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Nursing homes in Sweden provide housing and care for people aged 65 years or older who require assistance with everyday activities. An increasing number of nursing home residents have cognitive and functional decline, which can result in additional time needed for care provision. This study aimed to explore changes in resource use and associated factors in Swedish nursing homes over a 5-year period. This repeated cross-sectional study analyzed baseline (2013-2014) and follow-up (2018-2019) proxy-rated data from 4599 participants from the Swedish National Inventory of Care and Health in Residential Aged Care study. Resource use was measured using the Resource Use in Dementia scale. Descriptive statistics, t-tests, chi-square tests, and multiple linear regressions were performed. Total resource use increased from 7.15 h/day to 7.83 h/day between baseline and follow-up. The number of residents living in a dementia unit increased from 34.6% to 43%. Higher independence in activities of daily living was associated with lower total resource use at follow-up while living in a dementia unit was associated with higher total resource use. Higher total resource use was associated with seven neuropsychiatric symptoms. For residents living in a dementia unit, four neuropsychiatric symptoms were associated with higher total resource use. Resource use in Swedish nursing homes increased between baseline and follow-up. These results may inform future policy, financing, and implementation decisions to support resource utilization in nursing homes.

Worldwide metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease. Despite high global prevalence, MASLD is not yet recognized as a noncommunicable disease, although all of the criteria are fulfilled for such a classification. MASLD is strongly associated with type 2 diabetes, cardiovascular disease, chronic kidney disease, and certain extrahepatic cancers. At 65% and 37% the prevalence of MASLD is extremely high in adults and children with type 2 diabetes, respectively. The pathogenesis of MASLD is closely related to that of type 2 diabetes, and diabetes-associated hyperglycemia, hyperinsulinemia, and hyperlipidemia promote progression from simple steatosis to hepatic inflammation and fibrosis. Thus, MASLD is now considered a complication of diabetes. However, there is still a great deal of work to be done to implement screening for and treatment of MASLD in everyday clinical diabetes management. In this article, the major mechanisms involved in the pathogenesis of MASLD and type 2 diabetes are discussed. Furthermore, the heterogeneity in the pathophysiology of MASLD and clusters in MASLD that may be relevant for future stratification of MASLD-associated risk of diseases are addressed. Finally, because of their strong hepato-, cardio-, and nephroprotective effects this article provides support as to why sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor (co)agonists should be used as first-line pharmacotherapies in people with MASLD and type 2 diabetes.

Dual-task cost (DTC) is the performance decline observed during simultaneous motor and cognitive tasks. It is associated with cognitive and physiological vulnerability. However, it remains unclear how specific frailty dimensions and cognitive domains contribute to DTC during arithmetic and verbal fluency tasks. We aim to investigate the independent associations between physical, social and oral frailty dimensions versus cognition function with DTC in community-dwelling older adults. We studied 281 participants from the GeriLABS-2 study. Physical frailty was assessed using Fried's Frailty Phenotype, social frailty using the 8-item Social Frailty Scale (SF8) and oral frailty using the Oral Frailty Index-8 (OFI-8). Cognitive function was assessed with Chinese Mini Mental State Examination (CMMSE) and Chinese Frontal Assessment Battery (CFAB). DTC on gait was assessed with arithmetic (counting backwards from 100) and verbal fluency (animal naming) cognitive tasks. Association of DTC with frailty dimensions and cognition were evaluated via hierarchical linear regression, adjusted for demographics. Higher CFAB score was significantly associated with lower DTC in both arithmetic (B=-2.067, p < 0.001) and verbal fluency (B=-1.489, p = 0.020) tasks, suggesting individuals with better executive function showed lower DTC. Social frailty (Factor 2 - social activity and financial resources) and oral frailty (Factor 3 - dietary and social habits) were significantly associated with DTC for arithmetic task (B = 2.664, p = 0.030; B = 3.718, p = 0.007). No significant association was observed for physical frailty. The final composite model showed that CFAB has a significant associated with DTC arithmetic (B=-2.012, p < 0.001) and DTC verbal fluency (B=-1.537, p = 0.016) tasks. Cognitive frailty, particularly executive dysfunction, is a key factor contributing to difficulties with dual tasking. Social and oral frailty factors may influence DTC during arithmetic tasks, however their effects were attenuated after adjusting for cognition. Interventions addressing cognitive frailty may be a promising target for mitigating DTC in older adults.

Lumbar fusion alters spinal-pelvic biomechanics and may influence degenerative changes in the lower extremities. This study investigated whether fusion length is associated with radiographic progression of hip and knee osteoarthritis. In this retrospective, single-center cohort study, patients aged 40-65 years who underwent lumbar surgery between 2010 and 2021 were grouped as no fusion (N), short fusion (S; &#x2264;3 levels), or long fusion (L; &#x2265;4 levels). Hip joint space width was assessed using minimum joint space (MJS) and superointermediate joint space (SJS), including femoral head-standardized measures (sMJS and sSJS). Knee medial joint space width (KMJS) was measured when available. Spinopelvic parameters (LL, PI, PT, SS, PI-LL) and functional outcomes (ODI, HHS, WOMAC) were recorded. Multivariable linear and logistic regression analyses were performed to identify independent predictors of joint space narrowing and osteoarthritis risk. Hip joint space narrowing differed significantly among groups, with the highest annual narrowing rates in the long-fusion group, followed by the short-fusion group, and the lowest in the no-fusion group (p&#x2009;<&#x2009;0.001). In contrast, knee KL grade change and annual KMJS narrowing did not differ significantly between groups (p&#x2009;>&#x2009;0.05). In logistic regression, each additional fused level increased the odds of postoperative MJS&#x2009;&#x2264;&#x2009;2.0&#xa0;mm by 16-19%, and higher CEA was also associated with increased risk. Long-segment lumbar fusion (&#x2265;&#x2009;4 levels) was associated with greater hip joint space narrowing and greater radiographic progression of hip osteoarthritis, whereas knee degeneration did not differ by fusion status. Patients undergoing extensive fusion may benefit from closer hip surveillance to facilitate earlier recognition of degeneration.

Obesity and autoimmune diseases (AIDs) are each associated with elevated risk of cardiovascular and thromboembolic events. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular and metabolic benefits in patients with type 2 diabetes and obesity, but their effects in patients with obesity and comorbid AID remain uncertain. This study evaluated the association between GLP-1RA use and major adverse cardiovascular and thromboembolic event risk among adults with obesity and AID. This retrospective cohort study emulated a target trial using 2014 to 2024 electronic health record data from the OneFlorida+ network. Adults (aged &#x2265;18&#x2009;years) with AID and obesity eligible for antiobesity medication therapy were included. Exposure was defined as GLP-1RA use versus nonuse. Participants were matched using 1:1 time-dependent propensity scores. The primary outcomes were myocardial infarction, stroke or transient ischemic attack, pulmonary embolism, venous thromboembolism, and coronary revascularization. Secondary outcomes included hospitalization, emergency department visits, and all-cause mortality. We matched 13&#x2009;204 GLP-1RA users and 13&#x2009;204 nonusers (mean &#xb1; SD age, 54.7&#x2009;&#xb1;&#x2009;14.5&#x2009;years; 73.4% women; mean body mass index, 37&#x2009;kg/m2). GLP-1RA use was associated with lower hazard of stroke/transient ischemic attack (hazard ratio [HR], 0.87 [95% CI, 0.76-0.99]; P=0.039), pulmonary embolism (HR, 0.69 [95% CI, 0.56-0.86]; P=0.001), venous thromboembolism (HR, 0.83 [95% CI, 0.72-0.95]; P=0.007), emergency department visits (HR, 0.79 [95% CI, 0.75-0.83]; P<0.001), and mortality (HR, 0.56 [95% CI, 0.47-0.66]; P<0.001). Among adults with obesity and AID, GLP-1RA use was associated with reduced thromboembolic events, lower emergency department use, and decreased mortality, suggesting potential cardiovascular and survival benefits in this high-risk population.

Advanced amyloid beta (A&#x3b2;) pathology is associated with aberrant neuronal network activity and cognitive impairment in preclinical Alzheimer's disease (AD) models. Here, we assess A&#x3b2; pathology's impact on spatial information processing in the medial entorhinal cortex (MEC) of 18-month AppNL-G-F/NL-G-F knock-in (APP KI) mice during exploration of open field arenas. Spatial information scores are decreased in APP KI MEC neurons versus age-matched controls. Border cell firing preferences are unstable across sessions and grid cell spatial periodicity is disrupted. Ratemap stability analysis using the Earth Mover's Distance indicates increased instability in spatially tuned APP KI neurons. Spatial decoding analysis indicates deficits in position and speed coding in APP KI mice across all comparisons. Additionally, APP KI mice display a mild hyperactive phenotype driven by narrow-spiking putative interneurons. These findings tie A&#x3b2;-associated dysregulation in neuronal firing to disruptions in spatial information processing that may underlie cognitive deficits associated with AD.

Objectives: Identify post-traumatic growth (PTG) and the roles of mindfulness, social support, and loneliness in PTG among college students with and without disabilities post-COVID-19. Participants: Six hundred college students enrolled at two universities in Texas. Methods: Participants completed self-report questionnaires via an online Qualtrics survey. Descriptive, bivariate correlation, independent t-test, and regression analyses were conducted. Results: The average PTG score was 28.34 (SD = 12.66), with 45.2% scoring 32 or above, indicating personal growth. Students with disabilities had significantly lower PTG scores (p&#x2009;<&#x2009;.001). For these students, identifying as Black, family loss due to COVID-19, and friends support were associated with higher PTG. Among those without disabilities, racial minority status, family loss, and mentor support were associated with higher PTG. Conclusions: Post-pandemic PTG is notably low among college students, especially those with disabilities, underscoring the need for greater support. Strengthening social connections may improve their PTG, mental health, and academic success.

Accumulating evidence indicates that diabetes is associated with increased risk of several cancers. The strongest evidence has been reported for cancers of the breast, colorectum, endometrium, liver, pancreas, and gallbladder. However, distinguishing causal relationships from associations driven by shared risk factors such as obesity, aging, and lifestyle behaviors remains challenging. Several biological mechanisms have been proposed to explain these associations. Key pathways include the effects of insulin resistance and compensatory hyperinsulinemia on mitogenic signaling pathways, including PI3K/AKT/mTOR and MAPK, as well as the influence of adiposity, chronic inflammation, and altered metabolic substrates on tumor initiation and progression. Hyperglycemia may also contribute by promoting tumor metabolism and cellular proliferation, although its independent contribution remains debated. These mechanisms likely interact to create a protumorigenic metabolic environment in individuals with diabetes. Obesity, which frequently co-occurs with diabetes, further amplifies these risks through altered adipokine secretion and increased estrogen production, highlighting the interrelated contributions of metabolic and hormonal factors. The relationship between diabetes and cancer has important clinical implications. Diabetes has been associated with worse cancer prognosis and higher cancer-related mortality, highlighting the importance of integrated management strategies. The impact of antihyperglycemic therapy on cancer risk and progression has been extensively studied, and ongoing research continues to evaluate potential protective or tumor-modifying effects. In this article, we summarize the epidemiologic and pathophysiologic evidence describing the relationship between diabetes and cancer and discuss strategies for risk mitigation, screening, and management.

Do semen quality parameters differ between 'high' and 'low' levels of physical fitness in a cohort of Spanish men? Semen samples donated by 324 Spanish men without known reproductive disorders were analysed to determine sperm count, concentration and progressive motility. Overall fitness, cardiorespiratory fitness and muscular strength were self-reported using the International Fitness Scale. Additionally, muscular strength was assessed objectively using a handgrip dynamometer. Analyses of covariance and adjusted linear regression analyses were performed to explore the association between the components of physical fitness and semen quality parameters. Men with higher self-reported cardiorespiratory fitness and muscular strength presented higher sperm counts compared with men with lower values [adjusted raw mean difference 44.315 &#xd7; 106 (95% CI 7.699-80.931) spermatozoa/ejaculate and 42.766 &#xd7; 106 (95% CI 6.215-79.316) spermatozoa/ejaculate; adjusted mean Z-score difference 0.232 (95% CI 0.014-0.449) SDs and 0.236 (95% CI 0.019-0.453) SDs; P = 0.037 and 0.033, respectively]. Objectively measured handgrip muscular strength was not associated with any semen quality parameter. This cross-sectional study suggests that self-reported cardiorespiratory fitness and muscular strength are positively associated with semen quality parameters, while objectively measured handgrip strength shows no association. These results may provide insight into modifiable lifestyle factors potentially related to semen quality, and help guide future randomized controlled trials to clarify causal pathways.

This study represents the first case series from T&#xfc;rkiye to systematically examine autopsy-confirmed myocardial infarction [MI] in the pediatric age group. The aim of the study was to evaluate the demographic, clinical, and pathological features of pediatric MI cases and to identify potential associated factors. All the cases demonstrated histopathological evidence of MI, and MI was identified as the immediate cause of death in 41.7% of cases. Age, sex, scene of discovery, cause of death, body mass index [BMI], heart weight, and histopathological features were analyzed. Half of the cases were male. All cases had patent coronary lumens with no thromboembolic occlusion. Histopathological examination showed features consistent with approximately 24&#xa0;h in 75.0%, 72&#xa0;h in 16.7%, and 10-14 days in 8.3% of cases. In cases aged&#x2009;>&#x2009;24 months, MI-related deaths had higher mean heart weights and BMI than deaths due to other causes within the same age stratum. Although uncommon, pediatric MI can occur in the absence of coronary thrombosis. The findings of this study suggest that pediatric MI is frequently associated with non-atherosclerotic and multifactorial mechanisms. However, these observations are based on a limited forensic autopsy sample and should be interpreted with caution.

Autism is a heterogeneous neurodevelopmental condition arising from complex interactions between genetic susceptibility and environmental factors. Lithium, a naturally occurring element used therapeutically for bipolar disorder and present in food and drinking water, warrants careful evaluation because it readily crosses the placenta and modulates biological pathways critical for brain development. We conducted a structured literature review of PubMed, Embase, and Web of Science through February 20, 2026, and identified 72 human, animal, and in vitro studies examining lithium exposure in relation to autism or neurodevelopmental outcomes. Epidemiologic evidence remains limited, with few studies directly assessing prenatal exposure and insufficient evidence to establish environmental lithium exposure as a neurodevelopmental risk factor. Most human clinical studies reflect therapeutic contexts and demonstrate the mood-stabilizing effects of lithium, whereas human biomarker and experimental studies provide evidence for modulation of glycogen synthase kinase-3&#x3b2; (GSK3&#x3b2;) signaling and thyroid function. Experimental studies indicate that lithium can normalize disease-associated phenotypes in autism-relevant models, yet it also induces behavioral and neurological alterations in non-mutant control models, particularly following high-dose or prenatal exposure. Across evidence streams, convergent findings implicate phosphatidylinositol-calcium signaling, GSK3&#x3b2;-dependent pathways, glutamatergic synapse function, and thyroid hormone regulation, supporting the biological plausibility of lithium-related neurodevelopmental effects. Overall, lithium-associated neurodevelopmental effects appear dose-, context-, and timing-dependent. Knowledge gaps remain regarding environmentally relevant prenatal exposures and long-term neurodevelopmental outcomes, underscoring the need for rigorous epidemiologic and mechanistic studies incorporating refined exposure assessment, developmental timing, and genetic susceptibility.

Pancreatic cancer (PC) is a highly aggressive malignancy, with cancer stem cells (CSCs) playing a critical role in metastasis, therapy resistance, and recurrence, thereby presenting significant treatment challenges. Emerging evidence suggests that normal embryonic and adult progenitor stem cells share common gene signatures with CSCs. However, the early pluripotency-associated factors and stemness programs that become aberrantly reactivated during oncogenic transformation remain poorly defined. Here, we identify SLC22A3/OCT3 (Solute Carrier Family 22 Member 3) as a reactivated embryonic-associated signature that regulates PC stemness. SLC22A3 is markedly upregulated in CSC-enriched populations, and its silencing in PC cells grown in both 2D cultures and 3D organoid models significantly reduces key stemness features. Moreover, serotonin (5-HT) transport, mediated by SLC22A3, enhances overall stemness via downstream histone modifications, linking serotonin signaling to CSC regulation. Collectively, these findings establish SLC22A3 as a regulator of serotonin-driven stemness and a potential therapeutic target in PC.

Gout is increasingly recognized as a systemic metabolic and inflammatory disorder. The urate paradox-where uric acid shifts from a plasma antioxidant to an intracellular pro-oxidant-remains a clinical challenge in managing systemic complications. This study evaluates the association between systemic oxidative stress imbalance and high-sensitivity C-reactive protein (hs-CRP) as a marker of inflammatory burden in gouty patients. A case-control study was conducted on 200 participants (100 gouty patients and 100 healthy controls) in Yemen. Biomarkers including malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH), and hs-CRP were quantified. Multivariate linear regression was used to assess the independent predictive value of MDA for hs-CRP. Gouty patients exhibited significantly elevated MDA (6.45&#x2009;&#xb1;&#x2009;1.55&#xa0;nmol/mL) and hs-CRP (14.2&#x2009;&#xb1;&#x2009;5.1&#xa0;mg/L) compared to controls (P&#x2009;<&#x2009;0.001). Conversely, a profound depletion in TAC and GSH was observed. A statistically significant positive correlation (r&#x2009;=&#x2009;0.78, P&#x2009;<&#x2009;0.001) was observed between MDA and hs-CRP. In multivariate analysis, MDA remained a significant independent associate, explaining approximately 61% of the variance in hs-CRP levels (R2&#x2009;=&#x2009;0.61, P&#x2009;<&#x2009;0.001). Gout is characterized by a significant systemic oxidative stress imbalance which is independently associated with systemic inflammation. Clinical management should transcend urate-lowering therapy to include strategies aimed at restoring antioxidant capacity to mitigate systemic inflammatory damage. Key Points &#x2022; Gouty patients exhibit a profound state of systemic redox exhaustion, characterized by depleted antioxidant defenses. &#x2022; Lipid peroxidation (MDA) is strongly associated with the systemic inflammatory burden (hs-CRP) in gouty cohorts. &#x2022; The robust correlation between oxidative stress and inflammatory markers suggests their potential as biomarkers for assessing disease status. &#x2022; Systemic inflammation in gout appears to be closely linked to the severity of oxidative stress imbalance.

MicroRNAs (miRNAs) and the NAD+-dependent deacetylase SIRT1 are critical regulators of hepatic metabolism, inflammation, and stress responses. Growing evidence suggests that miRNA-SIRT1 interactions are frequently disrupted during the pathogenesis of liver diseases, including Metabolism-Associated Steatotic Liver Disease (MASLD), Alcohol-Associated Liver Disease, Drug-Induced Liver Injury (DILI), fibrosis, and hepatocellular carcinoma (HCC).In the context of metabolic liver diseases, specific miRNAs, such as miR-122, miR-93, miR-132, miR-34a, and miR-141, regulate lipid and energy metabolism by modulating SIRT1 and its downstream targets, notably AMPK and PGC-1&#x3b1;. Furthermore, miRNAs can suppress SIRT1 activity during liver injury, exacerbating oxidative stress, mitochondrial dysfunction, and inflammation. In HCC, the role of SIRT1 is context-dependent; influenced by the stage of differentiation and genetic factors such as p53, SIRT1 may exert either tumor-suppressive or tumor-promoting effects. While preclinical studies demonstrate the therapeutic potential of targeting the miRNA-SIRT1 pathway, current evidence remains largely experimental. Pharmacological modulation, via SIRT1 activators, small-molecule compounds, or RNA-based therapeutics, has shown promise in experimental models. However, significant hurdles impede clinical translation, including poor bioavailability, off-target effects, and, most critically, the complex, context-specific biological role of SIRT1 within the liver. Ultimately, while the miRNA-SIRT1 axis appears to be a central regulatory pathway in liver disease, its translational potential and safety in humans require further mechanistic and clinical investigation.

We aimed to assess the prognostic role of untreated moderate-to-severe tricuspid regurgitation (TR) by a systematic review and meta-analysis. We searched Pubmed from database inception to 14 August 2025. Studies reporting data on clinical outcomes associated with different TR grades not receiving treatment were considered eligible. The primary endpoint was all-cause mortality; secondary endpoints included cardiovascular (CV) mortality and heart failure (HF) hospitalization. Pooled estimates were calculated using random-effects models. Our literature search yielded 2,727 articles, of which 225 were assessed for full-text eligibility. A total of 106 studies (107 comparisons) comprising 961,136 patients, were included in the quantitative synthesis. The overall prevalence of untreated moderate-to-severe TR was 13.5%, but varied widely across population subgroups. Moderate-to-severe TR was associated with a significantly higher all-cause mortality compared with none-to-mild TR (unadjusted HR 2.07; 95% CI 1.89-2.26; p < 0.001). The association was confirmed in adjusted models and among different subgroups (i.e., patients performing a general echocardiographic irrespective of indication, patients with left-side valvular heart disease [LSVHD], HF without LSVHD, patients undergoing cardiac implantable electronic device implantation, left ventricular assist device recipients and in patients with pulmonary artery hypertension), but not after heart transplantation. A stepwise increase in mortality was observed with increasing TR severity. Moderate-to-severe TR was also associated with higher risk of CV mortality and HF hospitalization (HR 1.92 [1.64-2.26] and HR 1.63[1.44-1.84], respectively). Untreated moderate-to-severe TR is associated with higher risk of all-cause mortality, CV mortality and HF hospitalization, underlying the role of timely diagnosis and appropriate management.

Anti-programmed cell death-(ligand) 1 (anti-PD-[L]1) agents are approved for advanced and early-stage cancers. While they may offer clinical and economic benefits in the neoadjuvant and/or adjuvant setting, their population-level impact in Italy has not been thoroughly evaluated. This study aims to estimate health and productivity outcomes of introducing anti&#x2011;PD&#x2011;(L)1 agents for neoadjuvant and/or adjuvant therapy in early&#x2011;stage cancers in Italy (melanoma Stage IIB/C, melanoma Stage III, renal cell carcinoma, triple&#x2011;negative breast cancer and resectable non&#x2011;small&#x2011;cell lung cancer) over a 10-year horizon. We developed a model synthesising outputs from five indication-specific Markov models comparing two worlds: one without anti-PD-(L)1 agents use in the neoadjuvant and/or adjuvant settings versus one with their use. Italian-specific population and incidence inputs were used, with clinical and quality-of-life data from individual trials, from a societal perspective with 3% annual discount. Outcomes included total life years (LYs), recurrence- free (RF)/event-free (EF)/disease-free (DF) LYs, quality-adjusted LYs (QALYs), number of recurrences/events, metastatic treatments, total deaths and deaths after first event/recurrence. Productivity gains were estimated using a human capital approach. Between 2025 and 2034, 118,329 patients with early-stage cancer were estimated to be eligible for anti-PD-(L)1 agents in Italy. Compared with no early-stage use, neoadjuvant/adjuvant use was associated with increased total LYs (+&#x2009;20,458, +&#x2009;5%), RF/EF/DF LYs (+&#x2009;60,631, +&#x2009;19%), QALYs (+&#x2009;21,093, +&#x2009;6%) and fewer recurrences/events (-&#x2009;20,209, -&#x2009;33%), metastatic treatments (-&#x2009;25,220, -&#x2009;38%), total deaths (-&#x2009;7137, -&#x2009;24%) and deaths after first event/recurrence (-&#x2009;8021, -&#x2009;32%). Productive years gained were 35,897 (+&#x2009;30%). Our study suggests that the use of anti-PD-(L)1 agents in early-stage cancers is associated with substantial health and societal gains in Italy. Expanding their use across approved indications translates trial benefits into fewer recurrences, deaths and productivity losses, informing national planning and access decision.

Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Altered cytokine-chemokine profiles have been reported, but their relationship with Fontan pathophysiology remains poorly defined. Adult Fontan patients and matched controls were assessed for frailty, cardiopulmonary exercise capacity, and resting/exercise-augmented hemodynamics. Plasma cytokine-chemokine concentrations were measured using multiplex ELISA. Twenty Fontan patients (mean age 28.8 &#xb1; 9.8 years; 35% female) and 20 controls (29.7 &#xb1; 6.0 years; 30% female) were studied. Fontan patients had slower 5&#xd7; sit-to-stand times (9.6 &#xb1; 3.1 vs. 5.7 &#xb1; 1.3 sec; p<0.0001), lower VO&#x2082;max (% predicted), and reduced stroke index, cardiac index, and cardiac power index. TNF-&#x3b1;, IL-1&#x3b2;, IL-6, IFN-&#x3b3;, IL-8, IP-10, MCP-1, and SDF-1&#x3b1; were elevated in Fontan patients, while IL-10 and MIP-1&#x3b1; were not different. SDF-1&#x3b1; and IP-10 correlated with frailty, impaired oxygen uptake, and hemodynamic parameters. Elevated SDF-1&#x3b1; and IP-10 are associated with frailty and impaired exercise hemodynamics in Fontan patients. These novel findings suggest a role for inflammation in Fontan-associated dysfunction and warrant further investigation.