Risk Of Graft Failure Research Articles

Sequential Grafting of the Left Internal Thoracic Artery to the Left Anterior Descending Artery and Graft Failure.

There is concern that left internal thoracic artery (LITA) to diagonal to left anterior descending artery (LAD) grafts may be more susceptible to failure compared to single LITA-LAD grafts. Pooled individual patient data from eight clinical trials with systematic graft imaging were analyzed to assess the incidence of sequential LITA-Diagonal-LAD vs. single LITA-LAD grafts. Mixed-effects multivariable logistic regression, adjusting for patient characteristics and clustering within trials, was used. Of 3969 patients with LITA-LAD grafts, 283 (7.1%) patients received sequential LITA-Diagonal-LAD grafts. Patients with sequential LITA-Diagonal-LAD grafts were older (66 vs. 65 y, p=0.009) and more often male (88% vs. 83%, p=0.03). Overall, graft failure occurred in 9.3% of patients with LITA-LAD grafts, with more graft failure occurring in single (9.5%) than in sequential LITA-Diagonal-LAD grafts (6.4%, p=0.08) at a median (25th-75th percentile) time to imaging of 1.0 (1.0-1.1) years. After multivariable adjustment, sequential LITA-Diagonal-LAD grafting was not associated with graft failure (adjusted odds ratio: 1.22, 95% confidence interval: 0.68-2.18, p=0.55). There was no difference in mortality (2.8% vs. 5.3%, p=0.06), myocardial infarction (1.4% vs. 1.6%, p=0.90), revascularization (4.5% vs. 7.3%, p=0.08), or stroke (1.7% vs. 1.2%, p=0.40) between groups. In selected patients, LITA-Diagonal-LAD grafting was not associated with higher risk of graft failure or adverse clinical events at one year.

Abstract 4144521: Racial disparities in heart transplantation: long term graft survival and non-mortality outcomes

Background: There is conflicting evidence on whether racial disparities still exist in heart transplant (HT) outcomes, with prior studies focusing primarily on differences in short-term mortality. We examined disparities in HT survival over a longer follow-up duration alongside a broader range of post-HT outcomes. Methods: Using the United Network for Organ Sharing (UNOS) database, we evaluated adult HT recipients between 2017 and 2022 and classified each according to race as either Black, non-Hispanic White and Other. The primary outcome was graft survival and secondary outcomes included rejection, renal dysfunction, and post-transplant diabetes. Chi-squared tests were used to compare baseline clinical factors and selected outcomes by racial group. Kaplan-Meier and Cox proportional hazards analyses were performed to compare risks of the primary outcome by race. Results: Among 15,873 recipients (63% non-Hispanic White, 23% Black, 14% Other), Black recipients were more often female, less often college educated, and more often had public (vs. private) insurance. Blacks had higher use of durable ventricular assist devices (VAD) and intra-aortic balloon pump (IABP) at the time of HT. Graft survival at one year did not differ by race (91.8% for Blacks vs. 91.1% for non-Blacks), but at three years was significantly lower for Blacks (83.4%) than non-Blacks (85.7%). Blacks had higher risk of graft failure after adjustment for baseline socioeconomic status (SES) and clinical variables (HR 1.28, CI 1.17 - 1.41). Blacks also had significantly higher prevalences of acute rejection (12.4% vs. 10.2%), diabetes (10.8% vs. 7.1%), and progression of renal dysfunction at 3-years post HT (40.9% vs. 37.1%; p < 0.05 for all). Conclusions: Racial disparities in graft survival after HT remain in the contemporary era but are only evident after longer-term follow-up. These survival disparities could be mediated by concurrent disparities in shorter term outcomes such as development of acute rejection, chronic kidney disease, and new onset diabetes.

Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Fanconi Anemia: Results of a Single Center with a Fludarabine-Based Conditioning Regimen

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the only curative treatment for bone marrow failure (BMF) and hematologic complications of Fanconi anemia (FA). The evolution remains affected by the toxicity, the risk of graft failure, and clonal evolution. This study aimed to identify factors affecting outcomes in FA patients after allo-HSCT. We included FA patients who underwent allo-HSCT between January 2006 and December 2021. The conditioning regimen was cyclophosphamide/fludarabine (Cy/Flu) ± rabbit anti-thymocyte globulin (ATG). Bone marrow was the stem cell source from HLA-matched related donors in all transplants. Twenty-three patients, 19 with BMF and 4 with MDS/clonal evolution, were included. The median age was 11 years (5-39 years). Five patients (22%) received serotherapy with the conditioning regimen. Engraftment occurred in all patients without severe regimen-related toxicity. The 100-day cumulative incidence (CI) of grade II-IV acute GvHD (a GVHD) and 5-year CI of chronic GvHD (cGVHD) were 17% and 32%, respectively. The 5-year CI of late secondary graft failure was 10.5%. Two patients developed clonal evolution (AML; n = 2) and one patient developed nephrotic syndrome (n = 1). The 10-year overall survival (OS) and event-free survival (EFS) were 80% and 75%, respectively. There was a trend toward a better EFS in patients aged <10 years compared to patients aged ≥10 years (100% versus 61%; p = 0.06). At the last follow-up, 18 patients were alive, and 4 expired. Causes of death were infections with refractory GVHD (n = 1), graft failure (n = 2), and renal failure (n = 1). Despite the small patient population, we show excellent outcomes, particularly for those transplanted in the first decade.

Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients.

Kidney transplantation (KT) is the best kidney replacementtreatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identifyprognostic factors influencing outcomes in ADPKD. Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

Omidubicel for Hematopoietic Cell Transplants: Considerations for Patients and Treatment Outcomes.

For patients with hematologic malignancies requiring allogeneic stem cell transplantation, alternative donor sources are needed when lacking access to a matched related or unrelated donor. Umbilical cord blood (UCB) has been an important alternative allograft donor source for these patients; however, several limitations exist. Omidubicel is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from UCB. Omidubicel was approved in May 2023 by the United States Food and Drug Administration based on the results of a Phase III trial comparing it to UCB transplantation in patients with high-risk hematologic malignancies. Median time to neutrophil engraftment was faster with omidubicel compared to UCB transplantation (12 days vs 22 days; p<0.001). There was also a lower incidence of grade 2/3 bacterial or invasive fungal infections with omidubicel compared to UCB transplantation (37% vs 57%; p=0.027). From a safety perspective, omidubicel has a boxed warning due to the risk of life-threatening infusion reactions, graft-versus-host disease, graft failure, and engraftment syndrome. Omidubicel represents an important advancement in developing novel alternative allograft donor sources. This also has important implications in ensuring access to alternative donor sources for ethnic and minority populations.

MCL augmentation using a peroneus longus split tendon autograft satisfactorily restores knee stability with no impairment in foot function and with a low failure rate for concurrent ACL reconstruction.

Addressing grade 2 and 3 medial-sided instabilities during anterior cruciate ligament (ACL) reconstruction is crucial to reduce the risk of ACL graft failure. This study introduced a minimally invasive, medial collateral ligament (MCL) augmentation technique using a peroneus longus split tendon autograft, which was fixed to the femoral deep MCL insertion and tibial superficial MCL insertion. This prospective, longitudinal, single-centre case series included patients who underwent MCL augmentation concurrent with primary or revision ACL reconstruction due to anteromedial instability. Preoperatively and at 1-year follow-up, clinical examinations, such as rolimeter test of anterior tibial translation and medial instability, knee (International Knee Documentation Committee subjective knee form [IKDC], Lsyholm, Knee Injury and Osteoarthritis Outcome Score [KOOS]) and foot function scores (American Orthopaedic Foot and Ankle Society score [AOFAS]) and complications, were analyzed. Thirty-one patients with a mean follow-up of 13.5 ± 2.6 months and a mean age of 27.8 ± 9.6 years were included. The side-to-side difference for anterior tibial translation significantly improved from preoperative to 1-year follow-up with an ACL reconstruction failure rate of 6.5%. No patient retained a grade 2 or 3 medial instability on valgus stress testing with 30° flexion. Significant improvements from preoperative to 1-year postoperative follow-up were observed in knee function scores: IKDC (48.9 ± 26.9- 71.3 ± 11.5, p < 0.001) and Lysholm (59.9 ± 28.5-80.5 ± 11.2, p = 0.002) as well as KOOS pain, ADL, sport and QoL, each reaching the respective minimal clinically important difference values. The foot function score AOFAS showed no significant impairment (100 ± 0-99.3 ± 2.5, p = 0.250). Complications included cyclops lesions of ACL reconstruction in three patients. At 1-year follow-up, MCL augmentation using a peroneus longus split tendon autograft for patients simultaneously undergoing ACL reconstruction satisfactorily restores knee stability, has a low ACL reconstruction failure rate and does not significantly impair foot function. Level IV therapeutic study; case series.

Corneal Endothelial Keratoprosthesis EndoArt in Patients with Glaucoma at High Risk of Graft Failure After Keratoplasty.

The novel endothelial keratoprosthesis EndoArt improves corneal edema by reducing the inflow of aqueous humor into the cornea. We assessed the early outcome after EndoArt implantation in patients at a high risk of graft failure after keratoplasty. This retrospective study included 14 patients with high-risk eyes owing to at least one of the following risk factors for graft failure after keratoplasty: multiple previous surgeries (glaucoma surgery, keratoplasty) and recurrent intraocular inflammation because of uveitis, aniridia, or anterior synechia. After descemetorhexis, the EndoArt keratoprosthesis was placed on the posterior stroma, secured with a gas bubble and 1 to 3 transcorneal holding sutures. Best spectacle-corrected visual acuity and central corneal thickness were calculated preoperatively and postoperatively. In addition, detachment of the keratoprosthesis and the need for additional gas injections (rebubbling) were analyzed. Octafluoropropane (C3F8) 12% in 11 patients and sulfur hexafluoride 20% in 3 patients were used to attach EndoArt. Detachments requiring at least 1 rebubbling occurred in 8 eyes. Preoperative best spectacle-corrected visual acuity was 1.6 (±0.6) logarithm of the minimal angle of resolution and improved to 1.3 (±0.6) after 12 weeks. Preoperative central corneal thickness (771.8 μm ± 157) significantly decreased postoperatively in all patients (622.1 μm ± 184.7 [P = 0.025] and 562.8 μm ± 183.6 [P = 0.012] after 6 and 12 weeks, respectively). EndoArt improved visual acuity and significantly reduced corneal thickness within 3 months postoperatively, subjectively, but not statistically significantly. The rebubbling rates in this cohort with an altered anterior segment anatomy were relatively high. Patients at a high risk of graft failure may benefit from this novel endothelial keratoprosthesis.

Kidney Transplantation in Patients with Polycystic Kidney Disease: Increased Risk of Infection Does Not Compromise Graft and Patient Survival

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent &amp;gt;10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients we assessed the occurrence, frequency and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, p=0.022; 0.8±1.4 vs. 0.5±1.1 episodes, p&amp;lt;0.001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; p&amp;lt;0.001) and recipient age (RR 1.05; p=0.003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral: RR 0.60; p=0.088; bilateral: RR 0.45; p=0.020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients (HR 0.67; p=0.047) due to a lower risk of death-censored graft loss (HR 0.47; p=0.014). Donor age (HR 1.34; p=0.002) and rejection (HR 8.47; p&amp;lt;0.001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear. We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression. A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation. Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts. (Funded by OrganX. ClinicalTrials.gov number, NCT06496269.).

Evaluation of Return to Military Activities after Combining Anterior Cruciate Ligament Reconstruction with Modified Lateral Extra-articular Tenodesis Versus Anterior Cruciate Ligament Reconstruction Alone in Primary Anterior Cruciate Ligament Tear in Soldiers. A Randomized Comparative Study

Abstract Background: This study aimed to assess the clinical result, complications, failure rate, and return to resuming military duty of a single-stage anterior cruciate ligament reconstruction (ACLR) procedure utilizing quadrupled semitendinosus tendon graft joint with modified lateral extra-articular tenodesis (LET). This study evaluates the potential impact of combined modified LET with ACLR versus ACLR alone on the rate of return to high-impact military activities, which we call return to sports (RTSs), and the subsequent rate of the anterior cruciate ligament (ACL) graft failure. Materials and Methods: A total of 198 soldiers with primary ACL tears with a high-grade pivot test (grade 3) were included and randomized using the simple randomized method and divided into two groups. A consecutive cohort of military personnel with an isolated ACL tear undergoing ACLR with modified LET (group A, n = 116) and ACLR alone (group B, n = 82) were analyzed between 2016 and 2021. Both groups were followed up for a minimum of 2 years. Soldiers underwent a survey evaluating knee function (knee injury and osteoarthritis outcome score [KOOS]), RTS criteria (RTS type), symptoms (International Knee Documentation Committee [IKDC] subjective), activity level (Tegner score), and fear of movement (Tampa Scale of Kinesiophobia-11) to assess psychological readiness for sport participation. Results: Among these, a mean age of 32 ± 2.93 years underwent primary ACLR with modified LET (n = 116) or without LET (n = 82) procedure. A total of 31 soldiers (15.6%) experienced ACL graft failure, including 26 (31.7%) reconstructions without LET and 5 (4.3%) with LET. Combined with LET during primary ACLR, it lowered the risk of graft failure by 2.8 times. Multivariable analysis revealed a significant reduction in graft rupture risk (relative risk = 0.325, P = 0.029) associated with LET compared to ACLR alone after adjusting for age, anthropometric factors, and tibial slopes. 105 out of 113 (90.5%) soldiers were able to return to military duty in group A (combined ACLR with modified LET), whereas 51 of 81 (62.9%) of the soldiers who underwent ACLR alone (group B) returned to military duty (P = 0.05). Conclusion: At 24 months postoperatively, combined ACLR plus LET showed a significantly higher RTS rate than ACLR alone. The combined ACLR with the modified LET group also showed a lower failure rate than the ACLR alone group. No marked differences were observed in KOOS sub-scores, IKDCsubjective, and Tegner activity scores.

Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.

The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end-stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species-specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation-anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ-source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

Haploidentical hematopoietic stem cell transplantation for hematologic malignancies: a novel conditioning regimen with anti-T lymphocyte immunoglobulin instead of anti-thymocyte globulin for in vivo T cell depletion.

We evaluated the safety and efficacy of a novel protocol for haploidentical stem cell transplantation (haplo-SCT) in 312 patients with hematologic malignancies. The protocol evolved from the Beijing platform replacing ATG with ATLG; adding Fludarabine and removing cytarabine and Simustine. GVHD prophylaxis combined Basiliximab and low-dose cyclophosphamide post-transplant; overall, the conditioning duration was shortened. Median times to neutrophil and platelet recovery were both 11 days. Graft rejection occurred in 0.96% of patients. Cumulative incidences of grades II-IV and III-IV acute GVHD by day 200 were 35.3% and 8.9%, respectively. Probabilities of total and extensive chronic GVHD at 2 years were 40.7% and 14.7%. CMV viremia was observed in 35.6% of patients, with a 1.9% 100-day CMV pneumonia incidence and no CMV-related mortality. Cumulative incidences of non-relapse mortality at 100 days, 1 year, and 2 years were 2.9, 4.4, and 6.6%. The 4-year OS, RFS, and GRFS rates were 78.9, 70.7, and 47.3%. Older recipient age was associated with higher NRM, while positive pre-transplant MRD predicted worse OS, RFS, and higher relapse incidence. Our novel protocol for haplo-SCT is associated with low infection rates and acceptable risks of graft failure, severe GVHD, and mortality, representing a safe and effective haploidentical transplantation strategy.

Management of Multiligament Knee Injuries Using Anatomic Autograft Reconstructions: A Case Series.

While proven effective management of multiligament knee injury (MLKI) using allograft is often reported, it has shown an increased risk for graft failure compared with autograft and raises availability and cost issues. Osseous stock preservation and tunnel convergence avoidance led us to develop a compromise innovative surgical procedure using only ipsilateral autograft for anatomic reconstruction of Schenck III-L or higher MLKI. We report the description and early outcomes of our initial experience. Our strategy consisted of an anatomic single-bundle posterior cruciate ligament reconstruction with quadriceps tendon autograft and a "Versailles" reconstruction for the posterolateral corner, which we modified to reconstruct the anterolateral ligament in case of anteromedial rotatory instability, called "full lateral." A second-stage surgery was planned for anterior cruciate ligament reconstruction using a bone-patellar tendon-bone autograft. Outcomes were Lysholm, Tegner, and International Knee Documentation Committee (IKDC) scores for functional status, Short Form 12 (SF-12) for quality of life, and visual analog scale (VAS) for pain. Complications, full weight-bearing, return to work, and sport were also computed. Between March 2019 and August 2020, 10 patients were included. At follow-up, light pain was found in nine patients with a mean VAS of 1.2 ± 2.16 during the day. The mean Lysholm, Tegner, and subjective IKDC scores were good, with 61.2 ± 20.6, 2.8 ± 2.1, and 52.6 ± 20.4, respectively. However, quality of life was altered with poor SF-12 scores. In our first 10 patients with Schenck III-L or higher MLKI, our procedure using only ipsilateral autograft enabled correct daily knee functional activities while preserving osseous stock.

Delayed graft function has comparable associations with early outcomes in primary and repeat transplant among deceased-donor kidney transplant recipients.

Delayed graft function (DGF) is a common complication and is associated with worse outcomes among kidney transplant recipients (KTRs). There are various risk factors for DGF including previous transplant. We hypothesized that DGF among KTRs undergoing repeat transplant has a greater impact on outcomes compared to primary KTRs. All deceased-donor KTRs between 01/2000 and 12/2020 at our center were included. Recipients were categorized as primary KTR or repeat KTR (any number of previous kidney transplants). Outcomes of interest included acute rejection, death-censored graft failure, and patient mortality within 12months post-transplant. A total of 3137 deceased-donor KTRs were included; 2498(80%) were primary KTRs and 639(20%) were repeat KTRs. The rates of DGF were similar between the groups at 29% and 28%, respectively. Compared to KTRs without DGF, DGF was associated with a greater incidence of death and graft failure in both primary and repeat transplants; however, the risk of rejection was not significantly higher in repeat KTRs (p = 0.72). Comparing primary and repeat KTRs, there were no significant differences in either acute rejection (p-interaction = 0.11), death-censored graft failure (p-interaction = 0.38), or death (p-interaction = 0.37). In subgroup analysis among repeat KTRs with DGF, a repeat transplant with no prior DGF was associated with increased risk for death-censored graft failure and death but not for acute rejection. DGF in the prior transplant was protective against death-censored graft failure (HR: 0.07, 95% CI 0.005-0.98, p = 0.05) (p-interaction = 0.04), but this was not significantly associated with acute rejection or death. DGF is associated with similar detrimental outcomes among primary and repeat KTRs.

The effects of underlying inflammatory bowel disease on the outcomes of primary sclerosing cholangitis liver transplant recipients

IntroductionInflammatory bowel disease (IBD) influences primary sclerosing cholangitis (PSC) severity, however, the impact of IBD on PSC liver transplantation (LT) outcomes is poorly understood. We aimed to elucidate the impact of IBD in modulating PSC LT outcomes. MethodsUsing UNOS data from 2010 through 2021, we identified PSC LT candidates with and without (±) IBD. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to assess graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. ResultsOut of 5,586 PSC candidates added to the waitlist, 3,652 patients had IBD. Older age (SHR 1.01; 95 %CI 1.01–1.02) and initial MELD/PELD (SHR 1.03; 95 %CI 1.02–1.04) were associated with increased risk of waitlist mortality, while private insurance (SHR 0.00; 95 %CI 0.00–0.01) with reduced risk. PSC-IBD LT recipients had increased prevalence of cholangiocarcinoma (4.8 % vs 3.4 %, p=0.005). Longer donor cold ischemia times (HR 1.06; 95 %CI 1.03–1.09), presence of recipient diabetes (HR 1.52; 95 %CI 1.13–2.05), and employment (HR 0.75, 95 %CI 0.60–0.94) had an increased risk of graft failure among PSC patients with IBD, not seen in those without IBD. ConclusionRegardless of IBD, LT for PSC results in excellent outcomes. Certain clinicodemographic factors impacted waitlist and recipient mortality highlighting potential targets to enhance outcomes.

EndoArt®: results in patients with glaucoma drainage devices

EndoArt® (Eye Yon Medical, Ness Ziona, Israel) is anovel artificial corneal inner layer transplant and an innovative treatment alternative for patients at high risk for graft failure after posterior lamellar corneal transplantation (EK). We present the initial results of the EndoArt® implantation in patients with glaucoma drainage devices (GDD). In this study 12eyes with GDD were retrospectively evaluated. All had ahigh risk of transplant rejection in cases of EK (previous other glaucoma surgery in addition to GDD, n = 8, condition following Descemet membrane endothelial keratoplasty, DMEK, n = 9, uveitis, n = 2, or synechiae, n = 2). The EndoArt® was secured with agas bubble and one to three holding sutures. The preoperative and postoperative best spectacle-corrected visual acuity (BSCVA) and central corneal thickness (CCT) were determined. The need for additional gas injections (rebubbling) was analyzed. Octafluoropropane (C3F8) 12% was used in nine patients and sulfur hexafluoride (SF6) 20% in three patients as anterior chamber tamponade to ensure adhesion of the EndoArt®. At least one rebubbling was necessary in four eyes. The preoperative BSCVA was 1.6 (± 0.5) logMAR and significantly improved to 1.1 (± 0.6) logMAR after 12weeks (p = 0.028). The preoperative CCT was 719 µm ± 145.7, which significantly decreased to 622.4 µm ± 174.9 after six weeks (p = 0.004) and to 591.7 µm ± 190.8 after 12weeks (p = 0.096). In one eye, the prosthesis was explanted due to a suspected fibrotic remodelling of the cornea following multiple previous DMEKs. EndoArt® led to asignificant improvement in BSCVA and reduction in CCT; however, there was ahigh rebubbling rate in patients with GDD. In high-risk patients, the use of EndoArt® may be advantageous in avoiding graft failure after EK.

Graft Failure and Contralateral ACL Injuries After Primary ACL Reconstruction: An Analysis of Risk Factors Using Interpretable Machine Learning.

Anterior cruciate ligament (ACL) reconstruction (ACLR) can be successful in restoring knee stability. However, secondary ACL injury, either through graft failure or contralateral injury, is a known complication and can significantly impact the ability of a patient to return successfully to previous activities. To develop and internally validate an interpretable machine learning model to quantify the risk of graft failure and contralateral ACL injury in a longitudinal cohort treated with ACLR. Case-control study; Level of evidence, 3. An established geographic database of >600,000 patients was used to identify patients with a diagnosis of ACL rupture between 1990 and 2016 with a minimum 2-year follow-up. Medical records were reviewed for relevant patient information and 4 candidate machine learning algorithms were evaluated for prediction of graft failure and contralateral ACL injury in patients after ACLR as identified either on magnetic resonance imaging or via arthroscopy. Performance of the algorithms was assessed through discrimination, calibration, and decision curve analysis. Model interpretability was enhanced utilizing global variable importance plots and partial dependence curves. A total of 1497 patients met inclusion criteria. Among them, 140 (9.4%) had graft failure and 128 (8.6%) had a contralateral ACL injury after index surgery at a median follow-up of 140.7 months (interquartile range, 77.2-219.2 months). The best performing models achieved an area under the receiver operating characteristics curve of 0.70 for prediction of graft failure and 0.67 for prediction of contralateral ACL injury, outperforming a logistic regression fitted on the identical feature set. Notable predictors for increased risk of graft failure included younger age at injury, body mass index (BMI) <30, return to sports <13 months, initial time to surgery >75 days, utilization of allograft, femoral/tibial fixation with suspension/expansion devices, concomitant collateral ligament injury, and active or former smoking history. Predictors of contralateral ACL injury included greater preoperative pain, younger age at initial injury, BMI <30, active smoking history, initial time to surgery >75 days, history of contralateral knee arthroscopies, and involvement in contact sports. Less than 18% of all patients who undergo ACLR should be expected to sustain either a graft failure or contralateral ACL injury. Machine learning models outperformed logistic regression and identified greater preoperative pain, younger age, BMI <30, earlier return to higher activity, and time to surgical intervention >75 days as common risk factors for both graft failure as well as contralateral ACL injury after ACLR. Surgeon-modifiable risk factors for graft failure included allograft and femoral/tibial fixation with a suspension/expansion combination.

The role of anterolateral complex surgery and slope-reducing osteotomies in revision ACL reconstructions: a narrative review.

Anterior cruciate ligament reconstruction (ACLR) failures occur for various reasons including residual laxity, untreated concomitant injuries, poor graft quality, and high tibial slope. Various additional procedures can help to decrease revision ACLR failures including anterolateral complex (ALC) procedures and slope-reducing osteotomies for patients with high tibial slopes. This narrative review aims to review the literature on the roles of ALC augmentation procedures and slope-reducing osteotomies in the setting of patients undergoing revision ACLRs. A narrative review of relevant literature was performed in July 2024. Studies about anterolateral complex reconstructions and slope-reducing osteotomies in revision ACLRs were included. The literature reported that lateral extra-articular tenodesis (LET) and anterolateral ligament reconstructions (ALLR) can be used in revision ACLR cases to significantly reduce clinical knee laxity and the risk of repeated graft failure. There is not currently a strong opinion on which ALC procedure is superior. There are reported slight differences in lateral knee pain and knee stiffness, but both similarly significantly improve clinical and functional outcomes. In revision ACLR cases that also have a high posterior tibial slope (PTS), a slope-reducing tibial osteotomy is warranted. An anterior closing wedge proximal tibial osteotomy (ACW-PTO) significantly reduces anterior tibial translation and graft failure. There is concern about the changes to patellar height, but the literature has found that such changes are either slight or absent by 6 months postoperatively. The risk of ACLR failure is increased by risk factors like high tibial slope, preoperative knee laxity, and prior ACLR rupture. Anterolateral complex procedures and slope-reducing osteotomies may be used to address these specific concerns and reduce the risk of graft rupture. For revision ACLR cases with lower PTS, augmentation with a LET or an ALLR to reduce the risk of graft failure and improve rotational stability may be warranted. In the setting of a revision ACLR in patients with a high PTS of ≥12°, a concomitant ACW-PTO and ALC procedure should be considered to decrease the risk of an ACLR graft failure.

Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning.

Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5mg/dL. Significant cluster characteristics were determined, and outcomes were compared. The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.

Association of early steroid withdrawal with kidney transplant outcomes in first-transplant and retransplant recipients.

Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR=1.04 [95% CI=1.00-1.09]), slightly higher hazard of graft failure (HR=1.09 [95% CI=1.05-1.12]), and slightly lower mortality (HR=0.93 [95% CI=0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR=1.42 [95% CI=1.29-1.57]; interaction p<0.001) and graft failure (HR=1.24 [95% CI=1.14-1.34]; interaction p=0.003), and similar mortality (HR=1.01 [95% CI=0.94-1.08]; interaction p=0.04). In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.