Incidence Of Rejection Research Articles

Real-world cost-effectiveness analysis of thymoglobulin versus no induction therapy in kidney transplant recipients at low risk of graft loss.

A new induction therapy strategy of a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG) showed a lower incidence of acute rejection. The objective of this study was to use real-world data to determine the incremental cost-effectiveness ratio (ICER) of r-ATG induction for the prevention of acute rejection (AR) in the first year following kidney transplantation and for kidney graft survival over 1, 4, and 10 years of post-transplantation from the perspective of the national public healthcare system. A Markov state transition model was developed utilizing real-world data extracted from medical invoices from a single center. The study population consisted of adults at low immunological risk undergoing their initial transplantation and received kidneys from either living or deceased donors. The intervention of r-ATG induction was compared to no induction. The clinical outcomes considered for this analysis were acute rejection, cytomegalovirus infection/disease, death, graft loss, and retransplantation. The cost-effectiveness analysis in the first year revealed that the r-ATG group was more cost-effective, with an ICER of US$ 399.96 per avoided AR episode, an effectiveness gain of 0.01 year in graft survival and a total incremental cost of US$ 147.50. The 4- and 10-year analyses revealed an effectiveness gain of 0.06 and 0.16 years in graft survival in the r-ATG induction group, and a total incremental cost of US$ -321.68 and US$ -2,440.62, respectively. The single 3 mg/kg dose of r-ATG is cost-effective in preventing acute rejection episodes and dominant in the long term of transplantation, conferring survival gain.

Allograft tolerance after adult living donor liver transplantation: a case-control study.

To investigate the incidence and potential predictors of immune tolerance among adult living donor liver transplant (LDLT) recipients. This case-control study included adult recipients who underwent LDLT between May 2004 and January 2018, with at least a 5-year follow-up after LDLT. We divided the study recipients into two groups: Group 1 (Tolerance Group) included recipients who achieved operational or prope tolerance for at least one year; Group 2 (Control Group) included recipients who did not achieve tolerance. We used logistic regression analysis to study the potential predictors of tolerance after LDLT. We included 368 recipients, 275 (74.7%) in Group 1 and 93 (25.3%) in Group 2. Operational tolerance occurred in 13/275 (4.7%) recipients and prope tolerance in 262/275 (95.3%) recipients. Age was significantly higher in Group 1. The median time for tolerance among the study recipients was 60 months (36-168). During follow-up, Group 1 showed lower serum levels of bilirubin, liver enzymes, alkaline phosphatase, and gamma-glutamyl transferase. Group 1 had a lower incidence of acute cellular rejection (ACR), recurrent viral hepatitis, and biliary complications. Logistic regression identified preoperative MELD, indication for LDLT, ACR, recurrent viral hepatitis, and biliary complications as significant predictors for allograft tolerance after LDLT. Allograft tolerance occurred in 74.7% of this cohort. We suggest that the MELD score, indication for LT, ACR, recurrent viral hepatitis, and biliary complications are predictors of allograft tolerance after LDLT.

P-455. Post-Transplantation Infection and Rejection Outcomes in Kidney Transplant Recipients Living with Human Immunodeficiency Virus (HIV): A Single-Center Experience Over a Decade of Evolving Practices

Abstract Background The development of integrase inhibitor and injectable antiretroviral therapy (ART), use of lymphocyte-depleting induction, and implementation of the HIV Organ Policy Equity (HOPE) Act have revolutionized kidney transplant eligibility, peri-transplantation management, and post-transplantation outcomes for people living with HIV and advanced kidney disease in the last decade. We describe our experience with HIV-positive recipients over this important period. Methods We conducted a retrospective chart review of all adults living with HIV and advanced kidney disease who underwent kidney transplantation at our center between 2013-2024. Data was collected on demographics, ART and induction regimens, and post-transplantation outcomes: patient/allograft survival, infections, and rejection episodes within the first year. Results Sixteen patients (14 Male, 13 Black, Mean Age 51y) underwent 17 kidney transplantations. Ten transplantations occurred from 2013-2022; seven occurred within 18 months of our center’s implementation of the HOPE Act. HIV-associated nephropathy accounted for all six transplantations from 2013-2017; hypertension and diabetes mellitus accounted for most transplantations in later years. Four patients transplanted prior to 2017 received basiliximab, of whom one experienced rejection within a year; 13 subsequent transplantations were induced with anti-thymocyte globulin (ATG), with three complicated by rejection. Rejection incidence was comparable between recipients of 3 mg/kg and 4.5 mg/kg ATG. Two patients suffered graft loss (rejection, BK nephropathy). Eleven patients had infections within a year, predominantly urinary tract infections and cytomegalovirus viremia. No opportunistic infections were identified. Three out of the four patient deaths in this cohort were due to complications of coronavirus disease 2019. Conclusion Recent advancements in HIV care and solid organ transplantation practices converged to facilitate pre-transplantation optimization, increase opportunities for transplantation, and improve post-transplantation outcomes for people living with HIV and advanced kidney disease. When used with integrase inhibitor-based therapy, ATG can prevent rejection without precipitating opportunistic infections. Disclosures All Authors: No reported disclosures

P-2259. Incidence, Treatment, and Outcomes of Urinary Tract Infections Caused by Extended-Spectrum Beta-Lactamase Producing Bacteria in Kidney Transplant Recipients

Abstract Background Urinary tract infections (UTI) are the most common bacterial infection in kidney transplant recipients (KTR) during the first year post transplant. The objective of this study was to determine the incidence of UTI caused by extended-spectrum beta-lactamase (ESBL) producing bacteria in KTR and compare their outcomes to KTR with UTI caused by non-ESBL producing pathogens. Index Urinary Tract Infections (2013-2022) Methods This was a single-center, retrospective, chart review including adults who received their first, kidney-alone transplant from January 2013 through December 2022 and had a UTI within the first year post-transplant. A UTI was defined as a positive urine culture treated with antibiotics and presence of ESBL-producing bacteria was confirmed by susceptibility patterns. Patients were excluded if they had a rejection or received augmented immunosuppression prior to index UTI, received treatment for positive donor cultures, or were dialysis-dependent at 90 days post-transplant. Primary outcomes: incidence of index UTI caused by ESBL producing bacteria, location of treatment, and length of stay. Key secondary outcomes: patient and allograft survival, incidence of biopsy-proven rejection after treatment of index UTI, and number of UTI in the first year post-transplant. Primary Outcome: Hospitalizations Results Of 178 patients included, 21 (11.8%) had a UTI due to ESBL-producing bacteria and 157 (88.2%) had a UTI caused by a non-ESBL producing organism. The incidence of ESBL-UTIs increased from 0 to 18.5% during the observation period. No differences were identified in baseline characteristics except for receipt of a donation-after-cardiac-death kidney, 8 (38.1%) in the ESBL-UTI group and 28 (17.8%) in the non-ESBL UTI group, p = 0.03. Compared to the non-ESBL-UTI group, the ESBL-UTI group was more likely to be admitted for treatment 11/21 (52.2%) vs 40/157 (25.5%), p = 0.01, and had more UTIs in the first post-transplant year, mean (range) 2.7 (1-6) vs 1.8 (1-7), p = 0.003. No differences were identified in other outcomes. Empiric Therapy in Patients with Extended-Spectrum β-lactamase Urinary Tract Infections Conclusion The incidence of index UTI due to ESBL-producing bacteria is increasing while the UTI rate remains consistent, creating the need to identify optimal treatment and prevention strategies in KTR. Secondary Outcome: Total Urinary Tract Infections in the First Year Post-Transplant Disclosures All Authors: No reported disclosures

Impact of Fc-gamma receptor IIIA polymorphism on late-onset neutropenia and clinical outcomes in kidney transplant recipients following rituximab induction therapy.

This study aimed to investigate the association between the Fc-gamma receptor IIIA (FCGR3A) 158 polymorphism and clinical outcomes in kidney transplantation (KTx) patients. Specifically, we focused on late-onset neutropenia (LON) in ABO-incompatible (ABOi) or HLA-incompatible (HLAi) KTx recipients who underwent rituximab (RTx) desensitization therapy. FCGR3A 158F/V polymorphisms were identified in 85 ABOi or HLAi KTx recipients who underwent RTx desensitization at our institution between April 2008 and October 2021. We analyzed these polymorphism groups in relation to their preoperative background and incidence of LON, infection, and rejection. In addition, we examined the risk factors for LON development. The following FCGR3A 158F/V polymorphisms were identified: FF genotype (n = 45); FV genotype (n = 36), and VV genotype (n = 4). LON occurred in 25 out of 85 recipients within 1year after KTx, significantly more frequently in patients with the FCGR3A FV + VV genotype (17/40) than in those with the FF genotype (8/45) (p = 0.01). A multivariate analysis identified the V-allele as an independent risk factor for LON (OR, 4.03; 95% CI, 1.38-11.73, p = 0.01). However, there were no significant differences in the incidence rates of post-transplant infection and rejection between the FF and FV + VV genotypes. Recipients with the FCGR3A 158V-allele were identified as having a higher risk of developing LON following KTx with RTx desensitization therapy. However, the presence of this V-allele did not affect the safety or efficacy of RTx desensitization before KTx.

COVID-19 and renal allograft rejection: insight from controlled and non-controlled studies

Aim Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). Methods This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: ‘COVID’, ‘Renal’, ‘Kidney’, ‘Transplant’, and ‘Rejection’. The results from controlled and uncontrolled studies were separately collated and analyzed. Results A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. Conclusion In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.

"Effect of post-kidney transplant diabetes mellitus on long-term outcomes in a cohort of pediatric kidney transplant recipients from 2005 to 2022." Survival analysis.

Post-transplantation diabetes mellitus and carbohydrate intolerance (PTDM/iCHO) are complications following solid organ transplantation, which significantly increases the risk of graft loss and mortality. However, data concerning long-term outcomes in paediatric kidney transplant recipients with PTDM/iCHO are scarce. This study aimed to evaluate the risk of graft loss in paediatric kidney transplant recipients with PTDM or iCHO compared with non-PTDM/iCHO. The study cohort included patients aged <18 who underwent a kidney transplant in a transplant centre from 2005 to 2022. The primary outcome was graft survival loss; secondary outcomes were acute rejection, renal function and mortality. Cumulative incidence of graft loss and acute rejection was estimated, considering death a competing risk. Fine and Gray's proportional subdistribution hazard model was used to analyse the effect of PTDM/iCHO status on the event. Seventy-six paediatric kidney transplant recipients were included. The incidence of PTDM and iCHO was 6.6% and 9.2%, respectively. Patients with PTDM/iCHO had a significantly higher cumulative graft loss incidence than those without (34.4% vs 13.9% at 36 months, p<0.008). Multivariable analysis revealed a threefold increased risk of graft loss in patients with PTDM/iCHO (HRadjusted 3.33, 95% CI 1.19 to 9.30, p=0.022). PTDM/iCHO was associated with a higher incidence of acute rejection (33.3% vs 14.5% at 1 year, p=0.025). Patients with PTDM/iCHO also exhibited significantly worse eGFR at all time points compared with patients without PTDM/iCHO (p=0.036) CONCLUSION: Patients with PTDM and iCHO had a higher risk of graft loss and lower renal function in paediatric kidney transplant recipients. This justifies close monitoring of metabolic complications in these patients.

Efficacy Analysis of Modified Single-Incision Surgery for Repair of Pediatric Chest Wall Defects: A Retrospective Cohort Study.

This study aims to compare the efficacy of modified single-incision surgery with that of traditional modified Ravitch surgery for the repair of pectus excavatum in pediatric patients. In this retrospective study, we included patients who underwent surgical correction for sternal depression from January 2015 to December 2020 across four major medical centers. Patients were categorized into two specific groups on the basis of the surgical technique employed: the modified single-incision surgery group, which comprised patients treated using the novel single-incision approach, and the traditional modified Ravitch surgery group, which included patients who received the conventional Ravitch surgery with multiple incisions. This study only included patients in the age range of 10 to 18 years, diagnosed with moderate to severe pectus excavatum, and lacked remarkable comorbid conditions that could influence surgical outcomes. Comprehensive data on preoperative characteristics, intraoperative variables, and postoperative results were collected for analysis. The modified single-incision surgery group showed significantly lower mean blood loss, mean operating time, mean hospital stay, postoperative drainage rate, postoperative mean Haller index and mean Haller index after bar removal compared to the traditional modified Ravitch surgery group (p < 0.05). Furthermore, the surgical outcomes were significantly better in the modified single-incision surgery group (p = 0.010) than in the traditional modified Ravitch surgery group. The modified single-incision surgery group also had a significantly lower incidence of postoperative complications, including pneumothorax, pleural effusion, pulmonary infection, bar rejection, and bar flipping and displacement (p < 0.05), than the traditional modified Ravitch surgery group. The modified single-incision surgery group showed significantly greater improvement in sternal depression depth compared to the traditional modified Ravitch surgery group (p = 0.031). Corrected symmetry was significantly better in the modified single-incision surgery group (p = 0.037). The overall satisfaction of patients in the modified single-incision surgery group was significantly higher than that in the traditional modified Ravitch surgery group (p = 0.011). The modified single-incision procedure for the treatment of pectus excavatum offers considerable advantages over the traditional modified Ravitch surgery. The findings of this study suggest that the modified single-incision procedure is a safe and effective alternative for the correction of pectus excavatum.

Gut Microbial Dysbiosis and Implications in Solid Organ Transplantation.

The gut microbiome has been shown to play a significant role in solid organ transplantation, potentially influencing graft function and patient outcomes. Dysbiosis, characterized by reduced microbial diversity and an increase in pathogenic taxa, has been linked to higher incidences of allograft rejection, graft dysfunction, and post-transplant mortality. Several studies suggest that the gut microbiome might be able to serve as both a biomarker and a therapeutic target, potentially guiding personalized immunosuppressive therapies and other interventions to improve outcomes after solid organ transplantation. As summarized in this review, clinical studies have shown that specific microbial shifts correlate with adverse outcomes, including acute rejection and chronic allograft dysfunction. As research surrounding the relationship between the gut microbiome and solid organ transplant progresses, the integration of microbial analysis into clinical practice has the potential to revolutionize post-transplant care, offering new avenues to improve graft survival and patient quality of life. This review aims to provide a comprehensive overview of the relationship between gut microbial dysbiosis and transplantation outcomes, emphasizing the impact on kidney, liver, lung, and heart transplant recipients.

An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis.

Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients. An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.

Biopsy-Proven T-Cell Mediated Rejection After Belatacept Rescue Conversion: A Multicenter Retrospective Study.

After kidney transplantation, conversion to belatacept is a promising alternative in patients with poor graft function or intolerance to calcineurin inhibitors. The risk of acute rejection has not been well described under these conditions. Here we present a retrospective multicenter study investigating the occurrence of acute rejection after conversion in 901 patients (2011-2021). The incidence of cellular and humoral rejection was 5.2% and 0.9%, respectively. T-cell mediated rejection (TCMR) occurred after a median of 2.6months after conversion. Out of 47 patients with TCMR, death-censored graft survival was 70.1%, 55.1% and 50.8% at 1year, 3years and 5years post-rejection, respectively. Eight patients died after rejection, mainly from infectious diseases. We compared these 47 patients with a cohort of kidney transplant recipients who were converted to belatacept between 2011 and 2017 and did not develop rejection (n = 238). In multivariate analysis, shorter time between KT and conversion, and the absence of anti-thymocyte globulin induction after KT were associated with the occurrence of TCMR after belatacept conversion. The occurrence of rejection after conversion to belatacept appeared to be less frequent than with de novo use. Nevertheless, the risk of graft loss could be significant in patients with already low renal function.

Blood Gene Expression Profiling and Donor-derived Cell-free DNA to Noninvasively Diagnose Clinical and Subclinical Kidney Transplant Rejection: A Real-life Appraisal Study

Background. Peripheral blood biomarkers aim to noninvasively diagnose kidney allograft rejection, but most lack robust independent validation. TruGraf is intended to exclude subclinical cellular rejection (TCMR), whereas donor-derived cell-free DNA Viracor-TRAC has proven value in excluding antibody-mediated rejection (AMR). We aim to validate both biomarkers for accurate rejection diagnosis in a real-world clinical setting. Methods. We prospectively included 230 unselected, consecutive kidney transplants from 6 centers undergoing for-cause and protocol biopsies with paired blood samples from December 2021 to 2022. TruGraf and Viracor-TRAC were blindly run by a central laboratory. Results. The incidence of rejection was 22.6% (17.3% surveillance; 27% for-cause biopsies). Inflammation was associated with higher TRAC levels, with AMR/mixed and microvascular inflammation (MVI) showing the highest levels (P &lt; 0.05). TruGraf did not associate with any specific allograft injury. No biomarkers, individually or combined, accurately diagnosed any rejection (area under the receiver operating characteristic curve [AUROC] &lt; 0.65). However, high TRAC levels, when combined with DSA in for-cause biopsies, predicted AMR/mixed rejection or MVI (AUROC = 0.817; P &lt; 0.001), outperforming serum creatinine and DSA (AUROC &lt; 0.65). Conclusions. In this large, prospective, observational real-life study, we were unable to validate TruGraf and TRAC to diagnose rejection but found a useful context of use for TRAC to noninvasively diagnose AMR/mixed or MVI in conjunction with DSA in dysfunctioning graft.

Clinical characteristics, risk factor analysis and outcomes in 61 eyes with graft rejection after descemet stripping endothelial keratoplasty, with a review of literature.

To report the demographic profile, clinical characteristics, risk factors and outcomes of graft rejection after DSEK. A total of 3073 eyes had DSEK between 2012 and 2019, of which 1710 eyes that had follow up of more than one year. Sixty-one eyes who had graft rejection during this period were studied. Overall, incidence of graft rejection during the study period was 3.6% (61/1710 eyes) in those with follow up more than one year. The median age of patients was 58 (IQR 37.5-68) years. The indications were prior failed graft (34 eyes: 28 penetrating keratoplasty; 6 DSEK), post cataract surgery edema (12 eyes), Fuchs corneal endothelial dystrophy (6 eyes), corneal edema post inflammation (5 eyes) and iridocorneal endothelial syndrome (4 eyes). Of the 34 eyes with failed grafts, nine were post-rejection graft failures (two after endothelial keratoplasty and seven after penetrating keratoplasty), remaining 25 eyes were non-rejection graft failures. Ocular co-morbidities were noted in 41 eyes, of which secondary glaucoma was the most common (14 eyes). Clinical signs of graft rejection were diffuse edema, keratic precipitates and endothelial rejection line. Rejection episode occurred between 6-12months after surgery in 20 (33%) eyes, 12-24months in 15 (25%) eyes, 2-3years in 12 (20%) eyes, and beyond 3years in 14(23%) eyes. Graft clarity was restored in 55 (90%) eyes, which was complete in 41 (67%) eyes, partial in 14 (23%) eyes, and clarity was not restored in 6 (10%) eyes. The statistically significant risk factors for rejection were non-use of steroids (p value < 0.001), DSEK for failed graft (p value < 0.02) and DSEK for corneal edema post-inflammation (p value < 0.0014). DSEK for failed graft was a significant risk factor for graft failure after the rejection episode (p value < 0.05). Graft rejection may occur as late as 5years post-DSEK, emphasizing the need for long-term steroids instillation. Non-use of topical steroids, DSEK for failed graft and corneal edema post inflammation are risk factors for graft rejection. DSEK for failed graft was also seen as a risk factor for failure after the rejection episode The graft survival rate after the rejection episode was 90% at 6months, 50% at 2years and 10% at 5years.

Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis.

Valganciclovir (ValG) is the most widely used drug for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients (KTRs). However, it is associated with dose-limiting side effects and considerable costs. Some centers have identified valacyclovir (ValA) as an economically attractive alternative with a lower risk of bone marrow suppression. The comparative effectiveness of these two drugs is not well-established. This study aims to compare the efficacy and safety of ValA and ValG for CMV prophylaxis in KTRs. Searches were conducted of the Medline, Cochrane, Web of Science, Embase, and Ovid databases. Endpoints encompassed the incidence of CMV disease, CMV viremia, acute rejection, leukopenia/neutropenia, and other infections, including BK polyomavirus and non-CMV herpesviruses (HVs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies, comprising 888 patients (438 receiving ValA), were included. The groups were comparable in CMV viremia incidence (RR, 0.70; 95% CI, 0.31-1.57; P=0.4) and the development of CMV disease (RR, 0.74; 95% CI, 0.09-5.97; P=0.8). No significant differences in acute rejection rates were observed (RR, 0.97; 95% CI, 0.50-1.91; P=0.8). However, the rate of leukopenia/neutropenia was significantly lower in the ValA group (RR, 0.57; 95% CI, 0.42-0.77; P<0.01). No significant differences were noted for BK viremia (RR, 0.67; 95% CI, 0.24-1.87; P=0.4) or other HV infections (RR, 1.43; 95% CI, 0.61-3.38; P=0.4). The drugs demonstrate comparable efficacy in preventing CMV infection following kidney transplantation. However, ValA may have a lower impact on bone marrow suppression.

Combined Molecular Mismatch Approaches to Predict Immunological Events Within the First Year After Renal Transplantation.

Several molecular mismatch assessment approaches exist, but data on their combined use are limited. In this study, we aimed to define distinct risk groups for rejection based on the combination of three molecular mismatch assessment approaches (i.e., eplet mismatch count, the number of highly immunogenic eplets and PIRCHE-II score) in 439 consecutive immunological standard risk transplantations. For each molecular mismatch assessment approach, ROC analyses were used to define cut-offs for prediction of (sub) clinical rejection according to Banff 2019 classification within the first year post-transplant as a reference. If all three scores were below the cut-off, the patient was assigned to the low-risk group (19% of patients); if all three scores were above the cut-off, the patient was assigned to the high-risk group (21% of patients). The one-year incidence of (sub) clinical rejection was 12% in the low-risk group and 33% in the high-risk group (p = 0.003). Internal validation of the assigned risk groups for prediction of other outcomes revealed a high consistency: clinical rejection (6% vs. 24%; p = 0.004), ATG-treated rejection (1% vs. 16%; p < 0.001) and development of de novo HLA-DSA at 5 years post-transplant (6% vs. 25%; p = 0.003). The molecular mismatch risk group was an independent predictor for (sub) clinical rejection (high-risk vs. low-risk: hazard ratio 3.11 [95%-CI 1.50-6.45]; p = 0.002). We conclude that combining molecular mismatch approaches allows us to distinguish low- and high-risk groups among standard renal allograft recipients. Independent validation in other patient populations and different ethnicities is required.

"Expensive Sisters".

This perspective highlights a growing and concerning trend within the scientific publishing community: the increasing incidence of manuscript rejections within twenty-four hours of submission without peer review, followed by offers of transfer to a sister journal with a high article processing fee. Recommendations to address such issues, including increased transparency in the manuscript review process, the establishment of more robust editorial guidelines, and the promotion of equitable publishing opportunities regardless of financial capability have also been proposed.

Crescentic Autograft-Graft Salvage Technique for Undersized Donor Lenticules in Superficial Anterior Lamellar Keratoplasty.

To describe the use of crescentic autograft as a graft salvage technique for inadvertently undersized donor lenticules in superficial anterior lamellar keratoplasty (SALK). A prospective interventional study included 5 eyes of 4 patients who underwent SALK and had an inadvertently undersized donor lenticule. The described technique involves the preparation of a crescent-shaped graft from the host lenticule itself that is matched to fit into the remaining bare recipient stromal bed. At 6-week follow-up, the crescentic autograft was uniformly epithelized along with the donor tissue. There were no incidences of graft dehiscence, rejection, or infection. Crescentic autograft from the host lenticule offers a simple, easy-to perform, and unique technique to manage cases of undersized donor lenticules in SALK with no additional risks.

PIRCHE-II: a new tool to predict rejection in cardiac transplantation?

Abstract Aim This retrospective observational study aims to compare patients diagnosed with antibody-mediated or cell-mediated rejection with patients without episodes of rejection and study any predictors of rejection at follow-up with particular attention to PIRCHE-II scores. Materials and Methods We performed a retrospective evaluation of prospectively collected data of heart transplant patients from January 2022 to August 2023, at a single hospital. Preoperative, intraoperative and postoperative parameters are collected anonymously in our institutional database used for internal quality control. The primary endpoint was the incidence of rejection in one of three control endomyocardial biopsies. As pre-operative data, age, sex, BSA, blood group mismatch, risk such as dyslipidemia, hypertension, diabetes, peripheral vascular disease, COPD, previous cardiac surgery, PRA, ischemia time and post-operative infections. We evaluated patients at a mean follow-up of 106 (78 – 180) days. In patients who tested positive for cell-mediated or antibody-mediated rejection, the PIRCHE-II score was calculated. Results There were 45 patients with no diagnosis of rejection and they were aged 61 [50-65]; 22.2% were women, with a mean BSA of 1.87 ± 0.19. 22.2% had a blood type mismatch. They had a mean PIRCHE-II of 111.88 ± 43.6. There were 15 patients diagnosed with rejection and they were 63 years old [52 – 66]; 20.0% were women, with a mean BSA of 1.84 ± 0.23. 13.3% had a blood type mismatch. They had a mean PIRCHE-II of 113.70 ± 33.90. In multivariable analysis, the main predictors of rejection were plasma transfusions [OR 0.053, 95% CI, p=0.02], post-operative infections [OR 0.076, 95% CI, p=&amp;lt;0, 02] and the PIRCHE – II [OR 3.284, 95% CI, p=0.04]. The mean PIRCHE-II of patients who presented antibody-mediated or cell-mediated rejection was 113.70 ± 33.90 and that of patients who did not present any rejection was 111.88 ± 33.90; Conclusion According to the results obtained, the PIRCHE-II algorithm could be a tool in immunological risk stratification in patients undergoing cardiac transplantation. It is necessary, however, to apply PIRCHE-II to a larger number of patients and should also be considered in light of other factors such as the immunological status of the recipients, the immediate post-operative course (infections, CMV reactivation, blood component transfusions), which could constitute an immunological trigger and patient compliance in immunosuppressive therapy.Patients' featuresResuts

Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2±3.7 years (ESW) and 69.2±3.4 years (SCI, p=0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p=0.01) and 3 years (34.89% vs 44.29%, p=0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p=0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p=0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p<0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

BackgroundPer-oral(PO) administration of Tacrolimus(TAC) results in inadequate trough levels in early post-operative period in liver-transplant(LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration(SL) of tacrolimus provides an alternative route in such patients. ObjectiveTo assess feasibility and safety of SL tacrolimus in adult LT-recipients in early post-operative period and to compare therapeutic efficacy of SL administration of tacrolimus vs.PO route. Patients and MethodSingle-centre, retrospective, observational study carried out in adult living donor liver transplant(LDLT) recipients between January 2022 till December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction, received tacrolimus through SL route till post-operative day(POD)5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct(D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. Feasibility and safety of SL-Tacrolimus was assessed in terms of patient acceptance, need to discontinue SL-Tacrolimus, incidence of local adverse effects and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels(TAC level) achieved and incidence of graft rejection between two groups. Results212 patients underwent LT during the study period of which 125 were included(58 in SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved higher median TAC level(ng/ml) vs.PO route(5.85 vs 5(p=0.06)) despite similar median cumulative tacrolimus dose before assessing TAC-level. 50% patients achieved TAC level ≥6ng/ml in SL-group vs. 35.8% in PO-group(p=0.14). Incidence of neurotoxicity, nephrotoxicity and graft rejection during hospital stay were similar in both the groups(p=0.56,0.82 and 0.28 respectively). ConclusionSL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as viable alternative whenever inadequate TAC-levels are anticipated through per-oral route.