Search Results (906)

Human digital twins (HDTs) are patient-specific computational models that combine medical imaging, physiological measurements and predictive algorithms. They are moving from an exciting concept to a realistic clinical opportunity. The key question is no longer whether HDTs can be built. The key question is which methods are mature enough to support clinical decisions and what is still missing for routine use. This systematic review maps the methodological landscape of HDTs and highlights practical bottlenecks that limit clinical translation. A PRISMA 2020 guided search of PubMed, Scopus, IEEE Xplore, and the Cochrane Library, covering publications from 2016 to 2026, identified 151 eligible studies. Bibliometric mapping and thematic synthesis were used to characterize research clusters, computational paradigms, and collaboration patterns. Three dominant application streams were identified: cardiovascular HDTs for hemodynamic simulation and procedural planning, musculoskeletal HDTs for biomechanics-driven orthopedic innovation, and neurological HDTs integrating neuroimaging with computational neuroscience. Across domains, the strongest technical trend is the rise in hybrid pipelines that combine physics-based simulation, including finite element and computational fluid dynamics models, with machine learning for segmentation, parameter identification, reduced-order modeling, and faster inference. However, reporting of verification, validation, uncertainty quantification, and explicit context of use remains uneven and prospective clinical evidence is still limited. Overall, the literature shows rapid progress toward clinically credible HDTs, while highlighting the need for scalable computation, standardized credibility pipelines, and workflow-integrated platforms to support safe and reproducible clinical adoption. Full article

Background/Objectives: Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leakage and is typically diagnosed by clinical presentation and characteristic MRI signs; however, objective tools for monitoring physiological changes and treatment response remain limited. Cine phase-contrast MRI (PC-MRI) enables noninvasive quantification of aqueductal CSF dynamics, yet reliable analysis is challenging since the cerebral aqueduct is extremely small and susceptible to low contrast, partial volume effects, and ROI-dependent measurement variability—particularly in SIH where CSF pulsatility is often reduced. Methods: We propose an end-to-end automated framework that integrates (1) a cascade localization–segmentation strategy, consisting of Tiny YOLOv4 detection followed by MultiResUNet segmentation on a YOLOv4-derived cropped ROI; (2) physiology-informed pulsatility-based segmentation (PUBS) to refine anatomical masks into functional flow ROIs; and (3) one-dimensional convolutional neural networks (1D-CNNs) to extract exploratory waveform morphology features from 32-phase cardiac-cycle velocity waveforms. The study includes 39 participants, yielding 59 cine PC-MRI examinations: 11 controls, 28 Pre-treatment SIH scans and 20 Post-treatment Recovery scans. Results: The cascade model significantly improves segmentation robustness compared with a full-image baseline, achieving higher Dice scores and markedly lower boundary errors across cohorts (e.g., Pre-treatment SIH HD95: 1.66 ± 0.74 px vs. 15.37 ± 44.98 px). PUBS refinement reduces quantification deviation from expert manual references in SIH (mean relative error: 7.4% to 5.6%) and improves diagnostic performance for multiple hemodynamic parameters (e.g., downward mean flow AUC: 0.747 to 0.792). For waveform morphology analysis, the end-to-end 1D-CNN classifier was evaluated using repeated-seed participant-level grouped LOOCV. The repeated-seed ensemble prediction showed modest out-of-sample discrimination between Normal controls and Pre-treatment SIH scans, with an AUC of 0.646, a bootstrap 95% confidence interval of 0.455–0.826, and a permutation-test p-value of 0.072. Separately, exploratory analysis of the final baseline-trained 1D-CNN latent space showed marked, apparent Normal-versus-SIH separability and an intermediate recovery distribution in PCA space, suggesting that aqueductal waveform morphology may encode SIH-related physiological information. Conclusions: These findings suggest that SIH-related information may be reflected not only in flow magnitude but also in aqueductal CSF waveform morphology. However, the modest and statistically non-significant out-of-sample performance of the end-to-end 1D-CNN classifier indicates that morphology-based AI features should currently be regarded as exploratory biomarker candidates rather than validated stand-alone diagnostic tools. Larger independent cohorts are required to confirm their reproducibility, physiological meaning, and clinical utility. Full article

Background/Objectives: Myocardial microcirculatory dysfunction is a critical pathological feature of cardiovascular diseases, closely associated with inflammation, oxidative stress, and excessive neutrophil activation. Neutrophil extracellular traps (NETs) serve as crucial mediators of myocardial microvascular inflammatory injury. Dalbergia odorifera volatile oil (DOVO) demonstrates anti-inflammatory and antioxidant properties; however, its protective role against myocardial microcirculatory damage and its regulatory effect on NET formation remain inadequately characterized. This study investigates the protective effects of DOVO on myocardial microcirculatory disturbances and elucidates the underlying mechanisms related to NETs. Methods: A rat model of myocardial microcirculatory dysfunction was established through polyethylene microsphere injection, and an in vitro neutrophil inflammation model was generated using differentiated HL-60 cells. DOVO was administered at various doses both in vivo and in vitro, and hemodynamics, inflammatory cytokines, oxidative stress, and NET-related markers, including MPO and CitH3, were analyzed. Results: DOVO dose-dependently ameliorated microcirculatory impairment, hemodynamic disorders, inflammation, and oxidative stress in rats, significantly suppressing NET formation. In differentiated HL-60 cells, DOVO similarly reduced inflammatory gene expression and inhibited LPS-induced NETs production by downregulating MPO and CitH3. Conclusions: DOVO suggests a protective effect against myocardial microcirculatory injury by inhibiting oxidative stress, inflammatory responses, and subsequent NET formation. These findings elucidate a novel mechanism by which DOVO alleviates microcirculation-related cardiac damage and provide a theoretical basis for its application in cardiovascular injury. Full article

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with atherosclerosis and maladaptive vascular remodeling serving as central drivers of clinical events. Mechanistic investigation of arterial disease processes relies heavily on experimental animal models that permit precise control of vascular injury, hemodynamic forces, and ischemic stress. Over the past several decades, murine and rat models have become indispensable tools for studying endothelial dysfunction, intimal hyperplasia, flow-mediated remodeling, and ischemia–reperfusion injury. Each model reproduces distinct aspects of human vascular pathology while offering unique technical and biological advantages. This review summarizes commonly used murine and rat models of arterial disease, emphasizing the biological mechanisms they study, the surgical techniques used, pathophysiology, experimental endpoints, advantages, and limitations. Full article

Background: Endothelial dysfunction and renal injury are emerging as a common feature of long COVID, especially in those with hypertension. It is not yet well characterised whether SARS-CoV-2 infection exacerbates podocyte dysfunction, fibrotic signalling and renal hemodynamic remodelling, over and above the effects of hypertension alone and there are no reliable early biomarkers in this population. Methods: We conducted a comparative cross-sectional study with prospective 6-month treatment response follow-up in 120 adult patients (aged 30–60 years) with essential hypertension (Stage I, II or III; n = 40 per stage), at Bukhara Regional Multidisciplinary Hospital. Each stage subgroup was further divided into post-COVID (3–6 months after recovery; n = 20) and non-COVID (n = 20) strata. Patients with diabetes, known chronic kidney disease, previous myocardial infarction or stroke and other major comorbidities were excluded. Serum cystatin-C, creatinine, aldosterone, TGF-β1 and VEGF-A; urinary nephrin and microalbumin; cystatin-C-derived eGFR (CKD-EPI) and oral protein-loaded renal functional reserve (RFR); and renal Doppler indices (Vps, Ved, RI, PI) of the main, segmental and interlobar arteries were assessed before and after 6 months of guideline-based renin–angiotensin–aldosterone system (RAAS) blockade (enalapril 5–10 mg or azilsartan 40–80 mg, ±eplerenone). Comparisons were made by Student’s t-test—associations by Pearson correlation. Results: At baseline, post-COVID hypertensive patients exhibited consistently higher endothelial–podocyte injury markers than non-COVID counterparts. Urinary nephrin was elevated across all stages (Stage I: 126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01; Stage III: 203.3 ± 11.2 vs. 164.5 ± 9.7 pg/mL, p < 0.05), as were VEGF-A (Stage III: 286.1 ± 16.4 vs. 223.2 ± 12.6 pg/mL, p < 0.01) and TGF-β1 (Stage III: 186.4 ± 10.1 pg/mL, 1.3-fold higher; p < 0.01). The detection of microalbuminuria was 100% in Stage III post-COVID patients and 85% in non-COVID controls. The post-COVID groups had selective loss of renal functional reserve (7.8 ± 1.1% in Stage III compared to 12.5 ± 1.6% in non-COVID controls, p < 0.001). Nephrinuria correlated strongly with RFR (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001) and aldosterone (r = 0.613, p < 0.001). Six months of RAAS blockade reduced nephrinuria, microalbuminuria and TGF-β1 in both arms but the magnitude of biomarker reduction appeared smaller in the post-COVID group, particularly in Stage III. Conclusions: Long COVID appears to be associated with persistent endothelial dysfunction and podocyte injury in hypertensive patients. These results indicate that nephrinuria, VEGF-A, TGF-β1 and renal functional reserve are potential exploratory markers of endothelial and renal abnormalities in hypertensive patients following COVID-19. Before clinical utility can be determined, larger studies with multivariable modelling, diagnostic-performance analyses and correction for multiple testing are needed. The differences in biomarker response between groups observed in this study need to be confirmed in larger prospective studies with multivariable modelling and formal interaction analyses. Full article

Background: Hospitalized adults with chronic kidney disease (CKD) experience high morbidity and mortality. Acute inpatient events frequently occur in combination, yet most studies evaluate individual conditions in isolation. Acute hemodynamic and vascular stressors may represent interacting physiological stressors that define heterogeneous patterns of inpatient risk. Methods: Acute hemodynamic stressors (sepsis, shock, acute decompensated heart failure, and mechanical ventilation) and vascular stressors (acute myocardial infarction, major bleeding, stroke, pulmonary embolism, and deep vein thrombosis) were identified using ICD-10-CM and ICD-10-PCS codes. Stressor burden was defined as the number of stressors (0, 1, 2, or ≥3). Hospitalizations were categorized into mutually exclusive domains: none, hemodynamic only, vascular only, or both. Survey-weighted multivariable regression models examined associations with mortality, acute kidney injury (AKI), length of stay (LOS), and hospital charges. Prespecified sensitivity analyses excluded inter-hospital transfers, and interaction analyses assessed modification by age. Results: Among 1,062,813 CKD hospitalizations, 66.1% experienced at least one acute stressor. Increasing stressor burden demonstrated a marked dose–response relationship with mortality, with adjusted odds ratios of 2.15 (95% CI: 2.08–2.23), 7.36 (95% CI: 7.09–7.64), and 31.65 (95% CI: 30.40–32.95) for 1, 2, and ≥3 stressors, respectively. Increasing stressor burden was also associated with higher odds of AKI, longer LOS, and greater hospital charges. Significant dose–response relationships were observed for all outcomes (all P-trend < 0.001). Isolated hemodynamic stressors were associated with greater mortality risk than isolated vascular stressors (aOR: 4.97 vs. 2.15), while hospitalizations experiencing both domains had the greatest risk (aOR: 13.10, 95% CI: 12.52–13.71). These findings were robust in sensitivity analyses excluding inter-hospital transfers. The relative increase in mortality associated with higher stressor burden was greater among patients younger than 65 years than among older adults (P for interaction <0.001). Conclusions: Acute hemodynamic and vascular stressors define heterogeneous patterns of inpatient risk among hospitalized adults with CKD. Both cumulative stressor burden and stressor domain are strongly associated with mortality, AKI, and resource utilization, with robust dose–response relationships that highlight acute physiological stress as an important determinant of inpatient outcomes in CKD. Full article

Current evaluation of bypass graft performance relies predominantly on wall shear stress metrics, even though thrombosis and atherogenesis are fundamentally governed by particle transport and residence within disturbed flow regions. This disconnect limits the ability of conventional hemodynamic indicators to capture mechanisms directly linked to graft failure. In this study, we investigate how helical bypass geometry reorganises the flow and, consequently, modifies transport behaviour within the distal anastomosis by combining experimentally validated flow visualisation with computational fluid dynamics under pulsatile conditions. Particle transport was quantified using a controlled injection of 151 tracers, enabling direct assessment of retention and washout across the graft–anastomosis system. The straight configuration exhibited persistent recirculation structures that promoted localised particle retention and delayed clearance. In contrast, the helical geometry disrupted these structures, enhancing flow mixing and accelerating downstream transport. At late stages of the cardiac cycle, the helical configuration reduced residual particle retention by approximately 43% compared to the straight bypass. These findings demonstrate a transition from recirculation-driven retention to washout-dominated transport, providing a mechanistic basis for interpreting bypass performance beyond shear-based metrics. This transport-centred perspective provides a mechanistic link between flow organisation and particle residence, supporting the functional relevance of helical graft design while remaining distinct from direct modelling of biological thrombosis or atherogenesis. Full article

Background/Objectives: Strict hemodynamic stability is critical during supratentorial craniotomy. This systematic review and meta-analysis aimed to evaluate the efficacy of magnesium sulfate (MgSO₄) as a multimodal adjuvant on intraoperative hemodynamics, opioid consumption, and biomarker outcomes in this setting. Methods: We systematically searched PubMed, Scopus, EBSCO, and the Cochrane Library for randomized controlled trials (RCTs) comparing perioperative MgSO₄ administration to placebo or standard care in adult patients undergoing elective supratentorial craniotomy. Results: Meta-analysis of nine included RCTs using a random-effects model demonstrated that MgSO₄ significantly reduced intraoperative mean arterial pressure (mean difference [MD]: −4.65 mmHg; 95% confidence interval [CI]: −7.76 to −1.55; p = 0.0033; I² = 73.6%). Furthermore, MgSO₄ administration significantly lowered postoperative serum S100B levels (standardized MD [SMD]: −0.81; 95% CI: −1.24 to −0.38; p = 0.0002, I² = 0.0%), indicating mitigated cellular neural damage, and decreased perioperative fentanyl consumption (standardized MD: −1.01; 95% CI: −1.45 to −0.57; p < 0.0001; I² = 0.0%). Intraoperative blood loss volume did not differ significantly between groups (MD: −85.03 mL; 95% CI: −331.42 to 161.37; p = 0.4952; I² = 92.5%). Conclusions: MgSO₄ is a safe and effective multimodal adjuvant for supratentorial craniotomy, providing significant hemodynamic stability, opioid-sparing effects, and preliminary biochemical evidence suggestive of neuroprotection without compromising intraoperative hemostasis. Full article

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites. Full article

Background: While recent literature emphasizes the predictive value of composite inflammatory and nutritional indices for vascular outcomes, this study evaluates the actual predictive capacity of preoperative indices (PNI, GNRI, SII, NLR, PLR) for de novo arteriovenous fistula (AVF) maturation and 1-year primary patency. Methods: We retrospectively analyzed 945 end-stage renal disease patients who underwent strictly radio-cephalic autologous AVF creation. Preoperative indices were calculated from routine parameters. Diagnostic accuracy for predicting 1-year patency loss was assessed using receiver operating characteristic (ROC) curves, and a multivariate logistic regression model was constructed to adjust for baseline anatomical and clinical variables. Targeted subgroup analyses evaluated high-risk populations, including those with diabetes, coronary, and peripheral artery disease. Results: The 1-year primary and secondary patency rates were 73.3% and 93.1%, respectively. In contrast to prevalent reports, no significant differences in preoperative PNI, GNRI, NLR, PLR, or SII scores existed between patients with patent and thrombosed fistulas (p > 0.05). ROC analyses showed no predictive utility (AUC: 0.476–0.518). Crucially, multivariate logistic regression revealed that preoperative arterial (OR: 0.58, p < 0.001) and venous diameters (OR: 0.51, p < 0.001) were the strongest independent predictors of AVF failure, whereas all systemic biomarkers lacked independent predictive significance. Subgroup analyses confirmed these indices failed to predict AVF outcomes even in high-risk settings with severe endothelial dysfunction. Conclusions: Preoperative composite nutritional and inflammatory indices do not independently predict AVF maturation or long-term patency when adjusted for local anatomy. Local anatomical features and hemodynamics heavily dominate vascular outcomes, indicating that systemic biomarkers have limited standalone clinical utility for guiding preoperative vascular access planning. Full article

Background/Objectives: Acceleration of orthodontic tooth movement remains a major challenge in clinical orthodontics. Evidence suggests that increased local blood flow around the alveolar bone is key to bone remodeling and potentially reflects early biological responses associated with accelerated orthodontics. This study aimed to investigate the effects of non-invasive physical stimuli on gingival microcirculation. Methods: Eight healthy adult male volunteers were included in the analysis. Gingival blood flow was assessed using laser Doppler flowmetry under the following conditions: no-stimulation condition (None) and four types of stimuli: thermal stimulation (THM), electric field stimulation (ELF), vibration stimulation (VIB), and far-infrared stimulation (FIR). Gingival blood flow was recorded before and after each stimulation, and the rate of change was calculated. Statistical analysis was performed using a linear mixed-effects model with Type III ANOVA (Satterthwaite approximation), followed by Dunnett-adjusted comparisons. Results: A statistically significant difference was observed between stimulation conditions (p = 0.0087). VIB significantly increased gingival blood flow compared with the no-stimulation condition (p = 0.0041), whereas ELF showed a trend toward increased blood flow (p = 0.0936); THM and FIR showed no statistically significant effects. Conclusions: The findings of this study suggest that non-invasive physical stimuli, particularly vibration stimulation, can enhance gingival microcirculation. Although tooth movement was not directly evaluated, the observed hemodynamic changes may represent short-term physiological responses to non-invasive physical stimulation. Full article

Background: Neonatal aortic coarctation (CoA) remains difficult to diagnose before hemodynamic deterioration occurs after ductal closure. Pulse wave velocity (PWV) may reflect functional vascular alterations associated with CoA. Methods: A simplified hemodynamic mathematical model describing pulse wave propagation across aortic coarctation has been developed. The model is based on conservation of energy principles and incorporates simplified assumptions regarding arterial compliance to relate PWV changes to systolic–diastolic pressure. Results: The model suggests a nonlinear relationship between PWV reduction distal to the coarctation and pressure excursion damping. Specifically, a twofold PWV reduction corresponds theoretically to an approximately fourfold reduction in systolic–diastolic pressure variation. The derived relationships were shown to be conceptually consistent with the Moens–Korteweg formulation and Laplace law. Conclusions: This theoretical framework supports the physiological plausibility of combining PWV assessment with pressure-gradient evaluation in neonatal CoA screening. Future studies are required to validate the model in clinical settings and define diagnostic thresholds. Full article

Background/Objectives: Spontaneous bacterial peritonitis (SBP) is a serious complication of decompensated cirrhosis and is associated with acute kidney injury (AKI), organ failure, and death. Intravenous albumin is recommended in SBP because it reduces renal impairment and mortality, particularly in patients at higher risk of circulatory dysfunction and hepatorenal complications. However, the prognostic impact of early albumin administration on clinical outcomes in hospitalized SBP patients remains incompletely characterized in real-world practice. This study aimed to assess the association between early albumin administration and clinical outcomes in patients hospitalized with SBP compared to those without early albumin. Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Research Network, including adults hospitalized with SBP through February 2026. Patients were divided into those receiving early albumin administration (n = 1248) and those without early albumin (n = 4932) within 24 h of index SBP diagnosis. Propensity score matching (1:1) balanced cohorts (n = 1230 each) for demographics, comorbidities, liver disease severity surrogates, medications, and laboratory values. Relative risks (RR), risk differences (RD), and hazard ratios (HR) were calculated using propensity-matched and Cox proportional hazard models. Results: Early albumin administration was associated with significantly lower all-cause mortality (RR 0.620; 95% CI: 0.441–0.871; p = 0.005 at 5 days; RR 0.770; 95% CI: 0.651–0.910; p = 0.002 at 90 days). Secondary outcomes showed reduced risks for acute kidney injury (RR 0.654; 95% CI: 0.553–0.774; p < 0.001 at 5 days; RR 0.798; 95% CI: 0.706–0.903; p < 0.001 at 90 days), hepatorenal syndrome–AKI (RR 0.598; 95% CI: 0.445–0.804; p < 0.001 at 5 days; RR 0.756; 95% CI: 0.613–0.932; p = 0.009 at 90 days), vasopressor requirement (RR 0.633; 95% CI: 0.489–0.820; p < 0.001 at 5 days; RR 0.712; 95% CI: 0.572–0.887; p = 0.002 at 30 days), and renal replacement therapy (RR 0.533; 95% CI: 0.324–0.878; p = 0.011 at 5 days; RR 0.642; 95% CI: 0.442–0.932; p = 0.019 at 30 days). Cox models confirmed statistically significant risk reductions for all primary and secondary outcomes, including ICU admission (HR 0.82; 95% CI: 0.73–0.92; p = 0.001) and 30-day readmission (HR 0.84; 95% CI: 0.73–0.97; p = 0.015). Associations were strongest in the early period and attenuated over time. Conclusions: Early albumin administration was associated with reduced risks of mortality, AKI, HRS-AKI, and hemodynamic instability in patients hospitalized with SBP, with attenuation over time. These findings support timely implementation of guideline-concordant albumin therapy, although residual confounding cannot be excluded. Full article

Chronic exposure to fine particulate matter (PM_2.5) derived from wood combustion represents a major environmental health burden, particularly during pregnancy. However, the impact of pregestational and gestational (PM_2.5) exposure on the maternal great vasculature remains largely unexplored. This study evaluates the effects of wood smoke-derived (PM_2.5) on the structural architecture of the maternal aortic arch and associated hemodynamic changes during pregnancy in second-generation Sprague–Dawley rats. Animals were allocated into four groups (n = 12) according to filtered (FA) or non-filtered air (NFA) exposure during pregestational and gestational periods: FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Morphometric analysis revealed significant reductions in tunica media (p = 0.0251) and adventitia thickness (p = 0.0014) in exposed groups, without changes in integrated optical density, suggesting alterations in elastic matrix organization without evidence of net mass loss. Histological analysis supported exposure-dependent structural heterogeneity, including elastic lamellae fragmentation and extracellular matrix disorganization. Each exposed group exhibited a distinct systolic blood pressure trajectory across gestation, with FA/NFA reaching the highest values at day 18 (151.0 ± 17.0 mmHg) and NFA/FA displaying sustained elevations despite gestational low-exposure conditions. Principal component analysis (49.2% explained variance) revealed a structured multivariate distribution of vascular and hemodynamic variables across exposure conditions, consistent with an exposure-window-dependent pattern. These findings suggest that (PM_2.5) exposure is associated with coordinated structural and hemodynamic changes in the aortic arch and support the hypothesis that the pregestational period may represent a window of increased susceptibility. Full article

Background: Atrial septal defect (ASD) is common in adults and may cause chronic right ventricular (RV) volume overload and remodeling. Electrocardiography (ECG) may serve as a screening adjunct to echocardiography. Objectives: To evaluate the association of the terminal D1S + D3R ECG pattern, defined as a terminal S wave in lead I plus a terminal R wave in lead III, with structural and hemodynamic right heart involvement in adult secundum ASD. Methods: A total of 161 adult patients with secundum ASD were retrospectively analyzed. Right heart involvement was assessed using pulmonary-to-systemic flow ratio (Qp/Qs) ≥ 1.5 and a right ventricular/left ventricular (RV/LV) ratio > 1. ECG parameters, including right bundle branch block (RBBB), right axis deviation, V1–V2 R-wave positivity, and terminal D1S + D3R, were evaluated by two blinded cardiologists, with final classifications determined by consensus. Multivariable Firth penalized logistic regression, correlation analyses, and receiver operating characteristic (ROC) analyses were performed. Results: In the multivariable Firth penalized logistic regression model, pulmonary artery pressure (PAP) and ASD diameter were independently associated with Qp/Qs ≥ 1.5, whereas the terminal D1S + D3R pattern was not. The terminal D1S + D3R pattern was independently associated with RV dilatation after adjustment for age, sex, PAP, and ASD diameter (odds ratio [OR]: 9.90, 95% confidence interval [CI]: 2.82–38.20, p < 0.001) and showed good discriminatory performance for RV dilatation (area under the curve [AUC]: 0.881, 95% CI: 0.831–0.932). Conclusions: In adults with secundum ASD, a positive terminal D1S + D3R ECG pattern is independently associated with RV dilatation and may serve as a practical adjunctive screening marker. However, it should not replace echocardiographic assessment. Full article