Search Results (229)

Background: The incidence of early-onset colorectal cancer (EOCRC) is rising, yet the relative contribution of metabolic, inflammatory, and laboratory abnormalities remains incompletely defined. Objectives: We compared these associations between EOCRC and late-onset colorectal cancer (LOCRC) while addressing the possibility that some laboratory abnormalities may reflect occult cancer rather than antecedent risk. Methods: We conducted a matched case–control study using the TriNetX US Network. Adults diagnosed with CRC between 2010 and 2023 were identified as EOCRC (18–49 years) or LOCRC (50–75 years). Patients with prior malignancy, inflammatory bowel disease, hereditary or familial CRC risk, or prior colectomy were excluded. Three separate analyses were performed. First, a direct EOCRC-versus-LOCRC comparison evaluated gastrointestinal symptoms during the 6 months preceding diagnosis. Second, EOCRC and LOCRC were each compared with their respective matched cancer-free controls to assess clinical, metabolic, and laboratory features during the 24 months preceding diagnosis. When multiple laboratory values were available, the most recent value preceding the index date was used. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals, with Bonferroni correction applied for multiple comparisons. Results: The direct matched EOCRC-versus-LOCRC comparison included 7752 patients with CRC, comprising 2584 with EOCRC and 5168 with LOCRC. EOCRC more frequently presented with rectal bleeding, abdominal pain, diarrhea, iron-deficiency anemia, and weight loss. Rectal tumors were more common in EOCRC, whereas proximal tumors were more common in LOCRC. In separate control-based analyses, 3217 patients with EOCRC and 12,112 patients with LOCRC were compared with 6434 and 24,336 matched cancer-free controls, respectively. The strongest independent features associated with EOCRC were severe obesity (aOR 2.61), microcytosis (aOR 2.29), low ferritin (aOR 2.11), and elevated C-reactive protein (aOR 1.87). Similar but generally attenuated associations were observed in LOCRC. In adjusted EOCRC-versus-LOCRC analyses, obesity (aOR 1.38), metabolic syndrome (aOR 1.41), and MASH (aOR 1.22) remained more closely associated with EOCRC. Conclusions: EOCRC is associated with a distinct clinical–metabolic phenotype, with more pronounced metabolic, inflammatory, and hematologic abnormalities than LOCRC. These findings should be interpreted as hypothesis-generating prediagnostic associations, not as validated predictors or causal risk factors. Full article

Background. Orthotic and prosthetic devices for general-use and activity-specific function can provide critical preventive health benefits for individuals with limb loss, limb difference, and mobility impairments, and yet coverage remains inconsistent across U.S. states. Objective. To evaluate the fiscal impact of clarifying insurance coverage for orthotic and prosthetic devices across 23 states lacking comprehensive coverage. Methods. A cost consequence analysis was conducted using data from the U.S. Census Bureau, Kaiser Family Foundation, Government Accountability Office, and a recent actuarial analysis informing baseline cost, coverage, and prevalence assumptions. Per-member-per-month (PMPM) cost increases were compared against device enabled preventive health savings to estimate net fiscal impact. Sensitivity analyses modeled three scenarios based upon a combination of uptake (% eligible individuals accessing device) and physical activity equivalent annual cost saving, respectively: conservative (25% uptake, $1000), moderate (50% uptake, $2500), and high-impact (75% uptake, $5000). Return on investment (ROI) was calculated for the moderate scenario as the ratio of annual savings to implementation cost. Results. Under the assumptions of the moderate scenario, projected ROI remained positive across all states, ranging from approximately 1.5× in Florida to over 114× in Vermont, with 78% of states (18 of 23 states) demonstrating returns greater than 4×. Moderate scenario annual net savings ranged from approximately $10.8 million in Vermont to $437.0 million in California, with substantial projected savings also observed in Florida ($235.5 million), New York ($225.2 million), and Virginia ($143.8 million). PMPM cost increases for 70% of states range between $0.03 and $0.43, with all modeled states remaining below $1.46. Discussion. In our healthcare system dominated by high-cost and reactive care, the ROI obtained by this cost-consequence analysis (CCA) using evidence-based assumptions supports orthotic and prosthetic coverage clarification as preventive interventions to restore function. Full article

Aiming at the problems of the severe active–reactive power coupling, insufficient adaptive inertia–damping regulation, and degraded dynamic performance of virtual synchronous generators (VSGs) under the operating conditions of a weak grid, high resistance-to-reactance ratio, and large power angle, this paper proposes a cooperative control strategy that combines reactive power feedforward decoupling with adaptive damping–inertia regulation. First, a small-signal power model of the VSG is established, and a dynamic relative gain array is employed to quantitatively analyze the effects of the resistance-to-reactance ratio and power angle on power coupling characteristics, revealing that large power angles and high resistance-to-reactance ratios significantly aggravate active–reactive power coupling. Based on this analysis, a reactive-power-oriented feedforward decoupling strategy is designed to suppress the cross-coupling between reactive power and power angle while preserving the intrinsic inertia support characteristics of the active power loop. Eigenvalue migration analysis further demonstrates that the proposed reactive-power-oriented decoupling provides higher damping ratios and larger stability margins than conventional full active–reactive power decoupling. Furthermore, a deep deterministic policy gradient-based adaptive damping–inertia control method is developed by incorporating frequency deviation, power fluctuation, voltage deviation, and coupling degree into the state space, enabling the online coordinated optimization of virtual inertia and damping coefficients. The hardware-in-the-loop experimental results verify that the proposed strategy effectively suppresses active–reactive power coupling, reduces power overshoot and oscillation, enhances frequency support capability and dynamic response speed, and maintains superior stability under weak grid conditions. Sensitivity analysis under grid impedance estimation errors further confirms its strong robustness against parameter uncertainty, while tests under composite disturbance scenarios demonstrate excellent transient performance. The proposed strategy provides an effective solution for improving the grid-connected operation performance and adaptability of VSGs in low-inertia power systems. Full article

Background/Objectives: Evidence on spinal versus general anesthesia in unilateral total knee arthroplasty (TKA) may not extend to one-week-staged bilateral surgery, where older patients receive two anesthetics in a short interval and intra-operative spinal-to-general conversion is common but rarely reported transparently. We compared peri-operative acute kidney injury (AKI) and transfusion between strategies in this setting. Methods: We retrospectively analyzed 207 patients (414 surgeries) undergoing one-week-staged bilateral primary TKA at one center. Co-primary endpoints were creatinine-based AKI (patient level) and packed-red-blood-cell transfusion (surgery level). Because 42 general-anesthesia-classified surgeries had an attempted spinal injection, the primary analysis used the initial anesthetic plan (an intention-to-treat analogue), reclassifying these as spinal, with as-treated classification as a sensitivity analysis; AKI was modeled at the patient level (any general anesthesia versus spinal–spinal) and transfusion per surgery. Results: Median age was 75 years and 82.6% were female; AKI affected 74 of 207 patients (35.7%) and transfusion 185 of 414 surgeries (44.7%). The adjusted any-general-anesthesia versus spinal–spinal estimate was not statistically significant and opposite the spinal-protective hypothesis (adjusted odds ratio 0.49, 95% confidence interval 0.23–1.01, p = 0.054), and no pre-specified sensitivity scenario survived Benjamini–Hochberg correction. Transfusion did not differ between strategies; among secondary endpoints, length of stay, hemoglobin drop, peak C-reactive protein, and intra-operative hypotension likewise showed no significant difference after multiplicity correction. Conclusions: These hypothesis-generating findings do not support changing anesthetic practice; the choice should remain individualized. Approximately 12% of attempted spinal anesthetics converted intra-operatively to general anesthesia—a record-based observation, not a validated failure rate. Full article

p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF−. Clinical, anthropometric, and biochemical data were collected. Whole-blood TP53 and SIRT-1 mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of TP53 (0.0352 vs. 0.0253; p < 0.001) and miR-34a (0.0215 vs. 0.0099; p < 0.001), but significantly lower expression of SIRT-1 (0.0079 vs. 0.0145; p < 0.001). The level of SIRT-1 expression showed the highest discriminatory performance (exploratory AUC = 0.6987; p < 0.0001). TP53 expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61–5.28, p = 0.0006), whereas the expression levels of SIRT-1 and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of TP53 and SIRT-1 (Rho = 0.3609, p < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated SIRT-1 suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating TP53, SIRT-1, and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed. Full article

Background and Objectives: Cardiometabolic risk factors frequently cluster and substantially increase the risk of cardiovascular disease. While high-density lipoprotein cholesterol (HDL-C) and systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), are independently associated with cardiometabolic risk, whether systemic inflammation modifies the association between HDL-C and cardiometabolic risk clustering (CMRC) remains unclear. This study aimed to examine the independent associations of HDL-C and hs-CRP with CMRC and to evaluate the multiplicative product interaction between HDL-C and natural log-transformed hs-CRP in relation to CMRC among middle-aged adults. Materials and Methods: This cross-sectional study used data from 2283 adults aged 40–64 years who participated in the 2024 Korea National Health and Nutrition Examination Survey. CMRC was defined as the presence of ≥2 cardiometabolic risk factors. HDL-C and hs-CRP were analyzed as continuous variables. Complex sample logistic regression analyses were performed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), including a multiplicative product interaction term calculated as HDL-C × ln hs-CRP. Results: The prevalence of CMRC was 46.4%. HDL-C was inversely associated with CMRC (OR = 0.946, 95% CI = 0.937–0.956, p < 0.001), whereas ln hs-CRP was positively associated with CMRC (OR = 1.224, 95% CI = 1.020–1.468, p = 0.030). The HDL-C × ln hs-CRP product interaction term was significantly associated with CMRC (OR = 1.005, 95% CI = 1.001–1.009, p = 0.008). This finding indicates that the association between HDL-C and CMRC may vary across levels of ln hs-CRP, but it does not indicate a direct association between HDL-C and ln hs-CRP. Conclusions: HDL-C and ln hs-CRP were independently associated with CMRC. The significant HDL-C × ln hs-CRP product interaction term suggests possible statistical effect modification of the HDL-C–CMRC association by systemic inflammatory status. These findings should be interpreted cautiously and do not establish a causal or mechanistic relationship. Full article

Background: Concomitant HIV/HBV infection results in worse health outcomes, with HBV reactivations being observed in immunocompromised individuals. However, data on HBV infection in people with advanced HIV disease (AHD) remains sparse in Botswana. We aimed to determine the prevalence and molecular characteristics of HBV in people living with HIV (PLHIV) with CD4+ T-cell counts ≤100 cells/µL in Botswana. Methods: Plasma samples (n = 1097) of PLHIV with CD4+ T-cell count ≤100 cells/uL collected between 2014 and 2016 were screened for hepatitis B surface antigen (HBsAg) and HBV core antibodies (anti-HBc). A 415bp region of the HBV surface gene was amplified and sequenced using Sanger sequencing. Genotypic and mutational analysis was performed using Geno2pheno. Adjusted prevalence ratios (aPRs) were estimated from a modified Poisson regression model to explore factors associated with HBV infection. p-values < 0.05 indicated statistical significance. Results: The median age was 37 years (IQR: 32–43), and 565/1097 (51.5%) were male. HBsAg prevalence was 10.6% (95%CI: 8.8–12.5%) and anti-HBc prevalence was 50.0% (95%CI:46.9–52.9%). Factors associated with HBV infection were male sex [aPR: 1.6 (p < 0.01)] and those that were ART-experienced [aPR: 1.43 (p = 0.04). Eighteen samples were successfully genotyped. The prevalence of genotype A was (12/18, 66.7%) and D (6/18, 33.3%). Sixty-three mutations were identified as associated with drug resistance and immune and diagnostic escape. Highly prevalent immune escape mutations in the surface region were S207N (12/63, 19%) and A194V (9/63, 14.3%). V163I (12/63, 19%) and M129L (12/63, 19%) were highly prevalent in the reverse transcriptase region. Two classical lamivudine-associated drug resistance mutations were observed, each occurring in one participant (L180M and V173L). Conclusions: The prevalence of HBV in people with AHD is high, highlighting the importance of HBV screening and HIV/HBV co-management in this population. Full article

The glyoxalase pathway detoxifies reactive dicarbonyls generated during hyperglycemia, but the role of its epigenetic regulation in renal dysfunction and inflammatory dysregulation in older adults remains unclear. We investigated CpG-specific DNA methylation within the glyoxal detoxification pathway, focusing on the GLO1 gene, and examined associations with glycemic status, renal function, and systemic inflammation in hospitalized older adults. We identified a single CpG site within the GLO1 gene (cg26053840) significantly associated with fasting glycemia, suggesting that methylation levels at this locus reflects metabolic stress. Higher methylation at cg26053840 was also associated with impaired renal function, including increased serum creatinine and reduced estimated glomerular filtration rate. Additionally, GLO1 methylation correlated with multiple inflammatory indices, including C-reactive protein, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and the CRP-to-albumin ratio. Associations with circulating cytokines and immune activation markers such as IL-6, IL-17A, GDF-15, CXCL9, CD163, and soluble RAGE further indicated broader immune–metabolic dysregulation. In silico analyses revealed a significant inverse correlation between cg26053840 methylation and GLO1 mRNA expression in the Broad Institute GDAC Firehose dataset. Genomic annotation further identified putative CEBPD and MYF6 transcription factor binding sites in proximity to the CpG site, suggesting a potential regulatory context. These findings support a model in which glycemic dysregulation increases methylglyoxal production, while reduced renal clearance enhances dicarbonyl stress, potentially driving epigenetic modulation of GLO1. These findings suggest the presence of a metabolic–epigenetic–inflammatory axis, although longitudinal and mechanistic studies are required to determine whether it contributes to organ dysfunction and vulnerability in hospitalized older adults. Full article

Background: Arterial stiffness is a major predictor of cardiovascular-related mortality in chronic kidney disease (CKD). While acrolein—an endogenous reactive aldehyde that accumulates with declining renal function—may be linked to vascular injury, its association with high peripheral arterial stiffness (HPAS) remains unclear. Methods: This cross-sectional study used the cardio-ankle vascular index (CAVI) to examine the association between serum acrolein levels and HPAS (CAVI ≥ 9.0) in 204 adults with non-dialysis CKD stages 3–5. Results: HPAS was identified in 90 patients (44.1%) and was associated with a higher prevalence of diabetes (p = 0.047), older age (p = 0.023), higher spot urine protein–creatinine ratio (UPCR, p = 0.046), higher serum fasting glucose (p = 0.041), higher interleukin-6 (p = 0.025), and higher acrolein (p = 0.008). In multivariable logistic regression analysis, serum acrolein (odds ratio, 1.015; 95% confidence interval, 1.002–1.028; p = 0.025), age (p = 0.010), and UPCR (p = 0.046) remained independently associated with HPAS. Log-transformed acrolein was positively correlated with bilateral CAVI (all p < 0.001) and log-transformed UPCR (p < 0.001) but negatively correlated with the estimated glomerular filtration rate (p = 0.001). Conclusions: Elevated serum acrolein is independently associated with HPAS in non-dialysis CKD stages 3–5. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF) and can complicate the interpretation of symptoms, biomarker profiles, and clinical deterioration. Its prognostic significance at the time of sodium-glucose cotransporter 2 inhibitor (SGLT2i) initiation remains incompletely defined. We therefore evaluated whether baseline COPD was associated with a greater biomarker burden and worse 12-month outcomes in a real-world HF cohort at the time of SGLT2i initiation. Methods: This prospective single-centre observational cohort included patients with HF enrolled in a tertiary registry between May 2022 and November 2024 in whom SGLT2i therapy was initiated. HF was diagnosed according to contemporary European Society of Cardiology (ESC) criteria on the basis of compatible symptoms and/or signs, objective structural or functional cardiac abnormalities on echocardiography, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). COPD status was defined by a documented pre-existing diagnosis at baseline. The primary endpoint was the 12-month time-to-first composite of all-cause death or unplanned hospitalization for acute decompensated HF. Results: Among 996 patients, 122 (12.2%) had COPD. Compared with patients without COPD, those with COPD more often had a smoking history, a higher comorbidity burden, a worse New York Heart Association (NYHA) class, higher baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels, and a lower estimated glomerular filtration rate (eGFR), whereas baseline HF pharmacotherapy was broadly similar. NT-proBNP remained higher at 6 and 12 months, whereas CRP remained higher at 6 months but not at 12 months. In multivariable Cox analysis adjusting for age, sex, major comorbidities, left ventricular ejection fraction (LVEF), renal function, high-density lipoprotein cholesterol (HDL-C), glycated haemoglobin (HbA1c), CRP, and log NT-proBNP, COPD remained independently associated with the primary endpoint (hazard ratio [HR] 2.610, 95% confidence interval [CI] 1.707–3.991; p < 0.001) and all-cause death (HR 2.097, 95% CI 1.246–3.532; p = 0.005). Conclusions: Among patients with HF starting SGLT2i therapy, baseline COPD identified a higher-risk cardiopulmonary phenotype characterized by a greater comorbidity burden, higher inflammatory and natriuretic biomarker levels, and worse 1-year outcomes. These observational findings support closer integrated cardiology–pulmonology follow-up. Full article

Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, demonstrates robust efficacy in glycemic control and weight reduction. However, substantial interindividual variability in treatment response is observed in clinical practice. In this narrative review, we summarize current evidence on clinical, genetic, and molecular predictors of tirzepatide response and discuss their implications for a precision medicine framework. Data from pivotal clinical trials, post hoc analyses, and relevant preclinical and clinical studies were evaluated to identify determinants of glycemic and weight loss responses, as well as hepatic and renal protective effects. Key clinical predictors include tirzepatide dose, duration of diabetes, β-cell function, baseline glycated hemoglobin, sex, age, race, concomitant therapies, and early treatment response. Genetic factors implicated in treatment variability include variants in GLP-1 receptor, GIP receptor, β-arrestin 1, transcription factor 7-like 2, fat mass and obesity-associated protein, and melanocortin 4 receptor, although tirzepatide-specific validation remains limited. Molecular biomarkers such as branched-chain amino acids, insulin-like growth factor–binding protein-1 and -2, the adiponectin-to-leptin ratio, high-sensitivity C-reactive protein, and interleukin-6 show potential as pharmacodynamic indicators of metabolic response. For organ-specific outcomes, procollagen type III N-terminal peptide and magnetic resonance imaging–proton density fat fraction are supported for assessing hepatoprotective effects, while cystatin C–based estimated glomerular filtration rate and urine albumin-to-creatinine ratio are validated markers of renoprotection. Additional candidates—including tumor necrosis factor receptor 1/2, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin—are promising but require prospective validation. Overall, predicting response to tirzepatide’s multifaceted therapeutic effects necessitates an integrated, multidimensional approach that incorporates clinical characteristics, genetic variation, and molecular profiling. Ongoing validation and harmonization of these predictors may help establish a precision medicine framework for optimizing tirzepatide therapy. Full article

Objective: Peripheral arterial occlusive disease (PAOD) is characterized by impaired tissue perfusion, chronic ischemia, and increased platelet reactivity. Hyperbaric oxygen therapy (HBOT) is used as adjunctive treatment in advanced PAOD, but its effect on platelet function remains insufficiently studied. This study examined the association between HBOT and platelet aggregation. Methods: This prospective observational study included 90 patients with Fontaine stage IV PAOD and chronic ulceration, assigned to an HBOT group (n = 60) or waiting-list control group (n = 30). Patients were predominantly male; mean age was 66.82 ± 9.42 years in the study group and 63.00 ± 8.31 years in controls, and diabetes mellitus was present in 55.0% and 63.3%, respectively. Prior revascularization included open surgery in 33.3% and 30.0%, endovascular treatment in 36.7% and 43.3%, and no option for revascularization in 30.0% and 26.7%, respectively. HBOT was administered over 4 weeks (20 sessions, 2.0–2.5 ATA). Platelet aggregation was measured by impedance aggregometry using arachidonic-acid-induced aggregation (ASPI), adenosine-diphosphate-induced aggregation (ADP), and thrombin-receptor-activating peptide-induced aggregation (TRAP) agonists. Changes were analyzed using generalized estimating equation models adjusted for antiplatelet therapy, diabetes mellitus, smoking, and C-reactive protein (CRP). Results: Significant group × time interactions were observed for all platelet activation pathways, indicating greater reductions in the HBOT group than controls: ASPI (β = −290.5; p < 0.001), ADP (β = −243.6; p < 0.001), and TRAP (β = −330.9; p < 0.001). No significant change was observed in controls. HBOT was associated with reduced pain intensity, while CRP and platelet-to-lymphocyte ratio (PLR) remained stable. Ulcer size showed no significant change after 4 weeks. Conclusions: In patients with PAOD, HBOT was associated with reduced platelet reactivity independent of antiplatelet therapy. Further randomized studies are needed to determine its clinical significance. Full article

Objective: To analyze the relationship between weekly accumulated external load and pre-match neuromuscular performance assessed through the countermovement jump (CMJ), in under-21 (U21) football players across 10 competitive microcycles. Methods: Sixteen U21 football players (age: 18.9 ± 0.42 years; height: 180 ± 6.3 cm; body mass: 78.5 ± 8.5 kg) from a Chilean professional club were monitored over 10 consecutive weeks. In each microcycle, the relationship between changes in neuromuscular performance estimated from CMJ-derived variables and two components of external load was analyzed: (1) weekly accumulated external load and (2) the acute–chronic workload ratio (ACWR). External load variables included total distance (TD), high-speed running distance (HSR), accelerations (ACC), decelerations (DC), and PlayerLoad (PL). CMJ variables included jump height (JH), modified reactive strength index (RSI-mod), and peak eccentric velocity (PEV). Performance changes were calculated as the percentage change (Δ%) between MD + 2 (start of the microcycle) and MD − 1 (pre-match). Pearson or Spearman correlation coefficients were applied depending on data distribution. Results: Significant negative associations were observed between weekly accumulated external load and changes in CMJ performance. Reductions in JH were associated with TD, HSR, ACC, and PL. Similar patterns were found for RSI-mod, while PEV showed a particularly strong association with ACC. Additionally, ACWR demonstrated significant negative relationships with CMJ changes, especially for HSR, ACC, and PL. Conclusions: Higher weekly accumulated external loads and elevated ACWR, particularly in high-intensity metrics such as high-speed running and accelerations, are associated with impaired pre-match neuromuscular performance. Consequently, monitoring CMJ-derived variables alongside external load data is recommended to manage fatigue and optimize match readiness in young football players. Full article

Background/Objectives: Herpes zoster is caused by varicella-zoster virus reactivation, which often leads to a chronic pain condition named postherpetic neuralgia (PHN). Patients with immunosuppressive conditions face a heightened risk of developing PHN. This study aims to identify factors contributing to PHN development in immunosuppressive patients. Methods: This retrospective cohort study was conducted involving 219 immunosuppressive patients from two centers and split into training and test cohorts. Participants were divided into PHN (n = 88) and acute phase pain (ACP, n = 131) groups. Univariate and multivariate logistic regression analyses were used to identify clinical predictors of PHN. A nomogram was constructed to predict PHN risk by integrating significant predictors. The discrimination, calibration and clinical usefulness of the nomogram were evaluated. Results: Multivariate analysis revealed metabolic syndrome, older age, higher lactate dehydrogenase (LDH), and higher neutrophil-to-lymphocyte ratio (NLR) as significant PHN predictors. The nomogram showed good discrimination in both training (AUC of 0.83 [95% CI 0.77–0.90] with a specificity of 0.78, sensitivity of 0.87, NPV of 0.90, and PPV of 0.73) and test cohorts (AUC of 0.85 [95% CI 0.75–0.96] with a specificity of 0.82, sensitivity of 0.85, NPV of 0.89, and PPV of 0.76). Clinical decision curve analysis confirmed the practical utility of the nomogram. Conclusions: The nomogram incorporating age, metabolic syndrome, LDH, and NLR are useful in estimating PHN risk among immunosuppressed patients. Full article

Obesity is characterized by low-grade systemic inflammation and alterations in gut-related immune pathways that may contribute to metabolic dysfunction. Composite biomarker indices may better capture these complex processes than individual markers, although their performance may differ across biological domains. In this cross-sectional study, 88 adults without diabetes or infection were categorized as BMI < 25 kg/m² (n = 20), BMI 25–29.9 kg/m² (n = 34), or BMI ≥ 30 kg/m² (n = 34). Circulating biomarkers reflecting systemic inflammation (high-sensitivity C-reactive protein, ferritin, interleukin-6, presepsin) and intestinal barrier-related activity (β-defensin-2, regenerating islet-derived protein 3 alpha) were measured and subsequently combined into two composite indices: the Inflammatory Load Index, derived from inflammatory markers, and the Barrier Activation Index, derived from barrier-related markers. Group differences were assessed using analysis of variance with post hoc testing. Additional analyses included effect size estimation, receiver operating characteristic (ROC) analysis, and logistic regression. Individual biomarkers showed limited differences across BMI categories. The Inflammatory Load Index differed significantly across BMI categories (p = 0.040), with higher values observed in individuals with BMI ≥ 30 kg/m² compared with those with BMI 25–29.9 kg/m² (p = 0.032; Cohen’s d = 0.80), while the Barrier Activation Index did not differ (p = 0.257). In ROC analysis, the Inflammatory Load Index discriminated BMI ≥ 30 kg/m² with an area under the curve of 0.720 (95% confidence interval 0.576–0.851), yielding 77.8% sensitivity and 67.7% specificity. Each one standard deviation increase in the index was associated with higher odds of obesity (odds ratio 2.34, 95% confidence interval 1.22–4.49; p = 0.011). In conclusion, a composite inflammatory biomarker index, but not a barrier-related index, differentiates degrees of BMI in individuals without diabetes. These findings support integrated biomarker approaches for reflecting obesity-related biological burden beyond single markers. However, these observations are based on cross-sectional data and do not imply causality. Full article