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15 pages, 851 KB  
Article
Multicentre Retrospective Cohort Study on Current Practices in Treatment of Patients Presenting with Non-A Non-B Aortic Dissection and Factors Predicting the Need for Intervention and Mortality
by Ottavia Borghese, Gabriel Lopez-Pena, Athanasios Saratzis, Tryfon Vainas, Alice Lopes, Blandine Maurel and Tara Mastracci
J. Clin. Med. 2026, 15(1), 211; https://doi.org/10.3390/jcm15010211 - 27 Dec 2025
Viewed by 238
Abstract
Objectives: Non-A Non-B (NANB) aortic dissections (ADs) are uncommon. Because of their rarity, their therapeutic pathway is not yet standardized, and anatomic or goal-directed treatments are not reported in current practices. We reviewed the treatment strategies of NANB AD across Europe, aiming to [...] Read more.
Objectives: Non-A Non-B (NANB) aortic dissections (ADs) are uncommon. Because of their rarity, their therapeutic pathway is not yet standardized, and anatomic or goal-directed treatments are not reported in current practices. We reviewed the treatment strategies of NANB AD across Europe, aiming to identify factors associated with increased mortality and the need for intervention, outlining optimal management pathways for future care. Methods: This multicentre cohort study was carried out in four European aortic centres, retrospectively including patients affected by NANB AD over the last 10 years. Patients’ anatomical clinical and treatment data were collected with the aim of investigating the factors associated with their need for intervention and increased mortality, comparing the characteristics of those requiring surgery with those who responded to medical treatment alone. Results: Thirty-eight NANB patients (26, 68.4% men; mean age 60.6 ± 12.87) were included. The primary entry tear was identified in Ishimaru zone 1 or 2 in most cases (24, 63.2%) and the dissection extended distally to the ilio-femoral arteries in half of the patients (21, 55.3%). Surgical repair was indicated in 21 (55.3%) cases within 90 days of acute onset for end-organ ischemia, impending aortic rupture, or retrograde extension of the dissection (including 11 emergent/urgent operations), with most patients requiring surgery within 15 days of acute onset (17, 44.7%). The mean aortic diameter among patients requiring surgery was significantly higher in both zone 1 (7 37 IQR 3 versus 34 IQR 7, p = 0.043) and 2 (36 IQR 6 versus 32.5 IQR 7, p = 0.044) when compared with patients who underwent medical treatment alone. An increased in-hospital mortality rate was noted among patients with indication for surgery after medical treatment (0% versus 30.8%, p = 0.023). Conclusions: This cohort provides an additional description of clinical aspects and current practices in the treatment of NANB in Europe. Most patients of this series had an indication for surgery within two weeks of acute onset, demonstrating a frequently complicated course; moreover, this raises questions surrounding the most appropriate timing for interventional management. Although a diameter threshold was not identified, the baseline enlarged aortic diameter in zones 1 and 2 seemed to be associated with a need for early intervention. Further study is needed to fully refine the indications for treatment in NANB patients; this will support the study of the independent risk factors for increased mortality risk and complications among this group, and will allow the identification of subgroups of patients that may benefit from more aggressive treatment from acute onset. Full article
(This article belongs to the Special Issue Vascular Surgery: Current Advances and Future Directions)
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23 pages, 3017 KB  
Review
Targeting the Cellular Prion Protein as a Biomarker for Stem Cells, Cancer, and Regeneration
by Niccolò Candelise, Nicola Salvatore Orefice, Elisabetta Mantuano and Stefano Martellucci
Biologics 2026, 6(1), 1; https://doi.org/10.3390/biologics6010001 - 24 Dec 2025
Viewed by 444
Abstract
The cellular prion protein (PrPC) displays a functional repertoire that extends well beyond its classical link to transmissible spongiform encephalopathies. Abundant in the nervous system and localized within lipid raft microdomains, PrPC has emerged as a multifunctional signaling platform that [...] Read more.
The cellular prion protein (PrPC) displays a functional repertoire that extends well beyond its classical link to transmissible spongiform encephalopathies. Abundant in the nervous system and localized within lipid raft microdomains, PrPC has emerged as a multifunctional signaling platform that regulates cell differentiation, neurogenesis, neuroprotection, and synaptic plasticity. Recent evidence highlights its dynamic expression in stem cell populations, where it participates in multimolecular complexes that control lineage commitment, particularly during neuronal differentiation. PrPC expression tightly correlates with stem cell status, making it a promising biomarker of stemness and developmental progression. Through interactions with growth factors, extracellular matrix components, and synaptic proteins, PrPC functions as a molecular integrator of signals essential for tissue repair and regeneration. Preclinical studies demonstrate that recombinant PrPC can stimulate neurogenesis and tissue repair, while monoclonal antibodies modulate its physiological and pathological functions. Likewise, cell-based therapies leveraging PrPC-enriched stem cells or PrPC-dependent signaling profiles have shown promise in models of neurodegeneration and ischemia. Conversely, dysregulated PrPC expression has also been observed in solid tumors, where it contributes to cancer cell survival, proliferation, metastasis, and therapy resistance, reinforcing its role as a regulator of cell fate and an oncological target. This review integrates stem cell biology, tissue regeneration, and oncology into a unified framework, offering a novel perspective in which PrPC emerges as a shared molecular hub governing both physiological repair and pathological tumor behavior, opening previously unrecognized conceptual and translational opportunities. Full article
(This article belongs to the Section Protein Therapeutics)
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27 pages, 1490 KB  
Review
Damage-Associated Molecular Patterns in Perioperative Anesthesia Care: A Clinical Perspective
by Wiriya Maisat and Koichi Yuki
Anesth. Res. 2026, 3(1), 1; https://doi.org/10.3390/anesthres3010001 - 20 Dec 2025
Viewed by 509
Abstract
Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury that trigger sterile inflammation. In perioperative settings, common triggers include surgical trauma, ischemia–reperfusion injury, cardiopulmonary bypass, blood transfusion, and mechanical ventilation. When released extracellularly, DAMPs activate innate immune receptors such [...] Read more.
Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury that trigger sterile inflammation. In perioperative settings, common triggers include surgical trauma, ischemia–reperfusion injury, cardiopulmonary bypass, blood transfusion, and mechanical ventilation. When released extracellularly, DAMPs activate innate immune receptors such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), initiating signaling cascades that amplify inflammation, disrupt endothelial integrity, and promote coagulation and metabolic imbalance. This sterile inflammatory response may extend local tissue injury into systemic organ dysfunction, manifesting clinically as acute lung injury, acute kidney injury, myocardial dysfunction, disseminated intravascular coagulation, and perioperative neurocognitive disorders. Recognizing the central role of DAMPs reframes these complications as predictable consequences of endogenous danger signaling rather than solely as results of infection or hemodynamic instability. This understanding supports the use of established strategies such as protective ventilation and restrictive transfusion to minimize DAMP release. Emerging evidence also suggests that anesthetic agents may influence DAMP-mediated inflammation: propofol and dexmedetomidine appear to exert anti-inflammatory effects, whereas volatile anesthetics show variable results. Although clinical data remain limited, anesthetic choice and perioperative management may significantly affect systemic inflammatory burden and recovery. Future research validating DAMPs as biomarkers and therapeutic targets may inform precision anesthetic strategies aimed at modulating sterile inflammation, ultimately enhancing perioperative outcome. Full article
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12 pages, 497 KB  
Review
Temporary Portocaval Shunts During Liver Transplantation: A Narrative Review of Technical Solutions and Post-Transplant Outcomes
by Elisa Schirra, Alberto Mauro, Giuseppe Bianco, Marco Maria Pascale, Francesco Frongillo, Erida Nure, Alfonso Wolfango Avolio, Salvatore Agnes and Gabriele Spoletini
J. Clin. Med. 2025, 14(24), 8723; https://doi.org/10.3390/jcm14248723 - 9 Dec 2025
Viewed by 365
Abstract
Background: Liver transplantation (LT) continues to evolve with techniques aimed at minimizing perioperative complications associated with caval and portal vein clamping. Caval-sparing approaches, such as the piggyback technique, preserve hemodynamic stability; however, portal clamping remains necessary and may trigger postreperfusion syndrome, endotoxemia, [...] Read more.
Background: Liver transplantation (LT) continues to evolve with techniques aimed at minimizing perioperative complications associated with caval and portal vein clamping. Caval-sparing approaches, such as the piggyback technique, preserve hemodynamic stability; however, portal clamping remains necessary and may trigger postreperfusion syndrome, endotoxemia, and hepatic microcirculatory disturbances. Temporary portocaval shunts (PCSs) have been developed to maintain portal flow during LT, mitigating these adverse effects and allowing for hemodynamic stability and a reduced intraoperative bleeding. Portocaval Shunts: Various PCS techniques—including end-to-side, right-branch, portosaphenous, mesenterico-saphenous, iliac-venous conduit interposition, portoumbilical, and Rex-saphenous shunts—allow an individualized approach based on patient anatomy and surgical complexity. Review of Evidence: Available evidence demonstrates that PCS improves intraoperative hemodynamic stability, reduces blood transfusion requirements, and preserves renal function, particularly in patients with high portal flow or severe portal hypertension. PCS may also shorten warm ischemia time, facilitate hepatectomy, and enhance outcomes in extended criteria donor grafts or marginal organs. Meta-analyses and randomized studies support its role in reducing intraoperative blood loss, improving early graft function, and accelerating postoperative recovery. However, the effect of PCS on long-term survival and major postoperative morbidity remains variable, likely due to heterogeneity in patient populations, donor types, and perioperative management. Conclusions: Overall, PCS represents a safe and feasible adjunct in LT, offering significant hemodynamic and technical advantages. Its use should be individualized based on patient risk factors, intraoperative hemodynamics, and anticipated intraoperative challenges. PCS provides a practical strategy to preserve portal flow, minimizing intraoperative complications and facilitating the hepatectomy. However, the decision to create a PCS during LT still depends on the surgeon’s preference. Postoperative outcomes and impact on long-term survival require further investigation. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Hurdles and Future Perspectives)
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17 pages, 1415 KB  
Review
Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
by Arnau Panisello-Rosello, Teresa Carbonell, Joan Rosello-Catafau, Jordi Vengohechea, Amelia Hessheimer, René Adam and Constantino Fondevila
Int. J. Mol. Sci. 2025, 26(23), 11734; https://doi.org/10.3390/ijms262311734 - 4 Dec 2025
Cited by 1 | Viewed by 669
Abstract
Static cold storage (SCS) remains the most widely used method of liver graft preservation due to its simplicity, accessibility, and reduced cost in transplantation practice. Since the invention of the University of Wisconsin (UW) solution, several alternative preservation solutions—including histidine–tryptophan–ketoglutarate (HTK), Celsior, and [...] Read more.
Static cold storage (SCS) remains the most widely used method of liver graft preservation due to its simplicity, accessibility, and reduced cost in transplantation practice. Since the invention of the University of Wisconsin (UW) solution, several alternative preservation solutions—including histidine–tryptophan–ketoglutarate (HTK), Celsior, and more recently IGL-1 and IGL-2—have been formulated to optimize cellular and vascular protection during cold ischemia. More recently, the introduction of dynamic perfusion techniques, such as hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP), approximately fifteen years ago, has further enhanced transplantation protocols, being applied either alone or in combination with traditional SCS to ensure optimal graft preservation prior to implantation. Despite these technological advances, achieving fully effective dynamic perfusion remains a key challenge for improving outcomes in vulnerable grafts, particularly steatotic or marginal livers. This review details how Polyethylene Glycol 35 (PEG35)-based solutions activate multiple cytoprotective pathways during SCS, including AMP-activated protein kinase (AMPK), nitric oxide (NO) production, and the antioxidant transcription factor Nrf2. We propose that these molecular mechanisms serve as a form of preconditioning that is synergistically leveraged by HOPE to preserve mitochondrial function, endothelial glycocalyx integrity, and microvascular homeostasis. Furthermore, the oncotic and rheological properties of PEG35 reduce perfusate viscosity, mitigating shear stress and microcirculatory damage during dynamic perfusion—effects that are further enhanced by NO- and AMPK-mediated protection initiated during the SCS phase. This integrated approach provides a strong rationale for combining PEG35-mediated SCS with HOPE, particularly for grafts with high susceptibility to ischemia–reperfusion injury, such as fatty livers. Finally, we highlight emerging avenues in graft preservation, including the design of unified perfusion solutions that optimize endothelial, mitochondrial, and redox protection, with the potential to improve post-transplant outcomes and extend applicability to other solid organ grafts. Full article
(This article belongs to the Special Issue Molecular Insights into Transplantation and Machine Perfusion)
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16 pages, 545 KB  
Article
A Lumped Parameter Modelling Study of Leukoaraiosis Suggests Its Vascular Pathophysiology May Be Similar to Normal-Pressure Hydrocephalus
by Grant A. Bateman and Alexander R. Bateman
Brain Sci. 2025, 15(9), 1023; https://doi.org/10.3390/brainsci15091023 - 22 Sep 2025
Viewed by 773
Abstract
Introduction: Leukoaraiosis (LA) or white matter disease is a significant component of vascular dementia. There is a large overlap noted between normal-pressure hydrocephalus (NPH) and LA. A previously reported lumped parameter modelling study of NPH led to novel findings in this disease. Given [...] Read more.
Introduction: Leukoaraiosis (LA) or white matter disease is a significant component of vascular dementia. There is a large overlap noted between normal-pressure hydrocephalus (NPH) and LA. A previously reported lumped parameter modelling study of NPH led to novel findings in this disease. Given the overlap between LA and NPH, the purpose of the current study is to perform a lumped parameter study into LA to see if the vascular pathophysiology is similar to NPH. Methods: A lumped parameter model originally developed to study normal-pressure hydrocephalus was extended to investigate LA. The model was constrained by the known cerebral blood flow and cerebral blood volumes found in LA, as derived from the literature. Results: Similar to NPH, in LA, the model predicted a balanced increase in arterial and venous outflow resistance, with the resulting ischemia affecting the white matter rather than the grey matter. However, unlike NPH, in LA, the findings are irreversible, most likely due to structural venous wall changes. Conclusions: The model suggests that the vascular physiology of LA maybe similar to NPH. A common pathophysiology is discussed based on a pulsation-induced increase in the venous outflow resistance. Full article
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12 pages, 9892 KB  
Article
Alternative Transaxillary Access for Transcatheter Aortic Valve Implantation
by Konrad Wisniewski, Gerrit Kaleschke, Fernando De-Torres-Alba, Sven Martens and Heinz Deschka
J. Clin. Med. 2025, 14(14), 5127; https://doi.org/10.3390/jcm14145127 - 18 Jul 2025
Cited by 1 | Viewed by 1009
Abstract
Background/Objectives: Currently, the transfemoral approach is recognized as the primary method for accessing transcatheter aortic valve implantation (TAVI). However, alternative techniques are needed when the transfemoral access is not suitable. We proposed that a modified transaxillary approach through the distal left axillary artery [...] Read more.
Background/Objectives: Currently, the transfemoral approach is recognized as the primary method for accessing transcatheter aortic valve implantation (TAVI). However, alternative techniques are needed when the transfemoral access is not suitable. We proposed that a modified transaxillary approach through the distal left axillary artery is both viable and safe for conducting TAVI, potentially offering benefits for patients. Methods: From December 2018 to February 2024, a total of 24 patients (7 women, average age 77.9 ± 8 years) received TAVI using transaxillary access via the left axillary artery. The participants suffered from symptomatic severe aortic stenosis and were deemed TAVI candidates with iliofemoral anatomy unsuitable for a transfemoral route. The patient group displayed a high perioperative risk profile, with significant peripheral artery disease or severe obstructive infrarenal aortic conditions. The implantation of the aortic prosthesis was carried out through the left distal axillary artery. A balloon-expandable valve was used in every instance. Results: In the examined cohort, the 30-day mortality rate was 4.2%. A new pacemaker was necessary for four patients (16.7%). One case exhibited a new moderate neurological dysfunction. Additionally, one patient required surgical revision of the access point due to ischemia. Conclusions: Our findings indicate that transaxillary TAVI via the distal left axillary artery has yielded encouraging outcomes. This approach is practicable and safe, does not prolong the procedure, minimizes surgical trauma, ensures excellent access regardless of chest anatomy, and is sparing for the brachial plexus. As a single-center pilot study, our findings require confirmation in larger, prospective cohorts with extended follow-up to fully validate the safety and long-term efficacy of this technique. Full article
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18 pages, 1149 KB  
Article
Hypothermic Machine Perfusion Is Associated with Improved Short-Term Outcomes in Liver Transplantation: A Retrospective Cohort Study
by Alexandru Grigorie Nastase, Alin Mihai Vasilescu, Ana Maria Trofin, Mihai Zabara, Ramona Cadar, Ciprian Vasiluta, Nutu Vlad, Bogdan Mihnea Ciuntu, Corina Lupascu Ursulescu, Cristina Muzica, Irina Girleanu, Iulian Buzincu, Florin Iftimie and Cristian Dumitru Lupascu
Life 2025, 15(7), 1112; https://doi.org/10.3390/life15071112 - 16 Jul 2025
Viewed by 1932
Abstract
Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: [...] Read more.
Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article
(This article belongs to the Section Medical Research)
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13 pages, 986 KB  
Review
Chronic Total Occlusions: Current Approaches, Evidence and Outcomes
by Remi Arnold, Richard Gervasoni and Florence Leclercq
J. Clin. Med. 2025, 14(13), 4695; https://doi.org/10.3390/jcm14134695 - 2 Jul 2025
Cited by 1 | Viewed by 3032
Abstract
Chronic total occlusions (CTOs), defined as complete coronary artery blockages persisting for over three months, are frequently encountered in up to 25% of coronary angiograms. Although percutaneous coronary intervention (PCI) for CTO remains technically challenging, advancements in guidewires, microcatheters, re-entry devices, and intravascular [...] Read more.
Chronic total occlusions (CTOs), defined as complete coronary artery blockages persisting for over three months, are frequently encountered in up to 25% of coronary angiograms. Although percutaneous coronary intervention (PCI) for CTO remains technically challenging, advancements in guidewires, microcatheters, re-entry devices, and intravascular imaging, along with the expertise of specialized operators, have significantly improved procedural success rates, now exceeding 90% in expert centers. While recent evidence, such as the SYNTAX II study, emphasizes the importance of complete revascularization, over half of CTO cases continue to be managed conservatively with optimal medical therapy (OMT), partly due to the limited high-quality randomized evidence supporting revascularization. Observational studies have demonstrated that successful CTO-PCI is associated with improved angina relief, quality of life, left ventricular function, and possibly long-term survival. Extended observational follow-up, such as the Korean and Canadian registries, suggests long-term reductions in cardiac and all-cause mortality with CTO revascularization. However, randomized controlled trials (RCTs) have primarily shown symptomatic benefit, with no consistent reduction in major adverse cardiac events (MACE) or mortality, likely due to limited sample sizes, short follow-up, and treatment crossovers. Various strategies, including the hybrid algorithm, guide CTO interventions by balancing antegrade and retrograde techniques based on lesion complexity. Imaging modalities such as coronary CT angiography and intravascular ultrasound play a pivotal role in planning and optimizing these procedures. Future innovations, such as real-time fusion imaging of CCTA with coronary angiography, may enhance lesion visualization and guidewire navigation. While current guidelines recommend CTO-PCI in selected symptomatic patients with demonstrable ischemia or viable myocardium, the decision should be individualized, incorporating anatomical feasibility, comorbidities, patient preferences, and input from a multidisciplinary Heart Team. Looking ahead, adequately powered RCTs with extended follow-up are essential to determine the long-term clinical impact of CTO-PCI on hard outcomes such as mortality and myocardial infarction. Full article
(This article belongs to the Special Issue Advances in Coronary Artery Disease)
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39 pages, 7427 KB  
Article
Molecular Mediated Angiogenesis and Vasculogenesis Networks
by Claudiu N. Lungu, Ionel I. Mangalagiu, Aurelia Romila, Aurel Nechita, Mihai V. Putz and Mihaela C. Mehedinti
Int. J. Mol. Sci. 2025, 26(13), 6316; https://doi.org/10.3390/ijms26136316 - 30 Jun 2025
Cited by 2 | Viewed by 1650
Abstract
By stimulating living tissues with proper molecules, the angiogenesis and vasculogenesis processes can be observed. Prostaglandin E1 (PGE1), which is a molecule that widens blood vessels and which is used for several medical purposes, such as treating critical limb ischemia, is a typical [...] Read more.
By stimulating living tissues with proper molecules, the angiogenesis and vasculogenesis processes can be observed. Prostaglandin E1 (PGE1), which is a molecule that widens blood vessels and which is used for several medical purposes, such as treating critical limb ischemia, is a typical leading molecule in angiogenesis studies. Nevertheless, its involvement in vasculogenesis and morphogenesis is a more specific subject in the field of developmental biology and therapeutic research. Vasculogenesis is the embryonic phenomenon in which endothelial progenitor cells generate new blood vessels. This phenomenon is distinct and divergent from angiogenesis, which entails the creation of novel blood vessels extending from pre-existing ones. Morphogenesis is the biological phenomenon responsible for the development of an organism or its components into a specific shape. Embryonic development and tissue regeneration are essential components. Current research is investigating the broader consequences of prostaglandins, such as PGE1, in the fields of developmental biology and regenerative medicine. Gaining knowledge about the impact of PGE1 on morphogenesis could provide valuable insights into congenital vascular abnormalities and innovative approaches for tissue repair and regeneration, especially in limb ischemia. In this study, a histologic and morphogenesis study was carried out on Artemia salina napi (first stage of development) by simulating the angiogenesis and morphogenesis processes using PGE1 as the top molecule with vasoactive properties and a series of benopyridyne (3-aminoquinolines, 5-amino quinolines, 8-aminoquinolines, 8-hydroxyquinolines and quinolines, respectively). A series of 30 Artemia salina napi were exposed to the compound listed before. Also, a lot of 30 unexposed Artemia salina napi was taken into account. In total, 210 Artemia salina napi were studied as a model for angionensis and morphogenesis. The study used wet experiments together with imaging reconstruction and graph-generating methodologies. The results show that PGE1 can initiate the shape of the vessel formation. Also, some quinoline series have a pro-mild morphogenetic and angiogenetic effect. Overall, PGE1 plays a significant role in mediating vasculogenesis and morphogenesis through its vasodilatory, anti-inflammatory, and pro-proliferative effects on endothelial cells. PGE1 is involved mainly in increasing the length of the vessel, while the number of vascular branching has an all-simulating general impact. However, the molecules with mild vasculogenic effects tend to develop more complex, limited vascular networks, having a more localized role in the angiogenetic process. Overall imaging and graph analysis showed significant and distinct properties of the vascular network-derived graph. Full article
(This article belongs to the Special Issue Molecular Mechanism and Treatment of Hemangioma)
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20 pages, 2191 KB  
Article
Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage
by Iga Stryjak, Natalia Warmuzińska, Kamil Łuczykowski, Kacper Wnuk, Hernando Rosales-Solano, Patrycja Janiszek, Peter Urbanellis, Katarzyna Buszko, Janusz Pawliszyn, Markus Selzner and Barbara Bojko
Int. J. Mol. Sci. 2025, 26(13), 6295; https://doi.org/10.3390/ijms26136295 - 30 Jun 2025
Viewed by 1335
Abstract
Organ shortage is a major challenge in transplantation, prompting the use of extended criteria donor grafts. These require improved preservation techniques and reliable methods to assess graft function. This study aimed to evaluate changes in the kidney metabolome following three preservation methods: normothermic [...] Read more.
Organ shortage is a major challenge in transplantation, prompting the use of extended criteria donor grafts. These require improved preservation techniques and reliable methods to assess graft function. This study aimed to evaluate changes in the kidney metabolome following three preservation methods: normothermic ex vivo kidney perfusion (NEVKP), hypothermic machine perfusion (HMP) and static cold storage (SCS) in porcine autotransplant models. A chemical biopsy allowed minimally invasive sampling of metabolites, which were analyzed using liquid chromatography coupled with high-resolution mass spectrometry. The results highlighted metabolites affected by ischemia and oxidative stress in donor kidneys, as well as changes specific to each preservation method. Differences were observed immediately after transplantation and reperfusion and several days post-surgery. NEVKP was associated with the activation of physiological anti-oxidative and anti-inflammatory mechanisms, suggesting potential protective effects. However, some metabolites had dual roles, which may influence future graft treatment designs. HMP and SCS, while reducing energy demand in cells, also limit physiological repair mechanisms. These findings provide a basis for improving graft assessment and organ preservation, with chemical biopsy serving as both a tool for discovery and a potential diagnostic method for monitoring graft quality. Full article
(This article belongs to the Special Issue Mass Spectrometry in Molecular Biology)
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29 pages, 3375 KB  
Review
Spontaneous Intracranial Vertebral Artery Dissection: A Rare Cause of Ischemic Stroke
by Marialuisa Zedde and Rosario Pascarella
J. Cardiovasc. Dev. Dis. 2025, 12(5), 187; https://doi.org/10.3390/jcdd12050187 - 15 May 2025
Cited by 1 | Viewed by 4104
Abstract
The dissection of the V4 vertebral artery (VA) is the most prevalent form of intracranial dissection, which can manifest either as ischemia or as a subarachnoid hemorrhage (SAH). Patient outcomes are significantly affected by their initial presentation; ischemic symptoms often indicate that the [...] Read more.
The dissection of the V4 vertebral artery (VA) is the most prevalent form of intracranial dissection, which can manifest either as ischemia or as a subarachnoid hemorrhage (SAH). Patient outcomes are significantly affected by their initial presentation; ischemic symptoms often indicate that the dissection remains primarily subintimal or within the medial layer, though it can occasionally extend to the basilar artery. In contrast, patients with ruptured VA dissection (VAD) experience a considerably higher mortality rate, as the dissection can reach the adventitial layer, heightening the risk of recurrent hemorrhage. It can show fluctuating imaging findings, making an accurate diagnosis and timely treatment essential. Currently, there are no established diagnostic criteria for VAD, and its diagnosis largely depends on imaging. The presence of intramural hematoma, identified via three-dimensional, black-blood, T1-weighted imaging, has been recognized as the most reliable indicator for diagnosing VAD and is crucial for establishing a definitive diagnosis. DSA remains a fundamental diagnostic technique not only in hemorrhagic patients but also in ischemic patients. The medical treatment of ischemic patients has not yet been well defined, and evidence-based data are lacking. This review aims to summarize the main clinical, pathophysiological, and neuroradiological features of intracranial VAD presenting with ischemic stroke, providing to clinicians the available information in order to individualize the treatment. Full article
(This article belongs to the Special Issue Stroke in the Young)
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11 pages, 750 KB  
Article
Risk Factors of Acute Rejection: Impact on Graft Outcomes in a Cohort of Kidney Transplant Recipients
by Valeria Corradetti, Elisa Gessaroli, Federico Bari, Claudia Bini, Valeria Grandinetti, Angelodaniele Napoletano, Vania Cuna, Valeria Pizzuti, Marcello Demetri, Matteo Ravaioli, Michele Provenzano, Gaetano La Manna and Giorgia Comai
J. Clin. Med. 2025, 14(10), 3373; https://doi.org/10.3390/jcm14103373 - 12 May 2025
Cited by 2 | Viewed by 2309
Abstract
Background: Acute rejection (AR) in kidney transplant (KT) recipients remains a significant challenge for short- and long-term graft survival even in the most recent years characterized by extended criteria donors and older and more comorbid recipients. Methods: We analyzed risk factors [...] Read more.
Background: Acute rejection (AR) in kidney transplant (KT) recipients remains a significant challenge for short- and long-term graft survival even in the most recent years characterized by extended criteria donors and older and more comorbid recipients. Methods: We analyzed risk factors and outcomes of AR in 339 KT recipients treated at St. Orsola-Malpighi Hospital, Bologna (Italy), between 1 January 2019 and 31 December 2021. Demographic, immunological, and transplant data (type, cold ischemia time, complications) were recorded with a follow-up period of up to 24 months. Key outcomes included estimated glomerular filtration rate (eGFR), 24 h proteinuria, delayed graft function (DGF), biopsy-proven AR, and graft loss. Results: During the first year after transplant, 57 AR episodes occurred: 19 antibody-mediated rejections (AMR), 18 borderline T cell-mediated rejections (TCMR), 18 TCMR, 2 mixed AMR/TCMR, and 11 graft losses. AR was linked to older donor age (59.9 ± 12.8 vs. 55.5 ± 15.1, p = 0.040), longer cold ischemia time (690 vs. 570 min, p = 0.044), higher DGF rates (61.40% vs. 39.57%, p = 0.002), and lower eGFR (39 vs. 52 mL/min, p = 0.003). AR was consistently prevalent in patients who underwent an AB0-incompatible (AB0-i) transplant (8.8% vs. 2.5%, p = 0.020). HLA matching was strongly associated with a reduced risk of AMR (HLA-DR: OR 0.35, HLA-A: OR 0.33, HLA-C: OR 0.35), while DGF was linked to a higher risk (OR 4.04). TCMR risk was associated with donor age (OR 1.05). The development of post-transplant donor-specific antibodies (DSAs) at 24 months showed no significant association with AR (AMR: p = 0.769; TCMR: p = 0.938). The decline in eGFR over time (24 months) did not differ between patients with and without AR (difference, −0.69 mL/min/year; Standard Error, 0.92; p = 0.452). Similarly, 24 h proteinuria change over time did not differ between patients with and without AR (difference, −0.12 g/24 h; Standard Error, 0.28; p = 0.657). Conclusions: Understanding the risk factors of AR is crucial to identifying KTs at more risk of rejection and to guiding targeted therapeutic decisions. In the most recent era of extended criteria donors and more vulnerable recipients, early diagnosis and prompt and tailored treatment of AR play a critical role in stabilizing renal function over time. Full article
(This article belongs to the Special Issue Clinical Practice and Personalized Medicine in Kidney Transplantation)
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12 pages, 744 KB  
Review
Tissue Preservation and Access: Modern Innovation in Biobanking Moving Forwards a Personalized Treatment
by Chiara Tessari, Saima Jalil Imran, Nukhba Akbar and Gino Gerosa
J. Pers. Med. 2025, 15(5), 190; https://doi.org/10.3390/jpm15050190 - 7 May 2025
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Abstract
Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal [...] Read more.
Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal therapeutic approach that is still not fully resolved. There are multiple ways to preserve heart tissue grafts, and the choice of method is solely dependent upon the nature and complexity of the tissue and the length of storage. The conventional cold storage method provides the base to nearly all of the preservation protocols for short- and long-term storage. Short-term storage methods frequently rely on designing preserving solutions to protect the graft against warm and cold ischemia at the temperature above freezing point. As ice-nucleation is the major notorious phenomenon during graft preservation, the modern era of research is focusing on developing ice-free preservation techniques, termed vitrification. However, despite the promising outcomes of vitrification, there are several recognized hurdles required to be overcome to build a biobank of heart grafts for an extended period of time. Besides tissue deterioration due to extreme cold temperature, there is another extreme phenomenon of tissue rejection mainly caused by the presence of cellular antigens. The modern approach of decellularization has the potential to minimize the chances of tissue rejection by removing the cells and providing a structural support and sustained biochemical signal via keeping the extracellular matrix of the graft intact. In conclusion, both nano-warming and decellularization are the leading approaches that have great potential to store the graft tissue in its optimal form via keeping its viability safe for a longer time and extending its applicability. This review article outlines a variety of approaches for the preservation and bioengineering of tissue to fulfill the need for the availability of on-shelf long-lasting grafts both in clinical and laboratory setups. Full article
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Review
The Many Faces of Intestinal Tumors in Adults, Including the Primary Role of CT Imaging in Emergencies and the Important Role of Cross-Sectional Imaging: A Pictorial Review
by Barbara Brogna, Francesca Maccioni, Dolores Sgambato, Fabiana Capuano, Lorenzo Iovine, Salvatore Guarino, Lorenzo Di Libero, Alfonso Amendola, Lorenzo Faggioni and Dania Cioni
Healthcare 2025, 13(9), 1071; https://doi.org/10.3390/healthcare13091071 - 6 May 2025
Cited by 2 | Viewed by 1953
Abstract
Background/Objectives: Small bowel tumors (SBTs) encompass a diverse range of tumor types, with benign tumors being the most prevalent. However, the incidence of malignant SBTs is increasing, particularly small bowel adenocarcinoma; this poses a diagnostic challenge for clinicians and radiologists due to the [...] Read more.
Background/Objectives: Small bowel tumors (SBTs) encompass a diverse range of tumor types, with benign tumors being the most prevalent. However, the incidence of malignant SBTs is increasing, particularly small bowel adenocarcinoma; this poses a diagnostic challenge for clinicians and radiologists due to the varied and nonspecific clinical and radiological presentations associated with SBTs. In fact, SBTs can present differently in emergencies, often mimicking inflammatory diseases or manifesting as complications such as intussusception, small bowel obstruction (SBO), intestinal ischemia, perforation, gastrointestinal bleeding, or metastatic disease. These tumors can remain asymptomatic for extended periods. Methods: We present a pictorial review on the role of imaging in evaluating SBTs, focusing on the emergency setting where diagnosis can be incidental. We also include some representative cases that may be useful for radiologists and residents in clinical practice. Results: Despite these challenges, contrast-enhanced computed tomography (CECT) is usually the best modality to use in emergencies for evaluating SBTs, and in some cases, a diagnosis can be made incidentally. However, when possible, multimodal imaging through cross-sectional imaging remains crucial for the non-invasive diagnosis of SBTs in stable patients, as endoscopic procedures may also be impractical. A complementary CT study with distension using negative oral contrast media, such as water, polyethylene glycol, or mannitol solutions, can improve the characterization of SBTs and rule out multiple SBT locations, particularly in small bowel neuroendocrine tumor (NET) and gastrointestinal tumor (GIST) localization. Positive water-soluble iodine-based oral contrast, such as Gastrografin (GGF), can be used to evaluate and monitor the intestinal lumen during the nonsurgical management of small bowel obstruction (SBO) or in suspected cases of small bowel perforations or the presence of fistulas. Magnetic resonance enterography (MRE) can aid in improving the characterization of SBTs through a multiplanar and multisequence study. Positron emission tomography combined with CT is generally an essential modality in evaluating metastatic disease and staging and assessing tumor prognosis, but it has limitations for indolent lymphoma and small NETs. Conclusions: Therefore, the integration of multiple imaging modalities can improve patient management and provide a preoperative risk assessment with prognostic and predictive indicators. In the future, radiomics could potentially serve as a “virtual biopsy” for SBTs, allowing for better diagnosis and more personalized management in precision medicine. Full article
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