Transplantation proceedings最新文献

Objective

Hematomas of the liver graft, that is, postintervention, subcapsular or intrahepatic are rare yet potentially fatal complications following liver transplantation (LT), necessitating immediate diagnosis and management to avert devastating outcomes. This study was aimed to introduce our approach to manage graft hematoma subsequent to LT.

Methods

Among 131 orthotopic liver transplantations (OLT) conducted at our institution between January 2017 and May 2023, 3 cases of intrahepatic (n = 2) and extrahepatic (n = 1) hematoma were confirmed through computed tomography (CT) within 10 days after LT. The clinical outcomes of various treatment modalities for these three cases were analyzed.

Results

Three out of 131 (2.3%) LT recipients developed graft hematoma. Patient 1 developed a spontaneous intrahepatic hematoma, without evident predisposing factors, while patient 2 developed an intrahepatic hematoma following endoscopic retrograde cholangiopancreatography (ERCP). The third case that is extrahepatic hematoma was speculated to be a result of minor hepatic parenchymal injury stemming from compressive and volume-reducing manipulation of a large graft, or secondary to focal ischemic necrosis of the liver. Our management protocol was summarized as follows: (1). Immediate ultrasound and CT, particularly enhanced CT; (2). Puncture and percutaneous drainage (PD) of the hematoma; (3). Arterial embolization if the origin could be identified as a ruptured vessel; (4). Surgical evacuation of the hematoma in the presence of bile leakage, to avoid a compartment respectably secondary infection. All three patients responded favorably to treatment and remained alive to date.

Conclusion

Prompt diagnosis and sequential individualized management can successfully deal with intra-/extrahepatic graft hematoma after LT. Our results underscored that an individualized management considering potential future complications into account.

This study aimed to evaluate the effects of UDP-glucuronosyltransferase (UGT) polymorphisms on mycophenolic acid (MPA) metabolism in renal transplant patients. A total of 11 single nucleotide polymorphisms (SNPs) of UGT1A1, UGT1A7, UGT1A8, UGT1A9, UGT1A10, and UGT2B7 were genotyped in 79 renal transplant patients. The associations of SNPs and clinical factors with dose-adjusted MPA area under the plasma concentration-time curve (AUC/D), the dose-adjusted plasma concentration (C₀/D) of 7-O-MPA-glucuronide (MPAG), and the dose-adjusted plasma concentration (C₀/D) of acyl MPAG (AcMPAG) were analyzed. In the univariate analysis, UGT1A1 rs4148323, age, and anion gap were associated with MPA AUC/D. MPA AUC/D was higher in patients with the GA genotype of UGT1A1 rs4148323 compared to patients with the GG genotype. UGT1A1 rs4148323, UGT1A9 rs2741049 and clinical factors, including age, serum total bilirubin, adenosine deaminase, anion gap, urea, and creatinine, were associated with MPAG C₀/D. UGT2B7 rs7438135, UGT2B7 rs7439366, and UGT2B7 rs7662029 also were associated with AcMPAG C₀/D. Multiple linear regression analysis showed that UGT1A9 rs2741049 and indirect bilirubin were negatively correlated with MPAG C₀/D (P = .001; P = .039), and UGT2B7 rs7662029 was positively correlated with AcMPAG C₀/D (P = .008). This study demonstrates a significant influence of UGT1A9 rs2741049 and UGT2B7 rs7662029 polymorphisms on the metabolism of MPA in vivo.

Background

With the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages.

Materials and Methods

We conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010.

Results

In this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive.

Discussion

The review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes.

Background

Cellular therapy has emerged as a promising strategy to minimize the use of conventional immunosuppressive drugs and ultimately induce long-term graft survival. Myeloid-derived suppressor cells (MDSCs) can be used for immunosuppressive treatment of solid organ transplants.

Methods

Granular macrophage colony-stimulating factor (GM-CSF) and bexarotene, an X receptor-selective retinoid, were used for in vitro MDSC induction. Cell phenotypes were detected using flow cytometry, while mRNA was detected via real-time PCR. A mouse skin transplantation model was used to verify the inhibitory effects of this treatment.

Results

The combination of GM-CSF and bexarotene-induced MDSC differentiation. MDSCs induce immune tolerance by inhibiting T-cell proliferation, influencing cytokine secretion, and inducing T-cell transformation into Treg cells. Combination treatment significantly up-regulated Arg-1 expression in MDSCs. The Arg-1 inhibitor nor-NOHA neutralized the immunosuppressive activity of MDSCs, suggesting the involvement of Arg-1 in MDSC-mediated immunosuppression. GM-CSF and bexarotene-induced MDSCs prolong graft survival in mouse skin transplants, exhibiting in vivo immunosuppressive effects.

Conclusions

A new method for inducing MDSCs is presented. The combination of GM-CSF and bexarotene induces MDSCs with remarkable regulatory functions. Adoptive transfer of the induced MDSCs extended allograft survival. These results suggest that MDSCs can potentially be used in future clinical transplants to inhibit rejection, reduce adverse events, and induce operative tolerance.

Background

BK virus nephropathy (BKVN) is a significant complication in kidney transplant recipients, resulting in graft dysfunction and potentially leading to graft loss. This study aims to investigate the incidence and outcomes of BKVN in kidney transplant recipients receiving steroid-free maintenance immunosuppression in a Latin -American cohort.

Methods

Case series study of BKVN among kidney transplant recipients who underwent transplantation between 2008 and 2023. The primary outcome was graft loss caused by BKVN, excluding death with function. Secondary outcomes included graft function and acute rejection episodes. The statistical analysis involved descriptive statistics and the Kaplan-Meier (K-M) method to plot the overall probabilities of not initiating dialysis.

Results

During the 15-year period, 2236 kidney transplants were performed, BKVN was histologically diagnosed in 38 kidney recipients and 33 cases were analyzed. Median age was 50 years and men were 48.5% of patients. A total of 45.4% of BKVN occurred within the first 12 months of transplant. The incidence of BKVN was 1.6% but it varied by era. The rate of graft loss was 75.7% (25 cases). The K-M graft survival probability at 6 months and 12 months after diagnosis of BKVN was 38.3% (95% CI 24.7–59.4) and 22.3% (95% CI 11.7–42.8), respectively.

Conclusion

BKVN affected 1.6% of transplant recipients and it was associated with high-rate of graft loss. We observed that significant graft disfunction at the time of diagnosis resulted in worse outcomes with a reduced probability of graft survival.

Introduction

The widely employed Kidney Donor Profile Index (KDPI) scoring system, designed for assessing deceased donors (DD), plays a pivotal role in predicting graft function post kidney transplantation (KT). Given the dynamic nature of renal function, including serum creatinine (sCr), in managing DDs, it remains uncertain optimal timing to use KDPI for assessing postoperative graft function.

Methods

In this retrospective review, we assessed 246 DDs who were managed within a donor management program from January 2010 to December 2021. We collected sCr values for KDPI scoring at admission, peak, and last measurements before KT. Recipient data included occurrence of slow graft function (SGF), delayed graft function (DGF), and glomerular filtration rate (GFR) at one-year post-transplantation (1 Y). Using Receiver Operating Characteristic (ROC) and Pearson correlation analyses, we explored correlations of KDPI score (admission, peak, last) with graft function (SGF, DGF, GFR 1 Y).

Results

The average age of DDs and recipients was 49.78 ± 13.37 and 52.54 ± 10.49 years, respectively, with mean KDPI values at admission, peak, and last measurements of 62.36 ± 25.44, 66.94 ± 24.73, and 63.75 ± 25.80. After transplantation, SGF was observed in 81 recipients (32.9%) and DGF in 32 (13.0%). For SGF, the Area Under the Curve (AUC) from ROC analysis were 0.684 (95% CI, 0.615-0.753; P < .001) at admission, 0.691 (0.623-0.759; P < .001) at peak, and 0.697 (0.630-0.765; P < .001) at the last measurement. In predicting DGF, the corresponding AUC values were 0.746 (0.661-0.831; P < .001) at admission, 0.724 (0.637-0.810; P < .001) at peak, and 0.721 (0.643-0.809; P < .001) at the last. Moreover, KDPI scores at all time points—admission, peak, and last—moderately correlated with GFR 1 Y (R = -0.426, -0.423, -0.417).

Conclusion

KDPI measurements at all time points, particularly admission, would be more effective in predicting DGF in DDKT.

Introduction

Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel.

Materials and Methods

We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey.

Results

Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMIS_CF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMIS_CF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMIS_CF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001).

Conclusions

A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Background

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment for relapsed/refractory lymphoma patients. Yet, the widespread use of BEAM is hindered by carmustine accessibility. This study evaluates the efficacy and safety of PEAM (Cisplatin, Etoposide, Cytarabine, and Melphalan) versus BEAM in auto-HSCT for Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients.

Methods

We conducted a retrospective single-center study of adult lymphoma patients who received PEAM or BEAM pretransplant conditioning between January 2004 to December 2022, comparing efficacy and safety outcomes.

Results

Among 143 patients (median age of 33 years, 58% males), 55 had HL, and 88 had NHL. The overall response rate (ORR) was 86.7% for PEAM and 72.3% for BEAM, and the relapse rate (RR) was lower for PEAM than BEAM (22.9% vs 45.6%). Median time to relapse (TTR) and overall survival (OS) were not reached for either group. PEAM exhibited a shorter time to both neutrophil (NE) and platelet (PE) engraftment compared to BEAM (10 vs 12 days), with a more tolerable gastrointestinal (GI) toxicity profile.

Conclusions

Both BEAM and PEAM showed similar outcomes, demonstrating comparable efficacy in terms of ORR, TTR, and OS for both HL and NHL patients. However, PEAM-conditioning was associated with a shorter time to engraftment and fewer GI adverse events.

Chromoblastomycosis (CBM), also known as chromomycosis is a chronic, granulomatous fungal infection of the skin and subcutaneous tissue. It usually occurs by the traumatic inoculation of various dematiaceous fungi and is more common in the developing world. This condition is rare in North America and the developed world. Herein, we present a case of a 75-year-old man who received a bilateral lung transplant 4 months prior and presented for evaluation of a painful, erythematous papule on the elbow which was diagnosed as CBM. This case highlights that immunosuppression used in patients who undergo solid organ transplantation not only increases the risk of opportunistic infections like CBM but can also be confused for cutaneous squamous cell carcinoma as both these entities share many overlapping clinical and histopathologic features and may be a potential source of misdiagnosis.

Objectives

To compare the clinical benefit of using albumin versus crystalloids for volume resuscitation on organ function in adult patients after liver transplantation.

Design

A retrospective cohort study

Setting

Data from a tertiary care facility electronic medical records on liver transplantation patients admitted to the intensive care unit (ICU).

Patients

Adults admitted to the ICU after liver transplantation.

Interventions

Crystalloid fluid resuscitation compared to albumin 5% in the immediate postoperative period after liver transplant.

Measurements and main results

Adults who underwent liver transplant surgery and received a 5% albumin solution were compared with those who received a crystalloid solution. Demographic, etiology, clinical variables, perioperative, and outcome variables were collected. The data were analyzed using the t test, two-way analysis of variance, and multivariate analysis. After applying all the exclusion criteria, the study group comprised 57 adult patients (30 males; 52.6%) who underwent liver transplantation, including 27 patients in the crystalloid group (47.4%) and 30 patients in the albumin group (52.6%). The mean patient age was 52.2 years. Patient characteristics were similar in the 2 groups. Daily Sequential Organ Failure Assessment (SOFA) scores decreased gradually during the postoperative period in both groups, and the trend in SOFA scores was similar in the 2 groups. Analysis showed no statistical difference in SOFA score between the 2 groups postoperatively (P = .84). Multivariate linear regression analysis identified the Model for End-stage Liver Disease (MELD) score as a predictor of the 7-day postoperative SOFA score in this population.

Conclusions

In this study, the use of albumin or crystalloid solution in patients undergoing liver transplantation appeared to have no significant difference in terms of the risk of organ dysfunction. However, further research is needed to confirm these findings and fully understand the potential benefits and risks of using either type of fluid.