Am J Med Sci
· 2026 Jul · PMID 42019835
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BACKGROUND: Acute lung injury (ALI) is a serious inflammatory condition caused by several insults, including LPS-induced immunity dysregulation, among others. In vitro and in vivo models are used to study the protective...BACKGROUND: Acute lung injury (ALI) is a serious inflammatory condition caused by several insults, including LPS-induced immunity dysregulation, among others. In vitro and in vivo models are used to study the protective effect of Naftidrofuryl (NAF) against LPS-induced lung injury. METHODS: Murine RAW 264.7 cells were treated with NAF (10 µM). In addition, NAF (45 mg/kg) was injected intraperitoneally in a rat model for 28 days to assess its effects on LPS-induced acute lung injury (3 mg/kg). Several biomarkers in vitro cells and rat model tissue were used to investigate the mechanisms. ELISA, western blotting, and immunohistochemistry were used. RESULTS: LPS caused RAW 264.7 cells to express higher levels of CD11b, CD38, and CD206, indicating macrophage activation and inflammation. In rats, LPS increased CXCL1 and CXCL2 levels, NFκB activity, pyroptosis, and IL-1β via GSDMD signaling. Histopathological analysis and scoring showed that NAF treatment reduced LPS-induced ALI by normalizing biomarker levels and lung tissue damage. CONCLUSIONS: The findings showed that NAF can regulate innate immune responses, suppress inflammation, and reduce lung injury in LPS-induced ALI. These findings aid the development of anti-inflammatory treatments for bacterial and inflammatory pulmonary diseases.
Zou L, Mao L, Wang J
… +6 more, Zhao Y, Wang S, Wei S, Chao M, Zhu X, Wang D
Am J Med Sci
· 2026 Jul · PMID 41967804
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BACKGROUND: Diaphragmatic dysfunction (DD) is a prevalent complication in ischemic stroke patients, significantly compromising respiratory function and worsening clinical outcomes. However, early risk factors for post-st...BACKGROUND: Diaphragmatic dysfunction (DD) is a prevalent complication in ischemic stroke patients, significantly compromising respiratory function and worsening clinical outcomes. However, early risk factors for post-stroke DD and their prognostic implications remain poorly understood. MATERIALS AND METHODS: The cohort study enrolled 83 ischemic stroke patients. Demographics and diaphragmatic ultrasound assessments were obtained within 48 hours of admission. Clinical evaluations comprised the Glasgow Coma Scale, National Institutes of Health Stroke Scale, Fugl-Meyer Assessment for upper extremity (FMA-UE), Barthel Index (BI), modified Rankin Scale (mRS), Brunnstrom recovery stages (BRS) along with brain/chest imaging, dysphagia screening, inflammatory markers, arterial blood gas analysis. RESULTS: The incidence of DD among the 83 ischemic stroke patients was 55.42%. Patients with DD exhibited significantly lower FMA-UE and BI scores, but higher mRS and BRS scores. Laboratory analyses showed significantly higher C-reactive protein, but lower creatine kinase (CK), Pre-albumin, and Creatinine compared to non-DD controls. Diaphragmatic elevation (DE) was observed in 89.13% of DD patients versus only 13.51% of non-DD patients. Moreover, mean diaphragmatic mobility (DM) during quiet breathing was significantly reduced in the DD group. Both DM (r = 0.223, p = 0.044) and DE (r = 0.270, p = 0.014) showed significant independent correlations with mRS scores. Regression analysis identified mRS (β = 0.310; T = 2.097; p = 0.041), Creatinine (β = 0.308; T = 2.206; p = 0.032), pneumonia (β = 0.332; T = 2.625; p = 0.011), and DE (β = 0.331; T = 2.308; p = 0.025) as significant predictors of DM. CONCLUSIONS: Significant risk factors for DD include advanced age, poor nutritional status, concurrent pneumonia, lower CK levels, and greater neurological impairment severity measured by FMA-UE, BI, mRS and BRS.
Wilson S, Hooper Z, Devaney D
… +2 more, Geis N, Shah V
Am J Med Sci
· 2026 Jul · PMID 41937085
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ANCA-associated vasculitis is a systemic autoimmune disease that typically affects the kidneys, lungs, and upper respiratory tract. Muscle-predominant ANCA-associated vasculitis is exceedingly rare and frequently misdiag...ANCA-associated vasculitis is a systemic autoimmune disease that typically affects the kidneys, lungs, and upper respiratory tract. Muscle-predominant ANCA-associated vasculitis is exceedingly rare and frequently misdiagnosed as idiopathic inflammatory myopathy due to overlapping clinical and imaging findings. We report a 73-year-old male presenting with progressive proximal muscle weakness, normal creatine kinase, and MRI findings suggestive of myositis. Acute kidney injury prompted further investigation, and muscle and renal biopsies confirmed ANCA-associated vasculitis. The patient improved with rituximab and avacopan, an emerging glucocorticoid-sparing therapy. This case-based mini-review summarizes the epidemiology, diagnostic challenges, biopsy timing, and treatment strategies for muscle-predominant ANCAassociated vasculitis, underscoring the importance of tissue diagnosis and early, targeted therapy in atypical presentations.
Al-Hatamleh MAI, Hamid M, Vashisht M
… +2 more, Hatmal MM, Mussa A
Am J Med Sci
· 2026 Jul · PMID 41903650
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Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematologic malignancies but faces significant challenges in solid tumors such as breast cancer. A primary obstacle is the immunosuppressi...Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematologic malignancies but faces significant challenges in solid tumors such as breast cancer. A primary obstacle is the immunosuppressive tumor microenvironment (TME), which drives T-cell exhaustion and limits therapeutic efficacy. Lymphocyte-activation gene 3 (LAG-3) is a key mediator of this exhaustion, suppressing antitumor immunity upon engagement with ligands such as MHC class II. This review examines the rationale for targeting the LAG-3 pathway to enhance CAR T cell potency within the breast cancer TME. We critically evaluate emerging bioengineering strategies designed to counteract LAG-3-mediated suppression, focusing on two complementary approaches: (1) armored CAR T cells engineered to secrete anti-LAG-3 antibody fragments locally within the TME, and (2) CAR T cells modified to express dominant-negative LAG-3 receptors or with LAG-3 genetically ablated, conferring intrinsic resistance to this inhibitory axis. By combining precise tumor recognition with localized or intrinsic checkpoint disruption, these next-generation therapies aim to enhance T-cell persistence, proliferative capacity, and cytotoxic function. Interrupting LAG-3 signaling represents a transformative strategy to reverse TME-driven immunosuppression, offering the potential for more durable clinical responses in breast cancer. Translating this promise into reality will require rigorous preclinical validation and innovative clinical trial designs.
Wei Y, Liu X, Yang C
… +9 more, He D, Luo S, Wang J, Qiu Y, Bi H, Fu J, Qian P, Feng S, Liu X
Am J Med Sci
· 2026 Jul · PMID 41856279
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BACKGROUND: Although QT interval prolongation (QTP) is prevalent in sepsis, its implications for patient outcomes are not fully elucidated. METHODS: We analyzed MIMIC-IV data to determine the incidence and clinical profi...BACKGROUND: Although QT interval prolongation (QTP) is prevalent in sepsis, its implications for patient outcomes are not fully elucidated. METHODS: We analyzed MIMIC-IV data to determine the incidence and clinical profile of QTP within 7 days after sepsis diagnosis. QTP was defined as a corrected QT interval >450 ms in men and >460 ms in women.Confounding was addressed by employing propensity score matching (PSM). The association of QTP with 90-day mortality was evaluated using Cox regression. RESULTS: This study included 8988 patients, among whom 3954 cases (44.0 %) experienced QTP within one week of sepsis diagnosis. The incidence of QTP was 39.7 % on the first day, and then gradually declined to 32.5 % by the seventh day. QTP was associated with an increased risk of 90-day mortality among sepsis patients (unmatched: HR = 1.313, 95 % CI 1.203 - 1.434, P < 0.001; PSM: HR = 1.133, 95 % CI 1.024 - 1.253, P = 0.016). Gender significantly modified the QTP-mortality association (P for interaction = 0.015). Males demonstrated a 25.4 % increased risk (HR = 1.254, 95 % CI 1.099-1.430, P < 0.001). Notably, among patients with QTP, the mortality risk was similar whether the diagnosis was made within or after the first 24 hours (adjusted HR = 0.948, 95 % CI 0.813-1.105, P = 0.496). CONCLUSIONS: Over 40 % of sepsis patients developed QTP within one week. QTP independently predicted increased 90-day mortality, with a stronger effect in males. Among patients with QTP, the timing of QTP identification (≤24 h vs >24 h) was not associated with mortality..
Am J Med Sci
· 2026 Jul · PMID 41850526
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BACKGROUND: The association between hepatitis B virus (HBV) exposure (anti-HBc+) and metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a critical public health dilemma. Emerging evidence reveal...BACKGROUND: The association between hepatitis B virus (HBV) exposure (anti-HBc+) and metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a critical public health dilemma. Emerging evidence reveals paradoxical epidemiological patterns, with observational studies demonstrating lower NAFLD/MAFLD prevalence among individuals with HBV exposure despite its hepatotropic nature-contradicting conventional pathophysiological frameworks. Under the 2023 AASLD criteria requiring concurrent cardiometabolic risk factors with hepatic steatosis for MASLD diagnosis, understanding HBV-MASLD interactions across diverse populations becomes imperative. Current evidence predominantly derives from Asian cohorts, leaving U.S. population-level associations underexplored. OBJECTIVE: To investigate the population-level HBV-MASLD association among U.S. adults using nationally representative data. METHODS: We analyzed 2017-2020 NHANES data (n=6,342 adults, representing 181.71 million residents) through complex survey-weighted analyses. MASLD required hepatic steatosis (controlled attenuation parameter ≥285 dB/m) plus ≥1 CMRF. HBV exposure was diagnosed as HBcAb (+). Weighted multivariable logistic regression adjusted for demographic and metabolic confounders (R 4.2.2 and FreeStatistics v1.9.2; two-tailed α=0.05). RESULTS: The retrospective cross-sectional study (mean age 51.1±17.4 years; 52.5% female) included 509 HBV-exposed individuals (8.03%) and 1,712 MASLD cases (26.99%). HBV-exposed individuals demonstrated: 1) lower MASLD prevalence (21.6% vs. 27.5%); 2) persistently inverse association after full adjustment (OR 0.57, 95% CI 0.40-0.81); 3) consistent patterns across subgroups without significant interactions by demographics (all P > 0.05). Sensitivity analyses in the complete-case subset (n=5,355) confirmed robustness (OR 0.58, 95% CI 0.40-0.85). CONCLUSIONS: This observational U.S. study identifies an inverse association between HBV exposure and MASLD, suggesting the need for further investigation into metabolic assessment in this population.
Bolaji O, Bandaru R, Bahar Y
… +6 more, Bahar AR, Weze K, Pasupuleti S, Dodoo S, Frangieh AH, Alraies MC
Am J Med Sci
· 2026 Jun · PMID 41850525
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BACKGROUND: Patients with rheumatologic diseases (RD) present unique challenges in cardiovascular care due to systemic inflammation and complex medical management. However, transcatheter aortic valve replacement (TAVR) o...BACKGROUND: Patients with rheumatologic diseases (RD) present unique challenges in cardiovascular care due to systemic inflammation and complex medical management. However, transcatheter aortic valve replacement (TAVR) outcomes in this population remain poorly characterized. METHODS: Using the TriNetX database, we conducted a retrospective cohort study of patients undergoing TAVR between 2015 and 2023. Patients with RD (systemic lupus erythematosus, rheumatoid arthritis, or ankylosing spondylitis; n=4,447) were compared with non-RD patients (n=4,447) using 1:1 propensity score matching. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACCE), acute kidney injury, and other clinical endpoints. RESULTS: After propensity matching, baseline characteristics were well-balanced. During follow-up, RD patients demonstrated higher all-cause mortality compared to non-RD patients (25.4 % vs 23.2 %; hazard ratio [HR] 1.069; [1.002-1.139]; P=0.043). Kaplan-Meier survival analysis showed gradual curve separation over time. RD patients experienced significantly higher rates of MACCE (41.9 % vs 32.3 %; HR 1.266; [1.062-1.511]; P=0.008), acute kidney injury (20.5 % vs 18.0 %; HR 1.140; [1.016-1.279]; P=0.025), myocardial infarction (11.9 % vs 9.6 %; HR 1.236; [1.083-1.410; P=0.004), and heart failure events (7.3 % vs 6.1 %; HR 1.195; [1.002-1.424]; P=0.047). In multivariable Cox regression of the entire matched cohort, prednisone use was associated with increased mortality (HR 1.215; [1.167-1.264]; P < 0.001), while lipid-modifying agents showed protective effects (HR 0.947; [0.905-0.990]; P=0.016). CONCLUSIONS: TAVR in RD patients was associated with modestly higher all-cause mortality and significantly increased cardiovascular complications compared to non-RD patients. Optimized medication management, particularly regarding corticosteroid use and lipid modification, may improve outcomes in this high-risk population.
Am J Med Sci
· 2026 Jul · PMID 41845964
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INTRODUCTION: Both common diseases are gastroesophageal reflux disease (GERD) and gastroduodenal ulcer. However, whether GERD causes gastroduodenal ulcers remains uncertain or if the reverse relationship exists. Using Me...INTRODUCTION: Both common diseases are gastroesophageal reflux disease (GERD) and gastroduodenal ulcer. However, whether GERD causes gastroduodenal ulcers remains uncertain or if the reverse relationship exists. Using Mendelian randomisation, we investigated the potential causal link between GERD and gastroduodenal ulcers. METHODS: We conducted genome-wide genetic analyses based on extensive datasets: the European population GERD dataset (with 2320,781 SNPs) and the gastroduodenal ulcer dataset (with 16,380,400 SNPs). We used the R language to perform five MR Analyses, including inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple model, to speculate on the potential causal relationship between GERD and gastroduodenal ulcer. Additionally, sensitivity analysis, heterogeneity, and horizontal pleiotropy tests were performed to assess the robustness of the MR results. RESULTS: Our study suggest a possible causal relationship between GERD and an increased risk of gastroduodenal ulcer (GU, IVW method, OR = 1.01) (95% CI: 1.00 - 1.01, P = 0.025). The weighted median method produced a similar estimate (OR = 1.01) (95% CI: 1.00 - 1.02; P = 0.019), whereas MR-Egger showed no significant association. No evidence of horizontal pleiotropy was observed. The reverse MR analysis indicated that GU did not have a causal influence on GERD.7 CONCLUSIONS: Our two-sample MR analysis supports the notion that GERD elevates the risk of gastroduodenal ulcers. However, further investigation is needed to elucidate the underlying mechanisms.
Am J Med Sci
· 2026 Jun · PMID 41833689
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BACKGROUND: Acute kidney injury (AKI) is a sudden decline in kidney function associated with chronic kidney disease (CKD), recurrent AKI, and increased mortality. Identifying risk factors is essential for early detection...BACKGROUND: Acute kidney injury (AKI) is a sudden decline in kidney function associated with chronic kidney disease (CKD), recurrent AKI, and increased mortality. Identifying risk factors is essential for early detection and prevention of recurrence. OBJECTIVES: To update findings on the incidence, risk factors, and outcomes of recurrent AKI. METHODS: A systematic search of PubMed, Scopus, Ovid MEDLINE, Virtual Health Library, Web of Science, and Google Scholar identified studies on recurrent AKI risk factors in hospitalized adults (Feb 2018-June 2024). Study quality was assessed using the Newcastle-Ottawa Scale. Data were extracted into Excel and analyzed with Comprehensive Meta-Analysis software. The protocol was registered in PROSPERO (CRD42024572504). RESULTS: Seven studies (n = 160,898) were included. Pooled incidence of recurrent AKI was 22.8 % (95 % CI: 0.19-0.27). Continuous risk factors included higher blood urea nitrogen (MD = 2.30, 95 % CI: 1.14-3.46), lower hemoglobin (MD = -5.4, 95 % CI: -7.4 to -3.4), and higher baseline serum creatinine (MD = 11.5, 95 % CI: 3.5-19.5). Categorical risk factors included male sex, diabetes, and cardiovascular, liver, cerebrovascular, and respiratory diseases. Recurrent AKI was associated with higher mortality (OR = 2.81, 95 % CI: 1.77-4.47) and a slightly longer hospital stay (MD = 1.01 days, 95 % CI: 0.89-1.12). Evidence of potential publication bias was detected for mortality and hypertension. Meta-regression identified publication year as a source of heterogeneity (p = 0.004). CONCLUSIONS: Recurrent AKI is common in hospitalized adults and linked to poor outcomes. Early risk identification and structured post-discharge monitoring may reduce recurrence and improve outcomes.
Liu L, Zhao G, Gao Q
… +5 more, Zhao Y, Ma J, Zhao K, Wu Q, Xu G
Am J Med Sci
· 2026 Jul · PMID 41833687
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Atherosclerosis (AS) is a cardiovascular disease (CVDs) that seriously endangers human health. The accumulation of lipids and chronic inflammation are the main causes of AS formation. In the pathogenesis of AS, T lymphoc...Atherosclerosis (AS) is a cardiovascular disease (CVDs) that seriously endangers human health. The accumulation of lipids and chronic inflammation are the main causes of AS formation. In the pathogenesis of AS, T lymphocytes (T cells)recruitment to developing plaques represents an early pathogenic event, with regulatory T cells(Tregs) and T helper (Th) cell subsets playing central regulatory roles throughout disease progression. This article reviews the role of distinct T cell subsets in AS, covering pathogenic mechanisms, therapeutic approaches, and future directions in drug development.
Am J Med Sci
· 2026 Jun · PMID 41833686
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Systematic Review and Meta-Analyses (SRMAs) hold the highest rank in evidence hierarchy; however, their results are vulnerable to selective reporting and publication bias. Nonsignificant/secondary outcomes, such as adver...Systematic Review and Meta-Analyses (SRMAs) hold the highest rank in evidence hierarchy; however, their results are vulnerable to selective reporting and publication bias. Nonsignificant/secondary outcomes, such as adverse events or rare complications, are often omitted from the abstract due to word limits or pressure to publish. Academic databases index limited metadata but not the full-text, making outcomes that are not reported in the abstract resistant to search. This creates a modern "file drawer problem," where findings are available in full-text but remain inaccessible to search, leading to overestimated treatment effects and biased reported complication rates in SRMAs. To address this issue, this study proposed recommendations at three levels: Primary study researchers, secondary study researchers, and journals/academic databases. A collaborative effort among stakeholders is necessary to enhance the accessibility of nonsignificant outcomes through database searches, thereby reducing the risk of biased evidence that could influence clinical guidelines and patient care.
Am J Med Sci
· 2026 Jun · PMID 41796639
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BACKGROUND: The management of early liberal fluid resuscitation in post out-of-hospital cardiac arrest (OHCA) patients remains uncertain. This study aimed to evaluate its impact. METHODS: Data were retrospectively collec...BACKGROUND: The management of early liberal fluid resuscitation in post out-of-hospital cardiac arrest (OHCA) patients remains uncertain. This study aimed to evaluate its impact. METHODS: Data were retrospectively collected from the MIMIC-IV database. Post-OHCA patients admitted to the ICU were categorized into two groups based on the intravenous fluids received in the first 24 h: early liberal (>60 mL/kg) and usual (≤60 mL/kg) resuscitation groups. The primary endpoint was 30-day mortality, with secondary endpoints including discharge mortality and neurological function. Logistic regression assessed the association between early fluid resuscitation strategy and the endpoints. Propensity score was used as a sensitive analysis. Restricted cubic spline (RCS) and exploratory subgroup analysis was also performed. RESULTS: Early liberal fluid resuscitation group had significantly higher 30-day mortality (75.9 % vs. 51.6 %), discharge mortality (71.5 % vs. 50 %), and neurological dysfunction (78.8 % vs. 56.3 %) compared to the usual group. Early liberal fluid resuscitation was independently associated with increased risks in 30-day mortality (OR = 2.664, 95% CI: 1.21-5.865), discharge mortality (OR = 2.283, 95% CI: 1.052-4.955), and neurological dysfunction (OR = 2.436, 95% CI: 1.045-5.674). Sensitivity analyses produced consistent results. RCS analysis indicated that 30-day mortality increased when fluid volumes exceeded 62 mL/kg. Moreover, no potential beneficiaries of liberal fluid resuscitation were identified in the subgroup analysis. CONCLUSIONS: Early liberal fluid resuscitation was associated with increased 30-day mortality, discharge mortality and neurological dysfunction in patients post-OHCA. Additionally, a positive correlation exists between 30-day mortality and fluid volumes exceeding 62 mL/kg.
Madihi S, Aainouss A, Ei Messaoudi MD
… +1 more, Benani A
Am J Med Sci
· 2026 Jun · PMID 41794400
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Tuberculosis (TB) is a major health burden, the leading cause of death among people living with HIV, and one of the main causes of death linked to antimicrobial resistance. The World Health Organization (WHO) launched in...Tuberculosis (TB) is a major health burden, the leading cause of death among people living with HIV, and one of the main causes of death linked to antimicrobial resistance. The World Health Organization (WHO) launched in 2015 the End TB Initiative that aims to reduce TB cases and deaths by 2035. However, despite some progress, significant gaps persist in TB detection, treatment, prevention, and funding. Diagnosis is most often by sputum smear and culture and, when available, by nucleic acid amplification tests (NAATs), which revolutionizes TB diagnosis and monitoring, improving early detection, resistance surveillance, and treatment response evaluation. In this review, we report on the implication of various Real-Time PCR (RT-PCR) laboratory diagnostic tests and compare their performance in detecting MTB. We show that the Xpert MTB/RIF test is currently the most effective and widely validated molecular tool for diagnosing pulmonary TB, though its accuracy in extrapulmonary TB remains inconsistent. These findings suggest that combining molecular tests with other methods-such as radiology, microbiology, biomarkers, and immunological approaches-could provide a more reliable diagnostic strategy. Scaling up molecular tools worldwide, especially in high-burden regions, is essential to achieving the WHO End TB Strategy and ultimately eliminating TB.
LaForge J, Saleh A, Parcha V
… +9 more, Gonuguntla A, Iragavarapu S, Soto SR, Hasnie UA, Josey G, Nordberg M, Smith A, Rothenberg S, Clarkson SA
Am J Med Sci
· 2026 Jul · PMID 41794398
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BACKGROUND: The cardiothoracic ratio (CTR) is estimated by dividing cardiac width by thoracic width. The Area Deprivation Index (ADI) is a metric to quantify socioeconomic conditions. This study investigates the use of a...BACKGROUND: The cardiothoracic ratio (CTR) is estimated by dividing cardiac width by thoracic width. The Area Deprivation Index (ADI) is a metric to quantify socioeconomic conditions. This study investigates the use of artificial intelligence (AI) to identify elevated CTR as a predictor for heart failure (HF) and mortality and assessed ADI's influence on these risks. METHODS: This retrospective cohort study included 9,693 consecutive patients with non-cardiac chest CTs. An AI algorithm automated measurement of cardiac and thoracic diameters to calculate the cardiothoracic ratio (CTR). Patients were categorized into CTR tertiles: <0.5 (normal), 0.5-0.55 (borderline cardiomegaly), and ≥0.56 (cardiomegaly). Socioeconomic metrics were derived from electronic health records and stratified by ADI quartiles. Cardiovascular outcomes were extracted from ICD-10 codes over a six-year follow-up. Associations between CTR and cardiac outcomes were assessed using multivariate logistic regression and Cox proportional hazard models adjusted for age, sex, race, and ADI. RESULTS: Elevated CTR, notably in the cardiomegaly group, was associated with increased risk of prevalent HF (OR = 6.17, 95% CI = 5.27-7.23) and all-cause mortality (OR = 1.66, 95% CI = 1.47-1.87). Higher ADI scores were linked to increased risk of HF and mortality, although there was inconsistent interaction between elevated CTR and ADI regarding mortality. CONCLUSIONS: AI-derived CTR on non-cardiac chest CT may provide a cost-effective and efficient method for identifying patients at increased risk for HF and mortality. The utility of this technology proves to be efficacious amongst patients with high socioeconomic burden.