Search Results (5,321)

Fracturing-fluid retention caused by capillary trapping and surfactant loss during transport through porous media can impair post-fracturing productivity in tight reservoirs. In this study, a rhamnolipid/isopropanol/limonene/water nanosized dispersed formulation was developed as a biosurfactant-based flowback aid. Pseudo-ternary phase diagrams, dynamic light scattering, surface- and interfacial-tension measurements, contact-angle measurements, porous-medium transport experiments, and sand-packed drainage tests were employed to evaluate the formulation behavior and flowback-aiding performance. The largest optically clear single-phase region was obtained at a rhamnolipid/isopropanol mass ratio of 3:1. The formulation maintained nanoscale hydrodynamic dimensions at NaCl or CaCl₂ concentrations up to 10 g/L, while systems containing ≤80 wt.% water exhibited comparatively stable hydrodynamic sizes during 7 d of aging at 70 °C. The equilibrium surface tension reached 25.87 mN/m at 200 mg/L. After passage through the proppant/rock-powder-packed medium, the formulation retained a surface tension of 32.02 mN/m and produced a water contact angle of 95°, compared with 51.20 mN/m and 67°, respectively, for the rhamnolipid aqueous solution. The maximum relative aiding-drainage enhancement approached 89.2% at 2000 mg/L. These results indicate an association among formulation characteristics, interfacial properties, porous-medium transport behavior, and drainage performance, and support the potential of the rhamnolipid-based dispersed formulation as a flowback-aid candidate under the investigated laboratory conditions. Full article

Background/Objectives: Acute kidney injury (AKI) is a frequent complication following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The association between preoperative inflammatory and immune-nutritional indices and postoperative AKI after CRS-HIPEC remains unclear. We aimed to investigate whether these prespecified candidate preoperative markers are associated with postoperative AKI in patients undergoing CRS-HIPEC. Methods: This retrospective single-center study included 87 patients who underwent CRS-HIPEC between October 2022 and April 2025. All received intraoperative cisplatin and mitomycin C. AKI was defined according to Kidney Disease: Improving Global Outcomes serum creatinine criteria. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value, systemic inflammation response index, and C-reactive protein–albumin–lymphocyte (CALLY) index were calculated from routine laboratory parameters. Each candidate marker was evaluated in a separate model adjusted for age and sex, and then in a second model additionally adjusted for baseline estimated glomerular filtration rate. Discriminatory performance was assessed using receiver operating characteristic analysis. The CALLY index was calculated using albumin in g/dL, lymphocyte count in ×10⁹/L, and C-reactive protein in mg/L. Results: AKI developed in 24 patients (27.6%). In-hospital mortality was higher in patients with AKI than in those without AKI (25.0% vs. 1.6%; p = 0.002). A higher log10-transformed CALLY index remained associated with lower odds of AKI after adjustment for age and sex (adjusted OR, 0.276; 95% CI, 0.113–0.673; p = 0.005). The CALLY index had the numerically highest AUC among the evaluated indices, with moderate discriminatory performance (AUC, 0.708; 95% CI, 0.579–0.836). A data-derived exploratory cutoff of ≤1.640 yielded 79.2% sensitivity and 63.5% specificity. Conclusions: In this selected retrospective cohort of patients without established chronic kidney disease, a lower preoperative CALLY index was associated with postoperative AKI and showed moderate discrimination as an individual marker. The data-derived threshold should be considered exploratory and requires independent validation before clinical application. Full article

The neurological and neuropsychiatric manifestations of long COVID remain incompletely understood. Reactivation of latent herpesviruses has been proposed as a contributing mechanism, but human herpesvirus 7 (HHV-7) has received limited attention despite its neurotropic potential. We conducted a retrospective analysis of HHV-7 polymerase chain reaction (PCR) results in 30 patients (18 women and 12 men; age range, 21–55 years) with a neurological/neuropsychiatric long COVID phenotype tested within 24 months of SARS-CoV-2 infection at R.E.D. Laboratories SA, Belgium. HHV-7 positivity was compared with a historical pre-COVID-19 laboratory reference cohort comprising 320 diagnostic tests performed from 2012 to 2019. HHV-7 positivity was 29.1% (93/320; 95% CI, 24.4–34.3%) in the historical reference cohort and 76.7% (23/30; 95% CI, 59.1–88.2%) in the neurological/neuropsychiatric long COVID cohort. The between-cohort difference was significant using a two-sided Fisher’s exact test (p < 0.000001). All six patients tested within the first 12 months were HHV-7-positive. HHV-7-positive patients frequently reported neuropsychiatric symptoms, and in one longitudinal index case, viral load tracked self-reported symptom severity. In this patient-initiated retrospective study, HHV-7 positivity was substantially more frequent in the long COVID cohort than in the historical reference cohort. These findings are hypothesis-generating and support prospective investigation of HHV-7 in neurological and neuropsychiatric long COVID. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used but can cause clinically significant gastrointestinal adverse events (GI-AEs). However, genetic susceptibility to NSAID-related GI toxicity remains insufficiently characterized in East Asian populations. This exploratory study aimed to identify genetic loci associated with grade ≥ 2 NSAID-related GI-AEs in Korean patients treated with commonly used NSAIDs. Methods: We conducted an exploratory genome-wide association study in a multicenter Korean cohort of NSAID-treated patients recruited from four Korean hospitals. A total of 339 patients were included, comprising 28 cases with grade ≥ 2 GI-AEs and 311 controls without documented GI-AEs. Genotyping was performed using the Korea Biobank Array, followed by imputation and quality control. Genome-wide association analysis was conducted under an additive logistic regression model adjusted for age, sex, and the first two principal components, with additional sensitivity analyses accounting for the specific NSAID type, cumulative DDD, and concomitant medications. Polygenic risk score analysis was performed using summary statistics from an arthritis-treated subset of the KoGES Ansan/Ansung cohort, and the selected variant were further evaluated using multivariable Firth penalized logistic regression. The discriminatory performance of clinical, laboratory, and genetic models was assessed using bootstrap internal validation. Results: The exploratory GWAS identified 20 suggestive variants associated with NSAID-related GI-AEs at p < 1 × 10⁻⁵, although no variant reached genome-wide significance. The KoGES-derived polygenic risk score was significantly associated with GI-AE status in the NSAID cohort, and 10 suggestive variants overlapped with SNPs included in the best-fit PRS model. rs1925245 maintained a consistent association in multivariable Firth penalized logistic regression. Conclusions: These findings suggest that NSAID-related GI-AEs in Korean patients may reflect a multifactorial susceptibility pattern involving both clinical context and polygenic risk. Although exploratory, this study provides candidate genetic signals for future replication and supports the need for larger ancestry-matched pharmacogenomic studies of NSAID-related GI toxicity. Full article

Background/Objectives: Human immunodeficiency virus (HIV) and tuberculosis (TB) remain major public health challenges in sub-Saharan Africa, which bears the highest burden of HIV/TB co-infection. Evidence is limited on whether the severity of virological failure is associated with workplace absenteeism among employed adults with HIV/PTB co-infection. This study examined workplace absenteeism across two viral-load categories among employed adults with documented virological failure in the Govan Mbeki sub-district. Methods: A retrospective record review with secondary data analysis was conducted among 286 employed mine workers with HIV/PTB co-infection and a viral load ≥1000 copies/mL after at least six months of antiretroviral therapy (ART). Clinical data were extracted from medical, laboratory, and TB-treatment records and linked to workplace sick-leave registers; limited participant contact was used only to clarify essential missing information. The analytic dataset had an observed minimum viral load of 1200 copies/mL. Viral load was categorised as 1200–10,000 versus ≥10,001 copies/mL. Absenteeism was the number of recorded sick-leave days during the preceding three months and, for logistic regression, was classified as low (5–10 days) versus high (11–15 days). Multivariable logistic regression was adjusted for age, sex, education, and structural/socioeconomic barrier score. Results: Mean absenteeism was 10.05 days (SD = 2.44). Of 286 participants, 181 (63.3%) had a viral load ≥10,001 copies/mL and 105 (36.7%) had a viral load of 1200–10,000 copies/mL. High absenteeism occurred in 129 participants (45.1%) and lower absenteeism in 157 (54.9%). Viral load category was not associated with high absenteeism after adjustment (aOR = 1.21, 95% CI: 0.76–1.92; p = 0.432). The model was not statistically significant (χ² = 6.41, df = 5, p = 0.269), explained 3.0% of the variance (Nagelkerke R² = 0.030), and had an acceptable Hosmer–Lemeshow fit (p = 0.913). Conclusions: Within this selected employed cohort with virological failure, high-level virological failure and absenteeism were both common, but no evidence of an independent association between viral-load category and high absenteeism was detected. The cross-sectional temporal structure, healthy-worker selection, limited exposure contrast, and residual confounding constrain causal interpretation. Integrated public health and workplace interventions are suggested to improve both treatment outcomes and workforce participation in high-burden settings. Full article

Sn-polymetallic deposits in the Southern Great Xing’an Range (SGXR) are typically marked by the coexistence of Sn, Cu, Pb, Zn, and Ag, yet the mechanisms controlling their paragenesis and separation remain poorly constrained. The Hujiadian deposit hosts Sn, Cu, Pb, Zn, and Ag mineralization that occurs both as intergrown assemblages within individual orebodies and as distinct but spatially associated orebodies, making it an ideal natural laboratory to investigate element coexistence and fractionation. Three hydrothermal stages are identified: pyrite + cassiterite ± chalcopyrite + quartz + chlorite (Stage I); chalcopyrite + sphalerite ± galena + quartz + fluorite + chlorite ± amphibole ± epidote (Stage II); and sphalerite + galena + pyrite + quartz + chlorite + calcite (Stage III). The rhyolite porphyry yields a zircon U–Pb age of 132.3 ± 2.4 Ma, whereas the Sn ores yield cassiterite U–Pb ages of 129.9 ± 1.3 to 131.4 ± 0.8 Ma. These overlapping ages, within analytical uncertainties, constrain the Sn mineralization to the Early Cretaceous. The rhyolite porphyry is geochemically characterized by a peraluminous, high-K calc-alkaline affinity, coupled with elevated SiO₂ and alkali contents, strong negative Eu anomalies, and low fO₂ (ΔFMQ = −4.9 to 1.1). Collectively, these features are consistent with extensive fractionation under reducing conditions, which would have facilitated Sn accumulation in the residual melt. Pervasive chlorite in the deposit records the physicochemical evolution of the hydrothermal system; four chlorite generations document a shift from early acidic conditions during Sn mineralization to near-neutral or weakly alkaline conditions during late Pb–Zn precipitation. We propose that increasing pH played an important role in promoting cassiterite precipitation during Stage I, whereas cooling was the dominant control on Cu precipitation during Stage II. During Stage III, further cooling and increasing pH promoted Pb–Zn precipitation. The observed carbonatization and mineral assemblages are consistent with possible involvement of external fluids, including meteoric water. These changes may have been associated with fluid–rock interaction and possible mixing with meteoric water. Full article

Objective: To compare clinical and laboratory markers for 30-day mortality in older patients with perforated peptic ulcer and assess biochemical markers beyond age and American Society of Anesthesiologists (ASA) class. Methods: Patients aged ≥65 years undergoing emergency surgery for perforated peptic ulcer from January 2015 to February 2026 were retrospectively analyzed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC), and incremental value by likelihood-ratio tests and Brier scores. Six marker-specific incremental tests underwent Benjamini–Hochberg false discovery rate (FDR) adjustment. Models incorporating blood urea nitrogen-to-albumin ratio (BAR) or log₂-transformed creatinine underwent bootstrap internal validation. Results: Thirty-day mortality was 37.7% (26/69). Age and ASA class yielded AUCs of 0.785 and 0.755. BAR had the highest univariable biochemical discrimination (AUC, 0.777). Inflammation-based indices showed limited discrimination (AUC, 0.424–0.492); Prognostic Nutritional Index (PNI) had the highest discrimination among immune-nutritional/composite markers (AUC, 0.636; p = 0.061). BAR improved the age- and ASA-based model nominally (p = 0.023), but not after FDR adjustment (adjusted p = 0.068). Creatinine provided the strongest incremental information (AUC, 0.905; Brier score, 0.123; adjusted p = 0.008). In the joint model, creatinine improved fit beyond BAR (p = 0.024), whereas BAR did not improve fit beyond creatinine (p = 0.773). Conclusions: Prognostic information was concentrated in age, ASA class, and renal-protein markers. Creatinine provided the most consistent incremental information; BAR showed high univariable discrimination but did not retain significant incremental value after FDR adjustment. Inflammation-based indices remained limited. Independent validation is required. Full article

Methylation, catalyzed by a diverse family of S-adenosylmethionine (SAM)-dependent methyltransferases, is a fundamental biochemical process that regulates the function of proteins, DNA, and RNA. Among these modifications, protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), represents a critical post-translational mechanism regulating transcription, DNA repair, RNA splicing, and signal transduction. Emerging evidence highlights important roles of PRMTs in cardiovascular diseases (CVDs); however, current research is limited by several challenges, including the paradoxical and context-dependent functions of individual PRMTs and the lack of highly specific inhibitors or activators, leaving their therapeutic potential incompletely defined. This review summarizes the classification, structure, and functional characteristics of methyltransferases, with a particular focus on PRMTs and their roles in normal physiology and diverse CVDs. We integrate current knowledge to provide a comprehensive understanding of how PRMTs contribute to cardiovascular pathophysiology by methylating histones, transcription factors, and other functional proteins. Collectively, PRMTs emerge as pivotal regulators in CVD development and progression. Future studies should prioritize resolving the functional duality of specific PRMTs, developing targeted precision therapeutics, and elucidating the roles of less-characterized family members in CVDs. Full article

Background/Objectives: Invasive mechanical ventilation (IMV) in older intensive care unit (ICU) patients represents a critical turning point in disease trajectory. While acute illness severity is a key determinant of IMV, the independent contributions of frailty and comorbidity remain uncertain. This study evaluated whether integrating geriatric domains with acute physiological parameters provides additional information about the risk of IMV requirement, beyond acute severity alone. Methods: In this single-center retrospective cohort study, patients aged ≥65 years admitted to a tertiary ICU between January 2024 and December 2025 were included. Variables obtained within the first 24 h included Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), and laboratory parameters. The primary outcome was IMV requirement. Multivariable logistic regression models were constructed, and performance was assessed using discrimination (AUC) and calibration. Results: Among 285 patients (median age 77 years [IQR 71–86]), 161 (56.5%) required IMV. These patients had higher frailty, comorbidity burden, and illness severity on univariable comparison. In multivariable analysis, SOFA score showed the strongest independent association with IMV requirement (adjusted OR 1.91; 95% CI 1.63–2.23; p < 0.001), followed by serum lactate (adjusted OR 1.30; 95% CI 1.08–1.58; p = 0.006). Older age was independently associated with lower odds of IMV (adjusted OR 0.96 per year; 95% CI 0.92–1.00; p = 0.034). Neither frailty (CFS) nor comorbidity burden (CCI) remained independently associated after adjustment. The final SOFA- and APACHE II-based models demonstrated AUCs of 0.899 (95% CI 0.864–0.933) and 0.911 (95% CI 0.879–0.944), respectively. Conclusions: Acute organ dysfunction and early lactate remain the dominant determinants of IMV requirement in older ICU patients. Neither comorbidity burden nor frailty retained an independent association once acute severity was accounted for; instead, advancing age was independently associated with a lower likelihood of IMV, a finding that may reflect unmeasured treatment-limitation decisions and warrants further investigation. These findings suggest that frailty and comorbidity indices should not be used in isolation as triggers for ventilatory decision-making and instead support a framework centered on acute severity and perfusion markers, with age considered mainly as a marker of care-goal context. Full article

Background: Complicated malaria occurs in 15–40% of hospitalised imported cases, and European centres often define it more broadly than the WHO 2023 severe-malaria criteria, which, calibrated for semi-immune populations, may under-identify severe disease in non-immune travellers; Central and Eastern European data are limited. We examined the clinical spectrum, travel destinations, and admission correlates of complicated imported malaria in non-immune Polish travellers. Methods: This was a two-centre, 11-year retrospective cohort of 93 laboratory-confirmed episodes in 91 adults (December 2014–October 2025). Complicated disease was a composite of organ-specific complications on admission. We derived the exploratory nine-item IMSC-NIT severity-capture criteria, with a pre-specified analysis restricted to the four items not overlapping the outcome (age, C-reactive protein, procalcitonin, platelets). Results: Complicated disease affected 31/93 episodes (33.3%), exceeding the 10/93 that met the strictly assessable WHO criteria. Plasmodium falciparum predominated; 88.2% with documented status had used no chemoprophylaxis; age was the only independently associated variable (multiple-imputation odds ratio 1.07 per year, 95% CI 1.02–1.11). The restricted four-item score gave an area under the curve of 0.76 (95% CI 0.65–0.85; optimism-corrected 0.72). Conclusions: The WHO criteria alone may miss non-immune travellers with organ involvement at presentation. The IMSC-NIT is a hypothesis-generating severity-capture aid requiring external validation before clinical use. Full article

Background and Aim: Studies worldwide have documented a reduction in acute myocardial infarction (AMI) admissions during the COVID-19 pandemic. We aimed to assess AMI admissions, management, and in-hospital outcomes in Kosovo during the pandemic period. Methods: We conducted a retrospective single-centre study including all consecutive AMI admissions from 1 January 2018 to 31 December 2020 at the Clinic of Cardiology, University Clinical Centre of Kosovo, the only public tertiary primary percutaneous coronary intervention (PCI) centre in the country. The pre-pandemic (PP) period was defined as 1 January 2018–12 March 2020 and the ongoing pandemic (OP) period as 13 March–31 December 2020. Demographic, clinical, laboratory, angiographic, and outcome data were collected. In-hospital mortality was defined as death between admission and discharge. Interrupted time-series analyses were performed. Results: A total of 898 AMI patients were admitted during OP and 2955 during PP. Daily admissions decreased from 3.8/day to 3.05/day (p < 0.001). OP patients were younger, more often hypertensive and smokers, and more frequently male. Coronary angiography (81% vs. 76%, p = 0.001) and PCI (66% vs. 60%, p = 0.001) were more frequent during OP, while in-hospital mortality remained unchanged. Time-series analysis showed a sharp fall in admissions at OP (β = −12.66, p < 0.001) with gradual recovery, alongside an increase in PCI use (β = 0.184, p < 0.001) and stable mortality. The proportion of ST-segment elevation (STEMI) cases increased significantly during the pandemic period. Compared with the pandemic period, admission during the pre-pandemic period was associated with lower odds of undergoing PCI (aOR 0.81, 95% CI 0.69–0.95), while age ≥ 65 reduced the likelihood of PCI. Conclusions: AMI hospitalizations in Kosovo declined significantly during the COVID-19 pandemic. The pandemic cohort was younger, with the profile of admitted patients shifting toward younger age, male sex, and STEMI presentation. Despite fewer admissions, PCI use increased, while no statistically significant difference in in-hospital mortality was observed between the two periods. These findings describe changes in treatment patterns and short-term in-hospital outcomes during the pandemic but should not be interpreted as evidence of equivalent overall quality of AMI care. Full article

Background: Multidimensional evidence on exercise participation and frailty in older adults is limited. Methods: This 12-week preference-based, non-randomized study included 145 participants (mean age 82.25 years): walking (n = 50), resistance training (n = 20), Traditional Chinese exercise (n = 23), and control (n = 52). Frailty was the primary outcome; physical-performance and molecular analyses were exploratory. Paired trajectories, baseline-stratified binary transitions, and adjusted associations were examined. Results: Among paired participants, pre-frailty/frailty prevalence changed from 70.0% to 60.0% with walking, 90.0% to 70.0% with resistance training, 50.0% to 63.6% with Traditional Chinese exercise (n = 22), and 50.0% to 69.2% in controls. Baseline status constrained opportunities for binary improvement or deterioration. All adjusted frailty risk-ratio confidence intervals included 1. Walking was associated with faster Timed Up and Go and Five-Yard Walk Test performance after correction across eight outcomes. Molecular changes also occurred in controls; intervention timing and potential laboratory-batch confounding limited between-group interpretation. No microbiome taxon survived multiplicity correction; small paired samples limited precision. Conclusions: Walking and resistance-training groups showed descriptively more favorable prevalence trajectories, but adjusted frailty comparisons remained inconclusive. These findings do not establish frailty prevention, modality superiority, or exercise-specific molecular mechanisms. Full article

Background/Objectives: Early detection of cognitive decline is crucial for preventing dementia. Conventional diagnostic approaches, including neuropsychological test batteries, laboratory tests, neuroimaging, and cerebrospinal fluid analysis, may have limitations related to accessibility, cost, invasiveness, and the early detection of pathological changes. Dementia-related pathology can affect neural networks involved in sensory and motor functions, suggesting that changes in these functions may provide non-invasive indicators of subsequent cognitive decline. Therefore, this study aimed to investigate potential indicators associated with longitudinal cognitive decline by integrating multiple sensory and motor functions. Methods: Cognitive, sensory, balance, and gait function were measured longitudinally over two years in community-dwelling older adult men (≥65 years). Generalized estimating equations were applied to explore potential indicators by examining the association between longitudinal changes in multiple sensory and motor functions and the transition to cognitive decline. Results: Older age, lower uncorrected contrast sensitivity at 4 m, a lower binaural average sentence recognition score, poorer olfactory discrimination, shorter limits of stability test time, de-creased gait velocity, a reduced loading response proportion, and an increased proportion of pre-swing were related to higher odds of longitudinal cognitive decline. Conclusions: These results showed that specific sensory and motor functions were associated with longitudinal cognitive decline and suggested that their integration may provide information that could contribute to risk stratification for cognitive decline in older adults. Further studies with larger sample sizes and multiple cohorts are needed. Full article

Azole resistance in Aspergillus fumigatus is an emerging threat to invasive and chronic aspergillosis management, yet multicenter trend analyses rarely verify whether the composition of surveillance data remained stable over time. We performed a longitudinal, secondary-data analysis of 2111 Aspergillus isolates registered in the VIVLI AMR platform (ATLAS Antifungals, SENTRY Program) between 2010 and 2020. Because Clinical and Laboratory Standards Institute (CLSI) voriconazole breakpoints are established only for A. fumigatus in this dataset, the susceptibility-trend analysis was restricted to A. fumigatus isolates with a valid interpretation (n = 1482/1483). A. fumigatus accounted for 70.3% of all Aspergillus isolates; most originated from Europe (43.9%) and North America (35.2%). Region and clinical specialty differed significantly across the three study periods (both p < 0.0001), while species, age, sex and specimen-source distributions remained stable (p > 0.10). Voriconazole susceptibility in A. fumigatus declined from 97.9% (2010) to 90.4% (2020), with a significant linear downward trend (Cochran–Armitage Z = −3.03, p = 0.002). This decline was statistically robust, but the concurrent shift in participating regions and specialties indicates that compositional changes in surveillance sampling should be considered alongside biological resistance emergence when interpreting multicenter antifungal surveillance trends. Full article

Background/Objectives: Peripheral artery disease (PAD) remains underdiagnosed and suboptimally treated, with limited disease awareness and underutilization of available diagnostic strategies representing important contributing factors. The ankle–brachial index (ABI) is the gold-standard screening test for PAD and has been shown to correlate with limb outcomes. However, the current interpretation of ABIs does not account for clinically significant differences between legs, which may reflect asymmetric disease burden and have an impact on limb outcomes. The association between inter-leg ABI asymmetry and PAD outcomes is unclear and requires further study. Thus, we assessed the prognostic importance of a clinically significant difference in left and right ABI values (≥0.15) on limb outcomes in patients with PAD. Methods: A total of 3313 patients with PAD who received outpatient vascular care at a single institution were retrospectively analyzed. At baseline, ABIs were measured in a certified vascular laboratory by dividing the higher of the dorsalis pedis or posterior tibial artery systolic pressures in each leg by the higher brachial systolic pressure. Inter-leg ABI asymmetry was defined by an absolute difference between left and right ABI values ≥ 0.15, which has been shown to be clinically significant. The primary outcome was major adverse limb event (MALE) over 2 years of follow-up. MALE was defined as the need for vascular intervention (either open or endovascular lower extremity revascularization) or major lower extremity amputation above the ankle. The association between inter-leg ABI asymmetry and 2-year MALE was evaluated using univariable and multivariable logistic regression models adjusted for age, sex, body mass index (BMI), and ABI-defined hemodynamic severity. Results: The mean participant age was 58.4 years (SD 12.9), 966 (29.2%) participants were female, and the mean BMI was 28.8 kg/m² (SD 5.7). There were 666 (20.1%) patients who had inter-leg ABI asymmetry. The mean inter-leg ABI difference was 0.38 (SD 0.29) in the inter-leg ABI asymmetry group and 0.04 (SD 0.02) in the no inter-leg ABI asymmetry group (p < 0.001). Patients with inter-leg ABI asymmetry were more likely to have moderate PAD (36.0% vs. 6.5%, p < 0.001) and severe PAD (6.2% vs. 0.7%, p < 0.001), and less likely to have mild PAD (57.8% vs. 92.8%, p < 0.001), compared to patients with no inter-leg ABI asymmetry. Over the median follow-up period of 2 years, 304 (9.2%) participants experienced MALE. The 2-year MALE rate was significantly higher in patients with inter-leg ABI asymmetry compared to those without (26.0% vs. 4.9%, p < 0.001). Similarly, patients with inter-leg ABI asymmetry had a higher rate of the need for revascularization (21.5% vs. 4.1%, p < 0.001) and major amputation (10.2% vs. 1.8%, p < 0.001). Multivariable logistic regression controlling for age, sex, BMI, and ABI-defined hemodynamic severity showed that inter-leg ABI asymmetry was independently associated with 2-year MALE (adjusted OR 3.70, 95% CI 2.80–4.91, p < 0.001). Conclusions: In this study, over 20% of patients with PAD had clinically significant inter-leg ABI asymmetry, which was independently associated with a nearly four times higher odds of 2-year MALE, including the need for revascularization and major amputation. Our results suggest that inter-leg ABI asymmetry may represent a readily available prognostic marker of adverse limb outcomes in patients with PAD. Further external validation and prospective studies are needed to determine whether incorporating inter-leg ABI asymmetry into clinical assessment improves risk stratification or clinical outcomes. Full article