Search Results (2,578)

Background/Objectives:Helicobacter pylori infection is traditionally associated with gastrointestinal diseases; however, increasing evidence suggests that it may have systemic effects involving inflammatory, metabolic, and hematological pathways. Despite this, integrated evaluations of these domains remain limited, particularly in Middle Eastern populations. This study aimed to assess the impact of H. pylori infection on inflammatory, metabolic, and hematological parameters among adults. Methods: A case–control study was conducted including 100 participants (50 H. pylori-positive patients and 50 healthy controls) recruited from Qassim Health Cluster, Saudi Arabia. Demographic and clinical data were collected, and blood samples were analyzed for random blood sugar (RBS), glycated hemoglobin (HbA1c), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, ferritin, and white blood cell count (WBC). Statistical analyses included group comparisons, Spearman correlation, logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: The infected group showed significantly higher levels of RBS and HbA1c, indicating impaired glycemic control. Inflammatory markers (CRP and ESR) were also significantly elevated compared to controls (p < 0.001). Hemoglobin and ferritin levels were significantly lower in the infected group (p < 0.001), suggesting disturbed iron metabolism. Correlation analysis revealed positive associations between inflammatory markers and glycemic indices, and negative associations with hemoglobin and ferritin. Multivariable logistic regression identified CRP (adjusted OR = 1.33, 95% CI: 1.04–1.71) and ESR (adjusted OR = 1.09, 95% CI: 1.02–1.16) as independent predictors of H. pylori infection after adjustment for smoking status and fast-food consumption. The combined model demonstrated acceptable discriminatory performance with an AUC of 0.82 (95% CI: 0.74–0.90). Conclusions:Helicobacter pylori infection was associated with significant inflammatory, metabolic, and hematological alterations, supporting its potential role as a systemic condition beyond the gastrointestinal tract. These associations remained significant after adjustment for major lifestyle-related confounders, including smoking status and fast-food consumption. Although the combined inflammatory model demonstrated acceptable discriminatory performance, it should currently be considered mainly for research or preliminary screening purposes and not as a replacement for established diagnostic methods for active H. pylori infection. Further large-scale longitudinal and interventional studies are warranted to clarify causality and evaluate the impact of eradication therapy on systemic outcomes. Full article

Background and Objectives: C-reactive protein (CRP), a marker of systemic inflammation, is frequently elevated in individuals with excessive adiposity. However, the relationship between specific body fat parameters and CRP levels across sexes and age groups remains unclear. This study aimed to investigate the association between CRP levels and body fat parameters using data from the 2022 Korea National Health and Nutrition Examination Survey. Methods: A total of 3369 participants (representing 32,635,626 Korean adults) were included. Demographic, lifestyle, and clinical data were collected, and body composition parameters were measured using bioelectrical impedance analysis. The primary exposure variables included fat mass index (FMI; total body fat mass/height²) and trunk fat mass. The primary outcome was log-transformed high-sensitivity CRP (ln[hsCRP]). Pearson correlation and sex-stratified multivariate linear regression analyses were performed. Results: The mean age of participants was 49.6 years, and 53.3% were male. ln[hsCRP] was positively associated with body mass index, waist circumference, total body fat mass, FMI, appendicular fat mass, and trunk fat mass in both sexes (all p < 0.001). FMI showed a stronger association with ln[hsCRP] in females (r = 0.373) than in males (r = 0.232). In multivariable analyses, FMI remained independently associated with ln[hsCRP] in both males (β = 0.10) and females (β = 0.14), with a stronger effect observed in females. Trunk fat mass was also independently associated with ln[hsCRP] (β = 0.06 in males; β = 0.10 in females). Age-stratified analyses demonstrated that these associations were more pronounced in younger adults (19–40 years old) than in those aged 41–70 years. Conclusions: In Korean adults, total and truncal fat masses were independently associated with systemic inflammation, and this association was stronger among females and younger adults. Full article

Background/Objectives: Whether habitual dietary omega-3 fatty acid intake is reflected in circulating biomarkers of atrial fibrillation (AF)-related pathways is unclear. We assessed whether usual dietary intake of n-3 fatty acids—considered as total, marine-derived, or non-marine-derived—was associated with the trajectories of five serum markers that reflect AF-related mechanistic pathways [N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (CRP), the C-terminal propeptide of type-I procollagen (PICP), and 3-nitrotyrosine (3-NT)] over 5 years of follow-up. Methods: In 510 participants of the PREDIMED-Plus trial (older Spanish adults with metabolic syndrome), we measured plasma NT-pro-BNP, hs-TnT, CRP, PICP, and 3-NT at baseline and after 3 and 5 years. Energy-adjusted omega-3 intake was assessed with a validated 143-item food-frequency questionnaire. Cross-sectional and 5-year longitudinal associations according to tertiles of omega-3 fatty acid intake were estimated with linear regression and mixed-effects models. Results: Median total omega-3 intake was 2.0 g/day. Total omega-3 intake was not associated with any biomarker, neither cross-sectionally nor longitudinally. Marine omega-3 was directly associated cross-sectionally with 3-NT (highest vs. lowest tertile +28.4%, 95% CI 5.5 to 56.2; p-trend = 0.014) but not longitudinally. Moderate baseline non-marine omega-3 fatty acid intake was associated with a decrease in PICP after 5 years of follow-up. Conclusions: Overall, habitual total omega-3 fatty acid intake was not associated with circulating AF-related pathways. The sporadic association between marine omega-3 fatty acid intake and 3-NT in the cross-sectional assessment and the isolated non-linear association between baseline non-marine omega-3 fatty acid intake and PICP after 5 years warrant further investigation. Full article

Background/Objectives: This retrospective study aimed to evaluate the radiologic outcomes and changes in biochemical inflammatory markers following posterior lumbar interbody fusion (PLIF) with Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E.BMP-2), compared with conventional autologous bone grafting. Methods: The study included 112 patients undergoing single- or two-level PLIF for degenerative lumbar disease between 2022 and 2023, divided into E.BMP-2 (n = 50) and Control (n = 62) groups. Radiological outcomes, including Bridwell grading system and adjacent vertebral body (VB) changes, and changes in biochemical inflammatory markers—white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil count—were assessed. Clinical outcomes were also evaluated. Multivariate regression and propensity-score-matched analyses, and linear mixed-effects models were applied. Results: Fusion rates were comparable between the groups (90.8% vs. 96.7%; p = 0.466); adjusted analyses showed no independent association between E.BMP-2 use and fusion outcomes. The E.BMP-2 group demonstrated a higher prevalence of adjacent VB changes (78.5% vs. 54.3%; p = 0.001), and higher postoperative inflammatory markers including CRP levels on postoperative day 7 and at 1 month, along with increased neutrophil levels on postoperative day 4 (CRP day 7: 31.7 ± 26.4 mg/L vs. 18.7 ± 14.4 mg/L, p = 0.014; CRP 1 month: 7.2 ± 13.0 mg/L vs. 2.7 ± 3.8 mg/L, p = 0.022; neutrophil count day 4: 64.4 ± 10.6% vs. 60.6 ± 8.7%, p = 0.039). However, no significant differences in clinical outcomes, as assessed by VAS scores, were observed according to adjacent VB changes or inflammatory markers. Postoperative fever and infection rates were similar between groups. Conclusions: E.BMP-2 use in PLIF demonstrated fusion rates comparable to those of autografts, without demonstrated superiority. No significant differences in clinical outcomes were identified. Further large-scale prospective studies are needed to clarify its clinical role and optimal dosing. Full article

C-reactive protein (CRP) is one of the most essential biomarkers for the early detection of inflammation and infection. In this study, we developed a sensitive and selective electrochemical immunosensor for CRP detection, leveraging the unique properties of gold nanoparticles (AuNPs). A nanostructured layer of AuNPs was deposited onto a screen-printed carbon electrode (SPCE), followed by the formation of a self-assembled monolayer (SAM) of L-cysteine and EDC/sulfo-NHS chemistry. The antibody was covalently immobilized onto the modified electrode through optimized dual-crosslinking chemistry. Detection conditions were systematically optimized, with pH 8.0 in Tris buffer providing the best electrochemical response. Electrochemical characterization was performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) in a 5 mM K₃[Fe(CN)₆]/K₄[Fe(CN)₆] redox probe solution containing 0.1 M KCl. CRP detection was achieved by monitoring the increase in charge transfer resistance (Rct) upon specific binding of the target CRP antigen to the immobilized antibody. Spiked recovery experiments showed spiked recovery rates ranging from 98.01% to 107.14%, with a standard deviation below 4%. Regeneration studies demonstrated high efficiency, confirming the suitability of the sensor interface for repeated and reliable measurements. Under optimized conditions, the immunosensor exhibited excellent analytical performance, including a low limit of detection (LOD) of 0.16 µg/mL, a wide linear detection range of 5–100 µg/mL, high selectivity against 13 potential interferents (including inflammatory cytokines), and good reproducibility with a relative standard deviation (RSD) of 3.69%. The sensor also showed strong stability, retaining more than 95% of its signal after 15 days, and high regeneration efficiency of 97% over seven cycles. These results highlight the strong potential of the proposed immunosensor for point-of-care (POC) applications due to its simple fabrication, cost-effectiveness, user accessibility, and robust analytical performance. Full article

Objective: This study aimed to evaluate the prognostic value of inflammatory biomarkers and their interaction with nutritional status for risk stratification in patients with chronic limb-threatening ischemia (CTLI). Material and Methods: This was a prospective, single-center observational cohort study including adult patients admitted with CTLI. Clinical outcomes included major amputation, major vascular events (MACE), and all-cause mortality. Multivariate logistic regression analyses were performed using two separate models, one including IL-6 and another including hsCRP, to avoid potential collinearity between biomarkers. Model discrimination was assessed using ROC curves, and Kaplan–Meier survival analyses were performed. Results: A total of 170 patients were included (mean age 72 ± 12 years; 74% male), with high cardiovascular risk and frequent malnutrition and sarcopenia. At 6 months, major amputations occurred in 35.3% of patients, MACE in 35%, and all-cause mortality in 32%. In multivariable analyses, malnutrition was the strongest independent predictor of the composite endpoint. IL-6 (OR 2.90, 95% CI 1.45–5.81; p = 0.003) and hsCRP values above the median (OR 4.22, 95% CI 2.04–8.72; p < 0.001) remained independently associated with adverse outcomes, together with age > 72 years. The hsCRP-based model showed slightly higher discriminative performance than the IL-6 model (AUC = 0.77 VS AUC = 0.75). Kaplan–Meier analyses demonstrated significantly reduced event-free survival in patients with elevated inflammatory biomarkers. Conclusions: In CTLI, systemic inflammation and nutritional status jointly identify patients at extremely high risk of adverse outcomes. hsCRP, given its availability, may be a practical tool for clinical risk stratification. Full article

Objectives: We aimed to assess fractional exhaled nitric oxide (FeNO) and spirometry in pediatric patients with inflammatory bowel disease (IBD) and relate these parameters to disease activity, duration, and current treatment. Methods: This prospective case–control study included 161 subjects: children with newly diagnosed, active IBD (N = 55), children in clinical remission (N = 53), and healthy controls (N = 53). FeNO was measured using a chemiluminescent analyzer, and pulmonary function was assessed by spirometry. Results: FeNO was higher in patients with IBD than in controls (p = 0.025) and positively correlated with CRP (ρ = 0.22; p = 0.027). Respiratory function measured by spirometry in children with IBD was preserved. No association was found between respiratory parameters, disease activity, and duration. The correlation between FeNO and aminosalicylate treatment was of borderline significance (ρ = 0.28; p = 0.052). Conclusions: Children with IBD, although having normal pulmonary function measured by spirometry, do have increased FeNO, which is positively correlated with CRP. FeNO reflects systemic inflammation, but its role as a clinical marker of disease activity or relapse remains uncertain. Full article

Background: There is a positive relationship between mitochondrial damage in the cell and uptake in technetium Tc 99m monomer methoxy isobutyl isonitrile (^99mTc-MIBI) scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers (DFUs). To decide on the level of amputation, ^99mTc-MIBI scintigraphy should be considered. Methods: Prospectively, 24 patients with DFUs were included in the study. Based on treatment that started with the hospitalization, patients were divided into two groups: those whose DFUs healed and did not need surgical intervention (healed group) and those whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention (reoperation group). Before surgery, ^99mTc-MIBI scintigraphy was performed. The ^99mTc-MIBI uptake rates of the injured foot relative to the healthy foot were recorded. Deep-tissue culture was taken at surgery. Erythrocyte sedimentation rate, white blood cell count, and C-reactive protein (CRP) and albumin levels were measured. Results: The ^99mTc-MIBI uptake rates of patients with poor prognosis were higher at all times than those of patients who did not require revision surgery. A significant difference was found between these values in the 10 and 30 s rates. The mean ± SD CRP level was 86.04 ± 21.87 mg/dL in the healed group and 144.43 ± 27.54 mg/dL in the reoperation group (p = 0.040). There was a positive correlation between ulcerated foot and healthy foot ^99mTc-MIBI involvement rates at 10 and 30 s and CRP values, and a negative correlation between albumin values. Conclusions: There was a significant relationship between ^99mTc-MIBI involvement rates and poor prognosis and reamputation. The correlation between CRP and albumin levels, which are among the predictive values, and ^99mTc-MIBI uptake confirmed this relationship in DFUs, which are difficult to manage and treat. Full article

Background: Persistent histologic inflammation may remain present in patients with inflammatory bowel disease (IBD) despite endoscopic remission. This study evaluated a clinically interpretable cytokine-based framework for risk stratification of residual histologic activity. Methods: In this prospective cohort study, 59 patients with IBD undergoing colonoscopy were included. Primary analyses were restricted to patients with ulcerative colitis (UC) in endoscopic remission (n = 31). Histologic activity was assessed using the Geboes score. Serum interleukin-10 (IL-10), interleukin-23 (IL-23), and C-reactive protein (CRP) were measured prior to endoscopy. Receiver operating characteristic (ROC) analysis and ROC-derived thresholds were used to evaluate biomarker performance and construct a cytokine-based risk stratification framework. Results: Among patients with UC in endoscopic remission, 14/31 (45.2%) demonstrated persistent histologic activity. IL-10 showed the strongest discriminatory performance for histologic activity (AUC 0.850), with a threshold < 3.9 pg/mL associated with sensitivity of 84.6% and specificity of 77.8%. Similar performance was observed using raw assay-reported IL-10 values (AUC 0.906). IL-23 showed limited overall discrimination (AUC 0.615). A combined IL-10/IL-23 framework stratified patients into progressively higher-risk subgroups, with histologic activity observed in 1/14 patients (7.1%) in the low-risk subgroup, 1/2 patients (50.0%) in the Intermediate A subgroup, 9/12 patients (75.0%) in the Intermediate B subgroup, and 3/3 patients (100%) in the high-risk subgroup (p < 0.001), although estimates for smaller subgroups should be interpreted cautiously. Reduced IL-10 levels were independently associated with histologic activity, whereas IL-23 primarily refined subgroup classification without substantially improving discrimination. Conclusions: An exploratory cytokine-based framework incorporating IL-10 and IL-23 may support risk stratification of residual histologic activity in UC during endoscopic remission. Larger multicenter studies are required to validate these findings and define their clinical utility. Full article

Aims: Coronary heart disease (CHD) associated with rheumatoid arthritis (RA) is a primary driver of mortality in RA patients. In this study, we sought to establish a combined rat model of CHD and RA by integrating cardiac ischemia/reperfusion (I/R), high-fat diet (HFD), and intradermal administration of bovine type II collagen emulsified in complete Freund’s adjuvant. The aim of constructing this model is to investigate and analyze the pathogenesis of RA-induced CHD under the modulation of HFD and cardiac I/R exposure. Methods and Results: Sixty-four male Sprague–Dawley rats were randomly categorized into eight groups (n = 8 per group): control, I/R, HFD, collagen-induced arthritis (CIA), I/R + CIA, HFD + CIA, I/R + HFD, and I/R + HFD + CIA groups (n = 8 per group). We applied Synchrotron radiation-based X-ray micro-computed tomography (micro-CT) to observe the structural changes within the model over time. To further elucidate molecular mechanisms, transcriptome RNA-seq analysis was carried out to identify key signaling pathways, with particular emphasis on the homeostasis of Toll-like receptor 4 (TLR4)/Myd88 signaling in the ischemic myocardium. Furthermore, we conducted in vivo shRNA-mediated knockdown of polymerase I and transcription release factor (PTRF) and evaluated the co-localization of PTRF and TLR4 through immunofluorescence experiments. It is worth mentioning that our rat model of RA-induced (CHD) under a high-fat diet effectively manifested the relevant pathological features that align with the Traditional Chinese Medicine (TCM) definition of “bi” syndrome. The results indicate that the combined stimulation of HFD and CIA significantly elevated cardiac injury markers (CK-MB, LDH, CRP, and c-TNT) and was accompanied by a more severe expansion of the infarct area and increased cardiomyocyte apoptosis compared to the I/R group alone. In addition, the histopathological evaluation revealed significantly aggravated myocardial inflammation and fibrosis deposition, accompanied by extensive areas of tissue damage, further indicating a state of heightened inflammation and severe cardiac degenerative changes. Consistently, myocardial tissues from rats in the I/R + CIA + HFD group exhibited robust activation of the TLR4/MyD88 signaling pathway and a pronounced elevation in the p-JNK/JNK ratio. Moreover, pronounced co-localization between PTRF and TLR4 was evident in small vessels surrounding the infarcted myocardium. Importantly, AAV-mediated knockdown of PTRF attenuated the HFD- and CIA-induced exacerbation of myocardial injury in I/R rats. Conclusions: We successfully established a rat model of CHD with rheumatic syndrome using I/R in combination with RA and HFD. The present findings suggest that the PTRF-related TLR4/MyD88-JNK signaling pathway may act as an important regulatory mechanism underlying myocardial injury aggravated by combined HFD and CIA stimulation. Full article

Background/Objectives: Vaginal cuff hematoma is a recognized complication following hysterectomy, with a subset of patients requiring invasive intervention. No reliable bedside biomarker currently exists to identify at admission patients likely to fail conservative management. This study aimed to evaluate the incidence and clinical characteristics of symptomatic vaginal cuff hematoma across all hysterectomy approaches, and to assess the predictive performance of the CALLY index (CRP-albumin-lymphocyte index), a composite marker of inflammatory burden, immune function, and nutritional status, alongside the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) for identifying patients requiring interventional management. Methods: This retrospective cohort study included 61 patients with symptomatic vaginal cuff hematoma following hysterectomy in a major tertiary referral center (November 2022–July 2025). Patients were divided into conservative (n = 38) and interventional (n = 23) management groups. The CALLY index was calculated as [Albumin (g/dL) × Lymphocyte (×10⁹/L)] ÷ [CRP (mg/L) × 10⁻²]. Receiver operating characteristic (ROC) curve analysis with the DeLong method was used to compare predictive performance. Results: The overall incidence of symptomatic vaginal cuff hematoma was 1.9% (73/3852 hysterectomies), with the highest rate following vaginal hysterectomy (3.32%) and the lowest after robotic hysterectomy (0.74%). Interventional management was required in 37.7% of patients. The interventional group had significantly higher CRP (192 vs. 62 mg/L, p < 0.001), NLR (7.53 vs. 4.17, p < 0.001), and SII (2308 vs. 1207, p < 0.001), and significantly lower CALLY index values (2.00 vs. 9.80, p < 0.001). The CALLY index demonstrated the highest predictive performance (AUC = 0.863, 95% CI: 0.762–0.964), outperforming SII (AUC = 0.801), NLR (AUC = 0.789), and PLR (AUC = 0.654). At the optimal cutoff of ≤2.89, the CALLY index yielded a sensitivity of 65.2% and a specificity of 92.1%. Conclusions: The CALLY index is a simple, routinely available composite biomarker that may help identify patients at higher risk for interventional management in symptomatic vaginal cuff hematoma. Its incorporation into postoperative assessment may improve risk stratification and support timely clinical decision-making. Full article

Background: Computed tomography-based body composition parameters are emerging prognostic markers in pancreatic cancer. While sarcopenia and myosteatosis have been widely studied, the prognostic significance of ectopic fat deposition within the psoas muscle remains unclear. We aimed to evaluate the prognostic impact of the fat ratio within the psoas muscle (FRPM) in patients with stage IV pancreatic cancer receiving first-line systemic chemotherapy. Methods: This retrospective cohort study included 99 patients with stage IV pancreatic cancer treated with first-line chemotherapy. Baseline CT images at the L3 level were analyzed, and FRPM was calculated as the proportion of intramuscular fat to total psoas muscle area. FRPM was analyzed primarily as a continuous variable. Exploratory low- and high-FRPM groups were defined using sex-specific medians for descriptive comparisons and Kaplan–Meier analyses. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and Cox regression analyses. Multivariable models were adjusted for age, sex, ECOG performance status, liver metastasis, and C-reactive protein (CRP). Results: Among 99 patients, 48 were categorized as having low FRPM and 51 as having high FRPM based on exploratory sex-specific median-based groups. Higher FRPM correlated with older age and higher BMI and inversely correlated with psoas muscle size and PMI. Median OS was 9.76 months in the low-FRPM group versus 5.78 months in the high-FRPM group, and median PFS was 5.29 versus 3.68 months. In the main multivariable Cox model, higher FRPM was associated with worse OS when analyzed as a continuous variable and reported per 1-standard deviation increase (adjusted HR: 1.43, 95% CI: 1.08–1.91, p = 0.014). After additional adjustment for first-line treatment-regimen category, the association remained directionally consistent but did not retain conventional statistical significance (adjusted HR: 1.32, 95% CI: 0.99–1.77, p = 0.060). Conclusions: Higher FRPM was associated with shorter OS and PFS in patients with stage IV pancreatic cancer receiving first-line systemic chemotherapy. These findings suggest that ectopic fat deposition within the psoas muscle may represent a potential CT-based muscle-quality marker associated with adverse prognosis. External validation and comparison with conventional adiposity parameters are required before clinical application. Full article

Aims: The aim of this study was to investigate the associations between symptomatic hearing loss (HL), neuropathy, and nephropathy in subjects with Type 2 diabetes mellitus (T2DM). Furthermore, the study evaluated whether HL was associated with chronic low-grade inflammation, assessed based on plasma levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), and explored potential sex-specific differences. Materials and Methods: We included 4245 subjects with T2DM from The Danish Centre for Strategic Research in Type 2 Diabetes cohort. Symptomatic HL was defined using ICD-10 codes. In 2016, a questionnaire was sent out to evaluate neuropathy using the Michigan Neuropathy Screening Instrument (MNSI ≥ 4). Nephropathy was defined as urinary albumin-to-creatinine ratio (UACR) >30 mg/g. Plasma levels of TNF-α, IL-6, and hsCRP were measured at enrolment from 2010 to 2016. Multivariable logistic regression was used, adjusting for covariates. Results: Neuropathy was significantly associated with HL (OR = 1.83, 95%CI [1.42, 2.35], p < 0.001), and the association was stronger in women (OR = 2.74 [1.81, 4.14], p < 0.001) compared to men (OR = 1.44 [1.04, 1.99], p < 0.05) (P-interaction = 0.020). No significant association was found between nephropathy and HL. Among inflammatory markers, only the highest tertile of TNF-α levels was significantly associated with HL compared to the lowest tertile (OR = 1.40 [1.07, 1.82], p < 0.05) without any sex interaction. Conclusions: In subjects with T2DM, neuropathy was associated with symptomatic HL, and the association seemed to be stronger in females. Among chronic low-grade inflammation markers, only TNF-α was significantly associated with symptomatic HL. Additionally, no significant association was found between nephropathy and HL. Full article

Background: Venous thromboembolism (VTE) is a thromboinflammatory disorder involving coordinated activation of coagulation, endothelial dysfunction, and inflammatory signaling. Low-molecular-weight heparins (LMWHs) may exert pharmacological effects beyond anticoagulation. This study compared enoxaparin, bemiparin, and tinzaparin and explored potential multi-target mechanisms using molecular docking, network pharmacology, and enrichment analyses. Methods: In this retrospective cohort study, patients with acute VTE treated with therapeutic-dose LMWHs were analyzed. Stabilized IPTW based on multinomial propensity scores was used to reduce baseline imbalance between treatment groups. Clinical recovery was assessed using the Clinical Severity Score (CSS). Thromboinflammatory biomarkers (MPV, hs-CRP, NLR, fibrinogen) were evaluated during follow-up. Molecular docking, STRING/Cytoscape-based protein–protein interaction, and enrichment analyses were performed. Results: Median time to symptom resolution was 31 days with enoxaparin, 28 days with bemiparin, and 24 days with tinzaparin (log-rank p < 0.001). Recovery was faster with bemiparin (HR 1.28, 95% CI 1.05–1.56) and tinzaparin (HR 1.72, 95% CI 1.41–2.10). Tinzaparin showed greater reductions in hs-CRP, MPV, NLR, and fibrinogen (all p < 0.05) and less analgesic use beyond 10 days (19.7% vs. 27.0% and 33.2%; p < 0.001). Docking analyses identified plausible conformations (root-mean-square deviation, RMSD ≤ 2 Å). Given the structural flexibility and heterogeneous chain length of LMWHs, rigid docking algorithms may not fully capture biologically relevant conformations. Therefore, docking results should be interpreted as qualitative interaction mapping rather than quantitative binding affinity estimation. Network analysis highlighted F3, TNF, IL6, and VWF, while enrichment analyses suggested involvement of cytokine signaling, leukocyte migration, and thromboinflammatory pathways. Conclusions: LMWH therapy was associated with improved thromboinflammatory markers and clinical recovery, with tinzaparin showing comparatively more favorable thromboinflammatory biomarker trajectories and recovery dynamics within the limitations of this observational analysis. Integrated clinical and in silico findings provide hypothesis-generating insights into potential multi-target pharmacological effects beyond anticoagulation; however, these observations should be interpreted cautiously and require experimental validation. Full article

Background: Major cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response that contributes to postoperative organ dysfunction and hemodynamic instability. While C-reactive protein (CRP) is a well-established downstream marker of postoperative inflammation, the upstream determinants of interindividual variability in inflammatory burden are not fully understood. Platelet-activating factor (PAF) is a potent inflammatory mediator implicated in platelet activation, endothelial dysfunction, and vascular dysregulation, but its role in modulating postoperative inflammation and clinical outcomes after cardiac surgery has not been fully characterized. Methods: We conducted a retrospective observational study of 87 patients undergoing major cardiac surgery with CPB. Preoperative plasma PAF levels and postoperative CRP concentrations were measured, and patients were stratified according to postoperative CRP severity. Associations between PAF, inflammatory response, postoperative vasoactive–inotropic requirements, recovery parameters, acute kidney injury, and mortality were assessed using correlation analyses, multivariable regression models, and receiver operating characteristic curve analyses. Results: Preoperative PAF levels increased progressively across postoperative CRP strata (p < 0.001) and were strongly associated with postoperative CRP concentrations in both univariate and multivariable analyses. Specifically, each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of 36.0 mg/L in postoperative CRP (β = 36.0; p < 0.001). Each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of approximately 36 mg/L in postoperative CRP. Elevated PAF was also associated with increased intermediate postoperative vasoactive–inotropic requirements and a modest increase in hospital length of stay (r = 0.25, p = 0.023). However, neither PAF nor CRP independently predicted AKI or mortality after adjustment for clinical variables. Discriminative performance for mortality was modest for both biomarkers. Conclusions: Preoperative platelet-activating factor was strongly associated with postoperative inflammatory burden and early hemodynamic instability following major cardiac surgery. Although PAF and CRP were not independent predictors of adverse outcomes, they may help identify a biologically vulnerable phenotype characterized by exaggerated inflammatory and vascular responses to surgical stress. These findings support further investigation of platelet-mediated inflammatory pathways as targets for perioperative risk stratification and mechanistic research. Full article