Search Results (29)

Cardiac allograft vasculopathy (CAV) is a leading cause of allograft dysfunction and failure. CAV prevention, early detection, and management are essential to increasing allograft survival. In this comprehensive review, we discuss various invasive and non-invasive modalities that are being utilized for CAV detection. Invasive coronary angiography provides a visualization of vascular anatomy but is limited in detecting the microvasculature and diffuse and early structural changes. The addition of intracoronary assessment techniques, including intravascular ultrasound, optical coherence tomography, and coronary flow reserve assessment, offer(s) superior sensitivity in identifying CAV. Non-invasive imaging modalities, such as cardiac magnetic resonance imaging, computed tomography angiography, and positron emission tomography, provide complementary insights into CAV with myocardial perfusion and allograft function while reducing procedural risks. Our aim is to guide clinicians in selecting appropriate imaging strategies tailored to individual recipients, to improve detection, monitoring, and outcomes in CAV. Full article

Antibody-mediated rejection is a critical factor in acute and chronic allograft rejection, with Human Leukocyte Antigen as the primary target of the humoral immune response in kidney transplants. In addition to HLA antibodies, non-HLA Abs also play a significant role in AMR. These non-HLA Abs, which can target either autoantigens or alloantigens, may be present pre-transplantation or develop post-transplant. They are associated with various types of allograft injury. The major non-HLA Abs include those directed against the angiotensin II type 1 receptor, endothelin type A receptor, and MICA, as well as other antigens such as vimentin, collagens, and anti-endothelial cell antibodies. Factors such as ischemia, reperfusion injury, and calcineurin inhibitor toxicity can trigger the pathogenic activity of these Abs. The mechanisms underlying non-HLA Ab production are not yet fully understood but are thought to involve endothelial injury and the exposure of neoantigens. Research indicates that these non-HLA Abs can cause graft injury through both complement-dependent and complement-independent pathways. However, detecting non-HLA Abs remains a challenge due to the lack of reliable diagnostic tools. Current treatment strategies for managing the effects of pathogenic non-HLA Abs include intravenous immunoglobulin, plasmapheresis, rituximab, and bortezomib. Early identification of high-risk patients and timely intervention are crucial to preventing graft failure. This review examines the development, mechanisms, and clinical significance of non-HLA Abs in kidney transplantation, highlighting the need for improved diagnostic methods and tailored therapeutic approaches. Full article

Introduction: Renal transplantation ensures particular advantages for patients with end-stage kidney disease. However, in some cases, early complications may result in allograft dysfunction, which can ultimately lead to the loss of the graft. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. We focused on emerging serum biomarkers such as kidney injury molecule 1 (KIM-1) on a cohort of grafted patients. The motivation of this study was to analyze a predictive biological marker in comparison with standard markers for the evaluation of renal function, with the aim of observing if there are statistically significant differences regarding the performance and promptness of its increase compared to the current monitoring methods in order to improve graft survival, quality of life, and overall patient prognosis. Patients and Methods: We included 21 patients who had their first kidney transplantation (8 females, 13 males), with a follow-up period from transplantation of 3.14 years, without prior immunization, having complete HLA typing and a negative cross-match test before transplantation. We determined serum creatinine and KIM-1 in the whole cohort at the time of the enrollment in the study. Results: The mean creatinine value was 0.89 mg/dL ± 0.33. The mean value for KIM-1 was 13.56 +/− 21.52 in the Tx group vs. 5.91 +/− 3.26 in the control group with a p-value of 0.06. We defined patients at low risk (LR) of graft loss (serum creatinine < 0.9 mg/dL) and those at high risk (HR) (serum creatinine > 0.91 mg/dL). The mean values for KIM-1 were 6.09 +/− 1.67 in the LR vs. 21.77 +/− 29.71 in the HR group, with a p-value 0.01. Conclusions: There is a strong difference for KIM-1 at 24 h postTx between the two groups, showing a high correlation between KIM-1 and the predisposition of the graft dysfunction. Further studies are needed in order to clarify the utility of these novel biomarkers in the prediction of graft survival in renal transplantation patients. Full article

Objectives: Heart failure (HF) remains a significant public health issue, with heart transplantation (HT) being the gold standard treatment for end-stage HF. The increasing use of mechanical circulatory support, particularly left ventricular assist devices (LVADs), as a bridge to transplant (BTT), presents new perspectives for increasingly complex clinical scenarios. This study aimed to compare long-term clinical outcomes in patients in heart failure with reduced ejection fraction (HFrEF) receiving an LVAD as BTT to those undergoing direct-to-transplant (DTT) without mechanical support, focusing on survival and post-transplant complications. Methods: A retrospective, single-center study included 105 patients who underwent HT from 2010. Patients were divided into two groups: BTT (n = 28) and DTT (n = 77). Primary endpoints included overall survival at 1 and 7 years post-HT. Secondary outcomes involved late complications, including organ rejection, renal failure, cardiac allograft vasculopathy (CAV), and cerebrovascular events. Results: At HT, the use of LVADs results in longer cardiopulmonary bypass and cross-clamping times in the BTT group; nevertheless, surgical complexity does not affect 30-day mortality. Survival at 1 year was 89.3% for BTT and 85.7% for DTT (p = 0.745), while at 7 years, it was 80.8% and 77.1%, respectively (p = 0.840). No significant differences were observed in the incidence of major complications, including permanent dialysis, organ rejection, and CAV. However, a higher incidence of cerebrovascular events was noted in the BTT group (10.7% vs. 2.6%). Conclusions: LVAD use as BTT does not negatively impact early post-transplant survival compared to DTT. At long-term follow-up, clinical outcomes remained similar across groups, supporting LVADs as a viable option for bridging patients to transplant. Full article

Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years (p = 0.048). These data need to be confirmed in larger cohorts. Full article

Background: Early allograft failure (EAF) significantly contributes to mortality, necessitating re-transplantation following liver transplantation. The EAF simplified estimation (EASE) score has been recently developed to predict EAF. We aimed to assess the predictive capacity of high EASE scores for EAF and postoperative outcomes and to evaluate the association between the lymphocyte count-to-C-reactive protein ratio (LCR) and high EASE scores after living donor liver transplantation (LDLT). Methods: We retrospectively analyzed the data of 808 patients who underwent LDLT. After excluding 16 patients with incomplete laboratory data, the final cohort included 792 patients. Patients with EASE scores ≥−0.74 were categorized into the high EASE group. Multivariate logistic regression was used to examine the association between the LCR and high EASE scores. Results: High EASE scores demonstrated superior predictive accuracy for EAF development relative to that of the early allograft dysfunction (EAD) model (p = 0.018) and were more closely associated with overall mortality (p = 0.033). A preoperative LCR < 12.7 significantly increased the odds (odds ratio, 3.3; confidence interval, 1.997–5.493) of exhibiting high EASE scores post-LDLT, alongside preoperative hematocrit levels, operative duration, intraoperative continuous renal replacement therapy, administered calcium dose, mean heart rate, and donor age. Conclusions: The EASE score could offer enhanced utility for predicting EAF and overall mortality following LDLT relative to that of EAD. Identifying and managing risk factors, including low LCR values, for elevated EASE scores is essential for improving patient prognoses. Full article

Background/Objectives: With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients. Methods: A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus. Results: A total of 2056 patients were in each cohort after matching (mean age: 50.7–51 years, 17.9–20.0% African American, 60–60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort. Conclusions: This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients. Full article

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with a press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle > 10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage IV or higher cases. Conclusions: Early diagnosis and treatment before age 5, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management. Full article

Background/Objectives: Mental health and substance use disorders (MHDs and SUDs) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research currently exists on MHDs and SUDs in this population. Methods: This study compares the incidence of MHDs and SUDs in the transplant list, VAD, and post-transplant patients with that in heart failure patients. Study cohorts were derived from the TriNetX database using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with MHDs and SUDs before the window of time were excluded. All comparisons were made between propensity-matched cohorts. Statistical significance was set at p < 0.05. Results: Transplant waitlist patients showed a significant increase in the incidence of anxiety, depression, panic, adjustment, mood, alcohol use, and eating disorders. Post-transplant patients showed a significant increase in depression and opioid use. VAD patients showed a significant increase in depression and a decrease in panic disorder and anxiety. These results allow for further investigations on prevention and coping strategies. Conclusions: The deterioration of mental health can significantly impact medication compliance, survival, and quality of life. Opioid use for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction. Full article

Study Design: Retrospective case series. Objective: Cellular bone allografts (CBAs) contain the components of a successful bone graft with no autologous component and have been used extensively outside the head and neck. Descriptions of their utilization for mandible reconstruction are limited. We review our experience utilizing a CBA, with no autologous component, for the reconstruction of mandible defects. Methods: Patients undergoing reconstruction of a composite mandible defect with a CBA, no added autologous component, within a patient-specific graft cage and soft tissue free flap coverage were retrospectively identified. Graft survival and defect management are assessed and results of post-operative imaging reported. Results: Five subjects, aged 23–56 years, underwent reconstruction of mandible defects with the described technique. Defects resulted from gunshot wounds in 4 patients and the composite resection of a low-grade malignancy in one. The defect was definitively managed in 4 subjects, 3 of which had post-operative imaging demonstrating bone formation. The fifth experienced graft failure after developing an orocutaneous fistula and was successful salvaged with an osteocutaneous fibula free flap. Conclusions: Our early experience is promising that a CBA, with no autologous component, and soft tissue free flap coverage can be used for the reconstruction of composite mandible defects in select patients. Full article

Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing both active and chronic active AMR and highlight the ongoing clinical trials. Full article

The indications for cryopreserved allografts in aortic valve replacement are still debatable. We aim to identify factors influencing early and long-term durability of the aortic homograft and to define subgroups of patients with an improved long-term quality of life, survival, and freedom from structural valve degeneration (SVD). We evaluated our series of 210 patients who underwent allograft implantation with a retrospective cohort study design over a period of 20 years. Endpoints were overall mortality, cardiac mortality related to SVD, the incidence of SVD, reoperation, and a composite endpoint comprising major adverse cardiac and cerebrovascular events (MACCEs), which includes cardiac death both related and not related to SVD, subsequent aortic valve surgery, new or recurrent infection of implanted allograft, recurrent aortic regurgitation, rehospitalization for heart failure, an increase in New York Heart Association (NYHA) class of ≥1, or cerebrovascular events. The primary indication for surgery was endocarditis (48%), which was also a predisposing factor for increased cardiac mortality. Overall mortality was 32.4% with a 27% incidence of SVD and mortality associated with SVD of 13.8%. Reoperation occurred in 33.8% and MACCEs in 54.8%. Long-term NYHA functional class and echocardiographic parameters improved over time. Statistical analysis demonstrated that root replacement technique and adult age were protective factors for SVD. We found no statistically significant difference in the clinical outcomes analyzed between women of childbearing age who had children after surgery and the rest of the women. The cryopreserved allograft is still a valid option in aortic valve replacement, providing acceptable durability and clinical outcomes with optimal hemodynamic performance. SVD is influenced by the implantation technique. Women of childbearing age might have additional benefits from this procedure. Full article

The current gold standard technique for the treatment of anterior cruciate ligament (ACL) injury is reconstruction with a tendon autograft. These treatments have a relatively high failure and re-rupture rate and are associated with early-onset osteoarthritis, developing within two decades of injury. Furthermore, both autografting and allografting come with several drawbacks. Tissue engineering and additive manufacturing present exciting new opportunities to explore 3D scaffolds as graft substitutes. We previously showed that 3D-printed scaffolds using low-cost equipment are suitable for tissue engineering approaches to regenerative medicine. Here, we hypothesize that Lay-Fomm 60, a commercially available nanoporous elastomer, may be a viable tissue engineering candidate for an ACL graft substitute. We first printed nanoporous thermoplastic elastomer scaffolds using low-cost desktop 3D printers and determined the mechanical and morphological properties. We then tested the impact of different surface coatings on primary human ACL fibroblast adhesion, growth, and ligamentous matrix deposition in vitro. Our data suggest that poly-L-lysine-coated Lay-Fomm 60 scaffolds increased ligament fibroblast activity and matrix formation when compared to uncoated scaffolds but did not have a significant effect on cell attachment and proliferation. Therefore, uncoated 3D printed Lay-Fomm 60 scaffolds may be viable standalone scaffolds and warrant further research as ligament tissue engineering and reconstruction grafts. Full article

Background: When a partial liver graft is transplanted into a recipient with portal hypertension, it is subject to sinusoidal shear stress, which, in good measure, is essential for regeneration. However, portal hyperperfusion which exceeds the capacity of the graft results in the small-for-size syndrome manifested by ascites, cholestasis and coagulopathy. This review discusses intraoperative hemodynamic variables that have been described in the literature, and inflow modulation strategies and their outcomes. Apart from using donor grafts which are of adequate size for the recipient weight, portal hemodynamics are an important consideration to prevent early allograft dysfunction, graft failure and mortality. Summary: Understanding normal portal hemodynamics, how they change with the progression of cirrhosis, portal hypertension and changes after the implantation of a partial liver graft is key to managing patients with living-donor liver transplantation. If the intraoperative measurement of portal flow or pressure suggests graft portal hyperperfusion, inflow modulation strategies can be adopted. Splenic artery ligation, splenectomy and hemiportocaval shunts are well described in the literature. The proper selection of a donor to match the recipient’s anatomic, metabolic and hemodynamic environment and deciding which modulation strategy to use in which patient is an exercise in sound clinical judgement. Key message: The intraoperative assessment of portal hemodynamics in living-donor liver transplant should be standard practice. Inflow modulation in properly selected patients offers a point-of-care solution to alter portal inflow to the graft with a view to improve recipient outcomes. In patients with small (anatomically/metabolically) grafts, using inflow modulation can result in outcomes equivalent to those in patients in whom larger grafts are used. Full article

Solid organ transplantation (SOT) is a life-saving treatment for end-stage organ failure, but it comes with several challenges, the most important of which is the existing gap between the need for transplants and organ availability. One of the main concerns in this regard is the lack of accurate non-invasive biomarkers to monitor the status of a transplanted organ. Extracellular vesicles (EVs) have recently emerged as a promising source of biomarkers for various diseases. In the context of SOT, EVs have been shown to be involved in the communication between donor and recipient cells and may carry valuable information about the function of an allograft. This has led to an increasing interest in exploring the use of EVs for the preoperative assessment of organs, early postoperative monitoring of graft function, or the diagnosis of rejection, infection, ischemia-reperfusion injury, or drug toxicity. In this review, we summarize recent evidence on the use of EVs as biomarkers for these conditions and discuss their applicability in the clinical setting. Full article