Graft Surveillance Research Articles

B-234 Evaluating the diagnostic utility of dd-cf-dna in renal allograft surveillance: a single-center perspective

Abstract Background Donor-derived cell-free DNA (dd-cf-DNA) tests offer a non-invasive alternative to biopsy for allograft surveillance in solid organ transplantation. Unlike biopsies, dd-cf-DNA tests are not subject to interpretation bias and have the potential to detect subclinical rejection, which can lead to graft dysfunction and poor outcomes. At our institution, dd-cf-DNA testing is currently offered as a send out test and we sought to evaluate its efficacy in monitoring our post-transplant patients. Methods We retrospectively examined electronic health records of 50 renal transplant patients with dd-cf-DNA (using AlloSure and Prospera assays) between January 1st, 2019, and December 31st, 2022 to assess diagnostic utility of dd-cf-DNA relative to donor-specific antibodies (DSA) and biopsy (all predictors of graft function). Statistical analysis included correlation testing with t-tests. Results Overall, dd-cf-DNA levels correlated with DSA levels (p = 0.0002) and patients with both HLA-class I and II DSA had significantly higher dd-cf-DNA levels (p< 0.05). The Prospera dd-cf-DNA assay appeared to be a better predictor of DSA levels (p = 0.04) than the Allosure dd-cf-DNA assay. Though not statistically significant, there was trend towards an increase in dd-cf-DNA in patient with biopsy-proven graft injury and rejection vs no rejection. Interestingly, dd-cf-DNA levels were significantly elevated in patients with biopsy-proven antibody mediated rejection (ABMR). Because dd-cfDNA levels have been reported to be impacted by sensitizing events including prior transplant, we evaluated and observed levels of dd-cf-DNA to be higher in patients with a history of more than one graft vs single graft recipients (p< 0.0001) and this observation was prominent in the Allosure assay. Conclusions Our findings suggest that dd-cf-DNA testing holds promise as a valuable tool for graft surveillance and early detection of ABMR. The lack of correlation with biopsy-confirmed rejections may be attributed to the dd-cf-DNA assays’ ability to detect rejection events earlier in the disease progression process compared to biopsy. Time course analysis will be beneficial. Additionally, the observed differences between AlloSure and Prospera emphasize the significance of thoroughly evaluating and selecting assays, particularly in multi-transplant recipients. We highlight that our initial analysis is limited due to a small sample size. However, we aim to assess 200 patients by the conclusion of this study.

Perspective for Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection After Kidney Transplantation: Defining Context of Use and Clinical Implications.

Antibody-mediated rejection (AMR) is a major cause of graft failure limiting long-term graft survival after kidney transplantation. Current diagnostic strategy to detect AMR is suboptimal and requires further improvement. Previously suggested treatment regimens for AMR could not demonstrate efficacy, however novel therapeutic agents are currently under investigation. Donor-derived cell-free DNA (dd-cfDNA) is a novel non-invasive biomarker for allograft injury, that has been mainly studied in the context of rejection. Its short-half-life in circulation and injury-dependent release are its key advantages that contribute to its superior diagnostic accuracy, compared to traditional biomarkers. Moreover, previous studies showed that dd-cfDNA-release is well-linked to histological and molecular features of AMR, and thus able to reflect real-time injury. Further observations suggest that dd-cfDNA can be used as a suitable screening tool for early detection of AMR in patients with donor-specific-anti-HLA-antibodies (DSA), as well as for monitoring AMR activity after anti-rejection treatment. The weight of evidence suggests that the integration of dd-cfDNA in the graft surveillance of patients with AMR, or those suspicious of AMR (e.g., due to the presence of donor-specific anti-HLA-antibodies) has an added value and might have a positive impact on outcomes in this specific cohort.

Consequences of Nephrotic Proteinuria and Nephrotic Syndrome after Kidney Transplant.

Proteinuria is the main predictor of kidney graft loss. However, there is little information regarding the consequences of nephrotic proteinuria (NP) and nephrotic syndrome (NS) after a kidney transplant. We aimed to describe the clinical and histopathological characteristics of kidney recipients with nephrotic-range proteinuria and compare the graft surveillance between those who developed NS and those who did not. A total of 204 patients (18.6% of kidney transplants in the study period) developed NP, and 68.1% of them had NS. Of the 110 patients who underwent a graft biopsy, 47.3% exhibited ABMR, 21.8% the recurrence of glomerulonephritis, 9.1% IFTA, and 7.3% de novo glomerulonephritis. After a median follow-up of 97.5 months, 64.1% experienced graft loss. The graft survival after the onset of NP declined from 75.8% at 12 months to 38% at 5 years, without significant differences between those with and those without NS. Patients who developed NS fewer than 3 months after the onset of NP exhibited a significantly higher risk of death-censored graft loss (HR: 1.711, 95% CI: 1.147-2.553) than those without NS or those with late NS. In conclusion, NP and NS are frequent conditions after a kidney transplant, and they imply extremely poor graft outcomes. The time from the onset of NP to the development of NS is related to graft survival.

Hepatic Artery Delineation on Ultrasound Volumes Comparing B-Flow and Color Doppler for Postoperative Monitoring of Pediatric Liver Transplants.

(1) Background: Accurate hepatic artery (HA) depiction following pediatric liver transplantation (LT) is essential for graft surveillance but challenging on ultrasound (US). This study assesses if improved HA delineation can be achieved by recording two-dimensional US volumes in Color Doppler (CD) and B-flow technique. (2) Methods: Of 42 consecutive LT, 37 cases were included, and HA delineation was retrospectively rated using a four-point score (0 = HA not detectable, 3 = HA fully detectable, separable from portal vein) within 48 h post-LT (U1) and before discharge (U2). (3) Results: Adding B-flow compared with CD alone showed superior results at neohilar (U1: 2.2 ± 1.0 vs. 1.1 ± 0.8, p < 0.0001; U2: 2.5 ± 0.8 vs. 1.5 ± 0.9, p < 0.0001) and segmental levels (U1: 2.8 ± 0.6 vs. 0.6 ± 0.8, p < 0.0001; U2: 2.8 ± 0.6 vs. 0.7 ± 0.5, p < 0.0001). (4) Conclusions: Standardized US volume recordings combining B-flow and CD can effectively delineate the HA along its vascular course in pediatric LT. The technique should be further evaluated as a standard monitoring instrument to rule out vascular complications after LT.

Realtime monitoring of thrombus formation in vivo using a self-reporting vascular access graft

BackgroundChronic kidney disease (CKD) affects 10% of the global population costing over a hundred billion dollars per annum and leading to increased risk of cardiovascular disease. Many patients with CKD require regular haemodialyses. Synthetic arteriovenous grafts (AVG) are increasingly used to provide rapid vascular connection for dialysis. Initially, they have excellent patency rates but are critically limited by neointimal hyperplasia at the venous anastomosis, which drives subsequent thrombosis, graft failure and death.MethodsHere, we describe a system in which electrical impedance spectroscopy sensors are incorporated circumferentially into the wall of a synthetic arteriovenous graft. This is combined with an implantable radiotelemetry system for data transmission outside the patient. The system was tested using monolayers of endothelial and smooth muscle cells as well as swine blood and clots with explanted human carotid artery plaques. Sensor testing was then performed in vitro and the device was implanted in vivo in female swine.ResultsThe device can wirelessly report the accumulation of biological material, both cells and blood. Differences are also detected when comparing controls with pathological atheroma. In swine differences between blockage formation in a graft were remotely obtained and wireless reported.ConclusionsCombining electrical impedance spectroscopy and an implantable radiotelemetry system enables graft surveillance. This has the potential to be used for early detection of venous stenosis and blood clot formation in real-time in vivo. In principle, the concept could apply to other cardiovascular diseases and vascular implantable devices.

FLOW: Flow dysfunction of hemodialysis vascular access: A randomized controlled trial on the effectiveness of surveillance of arteriovenous fistulas and grafts.

It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice. The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups. As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients.

Cardiac magnetic resonance evaluation in recipients of hepatitis c virus-infected donor hearts

Hepatitis C Virus positive (HCV+) organ donors offer a viable strategy for expansion of the heart donor pool without an increased risk of recipient mortality. Cardiac magnetic resonance imaging (CMR) is an effective tool for graft surveillance in heart transplant (HT) recipients. However, there are no data comparing CMR findings in HT recipients based on donor HCV status. The aim of this propensity score matched case-control study was to evaluate baseline CMR characteristics of HCV+ HT recipients and HCV- HT recipients, as well as compare cardiac allograft structure, function, performance, and tissue characterization between groups. CMR normative values did not differ between groups in matched analysis. There were no significant differences in CMR-derived biventricular function, strain, LGE, or myocardial tissue characteristics by parametric mapping. This study suggests CMR can be a valuable tool for surveillance in HCV+ HT patients, and abnormalities on imaging should not be attributed to HCV infection.

Immune response, phenotyping and molecular graft surveillance in kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 vaccination.

Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23%vs. 0.21% respectively, p = 0.13), GEP scores (9.85vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

Exploring Views and Expectations of Clinicians, Nurses, and Kidney Transplant Recipients Regarding Protocol Development of a Study to Investigate Feasibility of the Implantable Doppler Probe in Kidney Transplantation: Patient-Public Involvement Consultations.

The shortage of donor organs is the most limiting factor in kidney transplant practice today. New monitoring technologies are being investigated to reduce graft loss due to vascular complications. We assessed the feasibility of a novel blood flow monitoring device, the implantable Doppler probe, in kidney transplant surgery. This patient-public involvement consultation explored the views and expectations of the stakeholders (kidney transplant recipients, surgeons, clinicians, and nurses with direct experience of the implantable Doppler probe) on the protocol development of our feasibility study. Our objective was to improve the protocol, understand stakeholder perceptions regarding research in postoperative graft surveillance, and identify potential confounding factors to the research and challenges to implementation of implantable Doppler probe in clinical practice. We conducted semi-structured interviews containing open-ended questions with 12 stakeholders. We performed thematic analysis of the data at the latent level by an inductive approach according to a 6-phase guide by Braun and Clarke using NVivo 12 software. Three key themes emerged. (1) Experiences with the implantable Doppler probe as a monitoring device showed that it was well received by the patients; however, there was a clinical equipoise among the health care professionals. (2) Recognition of the need for research in the early postoperative graft monitoring displayed stakeholder understanding regarding the role of a blood flow monitoring device to improve surgical outcomes. (3) Recommendations for smooth conduct of the proposed study include suggestions for improvement of the study protocol, informative sessions for the patients and nurses, and innovative ideas to improve the monitoring device. Patient-public involvement consultation was crucial for the research design of our proposed feasibility study. Useful strategies and a patient- centered approach were incorporated to mitigate the potential challenges to the conduct of the research.

Ultrasonographic Appearance of the Lower Extremity Arteries After Femoropopliteal Bypass Surgery

Objective: The aim of this study was to assess the ultrasonographic appearance of the lower extremity arteries, after a femoropopliteal bypass surgery. Materials and Methods: Ninety patients, with atherosclerotic peripheral artery disease, underwent either autologous vein (30 subjects) or synthetic femoropopliteal bypass grafting, using an end-to-side (30 subjects) or end-to-end anastomotic technique. The outcomes were compared to 30 volunteers, who were recruited to serve as healthy controls. A lower extremity duplex ultrasonogram (DUS) was performed 1 year after treatment. The healthy volunteers underwent DUS at the point of being included in the study. Results: In healthy volunteers, the angle between the profunda femoris artery (deep femoral artery, PFA) and common femoral artery (CFA) did not exceed 30° of angulation. The diameter of the CFA, in the bifurcation area, was 9.8 ± 1.5 mm. The bypass patency rates, CFA diameter, PFA angle, and neointimal hyperplasia rates differed between the groups as presented. Conclusion: The results that were obtained may indicate the importance of bypass graft surveillance, using DUS, with precise analysis of the topography and geometry of the lower extremity arteries and vascular conduits, during the perioperative period. In addition, in this cohort, femoropopliteal bypass procedures were associated with an increase in the angle of the PFA from 30° to 80° of angulation. An increase in the diameter of the CFA in the area of the proximal anastomosis from 9.8 to 15.1 mm was also noted. In these patients, the saphenous vein bypasses were associated with minimal changes of the vascular geometry and better patency rates.

343.9: Longitudinal Monitoring of Pancreas and Kidney Transplant Recipients Using Donor-Derived Cell-Free DNA

Introduction: Donor-derived cell-free DNA (dd-cfDNA) is validated for allograft surveillance in kidney transplant recipients; however, the utility in patients undergoing pancreas and kidney (PTx) transplantation has not been well studied. Pancreatic rejection remains a major clinical concern, yet diagnosis relies on pancreatic biopsy which is associated with significant risk of procedural complications. Early identification of allograft injury is imperative to optimize treatment and intervention. Here, we describe dd-cfDNA levels in PTx transplant recipients in the setting of clinical stability and immunological events. Methods: PTx recipients were monitored longitudinally with dd-cfDNA (AlloSure, CareDx) at the discretion of the treating physician. dd-cfDNA was collected in tandem with standard of care laboratory testing including serum creatinine, amylase, lipase, DSA and BK PCR. Pancreatic graft dysfunction was defined by elevations in serum amylase/lipase or dysregulated glucose control. The reference population was defined by stable allograft function in the absence of immunological or clinical events. Immunological events were defined as clinically suspected allograft rejection or documented subtherapeutic immunosuppression. Results: A total of 16 PTx patients were monitored longitudinally with dd-cfDNA, including 15 SPK recipients and 1 pancreas after kidney transplant (Table 1). 12 patients met criteria for the stable reference population with a median dd-cfDNA level of 0.22% (IQR 0.12 – 0.36%, n=248). There was a trend towards increased variability in dd-cfDNA levels in the first 2 months post-transplant, after which there was no significant difference in dd-cfDNA stratified by time (Figure 1A). 4 patients developed 6 independent immunological events, which were associated with a significantly increased median dd-cfDNA level of 1.15% (IQR 0.15 – 1.85%) compared to 0.22% in the reference population (p = 0.03, Figure 1B). Conclusions: In stable PTx recipients, dd-cfDNA levels remain low post-transplant and reflect the reference ranges validated in kidney transplant alone. Early variability in dd-cfDNA levels may be explained by recovery from ischemia reperfusion injury. Significant increases in dd-cfDNA were associated with immunological events including clinically suspected allograft rejection, highlighting its utility in longitudinal graft surveillance.

230.5: Antibody Response and Molecular Graft Surveillance in Kidney Transplant Recipients Following SARS-CoV-2 Vaccination

Introduction: Preliminary studies suggest that kidney transplant recipients (KTRs) show diminished humoral responses to SARS-CoV-2 vaccination. Although reports of allograft rejection around the time of SARS-CoV-2 vaccination have been rare, there is no recommended framework for monitoring for potential vaccine-related allograft injury. Here, we describe an approach for longitudinal assessment of immunogenicity and safety of SARS-COV-2 vaccination in KTRs. Methods: KTRs eligible for SARS-CoV-2 vaccination were identified through medical records, beginning March 12, 2021. Baseline and weekly blood samples were collected for routine assessment, SARS-CoV-2 spike protein antibody titers, dd-cfDNA (AlloSure, CareDx) and gene expression profiling (GEP) (AlloMap, CareDx) for 12 weeks. HLA DSA testing was performed at baseline, 2 weeks after completion of vaccine doses and at week 12. Antibody response was defined as a 10-fold increase in total binding IgG titers. Results: 49 KTRs were identified for analysis. Patient demographics are summarized in Table 1. 10 patients (20.4%) demonstrated a spike antibody response following completion of the vaccine series. Patients with a prior history of COVID-19 were more likely to mount a spike antibody response (n=8, 53.3%) compared to those with no reported history of COVID-19 (n=2, 5.8%). The odds ratio was 18.3 (95% CI 3.2, 105.0, p=0.0005). Median dd-cfDNA levels did not differ between pre- and post-vaccination (0.23% versus 0.21% respectively; Table 2). There was no significant difference between pre- and post-vaccination GEP scores (9.85 versus 10.4 respectively; Table 2). No patients developed clinically significant DSA, eGFR decline or allograft rejection following vaccination. Conclusions: Quantitative antibody responses were strongly associated with a diagnosis of prior SARS-CoV-2 infection. Stability of eGFR, dd-cfDNA, GEP profiles and lack of allosensitization reinforce the safety profile of SARS-CoV-2 vaccination in KTRs. Further studies are needed to better understand immunogenicity in SARS-CoV-2 naïve individuals, including whether cellular responses are protective in the absence of humoral responses.

577 Infra-Inguinal Bypass Graft Surveillance Is an Opportunity to Optimise Statin and Antiplatelet Therapy to Reduce 12-Month Major Amputation and Mortality Rates

Abstract Aim Infra-inguinal bypass graft failure within the first two postoperative years can result from stenotic lesions within the conduit and near anastomosis. This study assesses graft surveillance uptake, patency, amputation, and death rates among infra-inguinal bypass surgery patients at 1, 6 and 12-months postoperatively. Method Patients undergoing infra-inguinal bypass at a single vascular centre between 1st January 2018 and 31st December 2019 were identified from the prospectively collected database. Primary outcomes at 1, 6 and 12-months postoperatively included: duplex-ultrasound (DUS) surveillance uptake, patency, major amputations, and death rates. Statistical analysis with SPSS® was performed using chi-squared tests and paired sample t-tests. Results Of the 91 patients included, 79.1% were men and median(IQR) age was 71(62–76). At 1, 6 and 12 months, DUS uptake was 74.2%, 77.5% and 73.3% respectively, primary-assisted patency rates were 88.2%, 78.8% and 65.3% respectively and secondary patency rates were 97.6%, 96.3% and 96.3% respectively. Major amputation rates at 1, 6 and 12 months were 5.4%, 8.6%, 8.6% respectively. Death rates at 1, 6 and 12 months were 3.2%, 5.4% and 10.8% respectively. Patients on statin therapy post-operatively had lower 12-month mortality than those not on statin therapy (7.7% vs 30.0%, p=.028). Major amputation rate at 12 months was lower among patients prescribed antiplatelet therapy (6.3% vs 40%, p=.008). Conclusions DUS graft surveillance is a vital opportunity to adequately optimise statin and antiplatelet therapy post-revascularisation to reduce 12-month major amputation and mortality rates.

O069 Infra-inguinal bypass graft surveillance is an opportunity to optimise statin and antiplatelet therapy to reduce 12-month major amputation and mortality rates

Abstract Introduction Infra-inguinal bypass graft failure within the first two postoperative years can result from stenotic lesions within the conduit and near anastomosis. This study assesses graft surveillance uptake, patency, amputation and death rates among infra-inguinal bypass surgery patients at 1, 6 and 12-months postoperatively. Methods Patients undergoing infra-inguinal bypass at a single vascular centre between 1st January 2018 and 31st December 2019 were identified from the prospectively collected database. Primary outcomes at 1, 6 and 12-months postoperatively included: duplex-ultrasound (DUS) surveillance uptake, patency, major amputations and death rates. Statistical analysis with SPSS® was performed using chi-squared tests and paired sample t-tests. Results Of the 91 patients included, 79.1% were men and median (IQR) age was 71(62–76). At 1, 6 and 12 months, DUS uptake was 74.2%, 77.5% and 73.3% respectively, primary-assisted patency rates were 88.2%, 78.8% and 65.3% respectively and secondary patency rates were 97.6%, 96.3% and 96.3% respectively. Major amputation rates at 1, 6 and 12 months were 5.4%, 8.6%, 8.6% respectively. Death rates at 1, 6 and 12 months were 3.2%, 5.4% and 10.8% respectively. Patients on statin therapy post-operatively had lower 12-month mortality than those not on statin therapy (7.7% vs 30.0%, p=.028). Major amputation rate at 12 months was lower among patients prescribed antiplatelet therapy (6.3% vs 40%, p=.008). Conclusion DUS graft surveillance is a vital opportunity to adequately optimise statin and antiplatelet therapy post-revascularisation to reduce 12-month major amputation and mortality rates. Take-home message Infra-inguinal bypass graft surveillance is an opportunity to optimise statin and antiplatelet therapy to reduce 12-month major amputation and mortality rates.

Multimodality Imaging to Detect Rejection, and Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients—An Illustrative Review

The three most common modalities of graft surveillance in pediatric heart transplant (HT) recipients include echocardiography, coronary angiography, and endomyocardial biopsy (EMB). The survival outcomes after HT in children have improved considerably in recent years. However, allograft rejection and cardiac allograft vasculopathy remain the leading cause of death or re-transplantation. The routine surveillance by EMB and coronary angiography are invasive and risky. Newer noninvasive echocardiographic techniques, including tissue Doppler imaging (TDI), 2-D speckle tracking echocardiography, CT coronary angiography (CTCA), cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) and invasive techniques such as intravascular ultrasound (IVUS), functional flow reserve (CFR) of coronary arteries, optical coherence tomography (OCT), have emerged as powerful tools which may help early recognition of sub-clinical rejection, response to treatment, early detection, and progression of CAV. The multimodality imaging approach, including noninvasive and invasive tests, is the future for the transplanted heart to detect dysfunction, rejections, and early CAV. This review illustrates noninvasive and invasive imaging techniques currently used or could be considered for clinical use in detecting heart transplant rejection, dysfunction, and CAV in children.

Notch3 expression in capillary pericytes predicts worse graft outcome in human renal grafts with antibody-mediated rejection.

Microvasculature consisting of endothelial cells and pericytes is the main site of injury during antibody‐mediated rejection (ABMR) of renal grafts. Little is known about the mechanisms of activation of pericytes in this pathology. We have found recently that activation of Notch3, a mediator of vascular smooth muscle cell proliferation and dedifferentiation, promotes renal inflammation and fibrosis and aggravates progression of renal disease. Therefore, we studied the pericyte expression of Notch3 in 49 non‐selected renal graft biopsies (32 for clinical cause, 17 for graft surveillance). We analysed its relationship with patients’ clinical and morphological data, and compared with the expression of partial endothelial mesenchymal transition (pEndMT) markers, known to reflect endothelial activation during ABMR. Notch3 was de novo expressed in pericytes of grafts with ABMR, and was significantly correlated with the microcirculation inflammation scores of peritubular capillaritis and glomerulitis and with the expression of pEndMT markers. Notch3 expression was also associated with graft dysfunction and proteinuria at the time of biopsy and in the long term. Multivariate analysis confirmed pericyte expression of Notch3 as an independent risk factor predicting graft loss. These data suggest that Notch3 is activated in the pericytes of renal grafts with ABMR and is associated with poor graft outcome.

Tissue presentation of human pegivirus infection in liver transplanted recipients

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29–0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Chronic Limb Ischemia due to Thrombosis of an Aneurysmal Degeneration of the Autogenous Vein Graft: A Case Report.

Nonanastomotic aneurysmal degeneration of a great saphenous vein graft is an unusual condition, despite the common use of this conduit in arterial reconstructions. Vein grafts are at risk of degenerative changes, but the real cause remains unknown. Postoperative graft surveillance with duplex ultrasound scanning is important for maintaining patency of the venous graft. We present a rare case of chronic limb ischemia due to partial thrombosis of an aneurysm of the great saphenous vein graft.

Meta-analysis finds recurrent infection is more common after endovascular than after open repair of infected abdominal aortic aneurysm.

Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%]; OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8%; P< .0001). Fenestrated, branched, or concomitant visceral debranching EVAR was performed in 6.1% of cases. In OAR, surgical debridement was consistently performed, and in situ reconstruction was applied in 82.2% and an omental flap in 51.5%. In nine studies considered for quantitative analysis, the patients' background (EVAR, n= 264; OAR, n= 274) were statistically balanced. The crude rates of recurrent infection and related rupture or death were 13.6% (95% confidence interval [CI], 8.8%-18.5%) and 4.9% (95% CI 1.8%-8.0%), respectively. The pooled analyses depicted significantly higher rates of recurrent infection after EVAR than after OAR (relative risk [RR], 2.42; 95% CI, 1.80-3.27; P< .0001; I2= 0%). Recurrent infection-related rupture or death (RR, 1.51; 95% CI, 0.70-3.23; P= .29; I2= 0%), perioperative death (RR, 0.80; 95% CI, 0.39-1.65; P= .55; I2= 35%), 1-year mortality (hazard ratio, 1.12; 95% CI, 0.97-1.28; P=.13; I2= 0%), and readmission or reintervention (RR, 1.16; 95% CI, 0.74-1.82; P=.52; I2= 0%) were not significantly different statistically between the two groups. Funnel plots showed no evidence of publication bias. Sensitivity analyses of leave-one-out meta-analysis confirmed higher rates of recurrent infection after EVAR. EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.

Observed elevated donor-derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection.

Donor‐derived cell free DNA (dd‐cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd‐cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd‐cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd‐cfDNA results available during the first year. The median time to first elevated dd‐cfDNA level was 46 days, and the highest dd‐cfDNA recorded within 1 year was .31% [inter‐quartile range, .23–.45]. Twenty‐two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor‐specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non‐CMV infections and the longest time to first elevated dd‐cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd‐cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non‐invasive graft surveillance tool.