Search Results (75)

Vascularised composite allotransplantation (VCA) has an evolving role in the reconstruction of complex functional and aesthetic deficits non-amenable to autologous or implant-based reconstructive modalities. International applications of VCA span upper extremity, face, abdominal wall, uterus, and penile transplantation, with more than 300 procedures performed worldwide. Among these, abdominal wall transplantation has uniquely contributed to the development of the sentinel skin flap (SSF) concept, in which solid organ transplant patients undergo simultaneous transplantation of a solid organ and a donor-derived vascularised skin flap, with the skin component of the SSF being trialled internationally as a means of monitoring for rejection within the solid organ allograft. Despite growing clinical success, VCA continues to face substantial barriers to wider adoption. Acute rejection remains highly prevalent, affecting up to 89% of recipients, with significant morbidity linked to intensive systemic immunosuppression. Challenges are further amplified by the unique immunological heterogeneity of composite grafts, ethical concerns surrounding identity-linked tissues, and the lack of standardised outcomes reporting across VCA subtypes. Advances in machine perfusion technologies and emerging cellular and biomaterial-based immunomodulation strategies show promise in reducing immunosuppression burden and improving graft longevity. This review outlines the current state of VCA, including clinical applications, outcomes, and mechanistic insights from pre-clinical studies, while highlighting key ethical considerations and evolving regulatory frameworks. Future progress will depend on standardised reporting systems, improved donor–recipient matching, better understanding of ischemia–reperfusion injury, and the development of next-generation immunosuppressive/immuno-modulatory therapies. Collectively, these innovations position VCA as a rapidly advancing field with significant potential to redefine reconstructive and transplant surgery. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

This article explores the multifaceted role of micro-ribonucleic acids (RNAs) (miRNAs) as critical posttranscriptional regulators in renal physiology and disease, with a focus on their emerging significance in glomerulopathies. miRNAs, small endogenous noncoding RNAs, modulate gene expression by promoting messenger RNA degradation or inhibiting translation, thereby orchestrating essential cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Recent advances have revealed that aberrant miRNA expression profiles are intricately linked to the pathogenesis and progression of various renal diseases, including acute kidney injury, chronic kidney disease, alloimmune injury in solid organ transplantation and glomerulonephritis. This review summarizes the pathogenic and protective roles of miRNAs in major glomerulopathies, discusses their potential as diagnostic and prognostic biomarkers, and outlines future directions for their integration into personalized therapeutic strategies. At the moment, it is not fully established whether some of these mechanisms are the primary pathogenic driver or a secondary response. Combining miRNAs with other molecular markers may further enhance diagnostic and predictive accuracy, facilitating clinical translation, while selective targeting of specific miRNAs at different stages of disease progression could offer promising therapeutic opportunities. Full article

Polyomavirus-associated nephropathy was first reported over 50 years ago. However, it still represents a cause of renal injury in kidney transplant recipients, particularly in the first two years post-transplantation, with occurrence rates of 1–10%. The role played by immunosuppression in viral reactivation is well acknowledged, and the modulation of its level is the main strategy for clinical management. Viral and immunological evaluation are fundamental for optimizing its diagnostic and therapeutic pathway. In this review, the main features of BK polyomavirus and associated nephropathy in renal transplant patients are addressed and discussed from a virological point of view; the role of BK polyomavirus in hematopoietic stem cell transplantation and other solid-organ transplant patients is also briefly reported. Full article

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

Background and Objectives: The use of controlled donation after circulatory death (cDCD) donors has significantly increased during the past decades and successfully expanded the donors’ pool. However, warm ischemia may have detrimental effects on graft function. Italian Law requires a no-touch period of at least 20 min, which is much longer compared to the 5 min accepted in most European countries. Materials and Methods This is an Italian single-centre retrospective review of all cDCD procedures performed from April 2021 to June 2025. Patients with severe brain injury undergoing withdrawal of life-sustaining therapy (WLST) were considered for cDCD. After cardiac arrest and a no-touch period of 20 min, organ reperfusion was performed using abdominal or thoraco-abdominal normothermic regional perfusion (NRP) through femoral vessels cannulation. The primary endpoint was 30-day graft survival; secondary endpoints included: incidence of primary non-function (PNF) and non-anastomotic biliary stricture (NAS) in liver transplantation, PNF and delayed graft function (DGF) in kidney transplantation, primary graft dysfunction (PGD) in heart and lung transplantation, and recipient’s survival. Results: A total of 52 patients, 33 (63%) males, median age 74 (65–79) years, underwent WLST during the study period and were included in the cDCD program. Median functional warm ischemic time (WIT), total WIT, asystolic phase, and NRP duration were 37 (34–40), 40 (37–42), 24 (23–26), and 192 (166–212) min, respectively. A total of 123 organs (46 livers, 61 kidneys, 8 hearts, and 8 lungs) were considered suitable for transplantation, procured, and successfully transplanted in 115 recipients. We report the early and mid-term outcomes of 84 recipients, including 41 liver recipients, 32 kidney recipients, and 8 heart recipients transplanted at the Azienda Ospedaliera Universitaria Integrata of Verona, and 3 lung recipients transplanted at the Azienda Ospedale Università of Padova. The 30-day graft survival was 95% in liver recipients, 97% in kidney recipients, and 100% in heart and lung recipients. PNF was observed in two liver recipients, and PGD in two lung recipients. DGF was recorded in 3 (9%) kidney recipients. Six recipients died during the follow-up, and the mean survival time was 3.9 ± 0.1 years. Conclusions: Solid organ transplantation using cDCD donors is feasible and provides excellent early and mid-term results despite longer donor asystolic times. Larger data and longer follow-up are necessary to confirm these promising results. Full article

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success. Full article

Nowadays, there have truly been spectacular advances in surgical techniques, the preservation of organs for transplants, the optimal and efficient selection of both donors and recipients, a more efficient diagnosis and prediction of possible complications of transplants, and important progress in the advances of pharmacological immunosuppression protocols and procedures. In this sense, survival rates after transplantation of various organs have been progressively increasing, especially in the case of lung transplants, whose average survival rate is usually lower than that of other types of solid organ transplants. Thus, detecting acute and subclinical rejection and chronic allograft rejection of any implant is important. This is important in all transplants, such as heart and lung transplants. In this last type of transplant, particularly, and due to the chronic dysfunction of the lung allograft, it is key to detect rejection early and on time, since it can reach close to half of the transplant patient population. Therefore, practical diagnostic tools are needed to visualize the level of allograft damage using genomic methods such as those that measure donor-derived cell-free DNA, where its amount increases in the plasma component of the transplant after tissue injury or due to allograft infection. This biomarker has become a key element with light and hope, but with some shadows of caution due to its use as a panacea. Our research team has experience in solid organ transplantation in quantifying this parameter in the progression of the lesion of the implanted allograft, and our experience and comparison with the published literature will be presented in the following review, discussing validated and non-validated results. Full article

Systemic sclerosis (SSc) is a heterogeneous disease characterized by vascular alterations, immune dysregulation, and fibrosis. Solid evidence supports the hypothesis that endothelial dysfunction is the key player in SSc vascular injury and a critical factor concurring to the initiation of SSc pathogenesis. This narrative review reports on persistent endothelial dysfunction, resulting from oxidative stress, autoimmunity, and impaired vascular repair, in the course of SSc, and how it can trigger and sustain fibrotic remodeling of various organs. In this paper, we also analyze the impact on SSc of impaired angiogenesis and vasculogenesis, diminished endothelial progenitor cell function, and endothelial-to-mesenchymal transition, which can collectively disrupt vascular homeostasis and promote myofibroblast activation. These pathologic events underlie the hallmark clinical manifestations, i.e., Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. The review highlights how recognizing SSc as a paradigm of systemic endothelial dysfunction may reframe our understanding of its physiopathology, modify current therapeutic strategies, and unveil new therapeutic targets. Full article

The need for organs suitable for transplantation has continued to rise as need outweighs availability. Increased demand has driven innovation in the field. Over the past ten years, donation after circulatory death (DCD) donors have become a greater portion of the donor pool. This method of donation includes a period of warm ischemia time to the organs. Thus, its use is dependent on recovery methods. Historically, extracorporeal membrane oxygenation (ECMO) was one of the first pumping technologies to enhance organ preservation in the potential donor. Subsequently, the adoption of normothermic regional perfusion (NRP) technology has also shown promise in organ transplantation. These technologies have increased utilization of organs and enhanced the pool of donor organs. This review seeks to summarize the literature supporting in situ technologies (ECMO and NRP) utilized in procurement of solid organs from DCD donors. The benefit of in situ perfusion in DCD organ recovery is that these technologies increase the number of organs available for transplantation by reducing ischemic injury. The disadvantages include the added technical aspect, added operating room time, and the increased ethical concerns surrounding these technologies compared to conventional methods of organ recovery. Full article

Background: Coronavirus disease 2019 (COVID-19) involves a complex interplay of dysregulated immune responses, a pro-inflammatory cytokine storm, endothelial injury, and thrombotic complications. This study aimed to evaluate the impact of kidney function on clinical, laboratory, and outcome parameters in patients hospitalized with COVID-19. Methods: We conducted a retrospective analysis of 359 patients admitted during the first wave of COVID-19, stratified by estimated glomerular filtration rate (eGFR < 60 vs. ≥60 mL/min/1.73 m²). Data on demographics, vital signs, laboratory values, and clinical outcomes—including mortality, hemodialysis requirement, intensive care unit (ICU) admission, and mechanical ventilation (MV)—were collected. Univariate and multivariate linear regression, as well as area under the receiver operating characteristic curve (AUC-ROC) analyses, were performed. A p-value < 0.05 was considered statistically significant. Results: Patients with an eGFR < 60 were older and more likely to have systemic hypertension, chronic kidney disease, a history of solid organ transplantation, and immunosuppressive therapy. This group showed higher rates of mortality (41.6% vs. 19.2%), hemodialysis requirement (32.3% vs. 9.6%), ICU admission (50.9% vs. 37.9%), and MV (39.8% vs. 21.2%). Laboratory results revealed acidosis, anemia, lymphopenia, elevated inflammatory markers, and hyperkalemia. Conclusions: An admission eGFR < 60 mL/min/1.73 m² is associated with worse clinical outcomes in COVID-19 and may serve as a simple, early marker for risk stratification. Full article

Background: Immunosuppressive therapies are vital for solid organ transplant (SOT) recipients to ensure graft survival, but long-term use can lead to complications. This study aimed to comprehensively evaluate the complications associated with immunosuppressive agents across different types of major SOTs. Methods: In a retrospective cohort study using a national claims database, we analyzed adult SOT recipients who began immunosuppressive therapy from 2007 to 2018. We identified complications such as infections, acute kidney injury, hypertensive emergencies, chronic kidney disease, hypertension, diabetes, dyslipidemia, and osteoporosis. These outcomes were determined through diagnostic codes, medication usage data, and hospital or emergency department visits. Results: Among 30,997 transplants with three-year follow up, complication rates varied by transplant type. Pancreatic transplant recipients had the lowest complication rate (225.9 per 1000 patient-years), while lung transplant recipients experienced the highest rate (823.9 per 1000 patient-years). Serious infections and chronic kidney disease were most common 2 to 6 months post transplant. Other complications, like acute kidney injury, hypertensive emergencies, hypertension, diabetes, dyslipidemia, and osteoporosis, were predominantly observed in the first month. Opportunistic infections peaked between 7 months and 1 year after transplantation. Conclusions: This study emphasizes the varied complications related to immunosuppressive therapy among different SOT recipients, delineating specific timeframes for each complication and maintenance regimen. Full article

Background/Objectives: The global prevalence of obesity continues to rise. However, whether obesity affects the degree of intra-abdominal solid organ damage following blunt trauma remains unclear. This study aimed to investigate the correlation between obesity and intra-abdominal solid organ damage. Methods: This cross-sectional study was conducted at a regional trauma center in the Republic of Korea from January 2018 to December 2022 and included 582 patients aged 18–98 years with blunt abdominal trauma. Patients were categorized into four groups—underweight, normal weight, overweight, and obesity—based on their body mass index (BMI). Odds ratios (ORs), beta coefficients, and 95% confidence intervals (CIs) for intra-abdominal organ damage were calculated across BMI categories using multiple logistic regression analysis after adjusting for the confounding variables. Results: The obesity group exhibited a significant decrease in the prevalence of liver injury (OR: 0.553, CI: 0.316 to 0.966) and a reduction in liver injury severity (β: −0.214, CI: −0.391 to −0.037) compared with the normal-weight group after adjusting for the confounding factors. However, no significant association was observed between the BMI and injuries to other solid organs, such as the spleen, pancreas, and kidneys. Additionally, the younger obesity group (participants aged < 45 years) exhibited a significant negative association with both liver injury and injury grade. However, the older obesity group (participants aged > 65 years) exhibited a statistically significant association only with the liver injury grade compared with the normal-weight group. Conclusions: Obesity can serve as a predictive factor for the presence and severity of liver damage caused by blunt abdominal trauma. Full article

The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the reported cases. Dengue and West Nile infections seem to be more severe with higher mortality in SOT patients than in the general population. Acute kidney injury is more frequent in patients with dengue and chikungunya although persistent arthralgia with the latter is less frequent. There is no clear relationship between arboviral infection and acute cellular rejection. Pre-transplant screening of donors should be implemented during increased arboviral activity but, despite donor screening and negative donor nucleic acid amplification test (NAT), donor derived infection can occur. NAT may be transiently positive. IgM tests lack specificity, and neutralizing antibody assays are more specific but not readily available. Other tests, such as immunohistochemistry, antigen tests, PCR, metagenomic assays, and viral culture, can also be performed. There are a few vaccines available against some arboviruses, but live vaccines should be avoided. Treatment is largely supportive. More data on arboviral infection in SOT are needed to understand its epidemiology and clinical course. Full article

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts’ survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure. Full article