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28 pages, 2694 KB  
Systematic Review
Human Digital Twins in Personalized Medicine: A Systematic Review and Bibliometric–Thematic Synthesis of Methodological Advances and Clinical Applications
by Carlotta Fontana and Sina Zinatlou Ajabshir
Computation 2026, 14(7), 143; https://doi.org/10.3390/computation14070143 (registering DOI) - 23 Jun 2026
Abstract
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 [...] Read more.
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
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31 pages, 5802 KB  
Article
Automated Aqueductal CSF Flow Analysis in Spontaneous Intracranial Hypotension: Hemodynamic Quantification and Exploratory Waveform Morphology Assessment Using Cine PC-MRI
by Yi-Jhe Huang, Wen-Hsien Chen, Hung-Chieh Chen and Da-Chuan Cheng
Diagnostics 2026, 16(12), 1939; https://doi.org/10.3390/diagnostics16121939 (registering DOI) - 22 Jun 2026
Viewed by 123
Abstract
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 [...] Read more.
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
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19 pages, 538 KB  
Review
Artificial Intelligence in Cardiac Point-of-Care Ultrasound: A Narrative Review
by Evan Avraham Alpert, Toby Kwartz, Barry Hahn, Waid Abdulghani, Ahmad Nama and Ziv Dadon
Diagnostics 2026, 16(12), 1921; https://doi.org/10.3390/diagnostics16121921 (registering DOI) - 21 Jun 2026
Viewed by 197
Abstract
Background: Cardiac point-of-care ultrasound (POCUS) is widely used in emergency and acute care settings. Still, broader use remains limited by operator dependence and variability in image acquisition and interpretation. Artificial intelligence (AI), including machine learning and deep learning methods, has been applied [...] Read more.
Background: Cardiac point-of-care ultrasound (POCUS) is widely used in emergency and acute care settings. Still, broader use remains limited by operator dependence and variability in image acquisition and interpretation. Artificial intelligence (AI), including machine learning and deep learning methods, has been applied to cardiac POCUS to support image acquisition, automate quantitative measurements, and assist interpretation. Methods: We performed a narrative review of current applications of AI-assisted cardiac POCUS. A targeted literature search of PubMed and Google Scholar from 2018 to 2026 was conducted using terms related to AI, machine learning, deep learning, and cardiac ultrasound. Studies evaluating AI-assisted cardiac ultrasound in clinical, educational, or image-acquisition settings were included, with emphasis on recent, clinically relevant applications. Results: The most developed application of AI-assisted cardiac POCUS is an automated assessment of left ventricular systolic function, particularly the left ventricular ejection fraction (LVEF), where multiple studies report agreement with expert interpretation or formal echocardiography and improved performance among novice users. AI-assisted tools have also been evaluated for pericardial effusion detection, guidance for image acquisition, and education. More complex applications, including diastolic function assessment and hemodynamic measurements such as LVOT-VTI, remain less well validated and more dependent on image quality. Across studies, performance is closely linked to image acquisition quality and has often been evaluated under controlled rather than real-world conditions. Conclusions: Current evidence supports AI-assisted cardiac POCUS primarily as a decision-support tool, with the strongest data for automated assessment of LVEF. Other applications remain investigational. Full article
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19 pages, 1189 KB  
Article
A Follow-Up Study of the Supraaortic and Intracranial Vessels, Cerebrovascular Reactivity, Brain Vascular Lesions and Atrophy in Patients with Rheumatoid Arthritis
by Attila Sas, Dávid Jónyer, Attila Valikovics, László Kostyál, Zsuzsanna Oláh, Katalin Hodosi, Zsófia Kardos, Csaba Oláh and Zoltán Szekanecz
J. Clin. Med. 2026, 15(12), 4691; https://doi.org/10.3390/jcm15124691 - 17 Jun 2026
Viewed by 83
Abstract
Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression [...] Read more.
Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA. Full article
(This article belongs to the Section Immunology & Rheumatology)
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15 pages, 1170 KB  
Article
Association of Relaxin-1 Levels with Mortality in Sepsis and Septic Shock
by Seyda Kayhan Omeroglu, Ozden Yildirim Akan, Huseyın Ozkarakas, Ferhat Demirci and Ismail Demir
J. Clin. Med. 2026, 15(12), 4661; https://doi.org/10.3390/jcm15124661 - 16 Jun 2026
Viewed by 152
Abstract
Background/Objectives: Hemodynamic disturbances in sepsis and septic shock arise from the vasoactive effects of inflammatory mediators involved in the immune response. Relaxin-1 is a pleiotropic hormone associated with inflammation, angiogenesis, tissue repair, and vasodilation. This study aimed to investigate the changes in [...] Read more.
Background/Objectives: Hemodynamic disturbances in sepsis and septic shock arise from the vasoactive effects of inflammatory mediators involved in the immune response. Relaxin-1 is a pleiotropic hormone associated with inflammation, angiogenesis, tissue repair, and vasodilation. This study aimed to investigate the changes in relaxin-1 levels in septic shock and to evaluate their association with mortality. Methods: This prospective observational study was conducted in a Level II intensive care unit. Demographic characteristics, vital signs, APACHE II and SOFA scores, comorbidities, and routine laboratory parameters were recorded at admission and at 48 h. Serum relaxin-1 levels were measured at both time points and analyzed in relation to survival status. Binary logistic regression was additionally performed to evaluate variables associated with mortality in a multivariable framework. Results: A total of 48 patients with sepsis and septic shock were included (54.2% female; mean age 73.4 ± 14.7 years). Overall mortality was 33.3%. Relaxin-1 levels significantly increased from baseline (11.25 ± 4.85 pg/mL) to 48 h (12.64 ± 4.81 pg/mL) (p = 0.047). Baseline relaxin-1 levels were significantly higher in non-survivors compared to survivors (14.62 ± 4.47 pg/mL vs. 11.65 ± 4.73 pg/mL, p = 0.043). Conclusions: Elevated Relaxin-1 levels were associated with mortality in patients with sepsis and septic shock. The observed increase in Relaxin-1 during early follow-up suggests a potential link with the underlying pathophysiological processes. Although Relaxin-1 was associated with mortality, its independent prognostic value could not be established in multivariable analysis due to the limited sample size. Larger, adequately powered multicenter studies are required to confirm these findings. Full article
(This article belongs to the Section Anesthesiology)
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19 pages, 8176 KB  
Article
Hepatic Doppler Perfusion Index in Healthy Adults: Standardization, Physiological Reference Limit, and Clinical Perspectives
by Christian Lueders, Johannes Gladitz, Nils Eckstein, Judith Schulz, Thomas Kiefer, Heinz Völler, Carsten-Heinrich Weylandt and Daniel Merkel
Diagnostics 2026, 16(12), 1840; https://doi.org/10.3390/diagnostics16121840 - 14 Jun 2026
Viewed by 200
Abstract
Background/Objectives: The Doppler perfusion index (DPI) quantifies the ratio of arterial to total hepatic blood flow and reflects hepatic hemodynamic balance. Its clinical applicability is limited by insufficient standardization and the absence of clearly defined physiological reference conditions. This study aimed to establish [...] Read more.
Background/Objectives: The Doppler perfusion index (DPI) quantifies the ratio of arterial to total hepatic blood flow and reflects hepatic hemodynamic balance. Its clinical applicability is limited by insufficient standardization and the absence of clearly defined physiological reference conditions. This study aimed to establish an upper physiological reference limit for the DPI and to assess its dependence on standardized physiological conditions in healthy adults. Methods: In this prospective study, 44 healthy adults underwent Doppler ultrasonography under standardized conditions (fasting/resting, post-exercise, postprandial). Volumetric blood flow was measured in the portal vein and via the proper hepatic artery and, where feasible, the common hepatic artery. The DPI was calculated as the ratio of arterial to total hepatic inflow. Nonparametric statistical methods were applied. Results: After exclusion of participants with non-standard hepatic arterial anatomy, 39 individuals were analyzed. The DPI varied across physiological conditions, reflecting changes in the relative contributions of arterial and portal venous inflow. Under fasting/resting conditions, values based on the proper hepatic artery showed low variability (mean 0.242 ± 0.057) and normal distribution (Shapiro–Wilk p = 0.625). The empirically derived 90th percentile was 0.30. Measurements based on the common hepatic artery were higher and more variable. Conclusions: The DPI is a physiologically dynamic parameter whose clinical use requires standardized measurement conditions. Under defined protocols, a value of approximately 0.30 may be considered an upper physiological reference limit. Standardization of acquisition and use of the proper hepatic artery enable reproducible and interpretable measurements. This provides a methodological basis for further clinical applications, including oncological contexts in which functional alterations of hepatic perfusion may be relevant. Full article
(This article belongs to the Special Issue Abdominal Ultrasound: A Left Behind Area—2nd Edition)
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14 pages, 909 KB  
Article
Comparison of the Self-Expandable Intra-Annular Navitor Prosthesis with the Balloon-Expandable, Intra-Annular Sapien 3 Prosthesis: A Propensity-Matched Analysis
by Nazan Puluca, Melchior Burri, Julia Schreyer, Magdalena Erlebach, Felix Wirth, Caterina Campanella, Stephanie Voss, Markus Krane and Hendrik Ruge
J. Clin. Med. 2026, 15(12), 4528; https://doi.org/10.3390/jcm15124528 - 11 Jun 2026
Viewed by 105
Abstract
Background: The study aims to compare the short-term clinical outcomes of transcatheter aortic valve implantation (TAVI) with the novel self-expandable, intra-annular Navitor valve (NAV) and the balloon-expandable, intra-annular Sapien 3 Ultra valve (S3U). Methods: From a single-center TAVI database, patients receiving NAV and [...] Read more.
Background: The study aims to compare the short-term clinical outcomes of transcatheter aortic valve implantation (TAVI) with the novel self-expandable, intra-annular Navitor valve (NAV) and the balloon-expandable, intra-annular Sapien 3 Ultra valve (S3U). Methods: From a single-center TAVI database, patients receiving NAV and S3U were identified. We applied 1:2 propensity score matching for the selected variables (gender, age, aortic valve perimeter, area, diameter, mean aortic valve gradient, EuroScore2, coronary artery disease (CAD), previous stroke and previous pacemaker implantation), resulting in 153 patients. Results: Clinical outcomes at 30 days of 51 patients with NAV [mean age: 80.4 ± 6.7 years; 51% female; mean annulus diameter: 24.1 ± 1.40 mm; EuroScore2: 3.4 ± 3.1%] and 102 patients with S3U [mean age: 79.9 ± 6.5 years (p = 0.7); 51% female (p > 0.99); mean annulus diameter: 24.1 ± 1.4 mm (p > 0.99); EuroScore2: 3.2 ± 2.7 (p = 0.7)] were analyzed according to VARC-3 recommendations. Post-TAVI aortic valve mean (S3U: 11.0 [3–27] mmHg; NAV: 7 [3–15] mmHg; p < 0.001) and maximum (S3U: 22 [6–44] mmHg; NAV: 12 [5–28] mmHg; p < 0.001) gradients at discharge were significantly lower with NAV, whereas the effective orifice area (EOA) of the aortic valve measured significantly larger with NAV (S3U: 1.5 [0.8–3.8] cm2; NAV: 2.1 [0.9–3.5] cm2; p < 0.001). Rates of no to mild paravalvular regurgitation (PVL) were 92.1% after NAV and 91.2% after S3U implantation (p = 0.15), mild to moderate PVL were 2.0% after NAV vs. 2.9% after S3U (p = 0.1) and moderate PVL were 2% after NAV and 1% after S3U (p = 0.07). None of the patients had a severe regurgitation. Severe patient–prosthesis mismatch (PPM) occurred significantly less with NAV (S3U: 14.7%; NAV: 7.8%; p = 0.002). One (1%) non-disabling stroke occurred within the S3U group and none occurred within the NAV group (p = 0.1). Life-threatening (S3U: 2.9%; NAV= 1%; p > 0.99) and major (S3U: n = 2.9; NAV: 0%; p = 0.55) bleeding events were comparable between both groups. The incidence of major (S3U: 2.9%; NAV: 2.0%; p > 0.99) vascular complications and the need for permanent pacemaker implantation (S3U: 9.8%; NAV: 11.8%; p = 0.8) were comparable in both groups. The 30-day mortality rate was 0.7% [1 in NAV group (2%), none in S3U; p = 0.3]. Conclusions: In conclusion, at 30-day follow-up, the self-expanding intra-annular Navitor valve demonstrated excellent acute safety and superior early hemodynamic performance, characterized by significantly lower transvalvular gradients and lower rates of severe PPM compared to the balloon-expandable Sapien 3 Ultra. However, whether these acute hemodynamic advantages translate into superior long-term clinical outcomes remains to be determined in long-term follow-up studies. Full article
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13 pages, 1024 KB  
Article
Estimation of Intradialytic Blood Volume Reduction Using Hemoglobin Changes: A Prospective Validation Study of a Pragmatic Clinical Tool
by Nomy Levin Iaina, Muhamed Osman, Fadi Garzuzi, Sergey Bellov and Arie Feldman
J. Clin. Med. 2026, 15(11), 4323; https://doi.org/10.3390/jcm15114323 - 3 Jun 2026
Viewed by 232
Abstract
Background/Objectives: Accurate assessment of intradialytic blood volume (BV) changes is important for optimizing fluid management in hemodialysis, but continuous BV monitoring is not universally available. Hemoglobin changes reflect hemoconcentration and may provide a simple surrogate for estimating BV reduction. We prospectively evaluated a [...] Read more.
Background/Objectives: Accurate assessment of intradialytic blood volume (BV) changes is important for optimizing fluid management in hemodialysis, but continuous BV monitoring is not universally available. Hemoglobin changes reflect hemoconcentration and may provide a simple surrogate for estimating BV reduction. We prospectively evaluated a hemoglobin-based method for estimating intradialytic BV reduction compared with machine-based BV monitoring. Methods: In this prospective single-center observational study, 187 hemodialysis sessions with complete paired measurements were analyzed. Formula-based BV reduction was calculated from pre- and post-dialysis hemoglobin values and compared with machine-measured BV reduction. Agreement was assessed using Pearson correlation, predefined absolute-difference thresholds, and Bland–Altman analysis. Exploratory receiver operating characteristic analyses evaluated the ability of formula-based estimates to identify sessions with larger machine-measured BV reductions. Results: Formula-based and machine-measured BV reduction demonstrated a moderate-to-strong correlation (r = 0.645). The predefined pragmatic agreement criterion of ≥70% of measurements within ±5% was met, with 77.5% of measurements within this range. Bland–Altman analysis demonstrated a small mean bias of −1.5%, with 95% limits of agreement from −12.4% to 9.3%. Exploratory classification performance was favorable across machine-defined BV reduction thresholds, with area under curve (AUC) values ranging from 0.84 to 0.87. At the ≥8% threshold, sensitivity was 72%, specificity 85%, positive predictive value 83%, and negative predictive value 74%. Linear regression showed that 42% of variability in machine-measured BV reduction was explained by the formula-based estimate. Conclusions: A hemoglobin-based approach provides a simple approximation of intradialytic BV reduction. Although not interchangeable with continuous monitoring, it may support post-session assessment and longitudinal evaluation of intradialytic hemodynamic tolerance. Full article
(This article belongs to the Special Issue Peritoneal Dialysis and Hemodialysis: Early and Late Outcomes)
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11 pages, 1163 KB  
Article
Comparison of Costoclavicular Block and Infraclavicular Block Effects on Tissue Oxygen Saturation in Upper Extremity Surgery: A Randomized, Assessor-Blinded Controlled Trial
by Veysi Yazar, Mehmet Baki Bilsel, Tuğba Bingöl Tanriverdi, Ramazan Aslanparçasi, Abdullah Şengül and Mahmut Alp Karahan
Diagnostics 2026, 16(11), 1715; https://doi.org/10.3390/diagnostics16111715 - 2 Jun 2026
Viewed by 210
Abstract
Background/Objectives: Ultrasound-guided brachial plexus blocks are widely used in upper extremity surgery. The costoclavicular block (CCB) has been defined in recent years as an alternative to the infraclavicular block (ICB) and attracts attention due to its anatomical advantages. However, studies comparing these [...] Read more.
Background/Objectives: Ultrasound-guided brachial plexus blocks are widely used in upper extremity surgery. The costoclavicular block (CCB) has been defined in recent years as an alternative to the infraclavicular block (ICB) and attracts attention due to its anatomical advantages. However, studies comparing these two techniques using objective physiological parameters are limited. This study aimed to compare the effectiveness of CCB and ICB techniques by measuring tissue oxygenation with near-infrared spectroscopy (NIRS) and evaluating the role of NIRS in demonstrating block success. Methods: Eighty patients undergoing upper extremity surgery were included in this prospective, randomized, comparative study, and the patients were randomly divided into two groups: CCB (n = 40) and ICB (n = 40). Block success was evaluated using tissue oxygen saturation (StO2) and its change (ΔStO2) measured by NIRS in addition to sensory and motor assessments. In addition, hemodynamic parameters were recorded. Results: A statistically significant increase in StO2 and ΔStO2 values was observed after block application in both groups. In the costoclavicular block group, the median StO2 increased from 78.5 [8.5] at baseline to 86.5 [9.75] at 20 min (p < 0.001), while in the infraclavicular block group, it increased from 75.0 [12.0] to 85.0 [9.0] (p < 0.001). Similarly, the ΔStO2 values increased from 0.0 [0.0] to 9.5 [8.25] in the costoclavicular group and from 0.0 [0.0] to 11.0 [9.0] in the infraclavicular group (both p < 0.001). This increase began in the early period and paralleled sensory-motor block findings, indicating that NIRS measurements objectively reflect block success. An isolated intergroup difference in StO2 was observed at t10 (83.92 ± 6.17 vs. 80.33 ± 7.31, p = 0.023), but no consistent intergroup superiority was demonstrated across the follow-up period. No statistically significant intergroup differences were found for ΔStO2 at any time point (p > 0.05). The block success rates were similar between groups. The hemodynamic parameters remained stable in both groups, and no clinically significant adverse events were observed. Conclusions: CCB and ICB techniques have similar efficacy and safety profiles in upper extremity surgery. NIRS-derived StO2 and ΔStO2 changes appear to be promising complementary physiological markers associated with block onset. However, the present study was not designed to establish diagnostic cut-off values or predictive accuracy; therefore, NIRS should be interpreted as an adjunct to, rather than a replacement for, conventional sensory and motor block assessment. Full article
(This article belongs to the Section Biomedical Optics)
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39 pages, 6387 KB  
Review
The Geometry of Circulatory Shock: A Conceptual Multi-Scale Lagrangian Framework for Physiology-Informed Hemodynamic Phenotyping
by Athanasios Chalkias, Konstantina Katsifa, Stavroula Amanetopoulou, Georgios Karapiperis, Antonios Destounis, Ioanna Iatrelli, Eleni Laou, Athanasios Prekates and Paraskevi Tselioti
J. Clin. Med. 2026, 15(11), 4283; https://doi.org/10.3390/jcm15114283 - 1 Jun 2026
Viewed by 1020
Abstract
Background: Hemodynamic failure remains a major determinant of mortality in critical illness, yet its detection is often delayed because conventional monitoring relies predominantly on Eulerian measurements that quantify pressure and flow magnitude without resolving the spatial and temporal organization of circulation. Consequently, clinically [...] Read more.
Background: Hemodynamic failure remains a major determinant of mortality in critical illness, yet its detection is often delayed because conventional monitoring relies predominantly on Eulerian measurements that quantify pressure and flow magnitude without resolving the spatial and temporal organization of circulation. Consequently, clinically significant states of dysfunction may persist despite apparently stable hemodynamic indices. The Geometry of Shock is a conceptual and hypothesis-generating multi-scale framework intended to integrate established cardiovascular physiology with emerging computational approaches for the analysis of circulatory dysfunction. Framework: The proposed framework combines Guytonian venous return physiology and cardiopulmonary interactions with Lagrangian flow topology, geometric representations of circulatory equilibrium, topological data analysis, and physics-constrained inverse modeling. Rather than focusing exclusively on static thresholds of pressure and flow, the framework proposes a structural interpretation of circulation centered on the dynamic organization and coherence of blood transport across cardiovascular domains. Within this paradigm, under-recognized hemodynamic phenotypes—including stressed volume failure, oscillatory shock during spontaneous breathing, macro–microcirculatory decoupling, and pulmonary vascular pressure–flow dissociation—may emerge from disrupted coupling between vascular, cardiac, pulmonary, and microcirculatory systems. These states may represent reversible structural transitions in venous return geometry and cardiopulmonary interaction preceding overt circulatory collapse. Conclusions: By reframing shock as a disorder of circulatory structure and coherence rather than solely a deficit in flow, this framework proposes a mechanistic foundation that may support future approaches aimed at earlier recognition of instability, improved physiological characterization of hemodynamic phenotypes, and future development and prospective validation of physiology-informed computational decision-support strategies in critical care. These concepts remain exploratory and hypothesis-generating rather than clinically validated. Full article
(This article belongs to the Section Intensive Care)
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21 pages, 542 KB  
Review
Integrating Cardiopulmonary Exercise Testing, Stress Echocardiography and Near-Infrared Spectroscopy for Multimodal Assessment of Exercise Intolerance: A Narrative Review
by Geza Halasz, Raffaella Mistrulli, Marco Di Francesco, Guido Giacalone, Gianluca Ferri, Stefano Beato, Francesca Moschella Orsini, Giovanni Nardecchia, Bernadette Corica, Furio Colivicchi, Stefania Angela Di Fusco, Federica Re and Domenico Gabrielli
Healthcare 2026, 14(11), 1511; https://doi.org/10.3390/healthcare14111511 - 29 May 2026
Viewed by 284
Abstract
Cardiopulmonary exercise testing (CPET) is the reference method for the objective assessment of exercise capacity because it provides an integrated appraisal of cardiovascular, respiratory and metabolic responses to exertion. However, CPET alone quantifies the magnitude of functional impairment without fully resolving the central [...] Read more.
Cardiopulmonary exercise testing (CPET) is the reference method for the objective assessment of exercise capacity because it provides an integrated appraisal of cardiovascular, respiratory and metabolic responses to exertion. However, CPET alone quantifies the magnitude of functional impairment without fully resolving the central and peripheral mechanisms that determine exercise intolerance. The integration of CPET with exercise stress echocardiography and near-infrared spectroscopy (NIRS) has therefore emerged as a clinically relevant multimodal strategy. Stress echocardiography provides real-time information on ventricular reserve, filling pressures, pulmonary pressure response, valvular function, pulmonary congestion and dynamic outflow obstruction, whereas NIRS provides continuous insight into skeletal muscle oxygen delivery, extraction and utilization. This narrative review summarizes the physiological rationale, practical workflow, methodological limitations and clinical applications of combined CPET, stress echocardiography and NIRS across heart failure, pulmonary hypertension, peripheral artery disease, cardiomyopathies and sports cardiology. By linking systemic gas exchange, central hemodynamics and peripheral oxygen handling, this approach may move exercise evaluation from a descriptive measure of performance toward a mechanism-based framework for phenotyping, risk stratification and individualized therapeutic decision-making. Further studies are needed to harmonize protocols, validate reproducible multimodal indices and demonstrate incremental prognostic value over conventional testing. Full article
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9 pages, 4832 KB  
Brief Report
A Word of Caution: Aorto-Right Ventricular Fistula, an Uncommon Pitfall of Perceval Sutureless Valve
by Ziyad Gunga, Augustin Rigollot, Elsa Hoti, Zied Ltaief, Gabriel Saiydoun, Anna Nowacka, Valentina Rancati, Florine Valliet and Matthias Kirsch
J. Cardiovasc. Dev. Dis. 2026, 13(6), 230; https://doi.org/10.3390/jcdd13060230 - 28 May 2026
Viewed by 253
Abstract
Background: An aorto-right ventricular fistula (ARVF) secondary to membranous septum rupture is an exceptionally rare complication after surgical aortic valve replacement (SAVR). While sutureless prostheses such as the Perceval valve have gained wide acceptance due to reduced cross-clamp times and procedural simplification, the [...] Read more.
Background: An aorto-right ventricular fistula (ARVF) secondary to membranous septum rupture is an exceptionally rare complication after surgical aortic valve replacement (SAVR). While sutureless prostheses such as the Perceval valve have gained wide acceptance due to reduced cross-clamp times and procedural simplification, the reported adverse events predominantly include conduction disturbances and paravalvular leaks. Structural septal disruption remains sparsely described. We report a case of an early ARVF after Perceval implantation and review the pathophysiological and procedural mechanisms implicated in septal injury following sutureless and transcatheter aortic valve interventions. Case Description: A 66-year-old woman with severe bicuspid aortic valve stenosis underwent SAVR via a median sternotomy using a Perceval XL prosthesis after meticulous annular decalcification and sizing. Immediate intraoperative transesophageal echocardiography (TEE) confirmed optimal seating without any paravalvular regurgitation. Within 24 h, the patient developed a complete atrioventricular block followed by cardiogenic shock. A repeat TEE revealed a large ARVF with significant left-to-right shunt. Emergent re-exploration identified a membranous septum tear. The Perceval prosthesis was explanted, the defect was closed with a reinforced patch repair, and a 27 mm Inspiris Resilia bioprosthesis was implanted. Peripheral veno-arterial ECMO support was required temporarily. The patient recovered and remained free of prosthetic dysfunction at the two-year follow-up. Discussion: Membranous septum rupture after AVR has an estimated incidence of 0.4–1.5% in TAVR cohorts but is virtually unreported with Perceval valves. The mechanisms are thought to be chronic radial stress from oversized or malpositioned prostheses. Case reports with TAVR devices emphasize oversizing as a risk factor. Predictive factors for septal injury in sutureless AVR mirror those for conduction disturbances: valve oversizing, shallow infra-annular septal length, heavy calcification, and prior valve surgery. Preventive measures, such as strict sizing protocols, the avoidance of balloon dilation, and optimized implantation depth, have reduced conduction complications and may mitigate septal trauma. The treatment choice, whether percutaneous or surgical closure, depends on hemodynamic stability, defect size and anatomy, and operative risk. Conclusions: Early ARVF after Perceval implantation is exceedingly rare but potentially catastrophic. Strict adherence to sizing principles, awareness of septal anatomy, and prompt management, percutaneous in selected stable cases or surgical in acute large defects, are essential to optimize outcomes in sutureless AVR. Full article
(This article belongs to the Special Issue Advances in Surgical Treatment of Heart Valve Disease)
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13 pages, 1478 KB  
Article
Adverse Hemodynamics in Acute Heart Failure Patients Are Associated with Skeletal Muscle Stress Biomarkers
by Kamil A. Kobak, Monika Kasztura, Krystian Josiak, Robert Zymliński, Natalia Świątoniowska-Lonc, Waldemar Banasiak and Kinga Węgrzynowska-Teodorczyk
Int. J. Mol. Sci. 2026, 27(11), 4850; https://doi.org/10.3390/ijms27114850 - 28 May 2026
Viewed by 216
Abstract
Acute heart failure (AHF) causes abrupt hemodynamic disturbances, including reduced forward flow and venous congestion, which may extend beyond the heart and contribute to peripheral organ stress. Skeletal muscle may be particularly vulnerable to these changes, but the relationship between acute hemodynamic status [...] Read more.
Acute heart failure (AHF) causes abrupt hemodynamic disturbances, including reduced forward flow and venous congestion, which may extend beyond the heart and contribute to peripheral organ stress. Skeletal muscle may be particularly vulnerable to these changes, but the relationship between acute hemodynamic status and circulating markers of skeletal muscle stress and regulation remains unclear. We prospectively enrolled 35 men hospitalized with AHF and non-invasively assessed their cardiac index (CI) by impedance cardiography and right atrial pressure (RAP) by echocardiography. Plasma carbonic anhydrase III (CA3), creatine kinase-MM (CK-MM), lactate, myostatin, and follistatin were measured at admission, discharge, and 30 days after discharge. Patients were analyzed according to low CI, defined as CI < 2.2 L·min−1·m−2; elevated RAP, defined as RAP ≥ 8 mmHg; and combined CI/RAP profiles. CA3 and CK-MM were higher in patients with low CI or elevated RAP and were highest in the low-CI/elevated-RAP profile. CA3 and lactate did not significantly change during follow-up, whereas CK-MM modestly increased at 30 days. Myostatin and follistatin were highest at admission and decreased after clinical stabilization. In this pilot cohort of men hospitalized with AHF, estimated lower perfusion and greater venous congestion were associated with higher circulating markers of skeletal muscle stress, while muscle regulatory myokines declined after stabilization. These findings suggest that skeletal muscle-related biomarkers may reflect peripheral consequences of acute hemodynamic disturbance in AHF and warrant further investigation in larger cohorts. Full article
(This article belongs to the Special Issue Molecular Insights into Heart Failure: From Bench to Bedside)
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20 pages, 2325 KB  
Article
Time-Frequency, Complexity, and Fractal Analyses of Hemoglobin and Deoxyhemoglobin Responses to Quantify Mechanisms of Actions of Cupping Therapy
by Nasrin Dabirian, Mansoureh Samadi, Amir Babaniamansour, Yameng Li, Manuel E. Hernandez and Yih-Kuen Jan
Entropy 2026, 28(6), 597; https://doi.org/10.3390/e28060597 - 27 May 2026
Viewed by 259
Abstract
Cupping therapy has been demonstrated to improve hemodynamic regulation. Existing studies have reported mean changes of oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb), which do not capture the multi-scale regulatory dynamics of the microvasculature. It is therefore unclear whether cupping therapy modulates the complexity and [...] Read more.
Cupping therapy has been demonstrated to improve hemodynamic regulation. Existing studies have reported mean changes of oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb), which do not capture the multi-scale regulatory dynamics of the microvasculature. It is therefore unclear whether cupping therapy modulates the complexity and fractal property of hemodynamic signals. The objective of this study was to examine complexity of hemodynamic response to cupping therapy. A 2 by 2 factorial design with repeated measures was used to examine the main effect of pressure (−225 and −300 mmHg) and duration (5 and 10 min) and their interaction. A near infrared spectroscopy (NIRS) was used to measure OxyHb and DeoxyHb concentrations before and after cupping therapy. A total of 18 healthy participants were enrolled in this study. The wavelet analysis, sample entropy and detrended fluctuation analysis (DFA) were used to quantify the oscillatory, complexity, and fractal scaling properties of OxyHb and DeoxyHb signals. A two-way ANOVA with Bonferroni correction was used to examine the main and interaction effects. The results demonstrated that the combined effects of pressure and duration, rather than either factor independently, were the primary determinants of the dynamic hemodynamic response to cupping therapy, with significant Pressure × Duration interactions observed in DeoxyHb myogenic wavelet power (F = 4.636, p = 0.046, η2p = 0.214), OxyHb (F = 5.704, p = 0.029, η2p = 0.251) and DeoxyHb (F = 6.600, p = 0.020, η2p = 0.280) sample entropy, and DeoxyHb DFA scaling exponent (F = 5.598, p = 0.030, η2p = 0.248). In addition, cupping pressure selectively modulated neurogenic DeoxyHb oscillatory power (F = 5.001, p = 0.039, η2p = 0.227), and cupping duration significantly altered the fractal scaling properties of DeoxyHb signals (F = 7.775, p = 0.013, η2p = 0.314). The findings indicate that the interaction of pressure and duration of cupping therapy could effectively modulate hemodynamic responses. To the best of our knowledge, this is the first study investigating the complexity of hemodynamic responses after cupping therapy. Full article
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20 pages, 2411 KB  
Article
Pre-Procedural Vascular Phenotyping Is Associated with Radial Artery Functional Impairment After Transradial Catheterization
by Xenofon M. Sakellariou, Dimitrios N. Nikas, Panagiotis Papanagiotou, Evangelos Liberopoulos, Eleftheria M. Mastoridou, Antonios Halapas and Theofilos M. Kolettis
J. Clin. Med. 2026, 15(11), 4135; https://doi.org/10.3390/jcm15114135 - 27 May 2026
Viewed by 195
Abstract
Background/Objectives: Transradial access (TRA) is the preferred route for coronary catheterization, yet its consequences for radial artery vasoreactivity and hemodynamic parameters remain incompletely characterized. We prospectively quantified TRA-induced functional impairment, its clinical determinants, and the association of baseline parameters with post-procedural outcomes. Methods: [...] Read more.
Background/Objectives: Transradial access (TRA) is the preferred route for coronary catheterization, yet its consequences for radial artery vasoreactivity and hemodynamic parameters remain incompletely characterized. We prospectively quantified TRA-induced functional impairment, its clinical determinants, and the association of baseline parameters with post-procedural outcomes. Methods: Ninety-four consecutive patients undergoing elective TRA were assessed at baseline, 24 h, and one month using high-resolution Doppler ultrasound. Nine vascular parameters were measured: flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), peak systolic velocity (PSV), resistive index (RI), pulsatility index (PI), resting and hyperemic velocity-time integral, hyperemic blood flow volume, and lumen diameter. Non-parametric methods were applied throughout. Results: FMD declined at 24 h (−31.2%; p < 0.001) and showed no significant recovery at one month (p = 0.08 vs. 24 h). NMD showed a greater acute decline (−36.6%; p < 0.001) with partial but statistically significant recovery at one month (p < 0.001). PSV recovered fully by one month; RI fell below baseline, consistent with compensatory microvascular vasodilation. Radial artery lumen diameter remained significantly below baseline at one month. Radial artery occlusion occurred in 4 patients (4.3%), all with spontaneous recanalization. Female sex was selectively associated with greater NMD reduction (ΔNMD −8.3% vs. −5.8%; p = 0.005) without a statistically significant FMD difference (p = 0.40). Older age correlated with impaired FMD recovery at one month (ρ = −0.62; p < 0.001) but not with NMD outcomes. Baseline PSV demonstrated the highest discriminatory performance for significant FMD decline (AUC = 0.73). Conclusions: TRA causes multidomain, persistent radial artery functional impairment at one month, with distinct recovery trajectories for endothelial and smooth muscle function. Female sex and advanced age are selective determinants of injury and recovery, respectively. A pre-procedural phenotype comprising baseline diameter, PSV, RI, and age is associated with post-procedural outcomes and supports further investigation of pre-procedural phenotyping as a candidate framework for risk stratification. Full article
(This article belongs to the Section Cardiology)
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