Long-term Graft Research Articles

Bilateral Simultaneous Penetrating Keratoplasty: A 40-Year Odyssey

Purpose: The purpose of this study was to report 40-year follow-up on a case of bilateral simultaneous penetrating keratoplasty (PK) involving a contralateral autograft. Methods: This was a case report. Results: A 39-year-old man developed right corneal scarring and lipid keratopathy from previous herpes zoster keratouveitis with visual acuity of 20/200. The left eye had dense amblyopia with visual acuity of 20/300. In 1980, he underwent right PK using a contralateral autograft and simultaneous left PK with an allograft. The right autograft provided excellent visual acuity until the graft failed 40 years later. The left allograft underwent severe endothelial graft rejection 2 months after surgery with gradual corneal clearance over the next 21 months. The left allograft remained clear through 40 years without graft failure. Conclusions: Long-term useful vision and graft survival were achieved with a penetrating autograft by avoiding endothelial graft rejection in the setting of previous herpes zoster keratitis and the patient being functionally monocular. Despite almost failing from severe endothelial graft rejection in the absence of ocular risk factors, the left allograft recovered and remained clear through 40 years possibly because peripheral host endothelial cells repopulated the donor.

Clinical experience of reoperative right ventricular outflow tract reconstruction with valved conduits: risk factors for conduit failure in long-term follow-up.

Reconstruction of right ventricular outflow tract in patients with congenital heart disease in various age groups remains a controversial issue. Currently, a little is known about the fate of secondary and subsequent conduit. The aim of the study was to determine risk factors of conduit failure, evaluate long-term conduit survival, find out which type of conduit should be preferred in case of reoperations. We performed a retrospective analysis of a total of 249 records of valved conduit secondary and subsequent replacement in right ventricular outflow tract in 197 patients. Median follow-up was 5.7years. The study endpoints were defined as conduit explants; balloon dilatation of the graft (excluding balloon dilatation of left/right pulmonary artery), transcatheter pulmonary valve implantation; heart transplantation or death of the patient. There were total of 21 deaths (11% mortality) among 197 patients during the follow-up, 2 patients underwent heart transplant, in 23 implanted conduits pulmonary angioplasty or/including transcatheter pulmonary valve implantation was afterwards performed due to graft failure, conduit had to be explanted in 46 cases. After 28years follow-up, freedom from graft failure after 5years was 77%, 48% after 10years and 21% after 15years. Reoperative right ventricular outflow tract reconstruction demonstrates good mid-term and acceptable long-term outcomes regardless of the type of conduit implanted. Worse long-term graft survival of secondary and further conduits is associated with younger age of the recipient at implantation, small size of the conduit, younger age of donor and male donor in case of allograft implantation.

Skin cancer in solid organ transplant recipients: still an open problem.

In the last two decades, the optimization of organ preservation and surgical techniques, and the personalized immunosuppression have reduced the rate of acute rejections and early post-transplant complications. However, long-term graft survival rates have not improved over time, and evidence suggest a role of chronic calcineurin inhibitor toxicity in this failure. Solid organ transplant recipients may develop chronic dysfunction/damage and several comorbidities, including post-transplant malignancies. Skin cancers, mostly non-melanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), are the most common malignancies in Caucasian solid organ transplant recipients. Several factors, together with immunosuppression, may contribute to the susceptibility for skin cancers which, although often treatable, could be associated with a much higher mortality rate than in the general population. The rapid identification and treatment (including reduction of immunosuppression and early surgical treatments) have an important role to avoid an aggressive behavior of these malignancies. Organ transplant recipients with a history of skin cancer should be followed closely for developing new and metastatic lesions. Additionally, patient education on the daily use of sun-protective measures and the recognition of the early signs (self-diagnosis) of coetaneous malignancies are useful preventive measures. Finally, clinicians should make themselves aware of the problem and build, in every clinical follow-up center, collaborative network involving transplant clinicians, dermatologists and surgeons who should work together to easily identify and rapidly treat these complications. In this review, we discuss the current literature regarding the epidemiology, risk factors, diagnosis, preventive strategies and treatments of skin cancer in organ transplantation.

CT Coronary Angiography and Dynamic CT Myocardial Perfusion for Detection of Cardiac Allograft Vasculopathy

BackgroundCardiac allograft vasculopathy (CAV) is a major obstacle limiting long-term graft survival. Effective noninvasive surveillance modalities reflecting both coronary artery and microvascular components of CAV are needed. ObjectivesThe authors evaluated the diagnostic performance of dynamic computed tomography–myocardial perfusion imaging (CT-MPI) and coronary computed tomography angiography (CCTA) for CAV. MethodsA total of 63 heart transplantation patients underwent combined CT-MPI and CCTA plus invasive coronary angiography (ICA) with intravascular ultrasonography (IVUS) between December 2018 and October 2021. The median interval between CT-MPI and heart transplantation was 4.3 years. Peak myocardial blood flow (MBF) of the whole myocardium (MBFglobal) and minimum MBF (MBFmin) among the 16 segments according to the American Heart Association model, except the left ventricular apex, were calculated from CT-MPI. CCTA was assessed qualitatively, and the degree of coronary artery stenosis was recorded. CAV was diagnosed based on both ICA (ISHLT criteria) and IVUS. Patients were followed up for a median time of 2.3 years after CT-MPI and a median time of 5.7 years after transplantation. ResultsAmong the 63 recipients, 35 (55.6%) had diagnoses of CAV. The median MBFglobal and MBFmin were significantly lower in patients with CAV (128.7 vs 150.4 mL/100 mL/min; P = 0.014; and 96.9 vs 122.8 mL/100 mL/min; P < 0.001, respectively). The combined use of coronary artery stenosis on CCTA and MBFmin showed the highest diagnostic performance with an area under the curve of 0.886 (sensitivity: 74.3%, specificity: 96.4%, positive predictive value: 96.3%, and negative predictive value: 75.0%). ConclusionsThe combination of CT-MPI and CCTA demonstrated excellent diagnostic performance for the detection of CAV. One-stop evaluation of the coronary artery and microvascular components involved in CAV using combined CCTA and CT-MPI may be a potent noninvasive screening method for early detection of CAV.

Twenty-year outcomes of free and I-composite radial artery grafts for coronary artery revascularization.

To compare the 20-year outcomes of coronary artery grafting (CABG) using radial artery (RA) grafts (free and I-composite) and internal thoracic artery (ITA) grafts. Long-term graft patency was evaluated in patients who underwent isolated CABG between August, 1996 and January, 2022. The long-term graft patency of free RA grafts, I-composite ITA-RA grafts, and saphenous vein (SV) grafts were compared. The RA was used as a coronary bypass conduit in 111 of the 246 patients enrolled in this study. The RA patency after 10 and 20years was 94.2% and 76.6%, respectively. Landmark analysis showed that although graft patency for up to 10years did not differ between the RA and ITA grafts (hazard ratio = 0.87; P = 0.8), patency of the ITA grafts was better from 10 to 20years post-surgery (hazard ratio = 0.19; P = 0.013). The 20-year graft patency of the I-composite RA grafts was better than that of the free RA grafts (80.0% vs. 72.4%; P = 0.029), but not significantly different from that of the ITA grafts (80.0% vs. 90.7%; P = 0.24). The 20-year patency of the I-composite ITA-RA graft was better than that of the free RA graft; therefore, the I-composite graft may be an effective conduit for CABG.

Male Pectoralis Major Muscle Augmentation with Autologous Fat Transplantation Using VASER Lipoaspirate: Evaluation with MRI.

This is a prospective examination of 20 male patients (40 breasts) who underwent VASER-assisted liposuction and fat grafting surgery, and long-term fat graft viability was evaluated by magnetic resonance imaging scans. Participants had an average age of 34.85 ± 7.37 years with a mean BMI of 26.73 ± 2.63 kg/m2. The mean fat graft volume injected was 542.63 ± 144.78 mL on the right, and 548.95 ± 140.36 mL on the left side. On the magnetic resonance imaging follow-up, the mean intrapectoral adipose tissue thickness was 20.34 ± 6.31 mm on the right, and 18.94 ± 8.27 mm on the left sides and tissue viability was preserved in all cases. The mean follow-up duration was 22 ± 9.8 (range 14-44) months. VASER-assisted lipoaspiration and autologous fat grafting of the major pectoralis muscle provide a satisfactory outcome and long-term maintenance of the grafted adipose tissue.

Volumetric evaluations of the maxillary sinus before and post regenerative surgery.

The purpose of this study was to investigate possible differences in the filling of the various recesses of the maxillary sinus after the procedure of sinus floor elevation in relation with the initial volume of the same and if the sinus volume can influence long-term graft dimensions, by using cone beam computed tomography (CBCT) as diagnostic analysis device. This study included 32 sinuses corresponding to 16 patients referred for bilateral maxillary sinus augmentation procedures needing to increase the volume of the surgical site with the porcine cortical bone for dental implant placement in the posterior maxilla. The sinuses were analyzed by preoperative and postoperative (15 days and 6 months after sinus surgery) cone beam computed tomography. No statistically significant relations were observed between initial sinus dimensions and the entity of the contraction of the graft between T1 (15 days after surgery) and T2 (180 days after surgery). The behavior was the same either for the large sinus (> 15.65 cm3) and for the small one (< 15.65 cm3). Instead, about the filling of the various sinus recesses, a linear regression model was used to explain the difference between the mean preoperative and postoperative surgical spaces; in most of the samples, the filling of the anterior recess was ~15% of the total volume of the graft, i.e., the minor one among the main recesses. Our findings suggest that: (1) in the procedure of sinus floor augmentation by a lateral approach with deproteinized porcine bone there are no relations between the initial dimensions of the sinus and the long-term dimensional changes of the graft, and (2) that, among the main recesses of the sinus, the anterior one is generally the less filled.

Comparable kidney transplant outcomes in selected patients with a body mass index≥40: A personalized medicine approach to recipient selection.

Many kidney transplant (KT) centers decline patients with a body mass index (BMI) ≥40kg/m2 . This study's aim was to evaluate KT outcomes according to recipient BMI. We performed a single-center, retrospective review of adult KTs comparing BMI ≥40 patients (n=84, BMI=42±2kg/m2 ) to a matched BMI<40 cohort (n=84, BMI=28±5kg/m2 ). Patients were matched for age, gender, race, diabetes, and donor type. BMI ≥40 patients were on dialysis longer (5.2±3.2years vs. 4.1±3.5years, p=.03) and received lower kidney donor profile index (KDPI) kidneys (40±25%vs. 53±26%, p=.003). There were no significant differences in prevalence of delayed graft function, reoperations, readmissions, wound complications, patient survival, or renal function at 1year. Long-term graft survival was higher for BMI ≥40 patients, including after adjusting for KDPI (BMI ≥40: aHR=1.79, 95% CI=1.09-2.9). BMI ≥40 patients had similar BMI change in the first year post-transplant (delta BMI: BMI≥40 +.9±3.3 vs. BMI<40 +1.1±3.2, p=.59). Overall outcomes after KT were comparable in BMI ≥40 patients compared to a matched cohort with lower BMI with improved long-term graft survival in obese patients. BMI-based exclusion criteria for KT should be reexamined in favor of a more individualized approach.

Recurrent Portal Vein Thrombosis In Liver Transplantation With Renoportal Anastomosis Caused by Spontaneous Reno-Caval Shunts: A Case Report

Orthotopic liver transplantation (OLT) in patients with cirrhosis complicated by portal hypertension, portosystemic shunts, and chronic portal vein thrombosis (PVT) has long been challenging. Spontaneous spleno-renal shunts (SRS) allow new surgical techniques to restore portal vein patency and hepatopetal flow. Renoportal anastomosis (RPA) has emerged as an accepted method for transplanting these patients, with good long-term patient and graft survival. Orthotopic liver transplantation with RPA is known to be complicated by recurrent PVT, with few details discussed in the literature. We present a case of a 56-year-old woman with decompensated cirrhosis who underwent deceased donor whole graft OLT using RPA with iliac vein conduit. The postoperative course was complicated by occlusive thrombosis in the portal vein and iliac vein conduit. Venography revealed enlarged left gonadal and lumbar vein varices acting as reno-caval shunts with hepatofugal flow. Embolization of the varices re-established durable venous patency that was confirmed on post-transplant day 68 with no other hemodynamic complications. This showcases an interesting mechanism by which recurrent PVT may occur in patients undergoing OLT with RPA. Because durable portal vein patency can be achieved with Interventional Radiology embolization of reno-caval varices, assessing these communications is an important preoperative consideration for planned OLT with RPA.

Survivability of locally prepared versus imported Descemet membrane endothelial keratoplasty grafts in Edmonton

ObjectifNotre étude visait à évaluer la survie à long terme des greffons décapés sur place ou importés déjà décapés en vue d'une kératoplastie endothéliale de la membrane de Descemet (DMEK, pour Descemet's membrane endothelial keratoplasty) à Edmonton. NatureÉtude de cohorte prospective portant sur des patients qui ont subi une DMEK entre le 1er janvier 2020 et le 31 décembre 2020. ParticipantsTous les patients qui ont fait l'objet d'une DMEK à Edmonton pendant la période à l’étude. MéthodesAinsi, 2 techniciens locaux (Edmonton) ont été formés pour procéder au décapage préalable de greffons. Lorsqu'ils avaient accès à des tissus de donneurs locaux, les greffons étaient préalablement décapés en vue de la DMEK. Dans le cas contraire, on importait des greffons de DMEK déjà décapés auprès de banques de cornées accréditées aux États-Unis. Les caractéristiques des patients et des greffons de même que la survie des greffons ont été évaluées et comparées entre les 2 groupes. RésultatsPendant la période à l’étude, on a utilisé 32 greffons de DMEK prédécapés sur place et 35 greffons de DMEK prédécapés aux États-Unis. Les caractéristiques des donneurs de cornée de même que celles des patients étaient semblables dans les 2 groupes. La meilleure acuité visuelle corrigée s'est améliorée pendant une période pouvant atteindre 6 mois après l'intervention. Elle se chiffrait à 0,2 logMAR dans le groupe de greffons prédécapés localement et à 0,2 logMAR dans le groupe de greffons importés (p = 0,56). Les taux de réinjection postopératoire d'une bulle d'air (rebubbling) s’élevaient à 25 % dans le groupe de greffons décapés localement et à 19 % dans le groupe de greffons importés (p = 0,43). On déplore 1 échec du greffon primaire dans chaque groupe (p = 0,93). La densité des cellules endothéliales a diminué de 37 % dans le groupe de greffons décapés localement et de 33 % dans le groupe de greffons importés selon les mesures réalisées 2 ans après la DMEK. ConclusionsLa survie à long terme des greffons préparés localement est comparable à celle des greffons importés de banques de cornées américaines.

Outcomes following ipsilateral great saphenous vein bypass for lower extremity arterial injuries

ObjectiveUse of autologous great saphenous vein (GSV) grafts for repair of extremity arterial injuries is well established. Contralateral great saphenous vein (cGSV) is traditionally used in the setting of lower extremity vascular injury given the risk of occult ipsilateral superficial and deep venous injury. We evaluated outcomes of ipsilateral GSV (iGSV) bypass in patients with lower extremity vascular trauma. MethodsPatient records at an ACS verified Level I urban trauma center between 2001 and 2019 were retrospectively reviewed. Patients who sustained lower extremity arterial injuries managed with autologous GSV bypass were included. Propensity-matched analysis compared the iGSV and cGSV groups. Primary graft patency was assessed via Kaplan-Meier analysis at 1-year and 3-years following the index operation. ResultsA total of 76 patients underwent autologous GSV bypass for lower extremity vascular injuries. 61 cases (80%) were secondary to penetrating trauma, and 15 patients (20%) underwent repair with iGSV bypass. Arteries injured in the iGSV group included popliteal (33.3%), common femoral (6.7%), superficial femoral (33.3%), and tibial (26.7%), while those in the cGSV group included common femoral (3.3%), superficial femoral (54.1%), and popliteal (42.6%). Reasons for using iGSV included trauma to the contralateral leg (26.7%), relative accessibility (33.3%), and other/unknown (40%). On unadjusted analysis, iGSV patients had a higher rate of 1-year amputation than cGSV patients (20% vs. 4.9%), but this was not statistically significant (P = 0.09). Propensity matched analysis also found no significant difference in 1-year major amputation (8.3% vs. 4.8%, P = 0.99). Regarding ambulatory status, iGSV patients had similar rates of independent ambulation (33.3% vs. 38.1%), need for assistive devices (58.3% vs. 57.1%), and use of a wheelchair (8.3% vs. 4.8%) compared cGSV patients at subsequent follow-up (P = 0.90). Kaplan-Meier analysis of bypass grafts revealed comparable primary patency rates for iGSV versus cGSV bypasses at 1-year (84% vs. 91%) and 3-years post-intervention (83% vs. 90%, P = 0.364). ConclusionIpsilateral GSV may be used as a durable conduit for bypass in cases of lower extremity arterial trauma where use of contralateral GSV is not feasible, with comparable long-term primary graft patency rates and ambulatory status.

Evaluation of Kidney Donor Risk Index/Kidney Donor Profile Index as Predictor Tools of Deceased-Donor Kidney Transplant Outcomes in a Greek Cohort.

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor's age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI (hazard ratio-HR: 2.21, 95% confidence intervals-CI: 1.16-4.22), KDPI (HR: 1.01, 95% CI: 1.00-1.02), and donor's age (HR: 1.03, 95% CI: 1.00-1.05). The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor's age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure (p-value: 0.19). Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited.

Proteomic characterization of aqueous humor in corneal endothelial decompensation after penetrating keratoplasty

Corneal endothelial decompensation (CED) is the major cause of the long-term graft failure, but the underlying mechanisms remain unclear. The purpose of this study was to characterize the proteomic profile in CED aqueous humor (AH) after penetrating keratoplasty (PKP). We collected AH samples (n = 6/group) from CED patients underwent PKP and cataract patients, respectively. The label-free quantitative proteomic analysis was performed to identify the differentially-expressed proteins (DEPs). The biological functions of DEPs were evaluated using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis. The protein-protein interaction (PPI) network construction was employed to distinguish the hub proteins of DEPs, and the selected proteins were validated by parallel reaction monitoring (PRM). The human peripheral blood mononuclear cells (PBMCs) were adopted to investigate the effect of biglycan (BGN) on inflammatory response, and the subsequent outcomes of inflammation on human corneal endothelial cells (HCECs). A total of 174 DEPs were identified in CED AH of patients underwent PKP, including 102 up-regulated proteins and 72 down-regulated proteins. Bioinformatics analysis revealed the significant enrichment of cytokine-mediated signaling pathway and extracellular matrix (ECM) organization in the up-regulated proteins, as well as the alterations of cellular components, including the increase of collagen and complement component C1 complex, and reduction in extracellular exosomes. A hub protein cluster of 15 proteins was determined by Molecular Complex Detection (MCODE), including FN1, BGN, COMP, COL11A1, COLA3A1, and COL1A1. Moreover, BGN promoted pro-inflammatory cytokine (such as TNF-α, IL-1β and IL-6) production in PBMCs through NF-κB signaling pathway, which subsequently resulted in HCECs death. These findings provided a systemic protein profile of AH in CED patients after corneal transplantation, with the alterations implicated in cytokine-mediated signaling, ECM, complement system, and exsomes. The identified proteins and signaling pathways probably paved the novel insight into understanding the pathogenesis of the disease.

Evaluation of the effect and predictive role of vitamin D and vitamin D receptor expression in CD4 + , CD8 + , CD14 + , CD56 + cells on the development of chronic rejection and graft functions in kidney transplant patients.

It is known that vitamin D has positive effects on graft functions (reduce fibrosis, suppress excessive inflammatory response, improve graft functions). In our study, it was aimed to evaluate the effects and predictive roles of vitamin D, the expression of vitamin D receptor (VDR) in lymphocytes, monocytes, natural killer cells on chronic rejection and graft functions in kidney transplant patients. Seventy one people were included in the study and analyses were made by dividing them into 3 groups. Group 1: Healthy control (n = 29), Group 2: Kidney transplant patients with stable kidney function (n = 17), and Group 3: Kidney transplant patients with chronic rejection diagnosis (n = 25). Serum 25-hydroxycholecalciferol, 1.25 dihydroxycholecalciferol levels and VDR percentages in CD4 + , CD8 + , CD14 + , CD56 + cells were measured in 3 groups. ROC analyses and logistic regression models were performed to predict rejection and long-term graft functions. The percentage of VDR expression in CD4 + lymphocytes (p < 0.001) and CD14( +) monocytes (p < 0.001), 25-hydroxycholecalciferol and 1.25 dihydroxycholecalciferol levels were lower in group 3 was detected. In ROC analyses and logistic regression models, VDR expression in CD4( +)T lymphocytes was shown to have a statistically significant value in the development of chronic rejection (Odds ratio 0.86: 0.76-0.92; p = 0.001/AUC = 0.941, p < 0.001) and prediction of 5th-year graft functions (Odds ratio 0.93: 0.88-0.98; p = 0.017/AUC = 0.745, p = 0.007). In our study, it was shown that low vitamin D and VDR expression is associated with poor outcome and VDR expression in CD4( +)T lymphocytes is predictive in terms of graft function and rejection.

Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study.

A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function. This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan-Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan-Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period. Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival.

Increased frequency of CD39+CD73+ regulatory T cells and Deltex-1 gene expression level in kidney transplant recipients with excellent long-term graft function

BackgroundThe ability of regulatory T cells (Tregs) to limit inflammatory responses has been demonstrated. However, different subpopulations of this cell have varying abilities to suppress alloreactive immune responses. The primary goal of this study was to assess the frequency of CD4+FOXP3+CD39+CD73+ Tregs and Deltex-1 gene expression on long-term renal transplant function. MethodsA total of 49 subjects were divided into 3 groups: (i) the excellent long-term graft function (ELTGF) group, (ii) the chronic graft dysfunction (CGD) group, and (iii) the healthy control (HC) group. Following sample collection, peripheral blood mononuclear cells (PBMCs) were isolated, and the Deltex-1 gene expression level and the frequency of CD4+FOXP3+CD39+CD73+ Tregs were evaluated. ResultsThe ELTGF group had more CD4+FOXP3+ Tregs than the CGD group, but the difference was not statistically significant (P = 0.07). However, the frequency of CD4+FOXP3+CD39+CD73+ Tregs and the ratio of these cells to total CD4+ lymphocytes significantly increased in the ELTGF group than in the CGD group (P = 0.04 and P = 0.02 respectively). In addition, the expression level of the Deltex-1 gene was significantly lower in the CGD group than in the other 2 groups (P = 0.01 and P = 0.04 respectively). ConclusionsGiven the increased frequency of CD4+FOXP3+CD39+CD73+ Tregs and the expression level of the Deltex-1 gene in the ELTGF group, it appears that these factors probably improved function and long-term survival of the transplanted organ through the suppression of alloreactive responses and reduction of inflammation. In other words, one of the immunological mechanisms involved in the CGD group may be a deficiency in Tregs.

Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts.

Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD. To predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression. Clinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD. Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint.

Improving adherence to immunosuppression after liver or kidney transplantation in individuals with impairments in personality functioning - A randomized controlled single center feasibility study.

Although adherence to immunosuppressive medication is the key factor for long-term graft survival today, 20-70% of transplant recipients are non-adherent to their immunosuppressive medication. A prospective, randomized, controlled single-center feasibility study was designed to evaluate the impact of a step guided multicomponent interprofessional intervention program for patients after kidney or liver transplantation on adherence to their immunosuppressive medication in daily clinical practice. The intervention consisted of group therapy and daily training as well as individual sessions in a step guided approach. The primary endpoint of the study was adherence to immunosuppression as assessed with the "Basel Assessment of Adherence to Immunosuppressive Medications Scale" (BAASIS). The coefficient of variation (CV%) of Tacrolimus (TAC) through levels and the level of personality functioning was a secondary endpoint. We conducted six monthly follow-up visits. Forty-one age- and sex-matched patients [19 females, 58.5 (SD = 10.56) years old, 22 kidney- and 19 liver transplantation] were randomized to the intervention- (N = 21) or control-group (N = 20). No differences between intervention- and control groups were found in the primary endpoint adherence and CV% of TAC. However, in further exploratory analyses, we observed that individuals with higher impairments in personality functioning showed higher CV% of TAC in the controls. The intervention might compensate personality-related susceptibility to poor adherence as evident in CV% of TAC. The results of the feasibility study showed that this intervention program was highly accepted in the clinical setting. The Intervention group could compensate higher CV% of TAC after liver or kidney transplantation in individuals with lower levels of personality functioning and non-adherence. ClinicalTrials.gov, identifier NCT04207125.

Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation

ObjectivesThis study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BackgroundMB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. MethodsIn 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). ResultsIVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6–22.2)]. ConclusionMB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

Post-kidney transplant body mass index trajectories are associated with graft loss and mortality.

Early post-kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all-cause graft loss and mortality. We estimated 5-year post-KT (n=151170; SRTR) BMI trajectories using an adjusted mixed effects model. We estimated long-term mortality and graft loss risks by 1-year BMI change quartile (decrease [1st quartile]: change<-.07kg/m2 /month; stable [2nd quartile]: -.07 ≤ change ≤ .09kg/m2 /month; increase [3rd, 4th quartile]: change>.09kg/m2 /month) using adjusted Cox proportional hazards models. BMI increased in the 3years post-KT (.64kg/m2 /year, 95%CI: .63, .64) and decreased in years 3-5 (-.24kg/m2 /year, 95%CI: -.26, -.22). 1-year post-KT BMI decrease was associated with elevated risks of all-cause mortality (aHR=1.13, 95%CI: 1.10-1.16), all-cause graft loss (aHR=1.13, 95%CI: 1.10-1.15), death-censored graft loss (aHR=1.15, 95%CI: 1.11-1.19), and mortality with functioning graft (aHR=1.11, 95%CI: 1.08-1.14). Among recipients with obesity (pre-KT BMI≥30kg/m2 ), BMI increase was associated with higher all-cause mortality (aHR=1.09, 95%CI: 1.05-1.14), all-cause graft loss (aHR=1.05, 95%CI: 1.01-1.09), and mortality with functioning graft (aHR=1.10, 95%CI: 1.05-1.15) risks, but not death-censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all-cause graft loss (aHR=.97, 95%CI: .95-.99) and death-censored graft loss (aHR=.93, 95%CI: .90-.96) risks, but not all-cause mortality or mortality with functioning graft risks. BMI increases in the 3years post-KT, then decreases in years 3-5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post-KT.