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9 pages, 682 KB  
Case Report
Quadrilateral Pinwheel Flap Reconstruction for a Complex Colocutaneous Fistula-Associated Flank Wound in a Paraplegic Patient: A Case Report
by Joon Hyuk Lee and Tae Gon Kim
J. Clin. Med. 2026, 15(6), 2394; https://doi.org/10.3390/jcm15062394 - 20 Mar 2026
Abstract
Background/Objectives: Chronic wounds are a major source of morbidity in patients with paraplegia, often resulting in repeated treatment, prolonged hospitalization, and reduced quality of life. Reconstruction becomes particularly challenging when a wound arises in a scarred trunk region and is further complicated by [...] Read more.
Background/Objectives: Chronic wounds are a major source of morbidity in patients with paraplegia, often resulting in repeated treatment, prolonged hospitalization, and reduced quality of life. Reconstruction becomes particularly challenging when a wound arises in a scarred trunk region and is further complicated by deep infection, osteomyelitis, or enteric fistula. We describe the staged management of a complex left flank wound in a paraplegic patient, initially reconstructed with a quadrilateral pinwheel flap and later requiring multidisciplinary salvage for recurrence associated with rib osteomyelitis and a colocutaneous fistula. Methods: A paraplegic man in his 50s presented with a chronic left flank wound after repeated full-thickness skin graft failure and persistent Pseudomonas aeruginosa infection. After wide debridement, the approximately 7 × 7 cm defect was reconstructed with a quadrilateral pinwheel flap composed of four Limberg-style rhomboid fasciocutaneous flaps positioned at the 12, 3, 6, and 9 o’clock orientations, elevated at the level of the deep fascia, and transposed into the central defect, with adjunctive negative-pressure wound therapy (NPWT). Approximately 1 year later, recurrence with rib osteomyelitis required rib resection. During NPWT, feculent drainage led to the diagnosis of a colocutaneous fistula. Subsequent multidisciplinary treatment included fistula tract resection, colonic repair with omental patching, transposition of vascularized omentum into the chest wall cavity to obliterate dead space, continued NPWT, and delayed primary closure. Results: Initial local flap reconstruction achieved wound coverage, and immediate postoperative clinical assessment, including pinprick and refill testing, confirmed satisfactory flap perfusion; however, delayed recurrence developed in association with rib osteomyelitis. After definitive fistula surgery, dead-space management with vascularized omentum, wound conditioning with staged NPWT, and delayed primary closure, the wound healed completely. At 6 months after delayed closure, no recurrence of fistula, osteomyelitis, wound dehiscence, or soft-tissue breakdown was observed, and the patient’s daily comfort and functional independence were improved compared with the preoperative condition. Conclusions: A quadrilateral pinwheel flap may provide an effective tension-dispersing local fasciocutaneous option for selected scarred trunk defects in high-risk patients. However, when chronic wounds are compounded by deep infection and enteric fistula, durable healing depends not on flap design alone but on staged multidisciplinary management incorporating definitive source control, vascularized tissue transfer for dead-space elimination, NPWT, and appropriately timed closure. Full article
15 pages, 332 KB  
Article
Effect of Electromagnetic Field Therapy and Customized Foot Insole on Peripheral Circulation and Ankle–Brachial Pressure Index in Patients with Diabetic Foot Ulcer: A Randomized Controlled Clinical Trial
by Mshari Alghadier, Ibrahim Ismail Abuzaid and Hany M. Elgohary
Healthcare 2026, 14(6), 796; https://doi.org/10.3390/healthcare14060796 (registering DOI) - 20 Mar 2026
Abstract
Background: Diabetic foot ulcers (DFUs) are considered a prevalent complication of diabetes mellitus, frequently accompanied with compromised peripheral circulation, slower healing, as well as high risk of infection in addition to risk of amputation. Additional treatments that enhance microvascular perfusion and lessen plantar [...] Read more.
Background: Diabetic foot ulcers (DFUs) are considered a prevalent complication of diabetes mellitus, frequently accompanied with compromised peripheral circulation, slower healing, as well as high risk of infection in addition to risk of amputation. Additional treatments that enhance microvascular perfusion and lessen plantar pressure may accelerate the healing process. This study was carried out to examine the impact of pulsed electromagnetic field (EMF) therapy as well as customized silicone gel insoles in terms of peripheral circulation in addition to vascular indices in patients with DFUs. Methods: A randomized, controlled clinical trial, including sixty-six adults diagnosed with type II diabetes as well as plantar DFUs (Wagner grade I–II) were divided into three groups (n = 22 each): Group A was given low-frequency electromagnetic field therapy (15–50 Hz, 2–5 mT, 30 min, three times per week for 8 weeks), Group B was given a customized silicone gel insoles produced for ulcer offloading, and Group C (control) was given conventional physiotherapy along with wound care. Peripheral microcirculation as well as tissue perfusion were the primary outcomes, and they were measured using Laser Doppler Flowmetry (LDF), Photoplethysmography (PPG), in addition to the Toe–Brachial Index (TBI). The secondary outcome included the Ankle–Brachial Pressure Index (ABPI). A blinded assessor measured the outcomes at the beginning of the study, after the intervention (week 8), and again after the follow-up (week 16). Results: EMF therapy significantly improved LDF (baseline: 45.2 ± 6.5 PU; week 8: 62.5 ± 7.2 PU), PPG (0.42 ± 0.08 mV to 0.68 ± 0.10 mV), TBI (0.64 ± 0.07 to 0.82 ± 0.08), and ABPI (0.88 ± 0.06 to 0.97 ± 0.05) compared with insoles and controls (p < 0.001, partial η2 0.25–0.37). The insole group exhibited moderate enhancements, whereas the control group demonstrated minor changes. Between-group analyses showed substantial differences in favor of EMF therapy across all measured variables (F = 13.5–19.9, p < 0.001). Improvements continued at the 8-week follow-up. Conclusions: Patients with DFUs who receive EMF therapy experience a significant improvement in their peripheral microcirculation, tissue perfusion, as well as vascular indices. This is more effective than just mechanical offloading, and custom insoles offer extra benefits by redistributing pressure. Combining EMF therapy with regular DFU care may speed up healing and lower the risk of problems. Additional research should investigate the efficacy of combined EMF as well as off-loading interventions and their long-term outcomes. Full article
(This article belongs to the Section Clinical Care)
15 pages, 1794 KB  
Article
Central Aortic Cannulation in Minimally Invasive Cardiac Surgery via Right Thoracotomy: A Single-Center Retrospective Comparison
by Tayfun Özdem, Tuna Demirkıran, Mesut Akyol, Işıl Taşöz Özdaş, Furkan Burak Akyol, Yiğit Tokgöz, Veli Can Özdemir, Emre Kubat, Gökhan Arslan, Murat Kadan and Kubilay Karabacak
J. Clin. Med. 2026, 15(6), 2383; https://doi.org/10.3390/jcm15062383 - 20 Mar 2026
Abstract
Background/Objectives: Minimally invasive cardiac surgery via right thoracotomy commonly uses femoral arterial cannulation for cardiopulmonary bypass (CPB), which requires an additional groin incision and may be associated with access-related complications. Central aortic cannulation through the same thoracotomy allows antegrade perfusion without an extra [...] Read more.
Background/Objectives: Minimally invasive cardiac surgery via right thoracotomy commonly uses femoral arterial cannulation for cardiopulmonary bypass (CPB), which requires an additional groin incision and may be associated with access-related complications. Central aortic cannulation through the same thoracotomy allows antegrade perfusion without an extra incision. This study compared central aortic and femoral arterial cannulation strategies in minimally invasive cardiac surgery via right thoracotomy. Methods: This retrospective, single-center study included 139 consecutive patients undergoing minimally invasive right thoracotomy cardiac surgery with CPB between February 2021 and June 2023. Patients were grouped according to arterial cannulation strategy: central aortic cannulation (n = 93) and femoral arterial cannulation (n = 46). Demographic characteristics, operative variables, transfusion requirements, biochemical parameters, and early postoperative clinical outcomes were compared between the groups. Results: Baseline demographic characteristics differed between groups (age, height, body surface area, and sex distribution), and these differences should be considered potential confounders when interpreting outcome comparisons. Central cannulation was more frequently used in women (74.2% vs. 45.7%, p = 0.001). Patients in the femoral group were older (median 61.0 vs. 54.0 years, p = 0.004), taller (1.65 ± 0.10 vs. 1.59 ± 0.09 m, p < 0.001), and had a slightly higher body surface area (p = 0.043). Cross-clamp and CPB durations were longer in the femoral group (cross-clamp: 90.0 vs. 70.5 min, p = 0.015; CPB: 137.0 vs. 114.0 min, p = 0.003). Lymphatic leakage occurred in three patients in the femoral group (6.5% vs. 0%, p = 0.009). No significant differences were observed between groups for mortality, intensive care unit stay, or neurological events. Conclusions: Central aortic cannulation via right thoracotomy is a feasible alternative to femoral arterial cannulation, enabling antegrade perfusion without a groin incision, reducing operative time, and potentially decreasing access-related complications such as lymphatic leakage, while yielding comparable early clinical outcomes. These findings should be interpreted cautiously given the retrospective design and baseline differences between groups. Full article
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20 pages, 2327 KB  
Review
Toward Comprehensive In Vitro Evaluation of Serum Albumin Binding of Per- and Polyfluoroalkyl Substances
by Hannah M. Starnes and Scott M. Belcher
J. Xenobiot. 2026, 16(2), 54; https://doi.org/10.3390/jox16020054 - 20 Mar 2026
Abstract
Per- and polyfluoroalkyl substances (PFAS) constitute a large and chemically diverse class of synthetic compounds characterized by one or more fully fluorinated methyl or methylene groups. Many PFAS are toxic, environmentally persistent, bioaccumulative, and highly mobile, resulting in widespread contamination and biological exposure. [...] Read more.
Per- and polyfluoroalkyl substances (PFAS) constitute a large and chemically diverse class of synthetic compounds characterized by one or more fully fluorinated methyl or methylene groups. Many PFAS are toxic, environmentally persistent, bioaccumulative, and highly mobile, resulting in widespread contamination and biological exposure. Across taxa PFAS exhibit affinity for proteins and preferentially accumulates in protein-rich, highly perfused tissues. Protein binding critically influences PFAS distribution, bioaccumulation, toxicity, and elimination. A variety of different approaches for determining bind affinity have existed for decades; however, depending on experimental conditions, calculated affinities can vary over multiple orders of magnitude which limits comparison of protein–PFAS binding affinities across studies and across PFAS chemical space. Addressing this limitation requires robust and standardized experimental platforms capable of rapidly generating quantitative binding data. Among the most important targets is serum albumin—the principal transport protein in vertebrate blood—which plays a central role in governing PFAS toxicokinetics. This review summarizes current methodologies for measuring protein–PFAS binding affinities, evaluates the strengths and limitations of each approach, synthesizes the existing literature on serum albumin–PFAS interactions, and highlights differential scanning fluorimetry as a rapid, reproducible, and sensitive technique for in vitro assessment of relative protein–PFAS binding. Full article
(This article belongs to the Section Emerging Chemicals)
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19 pages, 556 KB  
Review
Transforming Stroke Diagnosis with Artificial Intelligence: A Scoping Review of Brainomix e-Stroke, Aidoc, RapidAI, and Viz.ai
by Mateusz Dorochowicz, Arkadiusz Kacała, Aleksandra Tołkacz, Aleksandra Kosikowska, Maja Gewald and Maciej Guziński
Medicina 2026, 62(3), 582; https://doi.org/10.3390/medicina62030582 - 19 Mar 2026
Abstract
Background and Objectives: Rapid diagnosis is fundamental to acute ischemic stroke management; however, access to neuroradiological expertise remains limited. This scoping review maps the diagnostic accuracy, workflow impact, and cost-effectiveness of leading AI platforms (Brainomix, Aidoc, RapidAI, and Viz.ai), characterizing industry and [...] Read more.
Background and Objectives: Rapid diagnosis is fundamental to acute ischemic stroke management; however, access to neuroradiological expertise remains limited. This scoping review maps the diagnostic accuracy, workflow impact, and cost-effectiveness of leading AI platforms (Brainomix, Aidoc, RapidAI, and Viz.ai), characterizing industry and peer-reviewed metrics. Materials and Methods: Following PRISMA-ScR guidelines, we searched PubMed, Cochrane Library, and HTA repositories for studies (2019–2025). Using a PICO-based framework, 29 studies were included for thematic mapping of the technological landscape. Results: Twenty-nine studies were included. Platforms show high proximal LVO sensitivity (78–97%), while performance for distal/MVO and posterior circulation occlusions was more variable. RapidAI is frequently mapped using historical perfusion trial parameters; however, volumetric discrepancies with platforms like Viz.ai indicate outputs are not interchangeable. Brainomix shows extensive validation for automated NCCT ASPECTS in triage. Aidoc demonstrates operational advantages via worklist prioritization, while. Viz.ai is associated with door-to-puncture time reductions (11–25 min). Economically, cost-effectiveness is driven by improved functional outcomes and expanded access to thrombectomy, rather than labor substitution. Conclusions: AI platforms function as diagnostic safety nets and workflow optimizers. Reported roles, such as perfusion-centric analysis (RapidAI) or workflow coordination (Viz.ai), reflect current research trends rather than definitive technological superiority. Institutional selection should consider these evidence clusters alongside local validation and specific clinical priorities. Full article
(This article belongs to the Special Issue AI in Imaging—New Perspectives, 2nd Edition)
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27 pages, 1089 KB  
Review
Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap
by Mingzhu Li, Shuhong Huang, Jinze Jia, Yixing Feng and Jing Zhang
Toxins 2026, 18(3), 149; https://doi.org/10.3390/toxins18030149 - 19 Mar 2026
Abstract
Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across [...] Read more.
Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across major toxin classes, including bacterial enterotoxins (e.g., cholera toxin, heat-stable enterotoxins, Shiga toxins), mycotoxins (e.g., aflatoxin B1, ochratoxin A, deoxynivalenol), and algal/cyanobacterial toxins (e.g., saxitoxin, domoic acid, microcystins, biliatresone). We emphasize studies that clearly define toxin identity and exposure context and that demonstrate mechanism-critical model competencies under assay conditions. We highlight decision-informative functional endpoints that align with the dominant pathophysiology. These include cystic fibrosis transmembrane conductance regulator (CFTR)-dependent secretion in human enteroids/colonoids, transporter-linked proximal tubular injury in kidney MPS, gut–kidney axis injury from Shiga toxin-producing E. coli in microfluidic systems, and multi-electrode array (MEA) network readouts in human 3D neural tissues. We then summarize best practices that improve cross-study comparability. These include reporting delivered versus nominal exposure, assessing recovery/mass balance and device/material interactions, applying proportional biological qualification (polarity, transporter/enzymatic competence, functional stability), defining a minimal comparable endpoint core, and preserving QIVIVE readiness in reporting. Finally, we outline near-term priorities for the field, including chronic low-dose and mixture designs, harmonized reference panels and acceptance criteria, and fit-for-purpose escalation to coupled OoC/MPS only when perfusion or organ–organ coupling is expected to change the interpretation. Full article
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30 pages, 1965 KB  
Article
Joint Denoising and Motion-Correction for Low-Dose CT Myocardial Perfusion Imaging Using Deep Learning
by Mahmud Hasan, Aaron So and Mahmoud R. El-Sakka
Electronics 2026, 15(6), 1286; https://doi.org/10.3390/electronics15061286 - 19 Mar 2026
Abstract
Computed Tomography (CT) is a widely used imaging modality that employs X-rays and computational reconstruction to visualize internal anatomy. Although higher radiation doses produce higher-quality images, they also increase long-term cancer risk, motivating the use of low-dose protocols. However, low-dose CT data inherently [...] Read more.
Computed Tomography (CT) is a widely used imaging modality that employs X-rays and computational reconstruction to visualize internal anatomy. Although higher radiation doses produce higher-quality images, they also increase long-term cancer risk, motivating the use of low-dose protocols. However, low-dose CT data inherently suffer from elevated Poisson–Gaussian noise, necessitating effective denoising strategies. In myocardial CT perfusion (CTP) imaging, this challenge is compounded by residual cardiac motion, which misaligns consecutive time points and impairs accurate estimation of perfusion maps for diagnosing coronary artery disease. Traditional approaches typically treat these two problems, noise and motion, separately, denoising the reconstructed images first or applying the registration first. Such serial pipelines often degrade clinically significant features; e.g., denoising may destroy structural details essential for registration, while motion correction can distort subtle intensity cues needed for noise modelling. To overcome these limitations, we propose a unified deep learning framework that performs noise suppression and motion correction jointly for low-dose myocardial CTP. The method integrates two complementary components through a parallel ensemble strategy: (i) a modified Fast and Flexible Denoising Network (FFDNet) that incorporates noise-level maps to mitigate blended noise effectively, and (ii) a CNN-based registration model, extended with Time Enhancement Curve (TEC) correction and 4D physiological consistency constraints to estimate temporally coherent and anatomically plausible motion fields. By combining their outputs without iterative dependencies, the proposed framework produces motion-corrected and denoised CTP sequences in a single unified processing step, thereby better preserving myocardial structure and perfusion dynamics than conventional serial pipelines. The model has been evaluated using both reference-based (MSE, PSNR, SSIM, PCC, Noise Variance, TRE) and no-reference (NIQE, FID, KID, AUC) image quality metrics, supplemented by expert human assessment. Results demonstrate that jointly learning noise characteristics and motion patterns enables restoration of low-dose CTP images while minimizing feature corruption, thereby advancing the clinical utility of low-dose myocardial CTP imaging. Full article
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22 pages, 3397 KB  
Review
Advances in Bone-on-a-Chips for In Vitro Modeling of Bone Physiology and Pathology
by Xiuyun Cheng, Mingxia Lu, Ming Ma, Shumin Zhou, Jun Xu, Yuhao Li and Hongxu Lu
Biomedicines 2026, 14(3), 710; https://doi.org/10.3390/biomedicines14030710 - 19 Mar 2026
Abstract
Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need [...] Read more.
Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article
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10 pages, 524 KB  
Article
Efficacy of Vitreous Biopsy and Clinical Course in Vitreoretinal Lymphoma: A Single-Center Retrospective Analysis
by Naoya Shiozaki, Tadamichi Akagi, Hiroko Terashima, Takumi Ando, Eriko Ueda, Daigo Kobayashi, Yohei Nozaki and Jun Ominato
J. Clin. Med. 2026, 15(6), 2344; https://doi.org/10.3390/jcm15062344 - 19 Mar 2026
Abstract
Background/Objectives: The high risk of CNS dissemination poses a significant challenge in the management of primary vitreoretinal lymphoma (PVRL). We evaluated the clinical value of our institutional protocol for PVRL, which combines targeted vitreous sampling with routine central nervous system (CNS) surveillance [...] Read more.
Background/Objectives: The high risk of CNS dissemination poses a significant challenge in the management of primary vitreoretinal lymphoma (PVRL). We evaluated the clinical value of our institutional protocol for PVRL, which combines targeted vitreous sampling with routine central nervous system (CNS) surveillance using magnetic resonance imaging (MRI) every 4–6 months. Methods: We retrospectively reviewed 34 consecutive patients who underwent vitreous biopsies at Niigata University Hospital between January 2010 and December 2021; 12 patients were initially diagnosed with PVRL without CNS involvement. The protocol mandates submission of both undiluted vitreous samples and the entire vitreous cassette contents, including perfusion fluid, for cytologic evaluation. Patients with PVRL underwent MRI surveillance every 4–6 months. Results: Among 12 patients with PVRL, vitreous cytology classified as Class IV or higher demonstrated a positivity rate of 75% (9/12) using undiluted samples alone, which increased to 92% (11/12) when cassette contents were included. Ancillary test results revealed an interleukin (IL)-10/IL-6 ratio > 1 in 75% (9/12) and immunoglobulin heavy chain gene rearrangement in 92% (11/12). Extraocular relapse occurred in 92% of patients (11/12), including 10 cases of CNS involvement and one systemic relapse, with a mean time to CNS progression of 11.8 months. The 5-year overall survival was 58%. Conclusions: Comprehensive vitreous sampling incorporating perfusion fluid may improve cytologic detection in PVRL within a single-center setting. Routine MRI surveillance facilitates early detection of CNS relapse in patients with PVRL; however, a survival benefit cannot be established from this retrospective analysis. Full article
(This article belongs to the Section Ophthalmology)
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15 pages, 622 KB  
Review
Biomarkers of Preclinical Diabetic Retinopathy Detected by OCT Angiography—A Descriptive Review
by Ilona Strauss and Maciej Gawęcki
Life 2026, 16(3), 496; https://doi.org/10.3390/life16030496 - 18 Mar 2026
Viewed by 107
Abstract
Background: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microvascular changes precede clinically detectable DR, creating an opportunity for early diagnosis and intervention. Optical coherence tomography angiography (OCTA) enables noninvasive, quantitative assessments of retinal and choroidal microcirculation and has [...] Read more.
Background: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microvascular changes precede clinically detectable DR, creating an opportunity for early diagnosis and intervention. Optical coherence tomography angiography (OCTA) enables noninvasive, quantitative assessments of retinal and choroidal microcirculation and has emerged as a promising tool for identifying early biomarkers of DR. The goal of this study was to review the literature on OCTA-derived biomarkers associated with preclinical diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. Methods: This descriptive literature review summarizes current evidence regarding OCTA-derived biomarkers associated with preclinical diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. A search of the PubMed/MEDLINE database was performed to identify original studies published between 2015 and 2025 evaluating OCTA parameters in diabetic patients without clinically detectable diabetic retinopathy. The findings were synthesized qualitatively due to methodological heterogeneity among studies in terms of OCTA devices, imaging protocols, and analyzed parameters. Results: The reviewed studies consistently reported early microvascular abnormalities detectable by OCTA prior to the development of clinically visible diabetic retinopathy. The most frequently described changes included reduced vessel density (VD) and perfusion parameters, enlargement and increased irregularity of the foveal avascular zone (FAZ), areas of capillary non-perfusion, and alterations in vascular network geometry and complexity. These changes were most consistently observed in the deep capillary plexus (DCP), suggesting that this vascular layer may be particularly susceptible to early diabetic microvascular damage. Conclusions: This review provides a comprehensive synthesis of OCTA-derived biomarkers associated with early retinal microvascular alterations in diabetic patients without clinically detectable diabetic retinopathy. By integrating findings from recent studies, the review highlights the potential role of OCTA in identifying preclinical microvascular changes and discusses current methodological challenges and future research directions. Full article
(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 3rd Edition)
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26 pages, 6215 KB  
Article
Modified Chitosan-Based Hemostatic Dressings Incorporating Heparin-Loaded Nanoparticles for Enhanced Hemostatic Activity
by Despoina Meimaroglou, Evi Christodoulou, Rizos Evangelos Bikiaris, Ioanna Koumentakou, Michiel Jan Noordam, Amalia Oikonomou, Ioannis Taitzoglou, Ioannis Tsamesidis, Eleana Kontonasaki, Zoi Terzopoulou, Lysimachos G. Papazoglou, George Z. Kyzas and Dimitrios N. Bikiaris
Pharmaceutics 2026, 18(3), 373; https://doi.org/10.3390/pharmaceutics18030373 - 18 Mar 2026
Viewed by 83
Abstract
Background/Objectives: Achieving effective hemostasis is a vital step in wound healing, particularly in cases of severe bleeding caused by surgical procedures or trauma. This study focuses on the development of chitosan-based dressings enriched with Heparin (hep)-loaded poly(butylene succinate) (PBSu) nanoparticles to combine [...] Read more.
Background/Objectives: Achieving effective hemostasis is a vital step in wound healing, particularly in cases of severe bleeding caused by surgical procedures or trauma. This study focuses on the development of chitosan-based dressings enriched with Heparin (hep)-loaded poly(butylene succinate) (PBSu) nanoparticles to combine hemostatic and anticoagulant properties. Methods: Chitosan, a biocompatible and biodegradable carbohydrate with inherent antibacterial and hemostatic properties, was chemically modified with 2-(N-morpholino)ethanesulfonic acid (MES) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) to enhance its swelling ability and hemostatic activity. PBSu nanoparticles were synthesized using an oil-in-water emulsification method and loaded with Hep to achieve controlled anticoagulant release. The dressings of the modified chitosan derivatives with the nanoparticles which were systematically characterized for morphology, chemical structure, swelling ability, loading capacity, and Hep release kinetics. Results: This dual-function system is designed to decouple local surface hemostasis from thrombotic processes: the chitosan matrix provides rapid topical hemostasis, while controlled heparin release from the nanoparticles aims to modulate excessive fibrin deposition, support microvascular perfusion, and exploit the pro-healing benefits of low-dose heparin reported in advanced wound dressings, particularly in high-risk or thrombotic-prone patients. In vitro and in vivo studies demonstrated their potential for promoting rapid hemostasis. Conclusions: These findings suggest that the integration of modified chitosan and Hep-loaded nanoparticles is a promising strategy for advancing wound care and hemostatic technologies. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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24 pages, 24019 KB  
Review
Clonal Hematopoiesis (CHIP) in Pulmonary Embolism and CTEPH: Evidence, Mechanisms, and Risk Stratification
by Lukasz Szarpak, Monika Jach, Michal Skoczylas, Sebastian Radej and Michal Pruc
Int. J. Mol. Sci. 2026, 27(6), 2750; https://doi.org/10.3390/ijms27062750 - 18 Mar 2026
Viewed by 100
Abstract
Pulmonary embolism (PE) is biologically heterogeneous. Despite guideline-directed anticoagulation, a subset of patients develops recurrent venous thromboembolism, persistent exertional limitation, residual perfusion defects, and progression to chronic thromboembolic pulmonary disease (CTEPD) or chronic thromboembolic pulmonary hypertension (CTEPH). Conventional risk factors explain much of [...] Read more.
Pulmonary embolism (PE) is biologically heterogeneous. Despite guideline-directed anticoagulation, a subset of patients develops recurrent venous thromboembolism, persistent exertional limitation, residual perfusion defects, and progression to chronic thromboembolic pulmonary disease (CTEPD) or chronic thromboembolic pulmonary hypertension (CTEPH). Conventional risk factors explain much of the index event but incompletely account for thrombus non-resolution and chronic sequelae. Clonal hematopoiesis of indeterminate potential (CHIP)—the age-associated expansion of hematopoietic clones carrying somatic mutations—defines a measurable thrombo-inflammatory endophenotype that is strongly genotype- and clone-size (variant allele frequency; VAF)-dependent. Across human studies, JAK2-CHIP and TET2-CHIP show the most consistent associations with VTE/PE, whereas isolated DNMT3A-CHIP is frequently neutral, and larger clones tend to confer stronger effects. Mechanistically, CHIP can bias myeloid cells toward inflammasome/IL-1β signaling and endothelial activation, increase monocyte tissue factor activity, and promote immunothrombosis with neutrophil extracellular trap (NET) formation. NET-rich thrombi may adopt a dense fibrin–DNA–histone architecture that resists endogenous fibrinolysis, favoring organization and persistence. CTEPH offers a translational window to interrogate this model because thrombotic material and deep phenotyping are accessible. We synthesize genotype- and VAF-resolved clinical and mechanistic evidence using a structured strength-of-evidence framework and propose a pragmatic phenotyping roadmap with testable predictions for prospective post-PE validation. CHIP testing in PE/CTEPH remains investigational and should not currently change standard care. Full article
(This article belongs to the Special Issue Molecular Mechanism in Pulmonary Embolism)
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20 pages, 26161 KB  
Review
Necrotizing (Abscessing) Lymphadenopathy and the Diagnostic Value of Contrast-Enhanced Ultrasound (CEUS): A Review with Clinical Vignettes
by Christian Görg, Yi Dong, Görg Friedemann, Christian Jenssen, Michael Kallenbach, Kathleen Möller, Findeisen Hajo, Nitin Chaubal and Christoph Frank Dietrich
Diagnostics 2026, 16(6), 888; https://doi.org/10.3390/diagnostics16060888 - 17 Mar 2026
Viewed by 113
Abstract
Necrotizing (abscessing) lymphadenopathy is a clinically relevant condition with a broad differential diagnosis, including acute bacterial infections, mycobacterial disease, zoonoses, fungal and parasitic infections, autoimmune disorders, and malignancies with central necrosis. Early and reliable differentiation between these causes is important to avoid misdiagnosis [...] Read more.
Necrotizing (abscessing) lymphadenopathy is a clinically relevant condition with a broad differential diagnosis, including acute bacterial infections, mycobacterial disease, zoonoses, fungal and parasitic infections, autoimmune disorders, and malignancies with central necrosis. Early and reliable differentiation between these causes is important to avoid misdiagnosis and to guide appropriate therapy. This review summarizes the pathophysiological mechanisms, typical imaging features, and diagnostic value of contrast-enhanced ultrasound (CEUS) in necrotizing lymphadenopathy. Representative clinical vignettes illustrate the disease spectrum and correlate CEUS patterns with underlying pathology. The literature review was narrative and based on targeted searches of PubMed/MEDLINE and Google Scholar focusing on CEUS in necrotizing lymphadenopathy. A brief literature overview highlights current evidence, limitations, and research gaps. Conventional B-mode ultrasound (BMUS) and Doppler typically demonstrate enlarged hypoechoic or heterogeneous nodes with reduced central vascularity but lack specificity for necrosis. CEUS provides real-time visualization of nodal microvascular perfusion, which may support clearer differentiation between viable tissue and necrotic or abscess cavities. Common but non-specific CEUS patterns include central non-enhancement with a peripheral hyperemic rim in abscesses, irregular avascular cores in tuberculous lymphadenopathy, patchy non-enhancing areas in autoimmune conditions, and heterogeneous enhancement with ill-defined necrosis in malignant nodes. CEUS can support biopsy targeting, facilitate drainage procedures, and enable radiation-free follow-up. CEUS may offer diagnostic and interventional advantages in the evaluation of necrotizing lymphadenopathy, offering more consistent characterization of nodal necrosis compared with conventional sonography. While most evidence focuses on tuberculosis and malignancy, growing experience with zoonotic and autoimmune diseases suggests broader utility. Most currently available evidence derives from observational studies and small case series, highlighting the need for prospective multicenter validation. Standardization of CEUS criteria, integration into multiparametric ultrasound protocols, and multicenter validation are needed to establish CEUS as a routine component in the diagnostic work-up of necrotizing lymphadenopathy. Full article
(This article belongs to the Special Issue Ultrasound Imaging: Current Status and Future Perspectives)
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25 pages, 1492 KB  
Review
The Role of CEUS in the Diagnosis and Follow-Up of Pleuropulmonary Diseases and Interventional Procedures
by Andrea Boccatonda, Alice Brighenti, Daniel Piamonti, Giulia Bandini, Giulia Fiorini, Luigi Vetrugno, Giampietro Marchetti, Esterita Accogli, Carla Serra and Damiano D’Ardes
J. Clin. Med. 2026, 15(6), 2292; https://doi.org/10.3390/jcm15062292 - 17 Mar 2026
Viewed by 104
Abstract
Background: Contrast-enhanced ultrasound (CEUS) recently emerged as a valuable imaging modality for evaluating pleuropulmonary diseases. By combining morphological information from conventional B-mode ultrasound with real-time assessment of microvascular perfusion, CEUS can provide functional insights that improve diagnostic accuracy, guide interventions, and support patient [...] Read more.
Background: Contrast-enhanced ultrasound (CEUS) recently emerged as a valuable imaging modality for evaluating pleuropulmonary diseases. By combining morphological information from conventional B-mode ultrasound with real-time assessment of microvascular perfusion, CEUS can provide functional insights that improve diagnostic accuracy, guide interventions, and support patient surveillance. Methods: This review summarizes the current evidence on the use of CEUS in major pleuropulmonary disorders, including pneumonia, pleural effusion, pulmonary embolism, neoplasms, and COVID-19-related lung injury. The most relevant clinical studies and meta-analyses were analyzed, focusing on CEUS parameters, diagnostic performance, and integration with other imaging techniques. Results: CEUS enables the differentiation between inflammatory, ischemic, and malignant lesions through qualitative and quantitative analyses of enhancement patterns. Early and homogeneous enhancement is typical of inflammatory or infectious processes, whereas heterogeneous or delayed enhancement with early washout strongly suggests malignancy or ischemia. In pneumonia and pleural infections, CEUS identifies non-perfused or necrotic areas, guiding drainage and evaluating therapeutic responses. In pulmonary embolism, it reveals avascular consolidations corresponding to infarction, even when CT angiography is inconclusive. For peripheral lung tumors, CEUS assesses angiogenesis and vascular supply, correlating perfusion parameters with histopathology, and improving biopsy targeting. Furthermore, in COVID-19 pneumonia, CEUS can detect microvascular alterations related to thrombosis and fibrosis. Conclusions: CEUS is a safe, noninvasive, and radiation-free technique that provides unique real-time information on pulmonary perfusion. Its integration with conventional ultrasound enhances diagnostic precision, optimizes interventional guidance, and allows for dynamic monitoring of treatment response. Future developments in quantitative analysis, artificial intelligence, and targeted contrast agents are expected to further expand CEUS clinical applications in pleuropulmonary imaging. Full article
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18 pages, 3502 KB  
Article
Comparison of Normothermic and Subnormothermic Machine Perfusion of Porcine Kidneys Using a Novel Fully Synthetic Perfusion Solution: A Proof-of-Concept Study
by Hannah K. Krüger, Benedict M. Doorschodt, Zoltan Czigany, Oliver Beetz, Felix Oldhafer, Alexander Theißen, Laura Zarnitz, Lisa Ernst, Felix von Lendenfeld, Jan Larmann, René H. Tolba and Christian Bleilevens
J. Clin. Med. 2026, 15(6), 2287; https://doi.org/10.3390/jcm15062287 - 17 Mar 2026
Viewed by 90
Abstract
Background/Objectives: The growing shortage of organs for transplantation requires optimized preservation techniques. Normothermic (NMP) and Subnormothermic Machine Perfusion (SMP) allow for the assessment of organ viability prior to transplantation and enable targeted therapeutic interventions while maintaining a metabolically active state in contrast [...] Read more.
Background/Objectives: The growing shortage of organs for transplantation requires optimized preservation techniques. Normothermic (NMP) and Subnormothermic Machine Perfusion (SMP) allow for the assessment of organ viability prior to transplantation and enable targeted therapeutic interventions while maintaining a metabolically active state in contrast to hypothermic settings. Methods: In this study, the synthetic perfusion solution “Omnisol” was used in a 6 h ex vivo setting with porcine kidneys (n = 6 NMP; n = 6 SMP). Perfusion parameters (arterial flow, intrarenal resistance and urinary flow), renal function (excretory and filtration performance), renal injury (cellular and circulating biomarkers) and tissue and perfusate oxygenation were assessed. Results: NMP resulted in better arterial flow and lower intrarenal resistance during the first 3 h of perfusion, while SMP surpassed NMP from 3 to 6 h. Renal injury biomarkers increased in the NMP group after 3 h, while no increase was detectable in the SMP group. Omnisol fully met the oxygen requirements of the kidneys in both groups, despite being fully synthetic. Conclusions: Both NMP and SMP offer distinct advantages for kidney preservation, and the synthetic perfusate Omnisol appears to be feasible for both methods. In this experimental setting, the data indicate that NMP of porcine kidneys was associated with favorable functional parameters during the early phase of perfusion, whereas SMP showed comparatively stable parameters at later time points. These findings should primarily be considered exploratory observations and require validation in future studies, especially for the translation into a clinical scenario using human kidneys. Full article
(This article belongs to the Section Nephrology & Urology)
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