Allostimulation leads to emergence of a human B cell population with increased expression of HLA class I antigen presentation associated molecules and the immunoglobulin receptor FcRL5.

In the extensive literature characterizing lymphocyte contributions to transplant-related pathologies including allograft rejection and graft-versus-host disease, T cell-focused investigation has outpaced investigation of B cells. Most B cell-related reports describe regulatory and antibody-producing functions, with less focus on the potential role of antigen-presenting capacity. Using in vitro human mixed lymphocyte reactions (MLRs) to model allostimulation, we analyzed responder B cells using transcriptional analysis, flow cytometry and microscopy. We observed emergence of an activated responder B cell subpopulation phenotypically similar to that described in individuals with graft-versus-host disease or allograft rejection. This population had markedly increased expression of FcRL5 (Fc receptor like 5) and molecules associated with HLA class I antigen presentation. Consistent with this phenotype, these cells demonstrated increased internalization of irradiated cell debris and dextran macromolecules. The proportion of this subpopulation within MLR responders also correlated with emergence of activated, cytotoxic CD8+ T cells. B cells of similar profile were quite infrequent in unstimulated blood from healthy individuals but readily identifiable in disaggregated human splenocytes and increased in both cases upon allostimulation. Further characterization of the emergence and function of this subpopulation could potentially contribute to identification of novel biomarkers and targeted therapeutics relevant to curbing transplant-related pathology.

Acute graft rejection mimicking constrictive pericarditis after heart transplantation. A case report.

Constrictive pericarditis (CP) is an infrequent complication following heart transplantation (HTx) and arises from diverse postoperative occurrences, including mediastinitis, pericardial effusion, or allograft rejection. Indeed, this rare clinical entity can be misdiagnosed as a rejection episode or restrictive cardiomyopathy. In this report, we present the case of a 43-year-old male who underwent HTx 1.5 years prior and was subsequently admitted to our center due to the gradual onset of symptoms indicative of right congestive heart failure, with an initial diagnosis of constrictive pericarditis.

La pericarditis constrictiva (PC) representa una complicación rara después de un trasplante de corazón (TC), derivada de diversos eventos posoperatorios como mediastinitis, derrame pericárdico o rechazo del injerto. De hecho, esta entidad clínica poco común puede ser diagnosticada erróneamente como un episodio de rechazo o miocardiopatía restrictiva. En este informe presentamos el caso de un hombre de 43 años que se sometió a un TC 1,5 años antes y que fue ingresado posteriormente a nuestra institución debido al inicio gradual de síntomas indicativos de insuficiencia cardíaca congestiva derecha, con diagnóstico inicial de pericarditis constrictiva.

Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

Immunogenicity and tolerance induction in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissues such as skin, muscle, bone, nerve, and vessels, as a functional unit (i.e., hand or face) to patients suffering from major tissue trauma and functional deficits. Though the surgical feasibility has been optimized, issues regarding graft rejection remains. VCA rejection involves a diverse population of cells but is primarily driven by both donor and recipient lymphocytes, antigen-presenting cells, macrophages, and other immune as well as donor-derived cells. In addition, it is commonly understood that different tissues within VCA, such as the skin, elicits a stronger rejection response. Currently, VCA recipients are required to follow potent and lifelong immunosuppressing regimens to maximize graft survival. This puts patients at risk for malignancies, opportunistic infections, and cancers, thereby posing a need for less perilous methods of inducing graft tolerance. This review will provide an overview of cell populations and mechanisms, specific tissue involved in VCA rejection, as well as an updated scope of current methods of tolerance induction.

Recurrent rejections after liver transplantation for hepatocellular carcinoma with stem cell features in an adult patient.

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

Impact of COVID-19 on anti-HLA antibodies in kidney transplantation.

The effects of COVID-19 on the immune profile of kidney transplant recipients are unknown. Immunosuppression adjustment during the illness can increase the risk for de novo donor-specific anti-HLA antibodies (DSA) and acute rejection episodes. This single-center retrospective study includes adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and December 2022, screened for anti-HLA antibodies (AbHLA) pre-transplant and after COVID-19. Analyzed data comprised demographics, immunosuppressive therapy before and during the illness, hospitalization rate, and AbHLA specificity. Two hundred sixty-seven transplant recipients were included and divided according to the pre-transplant AbHLA profile: absent [PRA- (n = 206, 77%)], non-DSA (N = 46, 17%), and DSA+ (n = 15, 6%). The DSA+ group was younger (40.5 ±â€¯16.5; PRA- 50.3 ±â€¯13.4; non-DSA 49.3 ±â€¯11.7 years; p = 0.02). The hospitalization rate was higher in groups with preformed AbHLA (DSA+ n = 8, 53%; non-DSA = 24, 52%; PRA- n = 54, 26%; p < 0.01). Immunosuppression was maintained in 222 (83%), withdrawn in 33 (12%), and reduced in 11 (4%) cases without difference among groups. Twenty-two (8%) cases of de novo DSA were observed after COVID-19 [PRA-, n = 16 (73%) and non-DSA, n = 6 (27%)]. In the DSA+ group, the AbHLA profile remained stable. There were 6 (2%) cases of post-COVID-19 antibody-mediated rejection (DSA+ n = 4, 66%; non-DSA n = 1, 17%, PRA- n = 1, 17%) without T cell-mediated rejection cases. Post-COVID-19 de novo DSA was more frequent in groups without pre-transplant AbHLA, not having association with changes in immunosuppressive therapy.

Evaluating the Clinical Relevance of Antibodies against Non-Human Leukocyte Antigen in Kidney Transplantation.

Introduction: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found to reduce mortality rates, improve quality of life, and is cost-effective compared to dialysis. Recent advancements in human leukocyte antigen (HLA) typing and donor-specific antibody (DSA) detection have helped to reduce the risk of rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest that rejection can be attributed to antibodies against Non-Human Leucocyte Antigens (non-HLAs). We aimed to acquire further understanding of the prevalence and distribution of non-HLA antibodies in our local population and attempt to correlate these findings with graft outcomes, as well as assess whether non-HLA antibodies can be utilized to determine graft impairment and dysfunction. Methods: We conducted a retrospective study involving kidney transplant recipients between January 2010 and December 2020. All included individuals were aged over 18 and underwent kidney-alone transplants; were ABO- and HLA-compatible; and were matched at A, B, and DR loci (mismatch 0:0:0). HLA testing was negative at the time of transplantation. The samples from both cases of early graft rejection and the control group were tested for non-HLA antibodies using One Lambda LABScreenTM, Autoantibody kit groups 1, 2, and 3, as well as the Immucor LIFECODES non-HLA autoantibody assay. Results: A total of 850 kidney transplant recipients were included, in which 12 patients experienced early graft rejection within the first month post transplant and 18 patients who did not experience graft rejection were selected as study controls. Our study reported no correlation between the total burden of non-HLA antibodies and early rejection, most likely as the result of a small sample size. Nevertheless, a sub-analysis revealed that specific high-frequency pre-transplant non-HLA antibodies such as GSTT, CXCL11, CXCL10, and HNR, detected by LIFECODES, were associated with rejection (Fisher's exact test with Bonferroni correction, p < 0.001). Most pre-transplant non-HLA antibody levels were reduced after transplantation, which was attributed to immunosuppression. Conclusion: The 'high frequency' non-HLA antibodies displayed an association with graft rejection, though the overall associations between the burden of non-HLA antibodies and rejection episodes remain inconclusive. Further work is needed to establish the rebound phenomenon of non-HLA antibodies, the development of de novo non-HLA antibodies in the long run, and their implications on graft survival.

Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure.

Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.

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

PURPOSE: To evaluate the association between donor-related factors and the risk of rejection in patients undergoing penetrating keratoplasty (PKP) for keratoconus. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

The influence of neighborhood income on healthcare utilization in pediatric liver transplant.

OBJECTIVES: Neighborhood contextual factors are associated with liver transplant outcomes. We analyzed associations between neighborhood-level socioeconomic status and healthcare utilization for pediatric liver transplant recipients. METHODS: We merged the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases and included liver transplant recipients ≤21 years hospitalized between January 2004 and May 2022. Outcomes were annual inpatient bed-days, risk of hospitalizations, and risk of liver biopsies. The primary exposure was zip code-based neighborhood income at transplant. We applied causal inference for variable selection in multivariable analysis. We modeled annual inpatient bed-days with mixed-effect zero-inflated Poisson regression, and rates of hospitalization and liver biopsy with a Cox-type proportional rate model. RESULTS: We included 1006 participants from 29 institutions. Children from low-income neighborhoods were more likely to be publicly insured (67% vs. 46%), Black (20% vs. 12%), Hispanic (30% vs. 17%), and have higher model for end-stage liver disease/pediatric end-stage liver disease model scores at transplant (17 vs. 13) than the remaining cohort. We found no differences in inpatient bed-days or rates of hospitalization across neighborhood groups. In univariable analysis, low-income neighborhoods were associated with increased rates of liver biopsy (rate ratio [RR]: 1.57, 95% confidence interval [CI]: 1.04-2.34, p = 0.03). These findings persisted after adjusting for insurance, race, and ethnicity (RR: 1.86, 95% CI: 1.23-2.83, p < 0.01). CONCLUSIONS: Children from low-income neighborhoods undergo more liver biopsies than other children. These procedures are invasive and potentially preventable. In addition to improving outcomes, interventions to mitigate health inequities among liver transplant recipients may reduce resource utilization.

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection.

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

The unnecessary use of short tandem repeat testing on bone marrow samples in patients after 1 year following allogeneic hematopoietic stem cell transplant.

OBJECTIVES: To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit. METHODS: Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance. RESULTS: Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR-/FCI-. Of all discordant cases, 75 (6%) were STR+/FCI-, with only 5 (6.7%) cases best explained as identification of disease relapse. Eight cases were STR-/FCI+, representing relapsed/residual disease. Analysis of cases 1 year or more from transplant (54% of all cases) indicated only 9 (1.5%) were STR+/FCI-, and none uniquely identified relapse. CONCLUSIONS: These data suggest that STR analysis performed 1 year or more post-HSCT does not identify unknown cases of relapse. Furthermore, while STR testing is critical for identifying graft failure/rejection within the first year posttransplant, FCI appears superior to STR at detecting late relapses with low-level disease. Therefore, STR testing from patients 1 year or more post-HSCT may be unnecessary, as BM biopsy evaluation is sufficient to identify disease relapse.

Model-Based Antithymocyte Globulin in αßhaplo-Hematopoietic Stem Cell Transplantation Facilitates Engraftment, Expedites T Cell Recovery, and Mitigates the Risk of Acute Graft-versus-Host Disease.

In αß T-cell/CD19 B-cell depleted hematopoietic stem cell transplantation (αßhaplo-HSCT) recipients, antithymocyte globulin (ATG; Thymoglobulin) is used for preventing graft rejection and graft-versus-host disease (GVHD). The optimal dosing remains to be established, however. Here we present the first comparative analysis of 3 different ATG dosing strategies and their impact on immune reconstitution and GVHD. Our study aimed to evaluate the effects of 3 distinct dosing strategies of ATG on engraftment success, αß+ and γδ+ T cell immune reconstitution, and the incidence and severity of acute GVHD in recipients of αßhaplo-HSCT. This comparative analysis included 3 cohorts of pediatric patients with malignant (n = 36) or nonmalignant (n = 8) disease. Cohorts 1 and 2 were given fixed ATG doses, whereas cohort 3 received doses via a new nomogram, based on absolute lymphocyte count (ALC) and body weight (BW). Cohort 3 showed a 0% incidence of day 100 grade II-IV acute GVHD, compared to 48% in cohort 1 and 27% in cohort 2. Furthermore, cohort 3 (the ALC/BW-based cohort) had a significant increase in CD4+ and CD8+ naïve T cells by day 90 (P = .04 and .03, respectively). Additionally, we found that the reconstitution and maturation of γδ+ T cells post-HSCT was not impacted across all 3 cohorts. Cumulative ATG exposure in all cohorts was lower than previously reported in T cell-replete settings, with a lower pre-HSCT exposure (<40 AU*day/mL) correlating with engraftment failure (P = .007). Conversely, a post-HSCT ATG exposure of 10 to 15 AU*day/mL was optimal for improving day 100 CD4+ (P = .058) and CD8+ (P = .03) immune reconstitution without increasing the risk of relapse or nonrelapse mortality. This study represents the first comparative analysis of ATG exposure in αßhaplo-HSCT recipients. Our findings indicate that (1) a 1- to 2-fold ATG to ATLG bioequivalence is more effective than previously established standards, and (2) ATG exposure post-HSCT does not adversely affect γδ+ T cell immune reconstitution. Furthermore, a model-based ATG dosing strategy effectively reduces graft rejection and day 100 acute GVHD while also promoting early CD4+/CD8+ immune reconstitution. These insights suggest that further optimization, including more distal administration of higher ATG doses within an ALC/BW-based strategy, will yield even greater improvements in outcomes.

The rationale behind grafting haploidentical hematopoietic stem cells.

The ability to perform hematopoietic cell transplant across major histocompatibility complex barriers can dramatically increase the availability of donors and allow more patients across the world to pursue curative transplant procedures for underlying hematologic disorders. Early attempts at haploidentical transplantation using broadly reactive T-cell depletion approaches were compromised by graft rejection, graft-versus-host disease and prolonged immune deficiency. The evolution of haploidentical transplantation focused on expanding transplanted hematopoietic progenitors as well as using less broadly reactive T-cell depletion. Significant outcome improvements were identified with technology advances allowing selective depletion of donor allospecific T cells, initially ex-vivo with evolution to its current in-vivo approach with the infusion of the highly immunosuppressive chemotherapy agent, cyclophosphamide after transplantation procedure. Current approaches are facile and portable, allowing expansion of allogeneic hematopoietic cell transplantation for patients across the world, including previously underserved populations.

Descemet's membrane endothelial keratoplasty rejection after SARS-COV2 infection or vaccination: 2-year retrospective study.

PURPOSE: To assess the incidence of Descemet's membrane endothelial keratoplasty (DMEK) rejection potentially associated with coronavirus disease 2019 (COVID-19) infection or vaccination, and its association with known rejection risk factors during the first two years of the pandemic. METHODS: This retrospective study included patients with DMEK rejection between January 2020 and December 2021. Diagnostic criteria were based on symptoms, visual acuity, and other clinical assessments. Risk factors for graft rejection were considered, and a telephone survey was conducted to identify possible preceding COVID-19 infection or vaccination. RESULTS: Of 58 patients, 44 were included. Six patients (14%) reported COVID-19 infection, with one immediate endothelial graft rejection (EGR) post-infection. After vaccine availability, 13 of 36 patients had EGR at an average of 2.7 months post-vaccination. Five (38%) had immediate EGR following vaccination, four of which had concomitant risk factors for rejection. CONCLUSION: Although the risk of endothelial graft rejection (EGR) associated with COVID-19 infection or vaccination appears to be extremely low, there may be a causative relationship, especially in patients with pre-existing risk factors for EGR. A temporary increase in anti-rejection treatment following COVID-19 infection or vaccination is recommended, especially in patients with pre-existing risk factors, along with closer monitoring during the subsequent 4 to 8 weeks.

Systematic Review and Meta-Analysis Provide no Guidance on Management of Asymptomatic Bacteriuria within the First Year after Kidney Transplantation.

(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment of ASB within the first year after KT. (2) Evidence acquisition: A systematic literature search was conducted in MEDLINE, the Cochrane Library CENTRAL and Embase. Inclusion criteria were manuscripts in English addressing the management of ASB after KT. The PICO questions concerned Patients (adults receiving a KT), Intervention (screening, diagnosis and treatment of ASB), Control (screening and no antibiotic treatment) and Outcome (UTIs, sepsis, kidney failure and death). (3) Evidence synthesis: The systematic review identified 151 studies, and 16 full-text articles were evaluated. Seven were excluded because they did not evaluate the effect of treatment of ASB. There was no evidence for a higher incidence of lower UTIs, acute pyelonephritis, graft loss, or mortality in patients not treated with antibiotics for ASB. Analysis of comparative non-randomized and observational studies did not provide supplementary evidence to guide clinical recommendations. We believe this lack of evidence is due to confounding risk factors that are not being considered in the stratification of study patients.

[Modern techniques and features of selective keratoplasty]. / Sovremennye tekhnologii i vozmozhnosti selektivnoi keratoplastiki.

Selective keratoplasty involves replacing the affected layers of the cornea with similar donor tissue. In case of pathological changes in the middle and posterior stroma, deep anterior lamellar keratoplasty (DALK) is performed. Chronic corneal edema caused by endothelial dysfunction is an indication for endothelial keratoplasty - Descemet membrane endothelial keratoplasty (DMEK) or Descemet Stripping Endothelial Keratoplasty (DSAEK). Compared to penetrating keratoplasty (PK), these operations are characterized by a low risk of damage to intraocular structures and a relatively short rehabilitation period. Complications of selective keratoplasty include the formation of a false chamber between the lamellar graft and the recipient's cornea, ocular hypertension during anterior chamber air tamponade. Persistent epithelial defect can be a sign of primary graft failure in DALK, DSAEK and DMEK. Selective keratoplasty is characterized by a lower incidence of immune rejection than PK. In some cases, DALK can be complicated by corneal changes related to suture fixation of the graft. Long-term postoperative use of topical glucocorticoids can cause ocular hypertension and cataracts.

Immunosuppressive protocols after laryngeal transplantation: a systematic review.

BACKGROUNDS: Larynx transplantation has been successfully performed four times, in 1998, 2010, 2015 and 2023 remained the ultimate goal of voice, feeding and breathing rehabilitation. OBJECTIVE: Immunosuppressive protocols used during the previous successful larynx allotransplantation are detailed. MATERIAL AND METHODS: A systematic review of the literature on PUBMED/Medline, Cochrane and Embase was conducted. Articles relating to actual human larynx transplantations were included. RESULTS: Bibliography search gathered N = 10 publications related to the performance and follow-up of human laryngeal transplantations. N = 8 publications were included corresponding to N = 3 actual human larynx transplantations performed in 1998 and 2010 in the USA and in 2015 in Poland. Immunosuppression protocols, induction and maintenance strategies, rejection monitoring and history of all the three previous laryngeal grafts were detailed. CONCLUSIONS: Beyond the surgical prowess, larynx transplantation is feasible and associated with a reasonably successful outcome when compared to other solid organ transplants. Immunosuppressive regimen protocols and technologies for the monitoring of the organ viability have evolved. SIGNIFICANCE: The reevaluation of this surgical option serves as the reminder of the critical necessity to implement a meticulous immunosuppression protocol when transplanting this inherently immunogenic composite organ, the larynx.