Search Results (2,596)

Background: Organ transplant offers patients a second chance at life, yet chronic rejection remains a formidable barrier to long-term success. Unlike the instantaneous storm of acute rejection, chronic rejection is a slow, unremitting process that silently remodels vessels, scars tissues, and diminishes graft function. At the center of this process are macrophages, immune “shapeshifters” that can heal or harm depending on their cues. Methods: This manuscript systematically reviews and synthesizes the current evidence from experimental studies and clinical observations, as well as molecular insights, to unravel how macrophages orchestrate chronic rejection. It travels over macrophage origins alongside their dynamic polarization into pro-inflammatory (M1) or pro-repair yet fibrotic (M2) states. The discussion integrates mechanisms of recruitment, antigen presentation, vascular injury, and fibrosis, while highlighting the molecular pathways (NF-κB, inflammasomes, STAT signaling, metabolic rewiring) that shape macrophage fate. Results: Macrophages play a central role in chronic rejection. Resident macrophages, once tissue peacekeepers, amplify inflammation, while recruited monocyte-derived macrophages fuel acute injury or dysfunctional repair. Together, they initiate transplant vasculopathy through cytokines, growth factors, and matrix metalloproteinases, slowly narrowing vessels and starving grafts. Donor-derived macrophages, often overlooked, act as early sentinels and long-term architects of fibrosis, blurring the line between donor and host immunity. At the molecular level, macrophages lock into destructive programs, perpetuating a cycle of inflammation, vascular remodeling, and scarring. Conclusions: Macrophages are not passive bystanders but pivotal decision makers in chronic rejection. Their plasticity, while a source of pathology, also opens therapeutic opportunities. Emerging strategies like macrophage-targeted drugs, immune tolerance approaches, gene and exosome therapies currently offer ways to reprogram these cells and preserve graft function. By shifting the macrophage narrative from saboteurs to guardians, transplantation medicine may transform chronic rejection from an inevitability into a preventable complication, extending graft survival from fleeting years into enduring decades. Full article

Background and Objectives: Preeclampsia (PE) complicates 2–8% of pregnancies globally, with a higher incidence in developing countries. This condition poses significant risks to maternal and fetal health, contributing substantially to maternal and perinatal mortality, particularly in cases of early-onset PE, which is associated with severe complications. This review aims to synthesize current evidence regarding the predictive utility of ophthalmic artery Doppler for preeclampsia. Current strategies focus on early prediction and prevention to mitigate adverse outcomes and reduce the economic burden of hypertensive disorders in pregnancy. The International Federation of Gynecology and Obstetrics (FIGO) recommends first-trimester screening combining maternal risk factors, mean arterial pressure, serum placental growth factor (PlGF), and uterine artery pulsatility index (UtA-PI). High-risk women are advised to take low-dose aspirin (150 mg daily) until 36 weeks of gestation. Materials and Methods: This review explores an innovative predictive tool for PE: ophthalmic artery (OA) Doppler. Results: As a non-invasive and easily accessible method, OA Doppler provides valuable insights into intracranial vascular resistance, offering potential advantages in early risk assessment, particularly for preterm PE, the most severe form of the disease. Conclusions: Our findings suggest that OA Doppler may serve as a promising adjunct in PE screening, enhancing the early identification of high-risk pregnancies and improving clinical outcomes. Further research is warranted to validate its role in routine prenatal care. Full article

Diabetic retinopathy (DR) has been classically considered a microvascular disease with all diagnostic and therapeutic resources focusing on its vascular components. However, during the past years, the obtained evidence highlighted the critical pathogenic role of early neuronal impairment redefining DR as a neurovascular complication. Retinal neurodegeneration is triggered by chronic hyperglycemia, which activates harmful biochemical pathways that lead to oxidative stress, metabolic overload, glutamate excitotoxicity, inflammation, and neurotrophic factor deficiency. These drivers of neurodegeneration can precede detectable vascular abnormalities. Simultaneously, endothelial injury, pericyte loss, and breakdown of the blood–retinal barrier compromise neurovascular unit integrity and establish a damaging cyclic loop in which neuronal and vascular dysfunctions reinforce each other. The interindividual variability of these processes highlights the need to properly redefine patient phenotyping by using advanced imaging and functional biomarkers. This would allow early detection of neurodegeneration and patient subtype classification. Nonetheless, translation of therapies based on neuroprotection has been limited by classical focus on vascular impairment. To meet this need, several strategies are emerging, with the most promising being those delivered through innovative ocular routes such as topical formulations, sustained-release implants, or nanocarriers. Future advances will depend on proper guidance of these therapies by integrating personalized medicine with multimodal biomarkers. Full article

Background: Intentional occlusion of the internal iliac artery (IIA) during endovascular repair of aorto-iliac aneurysms may predispose patients to pelvic ischemic complications such as gluteal claudication, erectile dysfunction, and bowel ischemia. Iliac branch devices (IBDs) have been developed to preserve hypogastric perfusion. E-Liac (Artivion/Jotec) is one of the latest modular IBDs yet reports on mid-term performance are limited to small single-center cohorts with short follow-up. The CAMpania PugliA bRanch IliaC (CAMPARI) study is a multicenter investigation of E-Liac outcomes. Methods: A retrospective observational cohort study was conducted across five Italian vascular centers. All consecutive patients undergoing E-Liac implantation for aorto-iliac or isolated iliac aneurysms between January 2015 and December 2024 were identified from prospectively maintained registries. Inclusion criteria comprised elective or urgent endovascular repair of aorto-iliac aneurysms in which an adequate distal sealing zone was not available without covering the IIA and suitability for the E-Liac device according to its instructions for use (IFU). Patients with a life expectancy < 1 year or hostile anatomy incompatible with the IFU were excluded. The primary end point was freedom from branch instability (occlusion/stenosis, kinking, or detachment of the bridging stent). Secondary end points included freedom from any endoleak, freedom from device-related reintervention, freedom from gluteal claudication, aneurysm-related and all-cause mortality, acute renal failure, and sac regression > 5 mm. Results: A total of 69 consecutive patients (68 male, 1 female, median age 72.0 years) received 74 E-Liac devices, including 5 bilateral implantations. The mean infrarenal aortic diameter was 45 mm and the mean CIA diameter 34 mm; 14 patients (20.0%) had a concomitant IIA aneurysm (>20 mm). Concomitant fenestrated or branched aortic repair was performed in 23% of procedures. Two patients received a standalone IBD without implantation of a proximal aortic endograft. Technical success was achieved in 71/74 cases (96.0%); three failures occurred due to inability to catheterize the IIA. Distal landing was in the main IIA trunk in 58 cases and in the posterior branch in 13 cases. Over a median follow-up of 18 (6; 36) months, there were four branch instability events (5.4%): three occlusions and one bridging stent detachment. Seven patients (9.5%) developed endoleaks (one type Ib, two type II, two type IIIa, and two type IIIc). Five patients (6.8%) required reintervention, and five (6.8%) reported gluteal claudication. There were seven all-cause deaths (10%), none within 30 days or related to aneurysm rupture; causes included COVID-19 pneumonia, acute coronary syndrome, melanoma, gastric cancer, and stroke. No acute renal or respiratory failure occurred. Kaplan–Meier analysis showed 92% (95% CI 77–100) freedom from branch instability in the main-trunk group and 89% (60–100) in the posterior-branch group (log-rank p = 0.69). Freedom from any endoleak at 48 months was 87% (95% CI 75–95), and freedom from reintervention was 93% (95% CI 83–98). Conclusions: In this multicenter cohort, the E-Liac branched endograft demonstrated high technical success and favorable early–mid-term outcomes. Preservation of hypogastric perfusion using E-Liac was associated with low rates of branch instability, endoleak, and reintervention, with no 30-day mortality or aneurysm-related deaths. These findings support the safety and efficacy of E-Liac for aorto-iliac aneurysm management, although larger prospective studies with longer follow-up are needed. Full article

Objectives: This study aims to evaluate the efficacy of hydroxyapatite-tricalcium phosphate (HAP-TCP) as a bone substitute in subantral augmentation for dental implants. Specifically, it investigates the effects of HAP-TCP on bone quality, density, and integration with implants over time. Methods: A prospective controlled longitudinal study was conducted on 22 patients (39–75 years of age) undergoing subantral augmentation and dental implantation. A total of 52 sites of augmented bone and 67 sites of native bone were analyzed using computed tomography (CT) to assess bone density in Hounsfield Units (HU), insertion torque measurements, and the Misch classification for bone quality. Augmented and native bone measurements were compared within each patient. Results: The augmented bone exhibited an average density of 1132.6 ± 334.9 HU, which is significantly higher (45.9%) than the average density of native bone at 519.3 ± 395.0 HU. Insertion torque values in the HAP-TCP augmented sites averaged 35 N·cm, showing a 71.4% increase compared to adjacent native bone sites (25 N·cm). The study found notable improvements in bone homogeneity and vascularization within the augmented zones. Conclusion: HAP-TCP demonstrates significant potential as a reliable and effective synthetic bone substitute for subantral augmentation in dental implants. It yields higher radiodensity and insertion torque than adjacent native bone, while mitigating complications associated with autogenous grafts. These observational findings support the potential clinical use of HAP-TCP for sinus augmentation. Full article

Ketones are metabolites primarily produced by the liver and are utilized by various organs outside of the liver. Recent advances have demonstrated that ketones serve not only as alternative energy sources but also as signaling molecules. Research indicates that ketones can influence cancer development and metastasis, cardiac metabolic and structural remodeling, physical performance, vascular function, inflammation, and the aging process. Emerging evidence from preclinical and early-phase clinical studies suggests that strategies such as ketone salts, ketone esters, and the ketogenic diet may offer therapeutic benefits for conditions like heart failure, acute cardiac injury, diabetic cardiomyopathy, vascular complications, atherosclerosis, hypertension, and aortic aneurysm. This literature review updates the current understanding of ketone metabolism and its contributions to cardiovascular health and diseases. We highlight the underlying molecular mechanism with post-translational modification known as β-hydroxybutyrylation, which affects the fate and function of target proteins. Additionally, we discuss the therapeutic challenges associated with ketone therapy, the potential of using ketone levels as biomarkers for cardiovascular diseases, as well as gender- and age-specific differences in ketone treatment. Finally, we explore future research directions and what is needed to translate these new insights into cardiovascular medicine. Full article

Background: Pre-eclampsia causes endothelial dysfunction and altered vascular reactivity, which may increase perioperative risk, particularly under the physiologic stress of general anesthesia (GA). However, the evidence regarding its independent effects under uniform GA conditions is limited. This study assessed the association between pre-eclampsia and intraoperative hemodynamic stability as well as postoperative complications in women undergoing cesarean section under GA. Methods: This retrospective cohort study screened 1242 women who underwent GA for cesarean delivery between January 2017 and July 2024. After applying exclusion criteria, 959 patients were included: 169 with and 790 without pre-eclampsia. The intraoperative blood-pressure and heart-rate trends, vasopressor use, operative variables, and postoperative complications were analyzed. Predictors of postoperative respiratory complications were identified using logistic regression with Firth correction. Results: Patients with pre-eclampsia showed consistently higher mean arterial pressures throughout induction and emergence, whereas trends in heart rate were similar. Postoperative morbidity was higher in the pre-eclampsia group (11.8% vs. 5.3%), with increased respiratory complications (3.6% vs. 1.1%) and longer hospital stays. Pre-eclampsia independently predicted postoperative respiratory complications in univariable (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.13–8.90, p = 0.03), multivariable (OR 3.13, 95% CI 1.09–8.98, p = 0.03), and Firth’s analyses (OR 3.21, 95% CI 1.11–8.77, p = 0.03). Conclusions: Pre-eclampsia was associated with persistent intraoperative hypertension and higher risks of postoperative respiratory morbidity under GA. These findings support the need for individualized hemodynamic control, cautious fluid management, and increased postoperative respiratory surveillance in patients with pre-eclampsia. Full article

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone models) with thoracic aortopathy and dissection models (BAPN alone or with AngII, genetic models including Marfan and smooth muscle contractile mutations, and AngII + TGF-β blockade). We highlight practical considerations on segment specificity, rupture incidence, lipid dependence, comorbidities, and outcome measurement, with emphasis on rigor and reporting standards. A translational thread on platelet–intraluminal thrombus biology, including the emerging biomarker and therapeutic targets such as glycoprotein VI (GPVI), is integrated across models. We offer a decision grid and rigor checklist to harmonize model use, enhance reproducibility, and accelerate translation. Full article

Hyaluronic acid (HA)-based fillers are widely used in aesthetic dermatology for their biocompatibility, reversibility, and safety; however, adverse events (AEs) may occur. This review evaluated the safety profile, focusing on short- and long-term AEs, of HA fillers manufactured with MACRO (MAtrix CROsslinking) Core Technology, encompassing both current saypha and former Princess products. A systematic PubMed search identified prospective clinical trials assessing safety outcomes following facial aesthetic use of these fillers. Eleven studies including 947 patients met the inclusion criteria. The most common short-term AEs were transient swelling, injection site pain, and bruising, which were predominantly mild to moderate and resolved within two weeks. Severe or serious treatment-related events were rare, with only one reported across all studies. Long-term AEs, such as delayed-onset nodules or inflammatory reactions, were infrequent and mild, with no granulomas, hypersensitivity responses, or vascular complications observed. Safety outcomes were consistent across formulations and between the legacy Princess and current saypha products. Overall, the saypha HA filler portfolio demonstrates a predictable and strong safety profile within the expected range reported in the broader literature, noting the limitations of cross-study comparisons. Most AEs were related to injection trauma rather than the filler itself, supporting its continued use in clinical aesthetic practice. Full article

This paper aims to examine the current landscape of novel biomarkers in diabetes mellitus (DM), with particular emphasis on emerging candidates, and their roles in early diagnosis, monitoring disease progression, risk stratification, and managing complications. Given the global prevalence of DM and its complex pathophysiology, identifying reliable biomarkers is critical for optimizing prevention strategies and personalized treatment approaches. This review highlights the shift from traditional glycemic markers, which remain clinically useful but limited, to a broader array of novel biomarkers that more accurately reflect the complex pathophysiology of DM. In addition to conventional measures, inflammatory and oxidative stress mediators, along with genetic and epigenetic regulators, provide added predictive value for disease susceptibility, progression, and complications. Recent research has identified emerging biomarkers, such as adiponectin, adropin, netrin-1, α-hydroxybutyrate, fetuin-A, lipo-protein(a), and lysophosphatidylcholine, which detect early metabolic imbalances and reveal mechanistic links to insulin resistance, β-cell dysfunction, and vascular injury. Their integration into multimarker panels holds particular promise for precision medicine, supporting tailored prevention, targeted therapy, and improved outcomes for individuals with prediabetes and DM. Full article

Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1–CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated β-galactosidase activity, and activated phosphorylated ERK1/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD. Full article

Background: Coffin–Siris syndrome 12 (CSS12) is a recently described neurodevelopmental disorder caused by heterozygous pathogenic variants in BICRA, a gene encoding a core subunit of the non-canonical BAF (ncBAF) chromatin-remodeling complex. The condition is characterized by developmental delay, hypotonia, hypertrichosis, and joint laxity. However, long-term data remain limited, and systemic manifestations are incompletely defined. Case Description: We report a 22-year-old male with a de novo BICRA frameshift variant, c.2479_2480delinsA (p.Ala827Thrfs*15), previously included in the original cohort reported by Barish et al. Longitudinal follow-up revealed an expanded phenotype extending beyond neurodevelopmental features. Early findings included global developmental delay, growth hormone deficiency, short stature, and joint hypermobility. In adolescence and adulthood, he developed severe intestinal dysmotility requiring total colectomy, recurrent spontaneous pneumothoraces from bilateral apical bullous disease, and portal-vein thrombosis, representing visceral and vascular complications not previously emphasized in BICRA-related disorders. The identified BICRA variant truncates the coiled-coil domain critical for BRD9/BRD4 interaction, consistent with a loss-of-function mechanism. The patient’s systemic features suggest that BICRA haploinsufficiency affects not only neurodevelopmental pathways but also smooth-muscle and connective-tissue integrity. Conclusions: This case expands the phenotypic spectrum of BICRA-related CSS12, demonstrating that visceral and vascular involvement can occur alongside neurodevelopmental and connective-tissue features. Recognition of these broader manifestations underscores the need for lifelong multidisciplinary surveillance and contributes to understanding the diverse biological roles of the ncBAF complex in human development. Full article

Background: Traumatic injuries of the duodenum are generally rare but when they occur, they can result in serious complications. Inaccurate injury classification, delayed diagnosis, or late treatment can significantly raise morbidity and mortality. A multidisciplinary approach is often necessary. Mechanisms of injury: Isolated duodenal injuries are relatively uncommon due to the duodenum’s proximity to pancreas and major vascular structures. Duodenal injuries can result from blunt or penetrating trauma. Classification: The 2019 World Society of Emergency Surgery (WSES)-American Association for the Surgery of Trauma (AAST) guidelines recommend incorporating both the AAST-OIS grading and the patient’s hemodynamic status to stratify duodenal injuries into four categories: Minor injuries WSES class I, Moderate injuries WSES class II, Severe injuries WSES class III, and WSES class IV. Diagnosis: The diagnostic approach involves a combination of clinical assessment, laboratory investigations, radiological imaging and, in particular situations, surgery. Prompt diagnosis is critical because delays exceeding 24 h are associated with a higher incidence of postoperative complications and a significant rise in mortality. Contrast-enhanced abdominal computed tomography (CT) represents the gold standard for diagnosis in patients who are hemodynamically stable. Management: Duodenal trauma requires a multimodal approach that considers hemodynamic stability, the severity of the injury and the presence of associated lesions. Non-operative management (NOM) is reserved for hemodynamically stable patients with minor duodenal injuries without perforation (AAST I/WSES I), as well as all duodenal hematomas (WSES I–II/AAST I–II) in the absence of associated abdominal organ injuries requiring surgical intervention. All hemodynamically unstable patients, those with peritonitis, or with CT findings consistent with duodenal perforations or AAST grade III or higher injuries are candidates for emergency surgery. If intervention is required, primary repair should be the preferred option whenever feasible, while damage control surgery is the best choice in cases of hemodynamic instability, severe associated injuries, or complex duodenal lesions. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated. The role of endoscopic techniques in the treatment of duodenal injuries and their complications is expanding. Conclusions: Duodenal trauma is burdened by potentially high mortality. Among the possible complications, duodenal fistula is the most common, followed by duodenal obstruction, bile duct fistula, abscess, and pancreatitis. The overall mortality rate for duodenal trauma persists to be significant with an average rate of 17%. Future prospective research needed to reduce the risk of complications following duodenal trauma. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM ComplexTea Extract (CTE) and the heat-treated postbiotic (BPL1^® HT) on the cardiometabolic alterations associated with MetS in a murine model. C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and treated with CTE, BPL1^® HT, or their combination for 20 weeks. Metabolic, inflammatory, oxidative, vascular parameters, and fecal microbiota composition were assessed. Both CTE and BPL1^® HT individually attenuated weight gain, organ hypertrophy, insulin resistance, and inflammation. However, their combined administration exerted synergistic effects, fully normalizing body weight, adipocyte size, lipid profiles, HOMA-IR index, and insulin sensitivity to levels comparable to lean controls. Co-treatment also restored PI3K/Akt signaling in liver and muscle, reduced hepatic steatosis, and normalized the expression of inflammatory and oxidative stress markers across multiple tissues. Furthermore, vascular function was significantly improved, with enhanced endothelium-dependent relaxation and reduced vasoconstrictor responses, particularly to angiotensin II. CTE, BPL1^®HT, and the blend prevented bacterial richness reduction caused by HFHS; the blend achieved higher bacterial richness than mice in Chow diet. Additionally, the blend prevented the increase in Flintibacter butyricus, which is associated with MetS clinical parameters, and showed a tendency to increase the abundance of Bifidobacterium. These findings suggest that the combination of CTE and BPL1^® HT offers a potential nutritional strategy to counteract the metabolic and cardiovascular complications of MetS through complementary mechanisms involving improved insulin signaling, reduced inflammation and oxidative stress, enhanced vascular function, and modulation of gut microbiota. Full article

Doppler assessment of fetal cerebral circulation has become a cornerstone of modern fetal medicine. It is used to evaluate cerebral vascular malformations, brain anomalies, fetal growth restriction due to placental insufficiency, fetal anemia, and hemodynamic complications arising from placental vascular anastomoses in monochorionic pregnancies. Emerging research also explores the predictive value of Doppler parameters for perinatal outcomes and long-term neurodevelopment. To review the anatomy and physiology of fetal cerebral vessels accessible to Doppler evaluation, outline key technical aspects, and summarize current obstetric applications. A PubMed search identified 113 relevant publications, published between 1984 and 2025. Three book chapters by authors recognized internationally within the scientific community were included. A total of 116 publications were critically analyzed in this narrative review. Strong evidence supports the use of Doppler ultrasound in obstetrics, particularly for evaluating fetal cerebral hemodynamics, where it contributes to reducing fetal morbidity and mortality. Doppler assessment of fetal brain circulation is a valuable tool for evaluating brain vascular malformations, other structural abnormalities, and for assessing fetuses with growth restriction, anemia, and twin-to-twin transfusion syndrome. It allows targeted fetal monitoring and timely interventions, providing critical prognostic information and aiding parental counseling. Ongoing advances in Doppler technology and understanding of fetal brain physiology are likely to broaden its clinical uses, improving both perinatal outcomes and long-term neurological health. Full article