explaining up to 43% of CAM-S score variance. These findings highlight the role of complement activation—particularly FD, C2, MBL—in the development and clinical expression of POD. Complement profiling may offer a novel approach for risk stratification and therapeutic targeting in perioperative neurocognitive disorders. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for approximately 10% of all cancer cases. Despite the proven effectiveness of conventional screening modalities such as colonoscopy and fecal immunochemical testing (FIT), their invasive nature, high cost, and limited patient compliance hinder widespread adoption. Recent advancements in artificial intelligence (AI) and bowel sound-based signal processing have enabled non-invasive approaches for gastrointestinal diagnostics. Among these, bowel sound analysis—historically considered subjective—has reemerged as a promising biomarker using digital auscultation and machine learning. Objective: This review explores the potential of AI-powered bowel sound analytics for early detection, screening, and characterization of colorectal cancer. It aims to assess current methodologies, summarize reported performance metrics, and highlight translational opportunities and challenges in clinical implementation. Methods: A narrative review was conducted across PubMed, Scopus, Embase, and Cochrane databases using the terms colorectal cancer, bowel sounds, phonoenterography, artificial intelligence, and non-invasive diagnosis. Eligible studies involving human bowel sound-based recordings, AI-based sound analysis, or machine learning applications in gastrointestinal pathology were reviewed for study design, signal acquisition methods, AI model architecture, and diagnostic accuracy. Results: Across studies using convolutional neural networks (CNNs), gradient boosting, and transformer-based models, reported diagnostic accuracies ranged from 88% to 96%. Area under the curve (AUC) values were ≥0.83, with F1 scores between 0.71 and 0.85 for bowel sound classification. In CRC-specific frameworks such as BowelRCNN, AI models successfully differentiate abnormal bowel sound intervals and spectral patterns associated with tumor-related motility disturbances and partial obstruction. Distinct bowel sound-based signatures—such as prolonged sound-to-sound intervals and high-pitched “tinkling” proximal to lesions—demonstrate the physiological basis for CRC detection through bowel sound-based biomarkers. Conclusions: AI-driven bowel sound analysis represents an emerging, exploratory research direction rather than a validated colorectal cancer screening modality. While early studies demonstrate physiological plausibility and technical feasibility, no large-scale, CRC-specific validation studies currently establish sensitivity, specificity, PPV, or NPV for cancer detection. Accordingly, bowel sound analytics should be viewed as hypothesis-generating and potentially complementary to established screening tools, rather than a near-term alternative to validated modalities such as FIT, multitarget stool DNA testing, or colonoscopy. Full article

MicroRNAs (miRNAs) are promising biomarkers for the early detection of various diseases, particularly cancer, driving active development of highly sensitive and selective detection technologies. This study aims to establish a novel miRNA detection technique that utilizes image analysis to track the Brownian motion (diffusivity) of fluorescent probe-modified miRNA particles. This method identifies the presence and concentration of miRNAs by exploiting the change in particle size upon hybridization with the target. Furthermore, the use of a probe modified with a photo-crosslinkable artificial nucleic acid (CNV-D) enables the covalent capture of the target miRNA, ensuring high selectivity in biological samples even under stringent washing conditions. By integrating Hybridization Chain Reaction (HCR), the complex size is significantly amplified, dramatically enhancing the detection sensitivity. Consequently, we successfully demonstrated the highly sensitive and specific detection of the cancer biomarker miR-21 in serum, achieving an exceptionally low limit of detection (LOD) of 1 fM. This technology holds great potential to contribute to the early diagnosis of cancer. Full article

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data. Full article

Background/Objectives: The increasing prevalence of overweight and obesity in adolescents represents a major global health concern. Adolescent weight gain frequently shows additional metabolic risk factors, including insulin resistance, hypertension, and dyslipidemia, whose co-occurrence defines the metabolic syndrome (MetS). Adherence to a healthy dietary pattern, such as the Mediterranean Diet (MD), has been shown to reduce the metabolic risk among adolescents. Skin carotenoid score has emerged as an objective and non-invasive indicator of MD adherence; however, its relationship with a cluster of metabolic parameters which characterize the MetS, including the triglyceride levels, diastolic blood pressure, and waist circumference, remains poorly explored. Here, we investigated the role of skin carotenoid score as an early biomarker of metabolic syndrome risk in adolescents. Methods: A sample of 634 healthy adolescents underwent anthropometric and clinical measurements, blood sample collection, and evaluation of the MD adherence by the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED) questionnaire and the skin carotenoid levels by the Veggie Meter^®. Student’s t-test, chi-square test, Pearson correlation, and the multivariable linear regression model were used for analyses. Results: Participants had a mean BMI Z-score of 0.02 ± 1.01; the metabolic serum profile and the cardiovascular parameters were within the normal range. Mean KIDMED and skin carotenoid scores were 5.21 ± 2.56 and 357 ± 96.58, respectively. Skin carotenoids were positively associated with height (p = 0.02), while they were inversely associated with weight (p = 0.008), BMI Z-score (p < 0.0001), diastolic blood pressure (p = 0.013), and triglycerides (p = 0.003). Moreover, the carotenoid score was positively associated with male gender and KIDMED score and negatively associated with waist circumference and triglyceride levels in multivariable regression analyses. Conclusions: Our results suggested the potential application of skin carotenoid score as a complementary biomarker for the early identification of adolescents at increased metabolic risk. Full article

Introduction: The global prevalence of chronic kidney disease (CKD) is increasing and it is associated with higher mortality rates. Transforming growth factor-beta (TGF-β) can serve as a novel biomarker for early prediction of chronic kidney disease (CKD) progression. Methods: This was a prospective longitudinal study among black patients with CKD who attended the Charlotte Maxeke Johannesburg Academic Hospital between September 2019 and March 2022. Patients provided urine and blood samples for laboratory investigations at study entry (0) and at 24 months follow up. Baseline serum and urine TGF-β1, TGF-β2 and TGF-β3 levels were measured using ELISAs. Multivariable logistic regression analysis was utilized to determine if TGF-β isoforms could predict CKD progression. Results: A total of 312 patients were enrolled at baseline, of whom 275 (88.1%) had early-stage CKD (Stage 1–3). A majority, 95.2% (297/312), of the patients completed the study after 2 years follow up. The prevalence of CKD progression was 47.8% when measured by a sustained decline in eGFR of >4 mL/min/1.73 m²/year or more and 51.9% when measured by a change in uPCR > 30%. The patients with CKD progression had significantly lower eGFR and increased urine protein–creatinine ratios compared to non-progressors. Furthermore, comparing progressors with non-progressors, the median serum TGF-β1 was 21210 (15915–25745) ng/L vs. 24200 (17570–29560) ng/L and the median urine TGF-β3 was 17.5 (5.4–76.2) ng/L vs. 2.8 (1.8–15.3) ng/L, respectively. Baseline serum and urine TGF-β isoforms were unable to discriminate between CKD progressors and non-progressors after multivariable logistic regression analysis. Conclusions: Despite the multiple roles of TGF-β isoforms in kidney disease, baseline levels were not predictive of chronic kidney disease progression. Full article

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, characterized by progressive neurodegeneration and cognitive decline. Early diagnosis remains critical for enabling timely intervention. However, detecting the earliest pathological changes is challenging due to the limited availability of reliable biomarkers that reflect early disease pathology in experimental models. This study evaluated molecular markers associated with AD-related processes in a rat model inoculated with human amyloid β (Aβ)_1-42 peptides. We assessed the levels of biomarkers: Aβ_1-42, Aβ₄₂, phosphorylated tau, monocyte chemoattractant protein-1 (MCP-1), nuclear factor kappa B (NF-κB p65) and superoxide dismutase 1 (SOD1) in hippocampal tissue and serum using enzyme-linked immunosorbent assay. A treatment group receiving Kelulut honey was included to evaluate biomarker responsiveness. Results showed significant elevation in hippocampal Aβ_1-42 and phosphorylated tau in diseased rats, with changes in inflammatory markers MCP-1 and NF-κB p65, whereas no significant change was observed in oxidative stress marker SOD1. Serum levels of Aβ_1-42 and MCP-1 did not differ significantly between groups, indicating limited peripheral sensitivity after a month of disease induction. These findings suggest that amyloid-, tau-, and inflammation-related markers in hippocampal tissue may be informative for early pathological changes in this acute model, while serum markers showed limited sensitivity. Full article

Background: Although Duchenne muscular dystrophy (DMD) is primarily characterized as a skeletal muscle-wasting disorder, the resulting pathophysiological changes extend to multiple non-muscle tissues and organ systems. Among these, renal and urinary tract dysfunctions have been reported, albeit in relatively few studies, as potential complications in DMD patients, sometimes occurring from an early age. Importantly, as life expectancy improves, the incidence of renal impairment is also expected to increase. This narrative review summarizes the available evidence on kidney involvement in DMD and discusses the associated biomarkers of renal dysfunction within the context of multisystem disease progression. Methods: The review draws on data from both human and animal studies and analyzes published evidence to explore kidney involvement in DMD, with a focus on clinical manifestations, biomarkers of renal dysfunction, and potential pathogenic mechanisms. Results: Available data indicate a close association between cardiac and renal dysfunction, particularly in patients with advanced-stage DMD. The review explores potential underlying mechanisms of renal impairment, including intrinsic dystrophin deficiency in the kidney, secondary effects of cardiovascular complications, and the nephrotoxic impact of drug therapies, highlighting renal function as an active determinant of clinical risk. Conclusions: While cardiac function monitoring is already a cornerstone of multidisciplinary care for this multisystem disease, systematic assessment of renal function should also be implemented, with implications for clinical management and drug safety. Moreover, the risk of drug-induced nephrotoxicity warrants attention in both clinical management and the development of novel therapeutic strategies for DMD. Full article

Ovarian cancer is frequently diagnosed at an advanced stage due to non-specific symptoms, contributing to high mortality. The limited diagnostic performance of current serum assays in early disease underscores the need for complementary circulating biomarkers. Circulating microRNAs and inflammation-related markers are promising candidates. Although miRNAs are implicated in cancer diagnostics, the role of miRNA-29a in ovarian cancer remains underexplored. Given that sST2 is elevated in several malignancies and is a direct target of miRNA-29a, concurrent evaluation may be informative. This pilot study compared serum miRNA-29a and sST2 levels in 23 ovarian cancer patients and 22 healthy female controls. miRNA-29a expression was quantified by real-time PCR (2^−ΔΔCt), and sST2 was measured by ELISA; diagnostic performance was assessed using ROC analysis. miRNA-29a levels were significantly reduced (p < 0.05), whereas sST2 concentrations were significantly increased (p < 0.001) in patients versus controls. ROC analysis showed modest discrimination for miRNA-29a (AUC 0.678) and higher performance for sST2 (AUC 0.825). No significant correlation was observed between the two markers. These findings suggest that circulating miRNA-29a and sST2 may have biomarker potential in ovarian cancer; larger, well-designed studies are required to confirm clinical utility. Full article

Background: Approximately 20–30% of ultra-high risk (UHR) individuals transition to psychosis within 2–3 years. Neurobiological markers predicting conversion remain critical for precision prevention strategies. Objective: To systematically identify and evaluate structural and functional neuroimaging biomarkers at UHR baseline that predict subsequent conversion to psychosis. Methods: Following PRISMA 2020 guidelines, we searched five databases from January 2000 to February 2025. Two independent reviewers screened studies and assessed quality using the Newcastle–Ottawa Scale. Eligible studies examined baseline neuroimaging measures (structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy) as predictors of psychosis conversion in UHR cohorts. Results: Twenty-five studies comprising 2436 UHR individuals (627 converters, 25.7%) were included (80.0% high quality). Reduced baseline gray matter volume in medial temporal structures (hippocampus: Cohen’s d = −0.45 to −0.68; parahippocampal gyrus: d = −0.52 to −0.71) and prefrontal cortex (d = −0.41 to −0.68) consistently predicted conversion. Progressive gray matter loss in superior temporal gyrus distinguished converters (d = −0.72). Reduced prefrontal–temporal functional connectivity predicted conversion (AUC = 0.73–0.82). Compromised white matter integrity in uncinate fasciculus (fractional anisotropy: d = −0.47 to −0.71) and superior longitudinal fasciculus predicted transition. Elevated striatal glutamate predicted conversion (d = 0.52–0.76). Thalamocortical dysconnectivity showed large effects (Hedges’ g = 0.66–0.88). Multimodal imaging models achieved 78–85% classification accuracy. Conclusions: Neuroimaging biomarkers, particularly medial temporal and prefrontal structural alterations, functional dysconnectivity, and white matter abnormalities, demonstrate moderate-to-large effect sizes in predicting UHR conversion. Multimodal approaches combining structural, functional, and neurochemical measures show promise for individualized risk prediction and early intervention targeting in precision prevention strategies. Full article

Background/Objective: Early detection of metastatic progression remains a major challenge in precision oncology. Conventional radiological imaging cannot reliably identify micrometastatic disease. Although circulating tumor DNA is promising for minimal residual disease detection, organ-derived response biomarkers reflecting tissue adaptation to secreted factors remain unexplored. We hypothesized that integrating such biomarkers with global laboratory parameters would generate a synthetic variable with improved discrimination for de novo metastasis and mortality. Methods: This prospective observational pilot study enrolled 30 patients (median age 64.4 years; 56.7% female) with heterogeneous solid malignancies. Peripheral blood biomarkers responsive to tumor-secreted soluble factors (n = 11) were quantified using a multiplexed beads Luminex immunoassay. Global analytical parameters (n = 20) were derived from routine laboratory assessments. Hierarchical agglomerative clustering analysis generated two synthetic variables: Stigma (Ϛ) and Qoppa (Ϙ). Receiver operating characteristic curve analysis, Kaplan–Meier survival analysis, and Cox regression were used to evaluate the performance. Results: Qoppa demonstrated acceptable discriminatory performance for de novo metastasis (AUC = 0.78). For mortality prediction, performance varied by disease status (overall AUC = 0.78): superior in non-metastatic patients (AUC = 0.98) but negligible in those with baseline metastases. Kaplan–Meier analysis confirmed significant survival differences (p = 0.042 overall survival; p = 0.024 for metastasis-free survival in the non-metastatic subgroup). Differences in biomarker expression and clinical variables (stage, tumor burden, and metastatic burden) were observed between the high and low Qoppa strata. Conclusions: In this small heterogeneous pilot cohort, Qoppa provides a proof of concept that integrating organ-derived response biomarkers with routine laboratory parameters may capture clinically relevant signals for metastatic risk stratification in oncology patients. This composite parameter supports the generation of hypotheses for future biomarker-driven research and clinical test development. External validation in larger multicenter cohorts is required before clinical implementation. Full article

Background/Objectives: Septic arthritis of native joints is an orthopedic emergency in which rapid discrimination from non-infectious arthritis is crucial. Because cartilage damage can occur within hours, urgent irrigation and debridement are often pursued on an emergency basis (ideally within the first 6–8 h) of presentation, underscoring the need for rapidly available biomarkers. The delta neutrophil index (DNI) quantifies circulating immature granulocytes and may complement conventional inflammatory biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and procalcitonin (PCT). We evaluated the diagnostic performance of DNI for native-joint septic arthritis against both microbiologic and clinical reference standards. Methods: We retrospectively analyzed 85 adults who underwent surgical irrigation and debridement for suspected native joint septic arthritis at a tertiary center. Serum CRP, ESR, WBC, DNI, and PCT (available in 67 patients) were recorded together with synovial leukocyte counts. Infection status was defined using either positive synovial culture (microbiologic reference) or clinical adjudication according to the Guideline for management of septic arthritis in native joints (SANJO). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC); exploratory cut-offs were identified by the Youden index, and pairwise AUCs were compared using DeLong’s test. Results: Synovial leukocyte analysis was highly sensitive but poorly specific (sensitivity 92.9%, specificity 10.3%). Against culture, DNI showed the highest discrimination (AUC = 0.914), exceeding CRP (0.687), ESR (0.643), WBC (0.648), and PCT (0.697); DeLong ΔAUC vs. CRP 0.227 (p < 0.001), ESR 0.270 (p < 0.001), WBC 0.266 (p < 0.001), PCT 0.227 (p = 0.001). At pre-specified cut-offs, DNI showed the most balanced sensitivity/specificity (94.3%/84.0%), corresponding to a negative predictive value (NPV) of 95.5% (42/44) and a positive predictive value (PPV) of 80.5% (33/41) against culture in this cohort. Against clinical infection, DNI outperformed others (AUC:0.921; ΔAUC vs. CRP = 0.204, ESR = 0.343, WBC = 0.244, PCT = 0.295; all p < 0.001). As a rule-in threshold, DNI ≥ 0.6 yielded a specificity of 100% with a sensitivity of 73.2%. In culture-negative patients (infected n = 21, uninfected n = 29), DNI remained discriminatory (AUC 0.80, p < 0.001), whereas other biomarkers were not. Conclusions: DNI demonstrated superior diagnostic accuracy compared with conventional inflammatory biomarkers. As a rapid parameter available with the initial complete blood count, DNI may support early risk stratification and rule-in decisions within the first hours of presentation; however, it should be used as a supplementary indicator alongside synovial fluid analysis and clinical assessment rather than as a stand-alone diagnostic tool. Full article

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes. Full article

Background: During the first 2 years of life, human white matter (WM) undergoes rapid development, establishing a structural foundation for later neurodevelopment. Methods: We conducted a mixed-model analysis for repeated measures to investigate the developmental trajectories of functionally distinct 26 WM pathways between preterm and full-term groups during the first 2 years of life using diffusion tensor imaging (total scans = 174; preterm = 58; full-term = 23). Results: We observed significant differences between the preterm and full-term groups in the developmental trajectories associated with motor function (left corticospinal tract and left pre-primary motor cortex connection tracts), visual processing (bilateral pathway between the V1/V2 and V4, PV-MT, pathway connecting the V1/V2 and V5/MT, and optic radiation), and cognition (genu, body, and splenium of the corpus callosum). Furthermore, inter-regional correlation matrix analysis revealed stronger connectivity, specifically within motor- and visual-related pathways, in the preterm group than that for the full-term group, suggesting an adaptive mechanism that supports circuit-level resilience following preterm birth. Moreover, in the model investigating the associations between the WM individual rate of change and long-term neurodevelopmental outcomes, the middle cerebellar peduncle (MCP) tract showed the strongest associations with motor scores, suggesting that faster maturation of the MCP tract may enhance motor functions as a key compensatory mechanism following preterm birth. Conclusions: Delineating the longitudinal change rates of specific WM pathways not only deepens our understanding of the neurodevelopmental sequelae of prematurity but also highlights their potential as early biomarkers to guide timely interventions. Full article