Search Results (2,701)

We characterized long-term, objectively measured physical activity trajectories surrounding total knee arthroplasty (TKA) and total hip arthroplasty (THA) and examined factors associated with wearable-derived physical activity recovery. In this observational study within the All of Us Research Program, linked electronic health records and Fitbit step count data spanning the two years before and the two years after surgery were analyzed using piecewise linear mixed-effects models to characterize preoperative and postoperative trajectories. Recovery of physical activity was defined relative to two preoperative baselines—activity measured immediately before surgery and a more remote baseline approximating longer-term habitual activity—and associated factors were examined using Cox proportional hazards models. Among 238 participants (147 TKA, 91 THA; mean age 64.9 [SD 8.3] years), both procedures showed progressive preoperative decline, with accelerated decline beginning earlier in TKA than in THA. Postoperative recovery followed a staged pattern, with rapid early improvement, slower intermediate gains, and later stabilization. Recovery to the immediate preoperative baseline occurred earlier than recovery to the remote baseline. Higher activity during the 4 weeks before surgery was associated with a greater likelihood of recovery to the remote baseline. These findings support long-term wearable monitoring as a complementary measure of physical activity recovery after arthroplasty. Full article

Interpreting and directing treatment based on comprehensive genomic testing for patients with cancer can be challenging. Molecular tumor boards (MTBs) can help by establishing collaborative frameworks to deliver patient care plans with the appropriate incorporation of genomic data. Our retrospective observational study evaluates the impact of MTB on the outcomes of adult patients diagnosed with advanced-stage cancer. Patients between 1 September 2017 and 1 January 2023 were grouped into those who received at least one treatment recommended by the MTB and those who did not. Hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and time on treatment (ToT) were determined using Kaplan–Meier analysis and multivariate Cox proportional hazards model adjusted for age, stage, line of therapy, and primary site of diagnosis. Of 238 evaluable patients, 138 (58%) received at least one treatment recommended by the MTB. Patient characteristics were well-balanced between the cohorts, except for higher proportions of lung adenocarcinoma, melanoma, and a lower proportion of glioblastoma in the matched cohort. Median OS, PFS, and ToT were all increased in patients on matched treatment compared to those who did not (18.5 months vs. 9.1 months, HR 0.64, 95% confidence interval (CI) 0.43–0.96, p = 0.030); 9.7 months vs. 4.3 months, HR 0.64, 95% CI 0.42–0.97, p = 0.035; and 4.3 months vs. 2.8 months, HR 0.58, 95% CI 0.41–0.83, p = 0.0027, respectively). Our findings show that MTB at a community cancer center is feasible and improves survival among patients with cancer, even after adjusting for confounding variables. Full article

Background: Immunosuppressed women are at increased risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2–3) after excisional treatment, yet long-term comparative data remain limited. Previous studies are often small and heterogeneous, and they rarely compare outcomes directly with immunocompetent populations. This study evaluated the long-term incidence, timing and associated factors of CIN 2–3 recurrence after large loop excision of the transformation zone (LLETZ), stratified by immune status. Methods: We conducted a retrospective cohort study including 283 women treated with LLETZ for CIN 2–3 between 1996 and 2016 at Bellvitge University Hospital in Barcelona, Spain. Of these, 41 were immunosuppressed and 242 immunocompetent. Clinical, histopathological, virological, and immunological variables were extracted from hospital and pathology registries. Kaplan–Meier estimates and Cox proportional hazards models adjusted for immunosuppression status were used to evaluate time-to-recurrence and factors associated with recurrence. Results: At 36 months post-treatment, the probability of residual/recurrent CIN 2–3 was 44% in immunosuppressed women versus 5% in immunocompetent women (HR = 10.42, 95% CI 4.70–23.08, p < 0.001). Recurrence appeared earlier in immunosuppressed women (median 7 vs. 13 months). Persistent high-risk HPV infection at first follow-up (HR = 23.6, 95% CI 5.44–102, p < 0.001) and positive surgical margins (HR = 3.88, 95% CI 1.45–10.3, p = 0.007) were among the factors most strongly associated with recurrence, and advanced immunodeficiency (CD4+ < 200 cells/mm³ or detectable HIV viral load) was associated with earlier recurrences, though this association was not maintained after accounting for immunosuppression status in Cox models. Conclusions: Immunosuppressed women are at significantly higher and earlier risk of residual/recurrent CIN 2–3 after LLETZ. These findings support a risk-adapted, multidisciplinary follow-up integrating gynecologic, infectious disease, and immunologic care. Tailored surveillance and perioperative HPV vaccination may enhance secondary prevention in this high-risk population. Full article

Background: Soft-tissue sarcomas (STSs) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLSs) have been identified as favorable prognostic indicators in several cancer types, yet their role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and density in resected STSs. Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (France) between 1990 and 2020. TLSs were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or -negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Results: The presence of fmTLS was significantly associated with improved 5-year OS (p = 0.012) and cause-specific survival (p = 0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p = 0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28–5.59, p = 0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and a high-immune phenotype (Φ = 0.30, p < 0.001). Conclusions: STSs with fmTLS are associated with improved OS but increased risk of local recurrence. These findings support fmTLS as a dual prognostic biomarker and highlight the need for tailored surveillance and adjuvant strategies in fmTLS⁺ patients. Full article

Background: Previous studies have confirmed an association between sarcopenia and depression but were mostly based on single baseline assessments, ignoring dynamic changes in sarcopenia status. This study aimed to investigate the association between changes in sarcopenia status and incident depression risk. Methods: Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS). Sarcopenia status was classified as non-sarcopenia, possible sarcopenia, or sarcopenia according to AWGS 2019 criteria. Changes in status were defined by comparing assessments at baseline (2011) and two years later (2013). Depression was assessed using the CESD-10 (score ≥10). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Participants who progressed from non-sarcopenia to possible sarcopenia or sarcopenia had a higher risk of depression than those who remained non-sarcopenic (HR 1.30, 95% CI 1.14–1.47). Conversely, participants who recovered from sarcopenia had a lower risk of depression than those with persistently stable sarcopenia (HR 0.65, 95% CI 0.45–0.94). Conclusions: Changes in sarcopenia status are differentially associated with the risk of incident depression. The progression of sarcopenia status is associated with an increased risk of incident depression, whereas recovery from sarcopenia is linked to a reduced risk. Full article

Background/Objectives: Preventing recurrent anaphylaxis is crucial for patient safety. This study aimed to identify predictive factors and develop a prediction model to estimate recurrence risk, thereby enhancing targeted preventive strategies. Methods: This prognostic prediction study used a retrospective observational cohort design, analyzing medical records from an anaphylaxis registry at Naresuan University Hospital, Phitsanulok, Thailand, between March 2011 and February 2021. We developed a prediction model using multivariable Cox proportional hazards regression analysis. Statistically significant and clinically relevant predictors were weighted into a risk score derived from hazard ratio regression coefficients. Model performance was evaluated using the area under the receiver operating characteristic curve (AuROC), calibration metrics, and decision curve analysis. Results: Over the 10-year period, 381 patients experienced 439 anaphylaxis episodes, including 58 recurrences (13.2%). The final model comprised six predictors: history of food, insect, and drug allergies; asthma; chest discomfort; and severe anaphylaxis. Corresponding risk scores were 4, 5, 5.5, 1, 2.5, and 1.5 points, respectively. Total scores ranged from 0 to 19.5 and were categorized into low (<3.0), moderate (3.0–9.0), and high (>9.0) risk groups. The high-risk group had a likelihood ratio positive (LHR+) of 4.65. The model demonstrated acceptable discrimination (AuROC 0.773 (95% CI: 0.714–0.832)) and good calibration. Bootstrap validation showed consistent performance (AuROC 0.773 (95% CI: 0.714–0.831)). Decision curve analysis indicated clinical utility across relevant threshold probabilities. Conclusions: This prediction model provides a simple, clinically applicable tool for estimating the risk of recurrent anaphylaxis and may support improved prevention and management strategies. Full article

Background: Human epidermal growth factor receptor 2 (HER2) alterations have been implicated as mechanisms of resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC). We aimed to evaluate the predictive and prognostic significance of HER2 expression in patients with RAS wild-type mCRC in a real-world setting. Methods: We conducted a multicenter retrospective cohort study across ten oncology centers in Turkey, including patients with RAS wild-type mCRC treated between 2015 and 2022. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between HER2-positive and HER2-negative groups. Multivariable Cox proportional hazards models were used to identify independent predictors of survival outcomes. Results: Among 204 patients, 28 (13.7%) were HER2-positive. Baseline characteristics were generally comparable; however, HER2-positive patients showed a trend toward higher-grade tumors and were significantly less likely to receive anti-EGFR therapy. HER2-positive patients had significantly shorter PFS compared to HER2-negative patients (median 10 vs. 13 months; p = 0.006). In multivariable analysis, HER2 positivity remained an independent predictor of shorter PFS (HR 1.76, 95% CI 1.01–3.07; p = 0.045). In the subgroup of 144 patients receiving anti-EGFR therapy, HER2-positive patients also demonstrated significantly shorter PFS (median 9.0 vs. 14.0 months; p = 0.023). No significant differences in OS were observed between groups. Conclusions: HER2 positivity is associated with reduced response to anti-EGFR therapy and independently predicts shorter PFS in patients with RAS wild-type mCRC. These findings further support the role of HER2 as a clinically relevant biomarker in RAS wild-type mCRC, particularly in predicting response to anti-EGFR therapy, while highlighting the need for optimized patient selection strategies in the era of HER2-targeted treatments. Full article

Background/Objectives: The therapeutic arsenal for axial spondyloarthritis (axSpA) now includes multiple biologic and targeted synthetic DMARDs (b/tsDMARDs). Following the failure of an advanced therapy, clinicians may either cycle (switch to another drug with the same mechanism of action) or swap (switch to a drug with a different mechanism). The optimal strategy remains unclear. This study aimed to compare the real-world effectiveness of cycling versus swapping in axSpA patients. Methods: This mono-centric, retrospective observational study included axSpA patients who failed ≥1 line of b/tsDMARD therapy. Subsequent treatment courses were classified as cycling (CG) or swapping (SG). Drug retention rates were compared using Kaplan–Meier analysis. A Cox proportional hazards model identified factors associated with treatment persistence. Results: We analyzed 156 patients (59 radiographic, 97 non-radiographic), corresponding to 343 treatment courses (CG: 213; SG: 130). Retention rates at 1, 2, and 3 years were 62.7%, 49.3%, and 39.2% (CG) versus 69.8%, 47.8%, and 31.8% (SG) (HR: 1.13, 95% CI: 0.83–1.53; p = 0.442). In the multivariable model, only a more recent prescription year was associated with higher discontinuation risk (HR: 1.08 per year, 95% CI: 1.03–1.12; p < 0.001). Conclusions: In this real-world cohort, cycling and swapping strategies demonstrated comparable treatment persistence over three years following advanced therapy failure in axSpA. The choice of subsequent therapy should be individualized, as no strategy proved superior. Full article

Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article

Introduction: Giant retroperitoneal liposarcomas (GRPLs) are rare tumors that often reach considerable size before diagnosis due to their indolent growth and deep anatomical location. Surgery represents the only potentially curative treatment, yet recurrence rates remain high. While histological subtype is a recognized predictor of recurrence, the prognostic role of tumor size, particularly in giant tumors, remains controversial. This study evaluates the impact of tumor size and histological subtype on recurrence risk in a literature-based retrospective cohort. Materials and Methods: Data were extracted from a literature-based database of GRLPs published between 2004 and 2023. Only tumors >20 cm treated without positive surgical margins were included; patients receiving adjuvant therapy or with missing follow-up were excluded. Histological subtype (well-differentiated vs. other) was the main variable of interest. Recurrence-free survival (RFS) was defined as the primary endpoint and estimated using the Kaplan–Meier method. The association between histological subtype and recurrence risk was evaluated using a Cox proportional hazards model. A sensitivity analysis was performed to explore the potential interaction between tumor size and histological subtype. Results: Our final cohort yielded a total of 81 patients, of whom 47 (58%) had a well-differentiated GRLPs. The median tumor size was 38 cm and median follow-up was 16 months, with 24 recurrences observed. At 24 months, RFS was higher in well-differentiated tumors than in other histological subtypes (81% vs. 41%). In multivariable Cox analysis, histology was independently associated with recurrence risk (HR 3.2, 95% CI 1.28–8.17, p = 0.01), whereas tumor size showed no association with recurrence. Interaction analysis confirmed no differential effect of tumor size across histological subtypes. Conclusions: In this literature-based cohort of GRLPs treated with surgery, histological subtype independently predicted recurrence, whereas tumor size showed no prognostic value, either overall or within individual histological subtypes. Full article

Background: The prognostic significance of histological transformation (HT) in treatment-naive diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate the clinical outcomes and failure patterns of treatment-naive transformed DLBCL (trDLBCL) compared with de novo DLBCL using a large-scale cohort. Methods: We retrospectively analyzed 1735 consecutively enrolled treatment-naive DLBCL patients (118 trDLBCL and 1617 de novo). Propensity score matching (PSM) was performed to balance baseline characteristics. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models. Subgroups were defined by pathology (t-FL vs. t-MZL) and pattern: concurrent (synchronous indolent lymphoma and DLBCL components at diagnosis) vs. pure transformation (DLBCL occurring as the sole histology in patients with a prior history of untreated indolent lymphoma). Results: In the overall cohort, trDLBCL was associated with significantly inferior progression-free survival (PFS) compared with de novo disease and remained an independent adverse prognostic factor in multivariable analysis (HR 1.754, p < 0.001). These findings were confirmed in a 1:1 propensity score-matched cohort (108 pairs), where trDLBCL continued to show worse PFS (p < 0.01), while overall survival (OS) was comparable (p = 0.99). Within trDLBCL patients, the underlying indolent subtype (t-FL vs. t-MZL) did not significantly affect survival (PFS p = 0.17, OS p = 0.35), whereas “pure transformation” was associated with markedly inferior PFS (p = 0.005) and OS (HR 2.56, p = 0.02) compared with concurrent transformation. Failure pattern analysis revealed a higher risk of early progression in trDLBCL (POD24: 30.56% vs. 18.52%; OR 1.94, 95% CI: 1.05–3.56), whereas central nervous system (CNS) involvement was low and comparable between groups (2.78% vs. 0.93%, p = 0.62). Conclusions: Treatment-naive trDLBCL is associated with inferior PFS driven by early progression, whereas OS is comparable due to effective salvage therapies. Pure transformation appeared to define a higher-risk subgroup with inferior disease control, supporting the need for future prospective studies to evaluate risk-adapted frontline, consolidation, or maintenance strategies. Full article

Background: Immunotherapy has become an integral part of systemic treatment for cervical cancer (CC). This study assessed the safety profile of cemiplimab and the association between immune-related adverse events (irAEs) and treatment outcomes in patients with persistent, recurrent or metastatic CC. Methods: This ambispective, multicenter, real-world cohort study included 101 patients treated in 13 reference oncology centers as part of the PCCIG-01 study. We evaluated the frequency and severity of irAEs and their association with progression-free survival (PFS) and overall survival (OS). Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards models, with p < 0.05 considered statistically significant. Results: After a median follow-up of 7.5 months, adverse events occurred in 45 patients (44.6%) and were mostly grade (G) 1–2. IrAEs were observed in 34 patients (33.7%). Endocrine toxicities predominated (n = 24, 58.5% of irAEs), followed by hepatic (n = 5, 12.2%) and gastrointestinal events (n = 4, 9.8%). G3 irAEs occurred in 8 patients (7.9%). Median PFS was 3.9 months (95% CI 2.9–5.6) in patients without irAEs and 10.9 months (95% CI 5.7–16.3) in those with irAEs (p = 0.03). Median OS was 15.3 months (95% CI 8.6–25.9) in patients without irAEs and was not reached in those with irAEs (95% CI 11.6-NR; p = 0.11). The development of irAEs was associated with a 54% reduction in the risk of progression (HR 0.46, 95% CI 0.27–0.80), with no statistically significant impact on OS. Conclusions: In exploratory analyses, the occurrence of irAEs was associated with improved PFS in cemiplimab-treated patients with persistent, recurrent or metastatic CC. Cemiplimab showed a manageable safety profile, with most toxicities being G1–G2. Full article

Background and Objectives: There is limited evidence supporting the incorporation of dietary patterns into heart failure (HF) management. The Dietary Approaches to Stop Hypertension (DASH) diet is linked to cardiovascular disease prevention, but evidence correlating DASH adherence to HF risk is sparse. This study is the first prospective investigation into the relationship between the DASH diet, incident HF and its associated risk factors—hypertension and diabetes mellitus (DM)—in Australian women. Materials and Methods: Survey data (2001–2022) from the Australian Longitudinal Study on Women’s Health (ALSWH) was analysed, where DASH diet scores were calculated from food frequency questionnaire (FFQ) responses and categorised into quintiles. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between DASH adherence and incident HF. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs for secondary endpoints, hypertension and DM, and dietary exposure was modelled as a time-varying covariate. Results: 10 594 women (mean age 52.5 ± 1.45 years) participated and, at 21-year follow-up, there were 136 (1.3%) cases of HF, 2182 (20.6%) and 994 (5.7%) cases of hypertension and DM, respectively. After adjustment for covariates (including age and socioeconomic factors), no association was found between the highest DASH quintile and incident HF [OR 0.73, 95% CI: 0.37–1.43; p = 0.20]. However, adjusted HRs for hypertension and DM—0.73 (95% CI: 0.63–0.84; p < 0.001) and 0.65 (95% CI: 0.53–0.81; p < 0.001), respectively—indicated significant associations. Conclusions: In Australian women, DASH diet adherence was associated with a significantly lower risk of hypertension and DM, both of which are HF risk factors. The finding of no direct statistically significant association between the DASH diet and incident HF might reflect the small incidence of HF in our cohort. Full article

Background: Lipoprotein(a) (Lp(a)) is a genetically determined lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). Its prognostic role in type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association of Lp(a) with first myocardial infarction (MI), cardiovascular (CV) mortality, and all-cause mortality, with a focus on sex differences. Methods: We retrospectively analysed patients with T2DM and no prior MI who were hospitalised between 2000 and 2018 and had baseline Lp(a) measurements. Patients were followed until MI, death, or the end of 2023. Lp(a) was categorised as ≤50, 51–90, and >90 mg/dL. Cox proportional hazards models were adjusted for low-density lipoprotein cholesterol, arterial hypertension, and estimated glomerular filtration rate < 60 mL/min/1.73 m², with attained age used as the time scale. Results: A total of 2967 patients (37.5% women) were included. During follow-up, 12.5% of patients experienced MI, 36.4% died from CV causes, and 68.8% died from any cause. A significant interaction between Lp(a) and sex was observed for MI. In sex-specific analyses, Lp(a) > 50 mg/dL was associated with a higher risk of first MI in women (51–90 mg/dL: HR 1.79, 95% CI 1.07–2.99; >90 mg/dL: HR 2.67, 95% CI 1.66–4.32), whereas no significant association was observed in men. Elevated Lp(a) ≥ 50 mg/dL was also associated with higher CV mortality overall (51–90 mg/dL: HR 1.42, 95% CI 1.07–1.89; >90 mg/dL: HR 1.38, 95% CI 1.01–1.91), without a significant interaction with sex. No significant associations were observed for all-cause mortality. Conclusions: In patients with T2DM, elevated Lp(a) > 50 mg/dL was associated with increased risk of first MI, predominantly in women, and with higher CV mortality overall. Lp(a) may serve as a valuable marker for CV risk stratification in this population. Full article

Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle–brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan–Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [>3.55 ng/mL], moderate [1.55–3.55 ng/mL], and low [<1.55 ng/mL]) and ABI tertiles (severe [<0.40], moderate [0.40–<0.70], and mild [0.70–0.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 ± 0.25 and mean FABP3 concentration was 2.97 ± 2.06 ng/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan–Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p < 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 < 1.55 group, compared with 71.1% in the FABP3 1.55–3.55 group and 67.7% in the FABP3 > 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60–2.25; p < 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60–2.24; p < 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI. Full article