世界移植杂志最新文献

Background: Hypothermic machine perfusion (HMP) has demonstrated benefits in terms of early kidney transplant function compared to static cold storage. While longer preservation times have shown detrimental effects, a previous paired study indicated that longer pump times (the second kidney in a pair) might lead to improved outcomes.

Aim: To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.

Methods: A total of 61 pairs of transplant recipients who received kidneys from the same donor (2012-2021) were analyzed. Patients were divided into two groups depending on whether they were transplanted first (K1) or second (K2). Therefore, the patients in each pair had identical donor characteristics, except for time on the pump. Statistical analyses included Kaplan-Meyer analysis and paired tests, including McNemar's test, student's paired t-test, or Wilcoxon's test, as appropriate.

Results: The two groups of recipients had similar demographics (age, body mass index, diabetes, time on dialysis, sensitization and retransplants). Cold ischemic times for K1 and K2 were 8.9 (95%CI: 7.9, 9.8) and 14.7 hours (13.7, 15.8) (P < 0.0001), respectively. Overall, K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year (P = 0.015). Delayed graft function was less common in K2, 12/61 (20%) than in K1, 20/61 (33%) (P = 0.046). Finally, K2 showed a higher graft survival than K1 (P = 0.023).

Conclusion: Our results agree with a previous study that suggested possible advantages to longer pump times. Both studies should encourage further research into HMP's potential anti-inflammatory effect.

Background: Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.

Aim: To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT.

Methods: This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing.

Results: Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes.

Conclusion: Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Background: Hepatitis B immunoglobulin (HBIG) in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation for HBV-associated disease.

Aim: To evaluate patients' satisfaction, preferences, and requirements for subcutaneous (SC), intramuscular (IM), and intravenous (IV) HBIG treatments.

Methods: A self-completion, cross-sectional, online, 22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France, Italy, and Turkey. Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint (trade-off) exercise.

Results: Ninety patients were enrolled; 32%, 17%, and 51% were SC, IM, and IV HBIG users, respectively. Mean duration of treatment was 36.2 months. SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient, easiest to administer, least painful, and had the highest self-rating of treatment compliance. More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive (67%, 28%, and 28%, respectively). In the target product profile assessment, 76% of patients were likely to use hypothetical SC HBIG. In the conjoint exercise, administration route, frequency, and duration were key drivers of treatment preferences.

Conclusion: Ease, frequency, duration, and side effects of HBIG treatment administration were key drivers of treatment preferences, and SC HBIG appeared advantageous over IM and IV HBIG for administration ease, convenience, and pain. A hypothetical SC HBIG product elicited a favorable response. Patient demographics, personal preferences, and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

Background: Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart, liver and kidney transplants. However, information on how functional status, before and after transplant impacts post-transplant survival outcomes is lacking.

Aim: To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.

Methods: We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022. The primary outcome was mortality. Using the Karnofsky Performance Status, functional impairment was categorized as severe, moderate and normal. Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.

Results: The median age was 41 years, majority (53.4%) were women. Severe impairment was present in 28.3% of recipients. The median survival time was 906.6 days. The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively. Recipients with severe impairment had a 56% higher risk of mortality at one year [Hazard ratio (HR) = 1.56; 95%CI: 1.23-1.98; P < 0.001] and 58% at five years (HR = 1.58; 95%CI: 1.24-2.00; P < 0.001) compared to patients with no functional impairment. Recipients with worse functional status after transplant also had poor survival outcomes.

Conclusion: Pre- and post-transplant recipient functional status is an important prognostic indicator for short- and long-term intestinal transplant outcomes.

Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

Background: Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria.

Aim: This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT.

Methods: A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed.

Results: 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence.

Conclusion: SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

Background: Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting.

Aim: To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.

Methods: Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.

Results: Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.

Conclusion: Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Background: Early hospital readmissions (EHRs) after kidney transplantation range in incidence from 18%-47% and are important and substantial healthcare quality indicators. EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs. EHRs have been extensively studied in American healthcare systems, but these associations have not been explored within a Canadian setting. Due to significant differences in the delivery of healthcare and patient outcomes, results from American studies cannot be readily applicable to Canadian populations. A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant.

Aim: To explore the burden of EHR on kidney transplant recipients (KTRs) and the Canadian healthcare system in a large transplant centre.

Methods: This single centre cohort study included 1564 KTRs recruited from January 1, 2009 to December 31, 2017, with a 1-year follow-up. We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge, excluding elective procedures. Multivariable Cox and linear regression models were used to examine EHR, late hospital readmissions (defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR), and outcomes including graft function and patient mortality.

Results: In this study, 307 (22.4%) and 394 (29.6%) KTRs had 30-d and 90-d EHRs, respectively. Factors such as having previous cases of rejection, being transplanted in more recent years, having a longer duration of dialysis pretransplant, and having an expanded criteria donor were associated with EHR post-transplant. The cumulative probability of death censored graft failure, as well as total graft failure, was higher among the 90-d EHR group as compared to patients with no EHR. While multivariable models found no significant association between EHR and patient mortality, patients with EHR were at an increased risk of late hospital readmissions, poorer kidney function throughout the 1^st year post-transplant, and higher hospital-based care costs within the 1^st year of follow-up.

Conclusion: EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system. The results warrant the need for effective strategies to reduce post-transplant EHR.

Background: The United States has witnessed significant advancements in the field of organ transplantation over the course of the last five decades, as demonstrated by a notable increase in the quantity of academic research. The presence of a highly dynamic research environment necessitates continuous evaluations to maintain the integrity and progress of the field.

Aim: To evaluate the total output and thematic emphasis of transplant research conducted in the United States.

Methods: On January 10, 2023, we conducted a bibliometric search of United States research output in transplantation journals from the Web of Science database's Science Citation Index Expanded. We excluded editorials, meeting abstracts, and other non-article types. We analyzed annual trends, authors, institutions, articles, keywords, and countries collaborating with the United States, using VOSviewer 1.6.18 to create figures and tables.

Results: The United States published 25956 papers (3078 reviews and 22878 articles) representing 37.7% of the world's scientific output. Canada emerged as the top collaborator with the United States, co-authoring 1263 articles. Leading institutions in United States transplantation research were the University of Pittsburgh (1749 articles), Mayo Clinic (1605 articles), Harvard Medical School (1549 articles), and Johns Hopkins University (1280 articles). The top three keywords with over 2000 occurrences were "recipients," "survival," and "outcomes," indicating a focus on graft and recipient outcome markers by United States researchers.

Conclusion: Our findings demonstrate the United States leadership in organ transplantation research, contributing significantly to the global scientific output in this field. However, opportunities exist for fostering expansive partnerships, particularly with developing countries. This study provides valuable insights into the transplantation research landscape in the United States, emphasizing the importance of ongoing evaluations to maintain and propel advancements in this critical medical discipline. The results may facilitate future collaborations, knowledge exchange, and the pursuit of innovative solutions in the realm of organ transplantation.

Background: Numerous reports have demonstrated that the pathophysiology of graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT) is closely related to vascular endothelial disorders and coagulation abnormalities. We previously presented the discovery of a principle and the development of a novel instrument for measuring whole blood coagulation. This was achieved by assessing the variations in the dielectric properties of whole blood.

Aim: To investigate how GVHD affects the changes of dielectric properties of whole blood in patients with HSCT.

Methods: We examined the changes of dielectric properties of whole blood and erythrocyte proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis sequentially in patients with HSCT and compared it with clinical symptoms and inflammatory parameters of GVHD.

Results: During severe GVHD, the dielectric relaxation strength markedly increased and expression of band3 decreased. The dielectric relaxation strength normalized with the improvement of GVHD. In vitro analysis confirmed that the increase of relaxation strength was associated with severe erythrocyte aggregates, but not with decreased expression of band3.

Conclusion: Severe erythrocyte aggregates observed in GVHD may cause coagulation abnor malities and circulatory failure, which, together with the irreversible erythrocyte dysfunction we recently reported, could lead to organ failure.