Frontiers in transplantation最新文献

Introduction: Lung transplantation has seen strides in survival over the past few decades, though long-term survival remains poor. Chronic lung allograft dysfunction (CLAD) is a leading cause of graft failure and mortality beyond the first year. Anti-thymocyte globulin (ATG) is commonly used for treating refractory CLAD, though its efficacy remains uncertain.

Methods: This retrospective study evaluated the impact of ATG on lung function decline and mortality among lung transplant recipients diagnosed with CLAD, defined as a persistent >20% decline in forced expiratory volume (FEV1) from baseline. Patients treated with ATG were compared to those who did not receive ATG, using mixed effects modeling for FEV1 decline and Fine-Gray competing risk modeling for mortality.

Results: Of the 124 patients with CLAD, 55 (44%) received ATG. Administration was not associated with a significant change in FEV1 decline when compared to rate of decline prior to ATG administration [-0.0881 L/year, 95% CI (-0.21, 0.034)] or compared to non-ATG recipients [0.0599 L/year, 95% CI (-0.057, 0.18)]. However, ATG was associated with a lower hazard of all-cause mortality [subhazard ratio 0.66, 95% CI (0.39-1.14)].

Discussion: While ATG improved survival, it did not alter lung function decline, affirming the need for prospective randomized studies.

Introduction: Lung transplantation (LT) is the standard treatment for end-stage chronic respiratory failure that does not respond to other therapies. Advances in surgical techniques and perioperative care have improved survival rates. However, postoperative complications, particularly atrial arrhythmias (AA) remain clinically significant. Although AAs are frequently observed in the early postoperative period, data regarding their incidence and impact on outcomes are scarce. This observational study aims to: (i) assess the incidence of new-onset postoperative AA within one month of bilateral LT; (ii) evaluate their impact on short- and mid-term outcomes; and iii) identify potential predictors.

Materials and methods: We retrospectively reviewed all consecutive bilateral LT recipients admitted to the Intensive Care Unit (ICU) of the University Hospital of Padua between October 2021 and December 2023. Clinical variables, perioperative right heart catheterization data, and echocardiographic measurements were collected.

Results: A total of 85 LT recipients were enrolled. Postoperative AA occurred in 27 patients (32%), with atrial fibrillation emerging as the most common arrhythmia (55.6%). The remaining 58 (68%) patients did not develop any arrhythmic disorder. Many AA patients (22, 81.5%) required treatment with antiarrhythmic drugs or electrical cardioversion. Compared to the control group, AA patients were older (p-value 0.002) and usually affected by coronary heart disease (18.5% vs. 5.2%, p-value 0.05) and obstructive respiratory disease (55.5% vs. 27.7%, p-value 0.004). AA patients more frequently experienced difficult weaning from mechanical ventilation, a higher incidence of postoperative V-A ECMO, more frequent anastomotic complications, and longer ICU stays, as compared to controls. Multivariate analysis identified older age (OR 1.11, 95% CI 1.01-1.25, p-value 0.047) and higher postoperative dobutamine dosage (OR 2.25, 95% CI 1.15-5.01, p-value 0.026) as the only significant predictors of new-onset AA within one month of LT.

Conclusions: In our cohort, the incidence of new-onset AAs was 32% after bilateral LT. AA patients experienced worse short- and mid-term outcomes compared to controls. Furthermore, this study highlights older age and postoperative dobutamine administration as significant predictors of new-onset AA following bilateral LT. Further research is needed to clarify the causal relationships and long-term implications of AA on the clinical course of LT recipients.

Background: Alcohol use disorder (AUD) treatment in liver transplant (LT) recipients requires multidisciplinary management. We aim to analyze post-LT patients' perceptions of the transplant clinic, local community resources, desired supports and barriers for AUD recovery resources.

Methods: A survey of adult recipients who received a LT within the last ten years with a history of AUD at a single Transplant Center was conducted. The survey consisted of five categories: demographics, strategies for AUD treatment used before and after LT, recent alcohol use, and challenges faced in AUD treatment. Results were reported using descriptive statistics.

Results: Forty-one of 203 approached participants completed the questionnaire over a 3-month period [median age 56 years (45.5-62), 68.3% male, 90.2% white, median time since transplant 21 months (9.4-50.7)]. Thirty-three (80.5%) had a period of abstinence from alcohol prior to LT: 17 (41.5%) 1-5 years, 7 (17%) 6-12 months, and 7 (17%) < 6 months. 88.9% reported their goal for alcohol was complete abstinence. Useful strategies for AUD management before LT included exercise (73.1%), family support (63.4%), and therapy (58.5%). Exercise was most effective post-LT resource to prevent return to alcohol use, followed by social work assistance (51.2%), and finding a new hobby (48.8%). Social support and difficulties with availability of AUD treatment resources were the main challenges perceived by survey participants.

Conclusion: Exercise, social support, social work assistance, finding new hobbies, and therapy were the preferred resources for AUD management. Future interventions should facilitate access to resources to assist with sobriety and incorporate their outside support network in assisting with recovery from AUD.

Introduction: Acute cellular rejection of transplanted lung allografts involves activated cytotoxic T cells and reduced Regulatory T (Treg) cell function. Calcineurin inhibitors, the cornerstone of immunosuppressive regimens, suppress T cell cytotoxicity but inhibit Treg proliferation. The DNA hypomethylating agent decitabine (DAC) can abrogate T cell cytotoxicity while stimulating Treg proliferation.

Methods: We sought to determine the effects of DAC treatment in a murine MHC-mismatched orthotopic lung transplant model.

Results: Rescue treatment with DAC maintains lung allograft gross and histologic integrity with a reduction in cytotoxic T cell responses. CD4+FoxP3+ T cell depletion in Foxp3DTR mice exacerbated rejection lung injury compared to CD4+FoxP3+ T cell sufficient mice and failed to abolish the protective effect of DAC in this model. The protective effect of DAC was associated with a reduction in cytokine production from host T-cells.

Discussion: Decitabine could offer a new line of treatment for acute lung allograft rejection, in part via its effects on Tregs.

The first successful renal transplantation, performed between the Herrick twins at Peter Bent Brigham Hospital (PBBH) in 1954, was the culmination of four decades of collaboration among an exceptional group of physician-scientists and hospital leadership. PBBH was built with the primary goal of establishing an institution dedicated to biomedical research. John Merrill, a cardiologist who would go on to lay the foundation of modern nephrology, was perhaps one of the most important leaders in this effort. In addition to his pioneering transplantation work, Merrill developed what became the first functional dialysis machine that played a crucial role in stabilizing the diseased Herrick twin brother in preparation for the transplantation surgery-an operation that would go down in history as the world's first successful organ transplantation. Through these collective efforts, PBBH became the only hospital in the world at the time capable of offering a lifesaving dialysis-transplant procedure that combined both groundbreaking interventions. The dialysis-to-transplant model developed by Merrill has subsequently been adopted worldwide and saved thousands of lives.

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. Outpatient treatment with tixagevimab/cilgavimab prevented clinical deterioration in unvaccinated patients with COVID-19 during periods of Alpha and Delta dominance. Data on the clinical outcomes in KTR receiving tixagevimab/cilgavimab for outpatient treatment during Omicron dominance are scarce. We retrospectively analyzed the clinical outcomes in a single-center cohort of 102 KTR who received tixagevimab/cilgavimab for outpatient treatment of SARS-CoV-2 infection within 7 days after symptom onset between June 29, 2022, and April 4, 2023 and compared them to a historical cohort of 219 KTR, who were infected during the Omicron period, but before tixagevimab/cilgavimab treatment was employed at our institution (January 15 until June 28, 2022). The hospitalization rate and need for ICU treatment was lower in the tixagevimab/cilgavimab group compared to the control group (2.9% vs. 15.5%, p = 0.001, and 0% vs. 5.9%, p = 0.012, respectively), while there was no statistically significant difference in COVID-19 mortality between both groups (0% vs. 2.3%, p = 0.124). These real-world data further support that outpatient treatment with monoclonal antibodies such as tixagevimab/cilgavimab can prevent clinical deterioration in kidney transplant recipients during a period of Omicron dominance. Novel therapeutics are needed for variants for which tixagevimab/cilgavimab shows no neutralization.

Background: Medical innovations and advancements, such as orthotopic liver transplantation (OLT) allow thousands of patients worldwide to live comfortably, despite previously life-threatening conditions. Procreation, one of the most powerful human instincts, drives the force behind the increasing popularity of pregnancies after OLT, with their numbers rising since the first documented case in 1976. Pregnancy post OLT remains a high-risk event, requiring careful management by a multidisciplinary team of hepatologists, obstetricians, transplant surgeons, and neonatologists. This review aims to synthesize current evidence on family planning, pregnancy management, and maternal and neonatal outcomes in women who have undergone OLT, based on studies indexed in PubMed up to December 2024.

Findings: Due to ethical constraints, international registries of pregnancies after OLTs play a critical role in collecting observational data and establishing comprehensive guidelines for clinical practice. As the data indicated, OLT can help restore hormonal balance and menstrual cycle, enabling many women to conceive after OLT. However, adequate family planning is crucial, as women must be aware of the potential risks. Preconception counseling is essential to choose the right timing for pregnancy, assess graft function, and optimize immunosuppressive therapy, as some medications must be discontinued due to teratogenic risks. The risks associated with pregnancy in OLT recipients include gestational hypertension, preeclampsia, and gestational diabetes. Neonates are significantly more likely to experience prematurity and low birth weight. Post-partum management focuses on monitoring graft function, managing complications, and guiding breastfeeding.

Conclusions: Available literature and observational studies consistently demonstrate that women post-OLT can achieve successful pregnancies and deliver healthy infants. However, due to the inherent risks described in this population, such patients require specialized care from a multidisciplinary team. Further research is essential to optimize birth control methods and clarify the mechanisms behind the higher prevalence of pregnancy complications. Establishing the long-term safety data for immunosuppressive therapies, particularly regarding breastfeeding, is also needed.

Introduction: Hematopoietic stem cell transplantation (HSCT) is a significant treatment option for acute myeloid leukemia (AML). However, some important questions remain related to its efficacy and safety, specifically when administered to various age cohorts among pediatric and adult patients.

Aim: This study aimed to investigate the efficacy of HSCT in treating pediatric patients compared to adult patients diagnosed with AML.

Methods: A systematic search was conducted in PubMed, Scopus, Google Scholar, and Medline for studies published in the English language from inception to 2023. The findings were reported using the PRISMA checklist. Statistical analysis was conducted using Cochrane's software (Rev Man) version 5.4, which used random and fixed effect models when necessary.

Results: In total, 14 studies met the criteria for meta-analysis. The results indicated a slightly positive trend in overall survival in the pediatric and combined pediatric-adult groups compared to adults alone, although the differences were not statistically significant. For relapse rate, no significant differences were observed in the adult and pediatric groups individually, while the combined pediatric-adult group showed a substantial benefit from HSCT (OR: 2.3, P-value: -0.05). A similar trend was observed in disease-free survival, where the combined group showed a modest, though not statistically significant, improvement with HSCT. Furthermore, regarding treatment-related mortality, a statistically protective effect of HSCT was observed in the adult group (OR: 0.26, P = 0.0005), while the pediatric and combined groups did not show significant effects. For graft-vs.-host disease, a significant association with HSCT was found in the pediatric group (OR: 2.58, P = 0.03), while the adult and combined groups showed no significant effects.

Conclusion: Our analysis showed mixed results, showing a slightly better effect of HSCT in treating pediatric patients diagnosed with AML compared to adult patients.

Evidence for the contribution of non-HLA antibodies on long-term allograft outcome was suggested in early studies by Paul Terasaki and colleagues who showed worse 10-year allograft outcome in HLA identical kidney transplant recipients with a positive panel reactive antibody (PRA) as determined by the micro cytotoxicity assay, in which cells express other targets beside HLA. More recent reports have shown worse graft outcome when antibodies against non-HLA antigens were detected with HLA-donor specific antibodies (HLA-DSA), and even suggest that non-HLA antibodies may serve as precursor to development of HLA antibodies. Unfortunately, the recent studies lack reproducibility, which then leads to skepticism as to the relevance of non-HLA antibody in transplantation outcome. Consequently, routine testing for non-HLA antibody along with monitoring of HLA-DSA as part of a post-transplant immune surveillance protocol is not standard practice. The Sensitization in Transplantation: Assessment of Risk (STAR) workgroup summarized the current literature on this topic, citing differences in cohort characteristics, variability in study design, selection of sample and timepoints for testing and variability in the assays used to detect non-HLA antibodies, as reasons that impact the accurate assessment on the relevance of non-HLA antibodies. However, correlation between test results and outcome can only be determined if the assay in question is detecting the correct analyte. Therefore, here we will make the case for a plan that requires a systematic validation of high-throughput bead-based assays, to include appropriate sequence selection for non-HLA antigenic targets and quality control metrics as a first step to solving this puzzle.