Transplantation proceedings最新文献

Ischemia-reperfusion injury (IRI) profoundly impacts organ transplantation, especially in orthotopic liver transplantation (OLT). Disruption of the mitochondrial respiratory chain during ischemia leads to ATP loss and ROS production. Reperfusion exacerbates mitochondrial damage, triggering the release of damage-associated molecular patterns (DAMPs) and inflammatory responses. Mitochondrial dysfunction, a pivotal aspect of IRI, is explored in the context of the regulatory role of ectonucleotidases in purinergic signaling and immune responses. CD39, by hydrolyzing ATP and ADP; and CD73, by converting AMP to adenosine, emerge as key players in mitigating liver IRI, particularly through ischemic preconditioning and adenosine receptor signaling. Despite established roles in vascular health and immunity, the impact of ectonucleotidases on mitochondrial function during hepatic IRI is unclear. This review aims to elucidate the interplay between CD39/73 and mitochondria, emphasizing their potential as therapeutic targets for liver transplantation.

This article explores the role of CD39/73 in tissue hypoxia, emphasizing adenosine production during inflammation. CD39 and CD73 upregulation under hypoxic conditions regulate immune responses, demonstrating protective effects in various organ-specific ischemic models. However, prolonged adenosine activation may have dual effects, beneficial in acute settings but detrimental in chronic hypoxia.

Herein, we raise questions about ectonucleotidases influencing mitochondrial function during hepatic IRI, drawing parallels with cancer cell responses to chemotherapy.

The review underscores the need for comprehensive research into the intricate interplay between ectonucleotidases, mitochondrial dynamics, and their therapeutic implications in hepatic IRI, providing valuable insights for advancing transplantation outcomes.

Background

Sarcopenia's impact on post-liver transplant outcomes remains a subject of debate, with limited data from South Asia on its association with post-liver transplant hospital stays. This study aims to investigate sarcopenia's influence on post-transplant hospitalization duration in South Asians.

Methods

In this retrospective study, patients with liver cirrhosis who underwent living-donor liver transplantation (LDLT) at Shifa International Hospital in Islamabad, Pakistan, between January 2022 and January 2023 were included. Computed tomography (CT) images were used to assess the skeletal muscle index (SMI). The areas of the psoas, erector spinae, multifidus, quadratus lumborum, rectus abdominis, transverse abdominis, and internal/external oblique muscles were quantified at the level of L3. The data were analyzed using SPSS version 29.0 (IBM).

Results

There was a total of 84 patients. Mean age was 47.4 ± 12.0 years. There were 62 (73.8%) male patients and 22 (26.2%) female patients. Hepatitis C was noted in 36 (42.9%) patients. Twenty-two (26.2%) patients had hepatocellular carcinoma. Sarcopenia was identified in 58 (69.0%) patients. No significant association was observed between sarcopenia and intensive care unit (ICU) or general floor stays. Regression analysis identified pre-transplant model for end-stage liver disease-sodium (MELD-Na) score as the sole significant factor associated with both ICU and total length of stay (P value .002; P value .009).

Conclusion

In our population, sarcopenia did not correlate with post-transplant ICU or overall hospital stay. The pre-transplant MELD-Na score emerged as the most influential predictor of length of stay. Therefore, delaying liver transplant procedures based on muscle mass estimations may not be a practical clinical approach for South Asian patients.

Purpose

Evaluate the safety/efficacy of novel potassium binders (patiromer, sodium zirconium cyclosilicate [SZ-9]) for early postoperative hyperkalemia following kidney transplantation.

Methods

Retrospective, single-center, cohort study of deceased-donor kidney recipients transplanted between 1/2018 and 12/2020. Potassium-binder use was evaluated from immediately posttransplant until discharge. Potassium binders were administered ≥2 hours before/after medications.

Results

A total of 179 patients were included, 24 (13%) of whom received potassium binders (16 [67%] patiromer, 7 [29%] SZ-9, 1 [4%] both) for a mean of 2.5 (±3.18) doses. Peak potassium levels were higher in the potassium-binder group (6.05 vs 5.35 mEq/L; P < .001). More patients on potassium binders transitioned to atovaquone than those on no binders (n = 21 [100%] vs n = 112 [75%], respectively; P = .005). Delayed graft function (DGF) was observed in 100 (56%) patients, with a higher proportion receiving potassium binders (18 [75%] vs 82 [53%], respectively; P = .042). There was no difference between groups in number of posttransplant dialysis sessions required in the general study population (P = .2), nor in the DGF group (P = .12). No difference was noted in the incidence of ileus (P = .2), or gastrointestinal symptoms (diarrhea, nausea, vomiting; P = .6). Of the 24 patients who received inpatient binders, 9 (37.5%) were discharged and remained on them for a mean of 46 (±49) days.

Conclusion

Patiromer and SZ-9 appear safe in the early posttransplant period, but larger prospective trials are needed. Potassium-binder use does not appear to be associated with fewer dialysis sessions in DGF patients, however, they may be used as additional tools for lowering potassium in these patients.

Kaposi's Sarcoma (KS) is a malignant vascular tumor commonly seen in immunocompromised individuals, particularly patients with acquired immunodeficiency syndrome. Lung transplant recipients are at high risk of developing KS due to a strong immunosuppressive regimen that can lead to donor-derived infection or reactivation of recipient human herpesvirus 8, the causative organism for KS. In this overview, we describe 2 lung transplant recipients who developed pulmonary KS with poor outcomes, reviewing the diagnosis, bronchoscopy findings, and treatment and surveillance strategies for pulmonary KS.

Background

Community-acquired respiratory viruses (CARVs) are associated with poor outcome in solid organ transplant recipients. We reviewed some of these outcomes such as respiratory support, length of stay, admission to the intensive care unit, steroid use, and 30-day all-cause mortality.

Methods

Multihospital, single center, retrospective review of electronic health records from January 1, 2014, to December 31, 2019.

Results

Twenty-three solid organ transplant recipients (20 male and 3 female) who tested positive for CARVs were identified. The mean age at admission was 60 years, average length of stay was 8 days with 2 patients needing >2 weeks. Six patients required intensive care unit and 8 required supplemental oxygen support. CARV distribution was rhinovirus in 48%, parainfluenza in 29%, metapneumovirus in 12%, respiratory syncytial virus in 0.03%, adenovirus in 0.03%, and non-novel coronavirus in 0.06%. All patients were immunosuppressed, intravenous immunoglobulins were used in 3 patients, antivirals in 7 patients (ribavirin in 6 and oseltamivir in 1), and steroids in 10 patients. Twelve patients had transplant organ biopsy with 5 showing acute cellular rejection. Thirty-five percent of patients died within 1 year (2 during the same admission).

Conclusion

Transplant recipients are at a high risk of infections, especially CARVs, which may increase morbidity and mortality. In our observational study, we assessed patients with solid organ transplants who were admitted and tested positive for CARVs, and the associated impact on their clinical course. Careful analysis of the results will help us to emphasize the importance of timely diagnosis and treatment in specific populations.

Introduction

We prospectively evaluated 3 cases regarding the usefulness of fully-covered self-expandable metal stents (FCSEMSs) for hepaticojejunostomy anastomotic stricture (HAS) after living donor liver transplantation (LDLT), which could not be resolved with conventional treatment using a plastic stent.

Case report

All patients underwent LDLT with Roux-en-Y reconstruction; therefore, a short-type double-balloon enteroscope was used for the endoscopic procedures. HAS was observed on enteroscopic view of endoscopy in patients 1 and 2, and cholangiography revealed dilatation of the intrahepatic bile duct. The FCSEMS was successfully placed without the report of adverse events. The FCSEMS was removed after 16 weeks, and the HAS improved in both patients. In addition, stone clearance was also achieved in patient 2. On the other hand, FCSEMS was not placed in patient 3 because there was no indication of FCSEMS placement due to the multiple segmental biliary strictures (pruned-tree appearance on cholangiography). Subsequent deceased-donor liver transplantation confirmed recurrent primary sclerosing cholangitis. In this case, magnetic resonance cholangiopancreatography (MRCP) was not performed prior to cholangiography to rule out PSC recurrence.

Conclusion

FCSEMS placement may be effective and safe for HAS after LDLT, which is not resolved with conventional treatment using a plastic stent. MRCP should be used to identify HAS prior to invasive cholangiography.

Background

To review the impact of the operating microscope (OM) for reconstruction of the hepatic artery (HA) by comparing the outcomes with standard loupe reconstruction (SL) in pediatric liver transplantation (LT).

Methods

Studies comparing the application of OM and SL for the reconstruction of the HA in primary pediatric LT were included from a systematic search of MEDLINE, Cochrane Library and EMBASE from inception to June 2022. Re-transplantation, dual grafts and auxiliary transplants were excluded. Primary outcome was the rate of HA thrombosis (HAT). Secondary outcomes were graft loss and mortality.

Results

There were 1261 liver recipients from 9 included studies published until June 2022. There were 484 patients in the OM group and 777 patients in the SL group. HAT incidence with OM was significantly lower with OR = 0.18 (95% CI: 0.07-0.48). The 1-year graft survival was significantly better in the OM group with OR = 2.77 (95% CI: 1.13-6.80). 1-year overall mortality was also significantly lower with OM with OR = 0.39 (0.18-0.86). The use of OM did not significantly impact the incidence of HAT in the living donor liver transplant subgroup. Differences in time for hepatic HA reconstruction, total operating time and length of hospital stay did not reach statistical significance.

Conclusion

The use of OM has reduced the risk of HAT, graft loss and mortality in pediatric liver transplantation. Adoption of microsurgical principles in general may have contributed to the improved outcomes with SL reconstruction of HA in pediatric LT.

Vascular endothelial cell dysfunction plays an important role in myocardial ischemia–reperfusion (I/R) injury, and pannexin 1 (Panx1), an ATP-permeable channel, is closely associated with the pathophysiological processes of I/R injury. The purpose of this study was to investigate the protective effects of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) and the underlying mechanism in a model of I/R injury. For the cellular model of I/R injury, human umbilical vein endothelial cells (HuVECs) were exposed to hypoxia/reoxygenation (H/R) conditions. The model cells were then treated with HuMSC-EVs, and the effects on cell survival and specific signaling activities were observed. The results showed that after H/R exposure, Panx1 expression and other markers of cellular damage were increased in HuVECs. However, treatment with HuMSC-EVs inhibited the H/R-induced increase in Panx1 expression and improved HuVEC survival. Mechanistically, HuMSC-EVs were found to inhibit the p38 mitogen-activated protein kinase (MAPK)-dependent apoptosis pathway, as evidenced by increased Bcl2 expression and reductions in p38 MAPK phosphorylation, Bax expression, and cleaved-caspase 3 expression. Together our data suggest that HuMSC-EVs alleviate H/R-induced apoptosis among HuVECs by inhibiting activity of the Panx1/p38-MAPK-dependent apoptosis pathway.

Background

Delayed graft function (DGF) is a common post-transplant event associated with increased resource utilization. As a center with experience in DGF, we aimed to assess differences in readmissions and post-transplant outcomes between patients with and without DGF.

Methods

This was a retrospective review of deceased donor kidney transplant recipients at Mayo Clinic Arizona between 2015 and 2020. Recipients with at least one early readmission following kidney transplantation were included in the study. Two groups were identified: (1) recipients with DGF who required early readmission and (2) recipients without DGF who required early readmission.

Results

Among recipients with DGF, 43.9% (n = 405) required early readmission compared to 29.1% (n = 179) without DGF (P < .0001). There were no differences in the initial hospital length of stay (P = .08), and most recipients in both groups only required a single readmission (61.7% vs 72.1%, P = .02). Recipients with DGF were more likely to have ≥2 readmissions (P = .02) and a higher total readmission rate (P = .006). Recipients with DGF who required readmission also required more outpatient clinic visits (P = .003). When comparing recipients with and without DGF who required readmission, there were no differences in patient (P = .22) or death-censored (P = .72) graft survival. When comparing patients with and without DGF requiring one versus ≥2 readmissions, there were no differences in patient survival (P = .15), however patients with DGF and ≥2 readmissions had lower death-censored graft survival (P = .001).

Conclusions

Recipients with DGF are at increased risk of readmission. Transplant center-level changes to reduce readmissions and infections could have an important impact on DGF outcomes.

Background

Cytomegalovirus retinitis (CMVR) is a well-described complication of CMV disease in immunocompromised hosts. While robust data exists for CMVR in patients with acquired immunodeficiency syndrome (AIDS), the incidence and risk factors for CMVR in solid organ transplant recipients (SOTR) with CMV viremia are less defined.

Methods

We performed a retrospective cohort study of SOTR who had CMV viremia and underwent routine ophthalmologic examination between 1/1/2018 and 3/16/2022. Univariate statistics were performed to evaluate risk factors for development of CMVR.

Results

Overall, 38 patients were included, primarily kidney (78.9%), heart (7.9%), and liver (7.9%) transplant recipients. Five patients (13.2%) developed CMVR during the study period. CMVR was diagnosed an average 281 days after index transplantation, 84 days from the most recent rejection episode, and 69 days from onset of viremia. Only 1 patient (20%) had symptoms at the time of CMVR diagnosis. CMVR was associated with preceding allograft rejection as well as transplanted organ type.

Conclusion

While CMV tissue disease more commonly manifests in other organs, CMVR occurred relatively frequently in this group of high-risk SOTR with CMV viremia. As most of the patients in our study did not have ocular symptoms at the time of diagnosis, routine ophthalmologic screening should be considered in SOTR with CMV viremia.