Transplantation最新文献

Rationale: Krabbe disease is a rare autosomal recessive genetic disorder for which no specific cure is currently available. In clinical practice, management primarily relies on supportive and symptomatic therapies aimed at alleviating patient suffering. Although the disease remains incurable, the intensity of medical interventions has decreased over time, highlighting the need for innovative and integrated therapeutic approaches. This case study presents a patient who received a combination of Western medicine and traditional Chinese medicine, resulting in a significant reduction in clinical symptoms.

Patient concerns: The patient primarily presents with unsteady gait, bilateral lower extremity weakness, and nocturnal muscle tremors in both lower limbs. Electromyography examination revealed functional impairment of the deep sensory pathways in both lower extremities. Additionally, the mutation sites identified in this patient are c.1901T>C and c.98T>G; notably, the mutation site c.98T>G has not been previously reported. The therapeutic efficacy of Western medicine for this condition appears to be unsatisfactory.

Diagnoses: This patient was diagnosed with Krabbe disease.

Interventions: On January 17, 2025, the patient decided to incorporate traditional Chinese medicine into the treatment regimen for concurrent therapy.

Outcomes: During the concurrent treatment with integrated traditional Chinese and Western medicine, the patient exhibited remission of clinical symptoms and a corresponding improvement in quality of life.

Lessons: The integrated treatment of traditional Chinese and Western medicine offers new therapeutic options for the management of Krabbe disease.

Background: Adopting donation after circulatory death (DCD) hearts can increase the donor pool. However, DCD hearts experience severe ischemia-reperfusion injury (IRI). Ferroptosis is a key contributor to organ IRI. Liproxstatin-1 (Lip-1), a selective ferroptosis inhibitor, markedly suppresses this form of cell death. This study evaluated the cardioprotective effect of Lip-1 on DCD hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model.

Methods: The donor hearts of Lewis rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 3 h, and then heterotopically transplanted into recipient rats. Dimethyl sulfoxide or Lip-1 was added to the perfusate of normothermic EVHP in the control or Lip-1 group. Cardiac function was assessed during EVHP and 4 h after heart transplantation. We investigated the histological changes and the levels of oxidative stress, inflammation, apoptosis, CD31 expression, and ferroptosis in the posttransplant DCD hearts.

Results: compared with the control group, Lip-1 treatment significantly improved the cardiac function of DCD hearts in the first hour of EVHP and 4 h after heart transplantation, attenuated the levels of myocardial ferroptosis (glutathione peroxidase 4, SLC7A11, ACSL4, COX2), inflammation (interleukin-1β, interleukin-6, tumor necrosis factor-α), oxidative stress (4-hydroxynonenal), apoptosis (Bax, Bcl-2, caspase-3), reduced histological injury, and ameliorates endothelial dysfunction (CD31) in the posttransplant DCD hearts.

Conclusions: Normothermic EVHP combined with Lip-1 treatment can be a promising DCD heart preservation strategy, which can alleviate myocardial IRI, ameliorate endothelial dysfunction, and improve posttransplant cardiac function for DCD hearts via inhibiting myocardial ferroptosis.

Background: Access to liver transplantation (LT) remains prioritized by patient acuity. Retrospective studies have demonstrated that patients with lower acuity still experience significant survival benefit with transplant; however, these results have yet to be confirmed by a randomized controlled trial.

Methods: We simulated a randomized controlled trial using the novel trial emulation method. Adults listed for liver-only transplant 2016-2019 were paired using a time-dependent 1:1 propensity score and randomized to transplant (TXP) versus waitlist-only (WL) arms. All patients randomized to TXP had undergone transplant during the study period, whereas the WL arm included both patients who underwent transplant (WL-TXP) and did not (WL-only). Follow-up was measured from the date of transplantation of the TXP patients until removal from the waitlist, loss to follow-up, retransplantation, or the end of our follow-up period (December 31, 2019), whichever occurred first for the WL patients.

Results: Of 23 672 total prematched patients, 8834 (37.3%) underwent transplant and 9460 had a lower Model for End-Stage Liver Disease (MELD) score of 6-14 (40.0%). 18.9% of MELD score 6-14 patients were transplanted compared with 49.6% of MELD score 15-24 patients. Nine thousand five hundred six patients were successfully matched. WL patients had a 73% increased risk of death compared with TXP patients (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.48-2.04). WL-only patients had a 2.83-fold greater mortality risk during follow-up compared with TXP or WL-TXP patients (HR, 2.83; 95% CI, 2.35-3.43). Trends were similar in MELD score 15-24 (HR, 3.74; 95% CI, 2.90-4.82) and MELD score 6-14 (HR, 1.52; 95% CI, 1.04-2.23) cohorts.

Conclusions: Patients with a low MELD score experience a significant survival advantage with transplantation, despite their lower-acuity disease.

Background: Xenotransplantation has emerged as a promising solution to the critical organ shortage, with encouraging results in preclinical nonhuman primate studies and recent first-in-human transplants. Our group previously performed pig-to-rhesus macaque renal xenotransplants using the clinically available costimulation blockade agent belatacept; however, graft survival was modest (>1 moh). Analysis of rejected xenografts identified natural killer (NK) cells as a predominant infiltrating population.

Methods: In this study, we investigated whether adding adjuvant αIL-15-an agent known to suppress T-cell subsets and deplete NK cells in rhesus macaques-could improve xenograft survival. αIL-15 was combined with a clinically relevant immunosuppressive regimen comprising T-cell depletion, belatacept, mycophenolate mofetil, and steroids.

Results: We found that the addition of αIL-15 significantly improved xenograft survival and function. Longitudinal analysis of NK cell subsets revealed a shift from a predominant cytotoxic CD16 + CD56 - population to a double-negative CD16 - CD56 - phenotype following αIL-15 treatment.

Conclusions: These findings deepen our understanding of NK cell subsets and their potential contributions to xenograft injury and suggest that targeted modulation of NK cell populations can enhance xenograft outcomes in a preclinical pig-to-rhesus macaque model of renal xenotransplantation.

Background: Hematopoietic cell transplantation (HCT) provides effective long-term management for some inborn errors of immunity. Genetic findings can inform donor selection, considerations in conditioning intensity and agents, and graft-versus-host disease prophylaxis. Exome/genome sequencing is increasingly accessible but of uncertain clinical utility. We aimed to evaluate the clinical utility of comprehensive genomic evaluations through review of HCT at our center.

Methods: We performed exome/genome sequencing on pre-HCT samples from participants between 2017 and 2023. We reported primary findings (PF) and secondary findings (SF). Post hoc, we analyzed medication and pharmacogenetic (PGx) data.

Results: We analyzed pre-HCT exome/genome sequencing (n = 84 exome, n = 63 genome, n = 32 with both) for 179 probands. Most (143/179; 79.9%) had a PF underlying the HCT indication, with GATA2 being most common (n = 59). Three percent of participants had an SF predisposing to cancer or cardiovascular disease. Most (n = 108/179; 60.3%) received ≥1 medication(s) that may have been further optimized with PGx. Using Kaplan-Meier survival analysis, we compared the survival rates of participants with 0, 1, and ≥2 genomic risk factors (GRF: absence of PF; presence of SF or PGx). Survival at 3 y was 94.8%, 84.8%, and 58.5% for those with 0, 1, and ≥2 GRF, respectively (log-rank: 16.10, df = 2, P  = 0.0003), indicating statistically significant survival differences by GRF.

Conclusions: Comprehensive genomic evaluation is an emerging avenue for tailoring HCT approaches, and identification of HCT-relevant findings may be common. On multivariate analysis, GRF was associated with survival in this retrospective cohort. Prospective research is warranted to further integrate genomic data into precision treatment.

Organ transplantation is the only definitive cure for end-stage organ failure. The primary obstacle is the scarcity of viable donor organs, resulting in many patients dying on the transplant waitlist. The last decade has brought a range of transformative technologies to address this shortage: machine perfusion has risen as an option to greatly increase the human donor organ utilization, while xenotransplantation further promises to fundamentally alter the calculus in supply constraints. Given this increasing availability, the logistics of allocation rises as the next key technological barrier. Cryopreservation strategies aim to increase the viable storage time for organs and thereby enable the creation of a cold-supply chain for clinical transplantation. This technology has the potential to overcome limitations related to preservation and transportation, histocompatibility matching, complex organ allocation and wastage, and in tandem with xenotransplantation, provide an unlimited off-the-shelf supply of organs. This review aims to cover the latest research updates in the use of cryopreservation, how it compares to current clinical preservation strategies, and discuss how its implementation into the world of transplantation may require new logistical, ethical and regulatory frameworks.

The nature and severity of the inflammatory response influences the outcome of organ allotransplantation and xenotransplantation. In allotransplantation, the source of the allograft, for example, from a living, brain-dead, or circulatory death donor, influences the inflammatory response, as do such factors as the preexisting comorbidities and the length of the period of chronic kidney disease in the recipient and the management he/she has received. There is also inflammation associated with the transplant surgery, for example, as a result of ischemia-reperfusion injury. In xenotransplantation, inflammation associated with donor factors will be reduced and, as the patients will receive a pig graft at a much earlier stage of their chronic organ failure, the contribution of recipient factors should also be reduced. However, there is a well-documented systemic inflammatory response to the presence of a pig xenograft (probably associated with species molecular differences) that plays a role in activating the innate immune response. Indeed, there is a complex interaction between inflammation, coagulation dysfunction, and the innate and adaptive immune responses. Suppression of the inflammatory response, for example, by interleukin-6 receptor blockade, would appear to be beneficial after xenotransplantation. Several biomarkers of inflammation have been identified that may be valuable in assessing the response to therapy.