Graft Rejection Episodes Research Articles

Ten-year follow-up after face transplantation—A single-center retrospective cohort study

Face transplantation has emerged as reconstructive option for the most challenging facial deformities. A comprehensive analysis of functional outcomes, medical complications, incidence of malignancy, and chronic rejection in face transplantation recipients over an extended follow-up period has not yet been published leaving a notable gap in the literature. We retrospectively collected data of morbidity, rejection, vasculopathy, metabolic side effects, as well as functional outcome of sensory return, facial motor function, and speech from 9 patients who underwent face transplantation at Brigham and Women’s Hospital between 2009 and 2020. The median follow-up was 120 months (54 and 154 months). Four grafts (40%) developed signs of clinical and histopathologic chronic rejection without evidence of vasculopathy on computed tomography angiograms. Sensory return assessed with Weinstein enhanced sensory testing-monofilament showed an increase in 6 patients (66.7%), and facial expression analysis showed improvement throughout the whole cohort at their most recent follow-up. Speech intelligibility was stable or increasing for 5 patients (55.6%). In conclusion, the long-term outcomes reveal promising results in terms of overall graft retention and functional recovery. Metabolic, malignant, and infectious complications, as well as graft rejection episodes, are expected to occur in this population, and some may be related to patient’s age and lifestyle.

Cytokine Dynamics and Herpesvirus Interactions in Pediatric Liver and Kidney Transplant Recipients: The Distinct Behavior of HCMV, HHV6, HHV7 and EBV.

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.

Risk factors for corneal graft rejection after penetrating keratoplasty for keratoconus.

To evaluate the association between donor-related factors and the risk of rejection in patients undergoing penetrating keratoplasty (PKP) for keratoconus. A retrospective review was performed of keratoconus patients with no corneal neovascularization who underwent PKP from November 2014 to December 2016 and completed at least two years of follow-up. Preoperative, donor, operative, and postoperative data were collected and analyzed to identify factors leading to corneal graft rejection. A total of 201 eyes (of 201 patients) that underwent PKP for keratoconus were included. Of these, 22.9% (95% CI 17.6-29.2%) had an episode of graft rejection. The overall graft survival rate was 98.5%. Receipts with a history of corneal transplant in the fellow eye (IRR 1.69, 95% CI 1.01, 2.80; p = 0.044) and those with postoperative stromal neovascularization (IRR 2.51, 95% CI 1.49, 4.21; p = 0.001) had a significantly higher incidence of rejection than those without these features. In univariate analysis, death-to-surgery time and death-to-excision time (DET) showed a weak association with graft rejection (p 0.05 and 0.08 respectively); However, in the multivariable analysis, this significance was lost. Grafts with a death-to-excision time (DET) greater than 8 h had a 0.53X lower risk of rejection compared with grafts with DET within 8 h or less (p = 0.05). Rejection was higher in patients receiving grafts with a preservation time within 7 days or less compared with preservation time greater than 7 days (30.6% vs. 21.2%, respectively, p = 0.291). In the multivariable analysis, none of the donor-related factors were significantly associated with graft rejection; however, short death-to-surgery time may be associated with rejection after PKP. Recipients with a history of PKP in the fellow eye and those who developed corneal neovascularization were also at increased risk of developing rejection after keratoplasty.

Post liver transplant refractory dyslipidemia

ABSTRACT A 53-year-old male presented with intractable pruritus and jaundice. He underwent liver transplantation for liver cirrhosis a year prior to the current presentation. Post-transplantation, he developed diabetes mellitus. He experienced an episode of early acute graft rejection, 2 months after transplantation, which was successfully treated. Subsequently, about a year after transplantation, he developed chronic graft rejection. He was treated with everolimus and prednisolone. Incidentally, he was found to have elevated blood cholesterol, triglycerides, and low density lipoprotein (LDL) levels. The lipid levels were significantly higher than those commonly encountered in post-liver transplant patients. Dyslipidemia was treated with maximum dose of high-intensity statin, ezetimibe, and fenofibrate. However, there was not much reduction in lipid levels, indicating resistance to treatment. Subsequently, injection evolocumab 140 mg subcutaneously was added, administered once every 2 weeks. Following that, after only three doses of injection, there was about 65% reduction in the LDL level, which sustained at lower levels with continued treatment using evolocumab. Evolocumab was proven to be highly effective in reducing lipid levels in post-liver transplant patients who are refractory to treatment with conventional lipid-reducing medications.

UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial

BackgroundGood vision highly depends on the transparency of the cornea, which is the “windscreen” of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient’s cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide.MethodsThis parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints).DiscussionBased on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness.Trial registrationClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

Management of Kidney Transplant Outpatients With COVID-19: A Single Center Experience.

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56years), serum creatinine 127 (101-153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1-3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15-22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106-159) µmol/L post-COVID-19 infection and 128 (101-161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients

Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Prospective Assessment of Loteprednol Etabonate 0.25% for Prevention of Immunologic Rejection After Descemet Membrane Endothelial Keratoplasty in Eyes With Fuchs Dystrophy.

The purpose of this study was to assess off-label use of loteprednol etabonate 0.25% ophthalmic suspension for prevention of immunologic rejection after Descemet membrane endothelial keratoplasty (DMEK). This prospective, open-label study enrolled 70 eyes of 70 participants without preexisting glaucoma 1 month after DMEK. Participants used topical loteprednol 0.25% 4 times daily for 2 months, tapered by 1 drop/month to once daily use, and continued use through 1 year after DMEK. Main outcomes were rate of intraocular pressure (IOP) elevation (defined as a relative increase of ≥10 mm Hg over the pretransplant IOP) and rate of initial allograft rejection episodes. The results were compared with historical data using the log-rank test. All participants had Fuchs dystrophy, and 40 of 70 (57%) were female. None (0%) experienced an immunologic graft rejection episode, matching the previously reported efficacy of prednisolone acetate 1% suspension and loteprednol 0.5% gel (both 0% incidence). One study eye developed IOP elevation 3 months after DMEK (cumulative risk 1.5%). Compared with historical data, this was similar to the risk with loteprednol 0.5% gel (4%, P = 0.36) and significantly lower than the risk with prednisolone 1% suspension (18%, P = 0.0025). Two participants (3%) complained of instillation site discomfort, consistent with the 5% rate reported on package labeling. Loteprednol 0.25% suspension, approved for short-term treatment of dry eyes, effectively prevented immunologic rejection episodes with minimal risk of IOP elevation when used from 1 month until 12 months after DMEK in patients without preexisting glaucoma.

Management and prevention of corneal graft rejection.

The management of an episode of corneal graft rejection (CGR) is primarily by corticosteroids. Immunomodulators are useful for long-term immunosuppression and in dealing with cases of high-risk (HR) corneal grafts. The classical signs of CGR following penetrating keratoplasty (PKP) include rejection line, anterior chamber (AC) reaction, and graft edema. However, these signs may be absent or subtle in cases of endothelial keratoplasty (EK). Prevention of an episode of graft rejection is of utmost importance as it can reduce the need for donor cornea significantly. In our previous article (IJO_2866_22), we had discussed about the immunopathogenesis of CGR. In this review article, we aim to discuss the various clinical aspects and management of CGR.

Descemet Stripping Automated Endothelial Keratoplasty versus Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy: A National Registry-Based Comparison

To compare the outcome between posterior lamellar corneal transplant procedures for Fuchs endothelial corneal dystrophy, taking preoperative patient characteristics in consideration. Surgical methods compared were Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and DSAEK with concomitant cataract surgery (phacoemulsification plus DSAEK). Registry-based study with propensity score matching. One thousand six hundred seventy-seven patients from all Swedish corneal transplantation units treated from 2012 through2019. All patients undergoing endothelial keratoplasty performed from 2012 through 2019 with completed 2-year follow-up data reported to The Swedish Corneal Transplant Register were included, totaling 1677 patients. Three comparable groups (DMEK, DSAEK, and phacoemulsification plus DSAEK) with 216 patients in each group were generated with propensity score matching based on preoperative visual acuity, age, sex, year of surgery, and preoperative risk factors such as inflammation, vascularization, and glaucoma. Best-corrected visual acuity (BCVA) at the 2-year follow-up, frequency of graft dislocation, graft rejection episodes, and graft failure within 2 years including primary graft failure. The preoperative corneal status was affected more severely in the DSAEK group before matching. In the matched groups, the median BCVA 2 years after surgery was 0.1 logarithm of the minimum angle of resolution (logMAR) in both the DMEK and the phacoemulsification plus DSAEK groups and 0.15 logMAR in the DSAEK group (P= 0.001). The frequency of graft dislocation was higher among the patients undergoing phacoemulsification plus DSAEK, but the frequency of graft failure and primary graft failure was higher in the DMEK group. Visual acuity improved in most patients (90%) with all 3 surgical methods. However, DMEK and phacoemulsification plus DSAEK reached higher levels of visual acuity 2 years after surgery, and phacoemulsification plus DSAEK was superior considering graft survival rate. All 3 surgical procedures showed both strengths and weaknesses, suggesting that the choice of surgical method should be individualized, taking into consideration not only the cornea, but each patient's complete medical status as well as the entire course of postoperative medical care. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Long-Term Endothelial Cell Viability After Deep Anterior Lamellar Versus Penetrating Keratoplasty for Keratoconus.

We compared long-term endothelial cell survival after penetrating versus after deep anterior lamellar keratoplasty for keratoconus. We retrospectively compared 64 eyes of 55 patients who had penetrating keratoplasty and 40 eyes of 37 patients who had deep anterior lamellar keratoplasty for keratoconus (October 2003-February 2021). Best-corrected visual acuity, Goldmann applanation tonometry, fundus examination with 90D lens, and specular microscopy with CEM-530 (Nidek) were performed preoperatively and every 6 months postoperatively. Main outcomes were endothelial cell density, central corneal thickness, and visual acuity. Secondary outcomes were coefficient of variation, hexagonality, graft rejection episodes, and graft clarity. We found no significant differences between the 2 treatment groups regarding patient age, donor age, preoperative vision, central corneal thickness, and recipient-donor trephine diameters. Mean follow-up was 92.5 months. In deep anterior lamellar keratoplasty, the endothelium was preserved significantly better for 10 years versus for penetrating keratoplasty. Mean endothelial density in penetrating versus deep anterior lamellar keratoplasty was 2006.7 versus 2354.7 cells/mm2 at 1 year (P = .010), 1170.5 versus 2048.2 at 5 years (P <.001), and 972.5 versus 1831.6 at 10 years (P < .001). Cumulative endothelial cell loss was 43% and 19.7% at 10 years for penetrating and anterior lamellar keratoplasty, respectively. Significantly more thickening of central cornea was shown in penetrating keratoplasty after 7 years. Corneal thickness was 583.0 µm in penetrating and 545.1 µm in deep anterior lamellar keratoplasty (P = .002) at 10 years. Vision gain and coefficient of variation were similar. Hexagonality decreased significantly in both groups at 10 years. Rates of rejection were 12.5% in penetrating and 7.5% in deep anterior lamellar keratoplasty. Graft survival rates were 97.5% and 96.9%, respectively. In keratoconus, endothelial vitality is better preserved with deep anterior lamellar keratoplasty than with penetrating keratoplasty over a 10-year follow-up.

Monoclonal gammopathy of unknown significance in kidney transplanted patients: novel insights into long-term outcomes.

Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, little is known about the consequences of MGUS on long-term outcomes. We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls. Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P=.03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P=.007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P=.04) and a trend for more bacterial infections (63% vs 48%, P=.08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival. MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression.

#6894 KIDNEY TRANSPLANTATION IN PATIENTS WITH AA AMYLOIDOSIS: A FRENCH MULTI-CENTER MATCHED COHORT STUDY IN THE ERA OF BIOTHERAPIES

Abstract Background and Aims Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting. Method We conducted a retrospective multicenter matched cohort study in 26 French centers reporting all patients with AA amyloidosis who received a kidney transplant between 2008 and 2018, and compared them to matched control patients (ratio 1:2 controls) who received a kidney transplant for other causes Results Eighty-six AA amyloidosis transplants and 157 control transplants were included. Median age was 49.4 years (interquartile range 39.7-61.1), and the main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. At 5 years, patient survival was 85.5% (95% confidence interval 77.8-94.0) and 86.2% (80.5-92.2) for cases and controls, respectively (p = 0.5). Death censored graft survival was 78.2% (78.2-93.5) and 91.7% (87.0-96.6), respectively (p = 0.05). Histologically proven AA amyloidosis recurrence was found in 5 patients (5.8%). 55.8% of amyloid patients had at least one infection requiring hospitalization and 27.9% an episode of acute graft rejection. In this group, multivariable analysis showed that CRP concentration at time of transplantation was associated with patient survival (HR 1.01, p = 0.01). Conclusion In this recent cohort, patient survival was comparable to controls and recurrence rates were lower than previously reported. Provided the underlying inflammatory disease is well controlled, patients with AA amyloidosis may be transplanted with similar patient and graft outcomes than that of matched controls.

Graft rejection episodes after keratoplasty in Japanese eyes

We aimed to investigate the clinical characteristics and risk factors for graft rejection after keratoplasty in Japanese patients. We enrolled 730 cases (566 patients) of penetrating keratoplasty (PK, N = 198), Descemet’s stripping automated endothelial keratoplasty (DSAEK, N = 277), non-Descemet’s stripping automated endothelial keratoplasty (nDSAEK, N = 138), and Descemet membrane endothelial keratoplasty (DMEK, N = 117). The incidence, clinical characteristics, and possible risk factors for graft rejection were analyzed. Graft rejection occurred in 65 cases (56 patients, 8.9%). The incidence rate of rejection was highest with PK (3.45/100 person-years), followed by DSAEK (2.34), nDSAEK (1.55), and DMEK (0.24). Cox regression analysis revealed keratoplasty type, younger age, indications (such as failed keratoplasty and infection), and steroid eyedrop use as possible risk factors. In the multivariate model adjusting baseline characteristics, PK and DSAEK had significantly higher hazard ratios (HRs) than DMEK (HR = 13.6, 95% confidence interval [CI] [1.83, 101] for PK, 7.77 [1.03, 58.6] for DSAEK). Although not statistically significant, the HR estimate of nDSAEK to DMEK (HR = 7.64, 95% CI [0.98, 59.6]) indicated higher HR in nDSAEK than in DMEK. DMEK is the favorable option among the four surgical procedures to avoid graft rejection after keratoplasty.

Gut microbiota might influence the risk of rejection after liver transplantation

IntroductionLiver transplantation is the only radical treatment option available for patients with end-stage chronic liver disease. However, severe post-transplant complications remain relevant, including acute graft rejection and infection. Thus, the impact of gut microbiota on the frequency of these complications is highly promising. Materials and methodsThis prospective, cohort, closed-label study included 24 adults who underwent liver transplantation. The mean age was 49.2 ± 13.4 years; Child-Turcotte-Pugh A, B, and C classes were distributed as follows: A: 8 (33.3%); B: 11 (45.8%); C: 5 (20.8%). Gut microbiota was evaluated using 16S RNA new-generation sequencing. Study registrationNCT04281797. ResultsAccording to etiological distribution, significant differences were observed in the number of Firmicutes (p = 0.03) and Chlorobi (p = 0.009) harbored by the patients of alcoholic liver disease. Similarly, the severity of hepatic decompensation varied significantly for patients harboring Chlorobi (p = 0.01) and coprothermobacterota (p = 0.03). The association between sarcopenia and the microbiota was not significant among all taxa (p>0.1). Acute graft rejection differences between groups were found: Protobacteria (p = 0.001); Chlamydiae (p = 0.02); Gammaproteobacteria (p = 0.01); Chloroflexia (p = 0.004); Chlamydiia (p = 0.01); Enterobacteriaceae (p = 0.001); and Candidatus Saccharibacteria (p = 0.04), the median of which was found to be lower in patients with an acute graft rejection episode. ConclusionsObtained results prove a reliable interaction between gut microbiota and the incidence of acute liver graft rejection in dominant taxa and Candidatus Saccharibacteria that had not yet been observed in patients with rejection episodes.

Outcomes of Pregnancies in Liver Transplant Recipients: Experience of a Single Center in Turkey.

Liver transplantation is the ultimate treatment for end-stage liver failure. As organ donation systems improve, more reproductive-age women are expected to undergo liver transplantation. Current studies indicate increased risk of some perinatal and maternal complications; however, the available data is still scarce. Therefore, we aimed to evaluate the maternal and fetal outcomes of pregnancies in liver transplant recipients. We retrospectively evaluated liver transplantations performed between 2011 and 2020 in a tertiary center. Perinatal, maternal, fetal outcomes and transplant status were assessed among pregnancies conceived after liver transplantation. Among 1137 patients, 82 (7.2%) were reproductive-age females. Ten pregnancies in nine patients were identified after liver transplantation. The mean age of patients was 29.3±6.1 at transplantation, and 32.5±5.4 at conception. The mean interval between conception and transplantation was 30.3±11.7 months. There were eight live births (80%), one miscarriage (10%) and one termination (10%). Three patients delivered<37th gestational week (37.5%). The median gestational age at birth was 38.5 (IQR: 5.21) weeks. The mean birth weight of infants was 2669.3±831 g. Two patients were diagnosed with preeclampsia (25%) and acute graft rejection episode was observed in one patient (10%) during pregnancy. Although the incidence of some perinatal complications, such as hypertensive disorders and preterm delivery, is increased in liver transplant recipients, pregnancy after liver transplantation appears to have favorable outcomes for the mother, fetus and transplant with close monitoring by a multidisciplinary team.

Risk factors and management of biliary stones after living donor liver transplant and its effect on graft outcome.

BackgroundBile stones are associated with numerous complications in liver transplant recipients. Endoscopic retrograde cholangiopancreatography (ERCP) has been proven to be safe and highly effective in dealing with most post-transplant biliary complications.ObjectiveThe objective of this study was to identify the possible risk factors for bile stone formation on top of biliary stricture, the effects of stones on graft outcomes, and their management.MethodsThis case–control study included 83 patients who underwent living donor liver transplant (LDLT) and suffered from postoperative biliary stricture with or without stones. Patients were divided into two groups. Group 1 (n = 55) included patients with biliary strictures with no stones and group 2 (n = 28) included patients who developed stones on top of biliary strictures. Data about the recipient and donor characteristics, surgical technique, blood lipid profile, immunosuppressive drugs, post-transplant complications, and interventions were collected from the medical records.ResultsThe frequency of hepatitis C virus (HCV) was significantly higher in group 2 compared to group 1 (71.4% vs. 47.3%, p = 0.036). The body mass index (BMI) of the donors was significantly higher in group 2 than in group 1 (25.17 ± 2.53 vs. 23.68 ± 2.63, p = 0.015). Episodes of acute rejection were significantly higher in group 2 than in group 1 (21.4% vs. 5.5%, p = 0.027). The ERCP was sufficient in most of the cases (89.2%) to ensure biliary drainage. The identified independent risk factors for biliary stones included HCV, biliary drain, donor's BMI, and serum cholesterol level.ConclusionPositive HCV, biliary drain insertion, donor's BMI, and serum cholesterol level were independent risk factors for developing bile stones on top of biliary strictures. Biliary stones were associated with high episodes of acute graft rejection, and they could be successfully managed by the ERCP modality.

Kidney transplantation outcomes: Single center experience

Introduction: Chronic kidney disease (CKD) is one of the main burden for healthcare system not only in Kazakhstan. The number of patients with CKD increases annually. Among renal replacement approaches, kidney transplantation (KTx) is the best therapeutic option. KTx is performed in Kazakhstan since 2010. Various factor can either improve or deteriorate outcome after KTx. Here we analyzed factors, influencing graft survival. We have performed this study in order to detect the factors, that significantly affects the KTx outcomes, preferably from living donorMethods: Clinical data of the 253 kidney recipients were collected from archives of National Research oncology center and retrospectively analyzed.Results: Immunological status before KTx was found to affect outcome. The presence of HLA class I antibodies was significantly related to graft loss (p=0.046).Coexistence of HLA class II antibodies and the graft loss was not significant (p=0.324). Acute postoperative rejection was highly correlated with graft loss (p<0.001). Of the cohort, 18 (7%) had acute rejection, and 13 (72%) of them were women (p<0.001). The graft survival was statistically significantly related to the gender of the recipient with p=0.002. The 5-year survival of a graft in females was 80.2%, while for males it was 95.3%. In addition, post-operational complications remarkably influenced the graft loss with p=0.005Conclusion: Recipients' gender, immunological status, and acute graft rejection episodes after transplantation were predictors of a worse kidney function 1 year after transplantation.

PO2 21% oxygenated hypothermic machine perfusion in kidney transplantation: Any clinical benefit?

In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016-December 2020. Oxygenation was performed at pO2 21%. The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min-31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41-94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9-1.78], p = 0.319), with similar post-transplant trend (p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.

A Randomized Controlled Trial Comparing Microthin Descemet Stripping Automated Endothelial Keratoplasty With Descemet Membrane Endothelial Keratoplasty: Two-Year Report

The purpose of this study was to report the 2-year outcomes of a double-blinded randomized controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) and microthin Descemet stripping automated endothelial keratoplasty (MT-DSAEK). Fifty-six eyes of 56 patients were randomized to DMEK or microthin DSAEK (MT-DSAEK). The main outcome measure was best spectacle-corrected visual acuity (BSCVA) at 24 months. Other secondary outcomes included complications, endothelial cell density, and vision-related quality-of-life (vQoL) scores. There was no statistically significant difference in BSCVA between the DMEK and MT-DSAEK groups at the 2-year time point (mean ± SD; 0.04 ± 0.14 vs. 0.12± 0.19, P = 0.061) in contrast to the 1-year results (mean ± SD; 0.04 ± 0.13 vs. 0.11 ± 0.09, P = 0.002) previously reported. Endothelial cell density did not show a statistically significant difference at 24 months between the DMEK and MT-DSAEK groups (1522 ± 293 cell/mm2 vs. 1432 ± 327 cells/mm2, P = 0.27). There were 2 additional graft rejection episodes in the MT-DSAEK group between the 1- and 2-year follow-up periods, but this did not result in graft failure. The mean vQoL scores between DMEK and MT-DSAEK indicated similar patient satisfaction between the groups (97.1 ± 4.0 vs. 92.6 ± 10.2, P = 0.13). In summary, the trial showed no significant difference in BSCVA at 24 months between the DMEK and MT-DSAEK groups. Both techniques continued to demonstrate comparable outcomes for complication rates, endothelial cell loss, and patient-reported vQoL scores. ISRCTN10578843.