Search Results (1,416)

Background: The aim of this study was to evaluate the diagnostic and prognostic performance of albumin-based inflammatory–nutritional indices in hyperemesis gravidarum (HG) and to determine their associations with disease severity and risk of re-hospitalization. Methods: This retrospective case–control study included 246 women with HG and 246 gestational-age-matched healthy pregnant controls at 6–16 weeks of gestation. Disease severity was classified as mild, moderate, or severe using the Pregnancy-Unique Quantification of Emesis (24 h scale) (PUQE-24) score. A comprehensive panel of albumin-based inflammatory indices—including C-reactive protein-to-albumin ratio (CAR), fibrinogen-to-albumin ratio (FAR), neutrophil-to-albumin ratio (NAR), leukocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), monocyte-to-albumin ratio (MAR), hemoglobin–albumin–lymphocyte–platelet (HALP) score, modified HALP (m-HALP) score, prognostic nutritional index (PNI) score, systemic immune-inflammation index-to-albumin (SII/Alb), and systemic inflammatory response index-to-albumin (SIRI/Alb)—was calculated from routine complete blood count and serum biochemistry results obtained at diagnosis. Receiver operating characteristic analysis, along with univariate and multivariate logistic regression models, was performed to evaluate diagnostic performance and identify predictors of severe HG and re-hospitalization. Results: Albumin-based indices exhibited severity-associated alterations, with an overall trend toward worsening immuno-nutritional status across increasing HG severity. Among these, m-HALP score demonstrated the strongest inverse correlations with PUQE-24 score, ketonuria grade, length of hospital stay, and re-hospitalization risk (r = −0.74 to −0.52; all p < 0.001) and achieved the highest discriminative accuracy for both severe HG (AUC 0.864, 95% CI 0.836–0.892, p < 0.001) and re-hospitalization (AUC 0.722, 95% CI 0.675–0.766, p < 0.001). In multivariable analysis, higher HALP, m-HALP, and PNI were independently associated with a lower likelihood of severe HG. For re-hospitalization, higher m-HALP and HALP were independently associated with a lower risk, whereas higher NPAR, higher ketonuria grade, and higher PUQE-24 score were independently associated with an increased risk of re-hospitalization. Conclusions: Albumin-based indices, particularly m-HALP, demonstrated robust diagnostic and prognostic performance in HG compared with conventional biomarkers. These readily available, cost-neutral composite biomarkers enable objective severity stratification and accurate identification of patients at elevated risk of recurrent hospitalization, offering immediate potential to guide personalized, evidence-based clinical management. Full article

Obesity arises from chronic energy imbalance, where energy intake exceeds energy expenditure. Emerging evidence supports a key role of DNA methylation in the regulation of adipose tissue development and metabolism. We have recently discovered a key role of DNA methylation, catalyzed by DNA methyltransferase 1 or 3a (Dnmt1 or 3a), in the regulation of adipocyte differentiation and metabolism. Here, we aimed to investigate the role of adipose progenitor cell Dnmt3b—an enzyme mediating de novo DNA methylation—in energy metabolism and obesity. We generated a genetic model with Dnmt3b knockout in adipocyte progenitor cells (PD3bKO) by crossing Dnmt3b floxed mice with Platelet-derived growth factor receptor alpha (PDGFRα) Cre mice. Dnmt3b deletion in adipocyte progenitors enhanced thermogenic gene expression in brown adipose tissue, increased overall energy expenditure, and mitigated high-fat diet (HFD)-induced obesity in female mice. PD3bKO mice also displayed a lower respiratory exchange ratio (RER), indicative of a metabolic shift favoring fat utilization as an energy source. Furthermore, female PD3bKO mice exhibited improved insulin sensitivity alongside their lean phenotype. In contrast, male PD3bKO mice showed no changes in body weight but demonstrated decreased insulin sensitivity, revealing a sexually dimorphic metabolic response to Dnmt3b deletion in adipose progenitor cells. These findings underscore the critical role of Dnmt3b in regulating energy homeostasis, body weight, and metabolic health, with significant implications for understanding sex-specific mechanisms of obesity and metabolism. Full article

Platelet-rich fibrin (PRF) is widely used in regenerative dentistry and oral surgery for its ability to promote tissue healing and modulate cellular responses. However, PRF contains not only platelets but also leukocytes and plasma components, complicating efforts to define the specific contribution of platelets to its biological activity. To address this, we used washed, leukocyte-depleted platelets activated with thrombin to generate platelet-released supernatant (PRS), which was applied to gingival fibroblasts. RNA sequencing identified 147 upregulated and 39 downregulated genes (|log₂ fold change| ≥ 2, FDR < 0.001), including cytokines IL11 and CXCL8 previously associated with PRF, as well as mitosis-related genes such as centromere-associated proteins, cell division cycle proteins, kinesin-like proteins, and shugoshins, consistent with gene ontology analyses. Validation by RT-PCR and immunoassays confirmed robust upregulation of IL11 and CXCL8. Functionally, PRS activated TGF-β signaling, indicated by Smad2/3 nuclear translocation, but did not induce NF-κB signaling. These findings demonstrate that platelets are major contributors to PRF’s biological effects, independent of leukocytes and plasma, and elicit a pronounced mitogenic and TGF-β-dominant response in gingival fibroblasts. They also provide insight into the cellular mechanisms underlying PRF-mediated tissue regeneration. Full article

Background/Objectives: Eltrombopag, a thrombopoietin receptor agonist, is widely used in the treatment of relapsed or refractory (R/R) immune thrombocytopenia (ITP). This study aimed to compare the efficacy, safety, and tolerability of generic eltrombopag (Rompag^®) with original eltrombopag (Revolade^®) in adult patients with R/R ITP. Methods: In this prospective, multicenter study conducted at 10 centers, 104 adult ITP patients were followed for at least 3 months. A total of 35 (33.7%) patients received Rompag^® and 69 (66.3%) received Revolade^®. The primary endpoint was platelet (PLT) response, defined as achieving a PLT count ≥50 × 10⁹/L and at least a twofold increase from baseline, without the need for rescue therapy or transfusion. Secondary endpoints included bleeding rates, fatigue-related quality of life, adverse events (AEs), and rescue therapy requirements. Results: PLT response was achieved in 94.2% of patients in the Revolade^® group and 85.7% in the Rompag^® group (p = 0.16). Bleeding rates decreased significantly in both groups (Revolade^®: 56.5% to 2.9%, p < 0.001; Rompag^®: 62.9% to 2.9%, p < 0.001). Although overall AE rates were similar (30.4% in the Revolade^® group and 42.9% in the Rompag^® group; p = 0.22), arthralgia (28.6% vs. 7.2%, p = 0.01) and vomiting (11.4% vs. 0%, p = 0.008) were more frequent with Rompag^®. Conclusions: Both generic and original eltrombopag demonstrated no statistically significant difference in efficacy in achieving PLT response, reducing bleeding, and improving fatigue-related quality of life in adult patients with R/R ITP. Although minor differences in AE profiles were observed, particularly arthralgia and vomiting, both formulations showed acceptable safety and tolerability. Full article

Post-cardiac arrest syndrome (PCAS) remains a major cause of mortality and neurological impairment following successful resuscitation, yet the mechanisms linking global ischemia–reperfusion injury to microvascular and systemic dysfunction are not yet completely understood. While prior work has focused on inflammation, endothelial injury, and circulatory collapse, the central role of platelets in coordinating these pathological processes has not been comprehensively examined. This review provides the first integrated framework positioning platelets as core modulators, rather than secondary participants, in PCAS pathophysiology. We synthesize emerging evidence demonstrating that ischemia and reperfusion transform platelets into potent thromboinflammatory effectors through oxidative stress, DAMP-mediated pattern recognition signaling, and mitochondrial dysfunction. Hyperactivated platelets drive cerebral microthrombus formation, coronary no-reflow, and peripheral organ hypoperfusion, while platelet–leukocyte aggregates, neutrophil extracellular traps, and platelet-derived microparticles amplify systemic inflammation and endothelial injury. We further highlight the clinical significance of dynamic platelet dysfunction in coagulopathy, prognostication, and responses to post-arrest therapies including targeted temperature management and ECMO. Finally, we outline a novel, platelet-centered therapeutic paradigm, emphasizing selective interventions, such as GPVI inhibition, P-selectin blockade, FXI/XIa inhibition, and NETosis modulation, that target pathological platelet activity while preserving essential hemostatic function. In this review, by reframing platelets as the central determinants of PCAS, we report new mechanistic insights and therapeutic opportunities that are complementary to the existing post-arrest strategies and have the potential to improve survival and neurological outcomes after cardiac arrest. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

Background/Objectives: Autologous dentin matrix (ADM) has been suggested as a biologically plausible biomaterial for alveolar bone regeneration after tooth extraction. However, clinical evidence regarding its biological activity and early healing outcomes is limited. This exploratory, randomized controlled pilot study aimed to descriptively assess early alveolar healing patterns and bone morphogenetic protein 4 (BMP4) expression following tooth extraction using ADM compared with other grafting approaches. Methods: Patients requiring tooth extraction were allocated to one of four groups: ADM, xenograft, ADM combined with platelet-rich fibrin, and a graft-free control group. Histological and immunohistochemical analyses were performed four months after extraction to descriptively assess cellular features of healing and BMP4 expression. The trial was registered at the Brazilian Registry of Clinical Trials (ReBEC; RBR-24mdgrf) and conducted under prior ethics committee approval. Results: BMP4 expression was detected in 67.9% of the analyzed histological fields, predominantly localized in osteocytic, osteoblastic, and medullary areas. Although descriptive differences in BMP4-positive fields were observed among the groups, no statistically significant differences were identified between the groups. Histological evaluation revealed an active cellular environment across all treatment modalities, consistent with early post-extraction healing. No adverse events related to surgical procedures or grafting materials were reported during the study period. Conclusions: Within the limitations of this pilot randomized clinical trial, ADM exhibited consistent biological behavior during early post-extraction alveolar healing. The observed BMP4 expression likely reflects a general physiological healing response rather than a material-specific effect. This finding supports the biological plausibility of dentin-derived grafts as osteoconductive biomaterials. These findings are hypothesis-generating, and larger, adequately powered randomized clinical trials with standardized molecular and histological assessments are required to determine their clinical relevance. Full article

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies. Full article

Background: Red cell distribution width (RDW) and the RDW-to-platelet ratio (RPR) have emerged as readily available hematologic markers reflecting systemic inflammation in neonates with hypoxic–ischemic encephalopathy (HIE); however, their early postnatal trajectories across the clinical spectrum of HIE remain insufficiently characterized. Methods: This retrospective cohort study included 229 term or near-term infants diagnosed with HIE. Among them, 166 infants received therapeutic hypothermia, whereas 63 infants who did not undergo cooling served as the reference group. RDW and RPR values were measured at birth and at 72 h of life (after completion of cooling in the hypothermia group). Results: In the reference group, RDW values significantly decreased at 72 h, reflecting normal postnatal hematologic adaptation. In contrast, the hypothermia group demonstrated a blunted decline, with RDW levels remaining relatively stable over the first 72 h, consistent with a blunted early postnatal RDW decline. RPR values showed a mild, non-significant upward trend during the first 72 h of life; however, exploratory analyses suggested an association between higher RPR levels and increasing HIE severity. Conclusions: Across the spectrum of hypoxic–ischemic encephalopathy, RDW demonstrated a blunted postnatal decline, whereas RPR showed a mild, non-significant increase during the early neonatal period. These readily available hematologic markers may provide complementary insights into early systemic inflammatory and hematologic responses in HIE. Prospective multicenter studies are needed to determine their prognostic value and relationship with clinical and neurodevelopmental outcomes. Full article

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes. Full article

With the intensification of global population aging, the co-morbidity rate of periodontitis and osteoporosis has significantly increased. The two are pathologically intertwined, forming a vicious cycle characterized by bone immunoregulatory dysfunction in the periodontal microenvironment, abnormal accumulation of reactive oxygen species (ROS), and disruption of bone homeostasis. Conventional mechanical debridement and anti-infective therapy can reduce the pathogen load, but in some patients, it remains challenging to achieve long-term stable control of inflammation and bone resorption. Furthermore, abnormal bone metabolism in the context of osteoporosis further weakens the osteogenic response during the repair phase, limiting the efficacy of these treatments. Bioinspired cell membrane-coated nanoparticles (CMNPs) have emerged as an innovative technological platform. By mimicking the biointerface properties of source cells—such as red blood cells, platelets, white blood cells, stem cells, and their exosomes—CMNPs enable targeted drug delivery, prolonged circulation within the body, and intelligent responses to pathological microenvironments. This review systematically explores how biomimetic design leverages the advantages of natural biological membranes to address challenges in therapeutic site enrichment and tissue penetration, in vivo circulation stability and effective exposure maintenance, and oxidative stress and immune microenvironment intervention, as well as functional regeneration supported by osteogenesis and angiogenesis. Additionally, we conducted an in-depth analysis of the key challenges encountered in translating preclinical research findings into clinical applications within this field, including issues such as the feasibility of large-scale production, batch-to-batch consistency, and long-term biosafety. This review lays a solid theoretical foundation for advancing the clinical translation of synergistic treatment strategies for periodontitis with osteoporosis and provides a clear research and development pathway. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory disease associated with systemic inflammation and comorbidities such as cardiovascular disease and metabolic syndrome. Blood-derived inflammatory indices like neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV) have been proposed as biomarkers of systemic inflammation and disease severity. This retrospective and prospective observational study aimed to evaluate the long-term effects of guselkumab, an IL-23 inhibitor, on these indices in moderate-to-severe psoriasis. Methods: We analyzed 208 patients with moderate-to-severe psoriasis treated with guselkumab, with hematologic evaluations available for 208 patients at baseline, 208 at week 52, 129 at week 104, and 94 at week 156. Systemic inflammatory indices were calculated from routine annual blood tests. Patients were stratified by obesity, cardiovascular comorbidities, treatment response, and prior biologic therapy. Longitudinal changes were assessed using Friedman tests with Wilcoxon post hoc comparisons, and correlations between PASI and inflammatory indices were evaluated using Spearman’s coefficients. Results: SIRI and PLR showed significant reductions at week 156 (p = 0.038 and p = 0.018, respectively), while MLR also decreased over time without reaching consistent significance. NLR and PIV showed minimal or inconsistent changes. Obese patients and those with cardiovascular disease had higher baseline SII and SIRI and less pronounced improvements. No significant differences were observed between super responders and others. Correlation between baseline PASI and most inflammatory markers was weak, except for a weak but significant correlation with PIV (ρ = 0.119, p = 0.049). Conclusions: Guselkumab treatment is associated with long-term reduction in systemic inflammatory indices, particularly SIRI. The weak correlation of these markers with skin severity highlights a dissociation between cutaneous and systemic inflammation. SIRI and SII may serve as useful biomarkers to monitor systemic inflammation and guide comprehensive management in psoriasis patients. Full article

The human body’s ability to recover from bone injuries is remarkable; however, in specific conditions, interventions are required to restore function and prevent complications. To accelerate osteogenesis, several strategies have been explored, including grafts, biomaterials, and adjuvant therapies. The aim of this narrative review was to analyze the preclinical evidence regarding the combination of particulate biomaterials and fibrin derivatives for bone regeneration. Publications using hydroxyapatite, bovine bone, β-tricalcium phosphate, and bioglass in association with fibrin glue, heterologous fibrin sealants, or platelet-rich fibrin were examined to identify recurrent experimental patterns and biological outcomes. According to the studies, hydroxyapatite and bovine bone were the most frequently investigated scaffolds, whereas fibrin glue and heterologous fibrin sealants showed consistent adhesion and favorable host response profiles in animal models. β-tricalcium phosphate demonstrated faster remodeling but lower volumetric stability, and bioglass showed high bioactivity in isolated reports. Despite heterogeneity in particle size, fibrin formulations, defect models, and follow-up periods, most studies reported enhanced bone deposition, vascularization, and integration when particulate biomaterials were combined with fibrin-based matrices. Overall, the evidence suggests that these combinations promote more organized and biologically favorable bone healing under experimental conditions. Future translational and clinical research is required to standardize protocols and determine the therapeutic applicability of these strategies in human bone repair. Full article

Background/Objectives: Pathological complete response (pCR) is an established surrogate marker of neoadjuvant chemotherapy (NACT) efficacy in breast cancer; however, reliable predictors of pCR remain limited. Immune–inflammation- and nutrition-based biomarkers derived from routine blood tests may offer accessible tools for early assessments of treatment response. This study aimed to evaluate both baseline values and dynamic (Δ) changes in multiple immune–nutritional indices to determine their predictive performance with regard topCR. Methods: A retrospective analysis was conducted on 236 early breast cancer patients who received neoadjuvant chemotherapy. Pre-treatment (B), post-treatment (A), and Δ values were calculated for the prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), hemoglobin–albumin–lymphocyte–platelet (HALP) score, systemic inflammation response index (SIRI), pan-immune–inflammation value (PIIV), global immune–nutrition-information index (GINI), nutritional risk index (NRI), and related biomarkers. Associations with pCR were examined using chi-square testing and univariate logistic regression, and diagnostic performance was assessed through receiver operating characteristic (ROC) analysis. Results: pCR was achieved in 116 patients (49.2%). Logistic regression identified the NRI (OR = 2.336), ΔGINI (OR = 2.323), ALI (OR = 1.318), PNI (OR = 1.365), HALP score (OR = 1.217), ΔSIRI (OR = 2.207), and ΔPIIV (OR = 2.001) as significant predictors. ROC analysis showed that the NRI (AUC = 0.840) and ΔGINI (AUC = 0.807) were the strongest discriminators of pCR. In aLASSO (Least Absolute Shrinkage and Selection Operator)-penalized logistic regression with 10-fold cross-validation, the NRI and ΔGINI emerged as independent predictors of pCR (OR = 1.28 and OR = 1.23, respectively), showing acceptable calibration particularly in the moderate-to-high probability range. Conclusions: Both baseline and Δ immune–nutritional biomarkers predict pCR following NACT in breast cancer. The NRI and ΔGINI demonstrated the best diagnostic performance, whereas ΔSIRI and ΔPIIV also showed meaningful associations. Easily obtainable, low-cost indices—particularly Δ markers—may support the early identification of responders and facilitate more personalized therapeutic decision-making in breast cancer management. Full article

Background/Objectives: Immunotherapy has improved outcomes for selected patients with advanced non-small-cell lung cancer (NSCLC), yet the predictive value of individual biomarkers such as PD-L1 remains limited. Systemic inflammatory indices derived from routine blood tests may complement molecular and immunohistochemical features, offering a broader view of host–tumor immunobiology. Methods: We conducted a retrospective study of 298 patients with stage IIIB–IV NSCLC treated with immune checkpoint inhibitors (ICIs) at a tertiary oncology center between 2022 and 2024. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune–inflammation index (SII) were collected alongside PD-L1 expression and molecular alterations (EGFR, KRAS, ALK, TP53). Patients were stratified into inflammatory–molecular clusters integrating these parameters. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan–Meier and multivariate Cox analyses. Results: Four distinct inflammatory–molecular clusters demonstrated significantly different outcomes (p < 0.001). Patients with low NLR and high PD-L1 expression (Cluster A) showed the highest ORR (41%), longest median PFS (13.0 months), and OS (22.5 months). The EGFR/ALK-driven, inflammation-dominant cluster (Cluster C) exhibited poor response (ORR 7%) and shortest survival (PFS 4.3 months). High NLR (HR 2.12), PD-L1 < 1% (HR 1.91), and EGFR mutation (HR 2.36) independently predicted shorter PFS. A combined model incorporating NLR, PD-L1, and molecular status outperformed individual biomarkers (AUC 0.82). Conclusions: Integrating systemic inflammatory indices with PD-L1 expression and molecular alterations identifies clinically meaningful NSCLC subgroups with distinct immunotherapy outcomes. This multidimensional approach improves prediction of ICI response and may enhance real-world patient stratification, particularly in settings with limited access to extended molecular profiling. Full article