Transplantation Direct最新文献

Background: Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.

Methods: All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.

Results: Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001).

Conclusions: Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.

Background: Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection.

Methods: We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies.

Results: Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns.

Conclusions: Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.

Background: The immunogenicity elicited by the Omicron BA.4/BA.5-adapted bivalent booster vaccine after solid organ transplantation (SOT) has not been characterized.

Methods: We assessed cell-mediated and neutralizing IgG antibody responses against the BA.4/BA.5 spike receptor-binding domain at baseline and 2 wk after the administration of an mRNA-based bivalent (ancestral strain and BA.4/BA.5 subvariants) vaccine among 30 SOT recipients who had received ≥3 monovalent vaccine doses. Previous coronavirus disease 2019 history was present in 46.7% of them. We also recruited a control group of 19 nontransplant healthy individuals. Cell-mediated immunity was measured by fluorescent ELISpot assay for interferon (IFN)-γ secretion, whereas the neutralizing IgG antibody response against the BA.4/BA.5 spike receptor-binding domain was quantified with a competitive ELISA.

Results: The median number of BA.4/BA.5 spike-specific IFN-γ-producing spot-forming units (SFUs) increased from baseline to 2 wk postbooster (83.8 versus 133.0 SFUs/10⁶ peripheral blood mononuclear cells; P = 0.0017). Seropositivity rate also increased (46.7%-83.3%; P = 0.001), as well as serum neutralizing activity (4.2%-78.3%; P < 0.0001). Patients with no prior coronavirus disease 2019 history experienced higher improvements in cell-mediated and neutralizing responses after booster vaccination. There was no correlation between BA.4/BA.5 spike-specific IFN-γ-producing SFUs and neutralizing activity. Nontransplant controls showed more robust postbooster cell-mediated immunity than SOT recipients (591.1 versus 133.0 IFN-γ-producing SFUs/10⁶ peripheral blood mononuclear cells; P < 0.0001), although no differences were observed for antibody responses in terms of postbooster seropositivity rates or neutralizing activity.

Conclusions: Booster with the BA.4/BA.5-adapted bivalent vaccine generated strong subvariant-specific responses among SOT recipients. Booster-induced cell-mediated immunity, however, remained lower than in immunocompetent individuals.

Background: Bacterial colonization (BC) of the lower airways is common in lung transplant recipients (LTRs) and increases the risk of chronic lung allograft dysfunction. Diagnosis often requires bronchoscopy. Exhaled breath analysis using electronic nose (eNose) technology may noninvasively detect BC in LTRs. Therefore, we aimed to assess the diagnostic accuracy of an eNose to detect BC in LTRs.

Methods: We performed a cross-sectional analysis within a prospective, single-center cohort study assessing the diagnostic accuracy of detecting BC using eNose technology in LTRs. In the outpatient clinic, consecutive LTR eNose measurements were collected. We assessed and classified the eNose measurements for the presence of BC. Using supervised machine learning, the diagnostic accuracy of eNose for BC was assessed in a random training and validation set. Model performance was evaluated using receiver operating characteristic analysis.

Results: In total, 161 LTRs were included with 80 exclusions because of various reasons. Of the remaining 81 patients, 16 (20%) were classified as BC and 65 (80%) as non-BC. eNose-based classification of patients with and without BC provided an area under the curve of 0.82 in the training set and 0.97 in the validation set.

Conclusions: Exhaled breath analysis using eNose technology has the potential to noninvasively detect BC.

Background: Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD).

Methods: A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023.

Results: Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%-65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD.

Conclusions: Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.

Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices.

Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed.

Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations.

Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Background: World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland.

Methods: In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics.

Results: A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB.

Conclusions: The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB.

Backgrounds: It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients.

Methods: In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death.

Results: Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation  = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008).

Conclusions: We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

Background: Many centers have removed 6-mo pretransplant alcohol abstinence requirements to provide early liver transplant (ELT) for individuals with severe alcohol-associated liver disease (ALD), but the practice remains controversial. Using data collected from a nationally distributed survey, this study examines the practices and attitudes of transplant centers in the United States regarding ELT.

Methods: A 20-item survey designed to assess center practices and provider attitudes was distributed to 225 medical and surgical directors from 143 liver transplant centers via email.

Results: Surveys were completed by 28.9% (n = 65) of directors and 39% (n = 56) of transplant centers. All responding centers reported evaluating patients for ELT. Circumstances for considering ELT included <6 mo of survival without a transplant (96.4%) and inability to participate in alcohol addiction therapy pretransplant (75%). Most (66%) directors indicated their center had established criteria for listing candidates with severe ALD for ELT. Regarding important factors for ELT candidate listing, 57.1% indicated patient survival, 37.5% indicated graft survival, and 55.4% indicated having a low risk of relapse. Only 12.7% of directors affirmed the statement, "Six months of pretransplant abstinence decreases the risk of relapse."

Conclusions: More centers are providing ELT for severe ALD. Inability to participate in alcohol addiction therapy and <6 mo of survival are commonly reported circumstances for considering ELT. Continued investigation of posttransplant outcomes in patients receiving ELT is essential to establishing a national consensus for distributing this valuable resource.