Search Results (1,114)

Background/Objectives: The objective of this retrospective, multicenter cohort study was to compare the incidence of viral load blips between two-drug and three-drug antiretroviral therapy regimens in human immunodeficiency virus (HIV) patients. Methods: A total of 121 patients were included, with 44 receiving two-drug regimens (e.g., dolutegravir/lamivudine) and 77 receiving three-drug regimens (e.g., bictegravir/tenofovir alafenamide/emtricitabine) at the time of analysis. The primary outcome was the occurrence of viral blips, defined as transient HIV-RNA elevations ≥ 50 copies/mL; a sensitivity analysis used ≥20 copies/mL. Results: Generalized estimating equation models adjusted for clinical covariates showed no significant difference in the odds of blip occurrence comparing three-drug with two-drug regimens, both for blips ≥ 50 (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 0.91–7.70; p = 0.075) and ≥20 (OR: 1.76; 95% CI: 0.76–4.08; p = 0.190). In the two- and three-drug groups, the predicted probabilities of blips were 1.4% and 3.7% (p = 0.075) for blips ≥ 50, and 6.9% and 11.5% (p = 0.190) for ≥20, respectively. No virologic failure was observed. Conclusions: These findings suggest that two-drug regimens provide virologic control comparable to three-drug regimens and may be a viable clinical option due to fewer drug interactions, lower toxicity, and reduced cost. Full article

Background: Patients with acute anterior circulation large-vessel occlusion (AC-LVO) stroke frequently experience poor outcomes despite successful mechanical thrombectomy (MT). Heparin-binding protein (HBP), a neutrophil-derived mediator of inflammation and vascular permeability, may contribute to neuroinflammation and prognosis; however, its role in stroke remains unclear. Methods: In this retrospective study, 163 patients with AC-LVO stroke who underwent MT were enrolled. Plasma HBP levels were measured within 24 h after thrombectomy. Functional outcomes were evaluated using the modified Rankin Scale (mRS) at 90 days, with an mRS score 3–6 suggesting a poor outcome. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed to assess associations between HBP and outcomes. Results: Of the 163 patients, 88 (54.0%) had poor functional outcomes. The median plasma HBP level of patients with poor outcomes was significantly higher than that of patients with good outcomes (28.80 vs. 18.42 ng/mL; p < 0.001). HBP remained independently associated with poor outcome (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.07; p = 0.002) after adjusting for demographic, clinical, procedural, and laboratory covariates. ROC analysis showed a modest predictive value of HBP alone (area under the curve [AUC] = 0.671), whereas adding HBP to clinical models improved prognostic accuracy (AUC = 0.835 for model 2; AUC = 0.889 for model 3). Conclusions: For patients with AC-LVO stroke, elevated plasma HBP within 24 h after MT serves as an independent predictor of unfavorable functional outcomes at 90 days. Thus, HBP may serve as a prognostic biomarker and potential target for immunomodulatory therapy. Full article

Background: Cardiac autonomic dysfunction is a frequent complication of diabetes type 2 (T2DM). Heart rate variability (HRV) is a sensitive biomarker, but its relationship with habitual physical activity adjusted for metabolic and anthropometric factors remains underexplored. This study aimed to compare HRV indices between physically active and inactive adults with T2DM and assess the association between physical activity and clinical variables. Methods: In this cross-sectional observational study, 41 T2DM adults were classified as physically active (n = 22) or inactive (n = 19) using the short form of the International Physical Activity Questionnaire IPAQ-S. Resting HRV recordings were performed under standardized procedures. We analyzed the following time- and frequency-domain HRV indices: root mean square of successive heartbeat interval differences (RMSSD), standard deviation of normal-to-normal R-R intervals (SDNN), low-frequency (LF) and high-frequency (HF) power and their ratio (LF/HF). The analysis has been performed between-groups, and backward stepwise quantile regression examined the independent association of physical activity with HRV, adjusting for covariates. Results: Active participants exhibited higher HRV indices (SDNN p = 0.021; RMSSD p = 0.028; LF p = 0.032; HF p = 0.030), despite similar anthropometric and metabolic profiles. BMI correlated negatively with mean RR (ρ = −0.339, p = 0.030) and positively with mean HR (ρ = 0.339, p = 0.030). Physical activity was positively associated with LF (p = 0.015), and remained independently associated with SDNN (p = 0.021) and RMSSD (p = 0.048) after adjusting for HbA1c. Conclusions: Habitual physical activity was independently associated with enhanced autonomic modulation, with SDNN emerging as an early marker, supporting HRV as a biomarker for guiding exercise interventions in T2DM. Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article

Background: Telerehabilitation can extend fall prevention to underserved groups. Clinician uptake remains limited. We evaluated factors associated with physical therapists’ belief in and readiness to implement the Otago Exercise Program (OEP) via telerehabilitation in Saudi Arabia. Methods: We conducted a national cross-sectional survey of physical therapists (n = 120). Exposures included fall-prevention training, education outside versus inside Saudi Arabia, and familiarity with telerehabilitation. Outcomes were belief in telerehabilitation efficacy for the OEP (5-point Likert) and high readiness, defined as familiarity plus knowledge ≥4 of 5 and belief ≥4 of 5. We utilized ordinal logistic regression for assessing belief and binary logistic regression for assessing readiness. We conducted two-sided tests with alpha equal to 0.05 and prespecified covariates. Sensitivity analyses using penalized likelihood methods confirmed the robustness of the results. Results: The OEP prescription did not differ with telerehabilitation familiarity (χ² = 0.28; p = 0.597). In multivariable models using complete cases (n = 117; 21 readiness events), fall-prevention training was associated with higher belief (odds ratio [OR] = 3.997; 95% CI = 1.568–10.184; p = 0.004) and higher readiness (OR = 4.520; 95% CI = 1.546–13.210; p = 0.006). Education outside Saudi Arabia was associated with higher readiness (OR = 5.170; 95% CI = 1.435–18.636; p = 0.012). Results were directionally consistent in Firth and pilot-exclusion analyses. Conclusions: Training and international educational exposure were associated with stronger beliefs and greater readiness to implement the OEP via telerehabilitation. Basic familiarity alone was not associated with the OEP use. Programs should prioritize competency-based training and curricular updates to support implementation. Full article

Background/Objectives: Pacemaker-associated heart failure (PaHF) is a recognized complication of chronic ventricular pacing, yet its long-term incidence and prognostic impact remain incompletely defined. Previous studies on PaHF have been largely limited by small sample sizes, single-center designs, and insufficient long-term or time-dependent analyses. We aimed to evaluate the incidence, clinical predictors, and mortality risk of PaHF in a nationwide real-world cohort. Methods: Using the Korean National Health Insurance Service database, we identified 32,216 patients who underwent de novo pacemaker implantation between 2008 and 2019 without prior heart failure. Results: During a median follow-up of 3.8 years, 4170 patients (12.9%) developed new-onset PaHF and 6184 (19.2%) died. PaHF was independently associated with increased all-cause mortality (adjusted hazard ratio [HR]: 3.11, 95% confidence interval [CI]: 2.93–3.32, p < 0.001), even after accounting for immortal-time bias and relevant covariates. The incidence of PaHF and its associated mortality risk both peaked within the first six months post implantation and remained persistently elevated throughout follow-up; notably, PaHF-associated mortality showed a late resurgence. Sensitivity and subgroup analyses consistently demonstrated higher mortality among patients with PaHF across a wide range of clinical characteristics. Conclusions: In this large, nationwide cohort, the development of PaHF was associated with a substantial and sustained increase in mortality risk following pacemaker implantation. Given the persistent and dynamic nature of this risk, longitudinal monitoring of cardiac function and individualized pacing strategies may be warranted to mitigate long-term adverse outcomes. Additionally, these findings provide real-world benchmarks to guide future pacing strategies and surveillance efforts. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article

Myelin is essential for efficient neural signaling and can be quantitatively evaluated using the T1-weighted/T2-weighted (T1w/T2w) ratio as a proxy for regional myelin content. Myelin covariance networks (MCNs) reflect correlated myelin patterns across brain regions, enabling the investigation of topological organization. However, a vertex-level map of myelin covariance gradients and their cognitive associations remains underexplored. The objective of this study was to construct and characterize vertex-level MCNs, identify their principal gradients, map their higher-order topological landscape, and determine their associations with cognitive functions and other multimodal cortical features. We conducted a cross-sectional, secondary analysis of publicly available data from the Human Connectome Project (HCP). The dataset included T1w/T2w MRI data from 1096 healthy adult participants (age 22–37). All original data collection and sharing procedures were approved by the Washington University institutional review board. Our procedures involved (1) constructing a vertex-wise MCN from T1w/T2w ratio data; (2) applying gradient analysis to identify principal organizational axes; (3) calculating network connectivity strength; (4) performing cognitive meta-analysis using Neurosynth; and (5) using graphlet analysis to assess higher-order topology. Our results show that the primary myelin gradient (Gradient 1) spans from sensory-motor to association cortices, strongly associates with connectivity strength (r = 0.66), and shows a functional dissociation between affective processing and sensorimotor domains. Furthermore, Gradient 2, as well as the positive and full connectivity strength, showed robust correlations with fractional anisotropy (FA), a DTI metric reflecting white matter microstructure. Our higher-order analysis also revealed that negative and positive myelin covariance connections exhibited distinct topologies. Negative connections were dominated by star-like graphlet structures, while positive connections were dominated by path-like and triangular structures. This systematic vertex-level investigation offers novel insights into the organizational principles of cortical myelin, linking gray matter myelin patterns to white matter integrity, and providing a valuable reference for neuropsychological research and the potential identification of biomarkers for neurological disorders. Full article

Background/Objectives: Dementia is a growing public health concern in rapidly aging Japan. Dietary factors, including dairy products, have been proposed as modifiable influences on cognitive health, although findings across studies remain inconsistent. This study aimed to examine the association between habitual cheese consumption and incident dementia in a large, population-based cohort of older Japanese adults, and to provide epidemiological evidence regarding its potential preventive role in populations with low baseline dairy intake. Methods: We analyzed data from the Japan Gerontological Evaluation Study (JAGES) 2019–2022 cohort, linking survey responses to long-term care insurance (LTCI) certification records. Participants aged ≥65 years without prior LTCI certification were included. Cheese consumption was assessed at baseline and categorized as ≥1 time/week vs. non-consumers. Propensity score matching (PSM) was applied on sociodemographic and health-related covariates. Cox proportional hazards models estimated hazard ratios (HRs) for incident dementia over three years. Results: After PSM, 7914 participants were analyzed (3957 consumers; 3957 non-consumers). Baseline covariates were well-balanced. Over 3 years, 134 consumers (3.4%) and 176 non-consumers (4.5%) developed dementia, corresponding to an absolute risk difference of 1.06 percentage points. Cheese consumption was associated with a lower hazard of dementia (HR = 0.76, 95% CI 0.60–0.95, p = 0.015). Conclusions: Habitual cheese consumption (≥1 time/week) was modestly associated with a reduced 3-year incidence of dementia in older Japanese adults. While the absolute risk reduction was small, these findings are consistent with prior observational evidence linking dairy intake to cognitive health. Further research is warranted to clarify dose–response relationships, cheese subtypes, and underlying mechanisms. Full article

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed in uremia due to decreased renal degradation and/or clearance and increased production. We sought to examine the association between the L/A ratio and mortality in a prospective hemodialysis cohort. Methods: Among a prospective cohort of 448 hemodialysis patients from the NIH “Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) (MADRAD) study who underwent leptin and adiponectin measurements, we examined characteristics associated with high leptin and adiponectin (defined as the highest tertile) using logistic regression. We then examined the association of L/A ratio levels (categorized as tertiles) with all-cause mortality using Cox regression. Results: Multivariable logistic regression analyses showed female sex, diabetes, presence of an arteriovenous fistula/graft, and lower serum albumin, IL-6, and adiponectin were associated with high leptin, whereas female sex, longer vintage, Black race, higher IL-6, and lower leptin were associated with high adiponectin. When examining L/A ratios, the highest tertile was associated with lower mortality in case-mix Cox models (ref: lowest tertile): HR (95% CI) 0.14 (0.06–0.35). These associations were robust in analyses that additionally adjusted for laboratory covariates: (HR 95% CI) 0.18 (0.07–0.46). Conclusions: In a prospective cohort of hemodialysis patients, inflammation and malnutrition markers were associated with lower leptin and higher adiponectin levels. Additionally, high L/A ratio levels were associated with lower mortality. Further studies are needed to determine the mechanisms relating adipocytokines, inflammation and nutrition, and survival in this population. Full article

The Educational Competition Optimizer (ECO) formulates search as a three-stage didactic process—primary, secondary and tertiary learning—but the original framework suffers from scarce information exchange, sluggish late-stage convergence and an unstable exploration–exploitation ratio. We present EECO, which introduces three synergistic mechanisms: a regenerative population strategy that uses the covariance matrix of elite solutions to maintain diversity, a Powell mechanism that accelerates exploitation within promising regions, and a trend-driven update that adaptively balances exploration and exploitation. EECO was evaluated on the 29 benchmark functions of CEC-2017 and nine real-world constrained engineering problems. Results show that EECO delivers higher solution accuracy and markedly smaller standard deviations than eight recent algorithms, including EDECO, ISGTOA, APSM-jSO, LSHADE-SPACMA, EOSMA, GLSRIME, EPSCA, and ESLPSO. Across the entire experimental battery, EECO consistently occupied the first place in the Friedman hierarchy: it attained average ranks of 2.138 in 10-D, 1.438 in 30-D, 1.207 in 50-D, and 1.345 in 100-D CEC-2017 benchmarks, together with 1.722 on the nine real-world engineering problems, corroborating its superior and dimension-scalable performance. The Wilcoxon rank sum test confirms the statistical significance of these improvements. With its remarkable convergence accuracy and reliable stability, EECO emerges as a promising variant of the ECO algorithm. Full article

Background: While diabetes is a recognized risk factor for asthma, the shared genetic components between diabetes/glycemic traits and asthma remain unclear. This study investigates the genetic associations, causal relationships, and underlying mechanisms linking these conditions. Methods: We assessed global genetic correlations using linkage disequilibrium score regression (LDSC), high-definition likelihood analysis (HDL), and genetic covariance analysis (GNOVA). Trait pairs with significant correlations subsequently underwent genetic overlap analysis (Genetic analysis integrating Pleiotropy and functional Annotation, GPA) and local genetic correlation analysis (Local Genetic Variant Association Analysis, LAVA). Cross-phenotype association (CPASSOC) and multitrait analysis of GWAS (MTAG) identified potential pleiotropic loci, followed by colocalization and functional annotation. Proteome-wide association study (PWAS) revealed proteins and pathways shared between diabetes/glycemic traits and asthma. Generalized summary-data-based Mendelian randomization (GSMR) was used to evaluate causal effects between diabetes/glycemic traits and asthma. Results: Significant genetic correlations were observed between body mass index (BMI) and asthma (rg = 0.280–0.397; FDR < 0.05), type 2 diabetes mellitus (T2DM) and asthma (rg = 0.240–0.289; FDR < 0.05) across all three methods. GPA revealed significant genome-wide genetic overlap, highest for BMI and asthma (pleiotropy association ratio [PAR] = 0.377) and T2DM-asthma (PAR = 0.353). LAVA identified 111 significant local correlation regions, predominantly between T2DM and asthma (70 regions). Colocalization analysis identified 24 shared pleiotropic loci, predominantly on chromosome 8. Local genetic correlation analysis revealed extensive correlations between T2DM and asthma. PWAS identified 46 shared proteins, with IL6R, MAPK3, and CSF2 being key hubs. Protein–protein interaction analysis highlighted enrichment in JAK-STAT signaling, Th1/Th2 differentiation, and IL-17 pathways. GSMR demonstrated causal effects of BMI (OR = 1.47, 95% CI: 1.42–1.53, FDR < 0.05) and T2DM (OR = 1.06, 95% CI: 1.04–1.08, FDR < 0.05) on increased asthma risk, with no evidence of reverse causality. Conclusions: Obesity (BMI) and T2DM exert causal effects on asthma risk via shared genetic loci and inflammatory pathways, particularly involving IL6R, MAPK3, CSF2, and JAK-STAT signaling. Targeting these colocalized proteins may offer potential therapeutic strategies. Full article

Background: Sarcopenia, characterized by loss of muscle mass, strength, and function, reduces independence and quality of life in older adults. Strength exercise (STR) mitigates these age-related declines, but evidence of short-term effectiveness remains limited. This study aimed to evaluate the effects of eight weeks of STR on body composition, muscle strength, and psycho-emotional state in community-dwelling elderly women. Methods: A prospective, controlled, non-randomized study included 44 women assigned to an STR (n = 20) or control (CON, n = 22) group. The STR group performed supervised exercise twice weekly for eight weeks. The outcomes were body composition, handgrip strength (HGS), quadriceps (Q) and hamstrings (H) strength, and perceived stress (PSS-10), assessed at baseline and after intervention. Within-group changes were analyzed using paired t-tests, and between-group differences were evaluated using analysis of covariance (ANCOVA) adjusted for baseline values. Results: After baseline adjustment, body mass (p = 0.041, partial η² = 0.103), BMI (body mass index, p = 0.030, partial η² = 0.115), and body fat percentage (p = 0.047, partial η² = 0.098) were significantly reduced in the STR group. Significant improvements were observed for H strength in both legs (p < 0.05, partial η² = 0.128–0.131), right HGS (p = 0.025, partial η² = 0.122), right HGS:BMI ratio (p = 0.013, partial η² = 0.150), and H:Q ratios on both sides (p < 0.05, partial η² = 0.109–0.118). No significant differences were observed for left-hand grip strength, knee extensor strength, or other body composition variables (p > 0.05). The perceived stress scores were significantly lower in the STR group post-intervention (p = 0.036, partial η² = 0.108). Conclusions: An eight-week supervised strength exercise program was associated with favorable changes in muscle strength, body composition, and psycho-emotional state in elderly women. Full article

Background/Objectives: The objective of this study was to assess the diagnostic accuracy of the Triglyceride-Glucose (TyG) index for screening gestational diabetes mellitus (GDM) at 24–28 weeks of gestation, to determine its optimal diagnostic threshold, and to compare its predictive performance with conventional lipid ratios (LDL/HDL, TG/HDL, and TC/HDL). Materials and Methods: We retrospectively analyzed 440 pregnant women with singleton pregnancies who underwent a 75 g oral glucose tolerance test (OGTT) between January and July 2025. The TyG index and lipid ratios were calculated, and their associations with GDM were evaluated. Subgroup analyses were conducted to assess the efficacy of the TyG index in predicting GDM, using logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), and receiver operating characteristic (ROC) curve analysis along with restricted cubic spline modeling to evaluate diagnostic performance and determine the optimal cutoff value. Results: The overall prevalence of GDM, as defined by the IADPSG (International Association of the Diabetes and Pregnancy Study Groups) criteria, was 22.7%. The median TyG index was significantly higher in the GDM group compared with the non-GDM group (9.1 vs. 8.9, p = 0.001). The TyG index was a significant predictor of GDM (p < 0.05), with each one-unit increase associated with significantly higher odds of GDM (OR = 12.29), after adjusting for covariates. ROC analysis demonstrated an AUC of 0.716 (95% CI: 0.627–0.793, p < 0.001) for the TyG index, and the optimal cut-off value was identified as 9.35, yielding a sensitivity of 38.5% and a specificity of 96.5% and a negative predictive value of 83.7%. Subgroup analyses indicated that the TyG index had limited discriminative ability for predicting GDM in both the post-load and insulin-requiring groups. Among conventional lipid ratios, TG/HDL demonstrated the highest predictive performance (AUC = 0.587), while LDL/HDL (AUC = 0.483) and TC/HDL (AUC = 0.509) demonstrated low predictive accuracy. Compared with conventional lipid ratios, the TyG index demonstrated superior predictive performance. Conclusions: A higher TyG index was positively associated with the development of GDM and showed better predictive ability than conventional lipid ratios. However, its low sensitivity limits its use as a standalone diagnostic tool, suggesting it may be most useful when combined with other clinical parameters. Full article

This study aimed to examine the associations between distinct tobacco smoke exposure (TSE) biomarkers and healthcare utilization patterns in U.S. children ages 3–11 years with and without current asthma. Secondary data from the 2013–2016 National Health and Nutrition Examination Survey were analyzed (N = 2838). TSE biomarkers included serum cotinine, urinary total nicotine equivalents (TNE2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the NNAL/TNE2 ratio, and the N-acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)/TNE2 ratio. We conducted Poisson regression analyses to examine the associations between each biomarker and healthcare visits and hospitalizations within the past 12 months, adjusting for sociodemographic and home TSE covariates. Children without asthma who had higher urinary TNE2 levels (adjusted incidence rate ratio [aIRR] = 1.03, 95% confidence interval [CI] = 1.02–1.04) and children with asthma who had higher urinary 2CyEMA/TNE2 ratio levels (aIRR = 1.05, 95%CI = 1.03–1.07) were at an increased risk of having more healthcare visits. Children without asthma who had higher serum cotinine (aIRR = 1.21, 95%CI = 1.07–1.37) and higher 2CyEMA/TNE2 ratio levels (aIRR = 1.25, 95%CI = 1.14–1.37) were at an increased risk of hospitalizations. Children with asthma who had higher NNAL/TNE2 ratio levels (aIRR = 1.52, 95%CI = 1.11–2.09) were at increased risk of hospitalizations. It is important to consider comprehensive biomarkers of TSE in children, such as TNE, tobacco-specific nitrosamines, and volatile organic compounds, along with healthcare utilization patterns. Child TSE reduction policies are urgently needed. Full article