Search Results (211)

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article

Background: Blood-accessible biomarkers may support future personalization of prostate cancer radiotherapy, but their interpretation depends on sampling timing relative to radiotherapy, androgen deprivation therapy, and post-treatment recovery. We mapped clinical evidence for selected biomarker domains beyond prostate-specific antigen: γ-H2AX/DNA damage response, IL-6/inflammatory mediators, testosterone/endocrine recovery and a prespecified galectin-1/3 immune–stromal domain evaluated as a potential evidence gap. Methods: We conducted a PRISMA-ScR scoping review of PubMed, Scopus, and Web of Science searched on 7 January 2026. Eligible original human studies evaluated soluble serum/plasma analytes or peripheral blood cell-based assays in prostate RT pathways. Data were charted by biomarker domain, treatment context, RT modality/fractionation, assay reporting, sampling schedule, and endpoint linkage. Results: Of 3499 records, 45 studies were included. No eligible study reported repeated circulating galectin-1/3 kinetics anchored to prostate radiotherapy, identifying a distinct clinical evidence gap. The remaining evidence was dominated by testosterone studies (n = 28), followed by IL-6/inflammatory mediators (n = 12) and γ-H2AX/DDR (n = 5). Testosterone studies were mapped as separate RT-only endocrine kinetics and ADT-anchored recovery streams. IL-6 studies mainly used during-RT or early post-RT sampling and linked trajectories to acute toxicity, fatigue, symptoms or inflammatory phenotypes; no included study directly validated serial IL-6/inflammatory trajectories against biochemical control, metastasis-free survival, or overall survival. γ-H2AX studies were characterized by ultra-acute, fraction-anchored sampling. Across domains, baseline definition and sampling timing limited interpretability more than assay platform alone. Conclusions: Evidence maturity was unequal across the selected domains. Testosterone provided the comparatively more developed longitudinal clinical literature, whereas IL-6/inflammatory mediators remained exploratory and were linked mainly to acute toxicity, fatigue, symptoms, and inflammatory phenotypes. γ-H2AX remained predominantly a translational and biodosimetry-oriented marker, while galectin-1/3 represented a hypothesis-generating clinical evidence gap. None of these biomarkers currently supports routine biomarker-guided prostate RT personalization. Future biomarker-embedded studies may benefit from domain-specific sampling considerations, explicit RT/systemic-therapy context stratification, standardized assay reporting, and clinically relevant endpoints. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by sustained synovial inflammation and systemic immune activation. Genetic polymorphisms in key immune-regulatory pathways are thought to influence both disease susceptibility and progression. This study aimed to characterize sequence variation within selected coding regions of TNFAIP3 and CTLA4 in Kurdish patients with RA and to evaluate circulating TNF-α and soluble CTLA-4 (sCTLA-4) levels in the same cohort. Methods: Eighty-seven participants (67 RA patients, 20 controls) were enrolled. Serum TNF-α and sCTLA-4 concentrations were quantified by ELISA. Genomic DNA was extracted and targeted Sanger sequencing of selected coding regions of TNFAIP3 and CTLA4 was performed in RA patients. Variant identification was conducted relative to GRCh38 and annotated using dbSNP and Genome Aggregation Database (gnomAD). GeneMANIA was used for network-based contextualization. Results: In the 218-bp targeted region of TNFAIP3, 103 sequence-level variant occurrences were identified in RA patients, including substitutions and insertion/deletion events. In the 136-bp targeted region of CTLA4, 33 sequence-level variant occurrences were identified, also including substitutions and insertion/deletion events. RA patients exhibited significantly elevated serum TNF-α levels compared with controls (p = 0.025), whereas sCTLA-4 levels did not differ significantly. Conclusions: This study provides the first targeted characterization of TNFAIP3 and CTLA4 genetic variation in Kurdish RA patients and integrates these findings with circulating inflammatory biomarkers. Although not designed to assess disease susceptibility, the study provides a valuable descriptive genetic resource for this population and complements existing evidence implicating NF-κB regulation and immune checkpoint signaling in RA. These findings establish a strong foundation for future case–control, genotype–phenotype, and functional investigations. Full article

Background: Polymorphonuclear (PMN) leukocyte recruitment to activated pulmonary endothelium is a central mechanism in acute respiratory distress syndrome (ARDS). This process is mediated by selectins and their counter-ligand, P-selectin glycoprotein ligand-1 (PSGL-1), encoded by SELPLG. Genetic variation in SELPLG has been associated with ARDS susceptibility, while disruption of PSGL-1/P-selectin interactions attenuates lung injury in preclinical models. Because inflammatory stimuli increase both SELPLG expression and circulating PSGL-1 levels, PSGL-1 represents a promising biomarker and therapeutic target. We sought to define the genetic determinants of plasma PSGL-1 levels and evaluate their causal relationships with key inflammatory and endothelial biomarkers. Methods: Genome-wide association study (GWAS) summary statistics for plasma PSGL-1 levels were obtained from the UK Biobank Pharma Proteomics Project (n = 35,571) and the SCALLOP consortium (n = 21,758 across 13 cohorts). Associated variants underwent functional annotation and in silico analyses to identify potential effects on protein structure and gene regulation. Bidirectional Mendelian randomization (MR) was performed using GWAS summary statistics for C-reactive protein (CRP), E-selectin, GlycA, and soluble intercellular adhesion molecule-1 (sICAM-1) to assess potential causal relationships with PSGL-1 levels. Results: Multiple cis- and trans-acting loci were significantly associated with plasma PSGL-1 concentrations. Three coding SELPLG variants (rs201689859, rs74792300, and rs139943851) were predicted to alter PSGL-1 protein structure and were associated with lower circulating PSGL-1 levels. Four promoter variants (rs1420663, rs1833245, rs1420664, and rs8179110) were linked to altered transcriptional activity, including a potential effect of rs1420664 on hypoxia-inducible factor binding. Bidirectional MR demonstrated that genetically predicted CRP, E-selectin, GlycA, and sICAM-1 levels were associated with increased plasma PSGL-1 concentrations. Additional loci implicated pathways related to immune signaling, cell adhesion, and protein stability. Conclusions: Large-scale GWAS and Mendelian randomization analyses identified genetic variants that regulate plasma PSGL-1 levels and demonstrated causal links between inflammatory and endothelial biomarkers and PSGL-1 expression. These findings provide new insights into the genetic regulation of leukocyte trafficking pathways and support a role for PSGL-1 in inflammatory diseases, including ARDS, sepsis, and cardiovascular disorders. Full article

Soluble immune checkpoints (sICs) have emerged as potential biomarkers in various cancers. However, their role in extensive-stage small cell lung cancer (ES-SCLC), an aggressive tumor type with limited therapeutic options and poor prognosis, remains poorly characterized. We analyzed 14 circulating sICs, leukocyte–platelet (PLT) complexes, and PD-L1 surface expression in ES-SCLC patients treated with chemoimmunotherapy (n = 41) prior to treatment and healthy donors (HD, n = 10). We assessed their associations with clinical and demographic factors and performed survival analyses using Kaplan–Meier and log-rank tests. Levels of soluble (s) PD-L1, PD-L2, BTLA, HVEM, TIM-3, and CD27 were higher in plasma from ES-SCLC patients compared to those from HD (p < 0.05). Patients with liver metastases exhibited higher sIC levels, and a multivariate model demonstrated discriminative power. Network analyses revealed distinct patterns of immune dysregulation between ES-SCLC and HD. We observed correlations among sICs and leukocyte–PLT complexes and leukocyte PD-L1 expression, indicating links between systemic immune status and tumor–immune interactions. Furthermore, increased concentrations of sTIM-3, sCD27, sHVEM and sPD-L1 were associated with a poor prognosis. Overall, sICs reflect relevant clinical, prognostic, and immunological features in ES-SCLC. Their plasma measurement could aid in non-invasive patient stratification regarding liver metastases and survival risk. Full article

Natural killer (NK) cells are key mediators of antitumor immunity; however, NK cell dysfunction in epithelial ovarian cancer should be considered not as a uniform defect, but rather as compartment-specific states that differ across the blood, ascites, primary tumor, and metastatic sites according to their local cellular interactions, soluble factors, and metabolic constraints. Peripheral blood provides an accessible systemic reference and may support immune monitoring. However, it does not fully reflect NK cell states in local or distant disease compartments. In ascites, cytokine-responsive and partially recoverable NK cell populations coexist with soluble, biochemical, and metabolic suppressive signals. In primary tumors, NK cells often acquire tissue-adapted suppressive phenotypes, characterized by altered activating receptors, increased inhibitory checkpoints, and reduced cytotoxic effector function. In metastatic lesions, NK cells appear to share suppressive phenotypes with primary tumors, although these phenotypes may be reinforced within metastatic niches through coordinated inhibitory receptor–ligand interactions. The above compartment-specific states imply that NK cell-targeted therapy for ovarian cancer should not rely on a unilateral strategy. Instead, therapeutic design may need to be multifaceted but coordinated, combining cytokine-based activation, adoptive NK cell transfer, checkpoint blockade, local delivery, and antigen-directed chimeric antigen receptor NK cell approaches according to the dominant biology of each compartment. Paired multi-compartment profiling and longitudinal functional assessment will be essential for biomarker development and compartment-guided treatment design. Full article

Blood-based biomarkers have emerged as promising, minimally invasive tools for the diagnosis, prognostic stratification, and treatment monitoring of non-small cell lung cancer (NSCLC), including markers of tumor burden, tumor dissemination, immune signaling, and post-transcriptional regulation. However, evidence across biomarker classes remains fragmented. This study aimed to synthesize published evidence on major blood-based biomarkers relevant to diagnosis, prognosis, treatment stratification, and monitoring in NSCLC. PubMed was searched for systematic reviews and meta-analyses of blood-based biomarkers in NSCLC. Of 356 screened records, 82 underwent full-text review, and 57 systematic reviews/meta-analyses were included. Biomarkers were grouped into four categories: circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines/soluble immune proteins, and non-coding RNAs (ncRNAs). Reported pooled effect estimates were extracted by biomarker class and evidence domain, and the methodological quality of included reviews was assessed using AMSTAR 2. Evidence was unevenly distributed across biomarker classes and evidence domains. Circulating ncRNAs were mainly represented in diagnostic and prognostic evidence; selected diagnostic ncRNAs, including miR-145, miR-25, and circRNAs, showed reported AUCs ranging from 0.83 to 0.85. ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence, with ctDNA positivity associated with poorer survival or recurrence outcomes and ctDNA clearance or decline associated with improved outcomes. CTC evidence was primarily prognostic, with CTC positivity associated with worse overall survival and disease-free survival. Soluble immune biomarker evidence was also primarily prognostic, with elevated soluble PD-L1 and IL-6 associated with adverse survival outcomes and limited exploratory monitoring evidence for exosomal PD-L1. Overall, the evidence suggested distinct but complementary roles across biomarker classes, although direct head-to-head comparisons were lacking. Blood-based biomarkers show potential to support diagnosis, prognosis, and longitudinal monitoring in NSCLC, but their reported utility differs by biomarker class and clinical context. In the available review-level evidence, ncRNAs were mainly represented in diagnostic and prognostic evidence, while ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence. CTCs were mainly represented in prognostic evidence, and soluble immune biomarkers were primarily represented in prognostic evidence, with limited exploratory evidence for dynamic monitoring. Further assay standardization, prospective validation, and direct comparative studies are needed before these biomarkers can be routinely integrated into clinical practice. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Clinically established biomarkers such as KL-6 and surfactant protein-D (SP-D) for SSc-associated interstitial lung disease (ILD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for pulmonary arterial hypertension (PAH), are already used as adjunctive tools in routine clinical assessment, whereas many other candidate biomarkers, including interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers remain at varying stages of clinical validation. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and future precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone. However, most candidate biomarkers still require external validation, assay standardization, and demonstration of incremental value over conventional clinical variables before routine clinical implementation. Full article

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article

Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included 44 treatment-naïve patients with nAMD. Patients received up to four monthly intravitreal Ranibizumab injections, followed by a treat-and-extend regimen. Best-corrected visual acuity using ETDRS letters, central retinal thickness by optical coherence tomography, fluorescein angiography, and OCT angiography were assessed at baseline and 12 months. Peripheral blood samples were collected at both time points to quantify seven circulating cytokines using an IMMULITE chemiluminescent immunoassay and to profile 37 candidate miRNAs by TaqMan OpenArray RT-qPCR from leukocyte-derived RNA. Treatment response was classified using composite anatomical and functional criteria, including intraretinal/subretinal fluid resolution, ≥25% central retinal thickness reduction, and a ≥5 ETDRS letter gain. Results: At one year, patients showed significant central retinal thickness reduction and overall visual stabilization, although good and poor responders differed according to composite response criteria. Statin use was numerically more frequent among poor responders, although this difference was not statistically significant. Soluble IL-2R increased significantly over time in the overall cohort, mainly driven by good responders who showed higher median levels at both visits. IL-8 also increased globally, without significant between-group differences. Among differentially expressed miRNAs, miR-3121 was the only candidate reaching statistical significance and was downregulated in good responders. ROC analysis showed moderate discriminative performance for miR-3121, with an AUC of 0.76. Conclusions: One-year response to Ranibizumab in nAMD may involve systemic immune activation and miRNA regulation. miR-3121 emerges as a candidate biomarker of treatment response, supporting further validation in larger independent cohorts. Full article

Orthohantavirus infections are classically associated with hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. However, accumulating evidence indicates that the clinical spectrum is considerably broader, with frequent involvement of organ systems beyond the kidney and lung. Hepatic manifestations, in particular, may mimic acute viral hepatitis, leading to diagnostic challenges and underrecognition. This paper synthesizes published evidence on hepatic involvement in orthohantavirus infection, with a focus on clinical presentation, pathogenic mechanisms, differential diagnosis, biomarkers, and public health implications. Relevant literature was identified through searches of peer-reviewed articles, with emphasis on studies reporting hypertransaminasemia, hepatitis-like illness, and liver injury in confirmed hantavirus infections. Mild to moderate elevations in aminotransferases are common during acute orthohantavirus infection, and in some patients the clinical picture may be dominated by fever, thrombocytopenia, and hepatitis-like abnormalities, closely resembling dengue, leptospirosis, or classical viral hepatitis. Hepatic injury appears to result primarily from systemic endothelial dysfunction, immune-mediated inflammation, and microvascular leakage rather than direct hepatocytopathic effects. Emerging biomarkers of severity, including thrombocytopenia, neutrophil-to-lymphocyte ratio, soluble thrombomodulin, and IL-6 trans-signaling, reflect widespread vascular and inflammatory activation. Diagnostic delays are frequent, particularly in non-endemic regions, due to low clinical awareness and overlapping features with more common febrile hepatotropic syndromes. Orthohantavirus infection should be considered in the differential diagnosis of acute febrile illness with unexplained hypertransaminasemia and thrombocytopenia, especially when epidemiological clues suggest rodent exposure or compatible environmental contexts. Recognizing hepatic involvement as part of a systemic endothelial syndrome may improve diagnostic accuracy, reduce underreporting, and facilitate earlier supportive management. Increased awareness among hepatologists, infectious disease specialists, and emergency physicians is warranted. Full article

Macrophages are highly plastic innate immune cells that adopt context-dependent phenotypes along a continuum, integrating developmental origin with local microenvironmental cues rather than conforming to discrete M1/M2 states. This review delineates the molecular circuits shaping macrophage identity—TLR/cytokine signaling, microRNA networks, metabolic rewiring, and epigenetic mechanisms including histone lactylation—and traces how circulating monocyte subsets contribute to tissue macrophage diversity. We examine macrophage plasticity across a broad disease spectrum—oncology, autoimmune and rheumatic diseases, inflammatory bowel disease, infectious diseases, metabolic disorders, and neurological conditions—showing that the pathogenic phenotype is strikingly context-dependent: for instance, M2-like tumor-associated macrophages promote immune evasion in solid tumors, whereas M1-skewed programs drive tissue damage in autoimmunity. Soluble markers (sCD163, sCD14, soluble mannose receptor) are emerging biomarkers of disease activity and prognosis. High-dimensional flow cytometry and mass cytometry (CyTOF) bridge molecular biology and clinical phenotyping, enabling integrated readouts of surface phenotype, intracellular signaling, and metabolic state. Therapeutic strategies discussed include selective tumor-associated macrophage (TAM) reprogramming, chimeric antigen receptor (CAR)-M cell therapies, and biomaterial-based platforms. Future priorities encompass spatially resolved multi-omics, epigenetic and metabolic targeting, and macrophage-centered vaccine approaches. Standardized cytometry panels will be essential for biomarker-guided stratification and context-specific interventions. Full article

Melanoma treatment has been transformed by immune checkpoint blockade, yet many patients still experience primary resistance, limited durability of response, or acquired resistance. These limitations underscore the need for additional targets that reflect melanoma biology while enabling new therapeutic strategies, particularly in biologically defined settings of immune escape such as checkpoint-resistant, HLA-low, dedifferentiated, or stress-adapted melanoma. The B7-H6/NKp30 axis has gained attention as a link between tumor cell stress, immune recognition, and therapy-related adaptation. B7-H6 (NCR3LG1), an inducible ligand for NKp30, has been detected in melanoma cell lines and tumor specimens, and soluble B7-H6 has been identified in a subset of patients. Membrane-bound B7-H6 may support NK-cell activation, whereas ligand shedding and accumulation of soluble B7-H6 may reduce effective antitumor recognition and promote immune evasion. Emerging evidence further suggests that B7-H6 expression may be linked to tumor-intrinsic programs relevant to melanoma cell survival, migration, and adaptation to therapeutic stress. However, B7-H6 is not yet a validated predictive biomarker or an established therapeutic target in melanoma, and current evidence remains limited by small melanoma-specific datasets, incomplete information on spatial and temporal heterogeneity, and the absence of melanoma-focused clinical validation. In this review, we examine the role of the B7-H6/NKp30 axis in immune surveillance, tumor escape, biomarker development, and therapeutic targeting, and discuss its translational potential in melanoma as an emerging but incompletely validated pathway that warrants focused investigation in melanoma states where conventional immune control is limited. Full article

Background/Objectives: Pediatric sepsis is increasingly recognized as a syndrome involving immune–vascular dysregulation. However, most pediatric biomarker studies focus on individual molecules rather than coordinated patterns of leukocyte–endothelial activation. This study aimed to evaluate whether children diagnosed with sepsis within 48 h of admission showed a coordinated soluble adhesion-molecule activation profile measured at enrollment. Methods: This prospective cohort study included 144 children aged 1–60 months with suspected infection enrolled at Dong Nai Children’s Hospital, Vietnam, from May 2021 to October 2022. Blood samples were collected at enrollment. Sepsis was classified according to the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria within 48 h of admission. Twelve soluble adhesion molecules were measured using a multiplex immunoassay. A composite adhesion activation score was derived by log2 transformation, z-score standardization, and averaging across the 12 markers. Principal component analysis (PCA) was used as an exploratory method to summarize the shared variation across the adhesion-molecule panel. C-reactive protein (CRP) was included as a routinely available inflammatory comparator. Results: Among 144 children, 32 (22.2%) were diagnosed with sepsis within 48 h of admission. Individual marker discrimination was strongest for L-selectin (area under the receiver operating characteristic curve [AUC] 0.883), followed by soluble vascular cell adhesion molecule-1 (sVCAM-1; AUC 0.855), intercellular adhesion molecule-3 (ICAM-3; AUC 0.838), P-selectin glycoprotein ligand-1 (PSGL-1; AUC 0.836), E-selectin (AUC 0.819), and intercellular adhesion molecule-2 (ICAM-2; AUC 0.819). CRP also differed between children with and without sepsis but had a lower AUC than the leading adhesion molecules in descriptive ROC analyses. The composite adhesion activation score was strongly associated with sepsis (odds ratio 7.95 per 1-standard deviation increase; 95% confidence interval 3.44–18.40; p < 0.001) and showed good discrimination (AUC 0.855; 95% confidence interval 0.776–0.931). The first principal component explained 70.0% of biomarker variance, consistent with coordinated elevation of correlated adhesion molecules. Conclusions: In this prospective Vietnamese pediatric cohort, children diagnosed with sepsis within 48 h of admission showed coordinated elevation of soluble adhesion molecules measured at enrollment. These findings support the biological relevance of leukocyte–endothelial activation in pediatric sepsis. However, the adhesion-molecule activation profile should be considered exploratory and hypothesis-generating, requiring external validation and further evaluation against simplified, clinically feasible biomarker approaches. Full article

Background: While Immune Checkpoint Inhibitors (ICIs) have significantly improved outcomes in lung cancer (LC), clinical responses remain heterogeneous. Static tissue biomarkers, like PD-L1, and tumor mutational burden (TMB) are limited by intratumoral heterogeneity and the inability to track temporal changes. This review aims to evaluate the current state and future potential of liquid biopsy as a dynamic tool for patient selection, treatment monitoring, and the identification of resistance mechanisms in LC immunotherapy. Methods: A literature search was conducted in the PubMed database up to March 2026. We identified 65 eligible publications, including clinical trials, observational studies, and systematic reviews, focusing on liquid biopsy analytes such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and soluble immune mediators. Results: Liquid biopsy provides a “pooled” representation of the total tumor burden, overcoming the spatial limitations of tissue biopsy. Key findings include that dynamic changes in ctDNA and bTMB can predict molecular progression weeks before radiological assessment; blood-based PD-L1 monitoring (soluble, exosomal, or on CTCs) correlates with survival outcomes and offers a real-time readout of immune checkpoint activity; novel markers like tumor-macrophage fusion (TMF) cells and cytokine signatures provide unique insights into the systemic immune microenvironment. Conclusions: Liquid biopsy is evolving from a complementary diagnostic tool into a central pillar of precision immuno-oncology. Although technical standardization remains a challenge, the integration of multi-omic blood-based biomarkers represents the future of personalized lung cancer management. Full article