Search Results (1,169)

Cerebral vasospasm (CVS) following a subarachnoid hemorrhage (SAH) is a critical complication driven by imbalances between vasodilators and vasoconstrictors. This review explores the bidirectional interplay between nitric oxide (NO) and endothelin-1 (ET-1) in CVS pathogenesis. NO, a potent vasodilator mainly produced by endothelial and neuronal nitric oxide synthase (eNOS/nNOS) under normal physiological conditions, is scavenged early after SAH by hemoglobin derivatives, leading to microcirculatory dysfunction, pericyte constriction, and impaired neurovascular coupling. Conversely, ET-1 exacerbates vasoconstriction by suppressing NO synthesis via ROS-dependent eNOS uncoupling and Rho-kinase activation. The NO/ET-1 axis further influences delayed cerebral ischemia (DCI) through mechanisms like 20-HETE-mediated cGMP suppression and oxidative stress. Emerging therapies—including NO donors, NOS gene therapy, and ET-1 receptor antagonists—aim to restore this balance. Understanding these pathways offers translational potential for mitigating CVS and improving outcomes post-SAH. Full article

Background/Objectives: Weight gain after kidney transplantation is frequent but heterogeneous, often accompanied by changes in body composition that influence long-term outcomes. This study analysed one-year changes in body compartments and their demographic and clinical determinants. Methods: A prospective cohort of 112 adult kidney recipients transplanted between September 2020 and June 2022 at a Spanish tertiary hospital was followed. Body weight, muscle mass, fat mass, visceral fat and total body water were assessed by multi-frequency bioelectrical impedance at discharge, and at 3, 6 and 12 months. Associations with sociodemographic, clinical and comorbidity variables were examined using repeated-measures ANOVA and comparative tests. Results: At 12 months, mean weight gain was 3.6 ± 6.5 kg (5.1%). Increases were greater in men, younger patients, non-dialysis candidates, those with previous transplantation and living donor grafts. Muscle mass rose during the first three months and then stabilised, with greater gains in men and haemodialysis patients. Fat mass decreased initially and then increased, particularly in women, younger recipients and living donor transplants. Visceral fat progressively increased after three months, with higher levels in men and older patients. Total body water declined in women, younger recipients and first transplant patients. Patients with new-onset diabetes gained less weight, while smokers gained more. Conclusions: Post-transplant body composition is shaped by sex, age, BMI, comorbidities and donor type. Monitoring compartments beyond body weight may allow early detection of adverse metabolic trajectories. Tailored nutritional and lifestyle interventions are needed to optimise long-term outcomes. Full article

Background: Breast reconstruction following mastectomy plays a crucial role in breast cancer management, restoring physical form and significantly impacting psychological well-being and quality of life. Implant-based breast reconstruction (IBBR) is the most performed technique worldwide due to its relative simplicity, shorter operative times, and avoidance of donor site morbidity. Achieving satisfactory aesthetic outcomes, however, remains challenging, as multiple factors—including patient characteristics, surgical technique, implant selection, timing of reconstruction, and adjuvant therapies—can influence the final appearance. Methods: Literature research was performed via PubMed, Scopus and Cochrane Library Database, focusing on studies examining aesthetic outcomes in implant-based breast reconstruction published between 2015 and 2025. Data on type of study, sample size, aesthetic evaluation methods, and duration of follow-up were collected and summarized. Results: Among 747 articles identified, only 25 articles fulfilled inclusion criteria, including mostly retrospective studies, but also prospective studies, randomized clinical trials, and reviews. Factors such as BMI, inframammary fold management, and implant selection were consistently reported to influence aesthetic outcomes. Surgical techniques including ADM use, axillary advancement sutures, hybrid reconstruction with fat grafting, and prepectoral implant placement were associated with improved patient satisfaction. Patient satisfaction often differs from surgeon-assessed outcomes, emphasizing the importance of subjective evaluation. Conclusions: Despite the heterogeneity and retrospective nature of many studies, evidence indicates that optimizing aesthetic outcomes in IBBR relies on careful patient selection, tailored surgical planning, and meticulous use of evidence-based techniques, including implant selection, flap-based support, and adjunctive strategies. Patient-reported outcomes are essential for evaluating success, and future research should focus on standardized outcome measures and prospective studies to further refine reconstructive approaches and maximize both cosmetic satisfaction and quality of life. Full article

Background: Cryopreservation of hematopoietic stem cells (HSCs) at −80 °C using uncontrolled-rate freezing is frequently employed in resource-constrained settings, yet concerns remain regarding long-term viability and clinical efficacy. Reliable post-thaw assessment is essential to ensure graft quality and engraftment success. Methods: This single-center, retrospective study evaluated 72 cryopreserved stem cell products from 25 patients stored at −80 °C for a median of 868 days. Viability was assessed using both acridine orange (AO) staining and 7-AAD (7-aminoactinomycin D) flow cytometry at three time points: collection (T0), pre-infusion (T1), and delayed post-thaw evaluation (T2). Associations between viability loss, storage duration, and clinical engraftment outcomes were analyzed. Results: Median post-thaw viability remained high (94.8%) despite a moderate time-dependent decline (~1.02% per 100 days; R² = 0.283, p < 0.001). Mean viability loss at T2 was 9.2% (AO) and 6.6% (flow cytometry). AO demonstrated greater sensitivity to delayed degradation, with a significant difference between methods (p < 0.001). Engraftment kinetics were preserved in most patients, with neutrophil and platelet recovery primarily influenced by disease type rather than product integrity. Notably, storage duration and donor age were not significantly associated with engraftment outcomes or CD34⁺ cell dose. Conclusions: Long-term cryopreservation at −80 °C maintains HSC viability sufficient for durable engraftment, despite gradual decline. While transplant outcomes are primarily dictated by disease biology and remission status, AO staining provides enhanced sensitivity for detecting delayed cellular damage. Notably, our viability-loss model offers a practical framework for predicting product quality, potentially supporting graft selection and clinical decision-making in real-world, resource-constrained transplant settings. Full article

Background: End-stage renal disease (ESRD) affects up to 25% of lung transplant recipients within 10 years. The selection process for kidney transplantation versus dialysis reflects complex clinical decision-making that has not been systematically characterized. Methods: This retrospective observational study analyzed all lung transplant recipients who developed ESRD at our center from 2010 to 2024 (n=32), comparing those receiving kidney transplantation (n = 18) versus those remaining on dialysis (n = 14). We developed an exploratory Clinical Selection Score to retrospectively characterize observed selection patterns and calculated E-values to assess robustness to unmeasured confounding. Results: Kidney transplant recipients were younger (35.7 ± 12.9 vs. 48.4 ± 14.8 years, p = 0.013) with better selection characteristics quantified by our Clinical Selection Score (4.1 ± 0.8 vs. 1.6 ± 1.1 points, p < 0.001). The score showed excellent discrimination (C-statistic 0.82). Living donors were available for 88.9% of transplanted patients versus 0% of dialysis patients. In our selected cohorts, mortality was 22.2% in kidney transplant recipients vs. 78.6% in dialysis patients (p = 0.002), with median survival of 161.6 vs. 126.6 months (p = 0.021). After adjustment for age, kidney transplantation was observed to be associated with 72% lower mortality risk (HR 0.28, 95% CI 0.09–0.89, p = 0.031), though selection bias limits causal interpretation. The E-value of 6.61 suggests robustness to unmeasured confounding. Conclusions: This observational study describes real-world selection patterns and their associated outcomes in lung transplant recipients with ESRD. While carefully selected patients receiving kidney transplantation experienced favorable results, many patients were appropriately managed with dialysis based on medical and non-medical factors. Our analysis provides transparency about selection criteria and outcomes to inform clinical decision-making. Larger multicenter studies are needed to validate these findings and develop prediction tools. Full article

Background: Carotid intima-media thickness (CIMT) is an established risk factor for adverse cardiovascular events in the general population, but its impact on patients after heart transplantation (HTX) remains unknown. We investigated the effects of an increased pre-transplant CIMT > 0.9 mm on outcomes after HTX. Methods: This observational retrospective single-center study included 311 patients receiving HTX at Heidelberg Heart Center between 2002 and 2014. Patients were stratified by degree of pre-transplant CIMT (CIMT ≤ or >0.9 mm, threshold defined by ESC guidelines). Analysis covered donor and recipient demographics, post-transplant medications, mortality (including causes of death after HTX), early post-transplant atrial fibrillation (AF), and stroke after HTX. Results: A total of 37 of 311 HTX recipients (11.9%) had a pre-transplant CIMT > 0.9 mm. These patients showed an increased 10-year post-transplant mortality (81.1% versus 41.2%, p < 0.001) and had a higher percentage of death due to graft failure (24.3% versus 10.6%, p = 0.017), as well as due to thromboembolic events/bleeding (10.8% versus 2.9%, p = 0.019). Multivariate analysis demonstrated pre-transplant CIMT > 0.9 mm as an independent risk factor for 10-year mortality after HTX (HR: 2.599, 95% CI: 1.683–4.014, p < 0.001). Secondary outcomes showed a significantly higher rate of 30-day post-transplant AF (27.0% versus 10.9%, p = 0.006) and 30-day stroke after HTX (10.8% versus 1.1%, p < 0.001) in patients with a pre-transplant CIMT > 0.9 mm. Conclusion: Pre-transplant CIMT > 0.9 mm is a prognostic marker for early post-transplant AF, stroke, and reduced long-term survival after HTX. Preventive measures, including close monitoring and management of cardiovascular risk factors, are warranted in these high-risk patients. Full article

Background: Corneal endothelial dysfunction continues to be a primary indication for corneal transplantation globally. Due to ongoing constraints in donor tissue availability and graft durability, artificial graft technologies are increasingly recognized as viable alternatives, particularly for eyes unsuitable for conventional allogeneic transplantation. Aim: This article examines the contemporary state of artificial corneal endothelial grafts, emphasizing technological advancements, incorporation into surgical procedures, and their developing function in meeting the unfulfilled requirements of endothelial keratoplasty. Methods: A comprehensive synthesis of recent preclinical and clinical literature was performed, concentrating on scaffold-based constructs, cell-seeded and acellular methodologies, biomaterial characteristics, and innovative surgical delivery techniques. The review highlights translational pathways and contrasts the initial outcomes of artificial and donor-derived endothelial grafts. Results: Advancements in regenerative biomaterials and cell culture systems have resulted in the development of functional endothelial substitutes. Engineered grafts, comprising decellularized stromal carriers, synthetic polymer matrices, and human cell-laden constructs, have demonstrated promising biocompatibility and functional results in preliminary trials. The integration of these constructs into methods akin to Descemet membrane endothelial keratoplasty (DMEK) has improved clinical viability, diminished immunologic risk, and shown potential for visual recovery. Conclusions: Artificial endothelial grafts signify a revolutionary advancement in corneal surgery, addressing donor shortages and expanding the applications of endothelial keratoplasty. Although additional clinical validation and regulatory processes are required, existing evidence indicates that these technologies may soon transform treatment protocols for corneal endothelial disease. Full article

Background/Objectives: Cytomegalovirus (CMV) infection is a frequent complication after lung transplantation, especially in high-risk donor-positive/recipient-negative (D+/R−) patients. CMV-specific hyperimmunoglobulin (CMV-HIG), administered either with antivirals or as monotherapy, may be beneficial for preventing or treating CMV infection in selected clinical scenarios. This study evaluated CMV-HIG indications and their impact on clinical outcomes in our lung transplant unit. Methods: We retrospectively analyzed adult lung transplant recipients (2010–2023) who received ≥2 doses of CMV-HIG for universal prophylaxis, monotherapy prophylaxis, preemptive therapy, or treatment of invasive disease. Results: CMV-HIG was administered to 204 out of 336 recipients (61%). CMV-HIG was well tolerated, with no treatment-related adverse events. Indications were preemptive therapy (63%), universal prophylaxis (24%), monotherapy prophylaxis (7%), and treatment of invasive disease (6%). CMV-HIG was well tolerated, with no treatment-related adverse events. No patients developed invasive disease during combination prophylaxis or preemptive treatment. The combination treatment of patients with invasive disease was also effective, and no cases of VGC resistance were detected. CMV-HIG monoprophylaxis has allowed us to delay or prevent viral replication in recipients who developed VGC side effects. Rates of acute rejection, Chronic Lung Allograft Dysfunction (CLAD), and overall survival were similar across CMV risk groups. Conclusions: Our results showed that the combined use of CMV-HIG and antiviral agents is effective in preventing CMV infection and disease in high-risk lung transplant recipients. This combination is also useful in treating invasive disease and preventing VGC resistance. Additionally, CMV-HIG monoprohylaxis can delay or prevent viral replication in recipients experiencing VGC-related side effects. These findings support the use of CMV-HIG in selected clinical settings, although prospective studies are needed to define its potential benefits within the current therapeutic armamentarium. Full article

Although heart transplantation remains the gold standard in the treatment of advanced heart failure, the limited availability of donor organs and the growing number of patients requiring long-term care have necessitated wider implementation of mechanical circulatory support (MCS). Ventricular assist devices (VADs) substantially improve survival and quality of life, yet their clinical use is still constrained by serious complications, most notably local infections at percutaneous exit sites. This challenge persists across all device generations, from extracorporeal pulsatile pumps to contemporary continuous-flow systems. While fourth-generation concepts based on transcutaneous energy transfer are under development, unresolved issues such as thermal tissue injury continue to impede their adoption. This review critically examines current evidence on local infections, with particular emphasis on the role of biomaterials in bacterial colonization. The clinical burden and microbial etiology, dominated by Staphylococcus aureus and Staphylococcus epidermidis, are outlined, together with the limitations of existing material solutions, which lack durable antimicrobial activity. These infections frequently result in tissue necrosis, sepsis, rehospitalization, and elevated treatment costs, and their management is further complicated by the global rise in antimicrobial resistance. By synthesizing available data and identifying key shortcomings of current materials, this review underscores the urgent need for next-generation biomaterials with enhanced biocompatibility, resistance to microbial adhesion, and intrinsic or functionalized antimicrobial activity. Such advances are essential to improve the long-term safety and clinical outcomes of MCS therapy. Full article

Background: Adult moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disorder for which surgical revascularization is the primary treatment. The standard direct superficial temporal artery–middle cerebral artery (STA-MCA) bypass uses the frontal and/or parietal branch of the STA as the donor. However, in some patients, conventional STA-MCA bypass may be suboptimal because of a large mismatch in caliber between the STA branch and the recipient artery, increasing the risk of cerebral hyperperfusion. This study aimed to investigate the impact of a modified STA-MCA bypass on MMD treatment. Methods: We retrospectively reviewed adult cases of MMD at our institution (2012–2025) for patients who underwent modified direct STA-MCA bypass using a small side branch of the STA as the donor artery. Surgical techniques and clinical outcomes of these cases were analyzed descriptively. Results: Five cases (five hemispheres in four patients) underwent side-branch STA-MCA bypass. All procedures were completed successfully, with 100% graft patency confirmed by intraoperative indocyanine green angiography, and a mild increase in cerebral blood flow confirmed by postoperative single-photon emission computed tomography. No patients developed postoperative cerebral hyperperfusion syndrome or wound healing complications. Clinically, all patients experienced a stable or improved neurological status, with no reported new ischemic or hemorrhagic events during follow-up. Conclusions: In this small feasibility series, the side-branch STA–MCA bypass was technically feasible and safe, with no cerebral hyperperfusion syndrome observed. Any risk-mitigating effect on hyperperfusion remains theoretical and requires confirmation in comparative studies. Full article

Machine perfusion technologies have redefined the landscape of organ preservation by enabling not just static cold storage, but graft optimization and assessment with the opportunity for additional therapeutic interventions. Preservation solutions, traditionally developed for static cold storage, are now being adapted for use in dynamic perfusion platforms. The optimal composition for machine perfusion remains unclear as we shift to creating biologically intelligent platforms tailored to mitigate ischemia–reperfusion injury. This review presents a mechanistic framework for understanding organ preservation through the lens of shared vulnerabilities, particularly: mitochondrial dysfunction, endothelial barrier breakdown, and the activation of inflammatory cascades. We discuss the evolution of classical preservation solutions, the rationale for redox-targeted and endothelial-stabilizing additives, and the promise of modular approaches adaptable to both static cold storage and machine perfusion. By integrating recent preclinical insights, systems biology, and emerging clinical trials, we outline the path toward unified, precision-preservation strategies capable of expanding the donor pool and improving transplant outcomes. Full article

Mesenchymal stromal cells (MSCs) exert their immunoregulatory properties after licensing by inflammatory signaling cues, e.g., interferon (IFN)-γ. However, MSCs licensing by IFN-γ may result in increased expression of human leukocyte antigen (HLA) class II, which is related to rapid cell elimination, impairment of their immunosuppressive properties, and patient sensitization. The aim of this study was to evaluate the impact of IFN-γ on mediated immunoregulation and HLA class II expression. In this study, Wharton’s jelly (WJ) MSCs were isolated from human umbilical cords. Well-defined WJ-MSCs were submitted to IFN-γ exposure, and after 96 h, evaluation of biomolecule secretion and HLA class II expression was performed. Typing of HLA alleles using a next-generation sequencing (NGS) platform was performed. IFN-γ-primed WJ-MSCs secreted a high amount of immunoregulatory biomolecules, while elevated expression of HLA-DRB1 was observed. Analyses the NGS results showed the possibility of WJ-MSCs cluster formation based on their frequency of detected HLA alleles and immunoregulatory potential. Taking into consideration that IFN-γ-primed WJ-MSCs express HLA class II alleles, it is suggested that the HLA histocompatibility between allogeneic donor and recipient should be strongly considered to acquire the most beneficial outcome for the MSCs therapeutic strategy. Full article

Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor–recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced ≥2R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8–1003.3] vs. 65.3 [40.2–163.3] pg/mL; p = 0.04). A trend toward lower mtDNA/gDNA ratio was also observed in the same group (10.5 [5.4–24.6] vs. 6.5 [3.3–10.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury. Full article

Background/Objectives: Human leukocyte antigens (HLAs) are major determinants of successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). Their alleles are closely linked to outcomes, even in HLA-identical sibling donor (ISD) HSCT. This retrospective study analyzed the impact of HLA alleles on HLA-ISD HSCT outcomes in Omani patients. Methods: Data were collected for a heterogenous cohort of patients registered at the Sultan Qaboos University Hospital (SQUH), who underwent HLA-ISD HSCT from 2012 to 2022 (n = 153). HSCT outcomes, namely acute GVHD (aGVHD), chronic GVHD (cGVHD), chimerism status (complete or mixed) at 6 to 12 months after HSCT, neutrophil and platelet engraftment time, and patient five-year overall survival, were included. Low-resolution HLA-typing records were collected for five HLA loci: HLA-A, B, C, DRB1 and DQB1. GVHD and chimerism were analyzed by logistic regression analysis. Platelet and neutrophil engraftment times were assessed by Mann–Whitney tests. Patient overall survival was evaluated by the Kaplan–Meier model and Log-rank testing. At a 95% confidence interval, the p-value threshold was corrected using Bonferroni correction. Results: The incidence rates of aGVHD and cGVHD from all grades were 16% and 15%, respectively. Although no association between HLA alleles or any of the investigated outcomes was identified, survival curve analyses indicated a significant protective effect of HLA-DQB1*05 (p = 0.01). Patients carrying this allele had a better-estimated 5-year overall survival (90%) than did DQB1*05 negative patients (68%). Conclusions: This study suggests that HLA-DQB1*05 in the Omani population could have an impact on overall survival and might be a predictive biomarker. Further studies on a larger scale in other regional populations are needed to validate our findings and explore the underlying mechanism. Full article

Excessive maternal fructose intake contributes to the developmental programming of hypertension in offspring, partly via gut microbiota dysbiosis and oxidative stress. Fecal microbiota transplantation (FMT) may restore microbial balance and modulate short-chain fatty acid (SCFA) production. We investigated whether maternal FMT from healthy donors could prevent hypertension in offspring exposed to a high-fructose (HF) diet. Pregnant Sprague Dawley rats (n = 12) were fed normal chow (ND) or a 60% HF diet from mating to delivery. Cross-FMT was performed: HF dams received FMT from ND donors, and ND dams received FMT from HF donors. Male offspring (n = 8/group) were assigned to ND, HF, ND + HF-FMT, or HF + ND-FMT groups. Offspring of HF dams developed higher systolic blood pressure (+13 mmHg vs. ND, p < 0.05). Maternal FMT from ND donors reduced this elevation by ~8 mmHg (p < 0.05). Protective effects were accompanied by higher plasma butyrate, increased expression of SCFA receptors (GPR41, GPR43), reduced renal oxidative stress markers (8-OHdG), and distinct gut microbiota profiles. Maternal FMT generated four enterotypes in offspring, each associated with differential blood pressure outcomes. These findings suggest that maternal microbiota-targeted interventions, such as FMT, can mitigate hypertension of developmental origin by restoring gut microbial and metabolic homeostasis. Full article