Machine Learning Analysis of Postkeratoplasty Endothelial Cell Images for the Prediction of Future Graft Rejection.

Purpose: This study developed machine learning (ML) classifiers of postoperative corneal endothelial cell images to identify postkeratoplasty patients at risk for allograft rejection within 1 to 24 months of treatment. Methods: Central corneal endothelium specular microscopic images were obtained from 44 patients after Descemet membrane endothelial keratoplasty (DMEK), half of whom had experienced graft rejection. After deep learning segmentation of images from all patients' last and second-to-last imaging, time points prior to rejection were analyzed (175 and 168, respectively), and 432 quantitative features were extracted assessing cellular spatial arrangements and cell intensity values. Random forest (RF) and logistic regression (LR) models were trained on novel-to-this-application features from single time points, delta-radiomics, and traditional morphometrics (endothelial cell density, coefficient of variation, hexagonality) via 10 iterations of threefold cross-validation. Final assessments were evaluated on a held-out test set. Results: ML classifiers trained on novel-to-this-application features outperformed those trained on traditional morphometrics for predicting future graft rejection. RF and LR models predicted post-DMEK patients' allograft rejection in the held-out test set with >0.80 accuracy. RF models trained on novel features from second-to-last time points and delta-radiomics predicted post-DMEK patients' rejection with >0.70 accuracy. Cell-graph spatial arrangement, intensity, and shape features were most indicative of graft rejection. Conclusions: ML classifiers successfully predicted future graft rejections 1 to 24 months prior to clinically apparent rejection. This technology could aid clinicians to identify patients at risk for graft rejection and guide treatment plans accordingly. Translational Relevance: Our software applies ML techniques to clinical images and enhances patient care by detecting preclinical keratoplasty rejection.

Establishing a Biomarker for the Prediction of Short-Term Graft Detachment After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to investigate the predictive value of pachymetry mapping 1 day after Descemet membrane endothelial keratoplasty (DMEK) as a biomarker for early graft detachment. METHODS: This was a post hoc analysis of 65 pseudophakic subjects with Fuchs endothelial dystrophy who underwent DMEK surgery between December 2018 and April 2021 as part of the Advanced Visualization In Corneal Surgery Evaluation international multicenter randomized controlled trial. One eye per patient was included. Preoperatively and 1 day postoperatively, patients underwent anterior segment optical coherence tomography imaging. Using a grid consisting of 25 zones (ie, pachymetry map), corneal thickness and presence of a graft detachment were mapped for each patient. Detachments of any size were considered, regardless of subsequent clinical interventions. Missing data were imputed and subsequently divided into a training and test set. Two prediction methods were evaluated: one model based on absolute corneal thickness and a regression model. RESULTS: A total of 65 eyes were included for analysis of which 33 developed any form of graft detachment. Preoperatively, no significant differences were observed between the groups ( P = 0.221). Corneal thickness in the corneal zones with a detached graft was significantly increased compared with corneal zones with an attached graft ( P < 0.001). The regression prediction model had an area under the curve of 0.87 (sensitivity: 0.79 and specificity: 0.75), whereas the absolute thickness cutoff model only reached 0.65. CONCLUSIONS: Pachymetry mapping 1 day after DMEK was predictive for early graft detachment, and the prediction model had a good to excellent performance. This aids in identifying patients at risk for graft detachment and subsequent tailored postoperative care.

Penetrating Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty in Children With Congenital Hereditary Endothelial Dystrophy: Long-Term Results.

PURPOSE: The purpose of this study was to compare the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PKP) in patients with congenital hereditary endothelial dystrophy (CHED). METHODS: This was a retrospective, comparative study of all the patients with a histopathological diagnosis of CHED who underwent PKP or DSAEK between January 1, 1990, and December 31, 2016. All the cases were included except those patients who had clear grafts but did not complete 2 years of postoperative follow-up. The main outcome measure was graft clarity 2 years after surgery. RESULTS: There were 111 eyes of 63 patients. Seventy-six eyes underwent PKP, and 35 eyes underwent DSAEK. The median age at surgery was 6.8 years in the PKP group and 10.32 years in the DSAEK group. At 2 years postoperatively, clear grafts were noted in 66 of 76 (86.8%) eyes in the PKP group and 30 of 35 (85.7%) eyes in the DSAEK group. At the last follow-up, 80.3% of PKP grafts and 82.8% of DSAEK grafts were clear ( P =0.5). The type and timing of complications differed between the 2 groups. The PKP group had a statistically significant higher rate of graft rejection (19.5%) versus the DSAEK group (0%) ( P =0.01). DSAEK complications were mainly lenticule detachment that developed within one month postoperatively. There was no statistically significant difference in the visual outcomes at the last follow-up between the groups. CONCLUSION: Endothelial keratoplasty is a safe alternative to conventional PKP in CHED. The visual outcome and survival rates were comparable, but DSAEK had a lower rejection rate and fewer suture-related complications.

Risk factors of rejection after penetrating keratoplasty: a retrospective monocentric study.

PURPOSE: To assess risk factors of rejection after penetrating keratoplasty (PKP). METHODS: This retrospective monocentric study assessed risk factors for rejection in patients who underwent PKP at Montpellier University Hospital between June 2005 and September 2018. Graft and donor data were obtained from our tissue bank in Montpellier. Clinical data of recipients were recorded from medical files. Survival was estimated by the Kaplan-Meir method. Potential risk factors of rejection were assessed by multivariate Cox proportional hazards analysis, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Among the 316 consecutive patients (59% male, mean SD] age 52 [17]), 360 eyes underwent PKP. Indications for PKP were bullous keratopathy (27%), infectious keratitis (20%), and keratoconus (15%). The median follow-up was 44 months (IQR 22-73). The overall graft survival and irreversible rejection rate at 5 years were 70% and 29%, respectively. Factors associated with risk of rejection were prior indication for graft rejection (SHR [CI 95%] = 7.8 [2.6-23.1]), trauma (SHR [CI 95%] = 3.6 [1.1-11.7]), and infectious keratitis (SHR [CI 95%] = 2.7 [1.2-11.1]), history of corneal neovascularization (SHR [CI 95%] = 2.1 [1.2-3.8]), hypertonia (SHR [CI 95%] = 2.8 [1.8-4.3]), and mixed sex matching (SHR [CI 95%] = 2.0 [1.01-4.0]). CONCLUSION: The significant risk factors of graft rejection after PKP found in this study agree with those from major international cohorts: prior indication for graft rejection, history of neovascularization and high intraocular pressure. Sex matching donor-recipient is a most recent parameter in the literature confirmed by the present analysis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04791696.

Lung Retransplantation.

Lung retransplantation remains the standard treatment of irreversible lung allograft failure. The most common indications for lung retransplantation are acute graft failure, chronic lung allograft dysfunction, and postoperative airway complications. Careful patient selection with regards to indications, anatomy, extrapulmonary organ dysfunction (specifically renal dysfunction), and immunologic consideration are of utmost importance. The conduct of the lung retransplantation operation is arduous with special considerations given to operative approach, type of surgery (single vs bilateral), use of extracorporeal circulatory support, and hematological management. Outcomes have improved significantly for most patients, nearing short and midterm outcomes of primary lung recipients in select cases.

'Posture-Less' DMEK: Is Posturing After Descemet Membrane Endothelial Keratoplasty Actually Necessary?

PURPOSE: To evaluate the clinical results of Descemet membrane endothelial keratoplasty (DMEK) without any intraoperative or postoperative posturing. DESIGN: Retrospective, noncomparative, and interventional case series. METHODS: One hundred thirty-four (134) consecutive eyes of 101 patients requiring DMEK for any cause of endothelial failure were included. Descemet membrane endothelial keratoplasty was performed with an intraoperative inferior PI. After unscrolling and centration of the graft, the anterior chamber was near completely filled with 20% SF6. After filling the eye with gas there was no intraoperative tamponade time, and patients did not posture postoperatively. Main outcome measures were: graft detachment rate, rebubbling rate, primary and secondary failure rates, rejection rate, intraoperative and postoperative complications, and visual acuity 3 and 12 months after surgery. RESULTS: Five of 134 (3.7%) developed graft detachment greater than one-third of the graft area, and 19 of 134 (14.2%) developed graft detachment less than one-third of the graft area. A rebubble procedure was performed in 19 of 134 (14.2%); of those, the average number of rebubbling procedures performed was 1.13 (range, 1-2). Primary failure occurred in 6 of 134 (4.5%).Twelve-month graft survival occurred in 122 of 134 eyes (91.0%), with secondary failure within the first 12 months accounting for failure of 6 of 134 (4.5%). Nine of 134 (6.7%) cases had a recorded episode of endothelial rejection. The average time for rejection episode was 9.5 months (range, 1-20 months) after surgery. CONCLUSIONS: A total of 134 'posture-less' DMEKs did not suffer very high rates of graft detachment, rebubbling, or other postoperative complications, even with immediate erect posturing after surgery.

Outcomes after heart retransplantation: A 50-year single-center experience.

OBJECTIVES: To evaluate outcomes after heart retransplantation. METHODS: From January 6, 1968, to June 2019, 123 patients (112 adult and 11 pediatric patients) underwent heart retransplantation, and 2092 received primary transplantation at our institution. Propensity-score matching was used to account for baseline differences between the retransplantation and the primary transplantation-only groups. Kaplan-Meier survival analyses were performed. The primary end point was all-cause mortality, and secondary end points were postoperative complications. RESULTS: Retransplantation recipient age was 39.6 ± 16.4 years, and donor age was 26.4 ± 11.2 years. Ninety-two recipients (74.8%) were male. Compared with recipients who only underwent primary heart transplantation, retransplantation recipients were more likely to have hypertension (44/73.3% vs 774/53.3%, P = .0022), hyperlipidemia (40/66.7% vs 447/30.7%, P < .0001), and require dialysis (7/11.7% vs 42/2.9%, P = .0025). The indications for heart retransplantation were cardiac allograft vasculopathy (32/80%), primary graft dysfunction (6/15%), and refractory acute rejection (2/5%). After matching, postoperative outcomes such as hospital length of stay, severe primary graft dysfunction requiring intra-aortic balloon pump or extracorporeal membrane oxygenation, cerebral vascular accident, respiratory failure, renal failure requiring dialysis, and infection were similar between the 2 groups. Matched median survival after retransplantation was 4.6 years compared with 6.5 years after primary heart transplantation (log-rank P = .36, stratified log-rank P = .0063). CONCLUSIONS: In this single-center cohort, the unadjusted long-term survival after heart retransplantation was inferior to that after primary heart transplantation, and short-term survival difference persisted after propensity-score matching. Heart retransplantation should be considered for select patients for optimal donor organ usage.

Acute Corneal Transplant Rejection After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccination.

PURPOSE: The purpose of this article was to report a case of full-thickness corneal transplant rejection 3 days after immunization with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Moderna mRNA-1273 vaccine. METHODS: Case Report. RESULTS: A 51-year-old man with a history of keratoconus and penetrating keratoplasty underwent repeat penetrating keratoplasty for graft failure. The patient had an uncomplicated intraoperative and postoperative course with improved vision and a healthy graft. The patient received the SARS-CoV-2 Moderna vaccine on postoperative week 3, and within 3 days, the patient began developing eye pain, photophobia, and blurred vision. The patient was found to have graft rejection with corneal edema and endothelial keratic precipitates. The rejection did not improve despite a trial of increased topical steroids and ultimately evolved into graft failure. CONCLUSIONS: To the best of our knowledge, this case of full-thickness graft rejection after the Moderna SARS-CoV-2 mRNA vaccination is the first to be reported worldwide. The temporal relationship between vaccination and subsequent rejection is highly suggestive of causation due to the short interval (3 days) between vaccination and rejection and the lack of other inciting factors in an otherwise healthy graft. Patients with corneal transplants who plan to take the COVID-19 vaccinations should be counseled on symptoms and closely monitored, and an individualized plan should be made in discussion with the ophthalmologist.

Lymphatic Trafficking in the Eye: Modulation of Lymphatic Trafficking to Promote Corneal Transplant Survival.

(Lymph)angiogenesis into the cornea prior to and after corneal transplantation is a critical risk factor for allograft rejection. Lymphatic vessels even more than blood vessels seem important in mediating immune responses, as they facilitate allograft sensitization in the draining lymph nodes. Thus, the concept of modulating lymphatic trafficking to promote corneal graft survival seems promising. A variety of approaches has been developed to inhibit progressive lymphangiogenesis in experimental settings. Recently, additionally to pharmacological approaches, clinically available techniques such as UVA-based corneal collagen crosslinking and fine needle diathermy were reported to be effective in regressing lymphatic vessels and to experimentally promote graft survival. Clinical pilot studies also suggest the efficacy of blocking antigen presenting cell trafficking to regional lymph nodes by regressing corneal lymphatic vessels to enhance allograft survival in high-risk eyes. In this article, we will give an overview of current strategies to modulate lymphatic trafficking with a special focus on recently reported strategies, which may be easy to translate into clinical practice. This novel concept of temporary, pretransplant regression of lymphatic vessels at the site of transplantation to promote subsequent corneal transplant survival ("lymphangioregressive preconditioning") may also be applicable to other transplantation sites later.

Re-transplantation in pediatric patients with failure of primary transplant due to recurrent focal segmental glomerulosclerosis: A pediatric nephrology research consortium study.

INTRODUCTION: Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns. METHODS: Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium. RESULTS: Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers. CONCLUSIONS: Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.

Rapid re-transplantation safety following early kidney graft loss.

INTRODUCTION: Early graft loss is a devastating kidney transplant complication associated with high mortality and an increased risk of sensitization to antigens from the failed graft. Moreover, if rapid re-transplantation were to occur, given that the human leukocyte antigen antibodies identification may not be reliable until several weeks after transplantation, the recipient's immunological status would be uncertain. Hence, there could be an increased immunological risk. To date, there is no information on whether a rapid re-transplantation after early graft loss, without a new reliable anti-HLA determination, is safe. METHODS: We retrospectively analysed the number of rejections and the graft survival of re-transplanted patients with early graft loss (defined as graft failure before 30 days from transplant) from our centre between June 2003 and November 2019. The studied population was divided into rapid re-transplantation (performed within 30 days of early graft loss) and late re-transplantation (performed beyond those 30 days). RESULTS: Forty-seven patients were re-transplanted after early graft loss. There were nine rapid re-transplantation cases with an 89% five-year graft survival and one antibody-mediated rejection episode. Furthermore, we identified 38 cases of late re-transplantation with a 69% five-year graft survival, 4 T cell-mediated, and 11 antibody-mediated rejections. CONCLUSIONS: Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor does it impact long-term graft survival when compared to late re-transplantation.

African American Pediatric Liver Transplant Recipients Have an Increased Risk of Death After Transferring to Adult Healthcare.

OBJECTIVE: To analyze the long-term outcomes in pediatric liver transplant recipients after they have transferred to an adult provider and assess for racial disparities in health outcomes. STUDY DESIGN: This is a single-center, retrospective review of pediatric patients who underwent liver transplantation between July 1990 and August 2015 at a tertiary healthcare system with a large transplant center. Patient mortality and retransplantation were assessed after transfer to adult care. RESULTS: There were 120 patients who were transferred, of whom 19 did not meet the inclusion criteria. Of the remaining 101 patients, 64 (63%) transferred care to a nearby affiliated tertiary adult facility, 29 (29%) were followed by other healthcare systems, and 8 (8%) were lost to follow-up. Of the patients followed at our affiliated adult center, 18 of the 64 (28%) died. Of those 18 deaths, 4 (22%) occurred within the first 2 years after transfer, and 10 (55%) within 5 years of transfer. Four patients were retransplanted by an adult provider, of whom 2 eventually received a third transplant. African Americans had higher rates of death after transfer than patients of other races (44% mortality vs 16%, representing 67% of all cases of death; P = .032), with nearly 50% mortality at 20 years from time of transplantation. CONCLUSIONS: Death is common in pediatric liver transplant recipients after transfer to adult care, with African Americans having disproportionately higher mortality. This period of transition of care is a vulnerable time, and measures must be taken to ensure the safe transfer of young adults with chronic health care needs.

The Cologne rebubbling study: a reappraisal of 624 rebubblings after Descemet membrane endothelial keratoplasty.

BACKGROUND/AIMS: To analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye. METHODS: In this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK. RESULTS: Mean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 µm. Mean axial diameter was 382.53±282.02 µm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 µm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000). CONCLUSIONS: The overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.

Renal artery embolization of non-functioning graft: an effective treatment for graft intolerance syndrome.

BACKGROUND: Percutaneous renal artery embolization is a valid non-invasive technique alternative to nephrectomy for patients with symptomatic non-functioning allograft (graft intolerance syndrome-GIS). The purpose of this article is to report the experience of our centre. METHODS: We analysed retrospectively 15 patients with symptomatic non-functioning renal allograft treated with percutaneous embolization from 2003 to 2017. Occlusion was obtained with the injection of calibrated microspheres of increasing size (from 100 to 900 µm) and completed with 5 to 8 mm metal coils placement in the renal artery. RESULTS: Technical success was achieved in all cases at the end of the procedure. Clinical success was obtained in 11 patients (73%). In four cases, nephrectomy was necessary: in one case because of septic fever and in three cases because of GIS persistence. In one case, it was possible to perform another procedure to embolize a perirenal collateral from a lumbar artery. Four patients (27%) reported minor complications which spontaneously resolved during the hospital stay. CONCLUSIONS: According to the scientific literature, we believe that, in selected patients, percutaneous renal artery embolization is a valid treatment option for GIS thanks to its efficacy, repeatability, minimal invasiveness and the absence of severe complications.

Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy.

INTRODUCTION: Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT: We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION: As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.

Acute Benign Paroxysmal Positional Vertigo After Endothelial Keratoplasty-A Unique Cause of Postoperative Nausea and Headache.

PURPOSE: To describe a case of new-onset benign paroxysmal positional vertigo (BPPV) after uncomplicated Descemet stripping automated endothelial keratoplasty. METHODS: Case report and review of literature. RESULTS: A 61-year-old woman with a history of steroid-induced glaucoma and penetrating keratoplasty for Fuchs endothelial dystrophy, and no history of BPPV or other vertigo, underwent Descemet stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure. On the third postoperative day, she developed acute spinning vertigo, nausea, and headache on sitting up after 3 days of strict supine positioning. Her ophthalmic examination was benign, with no evidence of a pupillary block, and she was diagnosed by an otologist with BPPV. Her symptoms resolved after 1 week without further intervention. CONCLUSIONS: BPPV is a benign but rare complication of nonotologic surgery and has not been previously reported with ophthalmic surgery. The overlap in symptomatology between BPPV and other serious and potentially vision-threatening causes of postoperative nausea and headache, such as pupillary block glaucoma, makes this a relevant etiology to consider in the spectrum of postendothelial keratoplasty complications.

Impact of Re-bubbling after Descemet Membrane Endothelial Keratoplasty on Long-term Results.

Purpose/Aim of the study: Graft detachment after DMEK can be treated easily with an additional air injection - re-bubbling. The aim of our study was to investigate the effect of a re-bubbling on the postoperative outcome.Materials and Methods: In this retrospective, comparative, cohort study we included eyes from patients that underwent DMEK surgery. A graft detachment was diagnosed by slit-lamp examination and OCT scan. All eyes were divided into three groups: no re-bubbling, one re-bubbling, more than one re-bubbling. We analyzed the visual acuity, endothelial cell density and rate of graft failure.Results: In 163 of 463 eyes (35.2%) a re-bubbling was performed (119 eyes 1 re-bubbling, 44 eyes more than one re-bubbling). Visual acuity improved significantly in all groups. After controlling for donor age, reason for surgery, time of cultivation of the graft and preoperative visual acuity, no difference in the visual acuity was seen at any point of follow-up. All patients showed a significant reduction in endothelial cell density 1 month after DMEK. Controlling for donor age, reason for surgery, type of surgery (DMEK-only or DMEK combined with cataract surgery) and the time of cultivation of the graft, the difference in endothelial cell density at 1 month post-surgery between no re-bubbling and one re-bubbling was 157 cells/mm2 (95% CI 2-310, p = .047) and between no re-bubbling and more than one re-bubbling 504 cells/mm2 (95% CI 267 - 741, p < .001). The difference in endothelial cell density remained over the course of follow-up. Twenty patients (4.3%) developed a graft failure during postoperative follow-up. Controlling for donor age, reason for surgery and the time of cultivation of the graft, we did not find any difference in the risk of graft failure between re-bubbling categories.Conclusions: Re-bubbling increased the risk for an endothelial cell loss, but did not influence the postoperative visual acuity and the rate of graft failure.

The impact of HLA-DR mismatch status on retransplant-free survival and bronchiolitis obliterans syndrome‒free survival among sensitized lung transplant recipients.

INTRODUCTION: Donor‒recipient HLA-DR locus matching may be protective against bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. It is unknown whether this benefit is more significant among sensitized (calculated panel reactive antibodies (CPRAs) of >0%) and highly sensitized (CPRAs of ≥80%) recipients who may be at a higher risk for BOS. METHODS: This was a retrospective cohort study of adults in the Scientific Registry of Transplant Recipients who underwent lung transplantation between May 5, 2005 and May 31, 2019. Retransplant-free survival and BOS-free survival were compared among recipients with 0 vs ≥1 DR mismatches, grouped according to sensitization. RESULTS: Among all 20,355 included recipients, 0 DR mismatch status was associated with improved retransplant-free survival (hazard ratio [HR] = 0.83, 95% CI = 0.74-0.93, p = 0.002) and BOS-free survival (HR = 0.86, 95% CI = 0.77-0.96, p = 0.007). Among sensitized recipients, 0 DR mismatch status was also associated with improved retransplant-free survival (HR = 0.79, 95% CI = 0.65-0.97, p = 0.02) and BOS-free survival (HR = 0.82, 95% CI = 0.67-1.00, p = 0.04). There was however no difference in retransplant-free or BOS-free survival between sensitized and non-sensitized recipients with 0 DR mismatches. Among highly sensitized recipients, 0 DR mismatch status was not associated with retransplant-free or BOS-free survival. Among sensitized and highly sensitized recipients, 0 DR mismatch status was not associated with reduced use of plasmapheresis or reduced biopsy-proven, treated acute cellular rejection compared with non-sensitized recipients. CONCLUSIONS: HLA-DR matching is associated with a similar improvement in retransplant-free and BOS-free survival among non-sensitized and sensitized lung transplant recipients. DR matching does not confer a more substantial retransplant-free or BOS-free survival benefit to highly sensitized recipients than to non-sensitized recipients.

Pediatric retransplantation of the liver: A prognostic scoring tool.

Few prognostic models have been created in children that receive liver retransplantation (rLT). We examined the SRTR database of 731 children that underwent second liver transplant between 2002 and 2018. Proportional hazards models using backward variable selection were used to identify recipient, donor, and surgical characteristics associated with survival. A simple prognostic scoring system or nomogram (ie, each risk factor was weighted on a five-point scale) was constructed based on the fitted model. Recipient age (P < .001), MELD/PELD (P < .001), recipient ventilated (P = .003), donor cause of death (P = .024), graft type (P = .045), first graft loss due to biliary tract complications (P = .048), and survival time of the first graft (P = .006) were significant predictors of retransplant survival. The bias-corrected Harrell's C-index for the multivariable model was 0.63. Survival was significantly different (P < .001) for those at low risk (0-4 points), medium risk (5-7 points), and high risk (8+ points). Survival was equivalent between low risk pediatric second transplant recipients and pediatric primary liver transplant recipients (P = .67) but significantly worse for medium- (P < .001) and high-risk (P < .001) recipients. With simple clinical characteristics, this scoring tool can modestly discriminate between those children at high risk and those children at low risk of poor outcomes after second liver transplant.