Risk Factor For Graft Failure Research Articles

Encouraging the outcomes of children with beta-thalassaemia major who underwent fresh cord blood transplantation from an HLA-matched sibling donor

ABSTRACT Background Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for thalassaemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. Methods We retrospectively analyzed 68 children with beta-thalassaemia major (β-TM) who underwent fresh cord blood transplantation (F-CBT) from an HLA-matched sibling donor (MSD) between June 2010 and July 2018 in the Department of Pediatrics, Nanfang Hospital and Haematology-Oncology, Shenzhen Children’s Hospital. Results The median infused doses of total nucleated cells (TNCs) and CD34 + cells were 8.51×107/kg and 3.16×105/kg, respectively. The median time to neutrophil and platelet engraftment were, respectively, 27 and 31 days. The cumulative probabilities of acute and chronic graft-versus-host disease (GVHD) were very low after F-CBT (7.8% and 0.0%, respectively). Of the 68 paediatric patients, 67 patients survived during a median follow-up period of 61 months. The estimated 5-year probability of overall survival (OS) and disease-free survival (DFS) were 98.5% and 87.9%, respectively. Three patients experienced graft rejection (GR) (4.5%), and we identified CD34 + cell dose as a significant risk factor for graft failure (p = 0.036) in stratify analysis. Conclusions The above results indicate that patients with β-TM have excellent outcomes after F-CBT from an HLA-MSD.

An increased posterior tibial slope is associated with a higher risk of graft failure following ACL reconstruction: a systematic review.

The posterior tibial slope (PTS) is considered a risk factor for anterior cruciate ligament (ACL) injury. However, the influence of PTS on graft failure following ACL reconstruction remains relatively unknown. Therefore, this systematic review was conducted to investigate whether PTS could be a potential risk factor for graft failure after ACL reconstruction. PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, and Wanfang Database were comprehensively searched from inception to March 31, 2021. Observational studies reporting the associations of medial tibial plateau slope (MTPS) or lateral tibial plateau slope (LTPS) with graft failure after ACL reconstruction were evaluated. Twenty studies involving 12 case-control studies, 4 retrospective studies and 4 cross-sectional studies including 5326 patients met the final inclusion criteria. The high heterogeneity and the characteristics of nonrandomized controlled trials limited data synthesis. Fifteen of the 20 included studies detected a significant association between increased PTS and ACL graft failure, while 5 studies concluded that increased PTS was not associated with ACL graft failure. Ten studies suggested that MTPS is associated with ACL graft failure, and six studies suggested that LTPS is associated with ACL graft failure. The mean MTPS values for nonfailure group ranged from 3.5° ± 2.5° to 14.4° ± 2.8°. For the graft failure group, MTPS ranged from 4.71° ± 2.41° to 17.2° ± 2.2°. The mean LTPS values for nonfailure group ranged from 2.9° ± 2.1° to 11.9° ± 3.0°. For the graft failure group, LTPS ranged from 5.5° ± 3.0° to 13.3° ± 3.0°. The reported PTS values that caused ACL graft failure was greater than 7.4° to 17°. Based on the current clinical evidence, increased PTS is associated with a higher risk of ACL graft failure after ACL reconstruction. Despite various methods of measuring PTS have high reliability, there is still vast disagreement in the actual value of PTS. IV.

Outcomes of Ahmed glaucoma valve implantation and risk factors for graft failure in eyes with Descemet's stripping endothelial keratoplasty.

The aim of this study was to assess the efficacy of Ahmed glaucoma valve (AGV) in eyes with Descemet's stripping endothelial keratoplasty (DSEK) and glaucoma and evaluate the risk factors for failure. Retrospective interventional study included 27 eyes (27 subjects) that underwent AGV implantation following DSEK. The main outcome measure was AGV success, defined as IOP between 6 and 21mmHg with or without topical antiglaucoma medications (AGMs). Secondary outcome measure was graft survival. Graft failure was defined as corneal edema for ≥ 1month or irreversible graft opacity requiring intervention. Eighteen eyes (66.7%) had anterior chamber tube and 9 eyes (33.3%) had sulcus tube placement. Median follow-up was 1.2years (interquartile range, IQR, 0.5-2.5years). Following AGV implantation, the median IOP decreased significantly (p < 0.0001), median number of AGMs reduced significantly (p < 0.001) and median visual acuity was maintained (p = 0.76). Cumulative success probability of AGV was 75.8 ± 10.6% at 1year, and 75.8 ± 10.6% at 2years. For 24 clear grafts before AGV, estimates of success post-AGV were 100% at 1year, 77.8 ± 10% at 2years and 51.9 ± 16.4% at 3years. Postoperative tube intervention was a borderline significant risk factor for graft failure (p = 0.05) with hazards ratio of 7.2; however, tube location was not associated with failure. AGV can be considered an effective surgical option for IOP control in eyes with DSEK and glaucoma. However, high risk of long-term graft failure in these eyes needs to be considered specially those eyes needing tube intervention.

Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: A propensity-matched analysis.

We investigated the current trends and outcomes of diabetic patients listed for heart transplants in the U.S. and provided a method for risk-stratification. Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetics, and waitlist mortality as well as post-transplant graft survival were compared between the two groups. Further risk-stratification of diabetic patients was done based on the risk factors that independently predict graft failure. 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher in diabetic patients compared to non-diabetics (HR=1.13 (95% CI=1.04-1.22, P=.002). Over the study period, 5739 patients with diabetes were transplanted. In the propensity-matched cohorts of transplant recipients, the rate of graft failure was significantly higher for diabetic patients (23.3%) compared to non-diabetics (20.4%); HR=1.17, 95% CI=1.08-1.26, P<.001. We identified 12 risk factors of graft failure among diabetic patients and developed a risk score that further risk-stratify these patients. Diabetic patients at low risk (score≤4) had similar graft survival as patients without diabetes (HR=.91, 95% CI=.82-1.01, P=.06). On the other hand, high-risk diabetic patients had worse graft survival compared to non-diabetics (HR=1.52, 95% CI=1.38-1.67, P<.001). Among patients with end-stage heart failure, pre-existing diabetes was associated with higher waitlist mortality and worse graft survival. However, with careful patient selection, graft survival is similar to those without diabetes.

High Expression of Leucine-Rich Repeat Neuronal 2 Is the Graft Quality Marker in Living Donor Liver Transplantation

Background: A significant concern in living donor liver transplantation (LDLT) is obtaining good quality and enough size grafts while ensuring donor safety. The indicator of graft quality is not well understood. This study aimed to find a new graft quality marker other than donor age. Methods: We performed PCA analysis based on the gene expression analysis by microarray in cynomolgus macaque among the age group. Results: In PCA analysis, we could identify these macaques into one young group and two subgroups in the elder group based on the expression of 21333 genes. There were two groups in the elder group: one group showed similar gene expression to the young group and the other group showed completely different gene expression. We focused on these genes that differ between elder groups and found that 136 genes differ specially in elder groups. To find a minimum combination of clinically useful biomarkers to indicate liver aging, we performed bioinformatic analysis and found 10 significant genes. We then investigated the expressions of these genes in human donor liver tissue. The recipients who have transplanted the graft with high target gene expression had a higher incidence of graft failure. Multivariate analysis identified that high expression of Leucine-Rich Repeat Neuronal 2 (LRRN2) in donor liver tissue was one of the independent risk factors of graft failure. Conclusions: We searched for novel graft quality markers independent of age and LRRN2 expression may be a useful predictor of graft quality in LDLT.

Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation.

Background:The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort.Methods:The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis.Results:Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation.Conclusion:Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.

Surgical management of ophthalmic abnormalities in Peters plus syndrome: case report

AbstractPurposeTo report a case of a patient with Peters plus syndrome (PPS) who underwent combined synechiolysis, penetrating keratoplasty, and trabeculectomy.MethodsA four‐year‐old female with bilateral central opacified cornea was referred to our department for corneal transplantation. Slit‐lamp examination demonstrated horizontal nystagmus, bilateral central corneal opacity and iridocorneal adhesion without lenticular involvement, which is characteristic of type I Peters anomaly. Intraocular pressure was 22 mmHg in the right eye and 26 mmHg in the left eye. Posterior segment ultrasonography showed no vitreous or retinal abnormalities. General and systemic examination revealed short stature and developmental delay without any other abnormality. The diagnosis of PPS was clinically made. The patient underwent combined synechiolysis, penetrating keratoplasty, and trabeculectomy of her left eye that was more affected.ResultsSix months postoperatively, corneal graft was clear with normal depth anterior chamber and normal intraocular pressure. For the right eye, the patient was put on antiglaucomatous eye drops while waiting for corneal transplantationConclusionsGlaucoma was proven to be a significant risk factor for graft failure and rejection after penetrating keratoplasty for Peters anomaly(1). In this case, combined surgeries were performed to allow better visual outcome and intraocular pressure control.Bibliography1. Dolezal KA, Besirli CG, Mian SI, Sugar A, Moroi SE, Bohnsack BL. Glaucoma and Cornea Surgery Outcomes in Peters Anomaly. Am J Ophthalmol 2019;208: 367–375.

Comparison of long-term outcomes of trabeculectomy and risk factors for failure in eyes post penetrating keratoplasty or Descemet's stripping endothelial keratoplasty.

Purpose:To evaluate the outcomes of trabeculectomy, graft survival, and risk factors for failure in post penetrating keratoplasty (PK) and Descemet’s stripping endothelial keratoplasty (DSEK) eyes.Methods:We reviewed charts of eyes that underwent trabeculectomy for post keratoplasty glaucoma PK [25 eyes] and DSEK [14 eyes] between 1993 and 2019. The demographics, clinical features, and surgical outcomes were evaluated. Success of trabeculectomy was defined as complete when the intraocular pressure (IOP) was >5 and ≤21 mmHg without antiglaucoma medications (AGM) and qualified with AGM. Clear and compact graft was considered for graft success.Results:Median (interquartile range [IQR] preoperative IOP in post-PK eyes and post-DSEK eyes was comparable, 32 (28–38) vs. 31.5 (25–36) mmHg, P = 0.38). Median number of preoperative AGMs was comparable (P = 0.78). Median postoperative follow-up was longer in post-PK, compared with post-DSEK, 2.5 (1.3–3.3) vs. 1 (0.3–2.9) years (P = 0.05). Kaplan–Meier survival estimates for complete and qualified success of trabeculectomy at 3 years were 23.7% and 73.3%, respectively, for PK and 45.8% and 71.6%, respectively, for DSEK. Kaplan–Meier survival estimates for graft survival were 91.8% up to 3 years for PK and 100% until 2 years and 77.8% at 3 years for DSEK. Higher IOP prior to trabeculectomy was a risk factor for failure of trabeculectomy (P = 0.03) and older age was a risk factor for graft failure (P = 0.05) in PK eyes. Number of prior corneal surgeries (P = 0.05) was associated with failure of trabeculectomy and graft failure in post-DSEK eyes.Conclusion:Trabeculectomy had moderate qualified success in post-PK and DSEK eyes at 3 years. Higher pretrabeculectomy IOP and higher number of prior corneal surgeries were significantly associated with failure of trabeculectomy in PK and DSEK eyes, respectively.

Does exercise produce hypertrophy and an increase in the stiffness of hamstring tendons?

Background: Anterior Cruciate ligament (ACL) tears are the most common ligamentous injury in the knee in athletes. To return to active sporting activity, ACL reconstructions are often necessary. Hamstring tendon autografts are most commonly used in Anterior Cruciate Ligament reconstruction [3] . An important consideration during ACL reconstruction is the size of the hamstring graft. Graft sizes of less that 8mm are reported to be a significant risk factor for graft failure [4] . Therefore, one should maximize the size of the tendon graft to avoid complications of graft failure. We hypothesize that 12 weeks of resistance training can produce hamstring tendons (gracilis, semitendinosus) hypertrophy and increase their stiffness. Methods: We conducted an interventional cohort study where subjects underwent 12 weeks of hamstring resistance training. A standardised ultrasound technique was used to measure the cross sectional tendon area of the gracilis and semitendinosus tendons before and after the intervention. Tendon elastography was used to measure tendon modulus. The primary outcome measure was the tendons’ cross-sectional area and secondary outcome measure was the tendon modulus. Results: 9 participants completed the study. The median increase in crosssectional area for left Semitendinosus, right Semitendinosus, and left Gracilis was 0.02mm2 (IQR = 0.07) (p-value = 0.76), 0.01mm2 (IQR =0.03) (p-value = 0.73) and 0.01mm2 (IQR = 0.02) (p-value = 0.44) respectively. There was a mean decrease in cross-sectional area of the right gracilis of 0.01mm2 . Utilising tendon elastography with the ultrasound, the tendon modulus was measured and had increase in tendon modulus in the left and right Semitendinosus and right gracilis (-4.58 (p=0.03), -3.32 (p=0.13) and -0.03 (p=0.66) respectively). The tendon modulus had a mean decrease in the left gracilis of 0.7 (p=1). Conclusion: 12 weeks of resistance training resulted in potentially clinically significant increase in semitendinosus cross-sectional area. These findings suggest that it is possible to increase the cross-sectional area of hamstring tendons through resistance training, thus increasing their mechanical strength for better ACL reconstruction outcomes. Larger patient numbers are required to determine if statistically significant tendon hypertrophy can be achieved.

Development of a Nomogram to Predict Graft Survival After Descemet Stripping Endothelial Keratoplasty.

The purpose of this study was to analyze Descemet stripping endothelial keratoplasty (DSEK) outcomes and develop a nomogram to compute the probability of 3- and 5-year DSEK graft survival based on risk factors. The medical records of 794 DSEK procedures between January 1, 2008, and August 1, 2019, were retrospectively reviewed to identify 37 variables. We also evaluated for the presence of corneal graft failure, defined as irreversible and visually significant graft edema, haze, or scarring. Variables were assessed by multivariable Cox models, and a nomogram was created to predict the probability of 3- and 5-year graft survival. Graft failure occurred in 80 transplants (10.1%). The strongest risk factors for graft failure included graft detachment [hazard ratio (HR) = 4.46; P < 0.001], prior glaucoma surgery (HR = 3.14; P = 0.001), and glaucoma (HR = 2.23; P = 0.018). A preoperative diagnosis of Fuchs dystrophy was associated with a decreased risk of graft failure (HR = 0.47; P = 0.005) compared with secondary corneal edema. Our nomogram has a concordance index of 0.75 (95% confidence interval, 0.69 to 0.81), which indicates that it may predict the probability of graft survival at 3 and 5 years with reasonable accuracy. We also analyzed graft rejection, which occurred in 39 cases (4.9%). The single risk factor found to be significantly associated with graft rejection was prior glaucoma surgery (HR = 2.87; P = 0.008). Our nomogram may accurately predict DSEK graft survival after 3 and 5 years based on 4 variables. This nomogram will empower surgeons to share useful data with patients and improve collective clinical decision-making.

Incidence and risk factors of graft failure after pediatric hematopoietic allogeneic stem cell transplantation: A single center experience

Incidence and risk factors of graft failure after pediatric hematopoietic allogeneic stem cell transplantation: A single center experience

Outcomes of Penetrating Keratoplasty After Open Globe Injury.

The purpose of this study was to investigate the clinical features, surgical outcomes, and prognostic factors of penetrating keratoplasty (PKP) after open globe injury (OGI). A retrospective review of all patients treated for OGI between January 2000 and July 2017 was conducted. Demographic, preoperative, perioperative, and postoperative data were collected for those who underwent PKP after OGI. The predictive value of each preoperative variable on graft failure was assessed using univariate and multivariable Cox proportional hazards models, and the predictive value of variables on post-PKP visual outcome was assessed using both univariate and multivariable logistic regression models. All eyes that underwent PKP after OGI were included unless they had less than 365 days of follow-up. Forty-six eyes that underwent PKP met inclusion criteria. The median age was 46 years (interquartile range = 23.00-61.25), median follow-up was 78.5 months (interquartile range = 38.63-122.02), and 37 of 46 subjects (80.4%) were male. The observed 1- and 5-year graft survival estimates were 80.4% and 41.7%, respectively. Factors statistically associated with graft failure in multivariable analyses were rejection episode, hazard ratio (HR) = 3.29; retinal detachment (RD), HR = 3.47; and endophthalmitis, HR = 6.27. Fifteen of 42 eyes (35.7%) regained ambulatory vision (20/200 or better). The strongest predictors of vision worse than 20/200 at the last follow-up were RD, odds ratio (OR) = 43.88; graft rejection, OR = 12.42; and injury outside the workplace, OR = 25.05. Despite a high graft survival at 1 year, most of the patients did not regain ambulatory vision. Graft rejection, RD, and endophthalmitis were risk factors for graft failure. These factors should be considered when counseling patients regarding PKP after OGI.

Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients.

Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes. Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-hproteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273. CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = -0.29, P=0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.

Pure T-cell mediated rejection following kidney transplant according to response to treatment.

The focus of studies on kidney transplantation (KT) has largely shifted from T-cell mediated rejection (TCMR) to antibody-mediated rejection (ABMR). However, there are still cases of pure acute TCMR in histological reports, even after a long time following transplant. We thus evaluated the impact of pure TCMR on graft survival (GS) according to treatment response. We also performed molecular diagnosis using a molecular microscope diagnostic system on a separate group of 23 patients. A total of 63 patients were divided into non-responders (N = 22) and responders (N = 44). Non-response to rejection treatment was significantly associated with the following factors: glomerular filtration rate (GFR) at biopsy, ΔGFR, TCMR within one year, t score, and IF/TA score. We also found that non-responder vs. responder (OR = 3.31; P = 0.036) and lower GFR at biopsy (OR = 0.56; P = 0.026) were independent risk factors of graft failure. The responders had a significantly superior overall GS rate compared with the non-responders (P = 0.004). Molecular assessment showed a good correlation with histologic diagnosis in ABMR, but not in TCMR. Solitary TCMR was a significant risk factor of graft failure in patients who did not respond to rejection treatment.

Single-cell profiling reveals distinct immune phenotypes that contribute to ischaemia-reperfusion injury after steatotic liver transplantation.

ObjectivesThe discrepancy between supply and demand of organ has led to an increased utilization of steatotic liver for liver transplantation (LT). Hepatic steatosis, however, is a major risk factor for graft failure due to increased susceptibility to ischaemia‐reperfusion (I/R) injury during transplantation.Materials and methodsTo assess the plasticity and phenotype of immune cells within the microenvironment of steatotic liver graft at single‐cell level, single‐cell RNA‐sequencing (scRNA‐Seq) was carried out on 23 675 cells from transplanted rat livers. Bioinformatic analyses and multiplex immunohistochemistry were performed to assess the functional properties, transcriptional regulation, phenotypic switching and cell‐cell interactions of different cell subtypes.ResultsWe have identified 11 different cell types in transplanted livers and found that the highly complex ecosystem was shaped by myeloid‐derived cell subsets that transit between different states and interact mutually. Notably, a pro‐inflammatory phenotype of Kupffer cells (KCs) with high expression of colony‐stimulating factor 3 (CSF3) that was enriched in transplanted steatotic livers was potentially participated in fatty graft injury. We have also detected a subset of dendritic cells (DCs) with highly expressing XCR1 that was correlated with CD8+ T cells, mediating the severer steatotic liver damage by I/R injury.ConclusionsThe findings of our study provide new insight into the mechanisms by which steatosis exacerbates liver damage from I/R injury. Interventions based on these observations create opportunities in attenuating fatty liver graft injury and expanding the donor pool.

Outcomes and factors leading to graft failure in kidney transplants from deceased donors with acute kidney injury-A retrospective cohort study.

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.

Long-term Outcomes of Descemet Stripping Endothelial Keratoplasty: Ten-Year Graft Survival and Endothelial Cell Loss

To determine 10-year outcomes for graft and endothelial cell survival after Descemet stripping endothelial keratoplasty (DSEK), including risk factors for graft failure. Retrospective clinical cohort study. Three hundred fifty-six consecutive DSEK grafts performed by 10 surgeons using a standardized protocol were analyzed. Primary outcomes were cumulative graft survival and percentage endothelial cell loss (ECL) from 6 months to 10 years; secondary outcomes included risk factors for graft failure, postoperative complications, visual outcomes, and central corneal thickness. Indications include Fuchs endothelial dystrophy (n=209), bullous keratopathy (n=88), and previous graft failure (n=39). One hundred and four eyes (29%) had preoperative glaucoma. Cumulative graft survival rates of all eyes at 1, 3, 5, and 10 years were 97%, 90%, 85%, and 79%, respectively. Ten-year graft survival for Fuchs endothelial dystrophy was 92%. Mean ± SD percentage ECL of all grafts was 46.6% ± 17.3% at year 1, 54.9% ± 18.7% at year 3, 59.6% ± 17.4% at year 5, and 73.1% ± 9.7% at year 10. Cox regression identified preoperative glaucoma (hazard ratio [HR]: 8.41; 95% CI, 1.30-54.5; P=.026), including previous glaucoma surgery (HR: 3.63; 95% CI: 1.03-12.74; P=.04) and regrafts (HR: 5.29; 95% CI: 2.02-13.89; P=.001) as significant risk factors for graft failure. At 10 years, DSEK survival rate was 79% for all eyes, including complex grafts, and ECL was 73%. For Fuchs endothelial dystrophy, 10-year graft survival rate was 92%. Despite a mean 10-year endothelial cell count of only 692 cells/mm2, graft survival remained high with good vision. DSEK continues to be a viable treatment option, especially in complex eyes with comorbidity.

Comparison of Survival Outcomes After Deceased Donor Split Versus Whole Liver Transplant for Hepatocellular Carcinoma.

To mitigate waiting time forlivertransplant for hepatocellular carcinoma, partial or split liver transplant has been utilized. There was concern that regeneration of these grafts would negatively affect oncologic outcomes. We compared posttransplant graft survival between hepatocellular carcinoma whole livertransplant and partial/splitlivertransplant using Scientific Registry of Transplant Recipients data (2002-2017). The 330 partial/split liver transplant recipients were compared with a logistic regressionbased propensity score 1:1 matched whole liver transplant cohort (n = 330) and a random unmatched whole livertransplant cohort(n = 4143). Kaplan-Meier and multivariable Cox regression models evaluated the effects of partial/split and whole liver transplant on survival. Unadjusted analysis demonstrated no difference in graft survivalbetween thepartial/split and whole liver transplant cohorts (overall log-rank P = .78). After adjustments for recipient age, last laboratory Modelfor End-stage LiverDisease score, hepatitisBviral infection co-diagnosis, liver donor risk index, donor historyofdiabetes, anddonorbodymass index category were made (all P ⟨ .05), multivariable analysis demonstrated no statistically significant difference in the risk of graftfailure in thepartial/splitlivertransplant cohort compared with either the matched or random whole livertransplant cohort (both P ≥ .23). Partial/split liver transplant was not an independent risk factor for graft failure. Additional studies are needed to further elucidate differences in these populations to determine the "right" candidate for partial/split liver transplant.

Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk

High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6–12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42–5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.

Advances in corneal graft rejection.

Immune rejection after corneal transplantation is a major risk for graft failure. We aim to summarize recent advances in the understanding and management of graft rejection. Immune rejection remains the leading cause of graft failure in penetrating keratoplasty (PKP). While ABO blood type and sex match between donor and recipient may reduce rejection, human leucocyte antigens class II matching in a randomized study did not reduce the risk of rejection in high-risk PKP. Compared with PKP, deep anterior lamellar keratoplasty, descemet stripping automated endothelial keratoplasty, and descemet membrane endothelial keratoplasty have lower immune rejection rates of 1.7-13%, 5-11.4%, and 1.7-2.8%, respectively, based on long-term (5 years and more) studies. Whether immune rejection is a major risk factor for graft failure in these lamellar keratoplasties is unclear. While there have not been major advances in the systemic management of graft rejection, topical nonsteroid agents such as tacrolimus and anti-vascular endothelial growth factor have shown promise in high-risk cases. Immune rejection remains the leading cause of graft failure in PKP. Lamellar keratoplasties have significantly lower rejection rates compared with PKP. The significance of rejection in the failure of lamellar grafts warrants further investigation.