Higher Graft Survival Research Articles

Acute Liver Failure Etiology Determines Long-Term Outcomes in Patients Undergoing Liver Transplantation: An Analysis of the UNOS Database

Background: Acute liver failure (ALF) involves rapid liver injury, often leading to multi-organ failure. Liver transplantation (LT) has improved survival rates, with U.S. rates reaching 92%. This study analyzes UNOS data (2002–2020) to evaluate long-term survival and identify risk factors affecting waitlist and post-LT outcomes in ALF patients. Methods: A retrospective analysis was performed on adult ALF patients waitlisted for LT (Status 1/1A). ALF etiologies, including viral infections, drug-induced liver injury (DILI), acetaminophen (APAP) overdose, autoimmune hepatitis (AIH), Wilson disease (WD), and unknown causes, were assessed with patient and donor characteristics. Kaplan–Meier and Cox regression analyses identified predictors of patient and graft survival. Sensitivity analysis confirmed the model’s robustness. Results: We identified 2759 ALF patients. APAP (HR 1.7; p < 0.001) and unknown etiology (HR 1.3; p = 0.037) were linked to higher waitlist removal risk, while WD (HR 0.36; p < 0.001) increased LT probability. Among 2014 LT recipients, WD showed improved survival (HR 0.53; p = 0.002). Black/African American race (HR 1.47; p < 0.001), diabetes (HR 1.81; p < 0.001), and encephalopathy (HR 1.27; p < 0.001) predicted higher mortality. AIH had the lowest 1- and 10-year survival (83% and 62%), while APAP had the lowest 5-year survival (76%). WD had the highest graft survival at 1, 5, and 10 years (93%, 88%, and 80%). Conclusions: ALF etiology significantly affects survival outcomes. AIH and APAP are associated with worse survival, while WD shows favorable outcomes. Tailored post-LT management is essential to improve survival in ALF patients.

Hepatic artery stenosis after pediatric liver transplantation: The potential role of conservative management

AimThis study aimed to investigate the outcomes and effectiveness of various treatment strategies in patients with hepatic artery stenosis (HAS) after pediatric liver transplantation (pLT). MethodsThis is a single center observational cohort study between January 1st, 2004 and August 1st, 2023, including pLT recipients aged <18 years. The primary outcome was graft and patient survival. The secondary outcomes included incidence of biliary complications, technical success of surgery or endovascular therapy (EVT), and changes in liver function. The cut-off for early and late HAS was 14 days after pLT. ResultsAmong a total of 327 pLT patients, 4 % (n = 13) developed HAS (n = 3 early; n = 10 late). Treatments included surgical revascularization for one early HAS, conservative management with anticoagulation for one early and four late HAS, and EVT for one early and six late HAS. Over a median follow-up of 28.2 months after the diagnosis of HAS, graft survival was 100 % and 83 % in early and late HAS groups, and patient survival reached 100 % in both groups. One graft loss occurred in the conservative group. Conversely, graft survival in the EVT group was 100 %. ConclusionThe long-term outcomes of HAS after pLT are excellent. Both EVT and conservative management exhibited high graft survival rates for late HAS, with EVT achieving high technical success.

Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation.

Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-GEV) levels could predict chronic lung allograft dysfunction (CLAD) development. We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-GEV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-GEV plasma levels. In patients with subsequent BOS, (1) HLA-GEV levels at M12 were significantly lower than those in STA patients (P = 0.013) and (2) also significantly lower than their previous levels at M6 (P = 0.04).A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-GEV plasma levels at M12 (high versus low HLA-GEVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-GEV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y (P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]). This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.

Organ Utilization From Donors Following Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review of Graft and Recipient Outcome.

The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR. We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024. From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%). Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Organ Donation from Patients Receiving Extracorporeal Membrane Oxygenation: A Systematic Review

The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors. Systematic literature review (Scopus and PubMed, up to October 11, 2023). All study designs. Organ recipients from patients on ECMO at the time of death. Outcome of organ donation from ECMO donors. The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years. Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage.

879 The Review of Autologous Fat Grafting Utilizing Negative Pressure for Breast Augmentation

Abstract Aim There may be a role for topical negative pressure in autologous fat grafting to breasts since it enhances angiogenesis during wound healing for open and closed wound. Here, we present a review of the literature on this topic. Method Medline and Embase were utilised, with searches ranging between 1960 – 2019. Terms (“Liposculpting” OR “Fat grafting” OR “Lipofilling” OR “Lipograft” OR “Fat transfer”) AND (“Negative Pressure” OR “Brava” OR “Kiwi”) AND (“Breast”) were merged as keywords. Inclusion criteria were females, autologous fat graft to breast with negative pressure prior to procedure. Studies were excluded if there was no primary endpoint or non-original article. Primary outcome measured was fat graft survival post breast augmentation with post-operative morbidity as a secondary outcome. Results Upon reviewing 219 articles, 2 met inclusion criteria. A total of 611 breasts were treated using negative pressure devices, with each cohort having different pre- and post-operative pressure settings. Khouri et al. cohort had higher graft survival (79%) compared to Del Vecchio et al. cohort (64%), however the latter had fewer complications compared to Khouri’s cohort e.g. fat necrosis, pneumothorax and infection. Conclusions There is still limited evidence regarding the use of topical negative pressure for fat grafting to the breasts. Autologus fat grafting to breasts without the use of negative pressure is shown to have graft survival of 60-70%. Given its potential benefits, more future studies are needed to fully understand the impact of this technique.

A Practical Guide to Hair Graft Placement Using the Sharp Implanter Method.

Hair transplantation using the sharp implanter method is increasing in popularity. However, there has been little discussion pertaining to surgical know-how or specific techniques that increase efficiency and precision. We describe surgical techniques that enable dense packing in a swift and efficient fashion with the sharp implanter method using photos and videos. Grafts were placed using the sharp implanter method while adhering to several important principles. Eleven principles regarding the following aspects of hair transplant surgery were explained: gripping the implanter, graft placing technique that minimizes graft popping and tissue trauma when using the implanter, efficient team surgery system with assistant staff, direction and sequence of graft insertion, effective regimen for using epinephrine to control bleeding, selection of appropriately sized implanter tip, selection and usage of wide and narrow channel implanter tips, importance and methods of depth control, and staff training. High graft survival and dense and natural hair density can be obtained with the sharp implanter method when performed in compliance with the principles described here. Appropriate use of the sharp implanter technique allows efficient and rapid graft insertion and achieves natural outcomes.

Cultivation and Transplantation of Three-Dimensional Skins with Laser-Processed Biodegradable Membranes.

For the treatment of irreversible, extensive skin damage, artificial skins or cultured skins are useful when allogeneic skins are unavailable. However, most of them lack vasculature, causing delayed perfusion and hence delay or failure in engraftment of the tissues. We previously developed a prevascularized three-dimensional (3D) cultured skin based on the layer-by-layer cell coating technique (LbL-3D skin), in which cells are seeded and laminated on a porous polymer membrane for medium supply to the thick cultured tissue. Recent animal studies have demonstrated that LbL-3D skin can achieve rapid perfusion and high graft survival after transplantation. However, there were practical issues with separating LbL-3D skins from the membranes before transplantation and the handling separated LbL-3D skins for transplantation. To address these problems, in this study, we examined the use of biodegradable porous polymer membranes that enabled the transplantation of LbL-3D skins together with the membranes, which could be decomposed after transplantation. Thin films made from poly (lactic-co-glycolic acid) (PLGA) were irradiated with femtosecond laser pulses to create micro through-holes, producing porous membranes. We designed and fabricated culture inserts with the PLGA membranes and cultivated LbL-3D skins with 2 × 106 neonatal normal human dermal fibroblasts and 1 × 104 human umbilical vein endothelial cells in the dermis of 20 cell layers and 1 × 105 neonatal human epidermal keratinocytes in the epidermis. Histological analyses revealed that the skins cultured on the PLGA membranes had thickness of about 400 μm and that there were no defects in the quality of the skins cultured on the PLGA membranes when compared with those cultured on the conventional (nonbiodegradable) commercial membranes. The cultured LbL-3D skins were then transplanted together with the PLGA membranes onto full-thickness excisional wounds in mice. At 7 days posttransplantation onto a mouse, the tissues above and below the membrane were connected through the holes with collagen-positive fibers that appeared to migrate from both the host and donor sides, and favorable reepithelization was observed throughout the transplanted skin region. However, insufficient engraftment was observed in some cases. Thus, further optimization of the membrane conditions would be needed to improve the transplantation outcome.

HLA amino acid Mismatch-Based risk stratification of kidney allograft failure using a novel Machine learning algorithm

ObjectiveWhile associations between HLA antigen-level mismatches (Ag-MM) and kidney allograft failure are well established, HLA amino acid-level mismatches (AA-MM) have been less explored. Ag-MM fails to consider the substantial variability in the number of MMs at polymorphic amino acid (AA) sites within any given Ag-MM category, which may conceal variable impact on allorecognition. In this study we aim to develop a novel Feature Inclusion Bin Evolver for Risk Stratification (FIBERS) and apply it to automatically discover bins of HLA amino acid mismatches that stratify donor-recipient pairs into low versus high graft survival risk groups. MethodsUsing data from the Scientific Registry of Transplant Recipients, we applied FIBERS on a multiethnic population of 166,574 kidney transplants between 2000 and 2017. FIBERS was applied (1) across all HLA-A, B, C, DRB1, and DQB1 locus AA-MMs with comparison to 0-ABDR Ag-MM risk stratification, (2) on AA-MMs within each HLA locus individually, and (3) using cross validation to evaluate FIBERS generalizability. The predictive power of graft failure risk stratification was evaluated while adjusting for donor/recipient characteristics and HLA-A, B, C, DRB1, and DQB1 Ag-MMs as covariates. ResultsFIBERS’s best-performing bin (on AA-MMs across all loci) added significant predictive power (hazard ratio = 1.10, Bonferroni adj. p < 0.001) in stratifying graft failure risk (where low-risk is defined as zero AA-MMs and high-risk is one or more AA-MMs) even after adjusting for Ag-MMs and donor/recipient covariates. The best bin also categorized more than twice as many patients to the low-risk category, compared to traditional 0-ABDR Ag mismatching (∼24.4% vs ∼ 9.1%). When HLA loci were binned individually, the bin for DRB1 exhibited the strongest risk stratification; relative to zero AA-MM, one or more MMs in the bin yielded HR = 1.11, p < 0.005 in a fully adjusted Cox model. AA-MMs at HLA-DRB1 peptide contact sites contributed most to incremental risk of graft failure. Additionally, FIBERS points to possible risk associated with HLA-DQB1 AA-MMs at positions that determine specificity of peptide anchor residues and HLA-DQ heterodimer stability. ConclusionFIBERS’s performance suggests potential for discovery of HLA immunogenetics-based risk stratification of kidney graft failure that outperforms traditional assessment.

Mid-Term Clinical and Radiological Outcomes of Lateral Meniscal Allograft Transplantation with Suture-Only Fixation Plus Capsulodesis.

Meniscal allograft transplantation (MAT) is an effective reconstructive procedure for treating a symptomatic postmeniscectomy syndrome. It consists of replacing the lost meniscal tissue aiming to improve the clinical outcomes and prevent progressive deterioration of the joint. The aim of this study was to evaluate meniscal graft survivorship and report on the radiographic (in terms of graft extrusion and joint space width and alignment) and the functional results through a midterm follow-up of lateral MAT performed with a soft tissue fixation technique after capsulodesis. In total, 23 patients who underwent lateral MAT as a single procedure were included. The Knee injury and Osteoarthritis Outcome Score, Lysholm, Tegner, and visual analog scale scales were used for patient assessment. Magnetic resonance imaging and a complete radiographic protocol were conducted to determine the degree of meniscal extrusion and the changes in the degree of osteoarthritis and coronal alignment. Assessments were performed after 2 and 7 years of follow-up. A significant improvement in all the scores, relative to preoperative values, was found after 7 years of follow-up. This improvement remained consistent throughout the first and second follow-up periods. A mean absolute extrusion of 2.2 mm ± 1.6 and an extrusion percentage of 28.0% ± 11.43 were found, with no significant differences throughout the follow-up periods. There was no statistically significant difference in terms of the frontal mechanical axis and joint space narrowing between the preoperative value and at the first and second follow-up periods. A survival rate of 85.7% was found after 7 years of follow-up. Capsulodesis results in a low degree of meniscal extrusion in isolated lateral MAT fixed with a suture-only technique, which is maintained after 7 years of follow-up, with a high graft survival index (>85%) and satisfactory results on the functional scales.

Grafting month and environmental condition influences on the success of softwood grafting in Cashew under Bastar region of Chhattisgarh

An experiment was conducted at Horticulture Nursery, Shaheed Gundadhur College of Agriculture and Research Station, Jagdalpur, Chhattisgarh during 2021-22 to identify the suitable month for grafting under different environmental conditions in cashew. Grafting was performed in five different months i.e., June, July, August, September, and October and grafts are placed in three conditions i.e., open condition, shade net, and mist chamber. Thus, in total, there were 15 treatment combinations that were replicated thrice under a factorial randomized complete block design. Among the individual effect of the month of grafting, July recorded the least days taken to sprouting (15.50) whereas August recorded the highest graft success (88.33 %), shoot height (25.88 cm), graft height (44.10 cm), graft diameter (0.661 cm), number of leaves (7.43), leaf area (29.71 cm2), graft fresh weight (25.90 g), graft dry weight (7.71 g), root volume (7.17 cm3), root to shoot ratio (0.306) and graft survival (92.38 %). Among the environmental conditions, mist chamber showed superiority over open and shade net conditions. Among the interactions between the treatments, the minimum days taken to sprouting was recorded when grafting was done in July under a mist chamber (13.83). The highest graft survival was recorded in July grafting under mist chamber (100.00 %) whereas grafting in the month of August under the mist chamber recorded the highest graft success (95.00 %), shoot height (28.50 cm), graft height (48.63 cm), graft diameter (0.689 cm), number of leaves (9.54), leaf area (41.50 cm2), graft fresh weight (26.46 g), graft dry weight (7.98 g), root volume (8.03 cm3) and root to shoot ratio (0.343). It can be concluded that grafting in the month of August under the mist chamber could be followed for the commercial propagation of cashew under Bastar region of Chhattisgarh.

MANAGEMENT OF PROSTATE CANCER IN KIDNEY TRANSPLANT RECIPIENTS.

Kidney transplantation is the treatment of choice in eligible patients with end-stage kidney disease. Prostate cancer (PC) is the second most common cancer in men worldwide. The prevalence of chronic kidney disease worldwide is 13.4%. The management of localized PC in these patients is challenging due to immunosuppressive therapy and pelvic graft localization. High graft and recipient survival rates have resulted in higher numbers of these patients in our everyday practice. A retrospective analysis of male patients who had undergone kidney transplantation at our center between 2002 and 2022 and were diagnosed and treated for PC was performed. We analyzed the incidence, treatment methods, and follow-up of PC patients in this population. A total of 1079 male patients were transplanted. PC was diagnosed in 12 patients (8 after and 4 before transplantation). The incidence of PC was 1.11%. Radical prostatectomy was performed in 11 patients, and one patient was treated with radical radiotherapy. Eleven patients had stable graft function; 1 graftectomy was performed, unrelated to PC. Three patients were indicated for salvage radiotherapy, one is in process for prostate-specific membrane antigen positron emission tomography (PSMA PET CT), and 7 patients are in follow-up and without recurrence. Radical prostatectomy is a safe treatment method for localized PC in kidney transplant recipients, which does not impair graft function and survival.

Antibody-Mediated Rejection in Kidney Transplantation: A Retrospective Study on the Impact of Donor-Specific Antibodies and on the Timing of Diagnosis.

Introduction Limitedinformation exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according toDSAstatus. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according toDSAstatus after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who hadDSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores,DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared toDSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years).Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targetingDSAstatus according to the time of biopsy. For KB performed less than six months after KT, GS was higher forDSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT,DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

Proteomics for Biomarker Discovery for Diagnosis and Prognosis of Kidney Transplantation Rejection.

Renal transplantation is currently the treatment of choice for end-stage kidney disease, enabling a quality of life superior to dialysis. Despite this, all transplanted patients are at risk of allograft rejection processes. The gold-standard diagnosis of graft rejection, based on histological analysis of kidney biopsy, is prone to sampling errors and carries high costs and risks associated with such invasive procedures. Furthermore, the routine clinical monitoring, based on urine volume, proteinuria, and serum creatinine, usually only detects alterations after graft histologic damage and does not differentiate between the diverse etiologies. Therefore, there is an urgent need for new biomarkers enabling to predict, with high sensitivity and specificity, the rejection processes and the underlying mechanisms obtained from minimally invasive procedures to be implemented in routine clinical surveillance. These new biomarkers should also detect the rejection processes as early as possible, ideally before the 78 clinical outputs, while enabling balanced immunotherapy in order to minimize rejections and reducing the high toxicities associated with these drugs. Proteomics of biofluids, collected through non-invasive or minimally invasive analysis, e.g., blood or urine, present inherent characteristics that may provide biomarker candidates. The current manuscript reviews biofluids proteomics toward biomarkers discovery that specifically identify subclinical, acute, and chronic immune rejection processes while allowing for the discrimination between cell-mediated or antibody-mediated processes. In time, these biomarkers will lead to patient risk stratification, monitoring, and personalized and more efficient immunotherapies toward higher graft survival and patient quality of life.

Topical administration of tacrolimus and corticosteroids in tapering doses is effective in preventing immune rejection\xa0in high-risk keratoplasty: a 5-year follow-up study

BackgroundTo evaluate the efficacy of the topical administration of immunosuppressants and corticosteroids in tapering doses in the management of patients with high-risk keratoplasty.MethodsOne hundred and six patients treated with topical immunosuppressants (50 eyes in the FK506 group and 56 eyes in the CsA group) and corticosteroid eye drops in tapering doses were enrolled in the study. The rates of rejection episodes, irreversible rejection, graft survival, and related influential factors were evaluated.ResultsThe mean follow-up period was 48.1 ± 7.9 months (range, 36–60 months). The rates of rejection episodes and irreversible rejection were 14.0% and 6.00% in the FK506 group and 37.5% and 7.1% in the CsA group, respectively. Kaplan-Meier survival analysis demonstrated a significantly higher graft survival rate in the FK506 group (81.6%±5.3%, 71.1%±6.3%) compared with that in the CsA group (71.1%±6.3%, 57.5%±7.5%) at 3 and 5 years after surgery (P = 0.006). Multivariate logistic regression revealed that preoperative risk score ≥ 3 (P = 0.016) and endothelial immune rejection (P = 0.033) were risk factors associated with graft survival.ConclusionsTopical administration of tacrolimus and corticosteroids in tapering doses is effective in decreasing the incidence of immune rejection in high-risk keratoplasty. Careful instruction of patients on the reasonable use of topical tacrolimus is critical to avoid immune rejection induced by sudden discontinuation of medication.

The proliferation of belatacept-resistant T cells requires early IFNα pathway activation

Belatacept was developed to replace calcineurin inhibitors in kidney transplantation. Its use is associated with better kidney transplant function, a lower incidence of anti-donor antibodies and higher graft survival. However, it is also associated with a higher risk of cellular rejection. We studied the activation and proliferation mechanisms of belatacept-resistant T lymphocytes (TLs), to identify new pathways for control. We performed a transcriptomic analysis on CD4+ CD57+ PD1- memory TLs, which are responsible for a higher incidence of graft rejection, after allogeneic stimulation with activated dendritic cells (aDCs) in the presence or absence of belatacept. After six hours of contact with aDCs, the (CD4+ CD57+ PD1- ) (CD4+ CD57+ PD1+ ) and (CD4+ CD57- ) lymphocytes had different transcriptional profiles with or without belatacept. In the CD4+ CD57+ PD1- population, the IFNα-dependent activation pathway was positively overrepresented, and IRF7 transcript levels were high. IRF7 was associated with IFNα/β and IL-6 regulation. The inhibition of both these cytokines in a context of belatacept treatment inhibited the proliferation of CD4+ CD57+ PD1- T cells. Our results show that IRF7 is rapidly upregulated in belatacept-resistant CD4+ CD57+ PD1- TLs. The inhibition of type I IFN or IL-6 in association with belatacept treatment reduces the proliferation of belatacept-resistant TLs, paving the way for new treatments for use in organ transplantation.

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.

A prospective, single-center study following operative treatment for osteochondral lesions of the talus

Background(1) To evaluate patient-reported outcomes and revision surgeries after various operative interventions for osteochondral lesions of the talus (OLT) in a prospective single center series over 10 years, and (2) to identify predicting factors related to subjective ankle status and quality of life pre- and postoperatively. MethodsNinety-nine patients underwent operative treatment due to primary or recurrent OLT, with an average follow up 3.5 (1.8) years. Treatment outcome was followed clinically (FAOS, EQ-5D, Tegner activity scale) and by pursuing any serious adverse events or graft failures. ResultsThere were 80 responding patients (81%) for the study. The mean lesion size was 2.0 (1.1) cm2. All FAOS values increased from preoperative to final follow-up values (Symptoms 60–68, Pain 58–69, ADL 71–80, Sport 36–54, QoL 30–45). EQ-5D increased from 0.49 to 0.62, while Tegner activity scale change from 3.2 to 3.4. There were 19 (24%) serious adverse events recorded; 13 (16%) of them were graft-related. Graft survival rates were 100% at 1 year, 94% (males)/93% (females) at 2 years, and 77% (males)/47% (females) at 5 years. Female gender, higher BMI, and higher Kellgren-Lawrence ankle OA score were negative predictors for preoperative patient-reported ankle joint status. The foremost improvement after operative intervention was observed in patients with large osteochondral lesions without postoperative adverse events. ConclusionVarious operative interventions for OLT significantly improved patients’ ankle status and quality of life. High graft survival rates were demonstrated over first two years, but notable decline was confirmed thereafter, especially in female patients.

Long-Term Results and Refractive Error After Cataract Surgery With a Scleral Incision in Eyes With Deep Anterior Lamellar Keratoplasty.

Phacoemulsification in eyes with deep anterior lamellar keratoplasty (DALK) is associated with possible decreased graft survival and difficult IOL power calculation. We assessed cataract surgery in eyes with previous DALK. Thirty-three consecutive eyes with DALK and further phacoemulsification with scleral incision were included in this retrospective study. At each postoperative visit, eyes were assessed with manifest refraction, optical coherence tomography, specular corneal topography, and noncontact wide-field specular microscopy. The average postkeratoplasty follow-up time was 102 months [95%-CI, (85-119)]. Cataract surgery was performed on average 43 months (30-56) after DALK. The average postphacoemulsification follow-up time was 58 months [42-74]. All grafts remained clear during follow-up. The best spectacle-corrected logarithm of the minimum angle of resolution visual acuity improved by 2.5 lines [1.8-3.1] on average after cataract surgery from 0.58 (20/77) to 0.34 (20/44) (P < 0.001). The spherical equivalent and intraocular pressure significantly improved from -4.1 D to -1.7 D and from 15.9 to 14.0 mm Hg, respectively. The corneal central thickness was not significantly modified, and the endothelial density decreased by 5.3% from 2081 to 1970 cells/mm2 (P = 0.003). The minimal difference between the achieved and predicted spherical equivalents [-0.05 D, (-2.33; +2.21)] was obtained with the Hoffer Q formula using the IOLMaster axial length and the Orbscan keratometry. Patients with DALK who underwent phacoemulsification with a scleral incision had a satisfying residual refractive error, very high graft survival, and very few complications. The Hoffer Q formula with the IOLMaster axial length and the specular corneal topography keratometry seems to be the most accurate for IOL calculation.