Impact of organ preservation using HTK for graft flush and subsequent storage in UW in rat kidney transplantation

BACKGROUND: In kidney transplantation, preservation has a significant influence on organ function. Since previous reports have indicated a benefit of combining histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution, we evaluated the effects of initial flush with low viscosity HTK, followed by storage in UW. MATERIAL AND METHODS: Kidneys from inbred Lewis rats were procured using HTK or UW for initially perfusion and re-flushed after 30 min with either solution. In a third group, after perfusion with HTK, organs were re-flushed with UW. Organs were stored for 16-24 h (4 degrees C). Study parameters were high-energy phosphates, histology, apoptosis, recipient survival and urine excretion of 15-F2t -isoprostanes (oxidative stress marker). RESULTS: Prior to transplantation, tissue ATP/ADP concentrations were: HTK/UW > UW-only > HTK-only. In transplanted kidneys, histological damage was highest after preservation in HTK-only. Twenty-four hours after transplantation (24 h cold ischemia time - CIT), cleaved-PARP was most abundant using UW-only. 16 h of CIT resulted in higher urine concentrations of isoprostanes in the order HTK-only (368 +/- 308) > UW-only (157 +/- 105) > HTK/UW (67 +/- 26), and was lower in HTK/UW after 24 h of CIT (146 +/- 38) vs. UW-only (507 +/- 33 pg/mg creatinine). Survival (24 h CIT) was significantly reduced, and percentage of initial non-functioning (INF) kidneys highest in HTK-only (2.6 +/- 0.3 days, 100%), compared to UW-only (13 +/- 4.4 days, 75%) and HTK/UW (18.5 +/- 4.6 days, 33%). CONCLUSIONS: In long-term preservation, UW is superior over HTK. However, our results indicate that perfusion with HTK prior to storage in UW may improve the results of UW alone which is reflected by better survival, lower rate of INF, higher cellular energy conservation and a decrease of free radicals.     

Analysis of KIR2D receptors on peripheral blood lymphocytes from liver graft recipients

KIR2D receptors are killer cell immunoglobulin-like receptors (KIRs) specific for HLA-C epitopes, that are expressed on NK cells as well as on minor peripheral blood T-cell subsets, and are able to control NK and T cells activity. The present work explores NK, and particularly CD8(+) T cells expressing KIR2D2L1/S1 (CD158a) or KIR2D2L2/3/S2 (CD158b) receptors in liver graft alloresponse. Flow cytometry was used to analyse peripheral blood mononuclear cells stained with anti-CD158a and anti-CD158b antibodies from 110 liver recipients and 46 healthy controls, previous to and along the first month after transplantation. Pre-transplantation data shows that both CD158a and CD158b molecules can be detected on NK and T cells from all patients and controls, but both KIR2D(+)NK cells are significantly under-represented in patients respect to controls (P<0.001), and CD3(+)CD8(+)CD158a(+) cells decreased particularly in patients suffering from acute rejection (4.03+/-1.33 cells/microL) compared with controls (7.8+/-2.4 cells/microL). Following transplantation, KIR2D(+)CD8(+) T-cell repertoires increased through the first month, mainly in recipients with a good graft acceptance. In summary, monitoring of KIR2D(+)CD8(+) T cells, particularly KIR2DL1/S1(+)CD8(+) T cells at pre-transplant, and both KIR2DL1/S1(+) and KIR2DL2/3/S2(+) T-cell subsets at early post-transplant period, could offer useful information for clinical follow-up of liver grafts.     

Homozygous status for HLA-E*0103 confers protection from acute graft-versus-host disease and transplant-related mortality in HLA-matched sibling hematopoietic stem cell transplantation

BACKGROUND: The posttransplant period following hematopoietic stem cell transplantation (HSCT) is potentially high risk for developing survival-compromising complications, many of which are known to be under the control of immunogenetic factors. Given the dual role of human leukocyte antigen (HLA)-E molecules in innate and adaptive immune processes, we analyzed the impact of HLA-E polymorphism in genoidentical HSCT setting. METHODS: We analyzed 187 HLA-genoidentical sibling pairs for HLA-E polymorphism. To explore its potential association with the incidence of acute and chronic graft versus host disease (aGVHD, cGVHD), severe infections, risk for transplant-related mortality (TRM), and overall survival, HLA-E locus was genotyped by a polymerase chain-reaction-sequence-specific primer (PCR-SSP) strategy. RESULTS: Multivariate analysis, taking into account the patient-, donor- and transplant-related factors, showed that the incidence of aGVHD and TRM at day 180 were low when the genotype was HLA-E*0103/E*0103, either in the donor or in the recipient, the pairs being identical for HLA-E alleles (hazard ratio [HR]=0.71, P=0.009; and HR=0.42, P=0.04, respectively). We also found a trend towards association between E*0103 homozygosity and improved survival (P=0.05). There was no association between HLA-E polymorphism and incidence of severe infections. CONCLUSIONS: These data suggest that the homozygous state for HLA-E*0103 allele behaves as a protective genetic factor against aGVHD and TRM and likely contributes to improved survival in HLA-genoidentical bone marrow transplantation.     

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta‐analysis

Mannose‐binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta‐analysis was primarily aimed at investigating the association between posttransplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5’ untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes. PubMed, EMBASE, and Web of Knowledge were searched for relevant articles up to August 2018. Eleven studies (comprising 1858 patients) were included, with liver transplant (LT) recipients accounting for 80.4% of the pooled population. As compared to high‐MBL expression haplotypes (YA/YA, YA/XA), any MBL‐deficient haplotype was associated with an increased risk of posttransplant bacterial and fungal infections (risk ratio [RR]: 1.30; P = .04). Low/null‐MBL expression haplotypes (XA/O, O/O) also increased the risk of primary outcome (RR: 1.51; P = .008) and CMV events (RR: 1.50; P = .006). No effect was observed for individual promoter SNPs. In conclusion, MBL‐deficient haplotypes are associated with a significant, albeit moderate, increase in the risk of posttransplant infection, with this association being mainly restricted to LT recipients.     

Impacto de la utilización de stents colónicos como puente a la cirugía de neoplasias colorrectales oclusivas potencialmente curables sobre los resultados quirúrgicos y oncológicos

Introduction

The outcomes of patients treated with colonic stents as a bridge to surgery (BTS) have recently been questioned in terms of safety and long-term oncologic outcomes. The aim of this study is to evaluate the effects on surgical and oncologic outcomes of colonic stents as a BTS for potentially resectable obstructive colorectal cancer.

Biomechanical investigation of two long bone growth modulation techniques by finite element simulations

Implants used to correct pathological varus–valgus deformities (VVD) and leg length discrepancies (LLD) may not be optimized for the specific treatment, as suggested by their off‐label use. Detailed analysis of this issue has been limited by the poorly understood mechanical behavior of the growing physis and ignorance of the loads acting on the implants. The aim of this study was to predict and compare the loading conditions of a growth modulation implant in VVD and LLD treatments. Idealized finite element (FE) models of the juvenile distal femur treated with the Eight‐Plate implant were developed for VVD and LLD. Bone growth was simulated using thermal strains. The axial force in the plate was compared between the two treatments. Case‐specific plate forces were predicted by virtually reproducing the screw deformation visible on radiographs of LLD (N = 4) and VVD (N = 4) clinical cases. The simple FE models reproduced the clinical implant deformations well. The resulting forces ranged from 129 to 580 N for the VVD patients. For LLD, this range was from 295 to 1002 N per plate, that is, 590–2004 N for the entire physis. The higher forces in LLD could be explained by restricted screw divergence in the double‐sided implant application. For the first time, the loading conditions of a growth modulation implant were investigated and compared between two treatments by FE analyses, and the range of case‐specific loads was predicted. These simulation tools may be utilized for guiding appropriate usage and for efficient development of implants. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1398–1405, 2018.

     

Hernias de la incisión de asistencia tras resección colorrectal laparoscópica. Influencia de la localización de la incisión y del uso de una malla profiláctica

Objectives

To determine the incidence of incisional hernia (IH) in the extraction incision (EI) in colorectal resection for cancer. To analyze whether the location of the incision has any relationship with the incidence of hernias and whether mesh could be useful for prevention in high-risk patients.