Search Results (715)

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but may induce pseudoprogression (PP), an atypical response pattern that may mimic progressive disease (PD). Although iRECIST criteria were developed to characterize such atypical responses, distinguishing PP from PD when progression is first observed remains challenging. We aimed to characterize patients with clinically suspected PP and explore clinical and biological factors associated with subsequent classification as PP versus PD. Methods: We conducted a retrospective single-center study including patients with metastatic cancer treated with ICIs at the Institut de Cancérologie de l’Ouest (ICO) in whom PP was clinically suspected. Clinical, biological, treatment, and outcome data were collected at ICI initiation, PP suspicion, and subsequent PP/PD classification. Associations with PP versus PD were explored using univariable and multivariable logistic regression. Results: Among 123 patients with clinically suspected PP, 56 were subsequently classified as PP and 67 as PD. The most frequent primary tumors were lung (38%), kidney (24%), and bladder (11%) cancers. Median time from ICI initiation to PP suspicion was 79 days. ECOG performance status of 0 at ICI initiation was more frequent in the PP than in the PD group (55% vs. 32%; p = 0.046). At PP suspicion, median LDH levels were lower in the PP than in the PD group (189 vs. 232.5 U/L; p = 0.003). After multivariable adjustment, higher LDH levels at PP suspicion remained associated with PD (adjusted OR 2.78 per 100 U/L increase; 95% CI, 1.19–6.52; p = 0.019). Conclusions: In patients with clinically suspected PP, LDH may provide complementary information but cannot reliably distinguish PP from PD when considered alone. Confirmatory imaging therefore remains essential for treatment decision-making. Full article

Background: Serum ALT is widely used to assess liver inflammation and fibrosis, yet metabolic steatohepatitis (MASH) and significant fibrosis can still occur in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with normal ALT. However, liver histology in patients with ALT below the cutoffs remains poorly characterized. This study aimed to compare the diagnostic performance of conventional and lower ALT thresholds for assessing MASH and significant fibrosis, using liver biopsy as the reference standard. Materials: This retrospective cross-sectional, two-center study included 404 patients with MASLD, without concurrent viral hepatitis, who underwent liver biopsy at two hospitals in Tianjin between October 2012 and October 2024. The assessment of inflammation and fibrosis was based on liver biopsy histology. Patients were stratified using both conventional and lower ALT thresholds (30 U/L for men, 19 U/L for women). Results: Among the 404 patients, 70.3% had MASH and 67.1% had significant fibrosis. Of those with conventionally normal ALT levels (n = 130), the prevalence of MASH and significant fibrosis was 49.23% and 50.00%, respectively. Using a lower ALT threshold, patients with ALT between the conventional and lower thresholds had significantly higher rates of significant fibrosis compared to those with ALT below the lower threshold (56.18% vs. 36.59%, p = 0.002). The incidence of MASH also showed a decreasing trend in the lower ALT group (53.93% vs. 39.02%, p = 0.082). Multivariate analysis showed that the application of a lower ALT ULN was independently associated with MASH (OR = 5.188, 95% CI: 1.494–18.018, p < 0.001). Conclusions: The study evaluated the association between liver histology and ALT under alternative externally proposed ALT thresholds. The lower ALT threshold was independently associated with MASH, but its diagnostic performance was limited; further prospective evaluation is warranted. Full article

Background/Objective: Patients with Inborn Errors of Immunity (IEI) are at increased cardiometabolic risk due to inflammation, immune dysfunction, and oxidative stress. Given selenium’s essential role in antioxidant defense, this study evaluated plasma selenium concentration in individuals with IEI and its associations with inflammatory and metabolic biomarkers and body mass index (BMI). Methods: A controlled cross-sectional study involved 85 patients, 22 with ataxia–telangiectasia (A-T), 32 with common variable immunodeficiency (CVI) and 31 with juvenile systemic lupus erythematosus (jSLE). The control group comprised 72 age- and sex-matched healthy individuals. Anthropometric, inflammatory, metabolic, and oxidative stress parameters were assessed, including BMI, ultrasensitive C-reactive protein (usCRP), lipid profile, fasting glucose, insulin, plasma Se concentrations, erythrocyte glutathione peroxidase (GPx) activity, and malondialdehyde levels. Results: Selenium concentrations below the reference value (46 µg/L) were observed in all groups, A-T (41%), CVI (50%), jSLE (48%) and the control group (33%). Low weight was more frequent in the A-T group (41%), whereas excess weight predominated in the CVI (47%) and jSLE (19%) groups. Multiple linear regression showed lower selenium concentrations in the jSLE (β = −10.1 ug/L) and CVI (β = −12.8 µg) groups compared with the controls (p < 0.05). Selenium concentrations were associated with age (β = 0.3 µg/L) and usCRP (p < 0.05). The GPx values were lower among all patient groups (jSLE: β = 3228 U/L, A-T: β = −2030 U/L, and CVI: β = −2060 U/L) (p < 0.05) compared with the controls. The GPx was also influenced by age (β = 56 U/L; p = 0.010). Conclusion: The present findings suggest alterations in the endogenous antioxidant defense system in patients with IEI, characterized by reduced erythrocyte GPx activity and lower plasma selenium concentrations. The inverse association between selenium and usCRP concentrations suggests a potential link between selenium status and systemic inflammation. However, these findings should be interpreted cautiously, as inflammation may influence circulating selenium concentrations, and the cross-sectional design does not establish causal inferences. Further longitudinal studies are warranted to clarify the relationship between selenium status, inflammation, and antioxidant defense in IEI. Full article

The widespread use of antibiotics in aquaculture has raised concerns regarding adverse physiological effects on fish, creating a need for dietary strategies that enhance fish resilience during antibiotic administration and support animal welfare under therapeutic treatment conditions. This study evaluated, for the first time, a phytochemically characterized supercritical fluid extract of Ulva lactuca (Ul-SFE), rich in flavan-3-ols (epigallocatechin, epicatechin gallate) and other phenolics, as a dietary supplement in common carp (Cyprinus carpio). Juvenile carp (n = 360; 20.20 ± 0.13 g) received a control or Ul-SFE-supplemented diet (50 mg kg⁻¹) for 10 weeks, followed by 10 days of florfenicol or oxytetracycline exposure at therapeutic doses. Growth, plasma biochemistry, oxidative stress, and innate immunity were assessed. Ul-SFE significantly improved FCR, SGR, and PER during growth. Under antibiotic challenge, both florfenicol and oxytetracycline affected growth performance and biochemical status, though with different predominant patterns: florfenicol exposure was mainly characterized by reduced growth performance, while oxytetracycline exposure was mainly characterized by biochemical disturbance—reduced total protein and globulin, elevated glucose, ALT, and lipid peroxidation, and impaired antioxidant/immune status. Ul-SFE consistently attenuated these effects, reducing malondialdehyde by 24–30% and increasing antioxidant capacity by 5–7%; its protective effect on lysozyme was strongly diet-dependent (Diet × Antibiotic, p < 0.001), ranging from a 20% increase without antibiotics to negligible under oxytetracycline. These findings show Ul-SFE improves feed utilization and confers partial, treatment-dependent resilience against antibiotic-induced stress, supporting its potential as a functional feed additive in aquaculture. Full article

Background: Pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma may differ between the primary tumor and regional lymph nodes. We evaluated pretreatment factors associated with pathological complete response (pCR) and the anatomical distribution of residual disease after esophagectomy. Methods: This retrospective single-center cohort included 100 patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. pCR was defined as ypT0N0. Associations with pCR were evaluated using logistic regression. Results: Among 99 response-evaluable patients, 59 achieved pCR (59.6%; 95% CI, 49.7–68.7%). Of 40 patients with non-pCR, residual disease involved only the primary tumor in 26 (65%), both primary and nodal compartments in 10 (25%), and only regional lymph nodes despite complete primary tumor regression in 4 (10%). Overall, 14 patients with non-pCR (35%) had residual nodal disease. In an exploratory adjusted analysis that could not account for baseline cT and cN categories, lower pretreatment lactate dehydrogenase (OR per 10 U/L increase, 0.93; 95% CI, 0.86–0.99; p = 0.026) and female sex (OR, 2.72; 95% CI, 1.02–7.24; p = 0.045) were associated with pCR. Conclusions: Response was heterogeneous across primary tumor and nodal compartments. Primary tumor regression did not invariably indicate nodal clearance, supporting compartment-specific response assessment. The lactate dehydrogenase and sex associations may reflect residual confounding by baseline disease extent and require external validation. Full article

Background/Objectives: Occupational pesticide exposure is a recognized hepatotoxic hazard; however, biomonitoring data characterizing liver function among Vietnamese agricultural workers remain scarce. This study compared serum hepatic biomarkers between pesticide-exposed fruit farmers (exposed group) and a non-exposed reference group (unexposed group) in a northern province in Vietnam, and evaluated whether biomarker alteration varied with cumulative exposure duration. Methods: A cross-sectional study using convenience sampling was conducted from April to October 2022 among 150 adults, comprising 100 fruit farmers with ≥1 year of direct occupational pesticide exposure and 50 unexposed controls. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and indirect bilirubin, alpha-fetoprotein (AFP), and glucose were quantified using clinical laboratory assays. Multivariable linear regression models, adjusting for age, sex, and body mass index (BMI), were used to evaluate associations between pesticide exposure duration and biomarker levels. Results: Pesticide-exposed farmers had significantly higher mean concentrations of ALT (28.88 vs. 22.36 U/L, p = 0.002), AFP (3.06 vs. 1.16 ng/mL, p < 0.001), total bilirubin (9.93 vs. 7.74 μmol/L, p < 0.001), and indirect bilirubin (8.40 vs. 5.26 μmol/L, p < 0.001) than unexposed controls. While mean AST did not differ (p = 0.105), the proportion of abnormal AST cases was significantly higher among exposed individuals (23% vs. 8%, p = 0.043). After adjustment for age, sex, and BMI in multivariable linear regression models, prolonged exposure (>10 years) remained modestly associated with higher AFP and bilirubin levels (p < 0.05), while associations with ALT and AST were not statistically evident (p > 0.05). Conclusions: These findings suggest a possible association between occupational pesticide exposure and subclinical hepatic alterations, supporting calls for regular health surveillance and enhanced protective measures among fruit farmers. Full article

The escalating environmental burden of conventional plastic food packaging has intensified the search for sustainable, biodegradable alternatives. However, single-component polysaccharide edible films often exhibit suboptimal mechanical and barrier properties, which limits their practical applicability. In this study, pullulan (PUL), konjac glucomannan (KGM) and low-acyl gellan gum (LGG) were blended as film-forming substrates with glycerol as a plasticiser. Single-factor experiments combined with Box–Behnken response surface methodology (RSM) were employed to optimise the formulation of ternary edible composite films. The effects of PUL, KGM and LGG concentrations on mechanical properties and water vapour permeability (WVP) were systematically investigated. The optimised film was comprehensively characterised for microstructure, physical barrier performance, antioxidant activity, soil disintegration, bacteriostatic capacity and plum preservation efficiency. The optimal formulation comprised 1.43 g/100 mL PUL, 0.24 g/100 mL KGM and 0.48 g/100 mL LGG. Under these conditions, the composite film exhibited a transparent and smooth appearance, with a continuous and dense internal microstructure. The comprehensive performance score (K) reached 0.805 ± 0.013, with a WVP of 2.75 ± 0.17 g·μm/(m²·h·kPa), light transmittance of 89.93% ± 1.26%, tensile strength (TS) of 3.05 ± 0.14 N/cm², elongation at break (EB) of 64.57% ± 0.58% and DPPH radical scavenging activity of 34.12% ± 0.96%. Storage trials on two plum varieties demonstrated that the composite coating effectively mitigated fruit weight loss, retarded peel browning and pulp softening, and maintained superior sensory quality throughout storage. Overall, the PUL/KGM/LGG ternary edible composite film exhibited favourable mechanical strength, promising water vapour barrier properties and moderate antioxidant activity, suggesting its potential as a useful reference for the further development and industrial adoption of biodegradable edible films in fruit and vegetable preservation. Full article

Background/Objective: Insufficient research has examined the muscle damage and inflammatory effects of training performed in a fasted state with reduced (low) glycogen reserves. Methods: This study aimed to investigate the acute effects of exercise sessions performed under fasting (FST) and liquid nutrient-supplemented postprandial (PPD) conditions, as well as with full and reduced body glycogen stores, on muscle damage markers creatine kinase (CK) and lactate dehydrogenase (LDH), and the inflammatory marker interleukin-6 (IL-6). Eleven male amateur football players (mean age 19.91 ± 1.64 years) were included in the study. Participants performed a single 60 min aerobic endurance exercise session at 70% VO₂max under the liquid nutrient-supplemented PPD condition, and two 60 min sessions with a 60 min recovery interval under 10–12 h FST conditions. Data were analyzed using paired samples t-test, ANOVA, Wilcoxon, and Friedman tests, depending on parametric and nonparametric assumptions. Results: In pre-exercise (PRE-FE) measurements, no significant differences were observed between the FST and PPD conditions for GLU, CK, LDH, and IL-6 levels. In postexercise (POST-FE) measurements, GLU levels were significantly higher in the PPD condition than in the FST condition (p < 0.05), whereas LA, CK, LDH, and IL-6 levels did not differ significantly between the two conditions. In the FST condition, following the second exercise session performed with default reduced glycogen availability (POST-SE), CK levels significantly increased from 279.36 ± 16.7 U/L to 335.63 ± 20.3 U/L, LDH levels from 178.72 ± 38.1 U/L to 208.09 ± 50.7 U/L, and IL-6 levels from 2.60 ± 2.4 pg/mL to 8.69 ± 5.8 pg/mL (p < 0.05). In the PPD condition, no significant changes were observed in any of the parameters following a single exercise session (p > 0.05). Conclusions: The two-a-day training approach performed with default reduced glycogen availability may increase muscle damage and inflammatory responses. These findings are considered as an inference that low-glycogen training should not be implemented during the pre-competition period because of the risk of inducing muscle damage. Full article

(1) Background/Objective: Routine blood tests may provide useful information at different stages of epithelial ovarian cancer (EOC) management. This study evaluated continuous lactate dehydrogenase (LDH), carbohydrate antigen 125 (CA125), and neutrophil-to-lymphocyte ratio (NLR) values for diagnostic discrimination in epithelial ovarian cancer (EOC) and, separately, triple-positive status in relation to platinum resistance and survival. (2) Methods: This retrospective study included 238 patients with EOC and 238 individually matched patients with benign ovarian lesions. Continuous biomarkers were entered into logistic regression models for diagnosis. Triple-positive status was defined as LDH > 195.5 U/L, CA125 > 35.37 U/mL, and NLR > 2.63. Logistic regression was used for platinum resistance and Cox regression for progression-free survival (PFS) and overall survival (OS). Bootstrap internal validation was performed for the diagnostic models and PFS nomogram. (3) Results: The continuous LDH + CA125 + NLR model yielded an AUC of 0.873, with 75.97% sensitivity and 88.66% specificity; AUCs were 0.751 in early-stage and 0.958 in advanced-stage EOC. Adding NLR to LDH + CA125 did not significantly improve the AUC overall or within stage groups. Triple-positive status was associated with platinum resistance (adjusted OR = 3.488, 95% CI 1.504–8.087; p = 0.004), shorter PFS (adjusted HR = 3.109, 95% CI 1.772–5.456; p < 0.001), and shorter OS in advanced-stage EOC (adjusted HR = 3.538, 95% CI 1.385–9.038; p = 0.008). The PFS nomogram had a bootstrap-corrected C-index of 0.7521. (4) Conclusions: The continuous three-marker model showed diagnostic discrimination in this selected surgical cohort, while triple-positive status was associated with platinum resistance and adverse survival outcomes. External validation is needed. Full article

Water color is an important optical proxy for trophic status and water quality, but its integration into regulatory assessment frameworks is still limited. This study assesses the potential of the Forel–Ule Index (FUI) derived from Sentinel-2 as a proxy indicator to support the assessment of the ecological status of reservoirs under the European Union’s Water Framework Directive (WFD). Seventeen reservoirs located in semi-arid Mediterranean climate agricultural basins in southern Portugal (Sorraia, Sado, and Guadiana) were analyed, combining 4316 FUI observations (2017–2024) with in situ water quality data and official WFD ecological status classifications. The results showed that the values on the FUI scale (which ranges from 1 to 21) fell, for the most part, between 12 and 18 and with marked spatial and seasonal contrasts, particularly between more transparent reservoirs and persistently turbid ones, probably eutrophicated reservoirs. Principal component analysis showed that the first component (PC1, 39.5% of variance) represents a trophic gradient dominated by turbidity, chemical oxygen demand and chlorophyll-a, and is positively, albeit moderately, correlated with FUI (Spearman’s ρ = 0.439, p < 0.001), while the second component, dominated by nitrogen, showed no significant association. To make the Water Framework Directive (WFD) regulations compatible with the structure of the available dataset, ecological status was dichotomized into “Satisfactory” and “Deterioration”. Binary logistic regression showed that increasing FUI values were significantly associated with a lower probability of classification as “Satisfactory” (β = −0.682, p = 0.0137; odds ratio = 0.51, 95% CI: 0.29–0.87). The model performance was moderate (balanced accuracy = 0.682; AUC = 0.754), with better identification of “Deterioration” conditions than “Satisfactory” conditions. The Mann–Whitney U test confirmed that mean FUI values differed significantly between the two ecological status groups (U = 65, p = 0.0166), with lower values associated with reservoirs meeting the “Good” threshold. Overall, FUI proved to be a low-cost and temporally flexible screening and early-warning tool, particularly useful for identifying departures from favorable ecological conditions. However, the index is not a direct substitute for the official ecological classification and is best applied in combination with physicochemical and biological metrics when assessing changes in water quality over a shorter period of time. Full article

Alcohol-associated liver disease (ALD) contributes substantially to the global burden of chronic liver disease, yet few effective pharmacological treatments are currently available. The hepatoprotective potential of Lactobacillus helveticus HY7804 was evaluated in ethanol-exposed HepG2 cells and in a modified chronic-binge ethanol-fed mouse model adapted from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) paradigm. Ethanol-induced cytotoxicity in HepG2 cells was attenuated by HY7804, as demonstrated by the recovery of cell viability and the reduction in lactate dehydrogenase release. HY7804 also decreased ethanol-induced inflammatory cytokine production, including IL-6, TNF-α, IL-1β, and IL-8, and modulated apoptosis-related gene expression. In chronic-binge ethanol-fed mice, HY7804 reduced serum AST from 183.4 ± 34.1 to 129.4 ± 16.4 U/L (p < 0.01) and ALT from 67.5 ± 4.5 to 52.1 ± 4.7 U/L (p < 0.05). Hepatic lipid accumulation was also significantly reduced by HY7804 treatment compared with the EtOH group, as indicated by the decreased Oil Red O-positive area (p < 0.01). Hepatic MDA levels decreased from 46.01 ± 3.38 to 30.58 ± 6.38 nmol/mg tissue (p < 0.01). In addition, HY7804 modulated hepatic inflammatory cytokine profiles, antioxidant-related responses, and the Bax/Bcl-2 expression ratio. These findings suggest that HY7804 mitigates ethanol-induced hepatic injury, with associated changes in inflammatory responses, antioxidant-related markers, lipid peroxidation, and apoptosis-related gene expression. Full article

Background/Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major complication after distal pancreatectomy. Postoperative pancreatic enzyme elevation is increasingly recognized as a marker of pancreatic remnant injury, but serum lipase after distal pancreatectomy has been less well characterized than serum amylase and drain-fluid markers. This study evaluated postoperative day 3 (POD3) serum lipase as a routine biochemical marker associated with CR-POPF. Methods: We retrospectively analyzed 202 consecutive adults who underwent distal pancreatectomy between 2016 and 2026. CR-POPF was defined as International Study Group on Pancreatic Surgery grade B or C. POD3 lipase was available in 157 patients, including 17 CR-POPF events. Results: POD3 lipase was higher in patients with CR-POPF than in those without it (median 74 vs. 31 U/L; p < 0.001). Each doubling of lipase was associated with higher odds of CR-POPF (OR 2.59, 95% CI 1.54–4.37). The AUC was 0.79 (95% CI 0.67–0.90) and remained 0.79 after bootstrap optimism correction. At 64 U/L, the negative predictive value was 96%; at 3 × ULN, specificity was 99%. Conclusions: POD3 serum lipase provides a readily available serum biochemical marker, not requiring drain-fluid sampling, associated with CR-POPF after distal pancreatectomy. The findings are exploratory and require external validation before clinical implementation. Full article

Introduction: Seborrheic dermatitis (SD) is a lipid-dependent inflammatory dermatosis in which sebaceous activity, Malassezia, barrier dysfunction and host inflammation interact. Whether scalp SD severity is associated with systemic lipid and liver-associated biochemical parameters remains unclear. Methods: In this exploratory cross-sectional observational study, we included 34 adults with clinically diagnosed scalp SD. Severity was assessed using a published 16-point scalp SD score and a study-specific 0–36 physician-assessed score. Fasting lipids, glucose, alanine aminotransferase (ALT), aspartate aminotransferase and gamma-glutamyl transferase (GGT) were recorded. The triglyceride/high-density lipoprotein cholesterol ratio and non-HDL cholesterol were calculated. Patients were stratified as having non-severe or severe disease according to the 16-point score. Results: Complete 16-point data were available in 33 patients: 15 with non-severe and 18 with severe scalp SD. Severe disease was associated with higher triglycerides (116.0 vs. 78.0 mg/dL; p = 0.004), triglyceride/high-density lipoprotein cholesterol ratio (2.57 vs. 1.23; p = 0.006), ALT (46.0 vs. 20.0 U/L; p = 0.028) and GGT (33.0 vs. 11.0 U/L; p = 0.003). The strongest correlations with the 16-point score were observed for GGT (rho = 0.745), triglycerides (rho = 0.634), ALT (rho = 0.572) and triglyceride/high-density lipoprotein cholesterol ratio (rho = 0.569; all p < 0.001). These prespecified associations remained significant after false-discovery-rate adjustment and after adjustment for age and BMI. The correlation pattern was strengthened using the 0–36 score and persisted after excluding one liver enzyme outlier. Conclusions: More severe scalp SD was associated with triglyceride-related lipid parameters and liver-associated enzymes, suggesting a broader lipid-liver metabolic phenotype. These findings require confirmation in larger controlled studies. Full article

Background and Clinical Significance: Tarui disease, or glycogen storage disease type VII, is a rare autosomal recessive metabolic myopathy caused by muscle phosphofructokinase deficiency. Its manifestations include exercise intolerance, exertional myalgia, muscle cramps, myoglobinuria, rhabdomyolysis, hyperuricemia, and compensated hemolysis. The hematologic phenotype may obscure the underlying metabolic disorder and raise concern for a clonal myeloid neoplasm. Case Presentation: A 23-year-old man was referred for persistent mild thrombocytopenia following evaluation for jaundice and hepatosplenomegaly. He had undergone cholecystectomy at 18 years of age and reported exercise-induced myalgia, muscle cramps, and episodes of dark urine. Laboratory investigations demonstrated mild monocytosis, reticulocytosis, thrombocytopenia, hyperuricemia, elevated lactate dehydrogenase, and predominantly unconjugated hyperbilirubinemia, with a negative direct antiglobulin test. Selected inherited hemolytic disorders, hemoglobinopathies, and paroxysmal nocturnal hemoglobinuria were excluded. Bone marrow examination showed marked erythroid hyperplasia and mild megakaryocytic dysplasia. Testing for JAK2, CALR, and MPL mutations and an extended myeloid next-generation sequencing panel identified no pathogenic variants, and monocytosis resolved during follow-up. Whole-exome sequencing identified a homozygous PFKM missense variant, NM_001354735.1:c.1087A>T, p.(Ile363Phe), classified as a variant of uncertain significance. The patient subsequently developed severe rhabdomyolysis, with a creatine kinase level of 225,000 U/L and recovered after intensive intravenous hydration without renal impairment. Conclusions: Tarui disease should be considered in young patients with compensated hemolysis, hyperuricemia, exertional muscle symptoms, dark urine, or rhabdomyolysis, even when hematologic abnormalities suggest a myeloid disorder. The highly concordant phenotype and homozygous PFKM variant support a clinically probable diagnosis, although pathogenicity remains unconfirmed. Functional and segregation evidence may strengthen causal interpretation and support future variant reclassification. Full article

Background/Objectives: Clinical outcomes with immune checkpoint inhibitors (ICIs), such as nivolumab, vary among patients with metastatic non-small cell lung cancer (NSCLC). The Lung Immune Prognostic Index (LIPI) may help stratify prognosis. This study evaluated the prognostic significance of LIPI in patients receiving second- or third-line nivolumab and developed a nomogram for individualized survival estimation. Methods: This single-center retrospective study included 142 patients with metastatic NSCLC who received second- or third-line nivolumab between February 2022 and December 2024, after progression on platinum-based chemotherapy. LIPI was calculated from baseline values obtained within 14 days before nivolumab initiation, based on a derived neutrophil-to-lymphocyte ratio (dNLR) > 3 and lactate dehydrogenase (LDH) > 225 U/L (institutional upper limit of normal), classifying patients as good-, intermediate-, or poor-risk (0, 1, or 2 factors, respectively). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method; independent prognostic factors were assessed by multivariable Cox regression, and a prognostic nomogram combining ECOG performance status, serum albumin, and LIPI was developed and internally validated. Results: By LIPI, 34.5%, 45.1%, and 20.4% of patients were at good, intermediate, and poor risk, respectively. Objective response and disease control rates were 29.6% and 55.6%. Median OS and PFS were 19.3/8.0/3.1 and 8.6/3.1/2.5 months across good, intermediate, and poor LIPI groups (log-rank p < 0.001). In multivariable analysis, ECOG 2 (hazard ratio [HR], 4.94), albumin per 1 g/dL (HR 0.27), and poor versus good LIPI (HR 3.74) were independently associated with OS. A nomogram combining these three factors showed acceptable discrimination (optimism-corrected Harrell C-statistic 0.742). Conclusions: LIPI was independently associated with prognosis in this cohort. Combining LIPI with ECOG and albumin may aid individualized risk assessment, pending external validation. Full article