Search

Abstract In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.

This systematic review updates the currently available evidence on medial patella-femoral ligament (MPFL) reconstruction using allografts. The outcomes were measured with patient-reported outcome measures (PROMs), redislocation and complication rates. This study was performed according to the 2020 PRISMA guidelines using the PubMed, Scopus, Web of Science databases, accessed in February 2023. Studies examining the clinical outcomes of MPFL reconstruction with allografts in adolescents and children with recurrent patellofemoral instability (PFI) were included. Data from three trials, including 113 surgical procedures in 121 children, were retrieved. 40% (48/121) of the included patients were girls. The mean age of the patients was 14.7 ± 0.8 years, and the mean follow-up length was 38.1 ± 16.5 months. With MPFL allograft reconstruction, the Kujala score improved by 14.7% (p < 0.0001) and the IKDC by 38.8% (p < 0.0001). The rate of dislocations was 5% (6 of 121), reoperation for instability was 11% (13 of 121), and subluxation was 2% (1 of 47). Conclusion: These results encourage the use of allografts for MPFL reconstruction in adolescent patients with recurrent patellofemoral instability. Though patellofemoral instability is common in clinical practice, the current literature lacks clinical evidence on allograft MPFL reconstruction. Additional high-quality investigations are required to properly establish the long-term advantages of allograft MPFL and its complication rate.

Zero-time biopsies are taken to determine the quality of the donor organ at the time of transplantation. Histological analyses alone have so far not been able to identify parameters that allow the prediction of subsequent rejection episodes or graft survival. This study investigated whether gene expression analyses of zero-time biopsies might support this prediction. Using a well-characterized cohort of 26 zero-time biopsies from renal transplant patients that include 4 living donor (LD) and 22 deceased donor (DD) biopsies that later developed no rejection (Ctrl, n = 7), delayed graft function (DGF, n = 4), cellular (T-cell mediated rejection; TCMR, n = 8), or antibody-mediated rejection (ABMR, n = 7), we analyzed gene expression profiles for different types of subsequent renal transplant complication. To this end, RNA was isolated from formalin-fixed, paraffin-embedded (FFPE) sections and gene expression profiles were quantified. Results were correlated with transplant data and B-cell, and plasma cell infiltration was assessed by immunofluorescence microscopy. Both principal component analysis and clustering analysis of gene expression data revealed marked separation between LDs and DDs. Differential expression analysis identified 185 significant differentially expressed genes (adjusted p < 0.05). The expression of 68% of these genes significantly correlated with cold ischemia time (CIT). Furthermore, immunoglobulins were differentially expressed in zero-time biopsies from transplants later developing rejection (TCMR + ABMR) compared to non-rejected (Ctrl + DGF) transplants. In addition, immunoglobulin expression did not correlate with CIT but was increased in transplants with previous acute renal failure (ARF). In conclusion, gene expression profiles in zero-time biopsies derived from LDs are markedly different from those of DDs. Pre-transplant ARF increased immunoglobulin expression, which might be involved in triggering later rejection events. However, these findings must be confirmed in larger cohorts and the role of early immunoglobulin upregulation in zero-biopsies needs further clarification.

This tutorial describes the necessary steps for designing and conducting a perception experiment in order to obtain design parameters for human–machine interactions. It is intended for engineers and product designers, which require design parameters not included in the current state of the art. Topics addressed are the preposition of hypotheses, the selection of parameters, psychophysical measurement procedures and the calculation of sample sizes. Relevant steps for data analysis from psychology and social sciences are applied to the engineering and design context and guidelines for reporting results are given. The required steps are illustrated with an example experiment assessing detection thresholds of damping parameters of haptic automotive rotary controls with regard to parameters like knob diameter and distraction. Results imply significant effects of knob diameter on both absolute and differential thresholds, but no effect of distraction, implying a good transferability of laboratory results to real-world applications.